Mixed Topics

Postpartum hemorrhage (PPH) contin­ues to be a leading cause of maternal morbidity and mortality both worldwide and in the United States.^1-3 A PPH is defined as the cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours following the birth process (including intrapartum loss).⁴

Approximately 70% to 80% of hemorrhages are due to abnormal uterine tone.⁵ Bimanual massage and medical management, the primary treatments for uterine atony, attempt to restore the normal uterine tone that compresses the vessels in the placental implantation site and limits bleeding. For women in whom the primary treatments are not effective, only uterine compression sutures in a laparotomy can achieve physiologic contracture of the uterus. The second-line treatment option, intrauterine tamponade, places pressure over the placental implantation site while distending the uterus.

In October 2020, the US Food and Drug Administration (FDA) granted clearance to a novel device that offers an alternative treatment option. The Jada System (Alydia Health), an intrauterine vacuum-induced hemorrhage control device, is placed in the uterus and uses wall suction to induce physiologic contraction of the uterus to control bleeding.⁶

In this article, within the context of a case vignette, we discuss the recent study on the Jada System and how this device can be used in the management of PPH.⁶

CASE Woman with PPH history fears repeat hemorrhage

Ms. B. is a 25-year-old woman (G2P1) who pre­sents for prenatal care at 10 weeks’ gestation. Her medical history is significant for asthma and PPH after her first delivery. When you review her prior delivery records, you learn that she had a protracted labor and delivered a healthy 10 lb 8 oz baby boy after 3 hours of pushing. After delivery, she received postpartum intravenous oxytocin followed by intramuscular uterotonics when her bleeding was heavy during her laceration repair. Her estimated blood loss at delivery was 600 mL. The team was called back to her bedside for the continued bleeding. Uterine atony was diagnosed. Although she received additional uterotonics, the bleeding continued. An intrauterine tamponade balloon was placed, and the bleeding ultimately was controlled. The total estimated blood loss (EBL) was 2.5 L, and the patient then was transfused with 2 U of packed red blood cells.

Currently, Ms. B. is very worried about having another hemorrhage as the bleeding terrified her and her partner, disrupted breastfeeding initiation while the tamponade was in place, and made her anxious about having another baby.

What steps would you take to prepare for a potential PPH in this patient?
 

Risk factors

While PPH often is unpredictable, many risk factors have been identified (TABLE).^7-9 Some risk factors are present during the antepartum period while others arise during labor. In some cases, obstetric clinicians may be able to intervene during prenatal care, such as by giving iron supplementation to address anemia. Other factors, however, are not modifiable, including multiparity, polyhydramnios, and multiple gestations. On presentation to the labor unit, new risk factors may arise, such as magnesium sulfate use, chorioamnionitis, protracted labor, or the need for general anesthesia. In addition, the presence of a fibroid uterus or a uterine inversion can impede effective uterine contractions.⁵

Various tools are available for assessing these risk factors on admission, during labor, and after delivery, such as the AWHONN postpartum hemorrhage risk assessment table and the CMQCC obstetric hemorrhage toolkit.^10,11

Continue to: CASE continued Patient’s history reveals risk factors...

 

 

CASE continued Patient’s history reveals risk factors

You review with Ms. B. that she had several risk factors present during labor. She had a large baby and a protracted labor. Knowing her history in this pregnancy will allow the clinical team to be prepared for a potential recurrent hemorrhage and to respond proactively to bleeding.

Consider the management options

The initial treatment for PPH includes bimanual massage, oxytocin, and other uterotonics (methylergonovine, 15-methyl prostaglandin F2α, and misoprostol). While various algorithms are available on the order of treatment, a single agent has not been shown superior to others.¹² The antifibrinolytic medication tranexamic acid also was shown to reduce the risk of death from obstetric hemorrhage in the international WOMAN trial.¹³

While these agents often are used simultaneously to achieve hemostasis, their systemic effects are associated with contraindications. Specifically, F2α prostaglandins cannot be used in patients with asthma or active hepatic, pulmonary, or cardiac disease. Ergot derivatives cannot be used in patients with hypertension, pre-eclampsia, or cardiovascular disease. Given the rising rate of medical comorbidities during pregnancy, such contraindications limit the treatment options for many patients.

In cases in which medical management is not sufficient or is contraindicated for controlling hemorrhage, second-line treatment includes the use of tamponade techniques, such as intrauterine packing or balloons. The tamponade applies pressure directly to the placental implantation site for 12 to 24 hours, which allows time for the uterus to contract and return to normal tone. While this method may seem counterintuitive to achieving uterine tone, studies suggest a success rate between 75% and 86% with balloon tamponade.¹²

Third-line treatment options are increasingly invasive but should be used to prevent further maternal morbidity and mortality. These include uterine artery embolization and surgery. Uterine artery embolization is an option for a stable patient at a center with available interventional radiology services. If embolization is either not successful or not available, an exploratory laparotomy should be performed. Uterine compression sutures can be placed along with vascular ligation sutures of the uterine arteries (O’Leary sutures) and the hypogastric arteries. If all other methods have failed, a hysterectomy is the definitive treatment for hemorrhage.

CASE continued Patient desires an alternative to tamponade if needed

Following your visit, Ms. B. has an ultrasound scan that shows a dichorionic diamniotic twin pregnancy. She also has a microcytic anemia. After you discuss iron supplementation with the patient, she asks if there are any other options should medical management fail in the event of a recurrent hemorrhage. While intrauterine tamponade balloon did treat her hemorrhage, she was not happy with the length of time it had to remain in place, the discomfort while it was used, and the disruption to her planned recovery. You inform her of a new treatment option available for PPH, a vacuum-induced hemorrhage control device that was recently FDA cleared.

Continue to: New device controls bleeding fast...

 

New device controls bleeding fast

In 2020, D’Alton and colleagues reported on their multicenter, prospective single-arm treatment study on the effectiveness and safety of an intrauterine vacuum-induced hemorrhage control device.⁶ This device, the Jada System, uses low-level vacuum to induce uterine contraction to control bleeding from uterine atony. The prospective study, which followed a 2016 feasibility study, enrolled more than 100 women at 12 centers across the United States.^6,14 Women were eligible to participate if they delivered at a gestational age of 34 weeks or later and had an EBL between 500 and 1,000 mL after a vaginal delivery or an EBL between 1,000 and 1,500 mL after a cesarean delivery.

Treatment with the vacuum device was successful in 94% (100/106, 95% confidence interval, 88%–98%) of women, and definitive control of abnormal bleeding was achieved in a median of 3 minutes (interquartile range [IQR], 2.0–5.0) after connection to the vacuum device.⁶

CASE continued Patient has questions

Your patient expresses interest in this device, but she wants to understand how it works. Would it require transfer to another unit or prolonged monitoring?

How the device works

Compared with intrauterine tamponade balloon devices, which apply pressure by distending the uterus, the Jada System applies low-level intrauterine vacuum to facilitate the physiologic forces of uterine contractions to constrict myometrial blood vessels and achieve hemostasis.⁶ The device is made of medical-grade silicone. Its distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitate creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The device’s proximal end has a vacuum connector. The vacuum source is hospital-grade wall suction, but a portable vacuum source also can be used (FIGURE 1).

Prior to placing the device, a manual sweep of the uterine cavity is performed. If needed, ultrasonography can be used with the manual sweep to ensure that there is no retained placental tissue or clot. The loop of the Jada System is then inserted in the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with sterile water.

Low-level vacuum (80 ± 10 mm Hg) is applied so that pooled blood is evacuated from the uterus as it collapses (FIGURE 2). The volume of any ongoing bleeding is measured in the suction tubing while the uterine response to treatment can be palpated. Once there is no bleeding without any need for further treatment, the device should remain in the uterus for at least 1 hour. The suction is then turned off, and bleeding is monitored for 30 minutes. If bleeding remains controlled, the device can be removed.

CASE continued The question of complications

Ms. B. is concerned about safety and asks about potential complications with the device’s use.

Safety findings

In the prospective study and FDA review, the device was deemed safe. There were 8 possibly related adverse events (endometritis, laceration disruption, and vaginal infection), which all resolved without serious clinical sequelae. Forty women (38%) received a blood transfusion, but only 5 required 4 U or more of red blood cells.⁶

Continue to: CASE continued What do other physicians think?...

 

CASE continued What do other physicians think?

Your patient is curious about the time it takes for the device to work and whether other clinicians like using this new device for hemorrhage treatment.

Duration of treatment

The times to achieve uterine collapse and control of hemorrhage are both relatively short. In the prospective study, the initial collapse of the uterus took a median of 1 minute (IQR, 1–2 min) from the time of vacuum connection.⁶ Bleeding was controlled in less than 5 minutes in 82% of women, with an overall median time of 3 minutes (IQR, 2–5 min). The median duration of vacuum treatment was 144.0 minutes (IQR, 85.8–295.8 min), which includes the required minimum of 60 minutes for vacuum treatment time and 30 minutes of observation without the vacuum connected but with the device still in place.⁶

When polled, the majority of clinicians—98%—reported that the intrauterine vacuum-induced hemorrhage control device was easy to use, and 97% would recommend its use for future patients.⁶

Further, recognizing the device’s potential, the Cleveland Clinic cited it as one of the top 10 health care innovations for 2021 for offering a low-tech and minimally invasive tool for obstetric clinicians.¹⁵

CASE continued Final questions

Ms. B. thanks you for the information and asks, should she know anything else about the device?

Vacuum device vs other treatments

The study by D’Alton and colleagues was a single-arm treatment trial that did not directly compare the effectiveness of the device with that of other PPH treatment options, such as balloon tamponade.⁶ At this point, we know that clinicians can safely and quickly use the device to treat uterine atony, but we do not know if it is superior to other treatments for PPH.

Key takeaways

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. When first-line uterotonics fail, obstetric clinicians previously had only balloon tamponade or invasive procedures to treat patients. The novel intrauterine vacuum-induced hemorrhage control device takes a new approach that simulates the physiologic process of uterine contractions. The device can rapidly and effectively control abnormal postpartum uterine bleeding. More studies are needed, however, to compare the device’s effectiveness with that of other PPH treatments and to consider its use in women with more severe degrees of postpartum hemorrhage as well as its cost-effectiveness. ●

Postpartum hemorrhage (PPH) contin­ues to be a leading cause of maternal morbidity and mortality both worldwide and in the United States.^1-3 A PPH is defined as the cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours following the birth process (including intrapartum loss).⁴

Approximately 70% to 80% of hemorrhages are due to abnormal uterine tone.⁵ Bimanual massage and medical management, the primary treatments for uterine atony, attempt to restore the normal uterine tone that compresses the vessels in the placental implantation site and limits bleeding. For women in whom the primary treatments are not effective, only uterine compression sutures in a laparotomy can achieve physiologic contracture of the uterus. The second-line treatment option, intrauterine tamponade, places pressure over the placental implantation site while distending the uterus.

In October 2020, the US Food and Drug Administration (FDA) granted clearance to a novel device that offers an alternative treatment option. The Jada System (Alydia Health), an intrauterine vacuum-induced hemorrhage control device, is placed in the uterus and uses wall suction to induce physiologic contraction of the uterus to control bleeding.⁶

In this article, within the context of a case vignette, we discuss the recent study on the Jada System and how this device can be used in the management of PPH.⁶

CASE Woman with PPH history fears repeat hemorrhage

Ms. B. is a 25-year-old woman (G2P1) who pre­sents for prenatal care at 10 weeks’ gestation. Her medical history is significant for asthma and PPH after her first delivery. When you review her prior delivery records, you learn that she had a protracted labor and delivered a healthy 10 lb 8 oz baby boy after 3 hours of pushing. After delivery, she received postpartum intravenous oxytocin followed by intramuscular uterotonics when her bleeding was heavy during her laceration repair. Her estimated blood loss at delivery was 600 mL. The team was called back to her bedside for the continued bleeding. Uterine atony was diagnosed. Although she received additional uterotonics, the bleeding continued. An intrauterine tamponade balloon was placed, and the bleeding ultimately was controlled. The total estimated blood loss (EBL) was 2.5 L, and the patient then was transfused with 2 U of packed red blood cells.

Currently, Ms. B. is very worried about having another hemorrhage as the bleeding terrified her and her partner, disrupted breastfeeding initiation while the tamponade was in place, and made her anxious about having another baby.

What steps would you take to prepare for a potential PPH in this patient?
 

Risk factors

While PPH often is unpredictable, many risk factors have been identified (TABLE).^7-9 Some risk factors are present during the antepartum period while others arise during labor. In some cases, obstetric clinicians may be able to intervene during prenatal care, such as by giving iron supplementation to address anemia. Other factors, however, are not modifiable, including multiparity, polyhydramnios, and multiple gestations. On presentation to the labor unit, new risk factors may arise, such as magnesium sulfate use, chorioamnionitis, protracted labor, or the need for general anesthesia. In addition, the presence of a fibroid uterus or a uterine inversion can impede effective uterine contractions.⁵

Various tools are available for assessing these risk factors on admission, during labor, and after delivery, such as the AWHONN postpartum hemorrhage risk assessment table and the CMQCC obstetric hemorrhage toolkit.^10,11

Continue to: CASE continued Patient’s history reveals risk factors...

 

 

CASE continued Patient’s history reveals risk factors

You review with Ms. B. that she had several risk factors present during labor. She had a large baby and a protracted labor. Knowing her history in this pregnancy will allow the clinical team to be prepared for a potential recurrent hemorrhage and to respond proactively to bleeding.

Consider the management options

The initial treatment for PPH includes bimanual massage, oxytocin, and other uterotonics (methylergonovine, 15-methyl prostaglandin F2α, and misoprostol). While various algorithms are available on the order of treatment, a single agent has not been shown superior to others.¹² The antifibrinolytic medication tranexamic acid also was shown to reduce the risk of death from obstetric hemorrhage in the international WOMAN trial.¹³

While these agents often are used simultaneously to achieve hemostasis, their systemic effects are associated with contraindications. Specifically, F2α prostaglandins cannot be used in patients with asthma or active hepatic, pulmonary, or cardiac disease. Ergot derivatives cannot be used in patients with hypertension, pre-eclampsia, or cardiovascular disease. Given the rising rate of medical comorbidities during pregnancy, such contraindications limit the treatment options for many patients.

In cases in which medical management is not sufficient or is contraindicated for controlling hemorrhage, second-line treatment includes the use of tamponade techniques, such as intrauterine packing or balloons. The tamponade applies pressure directly to the placental implantation site for 12 to 24 hours, which allows time for the uterus to contract and return to normal tone. While this method may seem counterintuitive to achieving uterine tone, studies suggest a success rate between 75% and 86% with balloon tamponade.¹²

Third-line treatment options are increasingly invasive but should be used to prevent further maternal morbidity and mortality. These include uterine artery embolization and surgery. Uterine artery embolization is an option for a stable patient at a center with available interventional radiology services. If embolization is either not successful or not available, an exploratory laparotomy should be performed. Uterine compression sutures can be placed along with vascular ligation sutures of the uterine arteries (O’Leary sutures) and the hypogastric arteries. If all other methods have failed, a hysterectomy is the definitive treatment for hemorrhage.

CASE continued Patient desires an alternative to tamponade if needed

Following your visit, Ms. B. has an ultrasound scan that shows a dichorionic diamniotic twin pregnancy. She also has a microcytic anemia. After you discuss iron supplementation with the patient, she asks if there are any other options should medical management fail in the event of a recurrent hemorrhage. While intrauterine tamponade balloon did treat her hemorrhage, she was not happy with the length of time it had to remain in place, the discomfort while it was used, and the disruption to her planned recovery. You inform her of a new treatment option available for PPH, a vacuum-induced hemorrhage control device that was recently FDA cleared.

Continue to: New device controls bleeding fast...

 

New device controls bleeding fast

In 2020, D’Alton and colleagues reported on their multicenter, prospective single-arm treatment study on the effectiveness and safety of an intrauterine vacuum-induced hemorrhage control device.⁶ This device, the Jada System, uses low-level vacuum to induce uterine contraction to control bleeding from uterine atony. The prospective study, which followed a 2016 feasibility study, enrolled more than 100 women at 12 centers across the United States.^6,14 Women were eligible to participate if they delivered at a gestational age of 34 weeks or later and had an EBL between 500 and 1,000 mL after a vaginal delivery or an EBL between 1,000 and 1,500 mL after a cesarean delivery.

Treatment with the vacuum device was successful in 94% (100/106, 95% confidence interval, 88%–98%) of women, and definitive control of abnormal bleeding was achieved in a median of 3 minutes (interquartile range [IQR], 2.0–5.0) after connection to the vacuum device.⁶

CASE continued Patient has questions

Your patient expresses interest in this device, but she wants to understand how it works. Would it require transfer to another unit or prolonged monitoring?

How the device works

Compared with intrauterine tamponade balloon devices, which apply pressure by distending the uterus, the Jada System applies low-level intrauterine vacuum to facilitate the physiologic forces of uterine contractions to constrict myometrial blood vessels and achieve hemostasis.⁶ The device is made of medical-grade silicone. Its distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitate creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The device’s proximal end has a vacuum connector. The vacuum source is hospital-grade wall suction, but a portable vacuum source also can be used (FIGURE 1).

Prior to placing the device, a manual sweep of the uterine cavity is performed. If needed, ultrasonography can be used with the manual sweep to ensure that there is no retained placental tissue or clot. The loop of the Jada System is then inserted in the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with sterile water.

Low-level vacuum (80 ± 10 mm Hg) is applied so that pooled blood is evacuated from the uterus as it collapses (FIGURE 2). The volume of any ongoing bleeding is measured in the suction tubing while the uterine response to treatment can be palpated. Once there is no bleeding without any need for further treatment, the device should remain in the uterus for at least 1 hour. The suction is then turned off, and bleeding is monitored for 30 minutes. If bleeding remains controlled, the device can be removed.

CASE continued The question of complications

Ms. B. is concerned about safety and asks about potential complications with the device’s use.

Safety findings

In the prospective study and FDA review, the device was deemed safe. There were 8 possibly related adverse events (endometritis, laceration disruption, and vaginal infection), which all resolved without serious clinical sequelae. Forty women (38%) received a blood transfusion, but only 5 required 4 U or more of red blood cells.⁶

Continue to: CASE continued What do other physicians think?...

 

CASE continued What do other physicians think?

Your patient is curious about the time it takes for the device to work and whether other clinicians like using this new device for hemorrhage treatment.

Duration of treatment

The times to achieve uterine collapse and control of hemorrhage are both relatively short. In the prospective study, the initial collapse of the uterus took a median of 1 minute (IQR, 1–2 min) from the time of vacuum connection.⁶ Bleeding was controlled in less than 5 minutes in 82% of women, with an overall median time of 3 minutes (IQR, 2–5 min). The median duration of vacuum treatment was 144.0 minutes (IQR, 85.8–295.8 min), which includes the required minimum of 60 minutes for vacuum treatment time and 30 minutes of observation without the vacuum connected but with the device still in place.⁶

When polled, the majority of clinicians—98%—reported that the intrauterine vacuum-induced hemorrhage control device was easy to use, and 97% would recommend its use for future patients.⁶

Further, recognizing the device’s potential, the Cleveland Clinic cited it as one of the top 10 health care innovations for 2021 for offering a low-tech and minimally invasive tool for obstetric clinicians.¹⁵

CASE continued Final questions

Ms. B. thanks you for the information and asks, should she know anything else about the device?

Vacuum device vs other treatments

The study by D’Alton and colleagues was a single-arm treatment trial that did not directly compare the effectiveness of the device with that of other PPH treatment options, such as balloon tamponade.⁶ At this point, we know that clinicians can safely and quickly use the device to treat uterine atony, but we do not know if it is superior to other treatments for PPH.

Key takeaways

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. When first-line uterotonics fail, obstetric clinicians previously had only balloon tamponade or invasive procedures to treat patients. The novel intrauterine vacuum-induced hemorrhage control device takes a new approach that simulates the physiologic process of uterine contractions. The device can rapidly and effectively control abnormal postpartum uterine bleeding. More studies are needed, however, to compare the device’s effectiveness with that of other PPH treatments and to consider its use in women with more severe degrees of postpartum hemorrhage as well as its cost-effectiveness. ●

Postpartum hemorrhage (PPH) contin­ues to be a leading cause of maternal morbidity and mortality both worldwide and in the United States.^1-3 A PPH is defined as the cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours following the birth process (including intrapartum loss).⁴

Approximately 70% to 80% of hemorrhages are due to abnormal uterine tone.⁵ Bimanual massage and medical management, the primary treatments for uterine atony, attempt to restore the normal uterine tone that compresses the vessels in the placental implantation site and limits bleeding. For women in whom the primary treatments are not effective, only uterine compression sutures in a laparotomy can achieve physiologic contracture of the uterus. The second-line treatment option, intrauterine tamponade, places pressure over the placental implantation site while distending the uterus.

In October 2020, the US Food and Drug Administration (FDA) granted clearance to a novel device that offers an alternative treatment option. The Jada System (Alydia Health), an intrauterine vacuum-induced hemorrhage control device, is placed in the uterus and uses wall suction to induce physiologic contraction of the uterus to control bleeding.⁶

In this article, within the context of a case vignette, we discuss the recent study on the Jada System and how this device can be used in the management of PPH.⁶

CASE Woman with PPH history fears repeat hemorrhage

Ms. B. is a 25-year-old woman (G2P1) who pre­sents for prenatal care at 10 weeks’ gestation. Her medical history is significant for asthma and PPH after her first delivery. When you review her prior delivery records, you learn that she had a protracted labor and delivered a healthy 10 lb 8 oz baby boy after 3 hours of pushing. After delivery, she received postpartum intravenous oxytocin followed by intramuscular uterotonics when her bleeding was heavy during her laceration repair. Her estimated blood loss at delivery was 600 mL. The team was called back to her bedside for the continued bleeding. Uterine atony was diagnosed. Although she received additional uterotonics, the bleeding continued. An intrauterine tamponade balloon was placed, and the bleeding ultimately was controlled. The total estimated blood loss (EBL) was 2.5 L, and the patient then was transfused with 2 U of packed red blood cells.

Currently, Ms. B. is very worried about having another hemorrhage as the bleeding terrified her and her partner, disrupted breastfeeding initiation while the tamponade was in place, and made her anxious about having another baby.

What steps would you take to prepare for a potential PPH in this patient?
 

Risk factors

While PPH often is unpredictable, many risk factors have been identified (TABLE).^7-9 Some risk factors are present during the antepartum period while others arise during labor. In some cases, obstetric clinicians may be able to intervene during prenatal care, such as by giving iron supplementation to address anemia. Other factors, however, are not modifiable, including multiparity, polyhydramnios, and multiple gestations. On presentation to the labor unit, new risk factors may arise, such as magnesium sulfate use, chorioamnionitis, protracted labor, or the need for general anesthesia. In addition, the presence of a fibroid uterus or a uterine inversion can impede effective uterine contractions.⁵

Various tools are available for assessing these risk factors on admission, during labor, and after delivery, such as the AWHONN postpartum hemorrhage risk assessment table and the CMQCC obstetric hemorrhage toolkit.^10,11

Continue to: CASE continued Patient’s history reveals risk factors...

 

 

CASE continued Patient’s history reveals risk factors

You review with Ms. B. that she had several risk factors present during labor. She had a large baby and a protracted labor. Knowing her history in this pregnancy will allow the clinical team to be prepared for a potential recurrent hemorrhage and to respond proactively to bleeding.

Consider the management options

The initial treatment for PPH includes bimanual massage, oxytocin, and other uterotonics (methylergonovine, 15-methyl prostaglandin F2α, and misoprostol). While various algorithms are available on the order of treatment, a single agent has not been shown superior to others.¹² The antifibrinolytic medication tranexamic acid also was shown to reduce the risk of death from obstetric hemorrhage in the international WOMAN trial.¹³

While these agents often are used simultaneously to achieve hemostasis, their systemic effects are associated with contraindications. Specifically, F2α prostaglandins cannot be used in patients with asthma or active hepatic, pulmonary, or cardiac disease. Ergot derivatives cannot be used in patients with hypertension, pre-eclampsia, or cardiovascular disease. Given the rising rate of medical comorbidities during pregnancy, such contraindications limit the treatment options for many patients.

In cases in which medical management is not sufficient or is contraindicated for controlling hemorrhage, second-line treatment includes the use of tamponade techniques, such as intrauterine packing or balloons. The tamponade applies pressure directly to the placental implantation site for 12 to 24 hours, which allows time for the uterus to contract and return to normal tone. While this method may seem counterintuitive to achieving uterine tone, studies suggest a success rate between 75% and 86% with balloon tamponade.¹²

Third-line treatment options are increasingly invasive but should be used to prevent further maternal morbidity and mortality. These include uterine artery embolization and surgery. Uterine artery embolization is an option for a stable patient at a center with available interventional radiology services. If embolization is either not successful or not available, an exploratory laparotomy should be performed. Uterine compression sutures can be placed along with vascular ligation sutures of the uterine arteries (O’Leary sutures) and the hypogastric arteries. If all other methods have failed, a hysterectomy is the definitive treatment for hemorrhage.

CASE continued Patient desires an alternative to tamponade if needed

Following your visit, Ms. B. has an ultrasound scan that shows a dichorionic diamniotic twin pregnancy. She also has a microcytic anemia. After you discuss iron supplementation with the patient, she asks if there are any other options should medical management fail in the event of a recurrent hemorrhage. While intrauterine tamponade balloon did treat her hemorrhage, she was not happy with the length of time it had to remain in place, the discomfort while it was used, and the disruption to her planned recovery. You inform her of a new treatment option available for PPH, a vacuum-induced hemorrhage control device that was recently FDA cleared.

Continue to: New device controls bleeding fast...

 

New device controls bleeding fast

In 2020, D’Alton and colleagues reported on their multicenter, prospective single-arm treatment study on the effectiveness and safety of an intrauterine vacuum-induced hemorrhage control device.⁶ This device, the Jada System, uses low-level vacuum to induce uterine contraction to control bleeding from uterine atony. The prospective study, which followed a 2016 feasibility study, enrolled more than 100 women at 12 centers across the United States.^6,14 Women were eligible to participate if they delivered at a gestational age of 34 weeks or later and had an EBL between 500 and 1,000 mL after a vaginal delivery or an EBL between 1,000 and 1,500 mL after a cesarean delivery.

Treatment with the vacuum device was successful in 94% (100/106, 95% confidence interval, 88%–98%) of women, and definitive control of abnormal bleeding was achieved in a median of 3 minutes (interquartile range [IQR], 2.0–5.0) after connection to the vacuum device.⁶

CASE continued Patient has questions

Your patient expresses interest in this device, but she wants to understand how it works. Would it require transfer to another unit or prolonged monitoring?

How the device works

Compared with intrauterine tamponade balloon devices, which apply pressure by distending the uterus, the Jada System applies low-level intrauterine vacuum to facilitate the physiologic forces of uterine contractions to constrict myometrial blood vessels and achieve hemostasis.⁶ The device is made of medical-grade silicone. Its distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitate creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The device’s proximal end has a vacuum connector. The vacuum source is hospital-grade wall suction, but a portable vacuum source also can be used (FIGURE 1).

Prior to placing the device, a manual sweep of the uterine cavity is performed. If needed, ultrasonography can be used with the manual sweep to ensure that there is no retained placental tissue or clot. The loop of the Jada System is then inserted in the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with sterile water.

Low-level vacuum (80 ± 10 mm Hg) is applied so that pooled blood is evacuated from the uterus as it collapses (FIGURE 2). The volume of any ongoing bleeding is measured in the suction tubing while the uterine response to treatment can be palpated. Once there is no bleeding without any need for further treatment, the device should remain in the uterus for at least 1 hour. The suction is then turned off, and bleeding is monitored for 30 minutes. If bleeding remains controlled, the device can be removed.

CASE continued The question of complications

Ms. B. is concerned about safety and asks about potential complications with the device’s use.

Safety findings

In the prospective study and FDA review, the device was deemed safe. There were 8 possibly related adverse events (endometritis, laceration disruption, and vaginal infection), which all resolved without serious clinical sequelae. Forty women (38%) received a blood transfusion, but only 5 required 4 U or more of red blood cells.⁶

Continue to: CASE continued What do other physicians think?...

 

CASE continued What do other physicians think?

Your patient is curious about the time it takes for the device to work and whether other clinicians like using this new device for hemorrhage treatment.

Duration of treatment

The times to achieve uterine collapse and control of hemorrhage are both relatively short. In the prospective study, the initial collapse of the uterus took a median of 1 minute (IQR, 1–2 min) from the time of vacuum connection.⁶ Bleeding was controlled in less than 5 minutes in 82% of women, with an overall median time of 3 minutes (IQR, 2–5 min). The median duration of vacuum treatment was 144.0 minutes (IQR, 85.8–295.8 min), which includes the required minimum of 60 minutes for vacuum treatment time and 30 minutes of observation without the vacuum connected but with the device still in place.⁶

When polled, the majority of clinicians—98%—reported that the intrauterine vacuum-induced hemorrhage control device was easy to use, and 97% would recommend its use for future patients.⁶

Further, recognizing the device’s potential, the Cleveland Clinic cited it as one of the top 10 health care innovations for 2021 for offering a low-tech and minimally invasive tool for obstetric clinicians.¹⁵

CASE continued Final questions

Ms. B. thanks you for the information and asks, should she know anything else about the device?

Vacuum device vs other treatments

The study by D’Alton and colleagues was a single-arm treatment trial that did not directly compare the effectiveness of the device with that of other PPH treatment options, such as balloon tamponade.⁶ At this point, we know that clinicians can safely and quickly use the device to treat uterine atony, but we do not know if it is superior to other treatments for PPH.

Key takeaways

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. When first-line uterotonics fail, obstetric clinicians previously had only balloon tamponade or invasive procedures to treat patients. The novel intrauterine vacuum-induced hemorrhage control device takes a new approach that simulates the physiologic process of uterine contractions. The device can rapidly and effectively control abnormal postpartum uterine bleeding. More studies are needed, however, to compare the device’s effectiveness with that of other PPH treatments and to consider its use in women with more severe degrees of postpartum hemorrhage as well as its cost-effectiveness. ●

Psychiatrists with expertise in delusional infestation have some advice for dermatologists, infectious disease specialists, and primary care physicians who encounter affected patients: If you want to try to help them, initiate treatment yourself.

“If you see it, try and treat it. These patients are unlikely to agree to see a psychiatrist,” Peter Lepping, MD, said at the Entomology 2020 annual meeting.

Indeed, one of the hallmarks of delusional infestation (DI) is a refusal to even consider referral to a mental health professional, noted Dr. Lepping, a consultation-liaison psychiatrist at Bangor (Wales) University who, together with an infectious disease specialist, codirects one of the world’s few DI multispecialty referral clinics, located at the University of Liverpool School of Tropical Medicine.

That being said, he offered another piece of advice: “Accept that it is not easy to help these patients.”

Dr. Lepping was among a group of distinguished psychiatrists, dermatologists, entomologists, and a neurologist at the annual meeting who participated in a comprehensive session devoted to DI. The experts shared tips on making the diagnosis, establishing the rapport necessary to persuade affected patients to try taking a very-low-dose antipsychotic agent for their delusion, and how to achieve a high rate of therapeutic success. They also highlighted recent research advances in the field, including brain MRI evidence suggesting that impaired somatosensory neural networks mediate symptoms in DI, but not in nonsomatic delusional disorders.


 

COVID-19 pandemic triggers surge in DI

Entomologist Gail E. Ridge, PhD, has taken notes on all of her thousands of consultations with individuals with suspected DI since the late 1990s. A sharp jump in such contacts occurred during the Great Recession of 2008 in conjunction with the widespread social distress of job loss and threatened economic ruin. Now the same thing is happening as the catastrophic COVID-19 pandemic stretches on. Indeed, during the first 8 months of the pandemic she documented 500 interactions involving people with suspected DI. She’s learned to identify the clues, including a chattering mind, defensiveness, physician avoidance, and rigid body tension.

Courtesy Dr. Gale E. Ridge

“They’re fearful of judgment and suggestions of madness. And they’ll pounce on any perceived negativity. I never debunk beliefs; that can immediately backfire. If the medical profession was educated about DI, then many cases could be caught early. I, as the entomologist, and the mental health professionals are often last in line to be seen,” said Dr. Ridge, director of the Insect Information Office at the Connecticut Agricultural Experiment Station in New Haven.

She has noticed a recurring theme in her interactions with these patients: DI often starts with a real underlying medical condition, such as, for example, a cutaneous drug reaction, which over time, progresses to gain a psychiatric component. And she has found that a tipping point often occurs after roughly 6 months of unrelieved symptoms and sensations. Prior to that, affected individuals are concerned about their condition and will seek medical help in a genuine effort to understand what’s going on. They can be redirected. After about 6 months, however, Dr. Ridge has observed “they slide into the rabbit hole of fanaticism and despair.”
 

