To the Editor:

A 57-year-old woman presented to an outpatient clinic with severe pruritus and burning of the skin as well as subjective fevers and chills. She had been discharged from a psychiatric hospital for attempted suicide 1 day prior. There were no recent changes in the medication regimen, which consisted of linaclotide, fluoxetine, lorazepam, and gabapentin. While admitted, the patient was started on the atypical antipsychotic cariprazine. Within 24 hours of the first dose, she developed severe facial erythema that progressed to diffuse erythema over more than 60% of the body surface area. The attending psychiatrist promptly discontinued cariprazine. During the next 24 hours, there were no reports of fever, leukocytosis, or signs of systemic organ involvement. Given the patient’s mental and medical stability, she was discharged with instructions to follow up with the outpatient dermatology clinic.

At the current presentation, physical examination revealed innumerable 1- to 4-mm pustules coalescing to lakes of pus on an erythematous base over more than 60% of the body surface area (Figure 1). The mucous membranes were clear of lesions, the Nikolsky sign was negative, and the patient’s temperature was 99.6 °F in the office. Complete blood cell count and complete metabolic panel results were within reference range.

A 4-mm abdominal punch biopsy showed subcorneal neutrophilic pustules, papillary dermal edema, and superficial dermal lymphohistiocytic inflammation with numerous neutrophils, eosinophils, and extravasated red blood cells, consistent with acute generalized exanthematous pustulosis (AGEP)(Figure 2). The patient was started on wet wraps with triamcinolone cream 0.1%.

Two days later, physical examination revealed the erythema noted on initial examination had notably decreased, and the patient no longer reported burning or pruritus. One week after initial presentation to the clinic, the patient’s rash had resolved, and only a few small areas of desquamation remained.

Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the development of numerous nonfollicular sterile pustules on an edematous and erythematous base. In almost 90% of reported cases, the cause is related to use of antibiotics, antifungals, antimalarials, or diltiazem (a calcium channel blocker). This rare cutaneous reaction occurs in 1 to 5 patients per million per year¹; it carries a 1% to 2% mortality rate with proper supportive treatment.

The clinical symptoms of AGEP typically present 24 to 48 hours after drug initiation with the rapid development of dozens to thousands of 1- to 4-mm pustules, typically localized to the flexor surfaces and face. In the setting of AGEP, acute onset of fever and leukocytosis typically occur at the time of the cutaneous eruption. These features were absent in this patient. The eruption usually starts on the face and then migrates to the trunk and extremities, sparing the palms and soles. Systemic involvement most commonly presents as hepatic, renal, or pulmonary insufficiency, which has been seen in 20% of cases.²

The immunologic response associated with the reaction has been studied in vitro. Drug-specific CD8 T cells use perforin/granzyme B and Fas ligand mechanisms to induce apoptosis of the keratinocytes within the epidermis, leading to vesicle formation.³ During the very first stages of formation, vesicles mainly comprise CD8 T cells and keratinocytes. These cells then begin producing CXC-18, a potent neutrophil chemokine, leading to extensive chemotaxis of neutrophils into vesicles, which then rapidly transform to pustules.³ This rapid transformation leads to the lakes of pustules, a description often associated with AGEP.

Treatment of AGEP is mainly supportive and consists of discontinuing use of the causative agent. Topical corticosteroids can be used during the pustular phase for symptom management. There is no evidence that systemic steroids reduce the duration of the disease.² Other supportive measures such as application of wet wraps can be used to provide comfort.

Cutaneous adverse drug reactions commonly are associated with psychiatric pharmacotherapy, but first-and second-generation antipsychotics rarely are associated with these types of reactions. In this patient, the causative agent of the AGEP was cariprazine, an atypical antipsychotic that had no reported association with AGEP or cutaneous adverse drug reactions prior to this presentation.

To the Editor:

A 57-year-old woman presented to an outpatient clinic with severe pruritus and burning of the skin as well as subjective fevers and chills. She had been discharged from a psychiatric hospital for attempted suicide 1 day prior. There were no recent changes in the medication regimen, which consisted of linaclotide, fluoxetine, lorazepam, and gabapentin. While admitted, the patient was started on the atypical antipsychotic cariprazine. Within 24 hours of the first dose, she developed severe facial erythema that progressed to diffuse erythema over more than 60% of the body surface area. The attending psychiatrist promptly discontinued cariprazine. During the next 24 hours, there were no reports of fever, leukocytosis, or signs of systemic organ involvement. Given the patient’s mental and medical stability, she was discharged with instructions to follow up with the outpatient dermatology clinic.

At the current presentation, physical examination revealed innumerable 1- to 4-mm pustules coalescing to lakes of pus on an erythematous base over more than 60% of the body surface area (Figure 1). The mucous membranes were clear of lesions, the Nikolsky sign was negative, and the patient’s temperature was 99.6 °F in the office. Complete blood cell count and complete metabolic panel results were within reference range.

A 4-mm abdominal punch biopsy showed subcorneal neutrophilic pustules, papillary dermal edema, and superficial dermal lymphohistiocytic inflammation with numerous neutrophils, eosinophils, and extravasated red blood cells, consistent with acute generalized exanthematous pustulosis (AGEP)(Figure 2). The patient was started on wet wraps with triamcinolone cream 0.1%.

Two days later, physical examination revealed the erythema noted on initial examination had notably decreased, and the patient no longer reported burning or pruritus. One week after initial presentation to the clinic, the patient’s rash had resolved, and only a few small areas of desquamation remained.

Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the development of numerous nonfollicular sterile pustules on an edematous and erythematous base. In almost 90% of reported cases, the cause is related to use of antibiotics, antifungals, antimalarials, or diltiazem (a calcium channel blocker). This rare cutaneous reaction occurs in 1 to 5 patients per million per year¹; it carries a 1% to 2% mortality rate with proper supportive treatment.

The clinical symptoms of AGEP typically present 24 to 48 hours after drug initiation with the rapid development of dozens to thousands of 1- to 4-mm pustules, typically localized to the flexor surfaces and face. In the setting of AGEP, acute onset of fever and leukocytosis typically occur at the time of the cutaneous eruption. These features were absent in this patient. The eruption usually starts on the face and then migrates to the trunk and extremities, sparing the palms and soles. Systemic involvement most commonly presents as hepatic, renal, or pulmonary insufficiency, which has been seen in 20% of cases.²

The immunologic response associated with the reaction has been studied in vitro. Drug-specific CD8 T cells use perforin/granzyme B and Fas ligand mechanisms to induce apoptosis of the keratinocytes within the epidermis, leading to vesicle formation.³ During the very first stages of formation, vesicles mainly comprise CD8 T cells and keratinocytes. These cells then begin producing CXC-18, a potent neutrophil chemokine, leading to extensive chemotaxis of neutrophils into vesicles, which then rapidly transform to pustules.³ This rapid transformation leads to the lakes of pustules, a description often associated with AGEP.

Treatment of AGEP is mainly supportive and consists of discontinuing use of the causative agent. Topical corticosteroids can be used during the pustular phase for symptom management. There is no evidence that systemic steroids reduce the duration of the disease.² Other supportive measures such as application of wet wraps can be used to provide comfort.

Cutaneous adverse drug reactions commonly are associated with psychiatric pharmacotherapy, but first-and second-generation antipsychotics rarely are associated with these types of reactions. In this patient, the causative agent of the AGEP was cariprazine, an atypical antipsychotic that had no reported association with AGEP or cutaneous adverse drug reactions prior to this presentation.

To the Editor:

A 57-year-old woman presented to an outpatient clinic with severe pruritus and burning of the skin as well as subjective fevers and chills. She had been discharged from a psychiatric hospital for attempted suicide 1 day prior. There were no recent changes in the medication regimen, which consisted of linaclotide, fluoxetine, lorazepam, and gabapentin. While admitted, the patient was started on the atypical antipsychotic cariprazine. Within 24 hours of the first dose, she developed severe facial erythema that progressed to diffuse erythema over more than 60% of the body surface area. The attending psychiatrist promptly discontinued cariprazine. During the next 24 hours, there were no reports of fever, leukocytosis, or signs of systemic organ involvement. Given the patient’s mental and medical stability, she was discharged with instructions to follow up with the outpatient dermatology clinic.

At the current presentation, physical examination revealed innumerable 1- to 4-mm pustules coalescing to lakes of pus on an erythematous base over more than 60% of the body surface area (Figure 1). The mucous membranes were clear of lesions, the Nikolsky sign was negative, and the patient’s temperature was 99.6 °F in the office. Complete blood cell count and complete metabolic panel results were within reference range.

A 4-mm abdominal punch biopsy showed subcorneal neutrophilic pustules, papillary dermal edema, and superficial dermal lymphohistiocytic inflammation with numerous neutrophils, eosinophils, and extravasated red blood cells, consistent with acute generalized exanthematous pustulosis (AGEP)(Figure 2). The patient was started on wet wraps with triamcinolone cream 0.1%.

Two days later, physical examination revealed the erythema noted on initial examination had notably decreased, and the patient no longer reported burning or pruritus. One week after initial presentation to the clinic, the patient’s rash had resolved, and only a few small areas of desquamation remained.

Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the development of numerous nonfollicular sterile pustules on an edematous and erythematous base. In almost 90% of reported cases, the cause is related to use of antibiotics, antifungals, antimalarials, or diltiazem (a calcium channel blocker). This rare cutaneous reaction occurs in 1 to 5 patients per million per year¹; it carries a 1% to 2% mortality rate with proper supportive treatment.

The clinical symptoms of AGEP typically present 24 to 48 hours after drug initiation with the rapid development of dozens to thousands of 1- to 4-mm pustules, typically localized to the flexor surfaces and face. In the setting of AGEP, acute onset of fever and leukocytosis typically occur at the time of the cutaneous eruption. These features were absent in this patient. The eruption usually starts on the face and then migrates to the trunk and extremities, sparing the palms and soles. Systemic involvement most commonly presents as hepatic, renal, or pulmonary insufficiency, which has been seen in 20% of cases.²

The immunologic response associated with the reaction has been studied in vitro. Drug-specific CD8 T cells use perforin/granzyme B and Fas ligand mechanisms to induce apoptosis of the keratinocytes within the epidermis, leading to vesicle formation.³ During the very first stages of formation, vesicles mainly comprise CD8 T cells and keratinocytes. These cells then begin producing CXC-18, a potent neutrophil chemokine, leading to extensive chemotaxis of neutrophils into vesicles, which then rapidly transform to pustules.³ This rapid transformation leads to the lakes of pustules, a description often associated with AGEP.

Treatment of AGEP is mainly supportive and consists of discontinuing use of the causative agent. Topical corticosteroids can be used during the pustular phase for symptom management. There is no evidence that systemic steroids reduce the duration of the disease.² Other supportive measures such as application of wet wraps can be used to provide comfort.

Cutaneous adverse drug reactions commonly are associated with psychiatric pharmacotherapy, but first-and second-generation antipsychotics rarely are associated with these types of reactions. In this patient, the causative agent of the AGEP was cariprazine, an atypical antipsychotic that had no reported association with AGEP or cutaneous adverse drug reactions prior to this presentation.

To the Editor:

A 47-year-old man presented at the dermatology clinic with a growing lesion on the left medial thigh. The patient traveled frequently for work. Although asymptomatic, the lesion was interfering with the patient’s ability to get through security because it routinely was getting detected by airport full-body scanners. These scanners use high-frequency radio waves or x-rays to detect nonmetallic objects under a traveler’s clothing. The patient would be frisked by security and had to explain that he had a growth in that location. He thankfully would be released by security on those occasions, but the delay in getting through security was becoming a nuisance.

Physical examination revealed a 5-cm, pedunculated, fatty nodule on the left medial thigh that was clinically consistent with nevus lipomatosis (NL)(Figure). Although benign, trouble traveling through airport security prompted the patient to request shave removal, which subsequently was performed. Histology showed a large pedunculated nodule with prominent adipose tissue, consistent with NL. At 3-month follow-up, the patient reported getting through airport security multiple times without incident.

Nevus lipomatosis is a benign fatty lesion most commonly found on the medial thighs or trunk of adults. The lesion usually is asymptomatic but can become irritated by rubbing or catching on clothing. Our patient had symptomatic NL that caused delays getting through airport security; he experienced full resolution after simple shave removal. In rare instances, both benign and malignant skin conditions have been seen on airport scanning devices since the introduction of increased security measures following September 11, 2001. In 2016, Heymann¹ reported a man with a 1.5-cm epidermal inclusion cyst detected by airport security scanners, prompting the traveler to request and carry a medically explanatory letter used to get through security. In 2015 Mayer and Adams² described a case of nodular melanoma that was detected 20 times over a period of 2 months by airport scanners, and in 2016, Caine et al³ reported a case of desmoplastic melanoma that was detected by airport security, but after its removal was not identified by security for the next 40 flights. Noncutaneous pathology also can be detected by airport scanners. In 2013, Naraynsingh et al⁴ reported a man with a large left reducible inguinal hernia who was stopped by airport security and subjected to an invasive physical examination of the area. These instances demonstrate the breadth of conditions that can be cumbersome when individuals are traveling by airplane in our current security climate.

