Extraesophageal reflux (EER) symptoms are a subset of gastroesophageal reflux disease (GERD) that can be difficult to diagnose because of its heterogeneous nature and symptoms that overlap with other conditions.

That puts the onus on physicians to take all symptoms into account and work across disciplines to diagnose, manage, and treat the condition, according to a new clinical practice update from the American Gastroenterological Association, which was published in Clinical Gastroenterology and Hepatology.

University of Michigan Health

GERD is becoming increasingly common, which in turn has led to greater awareness and consideration of EER symptoms. EER symptoms can present a challenge because they may vary considerably and are not unique to GERD. The symptoms often do not respond well to proton pump inhibitor (PPI) therapy.

EER symptoms can include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, postnasal drip, and throat clearing. Some patients with EER symptoms do not report heartburn or regurgitation, which leaves it up to the physician to determine if acid reflux is present and contributing to symptoms.

“The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies,” wrote the authors, who were led by Joan W. Chen, MD, MS, a gastroenterologist with the University of Michigan, Ann Arbor.

There is also debate over whether fluid refluxate is the source of damage that causes EER symptoms, and if so, whether it is sufficient that the fluid be acidic or that pepsin be present, or if the cause is related to neurogenic signaling and resulting inflammation. Because of these questions, a PPI trial will not necessarily provide insight into the role of acid reflux in EER symptoms.

American Gastroenterological Association

To guide physicians in diagnosing and managing EER symptoms, the authors created 10 advice statements based on a review of the published literature and expert opinion.

Best practice advice 1: The authors emphasized that gastroenterologists need to be aware of the potential extraesophageal symptoms of GERD. They should inquire with GERD patients to determine if laryngitis, chronic cough, asthma, and dental erosions are present.

Best practice advice 2: Consider a multidisciplinary approach to EER manifestations. Cases may require input from non-GI specialties. Tests performed by other specialists, such as bronchoscopy, thoracic imaging, or laryngoscopy, should be taken into account, since patients will also seek out multiple specialists to address their symptoms.

Best practice advice 3: There is no specific diagnostic test available to determine if GER is the cause of EER symptoms. Instead, physicians should interpret patient symptoms, response to GER therapy, and input from endoscopy and reflux tests.

Best practice advice 4: Rather than subject the patient to the cost and potential for even rare adverse events of a PPI trial, physicians should first consider conducting reflux testing. A PPI trial has clinical value but is insufficient on its own to help diagnose or manage EER. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.

Best practice advice 5: The inconsistent therapeutic response to PPI therapy means that positive effects of PPI therapy on EER symptoms can’t confirm a GERD diagnosis because a placebo effect may be involved, and because symptom improvement can occur through mechanisms other than acid suppression. A meta-analysis found that a PPI trial has a sensitivity of 71%-78% and a specificity of 41%-54% with typical symptoms of heartburn and regurgitation. “Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower,” the authors wrote.

Best practice advice 6: When EER symptoms related to GERD are suspected and a PPI trial of up to 12 weeks does not lead to adequate improvement, the physician should consider testing for pathologic GER. Additional trials employing other PPIs are unlikely to succeed.

Best practice advice 7: Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation. Potential methods to evaluate reflux include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy, which can assist with a GERD diagnosis, particularly when nonerosive reflux is present.

Best practice advice 8: About 50%-60% of patients with EER symptoms will not have GERD. Testing can be considered for those with an established objective diagnosis of GERD who do not respond well to high doses of acid suppression. Cost-effectiveness studies have confirmed the value of starting with ambulatory reflux monitoring, which can include a catheter-based pH sensor, pH impedance, or wireless pH capsule.

Ambulatory esophageal pH monitoring can also assist in making a GERD diagnosis, but it does not indicate whether GERD may be contributing to EER symptoms.

“Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms,” the authors wrote. They also pointed out that ambulatory reflux monitoring in EER patients should be done in the absence of acid suppression unless there is already objective evidence for the presence of GERD.

Best practice advice 9: Aside from acid suppression, EER symptoms can also be managed through other means, including lifestyle modifications, such as eating avoidance prior to lying down, elevation of the head of the bed, sleeping on the left side, and weight loss. Or, alginate containing antacids, external upper esophageal sphincter compression device, cognitive behavioral therapy, and neuromodulators.

Best practice advice 10: In cases where the EER patient has objectively defined evidence of GERD, physicians should employ shared decision-making before considering anti-reflux surgery. If the patient did not respond to PPI therapy, this predicts a lack of response to antireflux surgery.

All four authors reported financial ties to multiple pharmaceutical companies.

Extraesophageal reflux (EER) symptoms are a subset of gastroesophageal reflux disease (GERD) that can be difficult to diagnose because of its heterogeneous nature and symptoms that overlap with other conditions.

That puts the onus on physicians to take all symptoms into account and work across disciplines to diagnose, manage, and treat the condition, according to a new clinical practice update from the American Gastroenterological Association, which was published in Clinical Gastroenterology and Hepatology.

University of Michigan Health

GERD is becoming increasingly common, which in turn has led to greater awareness and consideration of EER symptoms. EER symptoms can present a challenge because they may vary considerably and are not unique to GERD. The symptoms often do not respond well to proton pump inhibitor (PPI) therapy.

EER symptoms can include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, postnasal drip, and throat clearing. Some patients with EER symptoms do not report heartburn or regurgitation, which leaves it up to the physician to determine if acid reflux is present and contributing to symptoms.

“The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies,” wrote the authors, who were led by Joan W. Chen, MD, MS, a gastroenterologist with the University of Michigan, Ann Arbor.

There is also debate over whether fluid refluxate is the source of damage that causes EER symptoms, and if so, whether it is sufficient that the fluid be acidic or that pepsin be present, or if the cause is related to neurogenic signaling and resulting inflammation. Because of these questions, a PPI trial will not necessarily provide insight into the role of acid reflux in EER symptoms.

American Gastroenterological Association

To guide physicians in diagnosing and managing EER symptoms, the authors created 10 advice statements based on a review of the published literature and expert opinion.

Best practice advice 1: The authors emphasized that gastroenterologists need to be aware of the potential extraesophageal symptoms of GERD. They should inquire with GERD patients to determine if laryngitis, chronic cough, asthma, and dental erosions are present.

Best practice advice 2: Consider a multidisciplinary approach to EER manifestations. Cases may require input from non-GI specialties. Tests performed by other specialists, such as bronchoscopy, thoracic imaging, or laryngoscopy, should be taken into account, since patients will also seek out multiple specialists to address their symptoms.

Best practice advice 3: There is no specific diagnostic test available to determine if GER is the cause of EER symptoms. Instead, physicians should interpret patient symptoms, response to GER therapy, and input from endoscopy and reflux tests.

Best practice advice 4: Rather than subject the patient to the cost and potential for even rare adverse events of a PPI trial, physicians should first consider conducting reflux testing. A PPI trial has clinical value but is insufficient on its own to help diagnose or manage EER. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.

Best practice advice 5: The inconsistent therapeutic response to PPI therapy means that positive effects of PPI therapy on EER symptoms can’t confirm a GERD diagnosis because a placebo effect may be involved, and because symptom improvement can occur through mechanisms other than acid suppression. A meta-analysis found that a PPI trial has a sensitivity of 71%-78% and a specificity of 41%-54% with typical symptoms of heartburn and regurgitation. “Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower,” the authors wrote.

Best practice advice 6: When EER symptoms related to GERD are suspected and a PPI trial of up to 12 weeks does not lead to adequate improvement, the physician should consider testing for pathologic GER. Additional trials employing other PPIs are unlikely to succeed.

Best practice advice 7: Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation. Potential methods to evaluate reflux include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy, which can assist with a GERD diagnosis, particularly when nonerosive reflux is present.

Best practice advice 8: About 50%-60% of patients with EER symptoms will not have GERD. Testing can be considered for those with an established objective diagnosis of GERD who do not respond well to high doses of acid suppression. Cost-effectiveness studies have confirmed the value of starting with ambulatory reflux monitoring, which can include a catheter-based pH sensor, pH impedance, or wireless pH capsule.

Ambulatory esophageal pH monitoring can also assist in making a GERD diagnosis, but it does not indicate whether GERD may be contributing to EER symptoms.

“Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms,” the authors wrote. They also pointed out that ambulatory reflux monitoring in EER patients should be done in the absence of acid suppression unless there is already objective evidence for the presence of GERD.

Best practice advice 9: Aside from acid suppression, EER symptoms can also be managed through other means, including lifestyle modifications, such as eating avoidance prior to lying down, elevation of the head of the bed, sleeping on the left side, and weight loss. Or, alginate containing antacids, external upper esophageal sphincter compression device, cognitive behavioral therapy, and neuromodulators.

Best practice advice 10: In cases where the EER patient has objectively defined evidence of GERD, physicians should employ shared decision-making before considering anti-reflux surgery. If the patient did not respond to PPI therapy, this predicts a lack of response to antireflux surgery.

All four authors reported financial ties to multiple pharmaceutical companies.

Extraesophageal reflux (EER) symptoms are a subset of gastroesophageal reflux disease (GERD) that can be difficult to diagnose because of its heterogeneous nature and symptoms that overlap with other conditions.

That puts the onus on physicians to take all symptoms into account and work across disciplines to diagnose, manage, and treat the condition, according to a new clinical practice update from the American Gastroenterological Association, which was published in Clinical Gastroenterology and Hepatology.

University of Michigan Health

GERD is becoming increasingly common, which in turn has led to greater awareness and consideration of EER symptoms. EER symptoms can present a challenge because they may vary considerably and are not unique to GERD. The symptoms often do not respond well to proton pump inhibitor (PPI) therapy.

EER symptoms can include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, postnasal drip, and throat clearing. Some patients with EER symptoms do not report heartburn or regurgitation, which leaves it up to the physician to determine if acid reflux is present and contributing to symptoms.

“The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies,” wrote the authors, who were led by Joan W. Chen, MD, MS, a gastroenterologist with the University of Michigan, Ann Arbor.

There is also debate over whether fluid refluxate is the source of damage that causes EER symptoms, and if so, whether it is sufficient that the fluid be acidic or that pepsin be present, or if the cause is related to neurogenic signaling and resulting inflammation. Because of these questions, a PPI trial will not necessarily provide insight into the role of acid reflux in EER symptoms.

American Gastroenterological Association

To guide physicians in diagnosing and managing EER symptoms, the authors created 10 advice statements based on a review of the published literature and expert opinion.

Best practice advice 1: The authors emphasized that gastroenterologists need to be aware of the potential extraesophageal symptoms of GERD. They should inquire with GERD patients to determine if laryngitis, chronic cough, asthma, and dental erosions are present.

Best practice advice 2: Consider a multidisciplinary approach to EER manifestations. Cases may require input from non-GI specialties. Tests performed by other specialists, such as bronchoscopy, thoracic imaging, or laryngoscopy, should be taken into account, since patients will also seek out multiple specialists to address their symptoms.

Best practice advice 3: There is no specific diagnostic test available to determine if GER is the cause of EER symptoms. Instead, physicians should interpret patient symptoms, response to GER therapy, and input from endoscopy and reflux tests.

Best practice advice 4: Rather than subject the patient to the cost and potential for even rare adverse events of a PPI trial, physicians should first consider conducting reflux testing. A PPI trial has clinical value but is insufficient on its own to help diagnose or manage EER. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.

Best practice advice 5: The inconsistent therapeutic response to PPI therapy means that positive effects of PPI therapy on EER symptoms can’t confirm a GERD diagnosis because a placebo effect may be involved, and because symptom improvement can occur through mechanisms other than acid suppression. A meta-analysis found that a PPI trial has a sensitivity of 71%-78% and a specificity of 41%-54% with typical symptoms of heartburn and regurgitation. “Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower,” the authors wrote.

Best practice advice 6: When EER symptoms related to GERD are suspected and a PPI trial of up to 12 weeks does not lead to adequate improvement, the physician should consider testing for pathologic GER. Additional trials employing other PPIs are unlikely to succeed.

Best practice advice 7: Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation. Potential methods to evaluate reflux include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy, which can assist with a GERD diagnosis, particularly when nonerosive reflux is present.

Best practice advice 8: About 50%-60% of patients with EER symptoms will not have GERD. Testing can be considered for those with an established objective diagnosis of GERD who do not respond well to high doses of acid suppression. Cost-effectiveness studies have confirmed the value of starting with ambulatory reflux monitoring, which can include a catheter-based pH sensor, pH impedance, or wireless pH capsule.

Ambulatory esophageal pH monitoring can also assist in making a GERD diagnosis, but it does not indicate whether GERD may be contributing to EER symptoms.

“Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms,” the authors wrote. They also pointed out that ambulatory reflux monitoring in EER patients should be done in the absence of acid suppression unless there is already objective evidence for the presence of GERD.

Best practice advice 9: Aside from acid suppression, EER symptoms can also be managed through other means, including lifestyle modifications, such as eating avoidance prior to lying down, elevation of the head of the bed, sleeping on the left side, and weight loss. Or, alginate containing antacids, external upper esophageal sphincter compression device, cognitive behavioral therapy, and neuromodulators.

Best practice advice 10: In cases where the EER patient has objectively defined evidence of GERD, physicians should employ shared decision-making before considering anti-reflux surgery. If the patient did not respond to PPI therapy, this predicts a lack of response to antireflux surgery.

All four authors reported financial ties to multiple pharmaceutical companies.

In two phase 3 trials, patients with prurigo nodularis (PN) randomized to receive dupilumab every 2 weeks for 24 weeks achieved statistically significant improvements in itch and skin lesions, compared with those who randomized to receive placebo.

The results, which were published online in Nature Medicine, were the basis for the FDA approval of dupilumab (Dupixent) for adults with PN in September 2022, the first treatment approved for treating PN in the United States.

“These positive studies support the involvement of type 2 cytokines in driving PN disease pathogenesis and the targeting of the [interleukin]-4/IL-13 axis as a novel therapeutic paradigm for patients with PN,” wrote the researchers, who were led by principal investigator Gil Yosipovitch, MD, professor of dermatology at the University of Miami, Fla. Dupilumab, an IL-4 receptor alpha antagonist, blocks the shared receptor component (IL-4R alpha) for IL-4 and IL-13.

For the two phase 3 trials, which were called LIBERTY-PN PRIME and PRIME2 and were sponsored by Sanofi and Regeneron Pharmaceuticals, researchers randomized adults with PN with 20 or more nodules and severe itch uncontrolled with topical therapies 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, which was measured by the proportion of patients with a 4-point or greater reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included a reduction in the number of nodules to 5 or fewer at week 24.