 

Arriving at the diagnosis

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), DI is classified as a “delusional disorder, somatic type 297.1 F22.” The diagnosis requires that the delusion be present for at least 1 month, criteria for schizophrenia are not met, and the condition cannot be attributed to other medical or neuropsychiatric conditions.

“Many of these people are very high-functioning. I have corporate CEOs who fly in to see me in their private jets. At work, they’re king of their domain. At home, their family is falling apart because of their delusion,” said Dirk M. Elston, MD, professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston.

“These people suffer, and the people around them suffer,” he emphasized.

Dozens of medical conditions can cause intractable itching or biting sensations. Far and away at the top of the medical differential diagnosis is thyroid disease, given its high incidence and frequent presentation with anxiety and itch. Other possibilities that can readily be ruled out via lab tests include substance use – especially involving amphetamine/methamphetamine, cocaine, or opioids – liver or kidney disease, diabetes and other sources of peripheral neuropathy, polycythemia, dermatitis herpetiformis, and pemphigus, Dr. Elston said.

Scott A. Norton, MD, MPH, MSc, a dermatologist and preventive medicine specialist at the Uniformed Services University of the Health Sciences in Bethesda, Md., noted that a diagnosis of DI requires three elements: The presence of abnormal sensations in the skin, a patient’s tenacious conviction that the sensations are caused by an infestation, and a lack of supporting evidence for that conviction.

Taking an accurate medical history can be a challenge in these patients because they are often so guarded. They won’t disclose that they’ve already seen other health care providers, or that they’ve been self-treating with OTC veterinary medicine products, such as high-dose topical or oral ivermectin. They’ll often even deny repeated scratching despite clear evidence to the contrary from the skin exam.

As a dermatologist, Dr. Norton considers his first task to be a search for evidence of an infestation. Scabies is usually the first diagnosis proposed to account for the uncomfortable skin sensations. The presentation can be subtle. While the classic teaching is that the telltale signs of infestation by Sarcoptes scabiei are burrows in the skin and a rash in the web spaces between the fingers, he finds these features are often absent or equivocal.

“I think there are two more reliable presentations of scabies: Check to see if there’s symmetric involvement of the volar or palm side of the wrists; if there isn’t, I’m skeptical of the diagnosis. And every male older than 1 year of age with scabies will have scabies nodules on their genitalia. If the penis, the glans, or the scrotum aren’t involved with the nodules, I discard scabies as a possible diagnosis and look for evidence of other skin conditions that can plausibly explain the sensations and skin lesions, like eczema, contact dermatitis, scalp folliculitis, or dry skin,” he said.

If he can’t find evidence of infestation, he next systematically looks for another dermatologic cause of the patient’s sensations. When that proves fruitless, he tries to determine if there might be a biomedical or neuropsychiatric cause, such as depression, anxiety, schizophrenia, or dementia.

Taking a personal hygiene history is helpful. Patients who believe they have an infestation may bathe or shower three to five times daily with harsh soaps, causing dry, inflamed, itchy and uncomfortable skin.

“Many patients are thrilled to hear the good news that the history, physical examination, and lab tests do not show an infestation and that we have another explanation to account for their unwanted sensations. However, there are some patients who vehemently reject that idea and immediately return to their unwavering, unalterable belief that they are in fact infested. At this point, the possible diagnosis of DI looms large,” the dermatologist said.

Clues suggestive of DI include a patient’s obsessive focus on collecting “specimens” of the offending pathogen in Ziplock bags for assessment during the office visit – “usually a mix of unhelpful household debris and environmental detritus” – and eager presentation of a lengthy and detailed infestation diary, Dr. Norton said.

“Among the most distinctive signs that the patient is detached from reality are the biologically implausible descriptions and explanations of the supposed attacking organism. It’s a fanciful amalgamation of mutable features, behaviors, and life cycles composed of a composite of taxonomically unrelated organisms – for example, fungal hyphae with wings – that shapeshift at will to evade detection,” he said.

Dr. Elston observed that DI skin lesions are typically excoriated, sometimes because of a patient’s systematic use of a sharp object in an effort to dig out the infestation.

“One of the clues is the angularity of the lesion,” the dermatologist noted. “We always say round-to-oval lesions suggest an inside job; angulated lesions suggest an outside job, like fingernail work. There’s often a row of good healing border showing there’s really nothing wrong with wound healing, but a fibrinoid base where the excoriations have occurred. And the lesions are often in various stages of healing.”

Don’t forget neuropathic itch in nondelusional individuals as a potential cause of sensations of infestation and self-injury due to relentless scratching, urged Anne Louise Oaklander, MD, PhD, associate professor of neurology, Harvard Medical School, Boston, who is director of the nerve unit and the neurodiagnostic skin biopsy lab at Massachusetts General Hospital, Boston.

“There’s no one cause of patients’ impressions that they may have insects. Let’s be sympathetic: It is a normal assumption that insects may be present if the skin itches. One problem is that when patients don’t get good medical diagnoses they make up their own explanations, and sometimes these include persistent ideas of infestation. Many of them don’t realize that their scratching is a cause, not a result, of their skin lesions,” said Dr. Oaklander, who has conducted pioneering research on unintentional self-injury due to neuropathic itch accompanied by loss of pain signaling.


 

 

“Rapport first, medication later”

“The office visits are typically difficult to conclude, but skills can be learned and make it much easier to help these people,” Dr. Elston said.

John Koo, MD, emphasized that establishing rapport is “by far” the most important part of managing patients with DI.

“Rapport first, medication later. This may require multiple visits,” said Dr. Koo, professor of dermatology at the University of California, San Francisco, who is a board-certified psychiatrist.

He makes sure he walks into the examination room all smiles and positivity. Patients with DI are eager to expound on their ailment; he lets them talk for a while, then when the timing is right, he actively encourages them to shift their focus away from etiology to treatment.

Dr. Koo and coworkers have described a spectrum of mental fixation in DI ranging from having only crawling and biting sensations, progressing to holding an overvalued idea as to their cause, then on to DSM-5 somatic preoccupation, followed by becoming truly delusional, and finally terminal delusion, where the patient doesn’t care about getting better, but only wants the physician to agree there is an infestation (J Clin Exp Dermatol Res. 2014 Oct. 3. doi: 10.4172/2155-9554.1000241).

“You cannot argue with people with delusions. How you talk to them as a clinician depends on whether they are entirely delusional or not,” he advised. “I cannot agree with their ideation, but I can agree with their misery – and that’s how I make a connection.”

Declining a DI patient’s request for a skin biopsy when it’s obvious there is no infestation can lead to a counterproductive power struggle. Instead, Dr. Koo turns the patient request into an opportunity to form a verbal contract: “I ask, ‘If the result comes back negative, can you be open-minded about the possibility of other etiologies besides parasites?’ ”

As for Dr. Norton, when his schedule shows a patient is coming in for a first visit for a supposed skin infestation, he tells his staff to expect a lengthy session as he works at establishing a good relationship.

“When my patients arrive with bags of specimens, I ask them to select two or three that they’re most confident will have a creature in them. Then I bring a two-headed microscope into the exam room and ask the patient to join me in examining the material. It helps with rapport by showing that I genuinely want to determine if there’s an infestation,” he explained.

He then sends the specimens to a laboratory, which provides a full report of the findings.

In performing a skin biopsy in a patient with suspected DI, Dr. Norton routinely biopsies two sites so the patient can’t claim sampling error when the pathology report comes back with no pathogens or parasites found. Also, he asks the patient to choose biopsy sites with intact skin where he or she believes the infestation exists. There is no point in biopsying excoriated lesions because they often contain snagged textile fibers.

Another rapport-building strategy: “I try to design a treatment regimen that will palliate the uncomfortable sensations and help relieve the patient’s misery while we continue working towards treating those delusions,” Dr. Norton said.

This might entail cutting back to one lukewarm shower per day with gentle or no soap, coupled with moisturizing, oral antihistamines or doxepin for itch, topical corticosteroids for the associated inflammation, and oral or topical antibiotics for any secondary bacterial skin infection.

What he doesn’t recommend as a rapport-building strategy or simply in order to get the patient out of the office is offering a therapeutic trial of an antiparasitic agent. That’s counterproductive. It may reinforce the false belief of infestation, and when the medication doesn’t bring lasting belief, the patient may conclude the infestation is resistant to conventional treatment.

Dr. Koo tells affected patients that he suspects they have Morgellons syndrome. He doesn’t call it DI in their presence.

“These people would not like their condition to be called delusional,” he explained. “Morgellons is a more neutral term. I tell them it’s a mysterious condition, and that what I’m really interested in is in trying to get them out of their misery.”
 

 

Treatment tips

Dr. Koo’s first-line medication for DI is pimozide (Orap), which in the United States has the advantage of being approved only for Tourette syndrome; it’s an antipsychotic without the perceived stigma of a psychiatric indication.

“Many of these patients will not consider taking any medication that has any psychiatric indication,” he noted.

Low-dose pimozide is highly effective, according to Dr. Koo, who recommends starting at 0.5 mg to 1 mg/day, increasing by 0.5 mg/day every 2-4 weeks. The drug is usually effective at a dose of 3 mg/day or less. Once a patient’s symptoms become clear or almost clear, the patient is maintained on that dose for another 3-4 months, then tapered by 0.5 mg/day every 2-4 weeks.

“In 35 years of seeing a new patient on average every week or two, I’ve had only five patients with one recurrence and one patient with two recurrences. All six responded to repeat therapy,” Dr. Koo said.

Side effects at these low doses are “very rare,” he added. Diphenhydramine (Benadryl) at 25 mg up to four times daily is effective for complaints of stiffness or restlessness. Prolongation of the QT interval is a potential concern, but Dr. Koo has never encountered it despite routinely ordering ECGs for patients on pimozide with known heart disease or who are over age 50.

When a patient can’t tolerate pimozide, Dr. Koo’s second-line antipsychotic for DI is low-dose risperidone (Risperdal), which is also highly effective.

Dr. Lepping noted that the European situation is different. There, unlike in the United States, pimozide has regulatory approval as an antipsychotic, so it loses the advantage of being an under-the-radar neuroleptic. His go-to medication is the first-generation antipsychotic sulpiride (Dogmatil), which he finds has a more favorable side effect profile than pimozide, particularly in the elderly. (Sulpiride is not approved in the United States.)

In treating DI, he prefers more dopaminergic-focused antipsychotics over those covering a broader spectrum of receptors. His alternatives to sulpiride include risperidone and olanzapine, atypical antipsychotics. He explains to patients that just as aspirin is used in low doses for its antiplatelet effect and in higher doses for pain relief, these medications can help them feel better at much lower doses than for schizophrenia.

“Once we get some rapport and a trusting relationship going, we normally try to persuade people to basically try something against their better judgment. We know that they don’t believe in it, but you try to get them to at least try something because everything else has failed,” Dr. Lepping explained. “We tell them it’s a condition we have seen before, and we have seen these medications to be useful because they are good for their distress, they help with making them calmer, and they might help with their symptoms. We say, ‘What do you have to lose if you trust us?’

“About 60% of our patients take the medication and almost invariably they all get better,” the psychiatrist said. “The others we either lose to follow-up or they just refuse to take the medication.”

A patient’s first visit to the Liverpool multispecialty DI referral clinic is 1 hour long. “They know that in advance, and we very much stick to that hour. We say to people up front, ‘We have an hour – that’s a lot, but we don’t have more,’ ” he said.

The initial visit is typically followed by two to four 30-minute follow-up visits. Dr. Lepping recommends that when possible, patients with DI should be seen jointly by a psychiatrist and a nonpsychiatrist physician. He finds this approach leads to substantially better clinical outcomes than with a single health care provider.

“If you have two people in the clinic with the patient, when you get really annoyed and your amygdala really starts going, that’s the time when you can then turn to your colleague and say, ‘Oh yes, and Professor Squire, what do you have to say to that?’ So as you see the red mist rising in yourself because you’re getting so exasperated, you have the other person there to take over so you can calm down. And then the other person does the same. That can be really important to deescalate a heated situation,” Dr. Lepping explained.

Roughly 10% of patients with DI have what is termed folie à deux, where the delusion of infestation is shared by another person.

“Anecdotally, I would say those are much more difficult to treat,” said Jason S. Reichenberg, MD, MBA, professor of medicine (dermatology) at the University of Texas at Austin and president of the Ascension Medical Group Texas.

“It’s like getting somebody to quit smoking when everybody else in the house is still smoking. It’s very hard to convince a single family member that they’re wrong when everybody else in their family keeps telling them they’re right,” he said.


Recent advances in DI research

Dr. Lepping and coinvestigators at multispecialist DI clinics in London, Italy, and Moscow reported in an unusually large observational study of 236 affected patients that longer duration of untreated psychosis was associated with significantly worse clinical outcome. It’s a finding consistent with Dr. Koo’s construct of progressive stages of delusionality, and it underscores the need for early treatment.

“Having said that, improvement is still possible, even if people have had quite a long time of untreated psychosis,” Dr. Lepping said. The same study also showed that older age at illness onset was inversely associated with good outcome.

In another study, Dr. Lepping and colleagues reported that substance use involving amphetamines, cocaine, opioids, and other drugs that can cause itch was roughly twice as common in a group of patients with DI compared to the general population. “I highly recommend, if at all possible, a drug screen in suspected DI,” he said.

In a large survey of U.S. and Canadian veterinarians, Dr. Lepping and coinvestigators found that these practitioners not infrequently encountered delusional infestation among pet owners who claimed their dog or cat is infested when it’s not. This is called “delusion by proxy,” and it often leads to unwarranted animal euthanasia. Some of these pet owners claim they, too, are infested, which the investigators termed “double delusional infestation.”

 

MRI studies

Recent structural brain MRI studies support the concept that impaired somatosensory neural networks mediate the delusional symptoms of DI, but not in delusional disorders without somatic content. This was demonstrated in an MRI study by Dr. Lepping and others conducted in 18 patients with DI, 19 others with nonsomatic delusional disorders centered on themes of persecution or jealousy, and 20 healthy volunteers. The DI group had lower gray matter volume in prefrontal, thalamic, striatal, and insular regions of the brain compared to the other two groups.

Of note, mapping of the insula and dorsal striatum indicates they are part of the peripersonal space network, which integrates tactile and visual perceptions involving the area near the body surface. The insula also mediates feelings of pain and disgust.

Some of the same investigators have also recently reported brain MRI evidence specifically of cerebellar dysfunction in patients with DI, who displayed decreased gray matter volume in left lobule VIIa of the cerebellum and increased gray matter volume in bilateral lobule VIIa/crus II compared to patients with non-somatic delusions. This points to a role for impaired cerebellar neural networks related to somatosensory perception in patients with DI but not in those with non-somatic delusions.
 

Delusional infestation: What’s in a name?

Ekbom syndrome. Delusional parasitosis. Morgellons syndrome. These and other terms are increasingly giving way to ‘delusional infestation’ as the preferred moniker for the disorder. That’s in part because the delusional focus in patients with this condition has shifted over time. In the 19th century, for example, affected patients often attributed their infestation to typhus.

In contemporary practice, roughly one-quarter of affected patients think they are infested by small inanimate objects, most commonly fibers or threads emerging from the skin, rather than by parasites, insects, or worms. In a study of 148 consecutive European patients with suspected DI, Dr. Lepping and coinvestigators reported only 35% believed they were infested by parasites.

“The name ‘delusional infestation’ emphasizes the constantly changing pathogens and covers all present and future variations of the theme that are bound to occur,” Dr. Lepping observed.

All speakers reported having no conflicts of interest.

[email protected]

Psychiatrists with expertise in delusional infestation have some advice for dermatologists, infectious disease specialists, and primary care physicians who encounter affected patients: If you want to try to help them, initiate treatment yourself.

“If you see it, try and treat it. These patients are unlikely to agree to see a psychiatrist,” Peter Lepping, MD, said at the Entomology 2020 annual meeting.

Indeed, one of the hallmarks of delusional infestation (DI) is a refusal to even consider referral to a mental health professional, noted Dr. Lepping, a consultation-liaison psychiatrist at Bangor (Wales) University who, together with an infectious disease specialist, codirects one of the world’s few DI multispecialty referral clinics, located at the University of Liverpool School of Tropical Medicine.

That being said, he offered another piece of advice: “Accept that it is not easy to help these patients.”

Dr. Lepping was among a group of distinguished psychiatrists, dermatologists, entomologists, and a neurologist at the annual meeting who participated in a comprehensive session devoted to DI. The experts shared tips on making the diagnosis, establishing the rapport necessary to persuade affected patients to try taking a very-low-dose antipsychotic agent for their delusion, and how to achieve a high rate of therapeutic success. They also highlighted recent research advances in the field, including brain MRI evidence suggesting that impaired somatosensory neural networks mediate symptoms in DI, but not in nonsomatic delusional disorders.


 

COVID-19 pandemic triggers surge in DI

Entomologist Gail E. Ridge, PhD, has taken notes on all of her thousands of consultations with individuals with suspected DI since the late 1990s. A sharp jump in such contacts occurred during the Great Recession of 2008 in conjunction with the widespread social distress of job loss and threatened economic ruin. Now the same thing is happening as the catastrophic COVID-19 pandemic stretches on. Indeed, during the first 8 months of the pandemic she documented 500 interactions involving people with suspected DI. She’s learned to identify the clues, including a chattering mind, defensiveness, physician avoidance, and rigid body tension.

Courtesy Dr. Gale E. Ridge

“They’re fearful of judgment and suggestions of madness. And they’ll pounce on any perceived negativity. I never debunk beliefs; that can immediately backfire. If the medical profession was educated about DI, then many cases could be caught early. I, as the entomologist, and the mental health professionals are often last in line to be seen,” said Dr. Ridge, director of the Insect Information Office at the Connecticut Agricultural Experiment Station in New Haven.

She has noticed a recurring theme in her interactions with these patients: DI often starts with a real underlying medical condition, such as, for example, a cutaneous drug reaction, which over time, progresses to gain a psychiatric component. And she has found that a tipping point often occurs after roughly 6 months of unrelieved symptoms and sensations. Prior to that, affected individuals are concerned about their condition and will seek medical help in a genuine effort to understand what’s going on. They can be redirected. After about 6 months, however, Dr. Ridge has observed “they slide into the rabbit hole of fanaticism and despair.”
 

 

Arriving at the diagnosis

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), DI is classified as a “delusional disorder, somatic type 297.1 F22.” The diagnosis requires that the delusion be present for at least 1 month, criteria for schizophrenia are not met, and the condition cannot be attributed to other medical or neuropsychiatric conditions.

“Many of these people are very high-functioning. I have corporate CEOs who fly in to see me in their private jets. At work, they’re king of their domain. At home, their family is falling apart because of their delusion,” said Dirk M. Elston, MD, professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston.

“These people suffer, and the people around them suffer,” he emphasized.

Dozens of medical conditions can cause intractable itching or biting sensations. Far and away at the top of the medical differential diagnosis is thyroid disease, given its high incidence and frequent presentation with anxiety and itch. Other possibilities that can readily be ruled out via lab tests include substance use – especially involving amphetamine/methamphetamine, cocaine, or opioids – liver or kidney disease, diabetes and other sources of peripheral neuropathy, polycythemia, dermatitis herpetiformis, and pemphigus, Dr. Elston said.

Scott A. Norton, MD, MPH, MSc, a dermatologist and preventive medicine specialist at the Uniformed Services University of the Health Sciences in Bethesda, Md., noted that a diagnosis of DI requires three elements: The presence of abnormal sensations in the skin, a patient’s tenacious conviction that the sensations are caused by an infestation, and a lack of supporting evidence for that conviction.

Taking an accurate medical history can be a challenge in these patients because they are often so guarded. They won’t disclose that they’ve already seen other health care providers, or that they’ve been self-treating with OTC veterinary medicine products, such as high-dose topical or oral ivermectin. They’ll often even deny repeated scratching despite clear evidence to the contrary from the skin exam.

As a dermatologist, Dr. Norton considers his first task to be a search for evidence of an infestation. Scabies is usually the first diagnosis proposed to account for the uncomfortable skin sensations. The presentation can be subtle. While the classic teaching is that the telltale signs of infestation by Sarcoptes scabiei are burrows in the skin and a rash in the web spaces between the fingers, he finds these features are often absent or equivocal.

“I think there are two more reliable presentations of scabies: Check to see if there’s symmetric involvement of the volar or palm side of the wrists; if there isn’t, I’m skeptical of the diagnosis. And every male older than 1 year of age with scabies will have scabies nodules on their genitalia. If the penis, the glans, or the scrotum aren’t involved with the nodules, I discard scabies as a possible diagnosis and look for evidence of other skin conditions that can plausibly explain the sensations and skin lesions, like eczema, contact dermatitis, scalp folliculitis, or dry skin,” he said.

If he can’t find evidence of infestation, he next systematically looks for another dermatologic cause of the patient’s sensations. When that proves fruitless, he tries to determine if there might be a biomedical or neuropsychiatric cause, such as depression, anxiety, schizophrenia, or dementia.

Taking a personal hygiene history is helpful. Patients who believe they have an infestation may bathe or shower three to five times daily with harsh soaps, causing dry, inflamed, itchy and uncomfortable skin.

“Many patients are thrilled to hear the good news that the history, physical examination, and lab tests do not show an infestation and that we have another explanation to account for their unwanted sensations. However, there are some patients who vehemently reject that idea and immediately return to their unwavering, unalterable belief that they are in fact infested. At this point, the possible diagnosis of DI looms large,” the dermatologist said.

Clues suggestive of DI include a patient’s obsessive focus on collecting “specimens” of the offending pathogen in Ziplock bags for assessment during the office visit – “usually a mix of unhelpful household debris and environmental detritus” – and eager presentation of a lengthy and detailed infestation diary, Dr. Norton said.

“Among the most distinctive signs that the patient is detached from reality are the biologically implausible descriptions and explanations of the supposed attacking organism. It’s a fanciful amalgamation of mutable features, behaviors, and life cycles composed of a composite of taxonomically unrelated organisms – for example, fungal hyphae with wings – that shapeshift at will to evade detection,” he said.

Dr. Elston observed that DI skin lesions are typically excoriated, sometimes because of a patient’s systematic use of a sharp object in an effort to dig out the infestation.

“One of the clues is the angularity of the lesion,” the dermatologist noted. “We always say round-to-oval lesions suggest an inside job; angulated lesions suggest an outside job, like fingernail work. There’s often a row of good healing border showing there’s really nothing wrong with wound healing, but a fibrinoid base where the excoriations have occurred. And the lesions are often in various stages of healing.”

Don’t forget neuropathic itch in nondelusional individuals as a potential cause of sensations of infestation and self-injury due to relentless scratching, urged Anne Louise Oaklander, MD, PhD, associate professor of neurology, Harvard Medical School, Boston, who is director of the nerve unit and the neurodiagnostic skin biopsy lab at Massachusetts General Hospital, Boston.

“There’s no one cause of patients’ impressions that they may have insects. Let’s be sympathetic: It is a normal assumption that insects may be present if the skin itches. One problem is that when patients don’t get good medical diagnoses they make up their own explanations, and sometimes these include persistent ideas of infestation. Many of them don’t realize that their scratching is a cause, not a result, of their skin lesions,” said Dr. Oaklander, who has conducted pioneering research on unintentional self-injury due to neuropathic itch accompanied by loss of pain signaling.


 

 

“Rapport first, medication later”

“The office visits are typically difficult to conclude, but skills can be learned and make it much easier to help these people,” Dr. Elston said.

John Koo, MD, emphasized that establishing rapport is “by far” the most important part of managing patients with DI.

“Rapport first, medication later. This may require multiple visits,” said Dr. Koo, professor of dermatology at the University of California, San Francisco, who is a board-certified psychiatrist.

He makes sure he walks into the examination room all smiles and positivity. Patients with DI are eager to expound on their ailment; he lets them talk for a while, then when the timing is right, he actively encourages them to shift their focus away from etiology to treatment.

Dr. Koo and coworkers have described a spectrum of mental fixation in DI ranging from having only crawling and biting sensations, progressing to holding an overvalued idea as to their cause, then on to DSM-5 somatic preoccupation, followed by becoming truly delusional, and finally terminal delusion, where the patient doesn’t care about getting better, but only wants the physician to agree there is an infestation (J Clin Exp Dermatol Res. 2014 Oct. 3. doi: 10.4172/2155-9554.1000241).

“You cannot argue with people with delusions. How you talk to them as a clinician depends on whether they are entirely delusional or not,” he advised. “I cannot agree with their ideation, but I can agree with their misery – and that’s how I make a connection.”

Declining a DI patient’s request for a skin biopsy when it’s obvious there is no infestation can lead to a counterproductive power struggle. Instead, Dr. Koo turns the patient request into an opportunity to form a verbal contract: “I ask, ‘If the result comes back negative, can you be open-minded about the possibility of other etiologies besides parasites?’ ”

As for Dr. Norton, when his schedule shows a patient is coming in for a first visit for a supposed skin infestation, he tells his staff to expect a lengthy session as he works at establishing a good relationship.

“When my patients arrive with bags of specimens, I ask them to select two or three that they’re most confident will have a creature in them. Then I bring a two-headed microscope into the exam room and ask the patient to join me in examining the material. It helps with rapport by showing that I genuinely want to determine if there’s an infestation,” he explained.

He then sends the specimens to a laboratory, which provides a full report of the findings.

In performing a skin biopsy in a patient with suspected DI, Dr. Norton routinely biopsies two sites so the patient can’t claim sampling error when the pathology report comes back with no pathogens or parasites found. Also, he asks the patient to choose biopsy sites with intact skin where he or she believes the infestation exists. There is no point in biopsying excoriated lesions because they often contain snagged textile fibers.

Another rapport-building strategy: “I try to design a treatment regimen that will palliate the uncomfortable sensations and help relieve the patient’s misery while we continue working towards treating those delusions,” Dr. Norton said.

This might entail cutting back to one lukewarm shower per day with gentle or no soap, coupled with moisturizing, oral antihistamines or doxepin for itch, topical corticosteroids for the associated inflammation, and oral or topical antibiotics for any secondary bacterial skin infection.

What he doesn’t recommend as a rapport-building strategy or simply in order to get the patient out of the office is offering a therapeutic trial of an antiparasitic agent. That’s counterproductive. It may reinforce the false belief of infestation, and when the medication doesn’t bring lasting belief, the patient may conclude the infestation is resistant to conventional treatment.

Dr. Koo tells affected patients that he suspects they have Morgellons syndrome. He doesn’t call it DI in their presence.

“These people would not like their condition to be called delusional,” he explained. “Morgellons is a more neutral term. I tell them it’s a mysterious condition, and that what I’m really interested in is in trying to get them out of their misery.”
 

 

Treatment tips

Dr. Koo’s first-line medication for DI is pimozide (Orap), which in the United States has the advantage of being approved only for Tourette syndrome; it’s an antipsychotic without the perceived stigma of a psychiatric indication.

“Many of these patients will not consider taking any medication that has any psychiatric indication,” he noted.

Low-dose pimozide is highly effective, according to Dr. Koo, who recommends starting at 0.5 mg to 1 mg/day, increasing by 0.5 mg/day every 2-4 weeks. The drug is usually effective at a dose of 3 mg/day or less. Once a patient’s symptoms become clear or almost clear, the patient is maintained on that dose for another 3-4 months, then tapered by 0.5 mg/day every 2-4 weeks.

“In 35 years of seeing a new patient on average every week or two, I’ve had only five patients with one recurrence and one patient with two recurrences. All six responded to repeat therapy,” Dr. Koo said.

Side effects at these low doses are “very rare,” he added. Diphenhydramine (Benadryl) at 25 mg up to four times daily is effective for complaints of stiffness or restlessness. Prolongation of the QT interval is a potential concern, but Dr. Koo has never encountered it despite routinely ordering ECGs for patients on pimozide with known heart disease or who are over age 50.

When a patient can’t tolerate pimozide, Dr. Koo’s second-line antipsychotic for DI is low-dose risperidone (Risperdal), which is also highly effective.

Dr. Lepping noted that the European situation is different. There, unlike in the United States, pimozide has regulatory approval as an antipsychotic, so it loses the advantage of being an under-the-radar neuroleptic. His go-to medication is the first-generation antipsychotic sulpiride (Dogmatil), which he finds has a more favorable side effect profile than pimozide, particularly in the elderly. (Sulpiride is not approved in the United States.)

In treating DI, he prefers more dopaminergic-focused antipsychotics over those covering a broader spectrum of receptors. His alternatives to sulpiride include risperidone and olanzapine, atypical antipsychotics. He explains to patients that just as aspirin is used in low doses for its antiplatelet effect and in higher doses for pain relief, these medications can help them feel better at much lower doses than for schizophrenia.

“Once we get some rapport and a trusting relationship going, we normally try to persuade people to basically try something against their better judgment. We know that they don’t believe in it, but you try to get them to at least try something because everything else has failed,” Dr. Lepping explained. “We tell them it’s a condition we have seen before, and we have seen these medications to be useful because they are good for their distress, they help with making them calmer, and they might help with their symptoms. We say, ‘What do you have to lose if you trust us?’

“About 60% of our patients take the medication and almost invariably they all get better,” the psychiatrist said. “The others we either lose to follow-up or they just refuse to take the medication.”

A patient’s first visit to the Liverpool multispecialty DI referral clinic is 1 hour long. “They know that in advance, and we very much stick to that hour. We say to people up front, ‘We have an hour – that’s a lot, but we don’t have more,’ ” he said.

The initial visit is typically followed by two to four 30-minute follow-up visits. Dr. Lepping recommends that when possible, patients with DI should be seen jointly by a psychiatrist and a nonpsychiatrist physician. He finds this approach leads to substantially better clinical outcomes than with a single health care provider.

“If you have two people in the clinic with the patient, when you get really annoyed and your amygdala really starts going, that’s the time when you can then turn to your colleague and say, ‘Oh yes, and Professor Squire, what do you have to say to that?’ So as you see the red mist rising in yourself because you’re getting so exasperated, you have the other person there to take over so you can calm down. And then the other person does the same. That can be really important to deescalate a heated situation,” Dr. Lepping explained.

Roughly 10% of patients with DI have what is termed folie à deux, where the delusion of infestation is shared by another person.

“Anecdotally, I would say those are much more difficult to treat,” said Jason S. Reichenberg, MD, MBA, professor of medicine (dermatology) at the University of Texas at Austin and president of the Ascension Medical Group Texas.

“It’s like getting somebody to quit smoking when everybody else in the house is still smoking. It’s very hard to convince a single family member that they’re wrong when everybody else in their family keeps telling them they’re right,” he said.


Recent advances in DI research

Dr. Lepping and coinvestigators at multispecialist DI clinics in London, Italy, and Moscow reported in an unusually large observational study of 236 affected patients that longer duration of untreated psychosis was associated with significantly worse clinical outcome. It’s a finding consistent with Dr. Koo’s construct of progressive stages of delusionality, and it underscores the need for early treatment.

“Having said that, improvement is still possible, even if people have had quite a long time of untreated psychosis,” Dr. Lepping said. The same study also showed that older age at illness onset was inversely associated with good outcome.

In another study, Dr. Lepping and colleagues reported that substance use involving amphetamines, cocaine, opioids, and other drugs that can cause itch was roughly twice as common in a group of patients with DI compared to the general population. “I highly recommend, if at all possible, a drug screen in suspected DI,” he said.

In a large survey of U.S. and Canadian veterinarians, Dr. Lepping and coinvestigators found that these practitioners not infrequently encountered delusional infestation among pet owners who claimed their dog or cat is infested when it’s not. This is called “delusion by proxy,” and it often leads to unwarranted animal euthanasia. Some of these pet owners claim they, too, are infested, which the investigators termed “double delusional infestation.”

 

MRI studies

Recent structural brain MRI studies support the concept that impaired somatosensory neural networks mediate the delusional symptoms of DI, but not in delusional disorders without somatic content. This was demonstrated in an MRI study by Dr. Lepping and others conducted in 18 patients with DI, 19 others with nonsomatic delusional disorders centered on themes of persecution or jealousy, and 20 healthy volunteers. The DI group had lower gray matter volume in prefrontal, thalamic, striatal, and insular regions of the brain compared to the other two groups.

Of note, mapping of the insula and dorsal striatum indicates they are part of the peripersonal space network, which integrates tactile and visual perceptions involving the area near the body surface. The insula also mediates feelings of pain and disgust.

Some of the same investigators have also recently reported brain MRI evidence specifically of cerebellar dysfunction in patients with DI, who displayed decreased gray matter volume in left lobule VIIa of the cerebellum and increased gray matter volume in bilateral lobule VIIa/crus II compared to patients with non-somatic delusions. This points to a role for impaired cerebellar neural networks related to somatosensory perception in patients with DI but not in those with non-somatic delusions.
 