Our patient had to go through the trouble of having the benign NL lesion removed to avoid the hassle of repeatedly being stopped by airport security. The patient had the lesion removed and is doing well, but the procedure could have been avoided if systems existed to help patients with dermatologic and medical conditions at airport security. Our patient likely will never be stopped again for the suspicious lump on the left inner thigh, but many others will be stopped for similar reasons.

To the Editor:

A 47-year-old man presented at the dermatology clinic with a growing lesion on the left medial thigh. The patient traveled frequently for work. Although asymptomatic, the lesion was interfering with the patient’s ability to get through security because it routinely was getting detected by airport full-body scanners. These scanners use high-frequency radio waves or x-rays to detect nonmetallic objects under a traveler’s clothing. The patient would be frisked by security and had to explain that he had a growth in that location. He thankfully would be released by security on those occasions, but the delay in getting through security was becoming a nuisance.

Physical examination revealed a 5-cm, pedunculated, fatty nodule on the left medial thigh that was clinically consistent with nevus lipomatosis (NL)(Figure). Although benign, trouble traveling through airport security prompted the patient to request shave removal, which subsequently was performed. Histology showed a large pedunculated nodule with prominent adipose tissue, consistent with NL. At 3-month follow-up, the patient reported getting through airport security multiple times without incident.

Nevus lipomatosis is a benign fatty lesion most commonly found on the medial thighs or trunk of adults. The lesion usually is asymptomatic but can become irritated by rubbing or catching on clothing. Our patient had symptomatic NL that caused delays getting through airport security; he experienced full resolution after simple shave removal. In rare instances, both benign and malignant skin conditions have been seen on airport scanning devices since the introduction of increased security measures following September 11, 2001. In 2016, Heymann¹ reported a man with a 1.5-cm epidermal inclusion cyst detected by airport security scanners, prompting the traveler to request and carry a medically explanatory letter used to get through security. In 2015 Mayer and Adams² described a case of nodular melanoma that was detected 20 times over a period of 2 months by airport scanners, and in 2016, Caine et al³ reported a case of desmoplastic melanoma that was detected by airport security, but after its removal was not identified by security for the next 40 flights. Noncutaneous pathology also can be detected by airport scanners. In 2013, Naraynsingh et al⁴ reported a man with a large left reducible inguinal hernia who was stopped by airport security and subjected to an invasive physical examination of the area. These instances demonstrate the breadth of conditions that can be cumbersome when individuals are traveling by airplane in our current security climate.

Our patient had to go through the trouble of having the benign NL lesion removed to avoid the hassle of repeatedly being stopped by airport security. The patient had the lesion removed and is doing well, but the procedure could have been avoided if systems existed to help patients with dermatologic and medical conditions at airport security. Our patient likely will never be stopped again for the suspicious lump on the left inner thigh, but many others will be stopped for similar reasons.

To the Editor:

A 47-year-old man presented at the dermatology clinic with a growing lesion on the left medial thigh. The patient traveled frequently for work. Although asymptomatic, the lesion was interfering with the patient’s ability to get through security because it routinely was getting detected by airport full-body scanners. These scanners use high-frequency radio waves or x-rays to detect nonmetallic objects under a traveler’s clothing. The patient would be frisked by security and had to explain that he had a growth in that location. He thankfully would be released by security on those occasions, but the delay in getting through security was becoming a nuisance.

Physical examination revealed a 5-cm, pedunculated, fatty nodule on the left medial thigh that was clinically consistent with nevus lipomatosis (NL)(Figure). Although benign, trouble traveling through airport security prompted the patient to request shave removal, which subsequently was performed. Histology showed a large pedunculated nodule with prominent adipose tissue, consistent with NL. At 3-month follow-up, the patient reported getting through airport security multiple times without incident.

Nevus lipomatosis is a benign fatty lesion most commonly found on the medial thighs or trunk of adults. The lesion usually is asymptomatic but can become irritated by rubbing or catching on clothing. Our patient had symptomatic NL that caused delays getting through airport security; he experienced full resolution after simple shave removal. In rare instances, both benign and malignant skin conditions have been seen on airport scanning devices since the introduction of increased security measures following September 11, 2001. In 2016, Heymann¹ reported a man with a 1.5-cm epidermal inclusion cyst detected by airport security scanners, prompting the traveler to request and carry a medically explanatory letter used to get through security. In 2015 Mayer and Adams² described a case of nodular melanoma that was detected 20 times over a period of 2 months by airport scanners, and in 2016, Caine et al³ reported a case of desmoplastic melanoma that was detected by airport security, but after its removal was not identified by security for the next 40 flights. Noncutaneous pathology also can be detected by airport scanners. In 2013, Naraynsingh et al⁴ reported a man with a large left reducible inguinal hernia who was stopped by airport security and subjected to an invasive physical examination of the area. These instances demonstrate the breadth of conditions that can be cumbersome when individuals are traveling by airplane in our current security climate.

Our patient had to go through the trouble of having the benign NL lesion removed to avoid the hassle of repeatedly being stopped by airport security. The patient had the lesion removed and is doing well, but the procedure could have been avoided if systems existed to help patients with dermatologic and medical conditions at airport security. Our patient likely will never be stopped again for the suspicious lump on the left inner thigh, but many others will be stopped for similar reasons.

In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.

This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides protection against persistent infection from HPV 16 and 18 similar to that provided by two or three doses.

Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.

With respect to the Indian study, Dr. Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless, “excellent news for developing countries where there are challenges when it comes to access to vaccination.”
 

India and France

During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”

In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.

“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Dr. Canlorbe.

“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.

This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.

In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
 

Indian study highlights

Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.

According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Dr. Basu and his team had recruited 17,729 eligible girls.

After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.

Vaccinated participants were followed up over a median duration of 9 years. In all, 4,348 participants had three doses, 4,980 had two doses (at 0 and 6 months), and 4,949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.

A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% confidence interval [CI], 85.0-99.9) in the single-dose default cohort (2,135 women assessed), 93.1% (95% CI, 77.3-99.8) in the two-dose cohort (1,452 women assessed), and 93.3% (95% CI, 77.5-99.7) in three-dose recipients (1,460 women assessed).

Dr. Canlorbe reported no relevant financial relationships regarding the content of this article.

This article was translated from the Medscape French edition. An English version appeared on Medscape.com.

In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.

This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides protection against persistent infection from HPV 16 and 18 similar to that provided by two or three doses.

Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.

With respect to the Indian study, Dr. Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless, “excellent news for developing countries where there are challenges when it comes to access to vaccination.”
 

India and France

During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”

In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.

“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Dr. Canlorbe.

“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.

This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.

In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
 

Indian study highlights

Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.

According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Dr. Basu and his team had recruited 17,729 eligible girls.

After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.

Vaccinated participants were followed up over a median duration of 9 years. In all, 4,348 participants had three doses, 4,980 had two doses (at 0 and 6 months), and 4,949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.

A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% confidence interval [CI], 85.0-99.9) in the single-dose default cohort (2,135 women assessed), 93.1% (95% CI, 77.3-99.8) in the two-dose cohort (1,452 women assessed), and 93.3% (95% CI, 77.5-99.7) in three-dose recipients (1,460 women assessed).

Dr. Canlorbe reported no relevant financial relationships regarding the content of this article.

This article was translated from the Medscape French edition. An English version appeared on Medscape.com.

In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.

This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides protection against persistent infection from HPV 16 and 18 similar to that provided by two or three doses.

Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.

With respect to the Indian study, Dr. Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless, “excellent news for developing countries where there are challenges when it comes to access to vaccination.”
 

India and France

During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”

In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.

“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Dr. Canlorbe.

“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.

This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.

In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
 

Indian study highlights

Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.

According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Dr. Basu and his team had recruited 17,729 eligible girls.

After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.

Vaccinated participants were followed up over a median duration of 9 years. In all, 4,348 participants had three doses, 4,980 had two doses (at 0 and 6 months), and 4,949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.

A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% confidence interval [CI], 85.0-99.9) in the single-dose default cohort (2,135 women assessed), 93.1% (95% CI, 77.3-99.8) in the two-dose cohort (1,452 women assessed), and 93.3% (95% CI, 77.5-99.7) in three-dose recipients (1,460 women assessed).

Dr. Canlorbe reported no relevant financial relationships regarding the content of this article.

This article was translated from the Medscape French edition. An English version appeared on Medscape.com.

A weekend, for most of us in solo practice, doesn’t really signify time off from work. It just means we’re not seeing patients at the office.

There’s always business stuff to do (like payroll and paying bills), legal cases to review, the never-ending forms for a million things, and all the other stuff there never seems to be enough time to do on weekdays.

So this weekend I started attacking the pile after dinner on Friday and found myself done by Saturday afternoon. Which is rare, usually I spend the better part of a weekend at my desk.

And then, unexpectedly faced with an empty desk, I found myself wondering what to do.

Boredom is one of the odder human conditions. Certainly, there are more ways to waste time now than there ever have been. TV, Netflix, phone games, TikTok, books, just to name a few.

But do we always have to be entertained? Many great scientists have said that world-changing ideas have come to them when they weren’t working, such as while showering or riding to work. Leo Szilard was crossing a London street in 1933 when he suddenly saw how a nuclear chain reaction would be self-sustaining once initiated. (Fortunately, he wasn’t hit by a car in the process.)

But I’m not Szilard. So I rationalized a reason not to exercise and sat on the couch with a book.

The remarkable human brain doesn’t shut down easily. With nothing else to do, most other mammals tend to doze off. But not us. It’s always on, trying to think of the next goal, the next move, the next whatever.

Having nothing to do sounds like a great idea, until you have nothing to do. It may be fine for a few days, but after a while you realize there’s only so long you can stare at the waves or mountains before your mind turns back to “what’s next.” Many patients tell me how retirement sounded good until they got there, then found themselves volunteering or taking new jobs just to keep busy.

This isn’t a bad thing. Being bored is probably constructive. Without realizing it we use it to form new ideas and start new plans.

Maybe this is why we’re here. The mind that keeps working is a powerful tool, driving us forward in all walks of life. Perhaps it’s this feature that pushed the development of intelligence further and led us to form civilizations.

Perhaps it’s the real reason we keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A weekend, for most of us in solo practice, doesn’t really signify time off from work. It just means we’re not seeing patients at the office.

There’s always business stuff to do (like payroll and paying bills), legal cases to review, the never-ending forms for a million things, and all the other stuff there never seems to be enough time to do on weekdays.

So this weekend I started attacking the pile after dinner on Friday and found myself done by Saturday afternoon. Which is rare, usually I spend the better part of a weekend at my desk.

And then, unexpectedly faced with an empty desk, I found myself wondering what to do.

Boredom is one of the odder human conditions. Certainly, there are more ways to waste time now than there ever have been. TV, Netflix, phone games, TikTok, books, just to name a few.

But do we always have to be entertained? Many great scientists have said that world-changing ideas have come to them when they weren’t working, such as while showering or riding to work. Leo Szilard was crossing a London street in 1933 when he suddenly saw how a nuclear chain reaction would be self-sustaining once initiated. (Fortunately, he wasn’t hit by a car in the process.)

But I’m not Szilard. So I rationalized a reason not to exercise and sat on the couch with a book.

The remarkable human brain doesn’t shut down easily. With nothing else to do, most other mammals tend to doze off. But not us. It’s always on, trying to think of the next goal, the next move, the next whatever.

Having nothing to do sounds like a great idea, until you have nothing to do. It may be fine for a few days, but after a while you realize there’s only so long you can stare at the waves or mountains before your mind turns back to “what’s next.” Many patients tell me how retirement sounded good until they got there, then found themselves volunteering or taking new jobs just to keep busy.

This isn’t a bad thing. Being bored is probably constructive. Without realizing it we use it to form new ideas and start new plans.

Maybe this is why we’re here. The mind that keeps working is a powerful tool, driving us forward in all walks of life. Perhaps it’s this feature that pushed the development of intelligence further and led us to form civilizations.

Perhaps it’s the real reason we keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A weekend, for most of us in solo practice, doesn’t really signify time off from work. It just means we’re not seeing patients at the office.

There’s always business stuff to do (like payroll and paying bills), legal cases to review, the never-ending forms for a million things, and all the other stuff there never seems to be enough time to do on weekdays.

So this weekend I started attacking the pile after dinner on Friday and found myself done by Saturday afternoon. Which is rare, usually I spend the better part of a weekend at my desk.

And then, unexpectedly faced with an empty desk, I found myself wondering what to do.

Boredom is one of the odder human conditions. Certainly, there are more ways to waste time now than there ever have been. TV, Netflix, phone games, TikTok, books, just to name a few.

But do we always have to be entertained? Many great scientists have said that world-changing ideas have come to them when they weren’t working, such as while showering or riding to work. Leo Szilard was crossing a London street in 1933 when he suddenly saw how a nuclear chain reaction would be self-sustaining once initiated. (Fortunately, he wasn’t hit by a car in the process.)

But I’m not Szilard. So I rationalized a reason not to exercise and sat on the couch with a book.