PRIME and PRIME2 enrolled 151 and 160 patients, respectively. In PRIME, 60% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 24, compared with 18.4% of patients in the placebo arm (P < .001). In PRIME2, 37.2% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 12, compared with 22% of patients in the placebo arm (P = .022).

The researchers also reported that, from an initial baseline of 20 to greater than 100 nodules, 32.0% of dupilumab-treated patients in PRIME and 25.6% in PRIME2 showed a reduction to 5 nodules or fewer, which corresponded to a response of “clear” or “almost clear” skin at week 12, compared with 11.8% and 12.2% of placebo-treated patients, respectively. This treatment effect on skin lesions continued to improve after week 12, with 48% of dupilumab-treated patients in PRIME and 44.9% in PRIME2 having five nodules or fewer at week 24, compared with 18.4% and 15.9% of placebo-treated patients, respectively. Safety was consistent with the known dupilumab safety profile.

“Validation is the first success of this paper,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study. “While both the safety and efficacy of dupilumab in these two phase 3 programs is the meat of the matter, nuanced highlights for me include the rigid nature of the exclusion criteria to ensure a study population that truly has PN as a stand-alone disease, rather than a secondary finding as we once believed to be the entire story. I think it’s important for us to recognize that it’s not one or the other, rather there is both ‘primary’ prurigo nodularis, and then there is secondary prurigo nodularis associated with something else [a wide range of underlying medical conditions], just like we divide primary and secondary hyperhidrosis.”

Dr. Yosipovitch reported having competing interests with several pharmaceutical companies, including Regeneron and Sanofi. Dr. Friedman disclosed that he is a consultant to and a speaker for Regeneron.

In two phase 3 trials, patients with prurigo nodularis (PN) randomized to receive dupilumab every 2 weeks for 24 weeks achieved statistically significant improvements in itch and skin lesions, compared with those who randomized to receive placebo.

The results, which were published online in Nature Medicine, were the basis for the FDA approval of dupilumab (Dupixent) for adults with PN in September 2022, the first treatment approved for treating PN in the United States.

“These positive studies support the involvement of type 2 cytokines in driving PN disease pathogenesis and the targeting of the [interleukin]-4/IL-13 axis as a novel therapeutic paradigm for patients with PN,” wrote the researchers, who were led by principal investigator Gil Yosipovitch, MD, professor of dermatology at the University of Miami, Fla. Dupilumab, an IL-4 receptor alpha antagonist, blocks the shared receptor component (IL-4R alpha) for IL-4 and IL-13.

For the two phase 3 trials, which were called LIBERTY-PN PRIME and PRIME2 and were sponsored by Sanofi and Regeneron Pharmaceuticals, researchers randomized adults with PN with 20 or more nodules and severe itch uncontrolled with topical therapies 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, which was measured by the proportion of patients with a 4-point or greater reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included a reduction in the number of nodules to 5 or fewer at week 24.

PRIME and PRIME2 enrolled 151 and 160 patients, respectively. In PRIME, 60% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 24, compared with 18.4% of patients in the placebo arm (P < .001). In PRIME2, 37.2% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 12, compared with 22% of patients in the placebo arm (P = .022).

The researchers also reported that, from an initial baseline of 20 to greater than 100 nodules, 32.0% of dupilumab-treated patients in PRIME and 25.6% in PRIME2 showed a reduction to 5 nodules or fewer, which corresponded to a response of “clear” or “almost clear” skin at week 12, compared with 11.8% and 12.2% of placebo-treated patients, respectively. This treatment effect on skin lesions continued to improve after week 12, with 48% of dupilumab-treated patients in PRIME and 44.9% in PRIME2 having five nodules or fewer at week 24, compared with 18.4% and 15.9% of placebo-treated patients, respectively. Safety was consistent with the known dupilumab safety profile.

“Validation is the first success of this paper,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study. “While both the safety and efficacy of dupilumab in these two phase 3 programs is the meat of the matter, nuanced highlights for me include the rigid nature of the exclusion criteria to ensure a study population that truly has PN as a stand-alone disease, rather than a secondary finding as we once believed to be the entire story. I think it’s important for us to recognize that it’s not one or the other, rather there is both ‘primary’ prurigo nodularis, and then there is secondary prurigo nodularis associated with something else [a wide range of underlying medical conditions], just like we divide primary and secondary hyperhidrosis.”

Dr. Yosipovitch reported having competing interests with several pharmaceutical companies, including Regeneron and Sanofi. Dr. Friedman disclosed that he is a consultant to and a speaker for Regeneron.

In two phase 3 trials, patients with prurigo nodularis (PN) randomized to receive dupilumab every 2 weeks for 24 weeks achieved statistically significant improvements in itch and skin lesions, compared with those who randomized to receive placebo.

The results, which were published online in Nature Medicine, were the basis for the FDA approval of dupilumab (Dupixent) for adults with PN in September 2022, the first treatment approved for treating PN in the United States.

“These positive studies support the involvement of type 2 cytokines in driving PN disease pathogenesis and the targeting of the [interleukin]-4/IL-13 axis as a novel therapeutic paradigm for patients with PN,” wrote the researchers, who were led by principal investigator Gil Yosipovitch, MD, professor of dermatology at the University of Miami, Fla. Dupilumab, an IL-4 receptor alpha antagonist, blocks the shared receptor component (IL-4R alpha) for IL-4 and IL-13.

For the two phase 3 trials, which were called LIBERTY-PN PRIME and PRIME2 and were sponsored by Sanofi and Regeneron Pharmaceuticals, researchers randomized adults with PN with 20 or more nodules and severe itch uncontrolled with topical therapies 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, which was measured by the proportion of patients with a 4-point or greater reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included a reduction in the number of nodules to 5 or fewer at week 24.

PRIME and PRIME2 enrolled 151 and 160 patients, respectively. In PRIME, 60% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 24, compared with 18.4% of patients in the placebo arm (P < .001). In PRIME2, 37.2% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 12, compared with 22% of patients in the placebo arm (P = .022).

The researchers also reported that, from an initial baseline of 20 to greater than 100 nodules, 32.0% of dupilumab-treated patients in PRIME and 25.6% in PRIME2 showed a reduction to 5 nodules or fewer, which corresponded to a response of “clear” or “almost clear” skin at week 12, compared with 11.8% and 12.2% of placebo-treated patients, respectively. This treatment effect on skin lesions continued to improve after week 12, with 48% of dupilumab-treated patients in PRIME and 44.9% in PRIME2 having five nodules or fewer at week 24, compared with 18.4% and 15.9% of placebo-treated patients, respectively. Safety was consistent with the known dupilumab safety profile.

“Validation is the first success of this paper,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study. “While both the safety and efficacy of dupilumab in these two phase 3 programs is the meat of the matter, nuanced highlights for me include the rigid nature of the exclusion criteria to ensure a study population that truly has PN as a stand-alone disease, rather than a secondary finding as we once believed to be the entire story. I think it’s important for us to recognize that it’s not one or the other, rather there is both ‘primary’ prurigo nodularis, and then there is secondary prurigo nodularis associated with something else [a wide range of underlying medical conditions], just like we divide primary and secondary hyperhidrosis.”

Dr. Yosipovitch reported having competing interests with several pharmaceutical companies, including Regeneron and Sanofi. Dr. Friedman disclosed that he is a consultant to and a speaker for Regeneron.

WASHINGTON – A bundled intervention combining point-of-care testing, electronic medical record support, and provider education significantly improved lipid screening rates in children aged 9-11 years, according to data from approximately 100 monthly visits over a 3-year period.

Guidelines from the National Heart, Lung, and Blood Institute currently recommend universal lipid screening for children aged 9-11 years, but screening rates in clinical practice remain low, according to Ruth E. Gardner, MD, of Penn State University, Hershey, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, Dr. Gardner and colleagues shared results of the implementation of a bundled testing protocol designed to improve screening.

The researchers reviewed data on lipid testing within 30 days for all 9- to 11-year-old well child visits at a single center between May 2019 and February 2022. The bundled intervention was introduced in May 2021.

The bundled protocol included in-office capillary testing and provider education. In addition, electronic medical record templates were modified to include prompts for lipid screening at relevant ages, and EMR orders were adjusted to include lipid testing. The researchers also collected targeted provider feedback on individualized screening rates in February 2022.

Screening rates were plotted monthly. For the period from May 2019 through May 2021, the rates averaged 6.5%. However, after the introduction of the bundled intervention, the rate increased to 29.9%. Following targeted provider feedback in February 2022, the researchers found an additional shift to 52.1% through March and April 2022.

The findings were limited by the use of data from a single center, and the researchers used an extended study period to account for disruptions to well-child care in the spring of 2020 related to the COVID-19 pandemic.

However, the results support the effectiveness of a bundled intervention for improving lipid screening rates in children aged 9-11 years, the researchers said, and targeted provider feedback and education could yield additional improvements, they concluded.
 

Preteen years are an optimal time for screening

“The current study is important because atherosclerosis begins in childhood, and screening at ages 9-11 is an optimal time to begin lifestyle changes to improve overall health and reduce risks of heart disease,” said Margaret Thew, DNP, FNP-BC, of the Medical College of Wisconsin, Milwaukee, in an interview.

Ms. Thew, who was not involved in the study, said, “The number of recommended and required screening items needed in pediatrics is vast, so many providers have to select which items to focus on for their health screenings with these ages.”

Overall, “I was impressed with the improvements that were made in this quality improvement study,” said Ms. Thew.

Barriers to lipid screening in this population include the reduced number of health screenings and immunizations recommended for this age group; the consequence is that access is limited to discuss preventive care opportunities, said Ms. Thew in an interview. Steps to overcome these barriers could include the use of many of the screening tools introduced in the current study, such as point-of-care testing in the office, use of the EMR to remind providers of testing, which can be done during well visits or school physicals, and educating providers about the current guidelines, she noted.

Other strategies to increase screening include moving the immunization series to provide more frequent appointments to children aged 9-11 years to offer education and preventive care, Ms. Thew added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
 

WASHINGTON – A bundled intervention combining point-of-care testing, electronic medical record support, and provider education significantly improved lipid screening rates in children aged 9-11 years, according to data from approximately 100 monthly visits over a 3-year period.

Guidelines from the National Heart, Lung, and Blood Institute currently recommend universal lipid screening for children aged 9-11 years, but screening rates in clinical practice remain low, according to Ruth E. Gardner, MD, of Penn State University, Hershey, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, Dr. Gardner and colleagues shared results of the implementation of a bundled testing protocol designed to improve screening.

The researchers reviewed data on lipid testing within 30 days for all 9- to 11-year-old well child visits at a single center between May 2019 and February 2022. The bundled intervention was introduced in May 2021.

The bundled protocol included in-office capillary testing and provider education. In addition, electronic medical record templates were modified to include prompts for lipid screening at relevant ages, and EMR orders were adjusted to include lipid testing. The researchers also collected targeted provider feedback on individualized screening rates in February 2022.

Screening rates were plotted monthly. For the period from May 2019 through May 2021, the rates averaged 6.5%. However, after the introduction of the bundled intervention, the rate increased to 29.9%. Following targeted provider feedback in February 2022, the researchers found an additional shift to 52.1% through March and April 2022.

The findings were limited by the use of data from a single center, and the researchers used an extended study period to account for disruptions to well-child care in the spring of 2020 related to the COVID-19 pandemic.

However, the results support the effectiveness of a bundled intervention for improving lipid screening rates in children aged 9-11 years, the researchers said, and targeted provider feedback and education could yield additional improvements, they concluded.
 

Preteen years are an optimal time for screening

“The current study is important because atherosclerosis begins in childhood, and screening at ages 9-11 is an optimal time to begin lifestyle changes to improve overall health and reduce risks of heart disease,” said Margaret Thew, DNP, FNP-BC, of the Medical College of Wisconsin, Milwaukee, in an interview.

Ms. Thew, who was not involved in the study, said, “The number of recommended and required screening items needed in pediatrics is vast, so many providers have to select which items to focus on for their health screenings with these ages.”

Overall, “I was impressed with the improvements that were made in this quality improvement study,” said Ms. Thew.

Barriers to lipid screening in this population include the reduced number of health screenings and immunizations recommended for this age group; the consequence is that access is limited to discuss preventive care opportunities, said Ms. Thew in an interview. Steps to overcome these barriers could include the use of many of the screening tools introduced in the current study, such as point-of-care testing in the office, use of the EMR to remind providers of testing, which can be done during well visits or school physicals, and educating providers about the current guidelines, she noted.

Other strategies to increase screening include moving the immunization series to provide more frequent appointments to children aged 9-11 years to offer education and preventive care, Ms. Thew added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
 

WASHINGTON – A bundled intervention combining point-of-care testing, electronic medical record support, and provider education significantly improved lipid screening rates in children aged 9-11 years, according to data from approximately 100 monthly visits over a 3-year period.

Guidelines from the National Heart, Lung, and Blood Institute currently recommend universal lipid screening for children aged 9-11 years, but screening rates in clinical practice remain low, according to Ruth E. Gardner, MD, of Penn State University, Hershey, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, Dr. Gardner and colleagues shared results of the implementation of a bundled testing protocol designed to improve screening.

The researchers reviewed data on lipid testing within 30 days for all 9- to 11-year-old well child visits at a single center between May 2019 and February 2022. The bundled intervention was introduced in May 2021.

The bundled protocol included in-office capillary testing and provider education. In addition, electronic medical record templates were modified to include prompts for lipid screening at relevant ages, and EMR orders were adjusted to include lipid testing. The researchers also collected targeted provider feedback on individualized screening rates in February 2022.

Screening rates were plotted monthly. For the period from May 2019 through May 2021, the rates averaged 6.5%. However, after the introduction of the bundled intervention, the rate increased to 29.9%. Following targeted provider feedback in February 2022, the researchers found an additional shift to 52.1% through March and April 2022.

The findings were limited by the use of data from a single center, and the researchers used an extended study period to account for disruptions to well-child care in the spring of 2020 related to the COVID-19 pandemic.

However, the results support the effectiveness of a bundled intervention for improving lipid screening rates in children aged 9-11 years, the researchers said, and targeted provider feedback and education could yield additional improvements, they concluded.
 

Preteen years are an optimal time for screening

“The current study is important because atherosclerosis begins in childhood, and screening at ages 9-11 is an optimal time to begin lifestyle changes to improve overall health and reduce risks of heart disease,” said Margaret Thew, DNP, FNP-BC, of the Medical College of Wisconsin, Milwaukee, in an interview.

Ms. Thew, who was not involved in the study, said, “The number of recommended and required screening items needed in pediatrics is vast, so many providers have to select which items to focus on for their health screenings with these ages.”