Delusional infestation: What’s in a name?

Ekbom syndrome. Delusional parasitosis. Morgellons syndrome. These and other terms are increasingly giving way to ‘delusional infestation’ as the preferred moniker for the disorder. That’s in part because the delusional focus in patients with this condition has shifted over time. In the 19th century, for example, affected patients often attributed their infestation to typhus.

In contemporary practice, roughly one-quarter of affected patients think they are infested by small inanimate objects, most commonly fibers or threads emerging from the skin, rather than by parasites, insects, or worms. In a study of 148 consecutive European patients with suspected DI, Dr. Lepping and coinvestigators reported only 35% believed they were infested by parasites.

“The name ‘delusional infestation’ emphasizes the constantly changing pathogens and covers all present and future variations of the theme that are bound to occur,” Dr. Lepping observed.

All speakers reported having no conflicts of interest.

[email protected]

Psychiatrists with expertise in delusional infestation have some advice for dermatologists, infectious disease specialists, and primary care physicians who encounter affected patients: If you want to try to help them, initiate treatment yourself.

“If you see it, try and treat it. These patients are unlikely to agree to see a psychiatrist,” Peter Lepping, MD, said at the Entomology 2020 annual meeting.

Indeed, one of the hallmarks of delusional infestation (DI) is a refusal to even consider referral to a mental health professional, noted Dr. Lepping, a consultation-liaison psychiatrist at Bangor (Wales) University who, together with an infectious disease specialist, codirects one of the world’s few DI multispecialty referral clinics, located at the University of Liverpool School of Tropical Medicine.

That being said, he offered another piece of advice: “Accept that it is not easy to help these patients.”

Dr. Lepping was among a group of distinguished psychiatrists, dermatologists, entomologists, and a neurologist at the annual meeting who participated in a comprehensive session devoted to DI. The experts shared tips on making the diagnosis, establishing the rapport necessary to persuade affected patients to try taking a very-low-dose antipsychotic agent for their delusion, and how to achieve a high rate of therapeutic success. They also highlighted recent research advances in the field, including brain MRI evidence suggesting that impaired somatosensory neural networks mediate symptoms in DI, but not in nonsomatic delusional disorders.


 

COVID-19 pandemic triggers surge in DI

Entomologist Gail E. Ridge, PhD, has taken notes on all of her thousands of consultations with individuals with suspected DI since the late 1990s. A sharp jump in such contacts occurred during the Great Recession of 2008 in conjunction with the widespread social distress of job loss and threatened economic ruin. Now the same thing is happening as the catastrophic COVID-19 pandemic stretches on. Indeed, during the first 8 months of the pandemic she documented 500 interactions involving people with suspected DI. She’s learned to identify the clues, including a chattering mind, defensiveness, physician avoidance, and rigid body tension.

Courtesy Dr. Gale E. Ridge

“They’re fearful of judgment and suggestions of madness. And they’ll pounce on any perceived negativity. I never debunk beliefs; that can immediately backfire. If the medical profession was educated about DI, then many cases could be caught early. I, as the entomologist, and the mental health professionals are often last in line to be seen,” said Dr. Ridge, director of the Insect Information Office at the Connecticut Agricultural Experiment Station in New Haven.

She has noticed a recurring theme in her interactions with these patients: DI often starts with a real underlying medical condition, such as, for example, a cutaneous drug reaction, which over time, progresses to gain a psychiatric component. And she has found that a tipping point often occurs after roughly 6 months of unrelieved symptoms and sensations. Prior to that, affected individuals are concerned about their condition and will seek medical help in a genuine effort to understand what’s going on. They can be redirected. After about 6 months, however, Dr. Ridge has observed “they slide into the rabbit hole of fanaticism and despair.”
 

 

Arriving at the diagnosis

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), DI is classified as a “delusional disorder, somatic type 297.1 F22.” The diagnosis requires that the delusion be present for at least 1 month, criteria for schizophrenia are not met, and the condition cannot be attributed to other medical or neuropsychiatric conditions.

“Many of these people are very high-functioning. I have corporate CEOs who fly in to see me in their private jets. At work, they’re king of their domain. At home, their family is falling apart because of their delusion,” said Dirk M. Elston, MD, professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston.

“These people suffer, and the people around them suffer,” he emphasized.

Dozens of medical conditions can cause intractable itching or biting sensations. Far and away at the top of the medical differential diagnosis is thyroid disease, given its high incidence and frequent presentation with anxiety and itch. Other possibilities that can readily be ruled out via lab tests include substance use – especially involving amphetamine/methamphetamine, cocaine, or opioids – liver or kidney disease, diabetes and other sources of peripheral neuropathy, polycythemia, dermatitis herpetiformis, and pemphigus, Dr. Elston said.

Scott A. Norton, MD, MPH, MSc, a dermatologist and preventive medicine specialist at the Uniformed Services University of the Health Sciences in Bethesda, Md., noted that a diagnosis of DI requires three elements: The presence of abnormal sensations in the skin, a patient’s tenacious conviction that the sensations are caused by an infestation, and a lack of supporting evidence for that conviction.

Taking an accurate medical history can be a challenge in these patients because they are often so guarded. They won’t disclose that they’ve already seen other health care providers, or that they’ve been self-treating with OTC veterinary medicine products, such as high-dose topical or oral ivermectin. They’ll often even deny repeated scratching despite clear evidence to the contrary from the skin exam.

As a dermatologist, Dr. Norton considers his first task to be a search for evidence of an infestation. Scabies is usually the first diagnosis proposed to account for the uncomfortable skin sensations. The presentation can be subtle. While the classic teaching is that the telltale signs of infestation by Sarcoptes scabiei are burrows in the skin and a rash in the web spaces between the fingers, he finds these features are often absent or equivocal.

“I think there are two more reliable presentations of scabies: Check to see if there’s symmetric involvement of the volar or palm side of the wrists; if there isn’t, I’m skeptical of the diagnosis. And every male older than 1 year of age with scabies will have scabies nodules on their genitalia. If the penis, the glans, or the scrotum aren’t involved with the nodules, I discard scabies as a possible diagnosis and look for evidence of other skin conditions that can plausibly explain the sensations and skin lesions, like eczema, contact dermatitis, scalp folliculitis, or dry skin,” he said.

If he can’t find evidence of infestation, he next systematically looks for another dermatologic cause of the patient’s sensations. When that proves fruitless, he tries to determine if there might be a biomedical or neuropsychiatric cause, such as depression, anxiety, schizophrenia, or dementia.

Taking a personal hygiene history is helpful. Patients who believe they have an infestation may bathe or shower three to five times daily with harsh soaps, causing dry, inflamed, itchy and uncomfortable skin.

“Many patients are thrilled to hear the good news that the history, physical examination, and lab tests do not show an infestation and that we have another explanation to account for their unwanted sensations. However, there are some patients who vehemently reject that idea and immediately return to their unwavering, unalterable belief that they are in fact infested. At this point, the possible diagnosis of DI looms large,” the dermatologist said.

Clues suggestive of DI include a patient’s obsessive focus on collecting “specimens” of the offending pathogen in Ziplock bags for assessment during the office visit – “usually a mix of unhelpful household debris and environmental detritus” – and eager presentation of a lengthy and detailed infestation diary, Dr. Norton said.

“Among the most distinctive signs that the patient is detached from reality are the biologically implausible descriptions and explanations of the supposed attacking organism. It’s a fanciful amalgamation of mutable features, behaviors, and life cycles composed of a composite of taxonomically unrelated organisms – for example, fungal hyphae with wings – that shapeshift at will to evade detection,” he said.

Dr. Elston observed that DI skin lesions are typically excoriated, sometimes because of a patient’s systematic use of a sharp object in an effort to dig out the infestation.

“One of the clues is the angularity of the lesion,” the dermatologist noted. “We always say round-to-oval lesions suggest an inside job; angulated lesions suggest an outside job, like fingernail work. There’s often a row of good healing border showing there’s really nothing wrong with wound healing, but a fibrinoid base where the excoriations have occurred. And the lesions are often in various stages of healing.”

Don’t forget neuropathic itch in nondelusional individuals as a potential cause of sensations of infestation and self-injury due to relentless scratching, urged Anne Louise Oaklander, MD, PhD, associate professor of neurology, Harvard Medical School, Boston, who is director of the nerve unit and the neurodiagnostic skin biopsy lab at Massachusetts General Hospital, Boston.

“There’s no one cause of patients’ impressions that they may have insects. Let’s be sympathetic: It is a normal assumption that insects may be present if the skin itches. One problem is that when patients don’t get good medical diagnoses they make up their own explanations, and sometimes these include persistent ideas of infestation. Many of them don’t realize that their scratching is a cause, not a result, of their skin lesions,” said Dr. Oaklander, who has conducted pioneering research on unintentional self-injury due to neuropathic itch accompanied by loss of pain signaling.


 

 

“Rapport first, medication later”

“The office visits are typically difficult to conclude, but skills can be learned and make it much easier to help these people,” Dr. Elston said.

John Koo, MD, emphasized that establishing rapport is “by far” the most important part of managing patients with DI.

“Rapport first, medication later. This may require multiple visits,” said Dr. Koo, professor of dermatology at the University of California, San Francisco, who is a board-certified psychiatrist.

He makes sure he walks into the examination room all smiles and positivity. Patients with DI are eager to expound on their ailment; he lets them talk for a while, then when the timing is right, he actively encourages them to shift their focus away from etiology to treatment.

Dr. Koo and coworkers have described a spectrum of mental fixation in DI ranging from having only crawling and biting sensations, progressing to holding an overvalued idea as to their cause, then on to DSM-5 somatic preoccupation, followed by becoming truly delusional, and finally terminal delusion, where the patient doesn’t care about getting better, but only wants the physician to agree there is an infestation (J Clin Exp Dermatol Res. 2014 Oct. 3. doi: 10.4172/2155-9554.1000241).

“You cannot argue with people with delusions. How you talk to them as a clinician depends on whether they are entirely delusional or not,” he advised. “I cannot agree with their ideation, but I can agree with their misery – and that’s how I make a connection.”

Declining a DI patient’s request for a skin biopsy when it’s obvious there is no infestation can lead to a counterproductive power struggle. Instead, Dr. Koo turns the patient request into an opportunity to form a verbal contract: “I ask, ‘If the result comes back negative, can you be open-minded about the possibility of other etiologies besides parasites?’ ”

As for Dr. Norton, when his schedule shows a patient is coming in for a first visit for a supposed skin infestation, he tells his staff to expect a lengthy session as he works at establishing a good relationship.

“When my patients arrive with bags of specimens, I ask them to select two or three that they’re most confident will have a creature in them. Then I bring a two-headed microscope into the exam room and ask the patient to join me in examining the material. It helps with rapport by showing that I genuinely want to determine if there’s an infestation,” he explained.

He then sends the specimens to a laboratory, which provides a full report of the findings.

In performing a skin biopsy in a patient with suspected DI, Dr. Norton routinely biopsies two sites so the patient can’t claim sampling error when the pathology report comes back with no pathogens or parasites found. Also, he asks the patient to choose biopsy sites with intact skin where he or she believes the infestation exists. There is no point in biopsying excoriated lesions because they often contain snagged textile fibers.

Another rapport-building strategy: “I try to design a treatment regimen that will palliate the uncomfortable sensations and help relieve the patient’s misery while we continue working towards treating those delusions,” Dr. Norton said.

This might entail cutting back to one lukewarm shower per day with gentle or no soap, coupled with moisturizing, oral antihistamines or doxepin for itch, topical corticosteroids for the associated inflammation, and oral or topical antibiotics for any secondary bacterial skin infection.

What he doesn’t recommend as a rapport-building strategy or simply in order to get the patient out of the office is offering a therapeutic trial of an antiparasitic agent. That’s counterproductive. It may reinforce the false belief of infestation, and when the medication doesn’t bring lasting belief, the patient may conclude the infestation is resistant to conventional treatment.

Dr. Koo tells affected patients that he suspects they have Morgellons syndrome. He doesn’t call it DI in their presence.

“These people would not like their condition to be called delusional,” he explained. “Morgellons is a more neutral term. I tell them it’s a mysterious condition, and that what I’m really interested in is in trying to get them out of their misery.”
 

 

Treatment tips

Dr. Koo’s first-line medication for DI is pimozide (Orap), which in the United States has the advantage of being approved only for Tourette syndrome; it’s an antipsychotic without the perceived stigma of a psychiatric indication.

“Many of these patients will not consider taking any medication that has any psychiatric indication,” he noted.

Low-dose pimozide is highly effective, according to Dr. Koo, who recommends starting at 0.5 mg to 1 mg/day, increasing by 0.5 mg/day every 2-4 weeks. The drug is usually effective at a dose of 3 mg/day or less. Once a patient’s symptoms become clear or almost clear, the patient is maintained on that dose for another 3-4 months, then tapered by 0.5 mg/day every 2-4 weeks.

“In 35 years of seeing a new patient on average every week or two, I’ve had only five patients with one recurrence and one patient with two recurrences. All six responded to repeat therapy,” Dr. Koo said.

Side effects at these low doses are “very rare,” he added. Diphenhydramine (Benadryl) at 25 mg up to four times daily is effective for complaints of stiffness or restlessness. Prolongation of the QT interval is a potential concern, but Dr. Koo has never encountered it despite routinely ordering ECGs for patients on pimozide with known heart disease or who are over age 50.

When a patient can’t tolerate pimozide, Dr. Koo’s second-line antipsychotic for DI is low-dose risperidone (Risperdal), which is also highly effective.

Dr. Lepping noted that the European situation is different. There, unlike in the United States, pimozide has regulatory approval as an antipsychotic, so it loses the advantage of being an under-the-radar neuroleptic. His go-to medication is the first-generation antipsychotic sulpiride (Dogmatil), which he finds has a more favorable side effect profile than pimozide, particularly in the elderly. (Sulpiride is not approved in the United States.)

In treating DI, he prefers more dopaminergic-focused antipsychotics over those covering a broader spectrum of receptors. His alternatives to sulpiride include risperidone and olanzapine, atypical antipsychotics. He explains to patients that just as aspirin is used in low doses for its antiplatelet effect and in higher doses for pain relief, these medications can help them feel better at much lower doses than for schizophrenia.

“Once we get some rapport and a trusting relationship going, we normally try to persuade people to basically try something against their better judgment. We know that they don’t believe in it, but you try to get them to at least try something because everything else has failed,” Dr. Lepping explained. “We tell them it’s a condition we have seen before, and we have seen these medications to be useful because they are good for their distress, they help with making them calmer, and they might help with their symptoms. We say, ‘What do you have to lose if you trust us?’

“About 60% of our patients take the medication and almost invariably they all get better,” the psychiatrist said. “The others we either lose to follow-up or they just refuse to take the medication.”

A patient’s first visit to the Liverpool multispecialty DI referral clinic is 1 hour long. “They know that in advance, and we very much stick to that hour. We say to people up front, ‘We have an hour – that’s a lot, but we don’t have more,’ ” he said.

The initial visit is typically followed by two to four 30-minute follow-up visits. Dr. Lepping recommends that when possible, patients with DI should be seen jointly by a psychiatrist and a nonpsychiatrist physician. He finds this approach leads to substantially better clinical outcomes than with a single health care provider.

“If you have two people in the clinic with the patient, when you get really annoyed and your amygdala really starts going, that’s the time when you can then turn to your colleague and say, ‘Oh yes, and Professor Squire, what do you have to say to that?’ So as you see the red mist rising in yourself because you’re getting so exasperated, you have the other person there to take over so you can calm down. And then the other person does the same. That can be really important to deescalate a heated situation,” Dr. Lepping explained.

Roughly 10% of patients with DI have what is termed folie à deux, where the delusion of infestation is shared by another person.

“Anecdotally, I would say those are much more difficult to treat,” said Jason S. Reichenberg, MD, MBA, professor of medicine (dermatology) at the University of Texas at Austin and president of the Ascension Medical Group Texas.

“It’s like getting somebody to quit smoking when everybody else in the house is still smoking. It’s very hard to convince a single family member that they’re wrong when everybody else in their family keeps telling them they’re right,” he said.


Recent advances in DI research

Dr. Lepping and coinvestigators at multispecialist DI clinics in London, Italy, and Moscow reported in an unusually large observational study of 236 affected patients that longer duration of untreated psychosis was associated with significantly worse clinical outcome. It’s a finding consistent with Dr. Koo’s construct of progressive stages of delusionality, and it underscores the need for early treatment.

“Having said that, improvement is still possible, even if people have had quite a long time of untreated psychosis,” Dr. Lepping said. The same study also showed that older age at illness onset was inversely associated with good outcome.

In another study, Dr. Lepping and colleagues reported that substance use involving amphetamines, cocaine, opioids, and other drugs that can cause itch was roughly twice as common in a group of patients with DI compared to the general population. “I highly recommend, if at all possible, a drug screen in suspected DI,” he said.

In a large survey of U.S. and Canadian veterinarians, Dr. Lepping and coinvestigators found that these practitioners not infrequently encountered delusional infestation among pet owners who claimed their dog or cat is infested when it’s not. This is called “delusion by proxy,” and it often leads to unwarranted animal euthanasia. Some of these pet owners claim they, too, are infested, which the investigators termed “double delusional infestation.”

 

MRI studies

Recent structural brain MRI studies support the concept that impaired somatosensory neural networks mediate the delusional symptoms of DI, but not in delusional disorders without somatic content. This was demonstrated in an MRI study by Dr. Lepping and others conducted in 18 patients with DI, 19 others with nonsomatic delusional disorders centered on themes of persecution or jealousy, and 20 healthy volunteers. The DI group had lower gray matter volume in prefrontal, thalamic, striatal, and insular regions of the brain compared to the other two groups.

Of note, mapping of the insula and dorsal striatum indicates they are part of the peripersonal space network, which integrates tactile and visual perceptions involving the area near the body surface. The insula also mediates feelings of pain and disgust.

Some of the same investigators have also recently reported brain MRI evidence specifically of cerebellar dysfunction in patients with DI, who displayed decreased gray matter volume in left lobule VIIa of the cerebellum and increased gray matter volume in bilateral lobule VIIa/crus II compared to patients with non-somatic delusions. This points to a role for impaired cerebellar neural networks related to somatosensory perception in patients with DI but not in those with non-somatic delusions.
 

Delusional infestation: What’s in a name?

Ekbom syndrome. Delusional parasitosis. Morgellons syndrome. These and other terms are increasingly giving way to ‘delusional infestation’ as the preferred moniker for the disorder. That’s in part because the delusional focus in patients with this condition has shifted over time. In the 19th century, for example, affected patients often attributed their infestation to typhus.

In contemporary practice, roughly one-quarter of affected patients think they are infested by small inanimate objects, most commonly fibers or threads emerging from the skin, rather than by parasites, insects, or worms. In a study of 148 consecutive European patients with suspected DI, Dr. Lepping and coinvestigators reported only 35% believed they were infested by parasites.

“The name ‘delusional infestation’ emphasizes the constantly changing pathogens and covers all present and future variations of the theme that are bound to occur,” Dr. Lepping observed.

All speakers reported having no conflicts of interest.

[email protected]

To the Editor:

Hailey-Hailey disease (HHD), or familial benign chronic pemphigus, is a genetic disorder caused by an autosomal-dominant mutation in ATPase secretory pathway Ca²⁺ transporting 1 gene, ATP2C1, which disrupts intracellular calcium signaling and blocks synthesis of junctional proteins required for cell-cell adhesion.^1,2 As a result, patients develop acantholysis of the suprabasilar epidermis resulting in chronic flaccid blisters and erosions, particularly in intertriginous areas.³ Patients often report associated itching, pain, and burning, and they frequently present with secondary polymicrobial infections.⁴ Although HHD is genetic, patients may present without a family history due to variable expressivity and sporadic germline mutations.⁵ Therapeutic options are numerous, and patients may attempt many treatments before a benefit is observed.⁴ Local disease improvement was noted in a case series of 3 patients treated with electron beam radiotherapy with no disease recurrence in treated sites at 38, 33, and 9 months’ follow-up.⁶ Herein, we present a case of HHD refractory to numerous prior therapies that was successfully treated with electron beam radiotherapy, highlighting the potential role for palliative radiotherapy in select refractory cases of HHD.

A 35-year-old woman with a 7-year of history of HHD presented with severe recalcitrant disease including extensive erosive patches and plaques in the intertriginous areas of the bilateral axillae, groin, and inframammary folds (Figure 1). The skin eruptions first appeared at 28 years of age after her last pregnancy and continued as painful blistering that worsened with each menstrual cycle. Initially the affected desquamated skin would heal between menstrual cycles, but large areas of desquamation remained unhealed in the groin and inframammary regions throughout her full menstrual cycles by the time of referral. Family history included 4 family members with HHD: 2 aunts, an uncle, and a cousin on the paternal side of her family. Over a 7-year period, treatment with clobetasol cream, clindamycin gel, tacrolimus ointment, doxycycline, dapsone, cyclosporine, methotrexate, etanercept, isotretinoin, and prednisone (15 mg every other day) all failed. Most recently, axillary abobotulinumtoxinA injections were attempted but failed. She had been prednisone dependent for more than 1 year. Due to the ongoing refractory disease, she was referred to radiation oncology to discuss radiotherapy treatment options.

At the time of presentation to the radiation oncology clinic, she continued to have extensive involvement of the intertriginous areas as well as involvement of the right neck at sites of skin chafing from clothing. Consistent with the limited available evidence, a dose of 20 Gy in 10 fractions was first prescribed to the axillae to assess response in the event of radiosensitivity, resulting in brisk desquamation. The conventional fractionation of 2 Gy per fraction allowed for assessment of response/tolerance and the opportunity to stop the treatment in the unlikely event of a severe skin reaction. Her skin tolerated treatment well with slight dryness and mild irritation that was less severe than the typical HHD flares. Concurrently with the axillary radiotherapy, we delivered a trial of low-level laser therapy to areas of severe disease in both inguinal regions in the hope that it could be used instead of radiotherapy to avoid any associated risks of radiation. Low-level laser therapy was administered with a light-emitting diode cluster probe at 2.5 Hz for 1 minute to 2 sites in each inguinal area daily for a total of 10 treatments. Unfortunately, this therapy temporarily exacerbated exudation present in the skin before it resolved to its pretreatment state with no improvement.

One month after treatment she had total resolution of the erosive patches and plaques with mild residual hyperpigmentation in the axillae, establishing that radiation therapy was reasonably effective. To lower the total radiation dose and decrease the risk of radiation-induced malignancy, we treated the bilateral groin and the inframammary region with a treatment schedule of 8 Gy in 2 fractions at a higher dose of 4 Gy per fraction instead of 2 Gy. At 12 days posttreatment, she had a dramatic response in the groin and a mixed response in the inframammary region, with a focus that had not yet regressed. Given the dramatic response in the treated sites, the patient requested treatment to the right side of the neck. Thus, we treated this area with a similar 8 Gy in 2 fractions, and an additional 6 Gy in 2 fractions boost was added to the slow responding focus in the inframammary fold for a total of 14 Gy in 4 fractions. The patient tolerated all treatments well with mild grade 1 skin irritation that was unlike the blistering of the typical HHD flares. Two months following completion of the first course of radiotherapy to the axillae and 2 weeks from the most recent course, she tapered off her prednisone regimen (15 mg every other day) but had a relapse of disease with her subsequent menstrual cycles that presented as a blistering skin reaction in the inframammary region, which healed in response to restarting steroids. This flare was less severe than those prior to radiotherapy. At 10 months posttreatment, the patient was free of disease in the neck and axillae (Figure 2). She continued to have relapses in the inframammary region with menstrual cycles and noted new disease in the popliteal regions; however, the relapses were less severe, and her skin had improved more with radiation than any of the prior therapies.

Our experience with low-level laser therapy indicated that it should be completely avoided in HHD. Our patient’s treatment with radiotherapy demonstrated excellent short-term responses in areas of pemphigus but later proved to be a mixed response with further follow-up including a mild posttreatment flare of the inframammary region that responded to steroids and new popliteal region involvement. As summarized in the Table, earlier reports of radiotherapy for the treatment of HHD have yielded varied results.^6-8 The mixed response seen in our patient suggests that response to radiotherapy may be site specific, related to underlying inflammation from microbial overgrowth, or a function of the disease severity.

Although the number of reports on radiotherapy in HHD is small, there have been several reports of Darier disease, another acantholytic autosomal-dominant genodermatosis affecting the ATP2A2 gene, successfully treated incidentally with radiation.^9,10 Total skin electron beam therapy also has been employed in the treatment of Darier disease; this patient experienced a severe flare after a relatively low treatment dose that required intensive care monitoring, possibly highlighting the potential radiosensitivity of patients with underlying genodermatoses and cautioning against radiotherapy dose escalation.¹¹ In light of the mixed responses seen, radiation therapy should be used sparingly for severe relapsing cases that have failed a plethora of prior treatments. The risk of second cancer induction is especially of concern when using radiotherapy in a benign disease.¹² We observed excellent initial responses in our patient, both with conventionally fractionated radiotherapy and hypofractionation. The risk of second malignancy induction is a linear function of radiotherapy dose.¹² Thus, utilization of hypofractionated regimens such as 4 Gy times 2 fractions seems most prudent. It remains unclear if further dose de-escalation may yield a similar response, as seen in studies utilizing radiotherapy for other benign disease.^13,14 Overall, given our mixed results with short follow-up, we conclude that the consideration of radiotherapy should be limited to patients with severe recalcitrant HHD.

To the Editor:

Hailey-Hailey disease (HHD), or familial benign chronic pemphigus, is a genetic disorder caused by an autosomal-dominant mutation in ATPase secretory pathway Ca²⁺ transporting 1 gene, ATP2C1, which disrupts intracellular calcium signaling and blocks synthesis of junctional proteins required for cell-cell adhesion.^1,2 As a result, patients develop acantholysis of the suprabasilar epidermis resulting in chronic flaccid blisters and erosions, particularly in intertriginous areas.³ Patients often report associated itching, pain, and burning, and they frequently present with secondary polymicrobial infections.⁴ Although HHD is genetic, patients may present without a family history due to variable expressivity and sporadic germline mutations.⁵ Therapeutic options are numerous, and patients may attempt many treatments before a benefit is observed.⁴ Local disease improvement was noted in a case series of 3 patients treated with electron beam radiotherapy with no disease recurrence in treated sites at 38, 33, and 9 months’ follow-up.⁶ Herein, we present a case of HHD refractory to numerous prior therapies that was successfully treated with electron beam radiotherapy, highlighting the potential role for palliative radiotherapy in select refractory cases of HHD.

A 35-year-old woman with a 7-year of history of HHD presented with severe recalcitrant disease including extensive erosive patches and plaques in the intertriginous areas of the bilateral axillae, groin, and inframammary folds (Figure 1). The skin eruptions first appeared at 28 years of age after her last pregnancy and continued as painful blistering that worsened with each menstrual cycle. Initially the affected desquamated skin would heal between menstrual cycles, but large areas of desquamation remained unhealed in the groin and inframammary regions throughout her full menstrual cycles by the time of referral. Family history included 4 family members with HHD: 2 aunts, an uncle, and a cousin on the paternal side of her family. Over a 7-year period, treatment with clobetasol cream, clindamycin gel, tacrolimus ointment, doxycycline, dapsone, cyclosporine, methotrexate, etanercept, isotretinoin, and prednisone (15 mg every other day) all failed. Most recently, axillary abobotulinumtoxinA injections were attempted but failed. She had been prednisone dependent for more than 1 year. Due to the ongoing refractory disease, she was referred to radiation oncology to discuss radiotherapy treatment options.

At the time of presentation to the radiation oncology clinic, she continued to have extensive involvement of the intertriginous areas as well as involvement of the right neck at sites of skin chafing from clothing. Consistent with the limited available evidence, a dose of 20 Gy in 10 fractions was first prescribed to the axillae to assess response in the event of radiosensitivity, resulting in brisk desquamation. The conventional fractionation of 2 Gy per fraction allowed for assessment of response/tolerance and the opportunity to stop the treatment in the unlikely event of a severe skin reaction. Her skin tolerated treatment well with slight dryness and mild irritation that was less severe than the typical HHD flares. Concurrently with the axillary radiotherapy, we delivered a trial of low-level laser therapy to areas of severe disease in both inguinal regions in the hope that it could be used instead of radiotherapy to avoid any associated risks of radiation. Low-level laser therapy was administered with a light-emitting diode cluster probe at 2.5 Hz for 1 minute to 2 sites in each inguinal area daily for a total of 10 treatments. Unfortunately, this therapy temporarily exacerbated exudation present in the skin before it resolved to its pretreatment state with no improvement.

One month after treatment she had total resolution of the erosive patches and plaques with mild residual hyperpigmentation in the axillae, establishing that radiation therapy was reasonably effective. To lower the total radiation dose and decrease the risk of radiation-induced malignancy, we treated the bilateral groin and the inframammary region with a treatment schedule of 8 Gy in 2 fractions at a higher dose of 4 Gy per fraction instead of 2 Gy. At 12 days posttreatment, she had a dramatic response in the groin and a mixed response in the inframammary region, with a focus that had not yet regressed. Given the dramatic response in the treated sites, the patient requested treatment to the right side of the neck. Thus, we treated this area with a similar 8 Gy in 2 fractions, and an additional 6 Gy in 2 fractions boost was added to the slow responding focus in the inframammary fold for a total of 14 Gy in 4 fractions. The patient tolerated all treatments well with mild grade 1 skin irritation that was unlike the blistering of the typical HHD flares. Two months following completion of the first course of radiotherapy to the axillae and 2 weeks from the most recent course, she tapered off her prednisone regimen (15 mg every other day) but had a relapse of disease with her subsequent menstrual cycles that presented as a blistering skin reaction in the inframammary region, which healed in response to restarting steroids. This flare was less severe than those prior to radiotherapy. At 10 months posttreatment, the patient was free of disease in the neck and axillae (Figure 2). She continued to have relapses in the inframammary region with menstrual cycles and noted new disease in the popliteal regions; however, the relapses were less severe, and her skin had improved more with radiation than any of the prior therapies.

Our experience with low-level laser therapy indicated that it should be completely avoided in HHD. Our patient’s treatment with radiotherapy demonstrated excellent short-term responses in areas of pemphigus but later proved to be a mixed response with further follow-up including a mild posttreatment flare of the inframammary region that responded to steroids and new popliteal region involvement. As summarized in the Table, earlier reports of radiotherapy for the treatment of HHD have yielded varied results.^6-8 The mixed response seen in our patient suggests that response to radiotherapy may be site specific, related to underlying inflammation from microbial overgrowth, or a function of the disease severity.

Although the number of reports on radiotherapy in HHD is small, there have been several reports of Darier disease, another acantholytic autosomal-dominant genodermatosis affecting the ATP2A2 gene, successfully treated incidentally with radiation.^9,10 Total skin electron beam therapy also has been employed in the treatment of Darier disease; this patient experienced a severe flare after a relatively low treatment dose that required intensive care monitoring, possibly highlighting the potential radiosensitivity of patients with underlying genodermatoses and cautioning against radiotherapy dose escalation.¹¹ In light of the mixed responses seen, radiation therapy should be used sparingly for severe relapsing cases that have failed a plethora of prior treatments. The risk of second cancer induction is especially of concern when using radiotherapy in a benign disease.¹² We observed excellent initial responses in our patient, both with conventionally fractionated radiotherapy and hypofractionation. The risk of second malignancy induction is a linear function of radiotherapy dose.¹² Thus, utilization of hypofractionated regimens such as 4 Gy times 2 fractions seems most prudent. It remains unclear if further dose de-escalation may yield a similar response, as seen in studies utilizing radiotherapy for other benign disease.^13,14 Overall, given our mixed results with short follow-up, we conclude that the consideration of radiotherapy should be limited to patients with severe recalcitrant HHD.

To the Editor:

Hailey-Hailey disease (HHD), or familial benign chronic pemphigus, is a genetic disorder caused by an autosomal-dominant mutation in ATPase secretory pathway Ca²⁺ transporting 1 gene, ATP2C1, which disrupts intracellular calcium signaling and blocks synthesis of junctional proteins required for cell-cell adhesion.^1,2 As a result, patients develop acantholysis of the suprabasilar epidermis resulting in chronic flaccid blisters and erosions, particularly in intertriginous areas.³ Patients often report associated itching, pain, and burning, and they frequently present with secondary polymicrobial infections.⁴ Although HHD is genetic, patients may present without a family history due to variable expressivity and sporadic germline mutations.⁵ Therapeutic options are numerous, and patients may attempt many treatments before a benefit is observed.⁴ Local disease improvement was noted in a case series of 3 patients treated with electron beam radiotherapy with no disease recurrence in treated sites at 38, 33, and 9 months’ follow-up.⁶ Herein, we present a case of HHD refractory to numerous prior therapies that was successfully treated with electron beam radiotherapy, highlighting the potential role for palliative radiotherapy in select refractory cases of HHD.