The remarkable human brain doesn’t shut down easily. With nothing else to do, most other mammals tend to doze off. But not us. It’s always on, trying to think of the next goal, the next move, the next whatever.

Having nothing to do sounds like a great idea, until you have nothing to do. It may be fine for a few days, but after a while you realize there’s only so long you can stare at the waves or mountains before your mind turns back to “what’s next.” Many patients tell me how retirement sounded good until they got there, then found themselves volunteering or taking new jobs just to keep busy.

This isn’t a bad thing. Being bored is probably constructive. Without realizing it we use it to form new ideas and start new plans.

Maybe this is why we’re here. The mind that keeps working is a powerful tool, driving us forward in all walks of life. Perhaps it’s this feature that pushed the development of intelligence further and led us to form civilizations.

Perhaps it’s the real reason we keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Sunil Khushalani and Antonio DePaolo,

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare”

(London: Routledge, Taylor & Francis, 2022)

Since the publication of our book, “Lean Behavioral Health: The Kings County Hospital Story” (Oxford, England: Oxford University Press, 2014) almost a decade ago, “Transforming Mental Healthcare” is the first major book published about the use of a system for quality improvement across the health care continuum. That it has taken this long is probably surprising to those of us who have spent careers on trying to improve what is universally described as a system that is “broken” and in need of a major overhaul.

Routledge, Taylor & Francis Group

Every news cycle that reports mass violence typically spends a good bit of time talking about the failures of the mental health care system. One important lesson I learned when taking over the beleaguered Kings County (N.Y.) psychiatry service in 2009 (a department that has made extraordinary improvements over the years and is now exclaimed by the U.S. Department of Justice as “a model program”), is that the employees on the front line are often erroneously blamed for such failures.

The failure is systemic and usually starts at the top of the table of organization, not at the bottom. Dr. Khushalani and Dr. DePaolo have produced an excellent volume that should be purchased by every mental health care CEO and given “with thanks” to the local leaders overseeing the direct care of some of our nation’s most vulnerable patient populations.

The first part of “Transforming Mental Healthcare” provides an excellent overview of the current state of our mental health care system and its too numerous to name problems. This section could be a primer for all our legislators so their eyes can be opened to the failures on the ground that require their help in correcting. Many of the “failures” of our mental health care are societal failures – lack of affordable housing, access to care, reimbursement for care, gun access, etc. – and cannot be “fixed” by providers of care. Such problems are societal problems that call for societal and governmental solutions, and not only at the local level but from coast to coast.

The remainder of this easy to read and follow text provides many rich resources for the deliverers of mental health care. Focusing on quality improvement at the systemic level and providing a basic and fundamental teaching about the lean improvement methodology, readers learn about each of the foundational tools (e.g., plan-do-act, standard work, and A3 thinking).

Dr. Joseph Merlino

The closing section focuses on leadership and culture – often overlooked to the detriment of any organization that doesn’t pay close attention to supporting both. Culture is cultivated and nourished by the organization’s leaders. Culture empowers staff to become problem solvers and agents of improvement. Empowered staff support and enrich their culture. Together a workplace that brings out the best of all its people is created, and burnout is held at bay.

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare” is a welcome and essential addition to the current morass, which is our mental health care delivery system, an oasis in the desert from which perhaps the lotus flower can emerge.

Dr. Merlino is emeritus professor of psychiatry, SUNY Downstate College of Medicine, Rhinebeck, N.Y., and formerly director of psychiatry at Kings County Hospital Center, Brooklyn, NY. He is the coauthor of “Lean Behavioral Health: The Kings County Hospital Story.” .

Sunil Khushalani and Antonio DePaolo,

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare”

(London: Routledge, Taylor & Francis, 2022)

Since the publication of our book, “Lean Behavioral Health: The Kings County Hospital Story” (Oxford, England: Oxford University Press, 2014) almost a decade ago, “Transforming Mental Healthcare” is the first major book published about the use of a system for quality improvement across the health care continuum. That it has taken this long is probably surprising to those of us who have spent careers on trying to improve what is universally described as a system that is “broken” and in need of a major overhaul.

Routledge, Taylor & Francis Group

Every news cycle that reports mass violence typically spends a good bit of time talking about the failures of the mental health care system. One important lesson I learned when taking over the beleaguered Kings County (N.Y.) psychiatry service in 2009 (a department that has made extraordinary improvements over the years and is now exclaimed by the U.S. Department of Justice as “a model program”), is that the employees on the front line are often erroneously blamed for such failures.

The failure is systemic and usually starts at the top of the table of organization, not at the bottom. Dr. Khushalani and Dr. DePaolo have produced an excellent volume that should be purchased by every mental health care CEO and given “with thanks” to the local leaders overseeing the direct care of some of our nation’s most vulnerable patient populations.

The first part of “Transforming Mental Healthcare” provides an excellent overview of the current state of our mental health care system and its too numerous to name problems. This section could be a primer for all our legislators so their eyes can be opened to the failures on the ground that require their help in correcting. Many of the “failures” of our mental health care are societal failures – lack of affordable housing, access to care, reimbursement for care, gun access, etc. – and cannot be “fixed” by providers of care. Such problems are societal problems that call for societal and governmental solutions, and not only at the local level but from coast to coast.

The remainder of this easy to read and follow text provides many rich resources for the deliverers of mental health care. Focusing on quality improvement at the systemic level and providing a basic and fundamental teaching about the lean improvement methodology, readers learn about each of the foundational tools (e.g., plan-do-act, standard work, and A3 thinking).

Dr. Joseph Merlino

The closing section focuses on leadership and culture – often overlooked to the detriment of any organization that doesn’t pay close attention to supporting both. Culture is cultivated and nourished by the organization’s leaders. Culture empowers staff to become problem solvers and agents of improvement. Empowered staff support and enrich their culture. Together a workplace that brings out the best of all its people is created, and burnout is held at bay.

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare” is a welcome and essential addition to the current morass, which is our mental health care delivery system, an oasis in the desert from which perhaps the lotus flower can emerge.

Dr. Merlino is emeritus professor of psychiatry, SUNY Downstate College of Medicine, Rhinebeck, N.Y., and formerly director of psychiatry at Kings County Hospital Center, Brooklyn, NY. He is the coauthor of “Lean Behavioral Health: The Kings County Hospital Story.” .

Sunil Khushalani and Antonio DePaolo,

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare”

(London: Routledge, Taylor & Francis, 2022)

Since the publication of our book, “Lean Behavioral Health: The Kings County Hospital Story” (Oxford, England: Oxford University Press, 2014) almost a decade ago, “Transforming Mental Healthcare” is the first major book published about the use of a system for quality improvement across the health care continuum. That it has taken this long is probably surprising to those of us who have spent careers on trying to improve what is universally described as a system that is “broken” and in need of a major overhaul.

Routledge, Taylor & Francis Group

Every news cycle that reports mass violence typically spends a good bit of time talking about the failures of the mental health care system. One important lesson I learned when taking over the beleaguered Kings County (N.Y.) psychiatry service in 2009 (a department that has made extraordinary improvements over the years and is now exclaimed by the U.S. Department of Justice as “a model program”), is that the employees on the front line are often erroneously blamed for such failures.

The failure is systemic and usually starts at the top of the table of organization, not at the bottom. Dr. Khushalani and Dr. DePaolo have produced an excellent volume that should be purchased by every mental health care CEO and given “with thanks” to the local leaders overseeing the direct care of some of our nation’s most vulnerable patient populations.

The first part of “Transforming Mental Healthcare” provides an excellent overview of the current state of our mental health care system and its too numerous to name problems. This section could be a primer for all our legislators so their eyes can be opened to the failures on the ground that require their help in correcting. Many of the “failures” of our mental health care are societal failures – lack of affordable housing, access to care, reimbursement for care, gun access, etc. – and cannot be “fixed” by providers of care. Such problems are societal problems that call for societal and governmental solutions, and not only at the local level but from coast to coast.

The remainder of this easy to read and follow text provides many rich resources for the deliverers of mental health care. Focusing on quality improvement at the systemic level and providing a basic and fundamental teaching about the lean improvement methodology, readers learn about each of the foundational tools (e.g., plan-do-act, standard work, and A3 thinking).

Dr. Joseph Merlino

The closing section focuses on leadership and culture – often overlooked to the detriment of any organization that doesn’t pay close attention to supporting both. Culture is cultivated and nourished by the organization’s leaders. Culture empowers staff to become problem solvers and agents of improvement. Empowered staff support and enrich their culture. Together a workplace that brings out the best of all its people is created, and burnout is held at bay.

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare” is a welcome and essential addition to the current morass, which is our mental health care delivery system, an oasis in the desert from which perhaps the lotus flower can emerge.

Dr. Merlino is emeritus professor of psychiatry, SUNY Downstate College of Medicine, Rhinebeck, N.Y., and formerly director of psychiatry at Kings County Hospital Center, Brooklyn, NY. He is the coauthor of “Lean Behavioral Health: The Kings County Hospital Story.” .

Almost half of adult patients with eosinophilic esophagitis (EoE) reported poor adherence to long-term medical and dietary therapy, with age younger than 40 years and low necessity beliefs being the strongest predictors, a new study finds.

Clinicians need to spend more time discussing the need for EoE therapy with their patients, especially if they are younger, according to lead author Maria L. Haasnoot, MD, of Amsterdam University Medical Center (UMC), the Netherlands, and colleagues.

“Chronic treatment is necessary to maintain suppression of the inflammation and prevent negative outcomes in the long-term,” they write.

Until the recent approval of dupilumab (Dupixent) by the U.S. Food and Drug Administration, patients with EoE relied upon off-label options, including proton pump inhibitors and swallowed topical steroids, as well as dietary interventions for ongoing suppression of inflammation. But only about 1 in 6 patients achieve complete remission at 5 years, according to Dr. Haasnoot and colleagues.

“It is uncertain to what degree limited adherence to treatment [plays] a role in the limited long-term effects of treatment,” they write.

The findings were published online in American Journal of Gastroenterology.
 

Addressing a knowledge gap

The cross-sectional study involved 177 adult patients with EoE treated at Amsterdam UMC, who were prescribed dietary or medical maintenance therapy. Of note, some patients were treated with budesonide, which is approved for EoE in Europe but not in the United States.

Median participant age was 43 years, with a male-skewed distribution (71% men). Patients had been on EoE treatment for 2-6 years. Most (76%) were on medical treatments. Nearly half were on diets that avoided one to five food groups, with some on both medical treatments and elimination diets.

Using a link sent by mail, participants completed the online Medication Adherence Rating Scale, along with several other questionnaires, such as the Beliefs about Medicine Questionnaire, to measure secondary outcomes, including a patient’s view of how necessary or disruptive maintenance therapy is in their life.

The overall prevalence of poor adherence to therapy was high (41.8%), including a nonsignificant difference in adherence between medical and dietary therapies.

“It might come as a surprise that dietary-treated patients are certainly not less adherent to treatment than medically treated patients,” the authors write, noting that the opposite is usually true.

Multivariate logistic regression showed that patients younger than 40 years were more than twice as likely to be poorly adherent (odds ratio, 2.571; 95% confidence interval, 1.195-5.532). Those with low necessity beliefs were more than four times as likely to be poorly adherent (OR, 4.423; 95% CI, 2.169-9.016). Other factors linked to poor adherence were patients with longer disease duration and more severe symptoms.

“Clinicians should pay more attention to treatment adherence, particularly in younger patients,” the authors conclude. “The necessity of treatment should be actively discussed, and efforts should be done to take doubts away, as this may improve treatment adherence and subsequently may improve treatment effects and long-term outcomes.”
 

More patient education needed

According to Jennifer L. Horsley-Silva, MD, of Mayo Clinic, Scottsdale, Ariz., “This study is important, as it is one of the first studies to investigate the rate of treatment adherence in EoE patients and attempts to identify factors associated with adherence both in medically and dietary treated patients.”

Dr. Horsley-Silva commented that the findings align with recent research she and her colleagues conducted at the Mayo Clinic, where few patients successfully completed a six-food elimination diet, even when paired with a dietitian. As with the present study, success trended lower among younger adults. “These findings highlight the need for physicians treating EoE to motivate all patients, but especially younger patients, by discussing disease pathophysiology and explaining the reason for maintenance treatment early on,” Dr. Horsley-Silva said.

Conversations should also address the discordance between symptoms and histologic disease, patient doubts and concerns, and other barriers to adherence, she noted.

“Shared decisionmaking is of utmost importance when deciding upon a maintenance treatment strategy and should be readdressed continually,” she added.

Gary W. Falk, MD, of Penn Medicine, Philadelphia, said that patients with EoE may be poorly adherent because therapies tend to be complicated and people often forget to take their medications, especially when their symptoms improve, even though this is a poor indicator of underlying disease. The discordance between symptoms and histology is “not commonly appreciated by the EoE GI community,” he noted.

Patients may benefit from knowing that untreated or undertreated EoE increases the risk for strictures and stenoses, need for dilation, and frequency of food bolus impactions, Dr. Falk said.