Overall, “I was impressed with the improvements that were made in this quality improvement study,” said Ms. Thew.

Barriers to lipid screening in this population include the reduced number of health screenings and immunizations recommended for this age group; the consequence is that access is limited to discuss preventive care opportunities, said Ms. Thew in an interview. Steps to overcome these barriers could include the use of many of the screening tools introduced in the current study, such as point-of-care testing in the office, use of the EMR to remind providers of testing, which can be done during well visits or school physicals, and educating providers about the current guidelines, she noted.

Other strategies to increase screening include moving the immunization series to provide more frequent appointments to children aged 9-11 years to offer education and preventive care, Ms. Thew added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
 

Overweight boy, infertile man?

When it comes to causes of infertility, history and science have generally focused on women. A lot of the research overlooks men, but some previous studies have suggested that male infertility contributes to about half of the cases of couple infertility. The reason for much of that male infertility, however, has been a mystery. Until now.

A group of Italian investigators looked at the declining trend in sperm counts over the past 40 years and the increase of childhood obesity. Is there a correlation? The researchers think so. Childhood obesity can be linked to multiple causes, but the researchers zeroed in on the effect that obesity has on metabolic rates and, therefore, testicular growth.

Collecting data on testicular volume, body mass index (BMI), and insulin resistance from 268 boys aged 2-18 years, the researchers discovered that those with normal weight and normal insulin levels had testicular volumes 1.5 times higher than their overweight counterparts and 1.5-2 times higher than those with hyperinsulinemia, building a case for obesity being a factor for infertility later in life.

Since low testicular volume is associated with lower sperm count and production as an adult, putting two and two together makes a compelling argument for childhood obesity being a major male infertility culprit. It also creates even more urgency for the health care industry and community decision makers to focus on childhood obesity.

It sure would be nice to be able to take one of the many risk factors for future human survival off the table. Maybe by taking something, like cake, off the table.

Fecal transplantation moves to the kitchen

Fecal microbiota transplantation is an effective way to treat Clostridioides difficile infection, but, in the end, it’s still a transplantation procedure involving a nasogastric or colorectal tube or rather large oral capsules with a demanding (30-40 capsules over 2 days) dosage. Please, Science, tell us there’s a better way.

CC BY-NC-ND 4.0, Adèle Rakotonirina et Nathalie Boulens

Science, in the form of investigators at the University of Geneva and Lausanne University Hospital in Switzerland, has spoken, and there may be a better way. Presenting fecal beads: All the bacterial goodness of donor stool without the tubal insertions or massive quantities of giant capsules.

We know you’re scoffing out there, but it’s true. All you need is a little alginate, which is a “biocompatible polysaccharide isolated from brown algae” of the Phaeophyceae family. The donor feces is microencapsulated by mixing it with the alginate, dropping that mixture into water containing calcium chloride, turning it into a gel, and then freeze-drying the gel into small (just 2 mm), solid beads.

Sounds plausible enough, but what do you do with them? “These brownish beads can be easily dispersed in a liquid or food that is pleasant to eat. They also have no taste,” senior author Eric Allémann, PhD, said in a statement released by the University of Geneva.

Pleasant to eat? No taste? So which is it? If you really want to know, watch fecal beads week on the new season of “The Great British Baking Show,” when Paul and Prue judge poop baked into crumpets, crepes, and crostatas. Yum.
 

We’re on the low-oxygen diet

Nine out of ten doctors agree: Oxygen is more important to your continued well-being than food. After all, a human can go weeks without food, but just minutes without oxygen. However, ten out of ten doctors agree that the United States has an obesity problem. They all also agree that previous research has shown soldiers who train at high altitudes lose more weight than those training at lower altitudes.

PBRC

So, on the one hand, we have a country full of overweight people, and on the other, we have low oxygen levels causing weight loss. The solution, then, is obvious: Stop breathing.

More specifically (and somewhat less facetiously), researchers from Louisiana have launched the Low Oxygen and Weight Status trial and are currently recruiting individuals with BMIs of 30-40 to, uh, suffocate themselves. No, no, it’s okay, it’s just when they’re sleeping.

Fine, straight face. Participants in the LOWS trial will undergo an 8-week period when they will consume a controlled weight-loss diet and spend their nights in a hypoxic sealed tent, where they will sleep in an environment with an oxygen level equivalent to 8,500 feet above sea level (roughly equivalent to Aspen, Colo.). They will be compared with people on the same diet who sleep in a normal, sea-level oxygen environment.

The study’s goal is to determine whether or not spending time in a low-oxygen environment will suppress appetite, increase energy expenditure, and improve weight loss and insulin sensitivity. Excessive weight loss in high-altitude environments isn’t a good thing for soldiers – they kind of need their muscles and body weight to do the whole soldiering thing – but it could be great for people struggling to lose those last few pounds. And it also may prove LOTME’s previous thesis: Air is not good.

Overweight boy, infertile man?

When it comes to causes of infertility, history and science have generally focused on women. A lot of the research overlooks men, but some previous studies have suggested that male infertility contributes to about half of the cases of couple infertility. The reason for much of that male infertility, however, has been a mystery. Until now.

A group of Italian investigators looked at the declining trend in sperm counts over the past 40 years and the increase of childhood obesity. Is there a correlation? The researchers think so. Childhood obesity can be linked to multiple causes, but the researchers zeroed in on the effect that obesity has on metabolic rates and, therefore, testicular growth.

Collecting data on testicular volume, body mass index (BMI), and insulin resistance from 268 boys aged 2-18 years, the researchers discovered that those with normal weight and normal insulin levels had testicular volumes 1.5 times higher than their overweight counterparts and 1.5-2 times higher than those with hyperinsulinemia, building a case for obesity being a factor for infertility later in life.

Since low testicular volume is associated with lower sperm count and production as an adult, putting two and two together makes a compelling argument for childhood obesity being a major male infertility culprit. It also creates even more urgency for the health care industry and community decision makers to focus on childhood obesity.

It sure would be nice to be able to take one of the many risk factors for future human survival off the table. Maybe by taking something, like cake, off the table.

Fecal transplantation moves to the kitchen

Fecal microbiota transplantation is an effective way to treat Clostridioides difficile infection, but, in the end, it’s still a transplantation procedure involving a nasogastric or colorectal tube or rather large oral capsules with a demanding (30-40 capsules over 2 days) dosage. Please, Science, tell us there’s a better way.

CC BY-NC-ND 4.0, Adèle Rakotonirina et Nathalie Boulens

Science, in the form of investigators at the University of Geneva and Lausanne University Hospital in Switzerland, has spoken, and there may be a better way. Presenting fecal beads: All the bacterial goodness of donor stool without the tubal insertions or massive quantities of giant capsules.

We know you’re scoffing out there, but it’s true. All you need is a little alginate, which is a “biocompatible polysaccharide isolated from brown algae” of the Phaeophyceae family. The donor feces is microencapsulated by mixing it with the alginate, dropping that mixture into water containing calcium chloride, turning it into a gel, and then freeze-drying the gel into small (just 2 mm), solid beads.

Sounds plausible enough, but what do you do with them? “These brownish beads can be easily dispersed in a liquid or food that is pleasant to eat. They also have no taste,” senior author Eric Allémann, PhD, said in a statement released by the University of Geneva.

Pleasant to eat? No taste? So which is it? If you really want to know, watch fecal beads week on the new season of “The Great British Baking Show,” when Paul and Prue judge poop baked into crumpets, crepes, and crostatas. Yum.
 

We’re on the low-oxygen diet

Nine out of ten doctors agree: Oxygen is more important to your continued well-being than food. After all, a human can go weeks without food, but just minutes without oxygen. However, ten out of ten doctors agree that the United States has an obesity problem. They all also agree that previous research has shown soldiers who train at high altitudes lose more weight than those training at lower altitudes.

PBRC

So, on the one hand, we have a country full of overweight people, and on the other, we have low oxygen levels causing weight loss. The solution, then, is obvious: Stop breathing.

More specifically (and somewhat less facetiously), researchers from Louisiana have launched the Low Oxygen and Weight Status trial and are currently recruiting individuals with BMIs of 30-40 to, uh, suffocate themselves. No, no, it’s okay, it’s just when they’re sleeping.

Fine, straight face. Participants in the LOWS trial will undergo an 8-week period when they will consume a controlled weight-loss diet and spend their nights in a hypoxic sealed tent, where they will sleep in an environment with an oxygen level equivalent to 8,500 feet above sea level (roughly equivalent to Aspen, Colo.). They will be compared with people on the same diet who sleep in a normal, sea-level oxygen environment.

The study’s goal is to determine whether or not spending time in a low-oxygen environment will suppress appetite, increase energy expenditure, and improve weight loss and insulin sensitivity. Excessive weight loss in high-altitude environments isn’t a good thing for soldiers – they kind of need their muscles and body weight to do the whole soldiering thing – but it could be great for people struggling to lose those last few pounds. And it also may prove LOTME’s previous thesis: Air is not good.

Overweight boy, infertile man?

When it comes to causes of infertility, history and science have generally focused on women. A lot of the research overlooks men, but some previous studies have suggested that male infertility contributes to about half of the cases of couple infertility. The reason for much of that male infertility, however, has been a mystery. Until now.

A group of Italian investigators looked at the declining trend in sperm counts over the past 40 years and the increase of childhood obesity. Is there a correlation? The researchers think so. Childhood obesity can be linked to multiple causes, but the researchers zeroed in on the effect that obesity has on metabolic rates and, therefore, testicular growth.

Collecting data on testicular volume, body mass index (BMI), and insulin resistance from 268 boys aged 2-18 years, the researchers discovered that those with normal weight and normal insulin levels had testicular volumes 1.5 times higher than their overweight counterparts and 1.5-2 times higher than those with hyperinsulinemia, building a case for obesity being a factor for infertility later in life.

Since low testicular volume is associated with lower sperm count and production as an adult, putting two and two together makes a compelling argument for childhood obesity being a major male infertility culprit. It also creates even more urgency for the health care industry and community decision makers to focus on childhood obesity.

It sure would be nice to be able to take one of the many risk factors for future human survival off the table. Maybe by taking something, like cake, off the table.

Fecal transplantation moves to the kitchen

Fecal microbiota transplantation is an effective way to treat Clostridioides difficile infection, but, in the end, it’s still a transplantation procedure involving a nasogastric or colorectal tube or rather large oral capsules with a demanding (30-40 capsules over 2 days) dosage. Please, Science, tell us there’s a better way.

CC BY-NC-ND 4.0, Adèle Rakotonirina et Nathalie Boulens

Science, in the form of investigators at the University of Geneva and Lausanne University Hospital in Switzerland, has spoken, and there may be a better way. Presenting fecal beads: All the bacterial goodness of donor stool without the tubal insertions or massive quantities of giant capsules.

We know you’re scoffing out there, but it’s true. All you need is a little alginate, which is a “biocompatible polysaccharide isolated from brown algae” of the Phaeophyceae family. The donor feces is microencapsulated by mixing it with the alginate, dropping that mixture into water containing calcium chloride, turning it into a gel, and then freeze-drying the gel into small (just 2 mm), solid beads.

Sounds plausible enough, but what do you do with them? “These brownish beads can be easily dispersed in a liquid or food that is pleasant to eat. They also have no taste,” senior author Eric Allémann, PhD, said in a statement released by the University of Geneva.

Pleasant to eat? No taste? So which is it? If you really want to know, watch fecal beads week on the new season of “The Great British Baking Show,” when Paul and Prue judge poop baked into crumpets, crepes, and crostatas. Yum.
 

We’re on the low-oxygen diet

Nine out of ten doctors agree: Oxygen is more important to your continued well-being than food. After all, a human can go weeks without food, but just minutes without oxygen. However, ten out of ten doctors agree that the United States has an obesity problem. They all also agree that previous research has shown soldiers who train at high altitudes lose more weight than those training at lower altitudes.

PBRC

So, on the one hand, we have a country full of overweight people, and on the other, we have low oxygen levels causing weight loss. The solution, then, is obvious: Stop breathing.

More specifically (and somewhat less facetiously), researchers from Louisiana have launched the Low Oxygen and Weight Status trial and are currently recruiting individuals with BMIs of 30-40 to, uh, suffocate themselves. No, no, it’s okay, it’s just when they’re sleeping.

Fine, straight face. Participants in the LOWS trial will undergo an 8-week period when they will consume a controlled weight-loss diet and spend their nights in a hypoxic sealed tent, where they will sleep in an environment with an oxygen level equivalent to 8,500 feet above sea level (roughly equivalent to Aspen, Colo.). They will be compared with people on the same diet who sleep in a normal, sea-level oxygen environment.

The study’s goal is to determine whether or not spending time in a low-oxygen environment will suppress appetite, increase energy expenditure, and improve weight loss and insulin sensitivity. Excessive weight loss in high-altitude environments isn’t a good thing for soldiers – they kind of need their muscles and body weight to do the whole soldiering thing – but it could be great for people struggling to lose those last few pounds. And it also may prove LOTME’s previous thesis: Air is not good.

A potassium hydroxide (KOH) preparation of pus and dry superficial skin taken from 1 of the pustules revealed multiple hyphae and confirmed a diagnosis of nodular granulomatous perifolliculitis, also called Majocchi granuloma.

Majocchi granuloma is a reactive process of inflammation caused by infection of the follicular unit(s) by a dermatophyte—most often the same Trichophyton species responsible for more superficial tinea. On exam, there may be a solitary papule, pustule, or nodule. More often, there are multiple papules and pustules grouped within an annular plaque in hair-bearing areas on the head, trunk, or extremities. Majocchi granuloma can occur in patients who are healthy and those who are immunosuppressed.¹ It can also occur when a topical steroid is applied to unsuspected tinea, as occurred here. In this case, the patient was accustomed to having multiple skin plaques of psoriasis and assumed this was a stubborn manifestation of that.

Because the infection penetrates deeper than most topical therapies can effectively reach at adequate concentrations, systemic medications are the treatments of choice. Terbinafine, itraconazole, and fluconazole are all effective options but need to be used for several weeks to be effective.

This patient received terbinafine 250 mg/d for 6 weeks and the pustules cleared completely. He continued with his other psoriasis medications throughout his treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME. 

A potassium hydroxide (KOH) preparation of pus and dry superficial skin taken from 1 of the pustules revealed multiple hyphae and confirmed a diagnosis of nodular granulomatous perifolliculitis, also called Majocchi granuloma.