A 35-year-old woman with a 7-year of history of HHD presented with severe recalcitrant disease including extensive erosive patches and plaques in the intertriginous areas of the bilateral axillae, groin, and inframammary folds (Figure 1). The skin eruptions first appeared at 28 years of age after her last pregnancy and continued as painful blistering that worsened with each menstrual cycle. Initially the affected desquamated skin would heal between menstrual cycles, but large areas of desquamation remained unhealed in the groin and inframammary regions throughout her full menstrual cycles by the time of referral. Family history included 4 family members with HHD: 2 aunts, an uncle, and a cousin on the paternal side of her family. Over a 7-year period, treatment with clobetasol cream, clindamycin gel, tacrolimus ointment, doxycycline, dapsone, cyclosporine, methotrexate, etanercept, isotretinoin, and prednisone (15 mg every other day) all failed. Most recently, axillary abobotulinumtoxinA injections were attempted but failed. She had been prednisone dependent for more than 1 year. Due to the ongoing refractory disease, she was referred to radiation oncology to discuss radiotherapy treatment options.

At the time of presentation to the radiation oncology clinic, she continued to have extensive involvement of the intertriginous areas as well as involvement of the right neck at sites of skin chafing from clothing. Consistent with the limited available evidence, a dose of 20 Gy in 10 fractions was first prescribed to the axillae to assess response in the event of radiosensitivity, resulting in brisk desquamation. The conventional fractionation of 2 Gy per fraction allowed for assessment of response/tolerance and the opportunity to stop the treatment in the unlikely event of a severe skin reaction. Her skin tolerated treatment well with slight dryness and mild irritation that was less severe than the typical HHD flares. Concurrently with the axillary radiotherapy, we delivered a trial of low-level laser therapy to areas of severe disease in both inguinal regions in the hope that it could be used instead of radiotherapy to avoid any associated risks of radiation. Low-level laser therapy was administered with a light-emitting diode cluster probe at 2.5 Hz for 1 minute to 2 sites in each inguinal area daily for a total of 10 treatments. Unfortunately, this therapy temporarily exacerbated exudation present in the skin before it resolved to its pretreatment state with no improvement.

One month after treatment she had total resolution of the erosive patches and plaques with mild residual hyperpigmentation in the axillae, establishing that radiation therapy was reasonably effective. To lower the total radiation dose and decrease the risk of radiation-induced malignancy, we treated the bilateral groin and the inframammary region with a treatment schedule of 8 Gy in 2 fractions at a higher dose of 4 Gy per fraction instead of 2 Gy. At 12 days posttreatment, she had a dramatic response in the groin and a mixed response in the inframammary region, with a focus that had not yet regressed. Given the dramatic response in the treated sites, the patient requested treatment to the right side of the neck. Thus, we treated this area with a similar 8 Gy in 2 fractions, and an additional 6 Gy in 2 fractions boost was added to the slow responding focus in the inframammary fold for a total of 14 Gy in 4 fractions. The patient tolerated all treatments well with mild grade 1 skin irritation that was unlike the blistering of the typical HHD flares. Two months following completion of the first course of radiotherapy to the axillae and 2 weeks from the most recent course, she tapered off her prednisone regimen (15 mg every other day) but had a relapse of disease with her subsequent menstrual cycles that presented as a blistering skin reaction in the inframammary region, which healed in response to restarting steroids. This flare was less severe than those prior to radiotherapy. At 10 months posttreatment, the patient was free of disease in the neck and axillae (Figure 2). She continued to have relapses in the inframammary region with menstrual cycles and noted new disease in the popliteal regions; however, the relapses were less severe, and her skin had improved more with radiation than any of the prior therapies.

Our experience with low-level laser therapy indicated that it should be completely avoided in HHD. Our patient’s treatment with radiotherapy demonstrated excellent short-term responses in areas of pemphigus but later proved to be a mixed response with further follow-up including a mild posttreatment flare of the inframammary region that responded to steroids and new popliteal region involvement. As summarized in the Table, earlier reports of radiotherapy for the treatment of HHD have yielded varied results.^6-8 The mixed response seen in our patient suggests that response to radiotherapy may be site specific, related to underlying inflammation from microbial overgrowth, or a function of the disease severity.

Although the number of reports on radiotherapy in HHD is small, there have been several reports of Darier disease, another acantholytic autosomal-dominant genodermatosis affecting the ATP2A2 gene, successfully treated incidentally with radiation.^9,10 Total skin electron beam therapy also has been employed in the treatment of Darier disease; this patient experienced a severe flare after a relatively low treatment dose that required intensive care monitoring, possibly highlighting the potential radiosensitivity of patients with underlying genodermatoses and cautioning against radiotherapy dose escalation.¹¹ In light of the mixed responses seen, radiation therapy should be used sparingly for severe relapsing cases that have failed a plethora of prior treatments. The risk of second cancer induction is especially of concern when using radiotherapy in a benign disease.¹² We observed excellent initial responses in our patient, both with conventionally fractionated radiotherapy and hypofractionation. The risk of second malignancy induction is a linear function of radiotherapy dose.¹² Thus, utilization of hypofractionated regimens such as 4 Gy times 2 fractions seems most prudent. It remains unclear if further dose de-escalation may yield a similar response, as seen in studies utilizing radiotherapy for other benign disease.^13,14 Overall, given our mixed results with short follow-up, we conclude that the consideration of radiotherapy should be limited to patients with severe recalcitrant HHD.

Afternoon napping was associated with better cognition in an older Chinese population, according to a new study in General Psychiatry.

The findings add to those seen in other observational studies showing afternoon napping promotes cognitive function, said the authors of the paper, published in General Psychiatry.

“The prevalence of afternoon napping has been increasing in older adults much more than in younger individuals,” wrote Han Cai, MS, of the department of geriatrics at The Fourth People’s Hospital of Wuhu, Anhui, China, and coauthors. “The elderly individuals who took afternoon naps showed significantly higher cognitive performance compared with those who did not nap.”

The researchers enrolled 2,214 people in the study – all Han Chinese and aged 60 or older. Afternoon napping was considered any period of inactivity of at least 5 minutes but less than 2 hours after lunch and outside of the person’s main sleep schedule. Those who reported ever napping – 1,534 subjects – were included in the napping group, and the others – 680 – in the nonnapping group. Patients with major physical conditions were excluded.

The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Neuropsychological Test Battery (NTB) were used to measure cognitive function, and 739 patients agreed to blood tests for lipid values.

The average total MMSE score was higher for the napping group at 25.3 points out of 30, than for the nonnapping group, at 24.56 (P = .003). Those in the napping group also had significantly higher scores in the orientation portion of the MoCA test, at 5.55 out of 6 points, compared with 5.41 for the nonnapping group (P = .006).

Those in the napping group scored significantly higher on the digit span and language fluency parts of the Neuropsychological Test Battery (P = .009 and .020, respectively).

Dementia was assessed with face-to-face visits with clinicians, but diagnoses of dementia were not different between the groups.

Triglycerides were found to be higher – though still in the normal range – in the napping group compared with the nonnapping group, 1.80 mmol/L to 1.75 mmol/L, the researchers found (P = .001). No differences were seen for HDL or LDL cholesterol levels, or in hypertension or diabetes, the researchers reported.

The authors noted that inflammation is likely an important feature in the relationship between napping and cognitive function. Inflammatory cytokines have been found to play a role in sleep disorders, and strong inflammatory responses can lead to adverse events, including cognitive impairment.

“Sleep is known to be a regulator of the immune response that counters these inflammatory mediators, whereas napping, in particular, is thought to be an evolved response to inflammation,” they said.

The average age of patients in the napping group was 72.8 years, slightly older than those in the nonnapping group at 71.3 years, and this was a significant difference (P = .016).

The researchers acknowledged that the study “could not show direct causality of napping, whether beneficial or harmful,” and that “a lack of detailed information regarding napping duration ... also limited the description of napping status.”

Junxin Li, PhD, RN, assistant professor at Johns Hopkins School of Nursing, Baltimore, who has studied napping and cognition, said that previous research generally supports a U-shaped relationship between napping and mental acuity, with shorter or medium-length naps benefiting cognition and no naps or naps that are too long being detrimental.

“This study looked at no nap versus naps of less than 2 hours and may not be able to capture this potential U-shaped association,” she said.

For clinicians, the duration, timing, frequency, and purpose of naps are important factors in making recommendations to patients, she said.

“For example, timing – napping in the early evening close to older adult’s bedtime may delay their bedtime and interfere with their nighttime sleep quality. Taking naps after lunchtime is hypothesized to provide the most therapeutic values to the health and usually recommended,” she said. Regular napping is better than “randomly dozing off,” Dr. Li added.

There are also cultural considerations – in east Asia, napping tends to be considered part of a healthy lifestyle, while in western countries it is not – and this could impact napping behaviors and how these behaviors affect cognition, she said.

Phyllis C. Zee, MD, PhD, director of the Center for Circadian and Sleep Medicine at the Northwestern University, Chicago, said the results are consistent with early cross-sectional studies that showed that regular, scheduled naps in the afternoon were associated with positive cognitive performance and lower cardiometabolic disease risk.

Dr. Zee noted that it’s important to recognize that the positive data are associated with naps that are planned, while older adults napping because of excess sleepiness are at a higher risk for cognitive impairment and other health issues.

The study authors, Dr. Li, and Dr. Zee reported no relevant financial disclosures.

Afternoon napping was associated with better cognition in an older Chinese population, according to a new study in General Psychiatry.

The findings add to those seen in other observational studies showing afternoon napping promotes cognitive function, said the authors of the paper, published in General Psychiatry.

“The prevalence of afternoon napping has been increasing in older adults much more than in younger individuals,” wrote Han Cai, MS, of the department of geriatrics at The Fourth People’s Hospital of Wuhu, Anhui, China, and coauthors. “The elderly individuals who took afternoon naps showed significantly higher cognitive performance compared with those who did not nap.”

The researchers enrolled 2,214 people in the study – all Han Chinese and aged 60 or older. Afternoon napping was considered any period of inactivity of at least 5 minutes but less than 2 hours after lunch and outside of the person’s main sleep schedule. Those who reported ever napping – 1,534 subjects – were included in the napping group, and the others – 680 – in the nonnapping group. Patients with major physical conditions were excluded.

The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Neuropsychological Test Battery (NTB) were used to measure cognitive function, and 739 patients agreed to blood tests for lipid values.

The average total MMSE score was higher for the napping group at 25.3 points out of 30, than for the nonnapping group, at 24.56 (P = .003). Those in the napping group also had significantly higher scores in the orientation portion of the MoCA test, at 5.55 out of 6 points, compared with 5.41 for the nonnapping group (P = .006).

Those in the napping group scored significantly higher on the digit span and language fluency parts of the Neuropsychological Test Battery (P = .009 and .020, respectively).

Dementia was assessed with face-to-face visits with clinicians, but diagnoses of dementia were not different between the groups.

Triglycerides were found to be higher – though still in the normal range – in the napping group compared with the nonnapping group, 1.80 mmol/L to 1.75 mmol/L, the researchers found (P = .001). No differences were seen for HDL or LDL cholesterol levels, or in hypertension or diabetes, the researchers reported.

The authors noted that inflammation is likely an important feature in the relationship between napping and cognitive function. Inflammatory cytokines have been found to play a role in sleep disorders, and strong inflammatory responses can lead to adverse events, including cognitive impairment.

“Sleep is known to be a regulator of the immune response that counters these inflammatory mediators, whereas napping, in particular, is thought to be an evolved response to inflammation,” they said.

The average age of patients in the napping group was 72.8 years, slightly older than those in the nonnapping group at 71.3 years, and this was a significant difference (P = .016).

The researchers acknowledged that the study “could not show direct causality of napping, whether beneficial or harmful,” and that “a lack of detailed information regarding napping duration ... also limited the description of napping status.”

Junxin Li, PhD, RN, assistant professor at Johns Hopkins School of Nursing, Baltimore, who has studied napping and cognition, said that previous research generally supports a U-shaped relationship between napping and mental acuity, with shorter or medium-length naps benefiting cognition and no naps or naps that are too long being detrimental.

“This study looked at no nap versus naps of less than 2 hours and may not be able to capture this potential U-shaped association,” she said.

For clinicians, the duration, timing, frequency, and purpose of naps are important factors in making recommendations to patients, she said.

“For example, timing – napping in the early evening close to older adult’s bedtime may delay their bedtime and interfere with their nighttime sleep quality. Taking naps after lunchtime is hypothesized to provide the most therapeutic values to the health and usually recommended,” she said. Regular napping is better than “randomly dozing off,” Dr. Li added.

There are also cultural considerations – in east Asia, napping tends to be considered part of a healthy lifestyle, while in western countries it is not – and this could impact napping behaviors and how these behaviors affect cognition, she said.

Phyllis C. Zee, MD, PhD, director of the Center for Circadian and Sleep Medicine at the Northwestern University, Chicago, said the results are consistent with early cross-sectional studies that showed that regular, scheduled naps in the afternoon were associated with positive cognitive performance and lower cardiometabolic disease risk.

Dr. Zee noted that it’s important to recognize that the positive data are associated with naps that are planned, while older adults napping because of excess sleepiness are at a higher risk for cognitive impairment and other health issues.

The study authors, Dr. Li, and Dr. Zee reported no relevant financial disclosures.

Afternoon napping was associated with better cognition in an older Chinese population, according to a new study in General Psychiatry.

The findings add to those seen in other observational studies showing afternoon napping promotes cognitive function, said the authors of the paper, published in General Psychiatry.

“The prevalence of afternoon napping has been increasing in older adults much more than in younger individuals,” wrote Han Cai, MS, of the department of geriatrics at The Fourth People’s Hospital of Wuhu, Anhui, China, and coauthors. “The elderly individuals who took afternoon naps showed significantly higher cognitive performance compared with those who did not nap.”

The researchers enrolled 2,214 people in the study – all Han Chinese and aged 60 or older. Afternoon napping was considered any period of inactivity of at least 5 minutes but less than 2 hours after lunch and outside of the person’s main sleep schedule. Those who reported ever napping – 1,534 subjects – were included in the napping group, and the others – 680 – in the nonnapping group. Patients with major physical conditions were excluded.

The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Neuropsychological Test Battery (NTB) were used to measure cognitive function, and 739 patients agreed to blood tests for lipid values.

The average total MMSE score was higher for the napping group at 25.3 points out of 30, than for the nonnapping group, at 24.56 (P = .003). Those in the napping group also had significantly higher scores in the orientation portion of the MoCA test, at 5.55 out of 6 points, compared with 5.41 for the nonnapping group (P = .006).

Those in the napping group scored significantly higher on the digit span and language fluency parts of the Neuropsychological Test Battery (P = .009 and .020, respectively).

Dementia was assessed with face-to-face visits with clinicians, but diagnoses of dementia were not different between the groups.

Triglycerides were found to be higher – though still in the normal range – in the napping group compared with the nonnapping group, 1.80 mmol/L to 1.75 mmol/L, the researchers found (P = .001). No differences were seen for HDL or LDL cholesterol levels, or in hypertension or diabetes, the researchers reported.

The authors noted that inflammation is likely an important feature in the relationship between napping and cognitive function. Inflammatory cytokines have been found to play a role in sleep disorders, and strong inflammatory responses can lead to adverse events, including cognitive impairment.

“Sleep is known to be a regulator of the immune response that counters these inflammatory mediators, whereas napping, in particular, is thought to be an evolved response to inflammation,” they said.

The average age of patients in the napping group was 72.8 years, slightly older than those in the nonnapping group at 71.3 years, and this was a significant difference (P = .016).

The researchers acknowledged that the study “could not show direct causality of napping, whether beneficial or harmful,” and that “a lack of detailed information regarding napping duration ... also limited the description of napping status.”

Junxin Li, PhD, RN, assistant professor at Johns Hopkins School of Nursing, Baltimore, who has studied napping and cognition, said that previous research generally supports a U-shaped relationship between napping and mental acuity, with shorter or medium-length naps benefiting cognition and no naps or naps that are too long being detrimental.

“This study looked at no nap versus naps of less than 2 hours and may not be able to capture this potential U-shaped association,” she said.

For clinicians, the duration, timing, frequency, and purpose of naps are important factors in making recommendations to patients, she said.

“For example, timing – napping in the early evening close to older adult’s bedtime may delay their bedtime and interfere with their nighttime sleep quality. Taking naps after lunchtime is hypothesized to provide the most therapeutic values to the health and usually recommended,” she said. Regular napping is better than “randomly dozing off,” Dr. Li added.

There are also cultural considerations – in east Asia, napping tends to be considered part of a healthy lifestyle, while in western countries it is not – and this could impact napping behaviors and how these behaviors affect cognition, she said.

Phyllis C. Zee, MD, PhD, director of the Center for Circadian and Sleep Medicine at the Northwestern University, Chicago, said the results are consistent with early cross-sectional studies that showed that regular, scheduled naps in the afternoon were associated with positive cognitive performance and lower cardiometabolic disease risk.

Dr. Zee noted that it’s important to recognize that the positive data are associated with naps that are planned, while older adults napping because of excess sleepiness are at a higher risk for cognitive impairment and other health issues.

The study authors, Dr. Li, and Dr. Zee reported no relevant financial disclosures.

Nutritional dermatoses are classically associated with dietary nutrient deficiencies; however, cutaneous disease as a consequence of nutrient excess often is overlooked. Chronic hyperglycemia and hyperinsulinemia resulting from excess carbohydrate intake may be implicated in a number of cutaneous pathologies, of which every dermatologist should be aware.^1-3

Although diabetic patients exhibit many cutaneous manifestations of excess carbohydrate consumption, the absence of a diagnosis of type 2 diabetes mellitus (T2DM) does not necessarily preclude them.^4-6 Emerging evidence now highlights the development of insulin resistance well before a patient ever meets the diagnostic criteria for T2DM.^7,8 Cutaneous disease can provide early insight into a patient’s glucose tolerance and may be the first sign of metabolic derangement. Prompt recognition of these cutaneous alterations and management of the patient’s underlying systemic disease can improve their quality of life and help prevent severe systemic complications associated with insulin resistance and impaired glucose tolerance.

The aim of this review is to highlight both common and rare cutaneous manifestations associated with the persistent consumption of high glycemic load diets, resultant hyperglycemic and hyperinsulinemic states, and the pathophysiologic mechanisms that underlie them.

Acanthosis Nigricans

Acanthosis nigricans (AN) is a highly prevalent cutaneous finding in individuals with insulin resistance that clinically presents as thickened, hyperpigmented, velvety plaques on the intertriginous and flexural surfaces. The most frequently involved sites include the neck, axillae (Figure), and inframammary and inguinal folds. Black and Hispanic patients most commonly are affected. Although classically associated with T2DM, AN also can be observed in normoglycemic individuals.^7-9 One recent study reported the rate of AN to be 36% in a cohort of middle-aged patients (N=320) with normal fasting blood glucose levels, while the rate of AN in matched patients with hyperglycemia (prediabetes and T2DM) was approximately 50%.⁷ Quantification of insulin resistance was performed using the homeostatic model assessment of insulin resistance index. Interestingly, the specificity for insulin resistance in normoglycemic and hyperglycemic subjects with AN was 85% and 90%, respectively.⁷ These findings suggest that AN may serve as a convenient surrogate marker for subclinical insulin resistance, a conclusion that has been reported in a series of previous studies.^8-10

Although the pathogenesis of AN has not been fully elucidated, it is known that persistently elevated blood glucose triggers continual secretion of insulin and insulinlike growth factor 1 (IGF-1), which results in the overstimulation of insulin and IGF-1 receptors on keratinocytes and dermal fibroblasts through direct and indirect pathways.^11,12 The resultant cellular proliferation can be observed histologically in the forms of orthokeratotic hyperkeratosis and papillomatosis, as occurs in AN.^11,13 Further supporting the association between elevated insulin and AN are reports of AN developing at sites of repeated insulin injection as well as genetic mutations in the insulin receptor resulting in severe AN in children.^14-16

The treatment of AN ultimately focuses on improving glycemic control and reducing insulin resistance through lifestyle modification and pharmacotherapy with agents such as metformin.^11,13 Dermatologic treatment with oral and topical keratolytic agents such as isotretinoin and other retinoids, salicylic acid, urea, or ammonium lactate may be used, but their efficacy generally has been limited.^11,13,17,18

Diabetic Dermopathy

Diabetic dermopathy (DD), commonly known as shin spots, refers to the red-brown, atrophic, circinate macules and patches that often appear on the lower extremities in patients with T2DM. Although the pretibial area is the most frequently involved site, other areas of bony prominence such as the forearms can be affected. The prevalence of DD in the diabetic population can be exceedingly high, with some studies reporting incidence rates greater than 50%, particularly in those with poorly controlled T2DM.^19-21 Interestingly, DD also has been documented in patients without T2DM and has been postulated to be an early sign of insulin resistance.^20,22

 

The pathogenesis of DD remains uncertain, but one proposed mechanism is through microvascular damage caused by hyperglycemia-induced, nonenzymatic glycation, possibly in conjunction with mild trauma, that leads to the deposition of hemosiderin and melanin in the skin.^20,23 A recent study identified increased vascularization of dermopathy lesions when compared with surrounding tissue.²⁴ Subcutaneous nerve ischemia and degeneration secondary to diabetic neuropathy also have been postulated as causative.^20,23 Given the lack of effective therapies and the asymptomatic nature of DD, treatment typically is not pursued. However, DD is associated with other diabetic microvascular complications, including diabetic nephropathy, retinopathy, and neuropathy. For this reason, identification of DD warrants further characterization and management of a patient’s underlying diabetes.^19,20

Scleredema Diabeticorum

Scleredema diabeticorum (SD) refers to the slowly progressive, painless thickening and woody induration of the neck, shoulders, and upper back in individuals with long-standing, poorly controlled diabetes. The condition is almost exclusively seen in the diabetic population, with prevalence rates reported to be as high as 14%.^25-27 Although SD generally is asymptomatic, some individuals may experience restricted mobility and decreased sensation in affected areas.^25,27,28 The diagnosis of SD frequently is missed or ignored clinically. Biopsy can provide diagnostic confirmation of this entity, as histopathology reveals a thickened reticular dermis with an accumulation of collagen and adjacent mucinous infiltrate with no edema or sclerosis.^28,29

Although the pathogenesis of SD is not well established, it is theorized that the binding of advanced glycation end products (AGEs) to collagen fibers impairs proper cross-linking and degradation by collagenase.^29-31 It is well known that hyperglycemic conditions can promote endogenous formation of AGEs, which occur when reducing sugar molecules become glycated through a nonenzymatic reaction.^30-32 The Western diet also is high in preformed AGEs, which are created primarily through certain high-heat cooking methods such as frying and grilling.^31,32 Hyperglycemia-induced stimulation of fibroblasts also has been proposed as a driver of increased collagen deposition observed histologically in SD.^28,29,33 Treatment of SD can be difficult, as there are no consistently reported therapies, and even improvement in glycemic control does not appear to reverse this condition.²⁹ Case reports have demonstrated some efficacy with various phototherapeutic modalities, including psoralen plus UVA and narrowband UVB phototherapy.^34-36

Ichthyosiform Skin Changes

Ichthyosiform skin changes refer to areas of xerosis and scaling that classically present on the anterior distal lower extremities. Although ichthyosiform alterations have been associated with numerous systemic diseases, they often represent an early finding in diabetic patients.^27,37 The development of ichthyosiform skin changes has been linked to the formation and accumulation of AGEs, which can cause defective cell adhesion in the stratum corneum.^37,38 Treatment with topical emollients and keratolytics may prove beneficial for the skin but do not improve the underlying systemic condition.³⁹

Acrochordons

Acrochordons (skin tags) are common benign fibroepithelial polyps that classically present on the face, neck, and trunk. The underlying mechanism responsible for the development of acrochordons is uncertain, but the association with insulin resistance and impaired carbohydrate metabolism is well validated.^40-46 Several large cross-sectional and case-control studies have reported rates of T2DM ranging from 23% to 72% in patients with acrochordons.^41,42,47 The pathophysiology may involve an increase in tissue and epidermal growth factors driven by elevated serum insulin levels, stimulation of IGF-1 receptors, and a localized proliferation of cutaneous tissue in elastin-poor areas.^45,48,49 Interestingly, the quantity of acrochordons has been positively correlated with fasting blood glucose levels. Additionally, the presence of 30 or more acrochordons was found to increase the risk of developing T2DM.⁴¹ Therefore, the presence and number of acrochordons may serve as a convenient indicator of systemic glycemic control and insulin resistance. Screening for T2DM is warranted in individuals without a prior diagnosis who present with multiple acrochordons.

Keratosis Pilaris

Keratosis pilaris (KP) is a benign skin condition characterized by pink-red, erythematous, monomorphic, follicular papules often seen on the extensor arms, thighs, buttocks, and cheeks. Keratosis pilaris is exceedingly common in the general population but occurs more frequently and with more extensive involvement in those with atopic dermatitis and T2DM.^27,50,51 The mechanism underlying the hyperkeratosis and inflammatory change observed in KP is not well understood and is likely multifactorial.^52,53 Hyperandrogenism, as a consequence of hyperinsulinemia, may play an important role in KP, as elevated circulating androgens are known drivers of keratinocyte proliferation of the pilosebaceous unit of hair follicles.^52,54 Support for this theory includes the clinical exaggeration of KP frequently encountered around puberty when androgen levels peak.^55,56 Moreover, one study found a higher incidence of KP among adolescent patients with type 1 diabetes mellitus than among healthy age-matched controls.²⁷ The most effective treatment of KP appears to be laser therapy, particularly the Q-switched Nd:YAG laser. Numerous topical modalities have been employed to treat KP but exhibit limited efficacy, including mineral oil, tacrolimus, azelaic acid, and salicylic acid, among others.⁵⁷

 

Necrobiosis Lipoidica

Necrobiosis lipoidica (NL) is a chronic granulomatous skin condition of unknown origin that presents with well-demarcated, yellow-brown, atrophic patches and plaques often found exclusively on the shins. There is a strong association with type 1 diabetes mellitus, with reported rates ranging from 11% to 65% in patients with NL.^58-60 In a recent retrospective study of 236 patients with NL, 58.5% of patients had diabetes.⁶¹ Nevertheless, NL is a rare entity that affects less than 1% of the diabetic population.⁶⁰ Given its correlation with diabetes, it has been postulated that the pathogenesis of NL is due to microvascular ischemic changes resulting from prolonged hyperglycemia.⁶⁰ However, studies revealing an increase in blood flow to NL lesions suggest that the condition may instead be attributed to an inflammatory process.⁶² Despite the disfiguring appearance, the lesions of NL often are asymptomatic. Pain or pruritus may develop secondary to ulceration, which occurs in approximately one-third of patients. Although many treatment options have been attempted—including topical and intralesional corticosteroids, immunomodulators, platelet inhibitors, and phototherapy—efficacy is limited.⁶⁰

Bullosis Diabeticorum

Bullosis diabeticorum (BD) is the abrupt onset of noninflammatory vesicles and bullae developing in the setting of diabetes. The prevalence of BD in the diabetic population ranges from 0.16% to 0.5%.^63-66 Bullosis diabeticorum occasionally has been reported to occur prior to the onset of diabetes, warranting screening hemoglobin A_1c in patients without an established diagnosis of diabetes.⁶⁷ Bullae most commonly present over the acral surfaces, but the lower extremities also are routinely affected. Bullae typically are large and painless, contain clear fluid, and may progress from tense to flaccid over the course of several days. Although histologic analysis reveals nonspecific findings, biopsy may be useful in excluding other bullous disorders. Because BD is a benign condition that spontaneously resolves over several weeks, treatment rarely is pursued.^63,64

Generalized Granuloma Annulare

Generalized granuloma annulare (GA) is an idiopathic inflammatory cutaneous disorder characterized by pink-red, arciform and annular, nonscaly, beaded papules and plaques. Granuloma annulare can be localized or generalized with perforating, patch, and palmoplantar variants. Although the pathogenesis is poorly understood, some studies have demonstrated a correlation between GA and type 1 diabetes mellitus.^68-71 Generalized GA appears to be most strongly associated with diabetes, and approximately 10% to 15% of cases occur in this population.^70,72 Because GA has been reported to precede the diagnosis of diabetes, patients with generalized or recurrent localized GA should be screened for persistent hyperglycemia with a hemoglobin A_1c test.^71,73 Although some GA is self-resolving, treatment options for persevering GA include topical and intralesional steroids, isotretinoin, dapsone, tacrolimus, antimalarials, biologic medications, and psoralen plus UVA therapy.⁷⁴

Final Thoughts

Mechanistic links between common cutaneous conditions and persistent hyperglycemic and hyperinsulinemic states are slowly emerging. Hyperglycemia promotes nonenzymatic glycation of the vascular endothelium as well as formation of AGEs that impair cross-linking of collagen in the skin. The consequent microangiopathic damage may lead to cutaneous conditions such as DD, NL, and BD. In addition to microvascular compromise, impaired collagen cross-linking may result in ichthyosiform skin changes and SD. Hyperinsulinemia causes increased circulating levels of IGF-1, which leads to the overactivation of IGF-1 receptors present on fibroblasts and keratinocytes. This aberrant IGF-1 signaling drives cellular hyperproliferation and differentiation, which may be responsible for cutaneous findings such as AN, KP, and/or acrochordons. An insulin-dependent increase in IGF-1 and androgenic signaling may have implications for hormonally driven inflammatory skin disorders such as acne vulgaris and hidradenitis suppurativa, warranting further investigation.

Physicians should be aware of these dermatologic manifestations and their proposed underlying pathophysiologic mechanisms related to impaired glucose tolerance and insulin resistance. A diagnosis of T2DM is not a prerequisite for metabolic disturbance, and the skin may serve as the first clue to underlying systemic disease. Early identification of these cutaneous conditions may lead to timely patient counseling, lifestyle modification, and/or medical management, preventing the long-term sequelae associated with metabolic disorders.

Nutritional dermatoses are classically associated with dietary nutrient deficiencies; however, cutaneous disease as a consequence of nutrient excess often is overlooked. Chronic hyperglycemia and hyperinsulinemia resulting from excess carbohydrate intake may be implicated in a number of cutaneous pathologies, of which every dermatologist should be aware.^1-3

Although diabetic patients exhibit many cutaneous manifestations of excess carbohydrate consumption, the absence of a diagnosis of type 2 diabetes mellitus (T2DM) does not necessarily preclude them.^4-6 Emerging evidence now highlights the development of insulin resistance well before a patient ever meets the diagnostic criteria for T2DM.^7,8 Cutaneous disease can provide early insight into a patient’s glucose tolerance and may be the first sign of metabolic derangement. Prompt recognition of these cutaneous alterations and management of the patient’s underlying systemic disease can improve their quality of life and help prevent severe systemic complications associated with insulin resistance and impaired glucose tolerance.

The aim of this review is to highlight both common and rare cutaneous manifestations associated with the persistent consumption of high glycemic load diets, resultant hyperglycemic and hyperinsulinemic states, and the pathophysiologic mechanisms that underlie them.