“The other thing we know is that once someone is induced into remission, and they stay on therapy ... long-term remission can be maintained,” he added.
 

The impact of Dupilumab

John Leung, MD, of Boston Food Allergy Center, also cited the complexities of EoE therapies as reason for poor adherence, though he believes this paradigm will shift now that dupilumab has been approved. Dupilumab injections are “just once a week, so it’s much easier in terms of frequency,” Dr. Leung said. “I would expect that the compliance [for dupilumab] will be better” than for older therapies.

Dr. Leung, who helped conduct the dupilumab clinical trials contributing to its approval for EoE and receives speaking honoraria from manufacturer Regeneron/Sanofi, said that dupilumab also overcomes the challenges with elimination diets while offering relief for concomitant conditions, such as “asthma, eczema, food allergies, and seasonal allergies.”

But Dr. Falk, who also worked on the dupilumab clinical trials, said the situation is “not straightforward,” even with FDA approval.

“There are going to be significant costs with [prescribing dupilumab], because it’s a biologic,” Dr. Falk said.

Dr. Falk also pointed out that prior authorization will be required, and until more studies can be conducted, the true impact of once-weekly dosing versus daily dosing remains unknown.

“I would say [dupilumab] has the potential to improve adherence, but we need to see if that’s going to be the case or not,” Dr. Falk said.

The authors disclosed relationships with Dr. Falk Pharma, AstraZeneca, and Sanofi/Regeneron (the manufacturers of Dupixent [dupilumab]), among others. Dr. Horsley-Silva, Dr. Falk, and Dr. Leung conducted clinical trials for dupilumab on behalf of Sanofi/Regeneron, with Dr. Leung also disclosing speaking honoraria from Sanofi/Regeneron. Dr. Horsley-Silva has acted as a clinical trial site principal investigator for Allakos and Celgene/Bristol-Myers Squibb.

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

Almost half of adult patients with eosinophilic esophagitis (EoE) reported poor adherence to long-term medical and dietary therapy, with age younger than 40 years and low necessity beliefs being the strongest predictors, a new study finds.

Clinicians need to spend more time discussing the need for EoE therapy with their patients, especially if they are younger, according to lead author Maria L. Haasnoot, MD, of Amsterdam University Medical Center (UMC), the Netherlands, and colleagues.

“Chronic treatment is necessary to maintain suppression of the inflammation and prevent negative outcomes in the long-term,” they write.

Until the recent approval of dupilumab (Dupixent) by the U.S. Food and Drug Administration, patients with EoE relied upon off-label options, including proton pump inhibitors and swallowed topical steroids, as well as dietary interventions for ongoing suppression of inflammation. But only about 1 in 6 patients achieve complete remission at 5 years, according to Dr. Haasnoot and colleagues.

“It is uncertain to what degree limited adherence to treatment [plays] a role in the limited long-term effects of treatment,” they write.

The findings were published online in American Journal of Gastroenterology.
 

Addressing a knowledge gap

The cross-sectional study involved 177 adult patients with EoE treated at Amsterdam UMC, who were prescribed dietary or medical maintenance therapy. Of note, some patients were treated with budesonide, which is approved for EoE in Europe but not in the United States.

Median participant age was 43 years, with a male-skewed distribution (71% men). Patients had been on EoE treatment for 2-6 years. Most (76%) were on medical treatments. Nearly half were on diets that avoided one to five food groups, with some on both medical treatments and elimination diets.

Using a link sent by mail, participants completed the online Medication Adherence Rating Scale, along with several other questionnaires, such as the Beliefs about Medicine Questionnaire, to measure secondary outcomes, including a patient’s view of how necessary or disruptive maintenance therapy is in their life.

The overall prevalence of poor adherence to therapy was high (41.8%), including a nonsignificant difference in adherence between medical and dietary therapies.

“It might come as a surprise that dietary-treated patients are certainly not less adherent to treatment than medically treated patients,” the authors write, noting that the opposite is usually true.

Multivariate logistic regression showed that patients younger than 40 years were more than twice as likely to be poorly adherent (odds ratio, 2.571; 95% confidence interval, 1.195-5.532). Those with low necessity beliefs were more than four times as likely to be poorly adherent (OR, 4.423; 95% CI, 2.169-9.016). Other factors linked to poor adherence were patients with longer disease duration and more severe symptoms.

“Clinicians should pay more attention to treatment adherence, particularly in younger patients,” the authors conclude. “The necessity of treatment should be actively discussed, and efforts should be done to take doubts away, as this may improve treatment adherence and subsequently may improve treatment effects and long-term outcomes.”
 

More patient education needed

According to Jennifer L. Horsley-Silva, MD, of Mayo Clinic, Scottsdale, Ariz., “This study is important, as it is one of the first studies to investigate the rate of treatment adherence in EoE patients and attempts to identify factors associated with adherence both in medically and dietary treated patients.”

Dr. Horsley-Silva commented that the findings align with recent research she and her colleagues conducted at the Mayo Clinic, where few patients successfully completed a six-food elimination diet, even when paired with a dietitian. As with the present study, success trended lower among younger adults. “These findings highlight the need for physicians treating EoE to motivate all patients, but especially younger patients, by discussing disease pathophysiology and explaining the reason for maintenance treatment early on,” Dr. Horsley-Silva said.

Conversations should also address the discordance between symptoms and histologic disease, patient doubts and concerns, and other barriers to adherence, she noted.

“Shared decisionmaking is of utmost importance when deciding upon a maintenance treatment strategy and should be readdressed continually,” she added.

Gary W. Falk, MD, of Penn Medicine, Philadelphia, said that patients with EoE may be poorly adherent because therapies tend to be complicated and people often forget to take their medications, especially when their symptoms improve, even though this is a poor indicator of underlying disease. The discordance between symptoms and histology is “not commonly appreciated by the EoE GI community,” he noted.

Patients may benefit from knowing that untreated or undertreated EoE increases the risk for strictures and stenoses, need for dilation, and frequency of food bolus impactions, Dr. Falk said.

“The other thing we know is that once someone is induced into remission, and they stay on therapy ... long-term remission can be maintained,” he added.
 

The impact of Dupilumab

John Leung, MD, of Boston Food Allergy Center, also cited the complexities of EoE therapies as reason for poor adherence, though he believes this paradigm will shift now that dupilumab has been approved. Dupilumab injections are “just once a week, so it’s much easier in terms of frequency,” Dr. Leung said. “I would expect that the compliance [for dupilumab] will be better” than for older therapies.

Dr. Leung, who helped conduct the dupilumab clinical trials contributing to its approval for EoE and receives speaking honoraria from manufacturer Regeneron/Sanofi, said that dupilumab also overcomes the challenges with elimination diets while offering relief for concomitant conditions, such as “asthma, eczema, food allergies, and seasonal allergies.”

But Dr. Falk, who also worked on the dupilumab clinical trials, said the situation is “not straightforward,” even with FDA approval.

“There are going to be significant costs with [prescribing dupilumab], because it’s a biologic,” Dr. Falk said.

Dr. Falk also pointed out that prior authorization will be required, and until more studies can be conducted, the true impact of once-weekly dosing versus daily dosing remains unknown.

“I would say [dupilumab] has the potential to improve adherence, but we need to see if that’s going to be the case or not,” Dr. Falk said.

The authors disclosed relationships with Dr. Falk Pharma, AstraZeneca, and Sanofi/Regeneron (the manufacturers of Dupixent [dupilumab]), among others. Dr. Horsley-Silva, Dr. Falk, and Dr. Leung conducted clinical trials for dupilumab on behalf of Sanofi/Regeneron, with Dr. Leung also disclosing speaking honoraria from Sanofi/Regeneron. Dr. Horsley-Silva has acted as a clinical trial site principal investigator for Allakos and Celgene/Bristol-Myers Squibb.

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

Almost half of adult patients with eosinophilic esophagitis (EoE) reported poor adherence to long-term medical and dietary therapy, with age younger than 40 years and low necessity beliefs being the strongest predictors, a new study finds.

Clinicians need to spend more time discussing the need for EoE therapy with their patients, especially if they are younger, according to lead author Maria L. Haasnoot, MD, of Amsterdam University Medical Center (UMC), the Netherlands, and colleagues.

“Chronic treatment is necessary to maintain suppression of the inflammation and prevent negative outcomes in the long-term,” they write.

Until the recent approval of dupilumab (Dupixent) by the U.S. Food and Drug Administration, patients with EoE relied upon off-label options, including proton pump inhibitors and swallowed topical steroids, as well as dietary interventions for ongoing suppression of inflammation. But only about 1 in 6 patients achieve complete remission at 5 years, according to Dr. Haasnoot and colleagues.

“It is uncertain to what degree limited adherence to treatment [plays] a role in the limited long-term effects of treatment,” they write.

The findings were published online in American Journal of Gastroenterology.
 

Addressing a knowledge gap

The cross-sectional study involved 177 adult patients with EoE treated at Amsterdam UMC, who were prescribed dietary or medical maintenance therapy. Of note, some patients were treated with budesonide, which is approved for EoE in Europe but not in the United States.

Median participant age was 43 years, with a male-skewed distribution (71% men). Patients had been on EoE treatment for 2-6 years. Most (76%) were on medical treatments. Nearly half were on diets that avoided one to five food groups, with some on both medical treatments and elimination diets.

Using a link sent by mail, participants completed the online Medication Adherence Rating Scale, along with several other questionnaires, such as the Beliefs about Medicine Questionnaire, to measure secondary outcomes, including a patient’s view of how necessary or disruptive maintenance therapy is in their life.

The overall prevalence of poor adherence to therapy was high (41.8%), including a nonsignificant difference in adherence between medical and dietary therapies.

“It might come as a surprise that dietary-treated patients are certainly not less adherent to treatment than medically treated patients,” the authors write, noting that the opposite is usually true.

Multivariate logistic regression showed that patients younger than 40 years were more than twice as likely to be poorly adherent (odds ratio, 2.571; 95% confidence interval, 1.195-5.532). Those with low necessity beliefs were more than four times as likely to be poorly adherent (OR, 4.423; 95% CI, 2.169-9.016). Other factors linked to poor adherence were patients with longer disease duration and more severe symptoms.

“Clinicians should pay more attention to treatment adherence, particularly in younger patients,” the authors conclude. “The necessity of treatment should be actively discussed, and efforts should be done to take doubts away, as this may improve treatment adherence and subsequently may improve treatment effects and long-term outcomes.”
 

More patient education needed

According to Jennifer L. Horsley-Silva, MD, of Mayo Clinic, Scottsdale, Ariz., “This study is important, as it is one of the first studies to investigate the rate of treatment adherence in EoE patients and attempts to identify factors associated with adherence both in medically and dietary treated patients.”

Dr. Horsley-Silva commented that the findings align with recent research she and her colleagues conducted at the Mayo Clinic, where few patients successfully completed a six-food elimination diet, even when paired with a dietitian. As with the present study, success trended lower among younger adults. “These findings highlight the need for physicians treating EoE to motivate all patients, but especially younger patients, by discussing disease pathophysiology and explaining the reason for maintenance treatment early on,” Dr. Horsley-Silva said.

Conversations should also address the discordance between symptoms and histologic disease, patient doubts and concerns, and other barriers to adherence, she noted.

“Shared decisionmaking is of utmost importance when deciding upon a maintenance treatment strategy and should be readdressed continually,” she added.

Gary W. Falk, MD, of Penn Medicine, Philadelphia, said that patients with EoE may be poorly adherent because therapies tend to be complicated and people often forget to take their medications, especially when their symptoms improve, even though this is a poor indicator of underlying disease. The discordance between symptoms and histology is “not commonly appreciated by the EoE GI community,” he noted.

Patients may benefit from knowing that untreated or undertreated EoE increases the risk for strictures and stenoses, need for dilation, and frequency of food bolus impactions, Dr. Falk said.

“The other thing we know is that once someone is induced into remission, and they stay on therapy ... long-term remission can be maintained,” he added.
 

The impact of Dupilumab

John Leung, MD, of Boston Food Allergy Center, also cited the complexities of EoE therapies as reason for poor adherence, though he believes this paradigm will shift now that dupilumab has been approved. Dupilumab injections are “just once a week, so it’s much easier in terms of frequency,” Dr. Leung said. “I would expect that the compliance [for dupilumab] will be better” than for older therapies.

Dr. Leung, who helped conduct the dupilumab clinical trials contributing to its approval for EoE and receives speaking honoraria from manufacturer Regeneron/Sanofi, said that dupilumab also overcomes the challenges with elimination diets while offering relief for concomitant conditions, such as “asthma, eczema, food allergies, and seasonal allergies.”

But Dr. Falk, who also worked on the dupilumab clinical trials, said the situation is “not straightforward,” even with FDA approval.

“There are going to be significant costs with [prescribing dupilumab], because it’s a biologic,” Dr. Falk said.

Dr. Falk also pointed out that prior authorization will be required, and until more studies can be conducted, the true impact of once-weekly dosing versus daily dosing remains unknown.

“I would say [dupilumab] has the potential to improve adherence, but we need to see if that’s going to be the case or not,” Dr. Falk said.