Majocchi granuloma is a reactive process of inflammation caused by infection of the follicular unit(s) by a dermatophyte—most often the same Trichophyton species responsible for more superficial tinea. On exam, there may be a solitary papule, pustule, or nodule. More often, there are multiple papules and pustules grouped within an annular plaque in hair-bearing areas on the head, trunk, or extremities. Majocchi granuloma can occur in patients who are healthy and those who are immunosuppressed.¹ It can also occur when a topical steroid is applied to unsuspected tinea, as occurred here. In this case, the patient was accustomed to having multiple skin plaques of psoriasis and assumed this was a stubborn manifestation of that.

Because the infection penetrates deeper than most topical therapies can effectively reach at adequate concentrations, systemic medications are the treatments of choice. Terbinafine, itraconazole, and fluconazole are all effective options but need to be used for several weeks to be effective.

This patient received terbinafine 250 mg/d for 6 weeks and the pustules cleared completely. He continued with his other psoriasis medications throughout his treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME. 

A potassium hydroxide (KOH) preparation of pus and dry superficial skin taken from 1 of the pustules revealed multiple hyphae and confirmed a diagnosis of nodular granulomatous perifolliculitis, also called Majocchi granuloma.

Majocchi granuloma is a reactive process of inflammation caused by infection of the follicular unit(s) by a dermatophyte—most often the same Trichophyton species responsible for more superficial tinea. On exam, there may be a solitary papule, pustule, or nodule. More often, there are multiple papules and pustules grouped within an annular plaque in hair-bearing areas on the head, trunk, or extremities. Majocchi granuloma can occur in patients who are healthy and those who are immunosuppressed.¹ It can also occur when a topical steroid is applied to unsuspected tinea, as occurred here. In this case, the patient was accustomed to having multiple skin plaques of psoriasis and assumed this was a stubborn manifestation of that.

Because the infection penetrates deeper than most topical therapies can effectively reach at adequate concentrations, systemic medications are the treatments of choice. Terbinafine, itraconazole, and fluconazole are all effective options but need to be used for several weeks to be effective.

This patient received terbinafine 250 mg/d for 6 weeks and the pustules cleared completely. He continued with his other psoriasis medications throughout his treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME. 

May is Mental Health Awareness Month, providing us a chance to go beyond discussing the screening, diagnosis, and evidence-based treatments for the mental illnesses of youth. Just as children are developing physical health, they are similarly establishing the foundations for their mental health. The World Health Organization defines good mental health as “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her own community.” While the science of mental health promotion and disease prevention in childhood and adolescence is relatively young, there are several discrete domains in which you can follow and support your patient’s developing mental health. This begins with the well-being of new parents, and then moves into how parents are helping their children to develop skills to manage their basic daily needs and impulses, their thoughts and feelings, their stresses and their relationships. With a little support from you, parents can confidently help their children develop the foundations for good mental health.

First year of life: Parental mental health

Perhaps the strongest risk factor for serious mental illness in childhood and adulthood is parental neglect during the first year of life, and neglect in the first several months of life is the most commonly reported form of child abuse. Infant neglect is associated with parental depression (and other mental illnesses), parental substance use, and a parent’s own experience of childhood abuse or neglect. Neglect is more common with teenaged parents and parents living in poverty. Pediatricians are uniquely connected to families during the first year of a child’s life. The American Academy of Pediatrics recommends screening new mothers for depression at 1-, 2-, 4-, and 6-month infant check-ups with the Edinburgh Postnatal Depression Screen. Even without a positive screen, new parents may need the fortifications of extra community support to adapt to the changes parenthood brings.

At checkups, ask (both) parents how they are managing the stresses of a new baby. Are they getting restful sleep? Do they have social supports? Are they connected to a community (friends, extended family, faith) or isolated? Are they developing confidence as parents or feeling overwhelmed? Simple guidance, such as “sleep when the baby sleeps” and reassurance that taking good care of themselves is taking good care of the baby is always helpful. Sometimes you will need to refer for treatment or to community supports. Have your list of online and in-person resources at the ready to provide parents with these prescriptions. Supporting parental mental health and adjustment in the first year of life is possibly the most important building block for their child’s future mental health.
 

Toddlers and up: Emotional literacy

Emotional literacy (sometimes called “emotional intelligence”) is the capacity to recognize, identify, and manage feelings in oneself and in others. This skill begins to develop in infancy when parents respond to their baby’s cries with attunement, feeding or changing them if needed, and at other times simply reflecting their feelings and soothing them with movement, singing, or quiet talking. As children grow, so does their range of feelings, and their (cognitive) capacity to identify and manage them. Parents support this development by being available whenever their young children experience strong emotions, calmly listening, and acknowledging their discomfort. Parents can offer words for describing those feelings, and even be curious with their young children where in their bodies they are feeling them, how they can stay patient while the feeling passes or things they might be able to do to feel better. Parents may want to remove their child’s distress, but staying calm, curious, and present while helping their child to manage it will build their child’s emotional health. Parents can nurture this development in a less intense way by reading books about feelings together and noticing and identifying feelings in other children or in cartoon characters.

School-age children: Adding mindfulness

While a child’s cognitive development unfolds naturally, school-age children can cultivate awareness of their thoughts. This becomes possible after awareness of feelings and parents can help their older children consider whether something they are experiencing is a thought, a feeling, or a fact. They do so in the same way they helped their child develop emotional literacy: By responding with calm, curiosity, and confidence every time their child comes to them in distress (especially mild distress, like boredom!) or with a challenge or a question. With a difficult situation, parents start by helping their child to identify thoughts and feelings before impulsively acting on them. Parents can help children identify what’s in their control, try different approaches, and be flexible if their first efforts don’t work. Children need to learn that failing at things is how we learn and grow. Just like learning to ride a bike, it builds their frustration tolerance, their knowledge that they can do difficult things, and that distress subsides. These are critical building blocks for adolescence, when the challenges become greater and they manage them more independently.

Learning “mindfulness” (a practice that cultivates nonjudgmental awareness of one’s own thoughts, feelings, and sensations) can help children (and parents) to cultivate quiet self-awareness outside of moments of difficulty. “Stop, Breathe, and Think” and “Mindful gNATs” are two free apps that are recommended by the American Academy of Child and Adolescent Psychiatry for children (and their parents) to use to practice this awareness of thoughts and feelings.
 

Early and later adolescence: Stress management skills

Building on this awareness of thoughts and emotions, adolescents develop adaptive coping skills by facing challenges with the support of their parents nearby. Parents should still be ready to respond to charged emotional moments with calm and curiosity, validating their child’s distress while helping them to consider healthy responses. Helping their teenager to describe their experience, differentiating feelings from thoughts (and facts), and considering different choices within their control is foundational to resilience in adulthood. Parents also help their teenagers by reminding them of the need for good self-care (sleep, exercise, nutrition), nourishing social relationships, and protecting time for rest and recharging activities. Sometimes, parents will think with their teenager about why they are engaged in an activity that is stressful, whether it is authentically important to them, and why. Adolescents should be deepening their sense of identity, interests, talents, and even values, and stressful moments are rich opportunities to do so, with the support of caring adults. Without intentionally building these skills, adolescents will be more prone to managing stress with avoidance or unhealthy coping, such as excessive eating, video gaming, drugs, or alcohol.

Infancy and up: Behavioral healthy habits (sleep, physical activity, nutrition, and screen time)

Healthy habits sound simple, but establishing them is not always easy. The idea of a habit is that it makes managing something challenging or important more automatic, and thus easier and more reliable. Many of the same habits that promote physical health in adulthood also promote mental health: adequate, restful sleep; daily physical activity; a nutritious diet and a healthy relationship with food; and managing screen time in a developmentally appropriate way. Infants depend entirely on their parents for regulation of these behaviors. As their children grow, parents will adapt these routines so that their children are gradually regulating these needs and activities more independently. In each of these areas, children need clear expectations and routines, consistent consequences and positive feedback, and the modeling and patient support of their parents. Educate parents about what good sleep hygiene looks like at each age. Discuss ways to support regular physical activity, especially as a family. Ask the parents about nutrition, including how they manage picky eating; how many family meals they enjoy together; and whether food is ever used to manage boredom or distress. Finally, talk with parents about a developmentally appropriate approach to rules and expectations around screen time and the importance of using family-based rules. Establishing expectations and routines during early childhood means children learn how good it feels to have restful sleep, regular exercise, and happy, healthy family meals. In adolescence, parents can then focus on helping their children to manage temptation, challenge, disappointment, and frustration more independently.

Infancy and up: Relational health

Children develop the skills needed for healthy relationships at home, and they are connected to all of the skills described above. Children need attuned, responsive, and reliable parenting to build a capacity for trust of others, to learn how to communicate honestly and effectively, to learn to expect and offer compassion and respect, and to learn how to handle disagreement and conflict. They learn these skills by watching their parents and by developing the emotional, cognitive, and behavioral healthy habits with their parents’ help. They need a consistently safe and responsive environment at home. They need parents who are attuned and flexible, while maintaining routines and high expectations. They need parents who make time for them when they are sad or struggling, and make time for joy, play, and mindless fun. While a detailed assessment of how the family is functioning may go beyond a check-up, you can ask about those routines that build healthy habits (family mealtime, sleep routines, screen time rules), communication style, and what the family enjoys doing together. Learning about how a family is building these healthy habits and how connected they are to one another can give you a clear snapshot of how well a child may be doing on their mental health growth curve, and what areas might benefit from more active guidance and support.

Dr. Swick is physician in chief at Ohana Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

May is Mental Health Awareness Month, providing us a chance to go beyond discussing the screening, diagnosis, and evidence-based treatments for the mental illnesses of youth. Just as children are developing physical health, they are similarly establishing the foundations for their mental health. The World Health Organization defines good mental health as “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her own community.” While the science of mental health promotion and disease prevention in childhood and adolescence is relatively young, there are several discrete domains in which you can follow and support your patient’s developing mental health. This begins with the well-being of new parents, and then moves into how parents are helping their children to develop skills to manage their basic daily needs and impulses, their thoughts and feelings, their stresses and their relationships. With a little support from you, parents can confidently help their children develop the foundations for good mental health.

First year of life: Parental mental health

Perhaps the strongest risk factor for serious mental illness in childhood and adulthood is parental neglect during the first year of life, and neglect in the first several months of life is the most commonly reported form of child abuse. Infant neglect is associated with parental depression (and other mental illnesses), parental substance use, and a parent’s own experience of childhood abuse or neglect. Neglect is more common with teenaged parents and parents living in poverty. Pediatricians are uniquely connected to families during the first year of a child’s life. The American Academy of Pediatrics recommends screening new mothers for depression at 1-, 2-, 4-, and 6-month infant check-ups with the Edinburgh Postnatal Depression Screen. Even without a positive screen, new parents may need the fortifications of extra community support to adapt to the changes parenthood brings.

At checkups, ask (both) parents how they are managing the stresses of a new baby. Are they getting restful sleep? Do they have social supports? Are they connected to a community (friends, extended family, faith) or isolated? Are they developing confidence as parents or feeling overwhelmed? Simple guidance, such as “sleep when the baby sleeps” and reassurance that taking good care of themselves is taking good care of the baby is always helpful. Sometimes you will need to refer for treatment or to community supports. Have your list of online and in-person resources at the ready to provide parents with these prescriptions. Supporting parental mental health and adjustment in the first year of life is possibly the most important building block for their child’s future mental health.
 

Toddlers and up: Emotional literacy

Emotional literacy (sometimes called “emotional intelligence”) is the capacity to recognize, identify, and manage feelings in oneself and in others. This skill begins to develop in infancy when parents respond to their baby’s cries with attunement, feeding or changing them if needed, and at other times simply reflecting their feelings and soothing them with movement, singing, or quiet talking. As children grow, so does their range of feelings, and their (cognitive) capacity to identify and manage them. Parents support this development by being available whenever their young children experience strong emotions, calmly listening, and acknowledging their discomfort. Parents can offer words for describing those feelings, and even be curious with their young children where in their bodies they are feeling them, how they can stay patient while the feeling passes or things they might be able to do to feel better. Parents may want to remove their child’s distress, but staying calm, curious, and present while helping their child to manage it will build their child’s emotional health. Parents can nurture this development in a less intense way by reading books about feelings together and noticing and identifying feelings in other children or in cartoon characters.

School-age children: Adding mindfulness

While a child’s cognitive development unfolds naturally, school-age children can cultivate awareness of their thoughts. This becomes possible after awareness of feelings and parents can help their older children consider whether something they are experiencing is a thought, a feeling, or a fact. They do so in the same way they helped their child develop emotional literacy: By responding with calm, curiosity, and confidence every time their child comes to them in distress (especially mild distress, like boredom!) or with a challenge or a question. With a difficult situation, parents start by helping their child to identify thoughts and feelings before impulsively acting on them. Parents can help children identify what’s in their control, try different approaches, and be flexible if their first efforts don’t work. Children need to learn that failing at things is how we learn and grow. Just like learning to ride a bike, it builds their frustration tolerance, their knowledge that they can do difficult things, and that distress subsides. These are critical building blocks for adolescence, when the challenges become greater and they manage them more independently.

Learning “mindfulness” (a practice that cultivates nonjudgmental awareness of one’s own thoughts, feelings, and sensations) can help children (and parents) to cultivate quiet self-awareness outside of moments of difficulty. “Stop, Breathe, and Think” and “Mindful gNATs” are two free apps that are recommended by the American Academy of Child and Adolescent Psychiatry for children (and their parents) to use to practice this awareness of thoughts and feelings.
 

Early and later adolescence: Stress management skills

Building on this awareness of thoughts and emotions, adolescents develop adaptive coping skills by facing challenges with the support of their parents nearby. Parents should still be ready to respond to charged emotional moments with calm and curiosity, validating their child’s distress while helping them to consider healthy responses. Helping their teenager to describe their experience, differentiating feelings from thoughts (and facts), and considering different choices within their control is foundational to resilience in adulthood. Parents also help their teenagers by reminding them of the need for good self-care (sleep, exercise, nutrition), nourishing social relationships, and protecting time for rest and recharging activities. Sometimes, parents will think with their teenager about why they are engaged in an activity that is stressful, whether it is authentically important to them, and why. Adolescents should be deepening their sense of identity, interests, talents, and even values, and stressful moments are rich opportunities to do so, with the support of caring adults. Without intentionally building these skills, adolescents will be more prone to managing stress with avoidance or unhealthy coping, such as excessive eating, video gaming, drugs, or alcohol.