Acanthosis Nigricans

Acanthosis nigricans (AN) is a highly prevalent cutaneous finding in individuals with insulin resistance that clinically presents as thickened, hyperpigmented, velvety plaques on the intertriginous and flexural surfaces. The most frequently involved sites include the neck, axillae (Figure), and inframammary and inguinal folds. Black and Hispanic patients most commonly are affected. Although classically associated with T2DM, AN also can be observed in normoglycemic individuals.^7-9 One recent study reported the rate of AN to be 36% in a cohort of middle-aged patients (N=320) with normal fasting blood glucose levels, while the rate of AN in matched patients with hyperglycemia (prediabetes and T2DM) was approximately 50%.⁷ Quantification of insulin resistance was performed using the homeostatic model assessment of insulin resistance index. Interestingly, the specificity for insulin resistance in normoglycemic and hyperglycemic subjects with AN was 85% and 90%, respectively.⁷ These findings suggest that AN may serve as a convenient surrogate marker for subclinical insulin resistance, a conclusion that has been reported in a series of previous studies.^8-10

Although the pathogenesis of AN has not been fully elucidated, it is known that persistently elevated blood glucose triggers continual secretion of insulin and insulinlike growth factor 1 (IGF-1), which results in the overstimulation of insulin and IGF-1 receptors on keratinocytes and dermal fibroblasts through direct and indirect pathways.^11,12 The resultant cellular proliferation can be observed histologically in the forms of orthokeratotic hyperkeratosis and papillomatosis, as occurs in AN.^11,13 Further supporting the association between elevated insulin and AN are reports of AN developing at sites of repeated insulin injection as well as genetic mutations in the insulin receptor resulting in severe AN in children.^14-16

The treatment of AN ultimately focuses on improving glycemic control and reducing insulin resistance through lifestyle modification and pharmacotherapy with agents such as metformin.^11,13 Dermatologic treatment with oral and topical keratolytic agents such as isotretinoin and other retinoids, salicylic acid, urea, or ammonium lactate may be used, but their efficacy generally has been limited.^11,13,17,18

Diabetic Dermopathy

Diabetic dermopathy (DD), commonly known as shin spots, refers to the red-brown, atrophic, circinate macules and patches that often appear on the lower extremities in patients with T2DM. Although the pretibial area is the most frequently involved site, other areas of bony prominence such as the forearms can be affected. The prevalence of DD in the diabetic population can be exceedingly high, with some studies reporting incidence rates greater than 50%, particularly in those with poorly controlled T2DM.^19-21 Interestingly, DD also has been documented in patients without T2DM and has been postulated to be an early sign of insulin resistance.^20,22

 

The pathogenesis of DD remains uncertain, but one proposed mechanism is through microvascular damage caused by hyperglycemia-induced, nonenzymatic glycation, possibly in conjunction with mild trauma, that leads to the deposition of hemosiderin and melanin in the skin.^20,23 A recent study identified increased vascularization of dermopathy lesions when compared with surrounding tissue.²⁴ Subcutaneous nerve ischemia and degeneration secondary to diabetic neuropathy also have been postulated as causative.^20,23 Given the lack of effective therapies and the asymptomatic nature of DD, treatment typically is not pursued. However, DD is associated with other diabetic microvascular complications, including diabetic nephropathy, retinopathy, and neuropathy. For this reason, identification of DD warrants further characterization and management of a patient’s underlying diabetes.^19,20

Scleredema Diabeticorum

Scleredema diabeticorum (SD) refers to the slowly progressive, painless thickening and woody induration of the neck, shoulders, and upper back in individuals with long-standing, poorly controlled diabetes. The condition is almost exclusively seen in the diabetic population, with prevalence rates reported to be as high as 14%.^25-27 Although SD generally is asymptomatic, some individuals may experience restricted mobility and decreased sensation in affected areas.^25,27,28 The diagnosis of SD frequently is missed or ignored clinically. Biopsy can provide diagnostic confirmation of this entity, as histopathology reveals a thickened reticular dermis with an accumulation of collagen and adjacent mucinous infiltrate with no edema or sclerosis.^28,29

Although the pathogenesis of SD is not well established, it is theorized that the binding of advanced glycation end products (AGEs) to collagen fibers impairs proper cross-linking and degradation by collagenase.^29-31 It is well known that hyperglycemic conditions can promote endogenous formation of AGEs, which occur when reducing sugar molecules become glycated through a nonenzymatic reaction.^30-32 The Western diet also is high in preformed AGEs, which are created primarily through certain high-heat cooking methods such as frying and grilling.^31,32 Hyperglycemia-induced stimulation of fibroblasts also has been proposed as a driver of increased collagen deposition observed histologically in SD.^28,29,33 Treatment of SD can be difficult, as there are no consistently reported therapies, and even improvement in glycemic control does not appear to reverse this condition.²⁹ Case reports have demonstrated some efficacy with various phototherapeutic modalities, including psoralen plus UVA and narrowband UVB phototherapy.^34-36

Ichthyosiform Skin Changes

Ichthyosiform skin changes refer to areas of xerosis and scaling that classically present on the anterior distal lower extremities. Although ichthyosiform alterations have been associated with numerous systemic diseases, they often represent an early finding in diabetic patients.^27,37 The development of ichthyosiform skin changes has been linked to the formation and accumulation of AGEs, which can cause defective cell adhesion in the stratum corneum.^37,38 Treatment with topical emollients and keratolytics may prove beneficial for the skin but do not improve the underlying systemic condition.³⁹

Acrochordons

Acrochordons (skin tags) are common benign fibroepithelial polyps that classically present on the face, neck, and trunk. The underlying mechanism responsible for the development of acrochordons is uncertain, but the association with insulin resistance and impaired carbohydrate metabolism is well validated.^40-46 Several large cross-sectional and case-control studies have reported rates of T2DM ranging from 23% to 72% in patients with acrochordons.^41,42,47 The pathophysiology may involve an increase in tissue and epidermal growth factors driven by elevated serum insulin levels, stimulation of IGF-1 receptors, and a localized proliferation of cutaneous tissue in elastin-poor areas.^45,48,49 Interestingly, the quantity of acrochordons has been positively correlated with fasting blood glucose levels. Additionally, the presence of 30 or more acrochordons was found to increase the risk of developing T2DM.⁴¹ Therefore, the presence and number of acrochordons may serve as a convenient indicator of systemic glycemic control and insulin resistance. Screening for T2DM is warranted in individuals without a prior diagnosis who present with multiple acrochordons.

Keratosis Pilaris

Keratosis pilaris (KP) is a benign skin condition characterized by pink-red, erythematous, monomorphic, follicular papules often seen on the extensor arms, thighs, buttocks, and cheeks. Keratosis pilaris is exceedingly common in the general population but occurs more frequently and with more extensive involvement in those with atopic dermatitis and T2DM.^27,50,51 The mechanism underlying the hyperkeratosis and inflammatory change observed in KP is not well understood and is likely multifactorial.^52,53 Hyperandrogenism, as a consequence of hyperinsulinemia, may play an important role in KP, as elevated circulating androgens are known drivers of keratinocyte proliferation of the pilosebaceous unit of hair follicles.^52,54 Support for this theory includes the clinical exaggeration of KP frequently encountered around puberty when androgen levels peak.^55,56 Moreover, one study found a higher incidence of KP among adolescent patients with type 1 diabetes mellitus than among healthy age-matched controls.²⁷ The most effective treatment of KP appears to be laser therapy, particularly the Q-switched Nd:YAG laser. Numerous topical modalities have been employed to treat KP but exhibit limited efficacy, including mineral oil, tacrolimus, azelaic acid, and salicylic acid, among others.⁵⁷

 

Necrobiosis Lipoidica

Necrobiosis lipoidica (NL) is a chronic granulomatous skin condition of unknown origin that presents with well-demarcated, yellow-brown, atrophic patches and plaques often found exclusively on the shins. There is a strong association with type 1 diabetes mellitus, with reported rates ranging from 11% to 65% in patients with NL.^58-60 In a recent retrospective study of 236 patients with NL, 58.5% of patients had diabetes.⁶¹ Nevertheless, NL is a rare entity that affects less than 1% of the diabetic population.⁶⁰ Given its correlation with diabetes, it has been postulated that the pathogenesis of NL is due to microvascular ischemic changes resulting from prolonged hyperglycemia.⁶⁰ However, studies revealing an increase in blood flow to NL lesions suggest that the condition may instead be attributed to an inflammatory process.⁶² Despite the disfiguring appearance, the lesions of NL often are asymptomatic. Pain or pruritus may develop secondary to ulceration, which occurs in approximately one-third of patients. Although many treatment options have been attempted—including topical and intralesional corticosteroids, immunomodulators, platelet inhibitors, and phototherapy—efficacy is limited.⁶⁰

Bullosis Diabeticorum

Bullosis diabeticorum (BD) is the abrupt onset of noninflammatory vesicles and bullae developing in the setting of diabetes. The prevalence of BD in the diabetic population ranges from 0.16% to 0.5%.^63-66 Bullosis diabeticorum occasionally has been reported to occur prior to the onset of diabetes, warranting screening hemoglobin A_1c in patients without an established diagnosis of diabetes.⁶⁷ Bullae most commonly present over the acral surfaces, but the lower extremities also are routinely affected. Bullae typically are large and painless, contain clear fluid, and may progress from tense to flaccid over the course of several days. Although histologic analysis reveals nonspecific findings, biopsy may be useful in excluding other bullous disorders. Because BD is a benign condition that spontaneously resolves over several weeks, treatment rarely is pursued.^63,64

Generalized Granuloma Annulare

Generalized granuloma annulare (GA) is an idiopathic inflammatory cutaneous disorder characterized by pink-red, arciform and annular, nonscaly, beaded papules and plaques. Granuloma annulare can be localized or generalized with perforating, patch, and palmoplantar variants. Although the pathogenesis is poorly understood, some studies have demonstrated a correlation between GA and type 1 diabetes mellitus.^68-71 Generalized GA appears to be most strongly associated with diabetes, and approximately 10% to 15% of cases occur in this population.^70,72 Because GA has been reported to precede the diagnosis of diabetes, patients with generalized or recurrent localized GA should be screened for persistent hyperglycemia with a hemoglobin A_1c test.^71,73 Although some GA is self-resolving, treatment options for persevering GA include topical and intralesional steroids, isotretinoin, dapsone, tacrolimus, antimalarials, biologic medications, and psoralen plus UVA therapy.⁷⁴

Final Thoughts

Mechanistic links between common cutaneous conditions and persistent hyperglycemic and hyperinsulinemic states are slowly emerging. Hyperglycemia promotes nonenzymatic glycation of the vascular endothelium as well as formation of AGEs that impair cross-linking of collagen in the skin. The consequent microangiopathic damage may lead to cutaneous conditions such as DD, NL, and BD. In addition to microvascular compromise, impaired collagen cross-linking may result in ichthyosiform skin changes and SD. Hyperinsulinemia causes increased circulating levels of IGF-1, which leads to the overactivation of IGF-1 receptors present on fibroblasts and keratinocytes. This aberrant IGF-1 signaling drives cellular hyperproliferation and differentiation, which may be responsible for cutaneous findings such as AN, KP, and/or acrochordons. An insulin-dependent increase in IGF-1 and androgenic signaling may have implications for hormonally driven inflammatory skin disorders such as acne vulgaris and hidradenitis suppurativa, warranting further investigation.

Physicians should be aware of these dermatologic manifestations and their proposed underlying pathophysiologic mechanisms related to impaired glucose tolerance and insulin resistance. A diagnosis of T2DM is not a prerequisite for metabolic disturbance, and the skin may serve as the first clue to underlying systemic disease. Early identification of these cutaneous conditions may lead to timely patient counseling, lifestyle modification, and/or medical management, preventing the long-term sequelae associated with metabolic disorders.

Nutritional dermatoses are classically associated with dietary nutrient deficiencies; however, cutaneous disease as a consequence of nutrient excess often is overlooked. Chronic hyperglycemia and hyperinsulinemia resulting from excess carbohydrate intake may be implicated in a number of cutaneous pathologies, of which every dermatologist should be aware.^1-3

Although diabetic patients exhibit many cutaneous manifestations of excess carbohydrate consumption, the absence of a diagnosis of type 2 diabetes mellitus (T2DM) does not necessarily preclude them.^4-6 Emerging evidence now highlights the development of insulin resistance well before a patient ever meets the diagnostic criteria for T2DM.^7,8 Cutaneous disease can provide early insight into a patient’s glucose tolerance and may be the first sign of metabolic derangement. Prompt recognition of these cutaneous alterations and management of the patient’s underlying systemic disease can improve their quality of life and help prevent severe systemic complications associated with insulin resistance and impaired glucose tolerance.

The aim of this review is to highlight both common and rare cutaneous manifestations associated with the persistent consumption of high glycemic load diets, resultant hyperglycemic and hyperinsulinemic states, and the pathophysiologic mechanisms that underlie them.

Acanthosis Nigricans

Acanthosis nigricans (AN) is a highly prevalent cutaneous finding in individuals with insulin resistance that clinically presents as thickened, hyperpigmented, velvety plaques on the intertriginous and flexural surfaces. The most frequently involved sites include the neck, axillae (Figure), and inframammary and inguinal folds. Black and Hispanic patients most commonly are affected. Although classically associated with T2DM, AN also can be observed in normoglycemic individuals.^7-9 One recent study reported the rate of AN to be 36% in a cohort of middle-aged patients (N=320) with normal fasting blood glucose levels, while the rate of AN in matched patients with hyperglycemia (prediabetes and T2DM) was approximately 50%.⁷ Quantification of insulin resistance was performed using the homeostatic model assessment of insulin resistance index. Interestingly, the specificity for insulin resistance in normoglycemic and hyperglycemic subjects with AN was 85% and 90%, respectively.⁷ These findings suggest that AN may serve as a convenient surrogate marker for subclinical insulin resistance, a conclusion that has been reported in a series of previous studies.^8-10

Although the pathogenesis of AN has not been fully elucidated, it is known that persistently elevated blood glucose triggers continual secretion of insulin and insulinlike growth factor 1 (IGF-1), which results in the overstimulation of insulin and IGF-1 receptors on keratinocytes and dermal fibroblasts through direct and indirect pathways.^11,12 The resultant cellular proliferation can be observed histologically in the forms of orthokeratotic hyperkeratosis and papillomatosis, as occurs in AN.^11,13 Further supporting the association between elevated insulin and AN are reports of AN developing at sites of repeated insulin injection as well as genetic mutations in the insulin receptor resulting in severe AN in children.^14-16

The treatment of AN ultimately focuses on improving glycemic control and reducing insulin resistance through lifestyle modification and pharmacotherapy with agents such as metformin.^11,13 Dermatologic treatment with oral and topical keratolytic agents such as isotretinoin and other retinoids, salicylic acid, urea, or ammonium lactate may be used, but their efficacy generally has been limited.^11,13,17,18

Diabetic Dermopathy

Diabetic dermopathy (DD), commonly known as shin spots, refers to the red-brown, atrophic, circinate macules and patches that often appear on the lower extremities in patients with T2DM. Although the pretibial area is the most frequently involved site, other areas of bony prominence such as the forearms can be affected. The prevalence of DD in the diabetic population can be exceedingly high, with some studies reporting incidence rates greater than 50%, particularly in those with poorly controlled T2DM.^19-21 Interestingly, DD also has been documented in patients without T2DM and has been postulated to be an early sign of insulin resistance.^20,22

 

The pathogenesis of DD remains uncertain, but one proposed mechanism is through microvascular damage caused by hyperglycemia-induced, nonenzymatic glycation, possibly in conjunction with mild trauma, that leads to the deposition of hemosiderin and melanin in the skin.^20,23 A recent study identified increased vascularization of dermopathy lesions when compared with surrounding tissue.²⁴ Subcutaneous nerve ischemia and degeneration secondary to diabetic neuropathy also have been postulated as causative.^20,23 Given the lack of effective therapies and the asymptomatic nature of DD, treatment typically is not pursued. However, DD is associated with other diabetic microvascular complications, including diabetic nephropathy, retinopathy, and neuropathy. For this reason, identification of DD warrants further characterization and management of a patient’s underlying diabetes.^19,20

Scleredema Diabeticorum

Scleredema diabeticorum (SD) refers to the slowly progressive, painless thickening and woody induration of the neck, shoulders, and upper back in individuals with long-standing, poorly controlled diabetes. The condition is almost exclusively seen in the diabetic population, with prevalence rates reported to be as high as 14%.^25-27 Although SD generally is asymptomatic, some individuals may experience restricted mobility and decreased sensation in affected areas.^25,27,28 The diagnosis of SD frequently is missed or ignored clinically. Biopsy can provide diagnostic confirmation of this entity, as histopathology reveals a thickened reticular dermis with an accumulation of collagen and adjacent mucinous infiltrate with no edema or sclerosis.^28,29

Although the pathogenesis of SD is not well established, it is theorized that the binding of advanced glycation end products (AGEs) to collagen fibers impairs proper cross-linking and degradation by collagenase.^29-31 It is well known that hyperglycemic conditions can promote endogenous formation of AGEs, which occur when reducing sugar molecules become glycated through a nonenzymatic reaction.^30-32 The Western diet also is high in preformed AGEs, which are created primarily through certain high-heat cooking methods such as frying and grilling.^31,32 Hyperglycemia-induced stimulation of fibroblasts also has been proposed as a driver of increased collagen deposition observed histologically in SD.^28,29,33 Treatment of SD can be difficult, as there are no consistently reported therapies, and even improvement in glycemic control does not appear to reverse this condition.²⁹ Case reports have demonstrated some efficacy with various phototherapeutic modalities, including psoralen plus UVA and narrowband UVB phototherapy.^34-36

Ichthyosiform Skin Changes

Ichthyosiform skin changes refer to areas of xerosis and scaling that classically present on the anterior distal lower extremities. Although ichthyosiform alterations have been associated with numerous systemic diseases, they often represent an early finding in diabetic patients.^27,37 The development of ichthyosiform skin changes has been linked to the formation and accumulation of AGEs, which can cause defective cell adhesion in the stratum corneum.^37,38 Treatment with topical emollients and keratolytics may prove beneficial for the skin but do not improve the underlying systemic condition.³⁹

Acrochordons

Acrochordons (skin tags) are common benign fibroepithelial polyps that classically present on the face, neck, and trunk. The underlying mechanism responsible for the development of acrochordons is uncertain, but the association with insulin resistance and impaired carbohydrate metabolism is well validated.^40-46 Several large cross-sectional and case-control studies have reported rates of T2DM ranging from 23% to 72% in patients with acrochordons.^41,42,47 The pathophysiology may involve an increase in tissue and epidermal growth factors driven by elevated serum insulin levels, stimulation of IGF-1 receptors, and a localized proliferation of cutaneous tissue in elastin-poor areas.^45,48,49 Interestingly, the quantity of acrochordons has been positively correlated with fasting blood glucose levels. Additionally, the presence of 30 or more acrochordons was found to increase the risk of developing T2DM.⁴¹ Therefore, the presence and number of acrochordons may serve as a convenient indicator of systemic glycemic control and insulin resistance. Screening for T2DM is warranted in individuals without a prior diagnosis who present with multiple acrochordons.

Keratosis Pilaris

Keratosis pilaris (KP) is a benign skin condition characterized by pink-red, erythematous, monomorphic, follicular papules often seen on the extensor arms, thighs, buttocks, and cheeks. Keratosis pilaris is exceedingly common in the general population but occurs more frequently and with more extensive involvement in those with atopic dermatitis and T2DM.^27,50,51 The mechanism underlying the hyperkeratosis and inflammatory change observed in KP is not well understood and is likely multifactorial.^52,53 Hyperandrogenism, as a consequence of hyperinsulinemia, may play an important role in KP, as elevated circulating androgens are known drivers of keratinocyte proliferation of the pilosebaceous unit of hair follicles.^52,54 Support for this theory includes the clinical exaggeration of KP frequently encountered around puberty when androgen levels peak.^55,56 Moreover, one study found a higher incidence of KP among adolescent patients with type 1 diabetes mellitus than among healthy age-matched controls.²⁷ The most effective treatment of KP appears to be laser therapy, particularly the Q-switched Nd:YAG laser. Numerous topical modalities have been employed to treat KP but exhibit limited efficacy, including mineral oil, tacrolimus, azelaic acid, and salicylic acid, among others.⁵⁷

 

Necrobiosis Lipoidica

Necrobiosis lipoidica (NL) is a chronic granulomatous skin condition of unknown origin that presents with well-demarcated, yellow-brown, atrophic patches and plaques often found exclusively on the shins. There is a strong association with type 1 diabetes mellitus, with reported rates ranging from 11% to 65% in patients with NL.^58-60 In a recent retrospective study of 236 patients with NL, 58.5% of patients had diabetes.⁶¹ Nevertheless, NL is a rare entity that affects less than 1% of the diabetic population.⁶⁰ Given its correlation with diabetes, it has been postulated that the pathogenesis of NL is due to microvascular ischemic changes resulting from prolonged hyperglycemia.⁶⁰ However, studies revealing an increase in blood flow to NL lesions suggest that the condition may instead be attributed to an inflammatory process.⁶² Despite the disfiguring appearance, the lesions of NL often are asymptomatic. Pain or pruritus may develop secondary to ulceration, which occurs in approximately one-third of patients. Although many treatment options have been attempted—including topical and intralesional corticosteroids, immunomodulators, platelet inhibitors, and phototherapy—efficacy is limited.⁶⁰

Bullosis Diabeticorum

Bullosis diabeticorum (BD) is the abrupt onset of noninflammatory vesicles and bullae developing in the setting of diabetes. The prevalence of BD in the diabetic population ranges from 0.16% to 0.5%.^63-66 Bullosis diabeticorum occasionally has been reported to occur prior to the onset of diabetes, warranting screening hemoglobin A_1c in patients without an established diagnosis of diabetes.⁶⁷ Bullae most commonly present over the acral surfaces, but the lower extremities also are routinely affected. Bullae typically are large and painless, contain clear fluid, and may progress from tense to flaccid over the course of several days. Although histologic analysis reveals nonspecific findings, biopsy may be useful in excluding other bullous disorders. Because BD is a benign condition that spontaneously resolves over several weeks, treatment rarely is pursued.^63,64

Generalized Granuloma Annulare

Generalized granuloma annulare (GA) is an idiopathic inflammatory cutaneous disorder characterized by pink-red, arciform and annular, nonscaly, beaded papules and plaques. Granuloma annulare can be localized or generalized with perforating, patch, and palmoplantar variants. Although the pathogenesis is poorly understood, some studies have demonstrated a correlation between GA and type 1 diabetes mellitus.^68-71 Generalized GA appears to be most strongly associated with diabetes, and approximately 10% to 15% of cases occur in this population.^70,72 Because GA has been reported to precede the diagnosis of diabetes, patients with generalized or recurrent localized GA should be screened for persistent hyperglycemia with a hemoglobin A_1c test.^71,73 Although some GA is self-resolving, treatment options for persevering GA include topical and intralesional steroids, isotretinoin, dapsone, tacrolimus, antimalarials, biologic medications, and psoralen plus UVA therapy.⁷⁴

Final Thoughts

Mechanistic links between common cutaneous conditions and persistent hyperglycemic and hyperinsulinemic states are slowly emerging. Hyperglycemia promotes nonenzymatic glycation of the vascular endothelium as well as formation of AGEs that impair cross-linking of collagen in the skin. The consequent microangiopathic damage may lead to cutaneous conditions such as DD, NL, and BD. In addition to microvascular compromise, impaired collagen cross-linking may result in ichthyosiform skin changes and SD. Hyperinsulinemia causes increased circulating levels of IGF-1, which leads to the overactivation of IGF-1 receptors present on fibroblasts and keratinocytes. This aberrant IGF-1 signaling drives cellular hyperproliferation and differentiation, which may be responsible for cutaneous findings such as AN, KP, and/or acrochordons. An insulin-dependent increase in IGF-1 and androgenic signaling may have implications for hormonally driven inflammatory skin disorders such as acne vulgaris and hidradenitis suppurativa, warranting further investigation.

Physicians should be aware of these dermatologic manifestations and their proposed underlying pathophysiologic mechanisms related to impaired glucose tolerance and insulin resistance. A diagnosis of T2DM is not a prerequisite for metabolic disturbance, and the skin may serve as the first clue to underlying systemic disease. Early identification of these cutaneous conditions may lead to timely patient counseling, lifestyle modification, and/or medical management, preventing the long-term sequelae associated with metabolic disorders.

Once upon a time, physicians wrote letters to peers and colleagues around the world, sharing their medical discoveries, theories, case reports, and questions; conferring on problems; and then waiting for return mail to bring a reply. And the science of medicine advanced at a glacial pace.

Today, communication in multiple mediums flows much faster, almost instantaneously, between many more physicians, regardless of distance, addressing a much greater complexity of medical topics and treatments. And one of the chief mediums for this rapid electronic conversation among doctors is Twitter, according to Charlie Wray, DO, MS, a hospitalist at the University of California, San Francisco.

Dr. Wray, associate editor and digital media editor for the Journal of Hospital Medicine, is one of the moderators of #JHMchat, a monthly get-together on Twitter for interested hospitalists to link up virtually; respond to questions posed by JHM editors and other moderators; exchange perspectives, experiences, and tips with their peers; and build professional relationships and personal friendships. Relationship building has become particularly important in the age of COVID-19, when opportunities to connect in person at events such as SHM’s annual conferences have been curtailed.

The online #JHMchat community began in 2015, shortly after Dr. Wray completed a hospitalist research fellowship at the University of Chicago. His fellowship mentor, Vineet Arora, MD, MAPP, MHM, associate chief medical officer for the clinical learning environment at University of Chicago Medicine, had noticed how other online medical communities were engaging in discussions around different topics.

“She thought it could be a great way for hospitalists to meet online and talk about the articles published in JHM,” Dr. Wray explained. “We were all getting into social media and learning how to moderate interactive discussions such as Twitter.”

The chat’s founders approached JHM’s then-editor Andrew Auerbach, MD, MHM, a hospitalist at UCSF, who agreed that it was a great idea. They asked Christopher Moriates, MD, author of a recently published paper on the advisability of nebulized bronchodilators for obstructive pulmonary symptoms and assistant dean for health care value at the University of Texas, Austin, to come on the chat and talk about his paper. Visiting Dr. Arora at the time, he joined her in her living room for the first chat on Oct. 12, 2015. Seventy-five participants posted 431 tweets, with a total of 2 million Twitter impressions, suggesting that they had tapped a latent need.

How the chat works

To participate in the JHM chats on Twitter, one needs to open an account on the platform (it’s free) and follow the Journal’s Twitter feed (@jhospmedicine). But that’s pretty much it, Dr. Wray said. The group convenes on a Monday evening each month for an hour, starting at 9 p.m. Eastern time. Upcoming chats and topics are announced on Twitter and at SHM’s website.

The chats have grown and evolved since 2015, shifting in focus given recent social upheavals over the pandemic and heated discussions about diversity, equity, and racial justice in medicine, he said. “When COVID hit, the journal’s editor – Dr. Samir Shah – recognized that we were in a unique moment with the pandemic. The journal took advantage of the opportunity to publish a lot more personal perspectives and viewpoints around COVID, along with a special issue devoted to social justice.”

Moderators for the chat typically choose three or four questions based on recently published articles or other relevant topics, such as racial inequities in health care or how to apply military principles to hospital medicine leadership. “We reach out to authors and tell them they can explain their articles to interested readers through the chat. I can’t think of a single one who said no. They see the opportunity to highlight their work and engage with readers who want to ask them questions,” Dr. Wray said.

The moderators’ questions are posed to stimulate participation, but another goal is to use that hour for networking. “It’s a powerful tool to allow SHM members to engage with each other,” he said. “Sometimes the chat has the feeling of trying to drink water from a fire hose – with the messages flashing past so quickly. But the key is not to try to respond to everything but rather to follow those threads that particularly interest you. We encourage you to engage, but it’s totally fine if you just sit back and observe. One thing we have done to make it a little more formal is to offer CME credits for participants.”

The chat welcomes hospitalists and nonhospitalists, nurse practitioners, physician assistants, academics, and nonacademics. “No matter how engaged you are with Twitter, if you have 10,000 followers or 10, we’ll amplify your voice,” he said. “We also have medical students participating and consider their perspectives valuable, too.”

Dr. Wray identified three main types of participants in the monthly chats. The first are regulars who come every month, rain or shine. Like the character Norm in the old television comedy “Cheers,” everybody knows their name. They become friends, sharing and reveling in each other’s accomplishments. “These are people who have multiple connections, personally and professionally, at a lot of different levels. I probably know a hundred or more people who I’ve primarily gotten to know online.”

A second and larger group might be drawn in because of an interest in a specific topic or article, but they’re also welcome to participate in the chat. And the third group may lurk in the background, following along but not commenting. The size of that third group is unknown, but metrics from SHM show a total of 796 participants posting 4,088 tweets during chats in 2020 (for an average of 132 participants and 681 tweets per chat). This adds up to a total of 34 million impressions across the platform for #JHMchat tweets for the year.
 

 

Creating community online

“Why do we do it? It’s difficult to read all of the relevant published articles and keep up to date,” said Dr. Arora, a medical educator whose job at Chicago Medicine is to improve the clinical learning environment for trainees and staff by aligning learning with the health system’s institutional quality, safety and value missions.

“Our idea was to bring together a kind of virtual journal club and have discussions around topics such as: how do you create a shared vision on rounds? How do you integrate that into clinical practice? How do we preserve work/life balance or address structural racism?” she said. Other topics have included work flow concerns, burnout, difficult conversations with patients, and career planning.

“The people we’re trying to reach are hospitalists – and they’re busy at the front lines of care. We also thought this was an interesting way to raise the journal’s profile and spark broader interest in the articles it publishes. But it’s really about creating community, with people who look forward to talking and connecting with each other each month through the chats,” Dr. Arora said. If they miss a chat, they feel they’ve missed important interactions.

“Many times when people log onto the chat, they give a status report on where they are at, such as ‘I’m home putting my kids to bed,’ or ‘I’m on call tonight,’ ” she added. “People are willing to engage with the medium because it’s easy to engage with. We can forget that physicians are like everyone else. They like to learn, but they want that learning to be fun.”

On Dec. 14, 2020, at 9 p.m. Eastern time, the first question for the monthly #JHMchat was posted: How will caring for COVID-19 patients this winter differ from caring for patients in the first wave? Given that another surge of hospitalized COVID patients is looming, participants posted that they feel familiar and more confident with effective clinical strategies for hospitalized COVID patients, having learned so much more about the virus. But they’re facing greater numbers of patients than in prior surges. “In March, we were in crisis, now we’re in complexity,” one noted.

Joining the moderators was the Pediatric Overflow Planning Contingency Response Network (POPCoRN), a group formed earlier this year to help mobilize pediatric medical capacity for COVID patients during pandemic surges (see “POPCoRN network mobilizes pediatric capacity during pandemic,” The Hospitalist, April 30, 2020). One of its questions involved the redeployment of physicians in response to COVID demands and what, for example, pediatric hospitalists need as resources and tools when they are reassigned to adult patients or to new roles in unfamiliar settings. A variety of educational resources were cited from POPCoRN, SHM, and ImproveDX, among others.
 

Defining medical communication

Another chat moderator is Angela Castellanos, MD, a pediatric hospitalist at Tufts Medical Center in Boston. Dr. Castellanos did a 1-year, full-time fellowship right after residency at the New England Journal of Medicine, participating hands-on as a member of the editorial team for the print and online editions of the venerable journal. She is now doing a digital media fellowship with JHM, a part-time commitment while holding down a full-time job as a hospitalist. She also puts together a Spanish language podcast covering primary care pediatric issues for parents and families.

“I’m interested in medical communication generally, as I try to figure out what that means,” she said. “I have continued to look for ways to be part of the social media community and to be more creative about it. The JHM fellowship came at a perfect time for me to learn to do more in digital media.”

COVID has created new opportunities for more immediate dialogue with colleagues – what are they seeing and what’s working in the absence of clinical trials, she explained. “That’s how we communicate, as a way to get information out fast, such as when hospitals began proning COVID patients to make it easier for them to breathe.”

Dr. Castellanos said she grew up with text messaging and social media and wants to continue to grow her skills in this area. “I think I developed some skills at NEJM, but the opportunity to see how they do things at another journal with a different mission was also valuable. I get to share the space with people in academic settings and leaders in my field. I tweet at them; they tweet at me. These two fellowships have given me unique insights and mentorships. I know I want to continue doing pediatric hospital medicine and to engage academically and learn how to do research.”

Twitter sometimes gets a bad reputation for hostile or incendiary posts, Dr. Wray noted. “If you look at social media writ large, it can sometimes seem like a dumpster fire.” But what has happened in the medical community and in most medical Twitter encounters is a more cordial approach to conversations. “People who work in medicine converse with each other, with room for respectful disagreements. We’re extra supportive of each other,” he said.

“I think if hospitalists are looking for a community of peers, to engage with them and network and to find colleagues in similar circumstances, the JHM chat is such a fantastic place,” Dr. Wray concluded. “Don’t just come once, come several times, meet people along the way. For me, one of the most beneficial ways to advance my career has been by connecting with people through the chat. It allows me to share my work and success with the hospitalist community, as well as highlighting my trainees’ and colleagues’ successes, and it has created opportunities I never would have expected for getting involved in other projects.”

Once upon a time, physicians wrote letters to peers and colleagues around the world, sharing their medical discoveries, theories, case reports, and questions; conferring on problems; and then waiting for return mail to bring a reply. And the science of medicine advanced at a glacial pace.

Today, communication in multiple mediums flows much faster, almost instantaneously, between many more physicians, regardless of distance, addressing a much greater complexity of medical topics and treatments. And one of the chief mediums for this rapid electronic conversation among doctors is Twitter, according to Charlie Wray, DO, MS, a hospitalist at the University of California, San Francisco.

Dr. Wray, associate editor and digital media editor for the Journal of Hospital Medicine, is one of the moderators of #JHMchat, a monthly get-together on Twitter for interested hospitalists to link up virtually; respond to questions posed by JHM editors and other moderators; exchange perspectives, experiences, and tips with their peers; and build professional relationships and personal friendships. Relationship building has become particularly important in the age of COVID-19, when opportunities to connect in person at events such as SHM’s annual conferences have been curtailed.