The authors disclosed relationships with Dr. Falk Pharma, AstraZeneca, and Sanofi/Regeneron (the manufacturers of Dupixent [dupilumab]), among others. Dr. Horsley-Silva, Dr. Falk, and Dr. Leung conducted clinical trials for dupilumab on behalf of Sanofi/Regeneron, with Dr. Leung also disclosing speaking honoraria from Sanofi/Regeneron. Dr. Horsley-Silva has acted as a clinical trial site principal investigator for Allakos and Celgene/Bristol-Myers Squibb.

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

To the Editor:

In response to the challenges of the COVID-19 pandemic, iPLEDGE announced that they would accept results from home pregnancy tests and explicitly permit telemedicine.¹ Given the financial and logistical burdens associated with iPLEDGE, these changes have the potential to increase access.² However, it is unclear whether these modifications will be allowed to continue. We sought to evaluate clinician perspectives on the role of telemedicine and home pregnancy testing for iPLEDGE.

After piloting among several clinicians, a 13-question survey was distributed using the Qualtrics platform to members of the American Acne & Rosacea Society between April 14, 2021, and June 14, 2021. This survey consisted of items addressing provider practices and perspectives on telemedicine and home pregnancy testing for patients taking isotretinoin (eTable). Respondents were asked whether they think telemedicine and home pregnancy testing have improved access to care and whether they would like to continue these practices going forward. In addition, participants were asked about their concerns with home pregnancy testing and how comfortable they feel with home pregnancy testing for various contraceptive strategies (abstinence, condoms, combined oral contraceptives, and long-acting reversible contraception). This study was deemed exempt (category 2) by the University of Pennsylvania (Philadelphia, Pennsylvania) institutional review board (Protocol #844549).

Among 70 clinicians who completed the survey (response rate, 6.4%), 33 (47.1%) practiced in an academic setting. At the peak of the COVID-19 pandemic, clinicians reported using telemedicine for a median of 90% (IQR=50%–100%) of their patients on isotretinoin, and 57 respondents (81.4%) reported having patients use a home pregnancy test for iPLEDGE (Table 1). More than 75% (55/70) agreed that they would like to continue to use telemedicine for patients on isotretinoin, and more than 75% (54/70) agreed that they would like to continue using home pregnancy testing for patients outside the setting of the COVID-19 pandemic. More than 75% (54/70) agreed that telemedicine has increased access for their patients, and more than 70% (52/70) agreed that home pregnancy testing has increased access (Table 2). Clinicians agreed that they would be comfortable using home pregnancy testing for patients choosing long-acting reversible contraception (63/70 [90.0%]), combined oral contraceptives (61/69 [88.4%]), condoms (47/70 [67.1%]), or abstinence (48/70 [68.6%])(Table 3).

The most common concerns about home pregnancy testing were patient deception (39/70 [55.7%]), logistical challenges with reviewing results (19/70 [27.1%]), accuracy of the tests (19/70 [27.1%]), and patient ability to interpret tests appropriately (18/70 [25.7%]). To document testing results, 50 respondents (73.5%) would require a picture of results, 4 (5.9%) would accept a written report from the patient, and 14 (20.6%) would accept a verbal report from the patient (Table 2).

In this survey, clinicians expressed interest in continuing to use telemedicine and home pregnancy testing to care for patients with acne treated with isotretinoin. More than 75% agreed that these changes have increased access, which is notable, as several studies have identified that female and minority patients may face iPLEDGE-associated access barriers.^3,4 Continuing to allow home pregnancy testing and explicitly permitting telemedicine can enable clinicians to provide patient-centered care.²

Although clinicians felt comfortable with a variety of contraceptive strategies, particularly those with high reported effectiveness,⁵ there were concerns about deception and interpretation of test results. Future studies are needed to identify optimal workflows for home pregnancy testing and whether patients should be required to provide a photograph of the results.

This survey study is limited by the possibility of sampling and response bias due to the low response rate. Although the use of national listservs was employed to maximize the generalizability of the results, given the response rate, future studies are needed to evaluate whether these findings generalize to other settings. In addition, given iPLEDGE-associated access barriers, further research is needed to examine how changes such as telemedicine and home pregnancy testing influence both access to isotretinoin and pregnancy prevention.

Acknowledgments—We would like to thank Stacey Moore (Montclair, New Jersey) and the American Acne & Rosacea Society for their help distributing the survey.

To the Editor:

In response to the challenges of the COVID-19 pandemic, iPLEDGE announced that they would accept results from home pregnancy tests and explicitly permit telemedicine.¹ Given the financial and logistical burdens associated with iPLEDGE, these changes have the potential to increase access.² However, it is unclear whether these modifications will be allowed to continue. We sought to evaluate clinician perspectives on the role of telemedicine and home pregnancy testing for iPLEDGE.

After piloting among several clinicians, a 13-question survey was distributed using the Qualtrics platform to members of the American Acne & Rosacea Society between April 14, 2021, and June 14, 2021. This survey consisted of items addressing provider practices and perspectives on telemedicine and home pregnancy testing for patients taking isotretinoin (eTable). Respondents were asked whether they think telemedicine and home pregnancy testing have improved access to care and whether they would like to continue these practices going forward. In addition, participants were asked about their concerns with home pregnancy testing and how comfortable they feel with home pregnancy testing for various contraceptive strategies (abstinence, condoms, combined oral contraceptives, and long-acting reversible contraception). This study was deemed exempt (category 2) by the University of Pennsylvania (Philadelphia, Pennsylvania) institutional review board (Protocol #844549).

Among 70 clinicians who completed the survey (response rate, 6.4%), 33 (47.1%) practiced in an academic setting. At the peak of the COVID-19 pandemic, clinicians reported using telemedicine for a median of 90% (IQR=50%–100%) of their patients on isotretinoin, and 57 respondents (81.4%) reported having patients use a home pregnancy test for iPLEDGE (Table 1). More than 75% (55/70) agreed that they would like to continue to use telemedicine for patients on isotretinoin, and more than 75% (54/70) agreed that they would like to continue using home pregnancy testing for patients outside the setting of the COVID-19 pandemic. More than 75% (54/70) agreed that telemedicine has increased access for their patients, and more than 70% (52/70) agreed that home pregnancy testing has increased access (Table 2). Clinicians agreed that they would be comfortable using home pregnancy testing for patients choosing long-acting reversible contraception (63/70 [90.0%]), combined oral contraceptives (61/69 [88.4%]), condoms (47/70 [67.1%]), or abstinence (48/70 [68.6%])(Table 3).

The most common concerns about home pregnancy testing were patient deception (39/70 [55.7%]), logistical challenges with reviewing results (19/70 [27.1%]), accuracy of the tests (19/70 [27.1%]), and patient ability to interpret tests appropriately (18/70 [25.7%]). To document testing results, 50 respondents (73.5%) would require a picture of results, 4 (5.9%) would accept a written report from the patient, and 14 (20.6%) would accept a verbal report from the patient (Table 2).

In this survey, clinicians expressed interest in continuing to use telemedicine and home pregnancy testing to care for patients with acne treated with isotretinoin. More than 75% agreed that these changes have increased access, which is notable, as several studies have identified that female and minority patients may face iPLEDGE-associated access barriers.^3,4 Continuing to allow home pregnancy testing and explicitly permitting telemedicine can enable clinicians to provide patient-centered care.²

Although clinicians felt comfortable with a variety of contraceptive strategies, particularly those with high reported effectiveness,⁵ there were concerns about deception and interpretation of test results. Future studies are needed to identify optimal workflows for home pregnancy testing and whether patients should be required to provide a photograph of the results.

This survey study is limited by the possibility of sampling and response bias due to the low response rate. Although the use of national listservs was employed to maximize the generalizability of the results, given the response rate, future studies are needed to evaluate whether these findings generalize to other settings. In addition, given iPLEDGE-associated access barriers, further research is needed to examine how changes such as telemedicine and home pregnancy testing influence both access to isotretinoin and pregnancy prevention.

Acknowledgments—We would like to thank Stacey Moore (Montclair, New Jersey) and the American Acne & Rosacea Society for their help distributing the survey.

To the Editor:

In response to the challenges of the COVID-19 pandemic, iPLEDGE announced that they would accept results from home pregnancy tests and explicitly permit telemedicine.¹ Given the financial and logistical burdens associated with iPLEDGE, these changes have the potential to increase access.² However, it is unclear whether these modifications will be allowed to continue. We sought to evaluate clinician perspectives on the role of telemedicine and home pregnancy testing for iPLEDGE.

After piloting among several clinicians, a 13-question survey was distributed using the Qualtrics platform to members of the American Acne & Rosacea Society between April 14, 2021, and June 14, 2021. This survey consisted of items addressing provider practices and perspectives on telemedicine and home pregnancy testing for patients taking isotretinoin (eTable). Respondents were asked whether they think telemedicine and home pregnancy testing have improved access to care and whether they would like to continue these practices going forward. In addition, participants were asked about their concerns with home pregnancy testing and how comfortable they feel with home pregnancy testing for various contraceptive strategies (abstinence, condoms, combined oral contraceptives, and long-acting reversible contraception). This study was deemed exempt (category 2) by the University of Pennsylvania (Philadelphia, Pennsylvania) institutional review board (Protocol #844549).

Among 70 clinicians who completed the survey (response rate, 6.4%), 33 (47.1%) practiced in an academic setting. At the peak of the COVID-19 pandemic, clinicians reported using telemedicine for a median of 90% (IQR=50%–100%) of their patients on isotretinoin, and 57 respondents (81.4%) reported having patients use a home pregnancy test for iPLEDGE (Table 1). More than 75% (55/70) agreed that they would like to continue to use telemedicine for patients on isotretinoin, and more than 75% (54/70) agreed that they would like to continue using home pregnancy testing for patients outside the setting of the COVID-19 pandemic. More than 75% (54/70) agreed that telemedicine has increased access for their patients, and more than 70% (52/70) agreed that home pregnancy testing has increased access (Table 2). Clinicians agreed that they would be comfortable using home pregnancy testing for patients choosing long-acting reversible contraception (63/70 [90.0%]), combined oral contraceptives (61/69 [88.4%]), condoms (47/70 [67.1%]), or abstinence (48/70 [68.6%])(Table 3).

The most common concerns about home pregnancy testing were patient deception (39/70 [55.7%]), logistical challenges with reviewing results (19/70 [27.1%]), accuracy of the tests (19/70 [27.1%]), and patient ability to interpret tests appropriately (18/70 [25.7%]). To document testing results, 50 respondents (73.5%) would require a picture of results, 4 (5.9%) would accept a written report from the patient, and 14 (20.6%) would accept a verbal report from the patient (Table 2).

In this survey, clinicians expressed interest in continuing to use telemedicine and home pregnancy testing to care for patients with acne treated with isotretinoin. More than 75% agreed that these changes have increased access, which is notable, as several studies have identified that female and minority patients may face iPLEDGE-associated access barriers.^3,4 Continuing to allow home pregnancy testing and explicitly permitting telemedicine can enable clinicians to provide patient-centered care.²

Although clinicians felt comfortable with a variety of contraceptive strategies, particularly those with high reported effectiveness,⁵ there were concerns about deception and interpretation of test results. Future studies are needed to identify optimal workflows for home pregnancy testing and whether patients should be required to provide a photograph of the results.

This survey study is limited by the possibility of sampling and response bias due to the low response rate. Although the use of national listservs was employed to maximize the generalizability of the results, given the response rate, future studies are needed to evaluate whether these findings generalize to other settings. In addition, given iPLEDGE-associated access barriers, further research is needed to examine how changes such as telemedicine and home pregnancy testing influence both access to isotretinoin and pregnancy prevention.

Acknowledgments—We would like to thank Stacey Moore (Montclair, New Jersey) and the American Acne & Rosacea Society for their help distributing the survey.

In the wake of the Supreme Court’s June decision to repeal a federal right to abortion, many women will now be faced with the prospect of carrying an unwanted pregnancy to term.

One group of researchers has studied the fate of these women and their families for the last decade. Their findings show that women who were denied an abortion are worse off physically, mentally, and economically than those who underwent the procedure.

“There has been much hypothesizing about harms from abortion without considering what the consequences are when someone wants an abortion and can’t get one,” said Diana Greene Foster, PhD, professor of obstetrics and gynecology at University of California, San Francisco.

Dr. Foster leads the Turnaway Study, one of the first efforts to examine the physical and mental health effects of receiving or being denied abortions. The ongoing research also charts the economic and social outcomes of women and their families in either circumstance.

Dr. Foster and her colleagues have followed women through childbirth, examining their well-being through phone interviews months to years after the initial interviews.

The economic consequences of carrying an unwanted pregnancy are clear. Women who did not receive a wanted abortion were more likely to live under the poverty line and struggle to cover basic living expenses like food, housing, and transportation.

The physical toll is also significant.

A 2019 analysis from the Turnaway Study found that eight out of 1,132 participants died, two after delivery, during the five-year follow up period – a far greater proportion than what would be expected among women of reproductive age. The researchers also found that women who carry unwanted pregnancies have more comorbid conditions before and after delivery than other women.