Infancy and up: Behavioral healthy habits (sleep, physical activity, nutrition, and screen time)

Healthy habits sound simple, but establishing them is not always easy. The idea of a habit is that it makes managing something challenging or important more automatic, and thus easier and more reliable. Many of the same habits that promote physical health in adulthood also promote mental health: adequate, restful sleep; daily physical activity; a nutritious diet and a healthy relationship with food; and managing screen time in a developmentally appropriate way. Infants depend entirely on their parents for regulation of these behaviors. As their children grow, parents will adapt these routines so that their children are gradually regulating these needs and activities more independently. In each of these areas, children need clear expectations and routines, consistent consequences and positive feedback, and the modeling and patient support of their parents. Educate parents about what good sleep hygiene looks like at each age. Discuss ways to support regular physical activity, especially as a family. Ask the parents about nutrition, including how they manage picky eating; how many family meals they enjoy together; and whether food is ever used to manage boredom or distress. Finally, talk with parents about a developmentally appropriate approach to rules and expectations around screen time and the importance of using family-based rules. Establishing expectations and routines during early childhood means children learn how good it feels to have restful sleep, regular exercise, and happy, healthy family meals. In adolescence, parents can then focus on helping their children to manage temptation, challenge, disappointment, and frustration more independently.

Infancy and up: Relational health

Children develop the skills needed for healthy relationships at home, and they are connected to all of the skills described above. Children need attuned, responsive, and reliable parenting to build a capacity for trust of others, to learn how to communicate honestly and effectively, to learn to expect and offer compassion and respect, and to learn how to handle disagreement and conflict. They learn these skills by watching their parents and by developing the emotional, cognitive, and behavioral healthy habits with their parents’ help. They need a consistently safe and responsive environment at home. They need parents who are attuned and flexible, while maintaining routines and high expectations. They need parents who make time for them when they are sad or struggling, and make time for joy, play, and mindless fun. While a detailed assessment of how the family is functioning may go beyond a check-up, you can ask about those routines that build healthy habits (family mealtime, sleep routines, screen time rules), communication style, and what the family enjoys doing together. Learning about how a family is building these healthy habits and how connected they are to one another can give you a clear snapshot of how well a child may be doing on their mental health growth curve, and what areas might benefit from more active guidance and support.

Dr. Swick is physician in chief at Ohana Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

May is Mental Health Awareness Month, providing us a chance to go beyond discussing the screening, diagnosis, and evidence-based treatments for the mental illnesses of youth. Just as children are developing physical health, they are similarly establishing the foundations for their mental health. The World Health Organization defines good mental health as “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her own community.” While the science of mental health promotion and disease prevention in childhood and adolescence is relatively young, there are several discrete domains in which you can follow and support your patient’s developing mental health. This begins with the well-being of new parents, and then moves into how parents are helping their children to develop skills to manage their basic daily needs and impulses, their thoughts and feelings, their stresses and their relationships. With a little support from you, parents can confidently help their children develop the foundations for good mental health.

First year of life: Parental mental health

Perhaps the strongest risk factor for serious mental illness in childhood and adulthood is parental neglect during the first year of life, and neglect in the first several months of life is the most commonly reported form of child abuse. Infant neglect is associated with parental depression (and other mental illnesses), parental substance use, and a parent’s own experience of childhood abuse or neglect. Neglect is more common with teenaged parents and parents living in poverty. Pediatricians are uniquely connected to families during the first year of a child’s life. The American Academy of Pediatrics recommends screening new mothers for depression at 1-, 2-, 4-, and 6-month infant check-ups with the Edinburgh Postnatal Depression Screen. Even without a positive screen, new parents may need the fortifications of extra community support to adapt to the changes parenthood brings.

At checkups, ask (both) parents how they are managing the stresses of a new baby. Are they getting restful sleep? Do they have social supports? Are they connected to a community (friends, extended family, faith) or isolated? Are they developing confidence as parents or feeling overwhelmed? Simple guidance, such as “sleep when the baby sleeps” and reassurance that taking good care of themselves is taking good care of the baby is always helpful. Sometimes you will need to refer for treatment or to community supports. Have your list of online and in-person resources at the ready to provide parents with these prescriptions. Supporting parental mental health and adjustment in the first year of life is possibly the most important building block for their child’s future mental health.
 

Toddlers and up: Emotional literacy

Emotional literacy (sometimes called “emotional intelligence”) is the capacity to recognize, identify, and manage feelings in oneself and in others. This skill begins to develop in infancy when parents respond to their baby’s cries with attunement, feeding or changing them if needed, and at other times simply reflecting their feelings and soothing them with movement, singing, or quiet talking. As children grow, so does their range of feelings, and their (cognitive) capacity to identify and manage them. Parents support this development by being available whenever their young children experience strong emotions, calmly listening, and acknowledging their discomfort. Parents can offer words for describing those feelings, and even be curious with their young children where in their bodies they are feeling them, how they can stay patient while the feeling passes or things they might be able to do to feel better. Parents may want to remove their child’s distress, but staying calm, curious, and present while helping their child to manage it will build their child’s emotional health. Parents can nurture this development in a less intense way by reading books about feelings together and noticing and identifying feelings in other children or in cartoon characters.

School-age children: Adding mindfulness

While a child’s cognitive development unfolds naturally, school-age children can cultivate awareness of their thoughts. This becomes possible after awareness of feelings and parents can help their older children consider whether something they are experiencing is a thought, a feeling, or a fact. They do so in the same way they helped their child develop emotional literacy: By responding with calm, curiosity, and confidence every time their child comes to them in distress (especially mild distress, like boredom!) or with a challenge or a question. With a difficult situation, parents start by helping their child to identify thoughts and feelings before impulsively acting on them. Parents can help children identify what’s in their control, try different approaches, and be flexible if their first efforts don’t work. Children need to learn that failing at things is how we learn and grow. Just like learning to ride a bike, it builds their frustration tolerance, their knowledge that they can do difficult things, and that distress subsides. These are critical building blocks for adolescence, when the challenges become greater and they manage them more independently.

Learning “mindfulness” (a practice that cultivates nonjudgmental awareness of one’s own thoughts, feelings, and sensations) can help children (and parents) to cultivate quiet self-awareness outside of moments of difficulty. “Stop, Breathe, and Think” and “Mindful gNATs” are two free apps that are recommended by the American Academy of Child and Adolescent Psychiatry for children (and their parents) to use to practice this awareness of thoughts and feelings.
 

Early and later adolescence: Stress management skills

Building on this awareness of thoughts and emotions, adolescents develop adaptive coping skills by facing challenges with the support of their parents nearby. Parents should still be ready to respond to charged emotional moments with calm and curiosity, validating their child’s distress while helping them to consider healthy responses. Helping their teenager to describe their experience, differentiating feelings from thoughts (and facts), and considering different choices within their control is foundational to resilience in adulthood. Parents also help their teenagers by reminding them of the need for good self-care (sleep, exercise, nutrition), nourishing social relationships, and protecting time for rest and recharging activities. Sometimes, parents will think with their teenager about why they are engaged in an activity that is stressful, whether it is authentically important to them, and why. Adolescents should be deepening their sense of identity, interests, talents, and even values, and stressful moments are rich opportunities to do so, with the support of caring adults. Without intentionally building these skills, adolescents will be more prone to managing stress with avoidance or unhealthy coping, such as excessive eating, video gaming, drugs, or alcohol.

Infancy and up: Behavioral healthy habits (sleep, physical activity, nutrition, and screen time)

Healthy habits sound simple, but establishing them is not always easy. The idea of a habit is that it makes managing something challenging or important more automatic, and thus easier and more reliable. Many of the same habits that promote physical health in adulthood also promote mental health: adequate, restful sleep; daily physical activity; a nutritious diet and a healthy relationship with food; and managing screen time in a developmentally appropriate way. Infants depend entirely on their parents for regulation of these behaviors. As their children grow, parents will adapt these routines so that their children are gradually regulating these needs and activities more independently. In each of these areas, children need clear expectations and routines, consistent consequences and positive feedback, and the modeling and patient support of their parents. Educate parents about what good sleep hygiene looks like at each age. Discuss ways to support regular physical activity, especially as a family. Ask the parents about nutrition, including how they manage picky eating; how many family meals they enjoy together; and whether food is ever used to manage boredom or distress. Finally, talk with parents about a developmentally appropriate approach to rules and expectations around screen time and the importance of using family-based rules. Establishing expectations and routines during early childhood means children learn how good it feels to have restful sleep, regular exercise, and happy, healthy family meals. In adolescence, parents can then focus on helping their children to manage temptation, challenge, disappointment, and frustration more independently.

Infancy and up: Relational health

Children develop the skills needed for healthy relationships at home, and they are connected to all of the skills described above. Children need attuned, responsive, and reliable parenting to build a capacity for trust of others, to learn how to communicate honestly and effectively, to learn to expect and offer compassion and respect, and to learn how to handle disagreement and conflict. They learn these skills by watching their parents and by developing the emotional, cognitive, and behavioral healthy habits with their parents’ help. They need a consistently safe and responsive environment at home. They need parents who are attuned and flexible, while maintaining routines and high expectations. They need parents who make time for them when they are sad or struggling, and make time for joy, play, and mindless fun. While a detailed assessment of how the family is functioning may go beyond a check-up, you can ask about those routines that build healthy habits (family mealtime, sleep routines, screen time rules), communication style, and what the family enjoys doing together. Learning about how a family is building these healthy habits and how connected they are to one another can give you a clear snapshot of how well a child may be doing on their mental health growth curve, and what areas might benefit from more active guidance and support.

Dr. Swick is physician in chief at Ohana Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

SEATTLE – Use of a new kind of assay – sequential beta-hydroxybutyrate testing – with a cut-off for ruling out insulinoma in patients with hypoglycemia may allow for a shortening of the standard 72-hour fasting time, therefore yielding significant hospital cost savings, new data suggest.

Insulinomas are small, rare types of pancreatic tumors that are benign but secrete excess insulin, leading to hypoglycemia. More than 99% of people with insulinomas develop hypoglycemia within 72 hours, hence, the use of a 72-hour fast to detect these tumors.

But most people who are evaluated for hypoglycemia do not have an insulinoma and fasting in hospital for 3 days is burdensome and costly.  

As part of a quality improvement project, Cleveland Clinic endocrinology fellow Michelle D. Lundholm, MD, and colleagues modified their hospital’s protocol to include measurement of beta-hydroxybutyrate (BHB), a marker of insulin suppression, every 12 hours with a cutoff of ≥ 2.7mmol/L for stopping the fast if hypoglycemia (venous glucose ≤ 45mg/dL) hasn’t occurred. This intervention cut in half the number of patients who needed to fast for the full 72 hours, without missing any insulinomas.

“We are excited to share how a relatively simple adjustment to our protocol allowed us to successfully reduce the burden of fasting on patients and more effectively utilize hospital resources. We hope that this encourages other centers to consider doing the same,” Dr. Lundholm said in an interview.

“These data support a 48-hour fast. The literature supports that’s sufficient to detect 95% of insulinomas. ... But, given our small insulinoma cohort, we are looking forward to learning from other studies,” she added.

Dr. Lundholm presented the late-breaking oral abstract at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.

Asked to comment, session moderator Jenna Sarvaideo, MD, said: “We’re often steeped in tradition. That’s why this abstract and this quality improvement project is so exciting to me because it challenges the history. … and I think it’s ultimately helping patients.”

Dr. Sarvaideo, of Clement J. Zablocki VA Medical Center, Milwaukee, noted that, typically, although the fast will be stopped before 72 hours if the patient develops hypoglycemia, “often they don’t, so we keep going on and on. If we just paid more attention to the beta-hydroxybutyrate, I think that would be practice changing.”

She added that more data would be optimal, given that there were under 100 patients in the study, “but I do think that devising protocols is … very much still at the hands of the endocrinologists. I think that this work could make groups reevaluate their protocol and change it, maybe even with a small dataset and then move on from there and see what they see.”

Indeed, Dr. Lundholm pointed out that some institutions, such as the Mayo Clinic, already include 6-hour BHB measurements (along with glucose and insulin) in their protocols.

“For any institution that already draws regular BHB levels like this, it would be very easy to implement a new stopping criterion without adding any additional costs,” she said in an interview.
 

All insulinomas became apparent in less than 48 hours

The first report to look at the value of testing BHB at regular intervals was published by the Mayo Clinic in 2005 after they noticed patients without insulinoma were complaining of ketosis symptoms such as foul breath and digestive problems toward the end of the fast.

However, although BHB testing is used today as part of the evaluation, it’s typically only drawn at the start of the protocol and again at the time of hypoglycemia or at the end of 72 hours because more frequent values hadn’t been thought to be useful for guiding clinical management, Dr. Lundholm explained. 

Between January 2018 and June 2020, Dr. Lundholm and colleagues followed 34 Cleveland Clinic patients who completed the usual 72-hour fast protocol. Overall, 71% were female, and 26% had undergone prior bariatric surgery procedures. Eleven (32%) developed hypoglycemia and stopped fasting. The other 23 (68%) fasted for the full 72 hours.

Dr. Lundholm and colleagues determined that the fast could have ended earlier in 35% of patients based on an elevated BHB without missing any insulinomas.

And so, in June 2020 the group revised their protocol to include the BHB ≥ 2.7mmol/L stopping criterion. Of the 30 patients evaluated from June 2020 to January 2023, 87% were female and 17% had undergone a bariatric procedure.

Here, 15 (50%) reached a BHB ≥ 2.7mmol/L and ended their fast at an average of 43.8 hours. Another seven (23%) ended the fast after developing hypoglycemia. Just eight patients (27%) fasted for the full 72 hours.

Overall, this resulted in approximately 376 fewer cumulative hours of inpatient admission than if patients had fasted for the full time.

Of the 64 patients who have completed the fasting protocol since 2018, seven (11%) who did have an insulinoma developed hypoglycemia within 48 hours and with a BHB < 2.7 mmol/L (median, 0.15).
 

Advantages: cost, adherence

A day in a general medicine bed at Cleveland Clinic was quoted as costing $2,420, based on publicly available information as of Jan. 1, 2023. “If half of patients leave 1 day earlier, this equates to about $1,210 per patient in savings from bed costs alone,” Dr. Lundholm told this news organization.  

The revised protocol required an additional two to four blood draws, depending on the length of the fast. “The cost of these extra blood tests varies by lab and by count, but even at its highest does not exceed the amount of savings from bed costs,” she noted.

Patient adherence is another potential benefit of the revised protocol.

“Any study that requires 72 hours of patient cooperation is a challenge, particularly in an uncomfortable position like fasting. When we looked at these adherence numbers, we found that the percentage of patients who prematurely ended their fast decreased from 35% to 17% with the updated protocol,” Dr. Lundholm continued.