The online #JHMchat community began in 2015, shortly after Dr. Wray completed a hospitalist research fellowship at the University of Chicago. His fellowship mentor, Vineet Arora, MD, MAPP, MHM, associate chief medical officer for the clinical learning environment at University of Chicago Medicine, had noticed how other online medical communities were engaging in discussions around different topics.

“She thought it could be a great way for hospitalists to meet online and talk about the articles published in JHM,” Dr. Wray explained. “We were all getting into social media and learning how to moderate interactive discussions such as Twitter.”

The chat’s founders approached JHM’s then-editor Andrew Auerbach, MD, MHM, a hospitalist at UCSF, who agreed that it was a great idea. They asked Christopher Moriates, MD, author of a recently published paper on the advisability of nebulized bronchodilators for obstructive pulmonary symptoms and assistant dean for health care value at the University of Texas, Austin, to come on the chat and talk about his paper. Visiting Dr. Arora at the time, he joined her in her living room for the first chat on Oct. 12, 2015. Seventy-five participants posted 431 tweets, with a total of 2 million Twitter impressions, suggesting that they had tapped a latent need.

How the chat works

To participate in the JHM chats on Twitter, one needs to open an account on the platform (it’s free) and follow the Journal’s Twitter feed (@jhospmedicine). But that’s pretty much it, Dr. Wray said. The group convenes on a Monday evening each month for an hour, starting at 9 p.m. Eastern time. Upcoming chats and topics are announced on Twitter and at SHM’s website.

The chats have grown and evolved since 2015, shifting in focus given recent social upheavals over the pandemic and heated discussions about diversity, equity, and racial justice in medicine, he said. “When COVID hit, the journal’s editor – Dr. Samir Shah – recognized that we were in a unique moment with the pandemic. The journal took advantage of the opportunity to publish a lot more personal perspectives and viewpoints around COVID, along with a special issue devoted to social justice.”

Moderators for the chat typically choose three or four questions based on recently published articles or other relevant topics, such as racial inequities in health care or how to apply military principles to hospital medicine leadership. “We reach out to authors and tell them they can explain their articles to interested readers through the chat. I can’t think of a single one who said no. They see the opportunity to highlight their work and engage with readers who want to ask them questions,” Dr. Wray said.

The moderators’ questions are posed to stimulate participation, but another goal is to use that hour for networking. “It’s a powerful tool to allow SHM members to engage with each other,” he said. “Sometimes the chat has the feeling of trying to drink water from a fire hose – with the messages flashing past so quickly. But the key is not to try to respond to everything but rather to follow those threads that particularly interest you. We encourage you to engage, but it’s totally fine if you just sit back and observe. One thing we have done to make it a little more formal is to offer CME credits for participants.”

The chat welcomes hospitalists and nonhospitalists, nurse practitioners, physician assistants, academics, and nonacademics. “No matter how engaged you are with Twitter, if you have 10,000 followers or 10, we’ll amplify your voice,” he said. “We also have medical students participating and consider their perspectives valuable, too.”

Dr. Wray identified three main types of participants in the monthly chats. The first are regulars who come every month, rain or shine. Like the character Norm in the old television comedy “Cheers,” everybody knows their name. They become friends, sharing and reveling in each other’s accomplishments. “These are people who have multiple connections, personally and professionally, at a lot of different levels. I probably know a hundred or more people who I’ve primarily gotten to know online.”

A second and larger group might be drawn in because of an interest in a specific topic or article, but they’re also welcome to participate in the chat. And the third group may lurk in the background, following along but not commenting. The size of that third group is unknown, but metrics from SHM show a total of 796 participants posting 4,088 tweets during chats in 2020 (for an average of 132 participants and 681 tweets per chat). This adds up to a total of 34 million impressions across the platform for #JHMchat tweets for the year.
 

 

Creating community online

“Why do we do it? It’s difficult to read all of the relevant published articles and keep up to date,” said Dr. Arora, a medical educator whose job at Chicago Medicine is to improve the clinical learning environment for trainees and staff by aligning learning with the health system’s institutional quality, safety and value missions.

“Our idea was to bring together a kind of virtual journal club and have discussions around topics such as: how do you create a shared vision on rounds? How do you integrate that into clinical practice? How do we preserve work/life balance or address structural racism?” she said. Other topics have included work flow concerns, burnout, difficult conversations with patients, and career planning.

“The people we’re trying to reach are hospitalists – and they’re busy at the front lines of care. We also thought this was an interesting way to raise the journal’s profile and spark broader interest in the articles it publishes. But it’s really about creating community, with people who look forward to talking and connecting with each other each month through the chats,” Dr. Arora said. If they miss a chat, they feel they’ve missed important interactions.

“Many times when people log onto the chat, they give a status report on where they are at, such as ‘I’m home putting my kids to bed,’ or ‘I’m on call tonight,’ ” she added. “People are willing to engage with the medium because it’s easy to engage with. We can forget that physicians are like everyone else. They like to learn, but they want that learning to be fun.”

On Dec. 14, 2020, at 9 p.m. Eastern time, the first question for the monthly #JHMchat was posted: How will caring for COVID-19 patients this winter differ from caring for patients in the first wave? Given that another surge of hospitalized COVID patients is looming, participants posted that they feel familiar and more confident with effective clinical strategies for hospitalized COVID patients, having learned so much more about the virus. But they’re facing greater numbers of patients than in prior surges. “In March, we were in crisis, now we’re in complexity,” one noted.

Joining the moderators was the Pediatric Overflow Planning Contingency Response Network (POPCoRN), a group formed earlier this year to help mobilize pediatric medical capacity for COVID patients during pandemic surges (see “POPCoRN network mobilizes pediatric capacity during pandemic,” The Hospitalist, April 30, 2020). One of its questions involved the redeployment of physicians in response to COVID demands and what, for example, pediatric hospitalists need as resources and tools when they are reassigned to adult patients or to new roles in unfamiliar settings. A variety of educational resources were cited from POPCoRN, SHM, and ImproveDX, among others.
 

Defining medical communication

Another chat moderator is Angela Castellanos, MD, a pediatric hospitalist at Tufts Medical Center in Boston. Dr. Castellanos did a 1-year, full-time fellowship right after residency at the New England Journal of Medicine, participating hands-on as a member of the editorial team for the print and online editions of the venerable journal. She is now doing a digital media fellowship with JHM, a part-time commitment while holding down a full-time job as a hospitalist. She also puts together a Spanish language podcast covering primary care pediatric issues for parents and families.

“I’m interested in medical communication generally, as I try to figure out what that means,” she said. “I have continued to look for ways to be part of the social media community and to be more creative about it. The JHM fellowship came at a perfect time for me to learn to do more in digital media.”

COVID has created new opportunities for more immediate dialogue with colleagues – what are they seeing and what’s working in the absence of clinical trials, she explained. “That’s how we communicate, as a way to get information out fast, such as when hospitals began proning COVID patients to make it easier for them to breathe.”

Dr. Castellanos said she grew up with text messaging and social media and wants to continue to grow her skills in this area. “I think I developed some skills at NEJM, but the opportunity to see how they do things at another journal with a different mission was also valuable. I get to share the space with people in academic settings and leaders in my field. I tweet at them; they tweet at me. These two fellowships have given me unique insights and mentorships. I know I want to continue doing pediatric hospital medicine and to engage academically and learn how to do research.”

Twitter sometimes gets a bad reputation for hostile or incendiary posts, Dr. Wray noted. “If you look at social media writ large, it can sometimes seem like a dumpster fire.” But what has happened in the medical community and in most medical Twitter encounters is a more cordial approach to conversations. “People who work in medicine converse with each other, with room for respectful disagreements. We’re extra supportive of each other,” he said.

“I think if hospitalists are looking for a community of peers, to engage with them and network and to find colleagues in similar circumstances, the JHM chat is such a fantastic place,” Dr. Wray concluded. “Don’t just come once, come several times, meet people along the way. For me, one of the most beneficial ways to advance my career has been by connecting with people through the chat. It allows me to share my work and success with the hospitalist community, as well as highlighting my trainees’ and colleagues’ successes, and it has created opportunities I never would have expected for getting involved in other projects.”

Once upon a time, physicians wrote letters to peers and colleagues around the world, sharing their medical discoveries, theories, case reports, and questions; conferring on problems; and then waiting for return mail to bring a reply. And the science of medicine advanced at a glacial pace.

Today, communication in multiple mediums flows much faster, almost instantaneously, between many more physicians, regardless of distance, addressing a much greater complexity of medical topics and treatments. And one of the chief mediums for this rapid electronic conversation among doctors is Twitter, according to Charlie Wray, DO, MS, a hospitalist at the University of California, San Francisco.

Dr. Wray, associate editor and digital media editor for the Journal of Hospital Medicine, is one of the moderators of #JHMchat, a monthly get-together on Twitter for interested hospitalists to link up virtually; respond to questions posed by JHM editors and other moderators; exchange perspectives, experiences, and tips with their peers; and build professional relationships and personal friendships. Relationship building has become particularly important in the age of COVID-19, when opportunities to connect in person at events such as SHM’s annual conferences have been curtailed.

The online #JHMchat community began in 2015, shortly after Dr. Wray completed a hospitalist research fellowship at the University of Chicago. His fellowship mentor, Vineet Arora, MD, MAPP, MHM, associate chief medical officer for the clinical learning environment at University of Chicago Medicine, had noticed how other online medical communities were engaging in discussions around different topics.

“She thought it could be a great way for hospitalists to meet online and talk about the articles published in JHM,” Dr. Wray explained. “We were all getting into social media and learning how to moderate interactive discussions such as Twitter.”

The chat’s founders approached JHM’s then-editor Andrew Auerbach, MD, MHM, a hospitalist at UCSF, who agreed that it was a great idea. They asked Christopher Moriates, MD, author of a recently published paper on the advisability of nebulized bronchodilators for obstructive pulmonary symptoms and assistant dean for health care value at the University of Texas, Austin, to come on the chat and talk about his paper. Visiting Dr. Arora at the time, he joined her in her living room for the first chat on Oct. 12, 2015. Seventy-five participants posted 431 tweets, with a total of 2 million Twitter impressions, suggesting that they had tapped a latent need.

How the chat works

To participate in the JHM chats on Twitter, one needs to open an account on the platform (it’s free) and follow the Journal’s Twitter feed (@jhospmedicine). But that’s pretty much it, Dr. Wray said. The group convenes on a Monday evening each month for an hour, starting at 9 p.m. Eastern time. Upcoming chats and topics are announced on Twitter and at SHM’s website.

The chats have grown and evolved since 2015, shifting in focus given recent social upheavals over the pandemic and heated discussions about diversity, equity, and racial justice in medicine, he said. “When COVID hit, the journal’s editor – Dr. Samir Shah – recognized that we were in a unique moment with the pandemic. The journal took advantage of the opportunity to publish a lot more personal perspectives and viewpoints around COVID, along with a special issue devoted to social justice.”

Moderators for the chat typically choose three or four questions based on recently published articles or other relevant topics, such as racial inequities in health care or how to apply military principles to hospital medicine leadership. “We reach out to authors and tell them they can explain their articles to interested readers through the chat. I can’t think of a single one who said no. They see the opportunity to highlight their work and engage with readers who want to ask them questions,” Dr. Wray said.

The moderators’ questions are posed to stimulate participation, but another goal is to use that hour for networking. “It’s a powerful tool to allow SHM members to engage with each other,” he said. “Sometimes the chat has the feeling of trying to drink water from a fire hose – with the messages flashing past so quickly. But the key is not to try to respond to everything but rather to follow those threads that particularly interest you. We encourage you to engage, but it’s totally fine if you just sit back and observe. One thing we have done to make it a little more formal is to offer CME credits for participants.”

The chat welcomes hospitalists and nonhospitalists, nurse practitioners, physician assistants, academics, and nonacademics. “No matter how engaged you are with Twitter, if you have 10,000 followers or 10, we’ll amplify your voice,” he said. “We also have medical students participating and consider their perspectives valuable, too.”

Dr. Wray identified three main types of participants in the monthly chats. The first are regulars who come every month, rain or shine. Like the character Norm in the old television comedy “Cheers,” everybody knows their name. They become friends, sharing and reveling in each other’s accomplishments. “These are people who have multiple connections, personally and professionally, at a lot of different levels. I probably know a hundred or more people who I’ve primarily gotten to know online.”

A second and larger group might be drawn in because of an interest in a specific topic or article, but they’re also welcome to participate in the chat. And the third group may lurk in the background, following along but not commenting. The size of that third group is unknown, but metrics from SHM show a total of 796 participants posting 4,088 tweets during chats in 2020 (for an average of 132 participants and 681 tweets per chat). This adds up to a total of 34 million impressions across the platform for #JHMchat tweets for the year.
 

 

Creating community online

“Why do we do it? It’s difficult to read all of the relevant published articles and keep up to date,” said Dr. Arora, a medical educator whose job at Chicago Medicine is to improve the clinical learning environment for trainees and staff by aligning learning with the health system’s institutional quality, safety and value missions.

“Our idea was to bring together a kind of virtual journal club and have discussions around topics such as: how do you create a shared vision on rounds? How do you integrate that into clinical practice? How do we preserve work/life balance or address structural racism?” she said. Other topics have included work flow concerns, burnout, difficult conversations with patients, and career planning.

“The people we’re trying to reach are hospitalists – and they’re busy at the front lines of care. We also thought this was an interesting way to raise the journal’s profile and spark broader interest in the articles it publishes. But it’s really about creating community, with people who look forward to talking and connecting with each other each month through the chats,” Dr. Arora said. If they miss a chat, they feel they’ve missed important interactions.

“Many times when people log onto the chat, they give a status report on where they are at, such as ‘I’m home putting my kids to bed,’ or ‘I’m on call tonight,’ ” she added. “People are willing to engage with the medium because it’s easy to engage with. We can forget that physicians are like everyone else. They like to learn, but they want that learning to be fun.”

On Dec. 14, 2020, at 9 p.m. Eastern time, the first question for the monthly #JHMchat was posted: How will caring for COVID-19 patients this winter differ from caring for patients in the first wave? Given that another surge of hospitalized COVID patients is looming, participants posted that they feel familiar and more confident with effective clinical strategies for hospitalized COVID patients, having learned so much more about the virus. But they’re facing greater numbers of patients than in prior surges. “In March, we were in crisis, now we’re in complexity,” one noted.

Joining the moderators was the Pediatric Overflow Planning Contingency Response Network (POPCoRN), a group formed earlier this year to help mobilize pediatric medical capacity for COVID patients during pandemic surges (see “POPCoRN network mobilizes pediatric capacity during pandemic,” The Hospitalist, April 30, 2020). One of its questions involved the redeployment of physicians in response to COVID demands and what, for example, pediatric hospitalists need as resources and tools when they are reassigned to adult patients or to new roles in unfamiliar settings. A variety of educational resources were cited from POPCoRN, SHM, and ImproveDX, among others.
 

Defining medical communication

Another chat moderator is Angela Castellanos, MD, a pediatric hospitalist at Tufts Medical Center in Boston. Dr. Castellanos did a 1-year, full-time fellowship right after residency at the New England Journal of Medicine, participating hands-on as a member of the editorial team for the print and online editions of the venerable journal. She is now doing a digital media fellowship with JHM, a part-time commitment while holding down a full-time job as a hospitalist. She also puts together a Spanish language podcast covering primary care pediatric issues for parents and families.

“I’m interested in medical communication generally, as I try to figure out what that means,” she said. “I have continued to look for ways to be part of the social media community and to be more creative about it. The JHM fellowship came at a perfect time for me to learn to do more in digital media.”

COVID has created new opportunities for more immediate dialogue with colleagues – what are they seeing and what’s working in the absence of clinical trials, she explained. “That’s how we communicate, as a way to get information out fast, such as when hospitals began proning COVID patients to make it easier for them to breathe.”

Dr. Castellanos said she grew up with text messaging and social media and wants to continue to grow her skills in this area. “I think I developed some skills at NEJM, but the opportunity to see how they do things at another journal with a different mission was also valuable. I get to share the space with people in academic settings and leaders in my field. I tweet at them; they tweet at me. These two fellowships have given me unique insights and mentorships. I know I want to continue doing pediatric hospital medicine and to engage academically and learn how to do research.”

Twitter sometimes gets a bad reputation for hostile or incendiary posts, Dr. Wray noted. “If you look at social media writ large, it can sometimes seem like a dumpster fire.” But what has happened in the medical community and in most medical Twitter encounters is a more cordial approach to conversations. “People who work in medicine converse with each other, with room for respectful disagreements. We’re extra supportive of each other,” he said.

“I think if hospitalists are looking for a community of peers, to engage with them and network and to find colleagues in similar circumstances, the JHM chat is such a fantastic place,” Dr. Wray concluded. “Don’t just come once, come several times, meet people along the way. For me, one of the most beneficial ways to advance my career has been by connecting with people through the chat. It allows me to share my work and success with the hospitalist community, as well as highlighting my trainees’ and colleagues’ successes, and it has created opportunities I never would have expected for getting involved in other projects.”

Dear colleagues,

I’m pleased to introduce the winter edition of The New Gastroenterologist – the first issue of 2021! The start of the new year has been very much anticipated because many hope that this year will bring some resolution to the challenges we faced in 2020.

With the pandemic came the widespread use of telemedicine, a feature of patient care that is likely here to stay. As physicians, it is imperative that we understand the legal implications of virtual medicine. Experienced medical malpractice lawyers Ashton Hyde and Grace Johnson (Younker Hyde Macfarlane) offer advice on this rapidly evolving realm of medicine.

Early career gastroenterologists often fall victim to self-doubt in a phenomenon referred to as impostor syndrome. Dr. Kimberly Brown (Wayne State University) discusses this important topic: what it is, how to recognize it, and how to mitigate it. One way to temper the effects of impostor syndrome is utilizing the art of coaching. Dr. Ami N. Shah (Rush) takes us through her journey and reviews the personal and professional benefits of implementing coaching in medicine.

Consults about feedings tubes can be daunting because experience with the placement and management of feeding tubes can be limited during training. This quarter’s “In Focus” article, written by Dr. John Fang and Dr. Gregory Toy (University of Utah) reviews the indications for placement, type of tubes available, and common complications and how to troubleshoot them. This is an absolute must-read for any new gastroenterologist.

How do you approach the patient who shows up for an open access endoscopy, but a quick chart review leads you to the realization that the procedure, is in fact, not indicated? There tends to be a lot of inertia which prevents cancellation of cases like this because the patient is already in the endoscopy suite, prepped, and has planned for this procedure in the preceding weeks or months. Dr. Laurel R. Fisher (University of Pennsylvania) unpacks the ethical considerations of this familiar scenario in this fantastic addition to our ethics case series.

In our postfellowship pathways section, Dr. Rena Yadlapati (University of California San Diego) and Dr. Kelli DeLay (University of Colorado) guide us through the path to becoming an esophagologist. In the DHPA Private Practice Perspectives article this quarter, Dr. Nadeem Baig (Allied Digestive Care) and Kevin Harlen (Capital Digestive Care) explain how clinical productivity is measured and how this translates into compensation in practice.

A silver lining of the pandemic is the way in which social media has been used to connect colleagues around the world in fostering medical education. Dr. Sultan Mahmood (State University of New York at Buffalo), Dr. Atoosa Rabiee (Washington DC VA Medical Center), Dr. Sunil Amin (University of Miami), Dr. Allon Kahn (Mayo Clinic Scottsdale), and Dr. Ijlal Akbar Ali (University of Oklahoma) discuss the inception of @GIJournal, a Twitter-based online journal club, and how it has gained popularity in recent months.

The AGA launched a new podcast, “Small Talk, Big Topics,” geared toward trainees and early career gastroenterologists, and through a brief question and answer session, we get to know the hosts: Dr. Matthew Whitson (Zucker School of Medicine at Hofstra-Northwell), Dr. Nina Nandy (Presbyterian Medical Group), and Dr. C.S. Tse (Brown University).

Lastly, I’d like to take a moment to recognize Lora McGlade, who has been instrumental in The New Gastroenterologist as the Medical Communications Editor for our publisher, Frontline. She assumed a new role at the end of last year, and I cannot thank her enough for her contributions in making this publication a success.

If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Ryan Farrell ([email protected]), managing editor of TNG.
 

Stay well,

Vijaya L. Rao, MD
Editor-in-Chief
Assistant Professor of Medicine, University of Chicago, Section of Gastroenterology, Hepatology & Nutrition

Dear colleagues,

I’m pleased to introduce the winter edition of The New Gastroenterologist – the first issue of 2021! The start of the new year has been very much anticipated because many hope that this year will bring some resolution to the challenges we faced in 2020.

With the pandemic came the widespread use of telemedicine, a feature of patient care that is likely here to stay. As physicians, it is imperative that we understand the legal implications of virtual medicine. Experienced medical malpractice lawyers Ashton Hyde and Grace Johnson (Younker Hyde Macfarlane) offer advice on this rapidly evolving realm of medicine.

Early career gastroenterologists often fall victim to self-doubt in a phenomenon referred to as impostor syndrome. Dr. Kimberly Brown (Wayne State University) discusses this important topic: what it is, how to recognize it, and how to mitigate it. One way to temper the effects of impostor syndrome is utilizing the art of coaching. Dr. Ami N. Shah (Rush) takes us through her journey and reviews the personal and professional benefits of implementing coaching in medicine.

Consults about feedings tubes can be daunting because experience with the placement and management of feeding tubes can be limited during training. This quarter’s “In Focus” article, written by Dr. John Fang and Dr. Gregory Toy (University of Utah) reviews the indications for placement, type of tubes available, and common complications and how to troubleshoot them. This is an absolute must-read for any new gastroenterologist.

How do you approach the patient who shows up for an open access endoscopy, but a quick chart review leads you to the realization that the procedure, is in fact, not indicated? There tends to be a lot of inertia which prevents cancellation of cases like this because the patient is already in the endoscopy suite, prepped, and has planned for this procedure in the preceding weeks or months. Dr. Laurel R. Fisher (University of Pennsylvania) unpacks the ethical considerations of this familiar scenario in this fantastic addition to our ethics case series.

In our postfellowship pathways section, Dr. Rena Yadlapati (University of California San Diego) and Dr. Kelli DeLay (University of Colorado) guide us through the path to becoming an esophagologist. In the DHPA Private Practice Perspectives article this quarter, Dr. Nadeem Baig (Allied Digestive Care) and Kevin Harlen (Capital Digestive Care) explain how clinical productivity is measured and how this translates into compensation in practice.

A silver lining of the pandemic is the way in which social media has been used to connect colleagues around the world in fostering medical education. Dr. Sultan Mahmood (State University of New York at Buffalo), Dr. Atoosa Rabiee (Washington DC VA Medical Center), Dr. Sunil Amin (University of Miami), Dr. Allon Kahn (Mayo Clinic Scottsdale), and Dr. Ijlal Akbar Ali (University of Oklahoma) discuss the inception of @GIJournal, a Twitter-based online journal club, and how it has gained popularity in recent months.

The AGA launched a new podcast, “Small Talk, Big Topics,” geared toward trainees and early career gastroenterologists, and through a brief question and answer session, we get to know the hosts: Dr. Matthew Whitson (Zucker School of Medicine at Hofstra-Northwell), Dr. Nina Nandy (Presbyterian Medical Group), and Dr. C.S. Tse (Brown University).

Lastly, I’d like to take a moment to recognize Lora McGlade, who has been instrumental in The New Gastroenterologist as the Medical Communications Editor for our publisher, Frontline. She assumed a new role at the end of last year, and I cannot thank her enough for her contributions in making this publication a success.

If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Ryan Farrell ([email protected]), managing editor of TNG.
 

Stay well,

Vijaya L. Rao, MD
Editor-in-Chief
Assistant Professor of Medicine, University of Chicago, Section of Gastroenterology, Hepatology & Nutrition

Dear colleagues,

I’m pleased to introduce the winter edition of The New Gastroenterologist – the first issue of 2021! The start of the new year has been very much anticipated because many hope that this year will bring some resolution to the challenges we faced in 2020.

With the pandemic came the widespread use of telemedicine, a feature of patient care that is likely here to stay. As physicians, it is imperative that we understand the legal implications of virtual medicine. Experienced medical malpractice lawyers Ashton Hyde and Grace Johnson (Younker Hyde Macfarlane) offer advice on this rapidly evolving realm of medicine.

Early career gastroenterologists often fall victim to self-doubt in a phenomenon referred to as impostor syndrome. Dr. Kimberly Brown (Wayne State University) discusses this important topic: what it is, how to recognize it, and how to mitigate it. One way to temper the effects of impostor syndrome is utilizing the art of coaching. Dr. Ami N. Shah (Rush) takes us through her journey and reviews the personal and professional benefits of implementing coaching in medicine.

Consults about feedings tubes can be daunting because experience with the placement and management of feeding tubes can be limited during training. This quarter’s “In Focus” article, written by Dr. John Fang and Dr. Gregory Toy (University of Utah) reviews the indications for placement, type of tubes available, and common complications and how to troubleshoot them. This is an absolute must-read for any new gastroenterologist.

How do you approach the patient who shows up for an open access endoscopy, but a quick chart review leads you to the realization that the procedure, is in fact, not indicated? There tends to be a lot of inertia which prevents cancellation of cases like this because the patient is already in the endoscopy suite, prepped, and has planned for this procedure in the preceding weeks or months. Dr. Laurel R. Fisher (University of Pennsylvania) unpacks the ethical considerations of this familiar scenario in this fantastic addition to our ethics case series.

In our postfellowship pathways section, Dr. Rena Yadlapati (University of California San Diego) and Dr. Kelli DeLay (University of Colorado) guide us through the path to becoming an esophagologist. In the DHPA Private Practice Perspectives article this quarter, Dr. Nadeem Baig (Allied Digestive Care) and Kevin Harlen (Capital Digestive Care) explain how clinical productivity is measured and how this translates into compensation in practice.

A silver lining of the pandemic is the way in which social media has been used to connect colleagues around the world in fostering medical education. Dr. Sultan Mahmood (State University of New York at Buffalo), Dr. Atoosa Rabiee (Washington DC VA Medical Center), Dr. Sunil Amin (University of Miami), Dr. Allon Kahn (Mayo Clinic Scottsdale), and Dr. Ijlal Akbar Ali (University of Oklahoma) discuss the inception of @GIJournal, a Twitter-based online journal club, and how it has gained popularity in recent months.

The AGA launched a new podcast, “Small Talk, Big Topics,” geared toward trainees and early career gastroenterologists, and through a brief question and answer session, we get to know the hosts: Dr. Matthew Whitson (Zucker School of Medicine at Hofstra-Northwell), Dr. Nina Nandy (Presbyterian Medical Group), and Dr. C.S. Tse (Brown University).

Lastly, I’d like to take a moment to recognize Lora McGlade, who has been instrumental in The New Gastroenterologist as the Medical Communications Editor for our publisher, Frontline. She assumed a new role at the end of last year, and I cannot thank her enough for her contributions in making this publication a success.

If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Ryan Farrell ([email protected]), managing editor of TNG.
 

Stay well,

Vijaya L. Rao, MD
Editor-in-Chief
Assistant Professor of Medicine, University of Chicago, Section of Gastroenterology, Hepatology & Nutrition

 

I am composing this editorial 4 days after the U.S. Capitol was invaded and 10 days before the presidential inauguration. It is impossible to ignore what is happening in our country, but I hesitate to add my thoughts to the overwhelming sea of opinions circulating in standard media, social media, and the dark web. I hope, as do many, that we return to a civil discourse, recognize the voices of all people, respect each other, and return to a belief in science and facts.

SARS-CoV-2 has devastated the world and will continue to cause preventable deaths until we adopt stricter mitigation measures, vaccinate most people, and develop widespread immunity. We are gaining immense knowledge about this virus, and as gastroenterologists, we are on the front lines in many aspects. A recent article in American Journal of Gastroenterology, among others, emphasized that mild GI symptoms may be the only presenting complaint for people with COVID-19. Responses to COVID-19, such as limits on elective procedures and social distancing, have upended our endoscopic processes and even altered the business models of GI practice. We will never go back to pre-COVID models.

The front page of this month’s GI & Hepatology News features important articles for our practice. One article delves into an extensive guideline from the American Gastroenterological Association on medical management of colonic diverticulitis. In another article, they also describe how efforts to encourage our patients with nonalcoholic fatty liver disease to exercise and manage their diet can make a real difference in their health. Finally, another explores how and why your immunocompromised patients (including those with inflammatory bowel disease) should and can be safely vaccinated for COVID-19.

Meanwhile, we need civility, science, and community. Without common purpose, we will experience the William Forster Lloyd’s Tragedy of the Commons. Incivility has economic and emotional costs, according to the Harvard Business Review. “Weathering,” the deterioration of Black women’s health over time that’s related to continued socioeconomic disadvantage, has multigenerational impacts; for example the Department of Health & Human Services reports that infant mortality among African American women is 2.3 times that of non-Hispanic Whites. Late effects of redlining continue to cause economic, health, and emotional harms (Badger E. “How Redlining’s Racist Effects Lasted for Decades” The New York Times. 2017 Aug 24).

“If Men were angels, no government would be necessary,” James Madison wrote. “In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and the next place, oblige it to control itself.”

John I. Allen, MD, MBA, AGAF
Editor in Chief

 

I am composing this editorial 4 days after the U.S. Capitol was invaded and 10 days before the presidential inauguration. It is impossible to ignore what is happening in our country, but I hesitate to add my thoughts to the overwhelming sea of opinions circulating in standard media, social media, and the dark web. I hope, as do many, that we return to a civil discourse, recognize the voices of all people, respect each other, and return to a belief in science and facts.

SARS-CoV-2 has devastated the world and will continue to cause preventable deaths until we adopt stricter mitigation measures, vaccinate most people, and develop widespread immunity. We are gaining immense knowledge about this virus, and as gastroenterologists, we are on the front lines in many aspects. A recent article in American Journal of Gastroenterology, among others, emphasized that mild GI symptoms may be the only presenting complaint for people with COVID-19. Responses to COVID-19, such as limits on elective procedures and social distancing, have upended our endoscopic processes and even altered the business models of GI practice. We will never go back to pre-COVID models.

The front page of this month’s GI & Hepatology News features important articles for our practice. One article delves into an extensive guideline from the American Gastroenterological Association on medical management of colonic diverticulitis. In another article, they also describe how efforts to encourage our patients with nonalcoholic fatty liver disease to exercise and manage their diet can make a real difference in their health. Finally, another explores how and why your immunocompromised patients (including those with inflammatory bowel disease) should and can be safely vaccinated for COVID-19.

Meanwhile, we need civility, science, and community. Without common purpose, we will experience the William Forster Lloyd’s Tragedy of the Commons. Incivility has economic and emotional costs, according to the Harvard Business Review. “Weathering,” the deterioration of Black women’s health over time that’s related to continued socioeconomic disadvantage, has multigenerational impacts; for example the Department of Health & Human Services reports that infant mortality among African American women is 2.3 times that of non-Hispanic Whites. Late effects of redlining continue to cause economic, health, and emotional harms (Badger E. “How Redlining’s Racist Effects Lasted for Decades” The New York Times. 2017 Aug 24).

“If Men were angels, no government would be necessary,” James Madison wrote. “In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and the next place, oblige it to control itself.”

John I. Allen, MD, MBA, AGAF
Editor in Chief

 

I am composing this editorial 4 days after the U.S. Capitol was invaded and 10 days before the presidential inauguration. It is impossible to ignore what is happening in our country, but I hesitate to add my thoughts to the overwhelming sea of opinions circulating in standard media, social media, and the dark web. I hope, as do many, that we return to a civil discourse, recognize the voices of all people, respect each other, and return to a belief in science and facts.

SARS-CoV-2 has devastated the world and will continue to cause preventable deaths until we adopt stricter mitigation measures, vaccinate most people, and develop widespread immunity. We are gaining immense knowledge about this virus, and as gastroenterologists, we are on the front lines in many aspects. A recent article in American Journal of Gastroenterology, among others, emphasized that mild GI symptoms may be the only presenting complaint for people with COVID-19. Responses to COVID-19, such as limits on elective procedures and social distancing, have upended our endoscopic processes and even altered the business models of GI practice. We will never go back to pre-COVID models.

The front page of this month’s GI & Hepatology News features important articles for our practice. One article delves into an extensive guideline from the American Gastroenterological Association on medical management of colonic diverticulitis. In another article, they also describe how efforts to encourage our patients with nonalcoholic fatty liver disease to exercise and manage their diet can make a real difference in their health. Finally, another explores how and why your immunocompromised patients (including those with inflammatory bowel disease) should and can be safely vaccinated for COVID-19.