Lauren J. Ralph, PhD, MPH, an epidemiologist and member of the Turnaway Study team, examined the physical well-being of women after delivering their unwanted pregnancies.

“They reported more chronic pain, more gestational hypertension, and were more likely to rate their health as fair or poor,” Dr. Ralph said. “Somewhat to our surprise, we also found that two women denied abortions died due to pregnancy-related causes. This is my biggest concern with the loss of abortion access, as all scientific evidence indicates we will see a rise in maternal deaths as a result.”

At least one preliminary study, released as a preprint and not yet peer reviewed, estimates that the number of women who will die each year from pregnancy complications will rise by 24%. For Black women, mortality could jump from 18% to 39% in every state, according to the researchers from the University of Colorado, Boulder.
 

State of denial

Regulations set in place at abortion clinics in each state individually determine who is able to obtain an abortion, dictated by a “gestational age limit” – how far along a woman is in her pregnancy from the end of her menstrual cycle. Some of the women from the Turnaway Study were unable to receive an abortion because of how far along they were. Others were granted the abortion because they were just under their state’s limit.

Before the latest Supreme Court ruling, this limit was 20 weeks in most states. Now, the cutoff can be as little as 6 weeks – before many women know they are pregnant – or zero weeks, under the most restrictive laws. 

Over 70% of women who are denied an abortion carry the pregnancy to term, according to Dr. Foster’s analysis. 

Interviews with nearly 1,000 women – in both the first and second trimester of pregnancy – in the Turnaway Study who sought abortions at 30 abortion clinics around the country revealed the main reasons for seeking the procedure were (a) not being able to afford a child; (b) the pregnancy coming at the wrong time in life; or (c) the partner involved not being suitable.

According to the U.S. Centers for Disease Control and Prevention, 59.7% of women seeking an abortion in the United States are already mothers. Having an unplanned child results in dramatically worse economic circumstances for their other children, who become nearly four times more likely to live below the poverty line than their peers. They also experience slower physical and mental development as a result of the arrival of the new sibling.

The latest efforts by states to ban abortion could make the situation much worse, said Liza Fuentes, DrPh, senior research scientist at the Guttmacher Institute. “We will need further research on what it means for women to be denied care in the context of the new restrictions,” Dr. Fuentes told this news organization. 

Researchers cannot yet predict how many women will be unable to obtain an abortion in the coming months. But John Donahue, PhD, JD, an economist and professor of law at Stanford (Calif.) University, estimated that state laws would prevent roughly one-third of the 1 million abortions per year based on 2021 figures.

Dr. Ralph and her colleagues with the Turnaway Study know that restricting access to abortions will not make the need for abortions disappear. Rather, women will be forced to travel, potentially long distances at significant cost, for the procedure or will seek medication abortion by mail through virtual clinics.

But Dr. Ralph said she’s concerned about women who live in areas where telehealth abortions are banned, or who discover their pregnancies late, as medical abortions are only recommended for women who are 10 weeks pregnant or less.

“They may look to self-source the medications online or elsewhere, potentially putting themself at legal risk,” she said. “And, as my research has shown, others may turn to self-managing an abortion with herbs, other drugs or medications, or physical methods like hitting themselves in the abdomen; with this they put themselves at both legal and potentially medical risk.”

Constance Bohon, MD, an ob.gyn. in Washington, D.C., said further research should track what happens to women if they’re forced to leave a job to care for another child.

“Many of these women live paycheck to paycheck and cannot afford the cost of an additional child,” Dr. Bohon said. “They may also need to rely on social service agencies to help them find food and housing.”

Dr. Fuentes said she hopes the Turnaway Study will inspire other researchers to examine laws that outlaw abortion and the corresponding long-term effects on women.

“From a medical and a public health standpoint, these laws are unjust,” Dr. Fuentes said in an interview. “They’re not grounded in evidence, and they incur great costs not just to pregnant people but their families and their communities as well.”

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

In the wake of the Supreme Court’s June decision to repeal a federal right to abortion, many women will now be faced with the prospect of carrying an unwanted pregnancy to term.

One group of researchers has studied the fate of these women and their families for the last decade. Their findings show that women who were denied an abortion are worse off physically, mentally, and economically than those who underwent the procedure.

“There has been much hypothesizing about harms from abortion without considering what the consequences are when someone wants an abortion and can’t get one,” said Diana Greene Foster, PhD, professor of obstetrics and gynecology at University of California, San Francisco.

Dr. Foster leads the Turnaway Study, one of the first efforts to examine the physical and mental health effects of receiving or being denied abortions. The ongoing research also charts the economic and social outcomes of women and their families in either circumstance.

Dr. Foster and her colleagues have followed women through childbirth, examining their well-being through phone interviews months to years after the initial interviews.

The economic consequences of carrying an unwanted pregnancy are clear. Women who did not receive a wanted abortion were more likely to live under the poverty line and struggle to cover basic living expenses like food, housing, and transportation.

The physical toll is also significant.

A 2019 analysis from the Turnaway Study found that eight out of 1,132 participants died, two after delivery, during the five-year follow up period – a far greater proportion than what would be expected among women of reproductive age. The researchers also found that women who carry unwanted pregnancies have more comorbid conditions before and after delivery than other women.

Lauren J. Ralph, PhD, MPH, an epidemiologist and member of the Turnaway Study team, examined the physical well-being of women after delivering their unwanted pregnancies.

“They reported more chronic pain, more gestational hypertension, and were more likely to rate their health as fair or poor,” Dr. Ralph said. “Somewhat to our surprise, we also found that two women denied abortions died due to pregnancy-related causes. This is my biggest concern with the loss of abortion access, as all scientific evidence indicates we will see a rise in maternal deaths as a result.”

At least one preliminary study, released as a preprint and not yet peer reviewed, estimates that the number of women who will die each year from pregnancy complications will rise by 24%. For Black women, mortality could jump from 18% to 39% in every state, according to the researchers from the University of Colorado, Boulder.
 

State of denial

Regulations set in place at abortion clinics in each state individually determine who is able to obtain an abortion, dictated by a “gestational age limit” – how far along a woman is in her pregnancy from the end of her menstrual cycle. Some of the women from the Turnaway Study were unable to receive an abortion because of how far along they were. Others were granted the abortion because they were just under their state’s limit.

Before the latest Supreme Court ruling, this limit was 20 weeks in most states. Now, the cutoff can be as little as 6 weeks – before many women know they are pregnant – or zero weeks, under the most restrictive laws. 

Over 70% of women who are denied an abortion carry the pregnancy to term, according to Dr. Foster’s analysis. 

Interviews with nearly 1,000 women – in both the first and second trimester of pregnancy – in the Turnaway Study who sought abortions at 30 abortion clinics around the country revealed the main reasons for seeking the procedure were (a) not being able to afford a child; (b) the pregnancy coming at the wrong time in life; or (c) the partner involved not being suitable.

According to the U.S. Centers for Disease Control and Prevention, 59.7% of women seeking an abortion in the United States are already mothers. Having an unplanned child results in dramatically worse economic circumstances for their other children, who become nearly four times more likely to live below the poverty line than their peers. They also experience slower physical and mental development as a result of the arrival of the new sibling.

The latest efforts by states to ban abortion could make the situation much worse, said Liza Fuentes, DrPh, senior research scientist at the Guttmacher Institute. “We will need further research on what it means for women to be denied care in the context of the new restrictions,” Dr. Fuentes told this news organization. 

Researchers cannot yet predict how many women will be unable to obtain an abortion in the coming months. But John Donahue, PhD, JD, an economist and professor of law at Stanford (Calif.) University, estimated that state laws would prevent roughly one-third of the 1 million abortions per year based on 2021 figures.

Dr. Ralph and her colleagues with the Turnaway Study know that restricting access to abortions will not make the need for abortions disappear. Rather, women will be forced to travel, potentially long distances at significant cost, for the procedure or will seek medication abortion by mail through virtual clinics.

But Dr. Ralph said she’s concerned about women who live in areas where telehealth abortions are banned, or who discover their pregnancies late, as medical abortions are only recommended for women who are 10 weeks pregnant or less.

“They may look to self-source the medications online or elsewhere, potentially putting themself at legal risk,” she said. “And, as my research has shown, others may turn to self-managing an abortion with herbs, other drugs or medications, or physical methods like hitting themselves in the abdomen; with this they put themselves at both legal and potentially medical risk.”

Constance Bohon, MD, an ob.gyn. in Washington, D.C., said further research should track what happens to women if they’re forced to leave a job to care for another child.

“Many of these women live paycheck to paycheck and cannot afford the cost of an additional child,” Dr. Bohon said. “They may also need to rely on social service agencies to help them find food and housing.”

Dr. Fuentes said she hopes the Turnaway Study will inspire other researchers to examine laws that outlaw abortion and the corresponding long-term effects on women.

“From a medical and a public health standpoint, these laws are unjust,” Dr. Fuentes said in an interview. “They’re not grounded in evidence, and they incur great costs not just to pregnant people but their families and their communities as well.”

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

In the wake of the Supreme Court’s June decision to repeal a federal right to abortion, many women will now be faced with the prospect of carrying an unwanted pregnancy to term.

One group of researchers has studied the fate of these women and their families for the last decade. Their findings show that women who were denied an abortion are worse off physically, mentally, and economically than those who underwent the procedure.

“There has been much hypothesizing about harms from abortion without considering what the consequences are when someone wants an abortion and can’t get one,” said Diana Greene Foster, PhD, professor of obstetrics and gynecology at University of California, San Francisco.

Dr. Foster leads the Turnaway Study, one of the first efforts to examine the physical and mental health effects of receiving or being denied abortions. The ongoing research also charts the economic and social outcomes of women and their families in either circumstance.

Dr. Foster and her colleagues have followed women through childbirth, examining their well-being through phone interviews months to years after the initial interviews.

The economic consequences of carrying an unwanted pregnancy are clear. Women who did not receive a wanted abortion were more likely to live under the poverty line and struggle to cover basic living expenses like food, housing, and transportation.

The physical toll is also significant.

A 2019 analysis from the Turnaway Study found that eight out of 1,132 participants died, two after delivery, during the five-year follow up period – a far greater proportion than what would be expected among women of reproductive age. The researchers also found that women who carry unwanted pregnancies have more comorbid conditions before and after delivery than other women.

Lauren J. Ralph, PhD, MPH, an epidemiologist and member of the Turnaway Study team, examined the physical well-being of women after delivering their unwanted pregnancies.

“They reported more chronic pain, more gestational hypertension, and were more likely to rate their health as fair or poor,” Dr. Ralph said. “Somewhat to our surprise, we also found that two women denied abortions died due to pregnancy-related causes. This is my biggest concern with the loss of abortion access, as all scientific evidence indicates we will see a rise in maternal deaths as a result.”

At least one preliminary study, released as a preprint and not yet peer reviewed, estimates that the number of women who will die each year from pregnancy complications will rise by 24%. For Black women, mortality could jump from 18% to 39% in every state, according to the researchers from the University of Colorado, Boulder.
 

State of denial

Regulations set in place at abortion clinics in each state individually determine who is able to obtain an abortion, dictated by a “gestational age limit” – how far along a woman is in her pregnancy from the end of her menstrual cycle. Some of the women from the Turnaway Study were unable to receive an abortion because of how far along they were. Others were granted the abortion because they were just under their state’s limit.

Before the latest Supreme Court ruling, this limit was 20 weeks in most states. Now, the cutoff can be as little as 6 weeks – before many women know they are pregnant – or zero weeks, under the most restrictive laws. 

Over 70% of women who are denied an abortion carry the pregnancy to term, according to Dr. Foster’s analysis. 

Interviews with nearly 1,000 women – in both the first and second trimester of pregnancy – in the Turnaway Study who sought abortions at 30 abortion clinics around the country revealed the main reasons for seeking the procedure were (a) not being able to afford a child; (b) the pregnancy coming at the wrong time in life; or (c) the partner involved not being suitable.

According to the U.S. Centers for Disease Control and Prevention, 59.7% of women seeking an abortion in the United States are already mothers. Having an unplanned child results in dramatically worse economic circumstances for their other children, who become nearly four times more likely to live below the poverty line than their peers. They also experience slower physical and mental development as a result of the arrival of the new sibling.

The latest efforts by states to ban abortion could make the situation much worse, said Liza Fuentes, DrPh, senior research scientist at the Guttmacher Institute. “We will need further research on what it means for women to be denied care in the context of the new restrictions,” Dr. Fuentes told this news organization. 

Researchers cannot yet predict how many women will be unable to obtain an abortion in the coming months. But John Donahue, PhD, JD, an economist and professor of law at Stanford (Calif.) University, estimated that state laws would prevent roughly one-third of the 1 million abortions per year based on 2021 figures.

Dr. Ralph and her colleagues with the Turnaway Study know that restricting access to abortions will not make the need for abortions disappear. Rather, women will be forced to travel, potentially long distances at significant cost, for the procedure or will seek medication abortion by mail through virtual clinics.