“This translates to fewer inconclusive results and fewer readmissions for repeat 72-hour fasting. While this was not our primary outcome, it was another noted benefit of our change,” she said.

Dr. Lundholm and Dr. Sarvaideo have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SEATTLE – Use of a new kind of assay – sequential beta-hydroxybutyrate testing – with a cut-off for ruling out insulinoma in patients with hypoglycemia may allow for a shortening of the standard 72-hour fasting time, therefore yielding significant hospital cost savings, new data suggest.

Insulinomas are small, rare types of pancreatic tumors that are benign but secrete excess insulin, leading to hypoglycemia. More than 99% of people with insulinomas develop hypoglycemia within 72 hours, hence, the use of a 72-hour fast to detect these tumors.

But most people who are evaluated for hypoglycemia do not have an insulinoma and fasting in hospital for 3 days is burdensome and costly.  

As part of a quality improvement project, Cleveland Clinic endocrinology fellow Michelle D. Lundholm, MD, and colleagues modified their hospital’s protocol to include measurement of beta-hydroxybutyrate (BHB), a marker of insulin suppression, every 12 hours with a cutoff of ≥ 2.7mmol/L for stopping the fast if hypoglycemia (venous glucose ≤ 45mg/dL) hasn’t occurred. This intervention cut in half the number of patients who needed to fast for the full 72 hours, without missing any insulinomas.

“We are excited to share how a relatively simple adjustment to our protocol allowed us to successfully reduce the burden of fasting on patients and more effectively utilize hospital resources. We hope that this encourages other centers to consider doing the same,” Dr. Lundholm said in an interview.

“These data support a 48-hour fast. The literature supports that’s sufficient to detect 95% of insulinomas. ... But, given our small insulinoma cohort, we are looking forward to learning from other studies,” she added.

Dr. Lundholm presented the late-breaking oral abstract at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.

Asked to comment, session moderator Jenna Sarvaideo, MD, said: “We’re often steeped in tradition. That’s why this abstract and this quality improvement project is so exciting to me because it challenges the history. … and I think it’s ultimately helping patients.”

Dr. Sarvaideo, of Clement J. Zablocki VA Medical Center, Milwaukee, noted that, typically, although the fast will be stopped before 72 hours if the patient develops hypoglycemia, “often they don’t, so we keep going on and on. If we just paid more attention to the beta-hydroxybutyrate, I think that would be practice changing.”

She added that more data would be optimal, given that there were under 100 patients in the study, “but I do think that devising protocols is … very much still at the hands of the endocrinologists. I think that this work could make groups reevaluate their protocol and change it, maybe even with a small dataset and then move on from there and see what they see.”

Indeed, Dr. Lundholm pointed out that some institutions, such as the Mayo Clinic, already include 6-hour BHB measurements (along with glucose and insulin) in their protocols.

“For any institution that already draws regular BHB levels like this, it would be very easy to implement a new stopping criterion without adding any additional costs,” she said in an interview.
 

All insulinomas became apparent in less than 48 hours

The first report to look at the value of testing BHB at regular intervals was published by the Mayo Clinic in 2005 after they noticed patients without insulinoma were complaining of ketosis symptoms such as foul breath and digestive problems toward the end of the fast.

However, although BHB testing is used today as part of the evaluation, it’s typically only drawn at the start of the protocol and again at the time of hypoglycemia or at the end of 72 hours because more frequent values hadn’t been thought to be useful for guiding clinical management, Dr. Lundholm explained. 

Between January 2018 and June 2020, Dr. Lundholm and colleagues followed 34 Cleveland Clinic patients who completed the usual 72-hour fast protocol. Overall, 71% were female, and 26% had undergone prior bariatric surgery procedures. Eleven (32%) developed hypoglycemia and stopped fasting. The other 23 (68%) fasted for the full 72 hours.

Dr. Lundholm and colleagues determined that the fast could have ended earlier in 35% of patients based on an elevated BHB without missing any insulinomas.

And so, in June 2020 the group revised their protocol to include the BHB ≥ 2.7mmol/L stopping criterion. Of the 30 patients evaluated from June 2020 to January 2023, 87% were female and 17% had undergone a bariatric procedure.

Here, 15 (50%) reached a BHB ≥ 2.7mmol/L and ended their fast at an average of 43.8 hours. Another seven (23%) ended the fast after developing hypoglycemia. Just eight patients (27%) fasted for the full 72 hours.

Overall, this resulted in approximately 376 fewer cumulative hours of inpatient admission than if patients had fasted for the full time.

Of the 64 patients who have completed the fasting protocol since 2018, seven (11%) who did have an insulinoma developed hypoglycemia within 48 hours and with a BHB < 2.7 mmol/L (median, 0.15).
 

Advantages: cost, adherence

A day in a general medicine bed at Cleveland Clinic was quoted as costing $2,420, based on publicly available information as of Jan. 1, 2023. “If half of patients leave 1 day earlier, this equates to about $1,210 per patient in savings from bed costs alone,” Dr. Lundholm told this news organization.  

The revised protocol required an additional two to four blood draws, depending on the length of the fast. “The cost of these extra blood tests varies by lab and by count, but even at its highest does not exceed the amount of savings from bed costs,” she noted.

Patient adherence is another potential benefit of the revised protocol.

“Any study that requires 72 hours of patient cooperation is a challenge, particularly in an uncomfortable position like fasting. When we looked at these adherence numbers, we found that the percentage of patients who prematurely ended their fast decreased from 35% to 17% with the updated protocol,” Dr. Lundholm continued.

“This translates to fewer inconclusive results and fewer readmissions for repeat 72-hour fasting. While this was not our primary outcome, it was another noted benefit of our change,” she said.

Dr. Lundholm and Dr. Sarvaideo have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SEATTLE – Use of a new kind of assay – sequential beta-hydroxybutyrate testing – with a cut-off for ruling out insulinoma in patients with hypoglycemia may allow for a shortening of the standard 72-hour fasting time, therefore yielding significant hospital cost savings, new data suggest.

Insulinomas are small, rare types of pancreatic tumors that are benign but secrete excess insulin, leading to hypoglycemia. More than 99% of people with insulinomas develop hypoglycemia within 72 hours, hence, the use of a 72-hour fast to detect these tumors.

But most people who are evaluated for hypoglycemia do not have an insulinoma and fasting in hospital for 3 days is burdensome and costly.  

As part of a quality improvement project, Cleveland Clinic endocrinology fellow Michelle D. Lundholm, MD, and colleagues modified their hospital’s protocol to include measurement of beta-hydroxybutyrate (BHB), a marker of insulin suppression, every 12 hours with a cutoff of ≥ 2.7mmol/L for stopping the fast if hypoglycemia (venous glucose ≤ 45mg/dL) hasn’t occurred. This intervention cut in half the number of patients who needed to fast for the full 72 hours, without missing any insulinomas.

“We are excited to share how a relatively simple adjustment to our protocol allowed us to successfully reduce the burden of fasting on patients and more effectively utilize hospital resources. We hope that this encourages other centers to consider doing the same,” Dr. Lundholm said in an interview.

“These data support a 48-hour fast. The literature supports that’s sufficient to detect 95% of insulinomas. ... But, given our small insulinoma cohort, we are looking forward to learning from other studies,” she added.

Dr. Lundholm presented the late-breaking oral abstract at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.

Asked to comment, session moderator Jenna Sarvaideo, MD, said: “We’re often steeped in tradition. That’s why this abstract and this quality improvement project is so exciting to me because it challenges the history. … and I think it’s ultimately helping patients.”

Dr. Sarvaideo, of Clement J. Zablocki VA Medical Center, Milwaukee, noted that, typically, although the fast will be stopped before 72 hours if the patient develops hypoglycemia, “often they don’t, so we keep going on and on. If we just paid more attention to the beta-hydroxybutyrate, I think that would be practice changing.”

She added that more data would be optimal, given that there were under 100 patients in the study, “but I do think that devising protocols is … very much still at the hands of the endocrinologists. I think that this work could make groups reevaluate their protocol and change it, maybe even with a small dataset and then move on from there and see what they see.”

Indeed, Dr. Lundholm pointed out that some institutions, such as the Mayo Clinic, already include 6-hour BHB measurements (along with glucose and insulin) in their protocols.

“For any institution that already draws regular BHB levels like this, it would be very easy to implement a new stopping criterion without adding any additional costs,” she said in an interview.
 

All insulinomas became apparent in less than 48 hours

The first report to look at the value of testing BHB at regular intervals was published by the Mayo Clinic in 2005 after they noticed patients without insulinoma were complaining of ketosis symptoms such as foul breath and digestive problems toward the end of the fast.

However, although BHB testing is used today as part of the evaluation, it’s typically only drawn at the start of the protocol and again at the time of hypoglycemia or at the end of 72 hours because more frequent values hadn’t been thought to be useful for guiding clinical management, Dr. Lundholm explained. 

Between January 2018 and June 2020, Dr. Lundholm and colleagues followed 34 Cleveland Clinic patients who completed the usual 72-hour fast protocol. Overall, 71% were female, and 26% had undergone prior bariatric surgery procedures. Eleven (32%) developed hypoglycemia and stopped fasting. The other 23 (68%) fasted for the full 72 hours.

Dr. Lundholm and colleagues determined that the fast could have ended earlier in 35% of patients based on an elevated BHB without missing any insulinomas.

And so, in June 2020 the group revised their protocol to include the BHB ≥ 2.7mmol/L stopping criterion. Of the 30 patients evaluated from June 2020 to January 2023, 87% were female and 17% had undergone a bariatric procedure.

Here, 15 (50%) reached a BHB ≥ 2.7mmol/L and ended their fast at an average of 43.8 hours. Another seven (23%) ended the fast after developing hypoglycemia. Just eight patients (27%) fasted for the full 72 hours.

Overall, this resulted in approximately 376 fewer cumulative hours of inpatient admission than if patients had fasted for the full time.

Of the 64 patients who have completed the fasting protocol since 2018, seven (11%) who did have an insulinoma developed hypoglycemia within 48 hours and with a BHB < 2.7 mmol/L (median, 0.15).
 

Advantages: cost, adherence

A day in a general medicine bed at Cleveland Clinic was quoted as costing $2,420, based on publicly available information as of Jan. 1, 2023. “If half of patients leave 1 day earlier, this equates to about $1,210 per patient in savings from bed costs alone,” Dr. Lundholm told this news organization.  

The revised protocol required an additional two to four blood draws, depending on the length of the fast. “The cost of these extra blood tests varies by lab and by count, but even at its highest does not exceed the amount of savings from bed costs,” she noted.

Patient adherence is another potential benefit of the revised protocol.

“Any study that requires 72 hours of patient cooperation is a challenge, particularly in an uncomfortable position like fasting. When we looked at these adherence numbers, we found that the percentage of patients who prematurely ended their fast decreased from 35% to 17% with the updated protocol,” Dr. Lundholm continued.

“This translates to fewer inconclusive results and fewer readmissions for repeat 72-hour fasting. While this was not our primary outcome, it was another noted benefit of our change,” she said.

Dr. Lundholm and Dr. Sarvaideo have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

To the Editor:

Pemphigoid gestationis (PG), or gestational pemphigoid, is a rare autoimmune bullous disease (AIBD) occurring in 1 in 50,000 pregnancies. It is characterized by abrupt development of intensely pruritic papules and urticarial plaques, followed by an eruption of blisters.¹ We present a case of new-onset PG that erupted 10 days following SARs-CoV-2 messenger RNA (mRNA) vaccination with BNT162b2 (Pfizer-BioNTech).

A 36-year-old pregnant woman (gravida 1, para 0, aborta 0) at 37 weeks’ gestation presented to our AIBD clinic with a pruritic dermatitis of 6 weeks’ duration that developed 10 days after receiving the second dose of BNT162b2. Multiple intensely pruritic, red bumps presented first on the forearms and within days spread to the thighs, hands, and abdomen, followed by progression to the ankles, feet, and back 2 weeks later. An initial biopsy was consistent with subacute spongiotic dermatitis with rare eosinophils. She found minimal relief from diphenhydramine or topical steroids. She denied oral, nasal, ocular, or genital involvement or history of any other skin disease. The pregnancy had been otherwise uneventful.

Physical examination revealed annular edematous plaques on the trunk and buttocks; excoriated and erythematous papules on the neck, trunk, arms, and legs; and scattered vesicles along the fingers, arms, hands, abdomen, back, legs, and feet (Figure 1). The Bullous Pemphigoid Disease Area Index (BPDAI) total skin activity score was 25.3, corresponding to moderate disease activity (validated at 20–56).² The BPDAI total pruritus component score was 20. A repeat biopsy for direct immunofluorescence showed faint linear deposits of IgG and bright linear deposits of C3 along the basement membrane zone. Indirect immunofluorescence showed linear deposits of IgG localized to the blister roof of salt-split skin at a dilution of 1:40. An enzyme-linked immunosorbent assay for anti-BP180 was 62 U/mL (negative, <9 U/mL; positive, ≥9 U/mL), and anti-BP230 autoantibodies were less than 9 U/mL (negative <9 U/mL; positive, ≥9 U/mL). Given these clinical and histopathologic findings, PG was diagnosed. 

The patient was started on prednisone 20 mg and antihistamines while continuing topical steroids. Pruritus and blistering improved close to delivery. Fetal monitoring with regular biophysical profiles remained normal. The patient delivered a healthy neonate without skin lesions at 40 weeks’ gestation. The disease flared 2 days after delivery, and prednisone was increased to 40 mg and slowly tapered. Two months after delivery, the patient remained on prednisone 10 mg daily with ongoing but reduced blistering and pruritus (Figure 2). The BPDAI total skin activity and pruritus component scores remained elevated at 20.3 and 14, respectively, and anti-BP180 was 44 U/mL. After a discussion with the patient on safe systemic therapy while breastfeeding, intravenous immunoglobulin (IVIG) was initiated. The patient received 3 monthly infusions at 2 g/kg and was able to taper the prednisone to 5 mg every other day without new lesions. Four months after completion of IVIG therapy, she achieved complete remission off all therapy.