Meanwhile, we need civility, science, and community. Without common purpose, we will experience the William Forster Lloyd’s Tragedy of the Commons. Incivility has economic and emotional costs, according to the Harvard Business Review. “Weathering,” the deterioration of Black women’s health over time that’s related to continued socioeconomic disadvantage, has multigenerational impacts; for example the Department of Health & Human Services reports that infant mortality among African American women is 2.3 times that of non-Hispanic Whites. Late effects of redlining continue to cause economic, health, and emotional harms (Badger E. “How Redlining’s Racist Effects Lasted for Decades” The New York Times. 2017 Aug 24).

“If Men were angels, no government would be necessary,” James Madison wrote. “In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and the next place, oblige it to control itself.”

John I. Allen, MD, MBA, AGAF
Editor in Chief

Introduction

Gastroenterologists are in a unique position to manage individuals with feeding tubes as their training underscores principles in digestion, absorption, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require a basic understanding of intestinal anatomy and physiology. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Indications for tube feeding

When deciding on the appropriate route for artificial nutrition support, the first decision to be made is enteral access versus parenteral nutrition support. Enteral nutrition confers multiple benefits, including preservation of the mucosal lining, reductions in complicated infections, decreased costs, and improved patient compliance. All attempts at adequate enteral access should be made before deciding on the use of parenteral nutrition. Following the clinical decision to pursue artificial means of nutrition support and enteral access, the next common decision is the anticipated duration of nutrition support. Generally, the oral or nasal tubes are used for short durations (i.e., less than 4 weeks) with percutaneous placement into the stomach or small intestine for longer-term feeding (i.e., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ]).

The most general indication for nutrition support is an inability to maintain adequate nutritional needs with oral intake alone. General categories of inadequate oral intake include neurologic disorders, malignancy, and gastrointestinal conditions affecting digestion and absorption (Table 1). Absolute and relative contraindications to PEG placement are listed in Table 2. If an endoscopic placement is not possible, alternative means of placement (i.e., surgery or interventional radiology) can be considered to avoid the consequences of prolonged malnutrition. In-hospital mortality following PEG placement has decreased 40% over the last 10 years, which can be attributed to improved patient selection, enhanced discharge practices, and exclusion of patients with the highest comorbidity and mortality rates, like those with advanced dementia or terminal cancer.¹

PEG placement in patients with dementia is controversial, with previous studies not demonstrating improved outcomes and association with high mortality rates,² so the practice is currently not recommended by the American Geriatrics Society in individuals with advanced dementia.³ However, a large Japanese study showed that careful selection of patients with mild dementia to undergo gastrostomy increased independence fourfold; therefore, multidisciplinary involvement is often necessary in the decision to pursue artificial means of nutrition support in this population.⁴

The recent coronavirus disease 2019 (COVID-19) pandemic has placed additional strains on endoscopic placement and has highlighted the effect of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) on GI symptoms. A recent meta-analysis showed an overall incidence of GI symptoms of 17.6% in the following conditions in decreasing order of prevalence: anorexia, diarrhea, nausea, vomiting, and abdominal discomfort.⁵ In addition, the prolonged ventilatory requirements among a subset of individuals with the most severe COVID-19 results in extended periods of nutrition support via enteral tube placements. In individuals with ICU-acquired weakness and discharge to long-term care facilities, the placement of percutaneous endoscopic tubes may be required, although with the additional consideration of the need for an aerosolizing procedure. Delay of placement has been advocated, in addition to appropriate personal protective equipment, in order to ensure safe placement for the endoscopy staff.⁶
 

 

Types of feeding tubes

After deciding to feed a patient enterally and determining the anticipated duration of enteral support, the next decision is to determine the most appropriate location of feeding delivery: into the stomach or the small bowel. Gastric feeding is advantageous most commonly because of its increased capacity, allowing for larger volumes to be delivered over shorter durations. However, in the setting of postsurgical anatomy, gastroparesis, or obstructing tumors/pancreatic inflammation, distal delivery of tube feeds may be required into the jejunum. Additionally, percutaneous tubes placed into the stomach can have extenders into the small bowel (GJ tubes) to allow for feeding into the small bowel and decompression or delivery of medications into the stomach.

In general, gastric feeding is preferred over small bowel feeding as PEG tubes are more stable and have fewer complications than either PEG-J or direct PEJ tubes. Gastrostomy tubes are generally shorter and larger in diameter making them less likely to clog. PEG-J tubes have separate lumens for gastric and small intestinal access, but the smaller-bore jejunal extension tubes are more likely to clog or become dislodged. While direct PEJ is shown to have higher rates of tube patency and decreased rates of endoscopic re-intervention, compared with PEG-J,⁷ one limitation of a direct PEJ is difficulty in placement and site selection, which can be performed with a pediatric colonoscope or balloon enteroscopy system. Most commonly, this procedure is performed under general anesthesia.

In the case of a critically ill patient in the ICU, it is recommended to start enteral nutrition within 24-48 hours of arrival to avoid complications of prolonged calorie deficits. Nasally inserted feeding tubes (e.g., Cortrak, Avanos Medical Devices, Alpharetta, Ga.) are most commonly used at the bedside and can be placed blindly using electromagnetic image guidance, radiographically, or endoscopy. However, the small caliber of nasoenteric tubes comes with the common complication of clogging, which can be overcome with slightly larger bore gastric feeding tubes. If gastric feeding is not tolerated (e.g., in the case of vomiting, witnessed aspiration), small bowel feeding should be initiated and can be a more durable form of enteral feeding with fewer interruptions as feedings do not need to be held for procedures or symptomatic gastric intolerance. In clinical areas of question, or if there is a concern for intolerance of enteral feeding, a short trial with nasogastric or nasojejunal tube placement should be performed before a more definitive percutaneous placement.

With respect to percutaneous tubes, important characteristics to choose are the size (diameter in French units), type of internal retention device, and external appearance of the tube (standard or low profile). All percutaneous tubes contain an external retention device (i.e., bumper) that fits against the skin and an internal retention device that is either a balloon or plastic dome or funnel that prevents the tube from becoming dislodged. Balloon retention tubes require replacement every 3-6 months, while nonballoon tubes generally require replacement annually in order to prevent the plastic from cracking, which can make removal complicated. Low-profile tubes have an external cap, which, when opened, allows for extension tubing to be securely attached while in use and detached while not in use. Low-profile tubes are often preferred among younger, active patients and those with adequate dexterity to allow for attachment of the external extension tubing. These tubes are most often inserted as a replacement for an initially endoscopically placed tube, although one-step systems for initial placement are available. The size of the low-profile tube is chosen based on the size of the existing PEG tube and by measuring the length of the stoma tract using specialized measuring devices.⁸ Patients and caregivers can also be trained to replace balloon-type tubes on their own to limit complications of displaced or cracked tubes. Low-profile tubes are commercially available for both gastric placement and gastric placement with extension into the small bowel, which often requires fluoroscopy for secure placement.

All percutaneous enteral tubes are being transitioned to the ENfit connector system, which prevents connections from the enteral system to nonenteral systems (namely intravenous lines, chest tubes) and vice versa. Tubing misconnections have been rarely reported, and the EnFIT system is designed to prevent such misadventures that have resulted in serious complications and even mortality.⁹ Adapter devices are available that may be required for patients with feeding tubes who have not been transitioned yet. Most commonly with new tube placements and replacements, patients and providers will have to become familiar with the new syringes and feeding bags required with EnFIT connectors.

Gastrostomy placement can be considered a higher-risk endoscopic procedure. One complicating factor is the increased use of antiplatelet and anticoagulant therapies in individuals with a history of neurologic insults. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend that coumadin be held 5 days before the procedure and bridged with heparin if the patient is at high risk of thromboembolic complications. For patients on dual anti-platelet therapy, thienopyridines like clopidogrel are often stopped 5-7 days prior to procedure with continuation of aspirin,¹⁰ but there are more recent data that PEG insertion is safe with continued use of DAPT.¹¹ Direct-acting anticoagulants (DOACs) are often stopped 24-48 hours prior to procedure and then restarted 48 hours after tube placement, but this is dependent on the half-life of the specific DOAC and the patient’s renal function. Patients with decreased creatinine clearance may need to hold the DOAC up to 3-4 days prior to the procedure. In this situation, referring to ASGE guidelines and consultation with a hematologist or managing anti-coagulation clinic is advised.¹⁰
 

 

Troubleshooting complications

Nasoenteric tubes: One of the most common and irritating complications with nasoenteric feeding tubes is clogging. To prevent clogging, the tube should be flushed frequently.¹² At least 30 mL of free water should be used to flush the tube every 4-8 hours for continuous feedings or before and after bolus feeding. Additionally, 15-30 mL of water should be given with each separate medication administration, and if possible, medication administration via small-bore small bowel feeding tubes should be avoided.¹² Water flushing is especially important with small-caliber tubes and pumps that deliver both feeding and water flushes. It is available for small bowel feeding in order to allow for programmed water delivery.

Warm water flushes can also help unclog the tube,¹² and additional pharmacologic and mechanical devices have been promoted for clogged tubes. One common technique is mixing pancreatic enzymes (Viokase) with a crushed 325-mg tablet of nonenteric coated sodium bicarbonate and 5 mL of water to create a solution that has the alkaline properties allowing for both pancreatic enzyme activation and clog dissolution. Additionally, an endoscopic retrograde cholangiopancreatography (ERCP) catheter can be placed into longer feeding tubes to directly infuse the activated agent to the site of the clog.¹³ If water and enzymes are not successful in unclogging the tube, commercially available brushes can help remove clogs. The TubeClear® system (Actuated Medical, Bellefonte, Penna) has a single-use stem that is connected to AC power to create a jackhammerlike movement to remove clogs in longer nasoenteral and gastrojejunal tubes.
 

PEG tubes (short-term complications): Procedural and immediate postprocedural complications include bleeding, aspiration, pneumoperitoneum, and perforation. Pneumoperitoneum occurs in approximately 50% of cases and is generally clinically insignificant. The risk of pneumoperitoneum can be reduced by using CO2 insufflation.¹⁴ If the patient develops systemic signs of infection or peritoneal signs, CT scan with oral contrast is warranted for further evaluation and to assess for inadvertent perforation of overlying bowel or dislodged tube. Aspiration during or following endoscopy is another common complication of PEG placement and risk factors include over-sedation, supine positioning, advanced age, and neurologic dysfunction. This risk can be mitigated by avoiding over-sedation, immediately aspirating gastric contents when the stomach is reached, and avoiding excessive insufflation.¹⁵ In addition, elevating the head of the bed during the procedure and dedicating an assistant to perform oral suctioning during the entire procedure is recommended.

PEG tubes (long-term complications): More delayed complications of PEG insertion include wound infection, buried bumper syndrome, tumor seeding, peristomal leakage, and tube dislodgement. The prevalence of wound infection is 5%- 25%,¹⁶ and randomized controlled trials have demonstrated the efficacy of a single dose of an IV antibiotic (i.e., cephalosporin) in those not already receiving a broad spectrum antibiotic and administered prophylactically before tube placement.¹⁷ The significance of this reduction is such that antibiotic administration before tube placement should be considered a quality measure for the procedure. A small amount of redness around the tube site (less than 5 mm) is typical, but extension of erythema, warmth, tenderness, purulent drainage, or systemic symptoms is consistent with infection and warrants additional antibiotic administration. Minor infections can be treated with local antiseptics and oral antibiotics, and early intervention is important to prevent need for hospital admission, systemic antibiotics, and even surgical debridement.

 

Peristomal leakage is reported in approximately 1%-2% of patients.¹⁸ Photographs of the site can be very useful in evaluating and managing peristomal leakage and infections. Interventions include reducing gastric secretions with proton pump inhibitors and management of the skin with barrier creams, such as zinc oxide (Calmoseptine®) ointment. Placement of a larger-diameter tube only enlarges the stoma track and worsens the leakage. In such cases, thorough evaluations for delayed gastric emptying (gastroparesis), distal obstruction, or constipation should be performed and managed accordingly. Opiates are common contributors to constipation and delayed gastric emptying and often require reduction in use or directed antagonist therapy to reduce leaking. Continuous feeding over bolus feedings and delivering nutrition distally into the small bowel (PEG-J placement) can improve leaking from gastrostomy tubes. Additional means of management include stabilizing the tube by replacing a traditional tube with a low-profile tube or using right-angle external bumpers. If all measures fail, removing the tube and allowing for stomal closure can be attempted,¹⁶ although this option often requires parenteral nutrition support to prevent prolonged periods of inadequate nutrition.

Buried bumper syndrome (BBS) occurs in 1.5%-8.8% of PEG placements and is a common late complication of PEG placement, although early reports have been described.¹⁸ The development of BBS occurs when the internal bumper migrates from the gastric lumen through and into the stomach or abdominal wall. It occurs more frequently with solid nonballoon retention tubes and is caused by excessive compression of the external bumper against the skin and abdominal wall. Patients with BBS usually present with an immobile catheter, resistance with feeds (because of a closure of the stomach wall around the internal portion of the gastrostomy tube), abdominal pain, or peristomal leakage. Physicians should be aware of and assess tubes for BBS, in particular when replacing an immobile tube (cannot be pushed into the free stomach lumen) or when there is difficulty in flushing water into the tube. This complication can be easily prevented by allowing a minimum of 0.5-1.0 cm (1 finger breadth) between the external bumper and the abdominal wall. In particular, patients and caregivers should be warned that if the patient gains significant amounts of weight, the outer bumper will need to be loosened. Once BBS is diagnosed, the PEG tube requires removal and replacement as it can cause bleeding, infection, or fasciitis. The general steps to replacement include endoscopic removal of the existing tube and replacement of new PEG in the existing tract as long as the BBS is not severe. In most cases a replacement tube can be pulled into place using the pull-PEG technique at the same gastrostomy site as long as the stoma tract can be cannulated with a wire after the existing tube is removed.

Similar to nasoenteric tubes, PEG tubes can become clogged, although this complication is infrequent. The primary steps for prevention include adequately flushing with water before and after feeds and ensuring that all medications are liquid or well crushed and dissolved before instilling. Timely tube replacement also ensures that the internal portions of the gastrostomy tube remain free of debris. Management is similar to that of unclogging nasoenteral tubes, as discussed above, and specific commercial declogging devices for PEG tubes include the Bionix Declogger® (Bionix Development Corp., Toledo, Ohio) and the Bard® PEG cleaning brush (Bard Peripheral Vascular Inc., Tempe, Ariz.). The Bionix system has a plastic stem with a screw and thread design that will remove clogs in 14-24 French PEG tubes, while the Bard brush has a flexible nylon stem with soft bristles at the end to prevent mucosal injury and can be used for prophylaxis against clogs, as well as removing clogs themselves.¹²

Lastly, a rare but important complication of PEG placement is tumor seeding of the PEG site in patients with active head and neck or upper gastrointestinal cancer.¹⁹ The presumed mechanism is shearing of tumor cells as the PEG is pulled through the upper aerodigestive tract and through the wall of the stomach, as prior studies have demonstrated frequent seeding of tubes and incision sites as shown by brushing the tube for malignant cells after tube placement.²⁰ It is important to recognize this complication and not misdiagnose it as granulation tissue, infection, or bleeding as the spread of the cancer generally portends a poor prognosis. Therefore, it is best to use a PEG insertion technique that does not involve pulling or pushing the PEG through the upper aerodigestive tract in patients with active cancer and instead place tubes via an external approach by colleagues in interventional radiology or via direct surgical placement.
 

 

Conclusion

Gastroenterologists occupy a unique role in evaluation, diagnosis, and management of patients requiring enteral feeding. In addition, they are best equipped to place, prevent, and manage complications of tube feeding. For this reason, it is imperative that gastroenterologists familiarize themselves with indications for enteral tubes and types of enteral tubes available, as well as the identification and management of common complications. Comprehensive understanding of these concepts will augment the practicing gastroenterologist’s ability to manage patients requiring enteral nutrition support with confidence.

References

1. Stein DJ et al. Dig Dis Sci. 2020 Jun 19. doi: 10.1007/s10620-020-06396-y.

2. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.

3. Dietrich CG, Schoppmeyer K. World J Gastroenterol. 2020;26(20):2464-71.

4. Suzuki Y et al. T Gastroenterology Res.2012 Feb;5(1):10-20.

5. Cheung KS et al. Gastroenterology. 2020 Jul;159(1):81-95.

6. Micic D et al. Am J Gastroenterol. 2020 Sep;115(9):1367-70.

7. Fan AC et al. Gastrointest Endosc. 2002;56(6):890-4.

8. Tang SJ. Video J Encycl GI Endosc. 2014;2(2):70-3.

9. Guenter P, Lyman B. Nutr Clin Pract. 2016;31(6):769-72.

10. Acosta RD et al. Gastrointest Endosc. 2016;83(1):3-16.

11. Richter JA et al. Gastrointest Endosc. 2011;74(1):22-34.

12. Boullata JI et al. JPEN. 2017;41(1):15-103.

13. McClave SA. Tech Gastrointest Endosc. 2021;3(1):62-8.

14. Murphy CJ et al. Endosc Int Open. 2016;4(3):E292. doi: 10.1053/tgie.2001.19915.

15. Lynch CR et al. Pract Gastroenterology. 2004;28:66-77.

16. Hucl T et al. Best Pract Res Clin Gastroenterol. 2016;30(5):769-81. doi: 10.1016/j.bpg.2016.10.002.

17. Jafri NS et al. Aliment Pharmacol & Therapeut. 2007;25(6):647-56. doi: 10.1111/j.1365-2036.2007.03247.x.

18. Blumenstein I et al. World J Gastroenterol. 2014;20(26):8505-24. doi: 10.3748/wjg.v20.i26.8505.

19. Fung E et al. Surgical Endosc. 2017;31(9):3623-7. doi: 10.1007/s00464-016-5394-8.

20. Ellrichmann M et al. Endoscopy. 2013;45(07):526-31. doi: 10.1055/s-0033-1344023.

Dr. Toy is with the department of internal medicine at the University of Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and hepatology at the University of Utah.

Introduction

Gastroenterologists are in a unique position to manage individuals with feeding tubes as their training underscores principles in digestion, absorption, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require a basic understanding of intestinal anatomy and physiology. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Indications for tube feeding

When deciding on the appropriate route for artificial nutrition support, the first decision to be made is enteral access versus parenteral nutrition support. Enteral nutrition confers multiple benefits, including preservation of the mucosal lining, reductions in complicated infections, decreased costs, and improved patient compliance. All attempts at adequate enteral access should be made before deciding on the use of parenteral nutrition. Following the clinical decision to pursue artificial means of nutrition support and enteral access, the next common decision is the anticipated duration of nutrition support. Generally, the oral or nasal tubes are used for short durations (i.e., less than 4 weeks) with percutaneous placement into the stomach or small intestine for longer-term feeding (i.e., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ]).

The most general indication for nutrition support is an inability to maintain adequate nutritional needs with oral intake alone. General categories of inadequate oral intake include neurologic disorders, malignancy, and gastrointestinal conditions affecting digestion and absorption (Table 1). Absolute and relative contraindications to PEG placement are listed in Table 2. If an endoscopic placement is not possible, alternative means of placement (i.e., surgery or interventional radiology) can be considered to avoid the consequences of prolonged malnutrition. In-hospital mortality following PEG placement has decreased 40% over the last 10 years, which can be attributed to improved patient selection, enhanced discharge practices, and exclusion of patients with the highest comorbidity and mortality rates, like those with advanced dementia or terminal cancer.¹

PEG placement in patients with dementia is controversial, with previous studies not demonstrating improved outcomes and association with high mortality rates,² so the practice is currently not recommended by the American Geriatrics Society in individuals with advanced dementia.³ However, a large Japanese study showed that careful selection of patients with mild dementia to undergo gastrostomy increased independence fourfold; therefore, multidisciplinary involvement is often necessary in the decision to pursue artificial means of nutrition support in this population.⁴

The recent coronavirus disease 2019 (COVID-19) pandemic has placed additional strains on endoscopic placement and has highlighted the effect of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) on GI symptoms. A recent meta-analysis showed an overall incidence of GI symptoms of 17.6% in the following conditions in decreasing order of prevalence: anorexia, diarrhea, nausea, vomiting, and abdominal discomfort.⁵ In addition, the prolonged ventilatory requirements among a subset of individuals with the most severe COVID-19 results in extended periods of nutrition support via enteral tube placements. In individuals with ICU-acquired weakness and discharge to long-term care facilities, the placement of percutaneous endoscopic tubes may be required, although with the additional consideration of the need for an aerosolizing procedure. Delay of placement has been advocated, in addition to appropriate personal protective equipment, in order to ensure safe placement for the endoscopy staff.⁶
 

 

Types of feeding tubes

After deciding to feed a patient enterally and determining the anticipated duration of enteral support, the next decision is to determine the most appropriate location of feeding delivery: into the stomach or the small bowel. Gastric feeding is advantageous most commonly because of its increased capacity, allowing for larger volumes to be delivered over shorter durations. However, in the setting of postsurgical anatomy, gastroparesis, or obstructing tumors/pancreatic inflammation, distal delivery of tube feeds may be required into the jejunum. Additionally, percutaneous tubes placed into the stomach can have extenders into the small bowel (GJ tubes) to allow for feeding into the small bowel and decompression or delivery of medications into the stomach.

In general, gastric feeding is preferred over small bowel feeding as PEG tubes are more stable and have fewer complications than either PEG-J or direct PEJ tubes. Gastrostomy tubes are generally shorter and larger in diameter making them less likely to clog. PEG-J tubes have separate lumens for gastric and small intestinal access, but the smaller-bore jejunal extension tubes are more likely to clog or become dislodged. While direct PEJ is shown to have higher rates of tube patency and decreased rates of endoscopic re-intervention, compared with PEG-J,⁷ one limitation of a direct PEJ is difficulty in placement and site selection, which can be performed with a pediatric colonoscope or balloon enteroscopy system. Most commonly, this procedure is performed under general anesthesia.

In the case of a critically ill patient in the ICU, it is recommended to start enteral nutrition within 24-48 hours of arrival to avoid complications of prolonged calorie deficits. Nasally inserted feeding tubes (e.g., Cortrak, Avanos Medical Devices, Alpharetta, Ga.) are most commonly used at the bedside and can be placed blindly using electromagnetic image guidance, radiographically, or endoscopy. However, the small caliber of nasoenteric tubes comes with the common complication of clogging, which can be overcome with slightly larger bore gastric feeding tubes. If gastric feeding is not tolerated (e.g., in the case of vomiting, witnessed aspiration), small bowel feeding should be initiated and can be a more durable form of enteral feeding with fewer interruptions as feedings do not need to be held for procedures or symptomatic gastric intolerance. In clinical areas of question, or if there is a concern for intolerance of enteral feeding, a short trial with nasogastric or nasojejunal tube placement should be performed before a more definitive percutaneous placement.

With respect to percutaneous tubes, important characteristics to choose are the size (diameter in French units), type of internal retention device, and external appearance of the tube (standard or low profile). All percutaneous tubes contain an external retention device (i.e., bumper) that fits against the skin and an internal retention device that is either a balloon or plastic dome or funnel that prevents the tube from becoming dislodged. Balloon retention tubes require replacement every 3-6 months, while nonballoon tubes generally require replacement annually in order to prevent the plastic from cracking, which can make removal complicated. Low-profile tubes have an external cap, which, when opened, allows for extension tubing to be securely attached while in use and detached while not in use. Low-profile tubes are often preferred among younger, active patients and those with adequate dexterity to allow for attachment of the external extension tubing. These tubes are most often inserted as a replacement for an initially endoscopically placed tube, although one-step systems for initial placement are available. The size of the low-profile tube is chosen based on the size of the existing PEG tube and by measuring the length of the stoma tract using specialized measuring devices.⁸ Patients and caregivers can also be trained to replace balloon-type tubes on their own to limit complications of displaced or cracked tubes. Low-profile tubes are commercially available for both gastric placement and gastric placement with extension into the small bowel, which often requires fluoroscopy for secure placement.

All percutaneous enteral tubes are being transitioned to the ENfit connector system, which prevents connections from the enteral system to nonenteral systems (namely intravenous lines, chest tubes) and vice versa. Tubing misconnections have been rarely reported, and the EnFIT system is designed to prevent such misadventures that have resulted in serious complications and even mortality.⁹ Adapter devices are available that may be required for patients with feeding tubes who have not been transitioned yet. Most commonly with new tube placements and replacements, patients and providers will have to become familiar with the new syringes and feeding bags required with EnFIT connectors.

Gastrostomy placement can be considered a higher-risk endoscopic procedure. One complicating factor is the increased use of antiplatelet and anticoagulant therapies in individuals with a history of neurologic insults. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend that coumadin be held 5 days before the procedure and bridged with heparin if the patient is at high risk of thromboembolic complications. For patients on dual anti-platelet therapy, thienopyridines like clopidogrel are often stopped 5-7 days prior to procedure with continuation of aspirin,¹⁰ but there are more recent data that PEG insertion is safe with continued use of DAPT.¹¹ Direct-acting anticoagulants (DOACs) are often stopped 24-48 hours prior to procedure and then restarted 48 hours after tube placement, but this is dependent on the half-life of the specific DOAC and the patient’s renal function. Patients with decreased creatinine clearance may need to hold the DOAC up to 3-4 days prior to the procedure. In this situation, referring to ASGE guidelines and consultation with a hematologist or managing anti-coagulation clinic is advised.¹⁰
 

 

Troubleshooting complications

Nasoenteric tubes: One of the most common and irritating complications with nasoenteric feeding tubes is clogging. To prevent clogging, the tube should be flushed frequently.¹² At least 30 mL of free water should be used to flush the tube every 4-8 hours for continuous feedings or before and after bolus feeding. Additionally, 15-30 mL of water should be given with each separate medication administration, and if possible, medication administration via small-bore small bowel feeding tubes should be avoided.¹² Water flushing is especially important with small-caliber tubes and pumps that deliver both feeding and water flushes. It is available for small bowel feeding in order to allow for programmed water delivery.

Warm water flushes can also help unclog the tube,¹² and additional pharmacologic and mechanical devices have been promoted for clogged tubes. One common technique is mixing pancreatic enzymes (Viokase) with a crushed 325-mg tablet of nonenteric coated sodium bicarbonate and 5 mL of water to create a solution that has the alkaline properties allowing for both pancreatic enzyme activation and clog dissolution. Additionally, an endoscopic retrograde cholangiopancreatography (ERCP) catheter can be placed into longer feeding tubes to directly infuse the activated agent to the site of the clog.¹³ If water and enzymes are not successful in unclogging the tube, commercially available brushes can help remove clogs. The TubeClear® system (Actuated Medical, Bellefonte, Penna) has a single-use stem that is connected to AC power to create a jackhammerlike movement to remove clogs in longer nasoenteral and gastrojejunal tubes.
 

PEG tubes (short-term complications): Procedural and immediate postprocedural complications include bleeding, aspiration, pneumoperitoneum, and perforation. Pneumoperitoneum occurs in approximately 50% of cases and is generally clinically insignificant. The risk of pneumoperitoneum can be reduced by using CO2 insufflation.¹⁴ If the patient develops systemic signs of infection or peritoneal signs, CT scan with oral contrast is warranted for further evaluation and to assess for inadvertent perforation of overlying bowel or dislodged tube. Aspiration during or following endoscopy is another common complication of PEG placement and risk factors include over-sedation, supine positioning, advanced age, and neurologic dysfunction. This risk can be mitigated by avoiding over-sedation, immediately aspirating gastric contents when the stomach is reached, and avoiding excessive insufflation.¹⁵ In addition, elevating the head of the bed during the procedure and dedicating an assistant to perform oral suctioning during the entire procedure is recommended.

PEG tubes (long-term complications): More delayed complications of PEG insertion include wound infection, buried bumper syndrome, tumor seeding, peristomal leakage, and tube dislodgement. The prevalence of wound infection is 5%- 25%,¹⁶ and randomized controlled trials have demonstrated the efficacy of a single dose of an IV antibiotic (i.e., cephalosporin) in those not already receiving a broad spectrum antibiotic and administered prophylactically before tube placement.¹⁷ The significance of this reduction is such that antibiotic administration before tube placement should be considered a quality measure for the procedure. A small amount of redness around the tube site (less than 5 mm) is typical, but extension of erythema, warmth, tenderness, purulent drainage, or systemic symptoms is consistent with infection and warrants additional antibiotic administration. Minor infections can be treated with local antiseptics and oral antibiotics, and early intervention is important to prevent need for hospital admission, systemic antibiotics, and even surgical debridement.

 

Peristomal leakage is reported in approximately 1%-2% of patients.¹⁸ Photographs of the site can be very useful in evaluating and managing peristomal leakage and infections. Interventions include reducing gastric secretions with proton pump inhibitors and management of the skin with barrier creams, such as zinc oxide (Calmoseptine®) ointment. Placement of a larger-diameter tube only enlarges the stoma track and worsens the leakage. In such cases, thorough evaluations for delayed gastric emptying (gastroparesis), distal obstruction, or constipation should be performed and managed accordingly. Opiates are common contributors to constipation and delayed gastric emptying and often require reduction in use or directed antagonist therapy to reduce leaking. Continuous feeding over bolus feedings and delivering nutrition distally into the small bowel (PEG-J placement) can improve leaking from gastrostomy tubes. Additional means of management include stabilizing the tube by replacing a traditional tube with a low-profile tube or using right-angle external bumpers. If all measures fail, removing the tube and allowing for stomal closure can be attempted,¹⁶ although this option often requires parenteral nutrition support to prevent prolonged periods of inadequate nutrition.

Buried bumper syndrome (BBS) occurs in 1.5%-8.8% of PEG placements and is a common late complication of PEG placement, although early reports have been described.¹⁸ The development of BBS occurs when the internal bumper migrates from the gastric lumen through and into the stomach or abdominal wall. It occurs more frequently with solid nonballoon retention tubes and is caused by excessive compression of the external bumper against the skin and abdominal wall. Patients with BBS usually present with an immobile catheter, resistance with feeds (because of a closure of the stomach wall around the internal portion of the gastrostomy tube), abdominal pain, or peristomal leakage. Physicians should be aware of and assess tubes for BBS, in particular when replacing an immobile tube (cannot be pushed into the free stomach lumen) or when there is difficulty in flushing water into the tube. This complication can be easily prevented by allowing a minimum of 0.5-1.0 cm (1 finger breadth) between the external bumper and the abdominal wall. In particular, patients and caregivers should be warned that if the patient gains significant amounts of weight, the outer bumper will need to be loosened. Once BBS is diagnosed, the PEG tube requires removal and replacement as it can cause bleeding, infection, or fasciitis. The general steps to replacement include endoscopic removal of the existing tube and replacement of new PEG in the existing tract as long as the BBS is not severe. In most cases a replacement tube can be pulled into place using the pull-PEG technique at the same gastrostomy site as long as the stoma tract can be cannulated with a wire after the existing tube is removed.

Similar to nasoenteric tubes, PEG tubes can become clogged, although this complication is infrequent. The primary steps for prevention include adequately flushing with water before and after feeds and ensuring that all medications are liquid or well crushed and dissolved before instilling. Timely tube replacement also ensures that the internal portions of the gastrostomy tube remain free of debris. Management is similar to that of unclogging nasoenteral tubes, as discussed above, and specific commercial declogging devices for PEG tubes include the Bionix Declogger® (Bionix Development Corp., Toledo, Ohio) and the Bard® PEG cleaning brush (Bard Peripheral Vascular Inc., Tempe, Ariz.). The Bionix system has a plastic stem with a screw and thread design that will remove clogs in 14-24 French PEG tubes, while the Bard brush has a flexible nylon stem with soft bristles at the end to prevent mucosal injury and can be used for prophylaxis against clogs, as well as removing clogs themselves.¹²

Lastly, a rare but important complication of PEG placement is tumor seeding of the PEG site in patients with active head and neck or upper gastrointestinal cancer.¹⁹ The presumed mechanism is shearing of tumor cells as the PEG is pulled through the upper aerodigestive tract and through the wall of the stomach, as prior studies have demonstrated frequent seeding of tubes and incision sites as shown by brushing the tube for malignant cells after tube placement.²⁰ It is important to recognize this complication and not misdiagnose it as granulation tissue, infection, or bleeding as the spread of the cancer generally portends a poor prognosis. Therefore, it is best to use a PEG insertion technique that does not involve pulling or pushing the PEG through the upper aerodigestive tract in patients with active cancer and instead place tubes via an external approach by colleagues in interventional radiology or via direct surgical placement.
 

 

Conclusion

Gastroenterologists occupy a unique role in evaluation, diagnosis, and management of patients requiring enteral feeding. In addition, they are best equipped to place, prevent, and manage complications of tube feeding. For this reason, it is imperative that gastroenterologists familiarize themselves with indications for enteral tubes and types of enteral tubes available, as well as the identification and management of common complications. Comprehensive understanding of these concepts will augment the practicing gastroenterologist’s ability to manage patients requiring enteral nutrition support with confidence.