But Dr. Ralph said she’s concerned about women who live in areas where telehealth abortions are banned, or who discover their pregnancies late, as medical abortions are only recommended for women who are 10 weeks pregnant or less.

“They may look to self-source the medications online or elsewhere, potentially putting themself at legal risk,” she said. “And, as my research has shown, others may turn to self-managing an abortion with herbs, other drugs or medications, or physical methods like hitting themselves in the abdomen; with this they put themselves at both legal and potentially medical risk.”

Constance Bohon, MD, an ob.gyn. in Washington, D.C., said further research should track what happens to women if they’re forced to leave a job to care for another child.

“Many of these women live paycheck to paycheck and cannot afford the cost of an additional child,” Dr. Bohon said. “They may also need to rely on social service agencies to help them find food and housing.”

Dr. Fuentes said she hopes the Turnaway Study will inspire other researchers to examine laws that outlaw abortion and the corresponding long-term effects on women.

“From a medical and a public health standpoint, these laws are unjust,” Dr. Fuentes said in an interview. “They’re not grounded in evidence, and they incur great costs not just to pregnant people but their families and their communities as well.”

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

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.

“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.

“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.

Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”

He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”

“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
 

Research findings

Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
 

Reassuring results for the standard of care

Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”

“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”

Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”

He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”

“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.

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

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.

“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.

“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.

Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”

He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”

“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
 

Research findings

Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
 

Reassuring results for the standard of care

Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”

“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”

Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”

He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”

“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.

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

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.

“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.

“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.

Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”

He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”

“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
 

Research findings

Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
 

Reassuring results for the standard of care

Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”

“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”

Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”

He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”

“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.

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

The current understanding of the pathogenesis of acne includes altered keratinization, follicular obstruction, overproduction of sebum, and microbial colonization ( Cutibacterium acnes ) of the pilosebaceous unit resulting in perifollicular inflammation. ¹ A deeper dive into the hormonal and molecular drivers of acne have implicated insulin, insulinlike growth factor 1 (IGF-1), corticotropin-releasing hormone, the phosphoinositide 3 -kinase/Akt pathway, mitogen-activated protein kinase pathway, and the nuclear factor κ B pathway. ^2-4 A Western diet comprised of high glycemic index foods, carbohydrates, and dairy enhances the production of insulin and IGF-1. A downstream effect of excess insulin and IGF-1 is overactivity of the mammalian target of rapamycin complex 1 (mTORC1), a major promoter of cellular growth and proliferation that primarily is regulated through nutrient availability. ⁵ This article will review our understanding of the impact of the Western diet on acne pathogenesis and highlight the existing evidence behind the contributions of the mTORC1 pathway in this process. Although quality randomized controlled trials analyzing these effects are limited, dermatologists should understand the existing evidence supporting the potential impacts of diet on acne.

The Western Diet

Glycemic Index—To assess the impact of a high glycemic index diet on acne, Kwon et al⁶ evaluated 32 patients with mild to moderate acne and placed them on a low or high glycemic index diet for 10 weeks. The low glycemic index diet group was found to have a 70% reduction in the mean number of inflammatory acne lesions from baseline (P<.05), while the high glycemic index diet group had no significant reduction. Noninflammatory lesion counts remained statistically unchanged.⁶ Smith et al⁷ studied 43 male patients with acne on either a low glycemic index diet or a self-directed high glycemic diet that was carbohydrate dense. The low glycemic index group showed greater improvement in lesion count as well as improved insulin sensitivity at 12 weeks. Specifically, the mean lesion count (SEM) decreased by 23.5 (3.9) in the low glycemic index group and by only 12.0 (3.5) in the control group (P=.03).⁷ Observational studies also have supported this hypothesis. After adjustment, an analysis of 24,452 participants in the NutriNet-Santé cohort found significant associations between current acne and the consumption of sugary beverages (adjusted OR, 1.18; 95% CI, 1.01-1.38) and the consumption of fatty and sugary products (adjusted OR, 1.54; 95% CI, 1.09-2.16).⁸ A Cochrane review that included only 2 studies (Kwon et al⁶ and Smith et al⁷) did not find evidence to suggest a low glycemic index diet for noninflammatory lesion count reduction but did note possible benefit for a reduction in inflammatory and total lesion counts; however, Kwon et al⁶ had incomplete data.⁹

Dairy—A large retrospective study including 47,355 nurses noted the frequency of milk intake was significantly associated with increased prevalence of acne in adolescence (prevalence ratio, 1.22; 95% CI, 1.03-1.44; P=.002).¹⁰ A 2019 meta-analysis further suggested a significant relationship between acne and milk in highest vs lowest intake groups (OR, 1.48; 95% CI, 1.31-1.66) with no significant heterogeneity between the studies (I²=23.6%, P=.24 for heterogeneity), as well as a positive relationship between the highest vs lowest intake of low-fat milk (OR, 1.25; 95% CI, 1.10-1.43) and skim milk (OR, 1.82; 95% CI, 1.34-2.47). In this meta-analysis, yogurt and cheese consumption were not significantly associated with acne (OR, 0.90; 95% CI, 0.73-1.11).¹¹ One non–evidence-based explanation for this may be that fermented dairy products have different biological actions. Pasteurized milk allows microRNAs that directly activate mTORC1 to persist, whereas the bacteria present in the fermentation process may augment this.¹² A separate meta-analysis from 2018 did find that yogurt consumption was positively associated with acne (OR, 1.36; 95% CI, 1.05-1.77; P=.022), highlighting the need for larger, more rigorous studies on this topic.¹³

Insulin and IGF-1—As reviewed above, acne has been considered a disease of Western society, with the Western diet at the center of this association.¹⁴ A typical Western diet consists of high glycemic index foods, carbohydrates, and dairy, all of which enhance the production of insulin and IGF-1. Insulin levels increase secondary to high blood glucose and to a lesser degree by protein intake.¹⁵ Insulinlike growth factor 1 production is most influenced by age and peaks during puberty; however, high protein diets also increase liver IGF-1 production and release.¹⁶ When present in excess, insulin can function as a growth factor. Insulin exerts its anabolic effects through the IGF-1 pathway; however, insulin and IGF-1 are produced in response to different signals.¹⁷ Endocrine production of IGF-1 represents 70% of blood levels, peaks at puberty, and rapidly declines in the third decade of life.¹⁸ Insulin is produced by the pancreas, and levels correspond to lifestyle and genetically induced insulin resistance.¹⁹

Adolescents have elevated levels of IGF-1 as a major driver of puberty-associated growth.²⁰ Despite the natural decrease in IGF-1 following puberty, acne persists in many patients and can even develop for the first time in adulthood in a subset of patients. A study of 40 acne patients and 20 controls found that patients with acne who consumed a high glycemic–load diet was significantly higher than the number of controls consuming a similar diet (P=.008). Additionally, significantly higher levels of mean (SD) serum IGF-1 on quantitative sandwich enzyme-linked immunosorbent assay in acne patients vs controls (543.2 [174.7] ng/mL vs 316.9 [95.7] ng/mL; P<.001) was identified, and these levels correlated significantly with high glycemic–load diet consumption.²¹ In another study, Kartal et al²² found that basal and fasting insulin levels and homeostasis model assessment scores evaluating for insulin resistance were significantly higher in 36 women compared with 24 age/sex-matched controls (P<.05). This finding remained significant even after excluding women with hyperandrogenemia (P<.05).²²

Highlighting the importance of IGF-1 in the pathogenesis of acne, patients with genetic disorders characterized by IGF-1 deficiency, such as Laron syndrome, do not develop acne despite having a functional androgen receptor. Treatment with IGF-1 in these patients induces acne, further supporting the role of IGF-1 in the pathogenesis of this condition.²³

The mTORC1 Pathway

Comprised of mTOR in addition to other proteins, mTORC1 is a nutrient-sensitive regulator of cellular growth, proliferation, lipid synthesis, and protein translation.⁵ Increased activity of mTORC1 has been described in diabetes, neurodegenerative disease, and cancer,^14,24 while decreased activity may promote longevity.²⁵ Regulation of mTORC1 occurs through several mechanisms. Growth factors such as insulin and IGF-1 promote mTORC1 activation through the PI3K/Akt pathway. Several amino acids—specifically branched chain amino acids such as alanine, arginine, asparagine, glutamine, histidine, leucine, methionine, serine, threonine, and valine—also can activate mTORC1 independently.²⁶ Excess glucose leads to decreased adenosine monophosphate–activated protein kinase and increased activity of mTORC1, which occurs separately from insulin or IGF-1.²⁷ Starvation blocks mTORC1 via increased adenosine monophosphate–activated protein kinase and starvation-induced hypoxia.^26,28 To activate mTORC1, both the IGF-1 or insulin signal and amino acid excess must be present.²⁹ Although not studied in acne, altering the dietary protein content in obese mice has been shown to perturb the mTORC1 pathway, leading to pathologic changes in the mTORC1-autophagy signaling axis, increased amino acid release into the blood, and an acute elevation in mTORC1 signaling.³⁰

Another major regulator of mTORC1 is Forkhead box protein O1 (FOXO1), which is a transcription factor that regulates mTORC1 through sestrin 3.^31,32 Sestrin 3 is a stress-induced protein that helps regulate blood glucose and promote insulin sensitivity.³³ When FOXO1 is translocated to the cell nucleus, it upregulates the expression of sestrin 3, resulting in mTORC1 inhibition.^31,32 Insulin, IGF-1, and nutrient excess lead to FOXO1 translocation to the cell cytoplasm where it can no longer mitigate mTORC1 activity, while the fasted state leads to translocation to the nucleus.³⁴ A single study evaluated the association between FOXO1, mTORC1, a high glycemic–load diet, and acne development. Immunohistochemical detection of mTORC1 assessed by digital image analysis revealed significantly greater expression in inflamed pilosebaceous units found in acne patients (P<.001). Immunohistochemical cytoplasmic expression of FOXO1 and mTOR (used as a proxy for mTORC1) was significantly higher in patients on a high glycemic–load diet (P=.021 and P=.009, respectively) as well as in patients with more severe forms of acne (P=.005 and P=.015, respectively) and elevated IGF-1 levels (P=.004 and P=.003, respectively).²¹

mTORC1 contributes to the proliferation of keratinocytes and excess sebum production, both independently and through androgen-mediated processes.^35-40 Insulinlike growth factor 1 binding the IGF-1 receptor leads to proliferation of keratinocytes lining the sebaceous gland and hair follicle in vivo.³⁵ In mice with epidermis-specific deletion of mTOR, keratinocyte proliferation was decreased and hair follicles were diminished both in number and development. Genetic loss of mTOR in the epidermis led to attenuated signaling pathways of mTORC1 and mTORC2.³⁶

Androgen function is augmented by mTORC1, FOXO1, and IGF-1 through several mechanisms, which may partially explain the hormonal relationship to acne. Androgens increase IGF-1 within the hair follicle.³⁷ In prostate cancer cells, IGF-1 then facilitates movement of FOXO1 to the cytoplasm, preventing it from blocking mTORC1. This effective inactivation of FOXO1 thus further augments the impact of androgens by both allowing unchecked mTORC1 pathway activity and increasing translocation of the androgen receptor (AR) to the nucleus where it exerts its effects.³⁸ Interestingly, genetic polymorphisms of the AR have been shown to cause variable affinity of FOXO1 for the AR; specifically, shorter CAG (cytosine, adenine, guanine) repeat length may lead to decreased FOXO1 binding and is associated with an increased risk for acne.^41-43 In addition to its effects on the hair follicle, IGF-1 stimulates production of testosterone and dehydroepiandrosterone as well as activates 5α-reductase, leading to higher dihydrotestosterone levels, which activate the AR with higher affinity than testosterone.⁴⁴ In some tissues, androgens help regulate the mTORC1 pathway through positive feedback loops.^45,46 At this time, we do not know if this occurs in the pathogenesis of acne.