Management of PG begins with topical corticosteroids, but most patients require systemic steroid therapy.¹ Remission commonly occurs close to delivery, and 75% of patients flare post partum, though the disease typically resolves 6 months following delivery.^1,3,4 For persistent intrapartum cases requiring more than prednisone 20 mg daily, therapy can include dapsone, IVIG, azathioprine, rituximab, or plasmapheresis.^4,5 Dapsone and IVIG are compatible with breastfeeding postpartum, but if dapsone is selected, the infant must be monitored for hemolytic anemia.⁵ Pemphigoid gestationis increases the risk for a premature or small-for-gestational-age neonate, necessitating regular fetal monitoring until delivery.¹ Cutaneous lesions may affect the newborn, though this occurrence is rare and self-limiting.⁶Pemphigoid gestationis may recur in subsequent pregnancies at a rate of 33% to 55%, with earlier and more severe presentations.⁴

Clinically and histologically, PG closely resembles bullous pemphigoid (BP), but the exact pathogenesis is not fully understood. Recently, another case of what was termed pseudo-PG has been described 3 days following administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.⁷ Since the introduction of COVID-19 mRNA vaccines, cases of postvaccination BP, BP-like eruptions, and pemphigus vulgaris have been described.^8-11 Tomayko et al¹⁰ reported 12 cases of subepidermal eruptions, including BP, in which 7 patients developed blisters after the second dose of either the Pfizer-BioNTech or Moderna mRNA vaccine. Three patients who developed BP after the first dose of the vaccine and chose to receive the second dose tolerated it well, with a mild flare observed in 1 patient.¹⁰ Similarly, subsequent vaccine doses in reports of vaccine-associated AIBD resulted in increased disease activity in 21% of cases.¹² COVID-19 vaccine–associated BP, similar to drug-induced BP, seemingly displays a milder course of disease compared to the classic form of BP.^10,13 More follow-up is needed to better understand these reactions and inform appropriate discussions on the administration of booster doses. Currently, completion of the vaccination series against COVID-19 is advisable given the paucity of reports of postvaccination AIBD and the risk for COVID-19 infection, but careful discussions on a case-by-case basis are warranted related to the risk for disease exacerbation following subsequent vaccinations.

The clinical presentation and diagnostic evaluation of our patient’s rash were consistent with PG. The temporal relationship between vaccine administration and PG lesion onset suggests the mRNA vaccine triggered AIBD in our patient. Interestingly, AIBD associated with COVID-19 is not unique to only the vaccines and has been observed following infection with the virus itself.¹⁴ The high rate of vaccination against COVID-19 in contrast with the low number of reported cases of AIBD after vaccination supports the overall safety of COVID-19 vaccines but identifies a need for further understanding of the processes that lead to the development of autoimmune conditions in at-risk populations.

To the Editor:

Pemphigoid gestationis (PG), or gestational pemphigoid, is a rare autoimmune bullous disease (AIBD) occurring in 1 in 50,000 pregnancies. It is characterized by abrupt development of intensely pruritic papules and urticarial plaques, followed by an eruption of blisters.¹ We present a case of new-onset PG that erupted 10 days following SARs-CoV-2 messenger RNA (mRNA) vaccination with BNT162b2 (Pfizer-BioNTech).

A 36-year-old pregnant woman (gravida 1, para 0, aborta 0) at 37 weeks’ gestation presented to our AIBD clinic with a pruritic dermatitis of 6 weeks’ duration that developed 10 days after receiving the second dose of BNT162b2. Multiple intensely pruritic, red bumps presented first on the forearms and within days spread to the thighs, hands, and abdomen, followed by progression to the ankles, feet, and back 2 weeks later. An initial biopsy was consistent with subacute spongiotic dermatitis with rare eosinophils. She found minimal relief from diphenhydramine or topical steroids. She denied oral, nasal, ocular, or genital involvement or history of any other skin disease. The pregnancy had been otherwise uneventful.

Physical examination revealed annular edematous plaques on the trunk and buttocks; excoriated and erythematous papules on the neck, trunk, arms, and legs; and scattered vesicles along the fingers, arms, hands, abdomen, back, legs, and feet (Figure 1). The Bullous Pemphigoid Disease Area Index (BPDAI) total skin activity score was 25.3, corresponding to moderate disease activity (validated at 20–56).² The BPDAI total pruritus component score was 20. A repeat biopsy for direct immunofluorescence showed faint linear deposits of IgG and bright linear deposits of C3 along the basement membrane zone. Indirect immunofluorescence showed linear deposits of IgG localized to the blister roof of salt-split skin at a dilution of 1:40. An enzyme-linked immunosorbent assay for anti-BP180 was 62 U/mL (negative, <9 U/mL; positive, ≥9 U/mL), and anti-BP230 autoantibodies were less than 9 U/mL (negative <9 U/mL; positive, ≥9 U/mL). Given these clinical and histopathologic findings, PG was diagnosed. 

The patient was started on prednisone 20 mg and antihistamines while continuing topical steroids. Pruritus and blistering improved close to delivery. Fetal monitoring with regular biophysical profiles remained normal. The patient delivered a healthy neonate without skin lesions at 40 weeks’ gestation. The disease flared 2 days after delivery, and prednisone was increased to 40 mg and slowly tapered. Two months after delivery, the patient remained on prednisone 10 mg daily with ongoing but reduced blistering and pruritus (Figure 2). The BPDAI total skin activity and pruritus component scores remained elevated at 20.3 and 14, respectively, and anti-BP180 was 44 U/mL. After a discussion with the patient on safe systemic therapy while breastfeeding, intravenous immunoglobulin (IVIG) was initiated. The patient received 3 monthly infusions at 2 g/kg and was able to taper the prednisone to 5 mg every other day without new lesions. Four months after completion of IVIG therapy, she achieved complete remission off all therapy.

Management of PG begins with topical corticosteroids, but most patients require systemic steroid therapy.¹ Remission commonly occurs close to delivery, and 75% of patients flare post partum, though the disease typically resolves 6 months following delivery.^1,3,4 For persistent intrapartum cases requiring more than prednisone 20 mg daily, therapy can include dapsone, IVIG, azathioprine, rituximab, or plasmapheresis.^4,5 Dapsone and IVIG are compatible with breastfeeding postpartum, but if dapsone is selected, the infant must be monitored for hemolytic anemia.⁵ Pemphigoid gestationis increases the risk for a premature or small-for-gestational-age neonate, necessitating regular fetal monitoring until delivery.¹ Cutaneous lesions may affect the newborn, though this occurrence is rare and self-limiting.⁶Pemphigoid gestationis may recur in subsequent pregnancies at a rate of 33% to 55%, with earlier and more severe presentations.⁴

Clinically and histologically, PG closely resembles bullous pemphigoid (BP), but the exact pathogenesis is not fully understood. Recently, another case of what was termed pseudo-PG has been described 3 days following administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.⁷ Since the introduction of COVID-19 mRNA vaccines, cases of postvaccination BP, BP-like eruptions, and pemphigus vulgaris have been described.^8-11 Tomayko et al¹⁰ reported 12 cases of subepidermal eruptions, including BP, in which 7 patients developed blisters after the second dose of either the Pfizer-BioNTech or Moderna mRNA vaccine. Three patients who developed BP after the first dose of the vaccine and chose to receive the second dose tolerated it well, with a mild flare observed in 1 patient.¹⁰ Similarly, subsequent vaccine doses in reports of vaccine-associated AIBD resulted in increased disease activity in 21% of cases.¹² COVID-19 vaccine–associated BP, similar to drug-induced BP, seemingly displays a milder course of disease compared to the classic form of BP.^10,13 More follow-up is needed to better understand these reactions and inform appropriate discussions on the administration of booster doses. Currently, completion of the vaccination series against COVID-19 is advisable given the paucity of reports of postvaccination AIBD and the risk for COVID-19 infection, but careful discussions on a case-by-case basis are warranted related to the risk for disease exacerbation following subsequent vaccinations.

The clinical presentation and diagnostic evaluation of our patient’s rash were consistent with PG. The temporal relationship between vaccine administration and PG lesion onset suggests the mRNA vaccine triggered AIBD in our patient. Interestingly, AIBD associated with COVID-19 is not unique to only the vaccines and has been observed following infection with the virus itself.¹⁴ The high rate of vaccination against COVID-19 in contrast with the low number of reported cases of AIBD after vaccination supports the overall safety of COVID-19 vaccines but identifies a need for further understanding of the processes that lead to the development of autoimmune conditions in at-risk populations.

To the Editor:

Pemphigoid gestationis (PG), or gestational pemphigoid, is a rare autoimmune bullous disease (AIBD) occurring in 1 in 50,000 pregnancies. It is characterized by abrupt development of intensely pruritic papules and urticarial plaques, followed by an eruption of blisters.¹ We present a case of new-onset PG that erupted 10 days following SARs-CoV-2 messenger RNA (mRNA) vaccination with BNT162b2 (Pfizer-BioNTech).

A 36-year-old pregnant woman (gravida 1, para 0, aborta 0) at 37 weeks’ gestation presented to our AIBD clinic with a pruritic dermatitis of 6 weeks’ duration that developed 10 days after receiving the second dose of BNT162b2. Multiple intensely pruritic, red bumps presented first on the forearms and within days spread to the thighs, hands, and abdomen, followed by progression to the ankles, feet, and back 2 weeks later. An initial biopsy was consistent with subacute spongiotic dermatitis with rare eosinophils. She found minimal relief from diphenhydramine or topical steroids. She denied oral, nasal, ocular, or genital involvement or history of any other skin disease. The pregnancy had been otherwise uneventful.

Physical examination revealed annular edematous plaques on the trunk and buttocks; excoriated and erythematous papules on the neck, trunk, arms, and legs; and scattered vesicles along the fingers, arms, hands, abdomen, back, legs, and feet (Figure 1). The Bullous Pemphigoid Disease Area Index (BPDAI) total skin activity score was 25.3, corresponding to moderate disease activity (validated at 20–56).² The BPDAI total pruritus component score was 20. A repeat biopsy for direct immunofluorescence showed faint linear deposits of IgG and bright linear deposits of C3 along the basement membrane zone. Indirect immunofluorescence showed linear deposits of IgG localized to the blister roof of salt-split skin at a dilution of 1:40. An enzyme-linked immunosorbent assay for anti-BP180 was 62 U/mL (negative, <9 U/mL; positive, ≥9 U/mL), and anti-BP230 autoantibodies were less than 9 U/mL (negative <9 U/mL; positive, ≥9 U/mL). Given these clinical and histopathologic findings, PG was diagnosed. 

The patient was started on prednisone 20 mg and antihistamines while continuing topical steroids. Pruritus and blistering improved close to delivery. Fetal monitoring with regular biophysical profiles remained normal. The patient delivered a healthy neonate without skin lesions at 40 weeks’ gestation. The disease flared 2 days after delivery, and prednisone was increased to 40 mg and slowly tapered. Two months after delivery, the patient remained on prednisone 10 mg daily with ongoing but reduced blistering and pruritus (Figure 2). The BPDAI total skin activity and pruritus component scores remained elevated at 20.3 and 14, respectively, and anti-BP180 was 44 U/mL. After a discussion with the patient on safe systemic therapy while breastfeeding, intravenous immunoglobulin (IVIG) was initiated. The patient received 3 monthly infusions at 2 g/kg and was able to taper the prednisone to 5 mg every other day without new lesions. Four months after completion of IVIG therapy, she achieved complete remission off all therapy.

Management of PG begins with topical corticosteroids, but most patients require systemic steroid therapy.¹ Remission commonly occurs close to delivery, and 75% of patients flare post partum, though the disease typically resolves 6 months following delivery.^1,3,4 For persistent intrapartum cases requiring more than prednisone 20 mg daily, therapy can include dapsone, IVIG, azathioprine, rituximab, or plasmapheresis.^4,5 Dapsone and IVIG are compatible with breastfeeding postpartum, but if dapsone is selected, the infant must be monitored for hemolytic anemia.⁵ Pemphigoid gestationis increases the risk for a premature or small-for-gestational-age neonate, necessitating regular fetal monitoring until delivery.¹ Cutaneous lesions may affect the newborn, though this occurrence is rare and self-limiting.⁶Pemphigoid gestationis may recur in subsequent pregnancies at a rate of 33% to 55%, with earlier and more severe presentations.⁴

Clinically and histologically, PG closely resembles bullous pemphigoid (BP), but the exact pathogenesis is not fully understood. Recently, another case of what was termed pseudo-PG has been described 3 days following administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.⁷ Since the introduction of COVID-19 mRNA vaccines, cases of postvaccination BP, BP-like eruptions, and pemphigus vulgaris have been described.^8-11 Tomayko et al¹⁰ reported 12 cases of subepidermal eruptions, including BP, in which 7 patients developed blisters after the second dose of either the Pfizer-BioNTech or Moderna mRNA vaccine. Three patients who developed BP after the first dose of the vaccine and chose to receive the second dose tolerated it well, with a mild flare observed in 1 patient.¹⁰ Similarly, subsequent vaccine doses in reports of vaccine-associated AIBD resulted in increased disease activity in 21% of cases.¹² COVID-19 vaccine–associated BP, similar to drug-induced BP, seemingly displays a milder course of disease compared to the classic form of BP.^10,13 More follow-up is needed to better understand these reactions and inform appropriate discussions on the administration of booster doses. Currently, completion of the vaccination series against COVID-19 is advisable given the paucity of reports of postvaccination AIBD and the risk for COVID-19 infection, but careful discussions on a case-by-case basis are warranted related to the risk for disease exacerbation following subsequent vaccinations.

The clinical presentation and diagnostic evaluation of our patient’s rash were consistent with PG. The temporal relationship between vaccine administration and PG lesion onset suggests the mRNA vaccine triggered AIBD in our patient. Interestingly, AIBD associated with COVID-19 is not unique to only the vaccines and has been observed following infection with the virus itself.¹⁴ The high rate of vaccination against COVID-19 in contrast with the low number of reported cases of AIBD after vaccination supports the overall safety of COVID-19 vaccines but identifies a need for further understanding of the processes that lead to the development of autoimmune conditions in at-risk populations.

The Diagnosis: Prurigo Pigmentosa 

Histopathology of the punch biopsy revealed subcorneal collections of neutrophils flanked by a spongiotic epidermis with neutrophil and eosinophil exocytosis. Rare dyskeratotic keratinocytes were identified at the dermoepidermal junction, and grampositive bacterial organisms were seen in a follicular infundibulum with purulent inflammation. The dermis demonstrated a mildly dense superficial perivascular and interstitial infiltrate composed of lymphocytes, histiocytes, scattered neutrophils, and eosinophils (Figure).

Given the combination of clinical and histologic findings, a diagnosis of prurigo pigmentosa (PP) was rendered and a urinalysis was ordered, which confirmed ketonuria. The patient was started on minocycline 100 mg twice daily and was advised to reintroduce carbohydrates into her diet. Resolution of the inflammatory component of the rash was achieved at 3-week follow-up, with residual reticulated postinflammatory hyperpigmentation.