References

1. Stein DJ et al. Dig Dis Sci. 2020 Jun 19. doi: 10.1007/s10620-020-06396-y.

2. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.

3. Dietrich CG, Schoppmeyer K. World J Gastroenterol. 2020;26(20):2464-71.

4. Suzuki Y et al. T Gastroenterology Res.2012 Feb;5(1):10-20.

5. Cheung KS et al. Gastroenterology. 2020 Jul;159(1):81-95.

6. Micic D et al. Am J Gastroenterol. 2020 Sep;115(9):1367-70.

7. Fan AC et al. Gastrointest Endosc. 2002;56(6):890-4.

8. Tang SJ. Video J Encycl GI Endosc. 2014;2(2):70-3.

9. Guenter P, Lyman B. Nutr Clin Pract. 2016;31(6):769-72.

10. Acosta RD et al. Gastrointest Endosc. 2016;83(1):3-16.

11. Richter JA et al. Gastrointest Endosc. 2011;74(1):22-34.

12. Boullata JI et al. JPEN. 2017;41(1):15-103.

13. McClave SA. Tech Gastrointest Endosc. 2021;3(1):62-8.

14. Murphy CJ et al. Endosc Int Open. 2016;4(3):E292. doi: 10.1053/tgie.2001.19915.

15. Lynch CR et al. Pract Gastroenterology. 2004;28:66-77.

16. Hucl T et al. Best Pract Res Clin Gastroenterol. 2016;30(5):769-81. doi: 10.1016/j.bpg.2016.10.002.

17. Jafri NS et al. Aliment Pharmacol & Therapeut. 2007;25(6):647-56. doi: 10.1111/j.1365-2036.2007.03247.x.

18. Blumenstein I et al. World J Gastroenterol. 2014;20(26):8505-24. doi: 10.3748/wjg.v20.i26.8505.

19. Fung E et al. Surgical Endosc. 2017;31(9):3623-7. doi: 10.1007/s00464-016-5394-8.

20. Ellrichmann M et al. Endoscopy. 2013;45(07):526-31. doi: 10.1055/s-0033-1344023.

Dr. Toy is with the department of internal medicine at the University of Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and hepatology at the University of Utah.

Introduction

Gastroenterologists are in a unique position to manage individuals with feeding tubes as their training underscores principles in digestion, absorption, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require a basic understanding of intestinal anatomy and physiology. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Indications for tube feeding

When deciding on the appropriate route for artificial nutrition support, the first decision to be made is enteral access versus parenteral nutrition support. Enteral nutrition confers multiple benefits, including preservation of the mucosal lining, reductions in complicated infections, decreased costs, and improved patient compliance. All attempts at adequate enteral access should be made before deciding on the use of parenteral nutrition. Following the clinical decision to pursue artificial means of nutrition support and enteral access, the next common decision is the anticipated duration of nutrition support. Generally, the oral or nasal tubes are used for short durations (i.e., less than 4 weeks) with percutaneous placement into the stomach or small intestine for longer-term feeding (i.e., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ]).

The most general indication for nutrition support is an inability to maintain adequate nutritional needs with oral intake alone. General categories of inadequate oral intake include neurologic disorders, malignancy, and gastrointestinal conditions affecting digestion and absorption (Table 1). Absolute and relative contraindications to PEG placement are listed in Table 2. If an endoscopic placement is not possible, alternative means of placement (i.e., surgery or interventional radiology) can be considered to avoid the consequences of prolonged malnutrition. In-hospital mortality following PEG placement has decreased 40% over the last 10 years, which can be attributed to improved patient selection, enhanced discharge practices, and exclusion of patients with the highest comorbidity and mortality rates, like those with advanced dementia or terminal cancer.¹

PEG placement in patients with dementia is controversial, with previous studies not demonstrating improved outcomes and association with high mortality rates,² so the practice is currently not recommended by the American Geriatrics Society in individuals with advanced dementia.³ However, a large Japanese study showed that careful selection of patients with mild dementia to undergo gastrostomy increased independence fourfold; therefore, multidisciplinary involvement is often necessary in the decision to pursue artificial means of nutrition support in this population.⁴

The recent coronavirus disease 2019 (COVID-19) pandemic has placed additional strains on endoscopic placement and has highlighted the effect of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) on GI symptoms. A recent meta-analysis showed an overall incidence of GI symptoms of 17.6% in the following conditions in decreasing order of prevalence: anorexia, diarrhea, nausea, vomiting, and abdominal discomfort.⁵ In addition, the prolonged ventilatory requirements among a subset of individuals with the most severe COVID-19 results in extended periods of nutrition support via enteral tube placements. In individuals with ICU-acquired weakness and discharge to long-term care facilities, the placement of percutaneous endoscopic tubes may be required, although with the additional consideration of the need for an aerosolizing procedure. Delay of placement has been advocated, in addition to appropriate personal protective equipment, in order to ensure safe placement for the endoscopy staff.⁶
 

 

Types of feeding tubes

After deciding to feed a patient enterally and determining the anticipated duration of enteral support, the next decision is to determine the most appropriate location of feeding delivery: into the stomach or the small bowel. Gastric feeding is advantageous most commonly because of its increased capacity, allowing for larger volumes to be delivered over shorter durations. However, in the setting of postsurgical anatomy, gastroparesis, or obstructing tumors/pancreatic inflammation, distal delivery of tube feeds may be required into the jejunum. Additionally, percutaneous tubes placed into the stomach can have extenders into the small bowel (GJ tubes) to allow for feeding into the small bowel and decompression or delivery of medications into the stomach.

In general, gastric feeding is preferred over small bowel feeding as PEG tubes are more stable and have fewer complications than either PEG-J or direct PEJ tubes. Gastrostomy tubes are generally shorter and larger in diameter making them less likely to clog. PEG-J tubes have separate lumens for gastric and small intestinal access, but the smaller-bore jejunal extension tubes are more likely to clog or become dislodged. While direct PEJ is shown to have higher rates of tube patency and decreased rates of endoscopic re-intervention, compared with PEG-J,⁷ one limitation of a direct PEJ is difficulty in placement and site selection, which can be performed with a pediatric colonoscope or balloon enteroscopy system. Most commonly, this procedure is performed under general anesthesia.

In the case of a critically ill patient in the ICU, it is recommended to start enteral nutrition within 24-48 hours of arrival to avoid complications of prolonged calorie deficits. Nasally inserted feeding tubes (e.g., Cortrak, Avanos Medical Devices, Alpharetta, Ga.) are most commonly used at the bedside and can be placed blindly using electromagnetic image guidance, radiographically, or endoscopy. However, the small caliber of nasoenteric tubes comes with the common complication of clogging, which can be overcome with slightly larger bore gastric feeding tubes. If gastric feeding is not tolerated (e.g., in the case of vomiting, witnessed aspiration), small bowel feeding should be initiated and can be a more durable form of enteral feeding with fewer interruptions as feedings do not need to be held for procedures or symptomatic gastric intolerance. In clinical areas of question, or if there is a concern for intolerance of enteral feeding, a short trial with nasogastric or nasojejunal tube placement should be performed before a more definitive percutaneous placement.

With respect to percutaneous tubes, important characteristics to choose are the size (diameter in French units), type of internal retention device, and external appearance of the tube (standard or low profile). All percutaneous tubes contain an external retention device (i.e., bumper) that fits against the skin and an internal retention device that is either a balloon or plastic dome or funnel that prevents the tube from becoming dislodged. Balloon retention tubes require replacement every 3-6 months, while nonballoon tubes generally require replacement annually in order to prevent the plastic from cracking, which can make removal complicated. Low-profile tubes have an external cap, which, when opened, allows for extension tubing to be securely attached while in use and detached while not in use. Low-profile tubes are often preferred among younger, active patients and those with adequate dexterity to allow for attachment of the external extension tubing. These tubes are most often inserted as a replacement for an initially endoscopically placed tube, although one-step systems for initial placement are available. The size of the low-profile tube is chosen based on the size of the existing PEG tube and by measuring the length of the stoma tract using specialized measuring devices.⁸ Patients and caregivers can also be trained to replace balloon-type tubes on their own to limit complications of displaced or cracked tubes. Low-profile tubes are commercially available for both gastric placement and gastric placement with extension into the small bowel, which often requires fluoroscopy for secure placement.

All percutaneous enteral tubes are being transitioned to the ENfit connector system, which prevents connections from the enteral system to nonenteral systems (namely intravenous lines, chest tubes) and vice versa. Tubing misconnections have been rarely reported, and the EnFIT system is designed to prevent such misadventures that have resulted in serious complications and even mortality.⁹ Adapter devices are available that may be required for patients with feeding tubes who have not been transitioned yet. Most commonly with new tube placements and replacements, patients and providers will have to become familiar with the new syringes and feeding bags required with EnFIT connectors.

Gastrostomy placement can be considered a higher-risk endoscopic procedure. One complicating factor is the increased use of antiplatelet and anticoagulant therapies in individuals with a history of neurologic insults. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend that coumadin be held 5 days before the procedure and bridged with heparin if the patient is at high risk of thromboembolic complications. For patients on dual anti-platelet therapy, thienopyridines like clopidogrel are often stopped 5-7 days prior to procedure with continuation of aspirin,¹⁰ but there are more recent data that PEG insertion is safe with continued use of DAPT.¹¹ Direct-acting anticoagulants (DOACs) are often stopped 24-48 hours prior to procedure and then restarted 48 hours after tube placement, but this is dependent on the half-life of the specific DOAC and the patient’s renal function. Patients with decreased creatinine clearance may need to hold the DOAC up to 3-4 days prior to the procedure. In this situation, referring to ASGE guidelines and consultation with a hematologist or managing anti-coagulation clinic is advised.¹⁰
 

 

Troubleshooting complications

Nasoenteric tubes: One of the most common and irritating complications with nasoenteric feeding tubes is clogging. To prevent clogging, the tube should be flushed frequently.¹² At least 30 mL of free water should be used to flush the tube every 4-8 hours for continuous feedings or before and after bolus feeding. Additionally, 15-30 mL of water should be given with each separate medication administration, and if possible, medication administration via small-bore small bowel feeding tubes should be avoided.¹² Water flushing is especially important with small-caliber tubes and pumps that deliver both feeding and water flushes. It is available for small bowel feeding in order to allow for programmed water delivery.

Warm water flushes can also help unclog the tube,¹² and additional pharmacologic and mechanical devices have been promoted for clogged tubes. One common technique is mixing pancreatic enzymes (Viokase) with a crushed 325-mg tablet of nonenteric coated sodium bicarbonate and 5 mL of water to create a solution that has the alkaline properties allowing for both pancreatic enzyme activation and clog dissolution. Additionally, an endoscopic retrograde cholangiopancreatography (ERCP) catheter can be placed into longer feeding tubes to directly infuse the activated agent to the site of the clog.¹³ If water and enzymes are not successful in unclogging the tube, commercially available brushes can help remove clogs. The TubeClear® system (Actuated Medical, Bellefonte, Penna) has a single-use stem that is connected to AC power to create a jackhammerlike movement to remove clogs in longer nasoenteral and gastrojejunal tubes.
 

PEG tubes (short-term complications): Procedural and immediate postprocedural complications include bleeding, aspiration, pneumoperitoneum, and perforation. Pneumoperitoneum occurs in approximately 50% of cases and is generally clinically insignificant. The risk of pneumoperitoneum can be reduced by using CO2 insufflation.¹⁴ If the patient develops systemic signs of infection or peritoneal signs, CT scan with oral contrast is warranted for further evaluation and to assess for inadvertent perforation of overlying bowel or dislodged tube. Aspiration during or following endoscopy is another common complication of PEG placement and risk factors include over-sedation, supine positioning, advanced age, and neurologic dysfunction. This risk can be mitigated by avoiding over-sedation, immediately aspirating gastric contents when the stomach is reached, and avoiding excessive insufflation.¹⁵ In addition, elevating the head of the bed during the procedure and dedicating an assistant to perform oral suctioning during the entire procedure is recommended.

PEG tubes (long-term complications): More delayed complications of PEG insertion include wound infection, buried bumper syndrome, tumor seeding, peristomal leakage, and tube dislodgement. The prevalence of wound infection is 5%- 25%,¹⁶ and randomized controlled trials have demonstrated the efficacy of a single dose of an IV antibiotic (i.e., cephalosporin) in those not already receiving a broad spectrum antibiotic and administered prophylactically before tube placement.¹⁷ The significance of this reduction is such that antibiotic administration before tube placement should be considered a quality measure for the procedure. A small amount of redness around the tube site (less than 5 mm) is typical, but extension of erythema, warmth, tenderness, purulent drainage, or systemic symptoms is consistent with infection and warrants additional antibiotic administration. Minor infections can be treated with local antiseptics and oral antibiotics, and early intervention is important to prevent need for hospital admission, systemic antibiotics, and even surgical debridement.

 

Peristomal leakage is reported in approximately 1%-2% of patients.¹⁸ Photographs of the site can be very useful in evaluating and managing peristomal leakage and infections. Interventions include reducing gastric secretions with proton pump inhibitors and management of the skin with barrier creams, such as zinc oxide (Calmoseptine®) ointment. Placement of a larger-diameter tube only enlarges the stoma track and worsens the leakage. In such cases, thorough evaluations for delayed gastric emptying (gastroparesis), distal obstruction, or constipation should be performed and managed accordingly. Opiates are common contributors to constipation and delayed gastric emptying and often require reduction in use or directed antagonist therapy to reduce leaking. Continuous feeding over bolus feedings and delivering nutrition distally into the small bowel (PEG-J placement) can improve leaking from gastrostomy tubes. Additional means of management include stabilizing the tube by replacing a traditional tube with a low-profile tube or using right-angle external bumpers. If all measures fail, removing the tube and allowing for stomal closure can be attempted,¹⁶ although this option often requires parenteral nutrition support to prevent prolonged periods of inadequate nutrition.

Buried bumper syndrome (BBS) occurs in 1.5%-8.8% of PEG placements and is a common late complication of PEG placement, although early reports have been described.¹⁸ The development of BBS occurs when the internal bumper migrates from the gastric lumen through and into the stomach or abdominal wall. It occurs more frequently with solid nonballoon retention tubes and is caused by excessive compression of the external bumper against the skin and abdominal wall. Patients with BBS usually present with an immobile catheter, resistance with feeds (because of a closure of the stomach wall around the internal portion of the gastrostomy tube), abdominal pain, or peristomal leakage. Physicians should be aware of and assess tubes for BBS, in particular when replacing an immobile tube (cannot be pushed into the free stomach lumen) or when there is difficulty in flushing water into the tube. This complication can be easily prevented by allowing a minimum of 0.5-1.0 cm (1 finger breadth) between the external bumper and the abdominal wall. In particular, patients and caregivers should be warned that if the patient gains significant amounts of weight, the outer bumper will need to be loosened. Once BBS is diagnosed, the PEG tube requires removal and replacement as it can cause bleeding, infection, or fasciitis. The general steps to replacement include endoscopic removal of the existing tube and replacement of new PEG in the existing tract as long as the BBS is not severe. In most cases a replacement tube can be pulled into place using the pull-PEG technique at the same gastrostomy site as long as the stoma tract can be cannulated with a wire after the existing tube is removed.

Similar to nasoenteric tubes, PEG tubes can become clogged, although this complication is infrequent. The primary steps for prevention include adequately flushing with water before and after feeds and ensuring that all medications are liquid or well crushed and dissolved before instilling. Timely tube replacement also ensures that the internal portions of the gastrostomy tube remain free of debris. Management is similar to that of unclogging nasoenteral tubes, as discussed above, and specific commercial declogging devices for PEG tubes include the Bionix Declogger® (Bionix Development Corp., Toledo, Ohio) and the Bard® PEG cleaning brush (Bard Peripheral Vascular Inc., Tempe, Ariz.). The Bionix system has a plastic stem with a screw and thread design that will remove clogs in 14-24 French PEG tubes, while the Bard brush has a flexible nylon stem with soft bristles at the end to prevent mucosal injury and can be used for prophylaxis against clogs, as well as removing clogs themselves.¹²

Lastly, a rare but important complication of PEG placement is tumor seeding of the PEG site in patients with active head and neck or upper gastrointestinal cancer.¹⁹ The presumed mechanism is shearing of tumor cells as the PEG is pulled through the upper aerodigestive tract and through the wall of the stomach, as prior studies have demonstrated frequent seeding of tubes and incision sites as shown by brushing the tube for malignant cells after tube placement.²⁰ It is important to recognize this complication and not misdiagnose it as granulation tissue, infection, or bleeding as the spread of the cancer generally portends a poor prognosis. Therefore, it is best to use a PEG insertion technique that does not involve pulling or pushing the PEG through the upper aerodigestive tract in patients with active cancer and instead place tubes via an external approach by colleagues in interventional radiology or via direct surgical placement.
 

 

Conclusion

Gastroenterologists occupy a unique role in evaluation, diagnosis, and management of patients requiring enteral feeding. In addition, they are best equipped to place, prevent, and manage complications of tube feeding. For this reason, it is imperative that gastroenterologists familiarize themselves with indications for enteral tubes and types of enteral tubes available, as well as the identification and management of common complications. Comprehensive understanding of these concepts will augment the practicing gastroenterologist’s ability to manage patients requiring enteral nutrition support with confidence.

References

1. Stein DJ et al. Dig Dis Sci. 2020 Jun 19. doi: 10.1007/s10620-020-06396-y.

2. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.

3. Dietrich CG, Schoppmeyer K. World J Gastroenterol. 2020;26(20):2464-71.

4. Suzuki Y et al. T Gastroenterology Res.2012 Feb;5(1):10-20.

5. Cheung KS et al. Gastroenterology. 2020 Jul;159(1):81-95.

6. Micic D et al. Am J Gastroenterol. 2020 Sep;115(9):1367-70.

7. Fan AC et al. Gastrointest Endosc. 2002;56(6):890-4.

8. Tang SJ. Video J Encycl GI Endosc. 2014;2(2):70-3.

9. Guenter P, Lyman B. Nutr Clin Pract. 2016;31(6):769-72.

10. Acosta RD et al. Gastrointest Endosc. 2016;83(1):3-16.

11. Richter JA et al. Gastrointest Endosc. 2011;74(1):22-34.

12. Boullata JI et al. JPEN. 2017;41(1):15-103.

13. McClave SA. Tech Gastrointest Endosc. 2021;3(1):62-8.

14. Murphy CJ et al. Endosc Int Open. 2016;4(3):E292. doi: 10.1053/tgie.2001.19915.

15. Lynch CR et al. Pract Gastroenterology. 2004;28:66-77.

16. Hucl T et al. Best Pract Res Clin Gastroenterol. 2016;30(5):769-81. doi: 10.1016/j.bpg.2016.10.002.

17. Jafri NS et al. Aliment Pharmacol & Therapeut. 2007;25(6):647-56. doi: 10.1111/j.1365-2036.2007.03247.x.

18. Blumenstein I et al. World J Gastroenterol. 2014;20(26):8505-24. doi: 10.3748/wjg.v20.i26.8505.

19. Fung E et al. Surgical Endosc. 2017;31(9):3623-7. doi: 10.1007/s00464-016-5394-8.

20. Ellrichmann M et al. Endoscopy. 2013;45(07):526-31. doi: 10.1055/s-0033-1344023.

Dr. Toy is with the department of internal medicine at the University of Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and hepatology at the University of Utah.

 

When starting a career in gastroenterology, physicians tend to work in the hospital, where there is usually high demand for services and productivity goals are easy to meet. This is a little different in private GI groups, where it takes some time to build up your patient base. This might be a significant concern for young physicians considering private practice. But understanding the role that productivity plays in compensation packages can help in choosing the right group to join.

While compensation models may differ from practice to practice, there is usually a base salary provided with a productivity bonus. Some practices may use productivity along with other measures to determine when a physician is eligible to become a partner in the practice. Partnership is often accompanied with the benefits of ancillary services ownership such as ambulatory surgery centers (ASCs) and anesthesia, pathology, and infusion services.

How is productivity measured?

Most practices utilize relative value units (RVUs), a standard used by Medicare to determine the amount to pay physicians according to their productivity. Most public and private payers are utilizing the RVU system first developed for Medicare as a useful, time-saving way to handle physician payments. The RVU defines the volume of work doctors perform for all procedures and services covered under the Medicare Physician Fee Schedule.

The Medicare Physician Payment System has three components:

• The geographic practice cost indices (GPCIs)

• Relative value units (RVUs)

• A conversion factor

It is important to understand the types of RVUs that exist to understand how to calculate them properly – these include the following categories:

• Physician work, which accounts for the time and effort to perform a procedure.

• Practice expense, which is for the costs of nonphysician labor such as rent and supplies.

• Global fees, which includes fees for initial visits, follow-ups, and practice expense, and applies during a predetermined length of time known as the “global periods,” primarily for major surgeries.

• Malpractice expense, such as costs for professional liability insurance.

There is no specific dollar amount attached to an RVU because RVUs are part of a resource-based relative value scale (RBRVS) which uses RVUs to relate medical procedures to each other. Payment for physician work is based on whether the procedure is performed in an ASC or hospital outpatient department or in an office. A separate facility fee payment is made to the ASC or hospital outpatient department for procedures performed there. Other elements include skills and the amount of time needed to perform a procedure. Calculating the reimbursement from an RVU involves several components and a significant amount of complex math.

 

Meeting goals while building a practice

 

For many young physicians working in the hospital where patients are plentiful, it might seem daunting to build your practice with productivity goals. Practices should, and many do, design their initial productivity plans to minimum or mean RVUs for young physicians rather than someone 10 years into practice. Younger physicians have fellowship and training, but it takes years to become highly efficient with time and productivity. It’s important for everyone involved to set attainable benchmarks.

The practice should also do its best to support your efforts to grow your patient base. While you should be expected to develop relationships with referring physicians, you’ll benefit from the practice’s marketing efforts. When new patients come in, they usually go to newly hired physicians because more senior physicians are booked weeks or months in advance.

Practice administrators also work hard to time new hires to overlap with expected retirements. Senior partners will always have follow-up colonoscopies and associates will need to take on these cases as their colleagues retire. In some practices, younger physicians are expected to take the hospital on call schedules or respond to emergency department calls, so it shouldn’t be difficult to meet productivity goals.

And once you become a partner and are further along on in your career, your productivity plan will change. Some groups have productivity-based compensation, which allows more senior partners to work when they want to – as long as they are meeting the productivity rates that will cover their portion of the practice expenses.

If a physician is consistently not meeting productivity measures, a practice may exercise the right to terminate the relationship, but this is rare. More often, physicians meet their productivity levels and receive certain bonuses for exceeding their goals. In most practices, the partners you work with will know if you aren’t meeting your goals. In most cases, they will take on a mentorship role to help you succeed.
 

Ask questions, be engaged

Another thing to be aware of is that all practices worth joining make sure productivity plans do not violate the Stark Law, anti-kickback statutes, or other regulations. A huge red flag to look out for is a productivity plan that is based on the number of procedures – it should never be tied to volume.

It’s also best to consider how often the productivity plan is measured. It might be a red flag if it is measured weekly or monthly or if there are heavy consequences for not meeting RVU goals. Most groups look at productivity on a quarterly basis and integrate those discussions into a standard review process.

The successful early-career GIs we interview in our practices are those who are interested in understanding the ins and outs of our practices and what they can achieve through practicing independently. The practices worth joining will likewise be interested in discussing your level of entrepreneurship, the opportunities for you to grow in your career, and what it takes to be on the track to partner.
 

Dr. Baig is a practicing gastroenterologist at Allied Digestive Care in New Jersey and is the chair of communications for the Digestive Health Physicians Association (DHPA); Mr. Harlen is the president of PE Practice Solutions and immediate past chief operating officer of Capital Digestive Care in Maryland. He is the executive director of DHPA.

 

When starting a career in gastroenterology, physicians tend to work in the hospital, where there is usually high demand for services and productivity goals are easy to meet. This is a little different in private GI groups, where it takes some time to build up your patient base. This might be a significant concern for young physicians considering private practice. But understanding the role that productivity plays in compensation packages can help in choosing the right group to join.

While compensation models may differ from practice to practice, there is usually a base salary provided with a productivity bonus. Some practices may use productivity along with other measures to determine when a physician is eligible to become a partner in the practice. Partnership is often accompanied with the benefits of ancillary services ownership such as ambulatory surgery centers (ASCs) and anesthesia, pathology, and infusion services.

How is productivity measured?

Most practices utilize relative value units (RVUs), a standard used by Medicare to determine the amount to pay physicians according to their productivity. Most public and private payers are utilizing the RVU system first developed for Medicare as a useful, time-saving way to handle physician payments. The RVU defines the volume of work doctors perform for all procedures and services covered under the Medicare Physician Fee Schedule.

The Medicare Physician Payment System has three components:

• The geographic practice cost indices (GPCIs)

• Relative value units (RVUs)

• A conversion factor

It is important to understand the types of RVUs that exist to understand how to calculate them properly – these include the following categories:

• Physician work, which accounts for the time and effort to perform a procedure.

• Practice expense, which is for the costs of nonphysician labor such as rent and supplies.

• Global fees, which includes fees for initial visits, follow-ups, and practice expense, and applies during a predetermined length of time known as the “global periods,” primarily for major surgeries.

• Malpractice expense, such as costs for professional liability insurance.

There is no specific dollar amount attached to an RVU because RVUs are part of a resource-based relative value scale (RBRVS) which uses RVUs to relate medical procedures to each other. Payment for physician work is based on whether the procedure is performed in an ASC or hospital outpatient department or in an office. A separate facility fee payment is made to the ASC or hospital outpatient department for procedures performed there. Other elements include skills and the amount of time needed to perform a procedure. Calculating the reimbursement from an RVU involves several components and a significant amount of complex math.

 

Meeting goals while building a practice

 

For many young physicians working in the hospital where patients are plentiful, it might seem daunting to build your practice with productivity goals. Practices should, and many do, design their initial productivity plans to minimum or mean RVUs for young physicians rather than someone 10 years into practice. Younger physicians have fellowship and training, but it takes years to become highly efficient with time and productivity. It’s important for everyone involved to set attainable benchmarks.

The practice should also do its best to support your efforts to grow your patient base. While you should be expected to develop relationships with referring physicians, you’ll benefit from the practice’s marketing efforts. When new patients come in, they usually go to newly hired physicians because more senior physicians are booked weeks or months in advance.

Practice administrators also work hard to time new hires to overlap with expected retirements. Senior partners will always have follow-up colonoscopies and associates will need to take on these cases as their colleagues retire. In some practices, younger physicians are expected to take the hospital on call schedules or respond to emergency department calls, so it shouldn’t be difficult to meet productivity goals.

And once you become a partner and are further along on in your career, your productivity plan will change. Some groups have productivity-based compensation, which allows more senior partners to work when they want to – as long as they are meeting the productivity rates that will cover their portion of the practice expenses.

If a physician is consistently not meeting productivity measures, a practice may exercise the right to terminate the relationship, but this is rare. More often, physicians meet their productivity levels and receive certain bonuses for exceeding their goals. In most practices, the partners you work with will know if you aren’t meeting your goals. In most cases, they will take on a mentorship role to help you succeed.
 

Ask questions, be engaged

Another thing to be aware of is that all practices worth joining make sure productivity plans do not violate the Stark Law, anti-kickback statutes, or other regulations. A huge red flag to look out for is a productivity plan that is based on the number of procedures – it should never be tied to volume.

It’s also best to consider how often the productivity plan is measured. It might be a red flag if it is measured weekly or monthly or if there are heavy consequences for not meeting RVU goals. Most groups look at productivity on a quarterly basis and integrate those discussions into a standard review process.

The successful early-career GIs we interview in our practices are those who are interested in understanding the ins and outs of our practices and what they can achieve through practicing independently. The practices worth joining will likewise be interested in discussing your level of entrepreneurship, the opportunities for you to grow in your career, and what it takes to be on the track to partner.
 

Dr. Baig is a practicing gastroenterologist at Allied Digestive Care in New Jersey and is the chair of communications for the Digestive Health Physicians Association (DHPA); Mr. Harlen is the president of PE Practice Solutions and immediate past chief operating officer of Capital Digestive Care in Maryland. He is the executive director of DHPA.

 

When starting a career in gastroenterology, physicians tend to work in the hospital, where there is usually high demand for services and productivity goals are easy to meet. This is a little different in private GI groups, where it takes some time to build up your patient base. This might be a significant concern for young physicians considering private practice. But understanding the role that productivity plays in compensation packages can help in choosing the right group to join.

While compensation models may differ from practice to practice, there is usually a base salary provided with a productivity bonus. Some practices may use productivity along with other measures to determine when a physician is eligible to become a partner in the practice. Partnership is often accompanied with the benefits of ancillary services ownership such as ambulatory surgery centers (ASCs) and anesthesia, pathology, and infusion services.

How is productivity measured?

Most practices utilize relative value units (RVUs), a standard used by Medicare to determine the amount to pay physicians according to their productivity. Most public and private payers are utilizing the RVU system first developed for Medicare as a useful, time-saving way to handle physician payments. The RVU defines the volume of work doctors perform for all procedures and services covered under the Medicare Physician Fee Schedule.

The Medicare Physician Payment System has three components:

• The geographic practice cost indices (GPCIs)

• Relative value units (RVUs)

• A conversion factor

It is important to understand the types of RVUs that exist to understand how to calculate them properly – these include the following categories:

• Physician work, which accounts for the time and effort to perform a procedure.

• Practice expense, which is for the costs of nonphysician labor such as rent and supplies.

• Global fees, which includes fees for initial visits, follow-ups, and practice expense, and applies during a predetermined length of time known as the “global periods,” primarily for major surgeries.

• Malpractice expense, such as costs for professional liability insurance.

There is no specific dollar amount attached to an RVU because RVUs are part of a resource-based relative value scale (RBRVS) which uses RVUs to relate medical procedures to each other. Payment for physician work is based on whether the procedure is performed in an ASC or hospital outpatient department or in an office. A separate facility fee payment is made to the ASC or hospital outpatient department for procedures performed there. Other elements include skills and the amount of time needed to perform a procedure. Calculating the reimbursement from an RVU involves several components and a significant amount of complex math.

 

Meeting goals while building a practice

 

For many young physicians working in the hospital where patients are plentiful, it might seem daunting to build your practice with productivity goals. Practices should, and many do, design their initial productivity plans to minimum or mean RVUs for young physicians rather than someone 10 years into practice. Younger physicians have fellowship and training, but it takes years to become highly efficient with time and productivity. It’s important for everyone involved to set attainable benchmarks.

The practice should also do its best to support your efforts to grow your patient base. While you should be expected to develop relationships with referring physicians, you’ll benefit from the practice’s marketing efforts. When new patients come in, they usually go to newly hired physicians because more senior physicians are booked weeks or months in advance.

Practice administrators also work hard to time new hires to overlap with expected retirements. Senior partners will always have follow-up colonoscopies and associates will need to take on these cases as their colleagues retire. In some practices, younger physicians are expected to take the hospital on call schedules or respond to emergency department calls, so it shouldn’t be difficult to meet productivity goals.

And once you become a partner and are further along on in your career, your productivity plan will change. Some groups have productivity-based compensation, which allows more senior partners to work when they want to – as long as they are meeting the productivity rates that will cover their portion of the practice expenses.

If a physician is consistently not meeting productivity measures, a practice may exercise the right to terminate the relationship, but this is rare. More often, physicians meet their productivity levels and receive certain bonuses for exceeding their goals. In most practices, the partners you work with will know if you aren’t meeting your goals. In most cases, they will take on a mentorship role to help you succeed.
 

Ask questions, be engaged

Another thing to be aware of is that all practices worth joining make sure productivity plans do not violate the Stark Law, anti-kickback statutes, or other regulations. A huge red flag to look out for is a productivity plan that is based on the number of procedures – it should never be tied to volume.

It’s also best to consider how often the productivity plan is measured. It might be a red flag if it is measured weekly or monthly or if there are heavy consequences for not meeting RVU goals. Most groups look at productivity on a quarterly basis and integrate those discussions into a standard review process.

The successful early-career GIs we interview in our practices are those who are interested in understanding the ins and outs of our practices and what they can achieve through practicing independently. The practices worth joining will likewise be interested in discussing your level of entrepreneurship, the opportunities for you to grow in your career, and what it takes to be on the track to partner.
 

Dr. Baig is a practicing gastroenterologist at Allied Digestive Care in New Jersey and is the chair of communications for the Digestive Health Physicians Association (DHPA); Mr. Harlen is the president of PE Practice Solutions and immediate past chief operating officer of Capital Digestive Care in Maryland. He is the executive director of DHPA.