Prurigo pigmentosa is a rare, albeit globally underrecognized, inflammatory dermatosis characterized by pruritic, symmetric, erythematous papules and plaques on the chest, back, neck, and rarely the arms and forehead that subsequently involute, leaving reticular postinflammatory hyperpigmentation.1 Prurigo pigmentosa is predominant in females (2.6:1 ratio). The mean age at presentation is 24.4 years, and it most commonly has been documented among populations in Asian countries, though it is unclear if a genetic predilection exists, as reports of PP are increasing globally with improved clinical awareness.^1,2

The etiology of PP remains unknown; however, associations are well documented between PP and a ketogenic state secondary to uncontrolled diabetes, a low-carbohydrate diet, anorexia nervosa, or bariatric surgery.³ It is theorized that high serum ketones lead to perivascular ketone deposition, which induces neutrophil migration and chemotaxis,⁴ as substantiated by evidence of rash resolution with correction of the ketogenic state and improvement after administration of tetracyclines, a drug class known for neutrophil chemotaxis inhibition.⁵ Improvement of PP via these treatment mechanisms suggests that ketone bodies may play a role in the pathogenesis of PP.

Interestingly, Kafle et al⁶ reported that patients with PP commonly have bacterial colonies and associated inflammatory sequelae at the level of the hair follicles, which suggests that follicular involvement plays a role in the pathogenesis of PP. These findings are consistent with our patient’s histopathology consisting of gram-positive organisms and purulent inflammation at the infundibulum. The histopathologic features of PP are stage specific.¹ Early stages are characterized by a superficial perivascular infiltrate of neutrophils that then spread to dermal papillae. Neutrophils then quickly sweep through the epidermis, causing spongiosis, ballooning, necrotic keratocytes, and consequent surface epithelium abscess formation. Over time, the dermal infiltrate assumes a lichenoid pattern as eosinophils and lymphocytes invade and predominate over neutrophils. Eventually, melanophages appear in the dermis as the epidermis undergoes hyperplasia, parakeratosis, and hyperpigmentation.¹ The histologic differential diagnosis for PP is broad and varies based on the stage-specific progression of clinical and histopathologic findings.

Similar to PP, subacute cutaneous lupus erythematosus has a female predominance and resolves with subsequent dyspigmentation; however, it initially is characterized by annular plaques with central clearing or papulosquamous lesions restricted to sun-exposed skin. Photosensitivity is a prominent feature, and roughly 50% of patients meet diagnostic criteria for systemic lupus erythematosus.⁷ Histopathology shows interface changes with increased dermal mucin and a perivascular lymphoplasmacytic inflammatory infiltrate.

Papular pityriasis rosea can present as a pruritic papular rash on the back and chest; however, it most commonly is associated with a herald patch and typically follows a flulike prodrome.⁸ Biopsy reveals mounds of parakeratosis with mild spongiosis, perivascular inflammation, and extravasated erythrocytes.

Galli-Galli disease can present as a pruritic rash with follicular papules under the breasts and other flexural areas but histopathologically shows elongated rete ridges with dermal melanosis and acantholysis.⁹

Hailey-Hailey disease commonly presents in the third decade of life and can manifest as painful, pruritic, vesicular lesions on erythematous skin distributed on the back, neck, and inframammary region, as seen in our case; however, it is histopathologically associated with widespread epidermal acantholysis unlike the findings seen in our patient.¹⁰

First-line treatment of PP includes antibiotics such as minocycline, doxycycline, and dapsone due to their anti-inflammatory properties and ability to inhibit neutrophil chemotaxis. In patients with nutritional deficiencies or ketosis, reintroduction of carbohydrates alone has been effective.^5,11

Prurigo pigmentosa is an underrecognized inflammatory dermatosis with a complex stage-dependent clinicopathologic presentation. Clinicians should be aware of the etiologic and histopathologic patterns of this unique dermatosis. Rash presentation in the context of a low-carbohydrate diet should prompt biopsy as well as treatment with antibiotics and dietary reintroduction of carbohydrates.

The Diagnosis: Prurigo Pigmentosa 

Histopathology of the punch biopsy revealed subcorneal collections of neutrophils flanked by a spongiotic epidermis with neutrophil and eosinophil exocytosis. Rare dyskeratotic keratinocytes were identified at the dermoepidermal junction, and grampositive bacterial organisms were seen in a follicular infundibulum with purulent inflammation. The dermis demonstrated a mildly dense superficial perivascular and interstitial infiltrate composed of lymphocytes, histiocytes, scattered neutrophils, and eosinophils (Figure).

Given the combination of clinical and histologic findings, a diagnosis of prurigo pigmentosa (PP) was rendered and a urinalysis was ordered, which confirmed ketonuria. The patient was started on minocycline 100 mg twice daily and was advised to reintroduce carbohydrates into her diet. Resolution of the inflammatory component of the rash was achieved at 3-week follow-up, with residual reticulated postinflammatory hyperpigmentation.

Prurigo pigmentosa is a rare, albeit globally underrecognized, inflammatory dermatosis characterized by pruritic, symmetric, erythematous papules and plaques on the chest, back, neck, and rarely the arms and forehead that subsequently involute, leaving reticular postinflammatory hyperpigmentation.1 Prurigo pigmentosa is predominant in females (2.6:1 ratio). The mean age at presentation is 24.4 years, and it most commonly has been documented among populations in Asian countries, though it is unclear if a genetic predilection exists, as reports of PP are increasing globally with improved clinical awareness.^1,2

The etiology of PP remains unknown; however, associations are well documented between PP and a ketogenic state secondary to uncontrolled diabetes, a low-carbohydrate diet, anorexia nervosa, or bariatric surgery.³ It is theorized that high serum ketones lead to perivascular ketone deposition, which induces neutrophil migration and chemotaxis,⁴ as substantiated by evidence of rash resolution with correction of the ketogenic state and improvement after administration of tetracyclines, a drug class known for neutrophil chemotaxis inhibition.⁵ Improvement of PP via these treatment mechanisms suggests that ketone bodies may play a role in the pathogenesis of PP.

Interestingly, Kafle et al⁶ reported that patients with PP commonly have bacterial colonies and associated inflammatory sequelae at the level of the hair follicles, which suggests that follicular involvement plays a role in the pathogenesis of PP. These findings are consistent with our patient’s histopathology consisting of gram-positive organisms and purulent inflammation at the infundibulum. The histopathologic features of PP are stage specific.¹ Early stages are characterized by a superficial perivascular infiltrate of neutrophils that then spread to dermal papillae. Neutrophils then quickly sweep through the epidermis, causing spongiosis, ballooning, necrotic keratocytes, and consequent surface epithelium abscess formation. Over time, the dermal infiltrate assumes a lichenoid pattern as eosinophils and lymphocytes invade and predominate over neutrophils. Eventually, melanophages appear in the dermis as the epidermis undergoes hyperplasia, parakeratosis, and hyperpigmentation.¹ The histologic differential diagnosis for PP is broad and varies based on the stage-specific progression of clinical and histopathologic findings.

Similar to PP, subacute cutaneous lupus erythematosus has a female predominance and resolves with subsequent dyspigmentation; however, it initially is characterized by annular plaques with central clearing or papulosquamous lesions restricted to sun-exposed skin. Photosensitivity is a prominent feature, and roughly 50% of patients meet diagnostic criteria for systemic lupus erythematosus.⁷ Histopathology shows interface changes with increased dermal mucin and a perivascular lymphoplasmacytic inflammatory infiltrate.

Papular pityriasis rosea can present as a pruritic papular rash on the back and chest; however, it most commonly is associated with a herald patch and typically follows a flulike prodrome.⁸ Biopsy reveals mounds of parakeratosis with mild spongiosis, perivascular inflammation, and extravasated erythrocytes.

Galli-Galli disease can present as a pruritic rash with follicular papules under the breasts and other flexural areas but histopathologically shows elongated rete ridges with dermal melanosis and acantholysis.⁹

Hailey-Hailey disease commonly presents in the third decade of life and can manifest as painful, pruritic, vesicular lesions on erythematous skin distributed on the back, neck, and inframammary region, as seen in our case; however, it is histopathologically associated with widespread epidermal acantholysis unlike the findings seen in our patient.¹⁰

First-line treatment of PP includes antibiotics such as minocycline, doxycycline, and dapsone due to their anti-inflammatory properties and ability to inhibit neutrophil chemotaxis. In patients with nutritional deficiencies or ketosis, reintroduction of carbohydrates alone has been effective.^5,11

Prurigo pigmentosa is an underrecognized inflammatory dermatosis with a complex stage-dependent clinicopathologic presentation. Clinicians should be aware of the etiologic and histopathologic patterns of this unique dermatosis. Rash presentation in the context of a low-carbohydrate diet should prompt biopsy as well as treatment with antibiotics and dietary reintroduction of carbohydrates.

The Diagnosis: Prurigo Pigmentosa 

Histopathology of the punch biopsy revealed subcorneal collections of neutrophils flanked by a spongiotic epidermis with neutrophil and eosinophil exocytosis. Rare dyskeratotic keratinocytes were identified at the dermoepidermal junction, and grampositive bacterial organisms were seen in a follicular infundibulum with purulent inflammation. The dermis demonstrated a mildly dense superficial perivascular and interstitial infiltrate composed of lymphocytes, histiocytes, scattered neutrophils, and eosinophils (Figure).

Given the combination of clinical and histologic findings, a diagnosis of prurigo pigmentosa (PP) was rendered and a urinalysis was ordered, which confirmed ketonuria. The patient was started on minocycline 100 mg twice daily and was advised to reintroduce carbohydrates into her diet. Resolution of the inflammatory component of the rash was achieved at 3-week follow-up, with residual reticulated postinflammatory hyperpigmentation.

Prurigo pigmentosa is a rare, albeit globally underrecognized, inflammatory dermatosis characterized by pruritic, symmetric, erythematous papules and plaques on the chest, back, neck, and rarely the arms and forehead that subsequently involute, leaving reticular postinflammatory hyperpigmentation.1 Prurigo pigmentosa is predominant in females (2.6:1 ratio). The mean age at presentation is 24.4 years, and it most commonly has been documented among populations in Asian countries, though it is unclear if a genetic predilection exists, as reports of PP are increasing globally with improved clinical awareness.^1,2

The etiology of PP remains unknown; however, associations are well documented between PP and a ketogenic state secondary to uncontrolled diabetes, a low-carbohydrate diet, anorexia nervosa, or bariatric surgery.³ It is theorized that high serum ketones lead to perivascular ketone deposition, which induces neutrophil migration and chemotaxis,⁴ as substantiated by evidence of rash resolution with correction of the ketogenic state and improvement after administration of tetracyclines, a drug class known for neutrophil chemotaxis inhibition.⁵ Improvement of PP via these treatment mechanisms suggests that ketone bodies may play a role in the pathogenesis of PP.

Interestingly, Kafle et al⁶ reported that patients with PP commonly have bacterial colonies and associated inflammatory sequelae at the level of the hair follicles, which suggests that follicular involvement plays a role in the pathogenesis of PP. These findings are consistent with our patient’s histopathology consisting of gram-positive organisms and purulent inflammation at the infundibulum. The histopathologic features of PP are stage specific.¹ Early stages are characterized by a superficial perivascular infiltrate of neutrophils that then spread to dermal papillae. Neutrophils then quickly sweep through the epidermis, causing spongiosis, ballooning, necrotic keratocytes, and consequent surface epithelium abscess formation. Over time, the dermal infiltrate assumes a lichenoid pattern as eosinophils and lymphocytes invade and predominate over neutrophils. Eventually, melanophages appear in the dermis as the epidermis undergoes hyperplasia, parakeratosis, and hyperpigmentation.¹ The histologic differential diagnosis for PP is broad and varies based on the stage-specific progression of clinical and histopathologic findings.

Similar to PP, subacute cutaneous lupus erythematosus has a female predominance and resolves with subsequent dyspigmentation; however, it initially is characterized by annular plaques with central clearing or papulosquamous lesions restricted to sun-exposed skin. Photosensitivity is a prominent feature, and roughly 50% of patients meet diagnostic criteria for systemic lupus erythematosus.⁷ Histopathology shows interface changes with increased dermal mucin and a perivascular lymphoplasmacytic inflammatory infiltrate.

Papular pityriasis rosea can present as a pruritic papular rash on the back and chest; however, it most commonly is associated with a herald patch and typically follows a flulike prodrome.⁸ Biopsy reveals mounds of parakeratosis with mild spongiosis, perivascular inflammation, and extravasated erythrocytes.

Galli-Galli disease can present as a pruritic rash with follicular papules under the breasts and other flexural areas but histopathologically shows elongated rete ridges with dermal melanosis and acantholysis.⁹

Hailey-Hailey disease commonly presents in the third decade of life and can manifest as painful, pruritic, vesicular lesions on erythematous skin distributed on the back, neck, and inframammary region, as seen in our case; however, it is histopathologically associated with widespread epidermal acantholysis unlike the findings seen in our patient.¹⁰

First-line treatment of PP includes antibiotics such as minocycline, doxycycline, and dapsone due to their anti-inflammatory properties and ability to inhibit neutrophil chemotaxis. In patients with nutritional deficiencies or ketosis, reintroduction of carbohydrates alone has been effective.^5,11

Prurigo pigmentosa is an underrecognized inflammatory dermatosis with a complex stage-dependent clinicopathologic presentation. Clinicians should be aware of the etiologic and histopathologic patterns of this unique dermatosis. Rash presentation in the context of a low-carbohydrate diet should prompt biopsy as well as treatment with antibiotics and dietary reintroduction of carbohydrates.

MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.

The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.

“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
 

Urgent need to improve childhood lupus outcomes

“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.

“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.

Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.

“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.

The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.

Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.

T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
 

The cSLE T2T international task force and cLLDAS definition

With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.

“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”

Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.

Next, they looked to develop an age-appropriate definition for low disease activity.

“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.

The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”

The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.

“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.

The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.

The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.

The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.

“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
 

Urgent need to improve childhood lupus outcomes

“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.

“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.

Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.

“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.

The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.

Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.

T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
 

The cSLE T2T international task force and cLLDAS definition

With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.

“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”

Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.

Next, they looked to develop an age-appropriate definition for low disease activity.

“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.

The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”

The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.

“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.

The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.

The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.

The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.

“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
 

Urgent need to improve childhood lupus outcomes

“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.

“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.

Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.

“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.

The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.

Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.

T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
 

The cSLE T2T international task force and cLLDAS definition

With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.

“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”

Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.

Next, they looked to develop an age-appropriate definition for low disease activity.

“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.

The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”

The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.

“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.

The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.

The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.