Isotretinoin is the treatment of choice for refractory acne. It has been hypothesized that isotretinoin induces sebocyte apoptosis via the upregulation of FOXO transcription factors and p53.⁴⁷ Elevated levels of nuclear FOXO1 have been found in the sebaceous glands of patients following initiation of treatment with isotretinoin and are hypothesized to play a major role in the drug’s effectiveness. Specifically, biopsies from 14 acne patients before and after 6 weeks of isotretinoin therapy were analyzed with immunohistochemical staining and found to have a significantly improved nuclear to cytoplasmic ratio of nonphosphorylated FOXO1 (P<.001).⁴⁷

Practical Recommendations

Given the available evidence, it is important for dermatologists to address dietary recommendations in acne patients. Although large randomized controlled trials on diet and acne severity are challenging to conduct in this population, the existing literature suggests that patients should avoid high glycemic index simple sugars and processed grains, and patients should focus on eating more complex carbohydrates in the form of legumes, vegetables, fruits, and tubers.^6-8 With regard to dairy, milk (especially skim) has been associated with increased risks for acne.^11,13 Fermented dairy products may have less impact on acne severity and include cheese, yogurt (unsweetened to keep glycemic index low), and sour cream.¹² Additionally, dermatologists can consider evaluating acne patients for insulin resistance with a hemoglobin A_1c or oral glucose tolerance test; however, these are not perfect markers of insulin sensitivity. This should be considered in patients with clinical features suggesting metabolic derangement such as acanthosis nigricans; elevated nonfasting triglycerides; or symptoms of polycystic ovarian syndrome, which include irregular menstruation, hirsutism, and early-onset androgenetic alopecia (also an independent sign of insulin resistance in men).^48-51

The current understanding of the pathogenesis of acne includes altered keratinization, follicular obstruction, overproduction of sebum, and microbial colonization ( Cutibacterium acnes ) of the pilosebaceous unit resulting in perifollicular inflammation. ¹ A deeper dive into the hormonal and molecular drivers of acne have implicated insulin, insulinlike growth factor 1 (IGF-1), corticotropin-releasing hormone, the phosphoinositide 3 -kinase/Akt pathway, mitogen-activated protein kinase pathway, and the nuclear factor κ B pathway. ^2-4 A Western diet comprised of high glycemic index foods, carbohydrates, and dairy enhances the production of insulin and IGF-1. A downstream effect of excess insulin and IGF-1 is overactivity of the mammalian target of rapamycin complex 1 (mTORC1), a major promoter of cellular growth and proliferation that primarily is regulated through nutrient availability. ⁵ This article will review our understanding of the impact of the Western diet on acne pathogenesis and highlight the existing evidence behind the contributions of the mTORC1 pathway in this process. Although quality randomized controlled trials analyzing these effects are limited, dermatologists should understand the existing evidence supporting the potential impacts of diet on acne.

The Western Diet

Glycemic Index—To assess the impact of a high glycemic index diet on acne, Kwon et al⁶ evaluated 32 patients with mild to moderate acne and placed them on a low or high glycemic index diet for 10 weeks. The low glycemic index diet group was found to have a 70% reduction in the mean number of inflammatory acne lesions from baseline (P<.05), while the high glycemic index diet group had no significant reduction. Noninflammatory lesion counts remained statistically unchanged.⁶ Smith et al⁷ studied 43 male patients with acne on either a low glycemic index diet or a self-directed high glycemic diet that was carbohydrate dense. The low glycemic index group showed greater improvement in lesion count as well as improved insulin sensitivity at 12 weeks. Specifically, the mean lesion count (SEM) decreased by 23.5 (3.9) in the low glycemic index group and by only 12.0 (3.5) in the control group (P=.03).⁷ Observational studies also have supported this hypothesis. After adjustment, an analysis of 24,452 participants in the NutriNet-Santé cohort found significant associations between current acne and the consumption of sugary beverages (adjusted OR, 1.18; 95% CI, 1.01-1.38) and the consumption of fatty and sugary products (adjusted OR, 1.54; 95% CI, 1.09-2.16).⁸ A Cochrane review that included only 2 studies (Kwon et al⁶ and Smith et al⁷) did not find evidence to suggest a low glycemic index diet for noninflammatory lesion count reduction but did note possible benefit for a reduction in inflammatory and total lesion counts; however, Kwon et al⁶ had incomplete data.⁹

Dairy—A large retrospective study including 47,355 nurses noted the frequency of milk intake was significantly associated with increased prevalence of acne in adolescence (prevalence ratio, 1.22; 95% CI, 1.03-1.44; P=.002).¹⁰ A 2019 meta-analysis further suggested a significant relationship between acne and milk in highest vs lowest intake groups (OR, 1.48; 95% CI, 1.31-1.66) with no significant heterogeneity between the studies (I²=23.6%, P=.24 for heterogeneity), as well as a positive relationship between the highest vs lowest intake of low-fat milk (OR, 1.25; 95% CI, 1.10-1.43) and skim milk (OR, 1.82; 95% CI, 1.34-2.47). In this meta-analysis, yogurt and cheese consumption were not significantly associated with acne (OR, 0.90; 95% CI, 0.73-1.11).¹¹ One non–evidence-based explanation for this may be that fermented dairy products have different biological actions. Pasteurized milk allows microRNAs that directly activate mTORC1 to persist, whereas the bacteria present in the fermentation process may augment this.¹² A separate meta-analysis from 2018 did find that yogurt consumption was positively associated with acne (OR, 1.36; 95% CI, 1.05-1.77; P=.022), highlighting the need for larger, more rigorous studies on this topic.¹³

Insulin and IGF-1—As reviewed above, acne has been considered a disease of Western society, with the Western diet at the center of this association.¹⁴ A typical Western diet consists of high glycemic index foods, carbohydrates, and dairy, all of which enhance the production of insulin and IGF-1. Insulin levels increase secondary to high blood glucose and to a lesser degree by protein intake.¹⁵ Insulinlike growth factor 1 production is most influenced by age and peaks during puberty; however, high protein diets also increase liver IGF-1 production and release.¹⁶ When present in excess, insulin can function as a growth factor. Insulin exerts its anabolic effects through the IGF-1 pathway; however, insulin and IGF-1 are produced in response to different signals.¹⁷ Endocrine production of IGF-1 represents 70% of blood levels, peaks at puberty, and rapidly declines in the third decade of life.¹⁸ Insulin is produced by the pancreas, and levels correspond to lifestyle and genetically induced insulin resistance.¹⁹

Adolescents have elevated levels of IGF-1 as a major driver of puberty-associated growth.²⁰ Despite the natural decrease in IGF-1 following puberty, acne persists in many patients and can even develop for the first time in adulthood in a subset of patients. A study of 40 acne patients and 20 controls found that patients with acne who consumed a high glycemic–load diet was significantly higher than the number of controls consuming a similar diet (P=.008). Additionally, significantly higher levels of mean (SD) serum IGF-1 on quantitative sandwich enzyme-linked immunosorbent assay in acne patients vs controls (543.2 [174.7] ng/mL vs 316.9 [95.7] ng/mL; P<.001) was identified, and these levels correlated significantly with high glycemic–load diet consumption.²¹ In another study, Kartal et al²² found that basal and fasting insulin levels and homeostasis model assessment scores evaluating for insulin resistance were significantly higher in 36 women compared with 24 age/sex-matched controls (P<.05). This finding remained significant even after excluding women with hyperandrogenemia (P<.05).²²

Highlighting the importance of IGF-1 in the pathogenesis of acne, patients with genetic disorders characterized by IGF-1 deficiency, such as Laron syndrome, do not develop acne despite having a functional androgen receptor. Treatment with IGF-1 in these patients induces acne, further supporting the role of IGF-1 in the pathogenesis of this condition.²³

The mTORC1 Pathway

Comprised of mTOR in addition to other proteins, mTORC1 is a nutrient-sensitive regulator of cellular growth, proliferation, lipid synthesis, and protein translation.⁵ Increased activity of mTORC1 has been described in diabetes, neurodegenerative disease, and cancer,^14,24 while decreased activity may promote longevity.²⁵ Regulation of mTORC1 occurs through several mechanisms. Growth factors such as insulin and IGF-1 promote mTORC1 activation through the PI3K/Akt pathway. Several amino acids—specifically branched chain amino acids such as alanine, arginine, asparagine, glutamine, histidine, leucine, methionine, serine, threonine, and valine—also can activate mTORC1 independently.²⁶ Excess glucose leads to decreased adenosine monophosphate–activated protein kinase and increased activity of mTORC1, which occurs separately from insulin or IGF-1.²⁷ Starvation blocks mTORC1 via increased adenosine monophosphate–activated protein kinase and starvation-induced hypoxia.^26,28 To activate mTORC1, both the IGF-1 or insulin signal and amino acid excess must be present.²⁹ Although not studied in acne, altering the dietary protein content in obese mice has been shown to perturb the mTORC1 pathway, leading to pathologic changes in the mTORC1-autophagy signaling axis, increased amino acid release into the blood, and an acute elevation in mTORC1 signaling.³⁰

Another major regulator of mTORC1 is Forkhead box protein O1 (FOXO1), which is a transcription factor that regulates mTORC1 through sestrin 3.^31,32 Sestrin 3 is a stress-induced protein that helps regulate blood glucose and promote insulin sensitivity.³³ When FOXO1 is translocated to the cell nucleus, it upregulates the expression of sestrin 3, resulting in mTORC1 inhibition.^31,32 Insulin, IGF-1, and nutrient excess lead to FOXO1 translocation to the cell cytoplasm where it can no longer mitigate mTORC1 activity, while the fasted state leads to translocation to the nucleus.³⁴ A single study evaluated the association between FOXO1, mTORC1, a high glycemic–load diet, and acne development. Immunohistochemical detection of mTORC1 assessed by digital image analysis revealed significantly greater expression in inflamed pilosebaceous units found in acne patients (P<.001). Immunohistochemical cytoplasmic expression of FOXO1 and mTOR (used as a proxy for mTORC1) was significantly higher in patients on a high glycemic–load diet (P=.021 and P=.009, respectively) as well as in patients with more severe forms of acne (P=.005 and P=.015, respectively) and elevated IGF-1 levels (P=.004 and P=.003, respectively).²¹

mTORC1 contributes to the proliferation of keratinocytes and excess sebum production, both independently and through androgen-mediated processes.^35-40 Insulinlike growth factor 1 binding the IGF-1 receptor leads to proliferation of keratinocytes lining the sebaceous gland and hair follicle in vivo.³⁵ In mice with epidermis-specific deletion of mTOR, keratinocyte proliferation was decreased and hair follicles were diminished both in number and development. Genetic loss of mTOR in the epidermis led to attenuated signaling pathways of mTORC1 and mTORC2.³⁶

Androgen function is augmented by mTORC1, FOXO1, and IGF-1 through several mechanisms, which may partially explain the hormonal relationship to acne. Androgens increase IGF-1 within the hair follicle.³⁷ In prostate cancer cells, IGF-1 then facilitates movement of FOXO1 to the cytoplasm, preventing it from blocking mTORC1. This effective inactivation of FOXO1 thus further augments the impact of androgens by both allowing unchecked mTORC1 pathway activity and increasing translocation of the androgen receptor (AR) to the nucleus where it exerts its effects.³⁸ Interestingly, genetic polymorphisms of the AR have been shown to cause variable affinity of FOXO1 for the AR; specifically, shorter CAG (cytosine, adenine, guanine) repeat length may lead to decreased FOXO1 binding and is associated with an increased risk for acne.^41-43 In addition to its effects on the hair follicle, IGF-1 stimulates production of testosterone and dehydroepiandrosterone as well as activates 5α-reductase, leading to higher dihydrotestosterone levels, which activate the AR with higher affinity than testosterone.⁴⁴ In some tissues, androgens help regulate the mTORC1 pathway through positive feedback loops.^45,46 At this time, we do not know if this occurs in the pathogenesis of acne.

Isotretinoin is the treatment of choice for refractory acne. It has been hypothesized that isotretinoin induces sebocyte apoptosis via the upregulation of FOXO transcription factors and p53.⁴⁷ Elevated levels of nuclear FOXO1 have been found in the sebaceous glands of patients following initiation of treatment with isotretinoin and are hypothesized to play a major role in the drug’s effectiveness. Specifically, biopsies from 14 acne patients before and after 6 weeks of isotretinoin therapy were analyzed with immunohistochemical staining and found to have a significantly improved nuclear to cytoplasmic ratio of nonphosphorylated FOXO1 (P<.001).⁴⁷

Practical Recommendations

Given the available evidence, it is important for dermatologists to address dietary recommendations in acne patients. Although large randomized controlled trials on diet and acne severity are challenging to conduct in this population, the existing literature suggests that patients should avoid high glycemic index simple sugars and processed grains, and patients should focus on eating more complex carbohydrates in the form of legumes, vegetables, fruits, and tubers.^6-8 With regard to dairy, milk (especially skim) has been associated with increased risks for acne.^11,13 Fermented dairy products may have less impact on acne severity and include cheese, yogurt (unsweetened to keep glycemic index low), and sour cream.¹² Additionally, dermatologists can consider evaluating acne patients for insulin resistance with a hemoglobin A_1c or oral glucose tolerance test; however, these are not perfect markers of insulin sensitivity. This should be considered in patients with clinical features suggesting metabolic derangement such as acanthosis nigricans; elevated nonfasting triglycerides; or symptoms of polycystic ovarian syndrome, which include irregular menstruation, hirsutism, and early-onset androgenetic alopecia (also an independent sign of insulin resistance in men).^48-51

The current understanding of the pathogenesis of acne includes altered keratinization, follicular obstruction, overproduction of sebum, and microbial colonization ( Cutibacterium acnes ) of the pilosebaceous unit resulting in perifollicular inflammation. ¹ A deeper dive into the hormonal and molecular drivers of acne have implicated insulin, insulinlike growth factor 1 (IGF-1), corticotropin-releasing hormone, the phosphoinositide 3 -kinase/Akt pathway, mitogen-activated protein kinase pathway, and the nuclear factor κ B pathway. ^2-4 A Western diet comprised of high glycemic index foods, carbohydrates, and dairy enhances the production of insulin and IGF-1. A downstream effect of excess insulin and IGF-1 is overactivity of the mammalian target of rapamycin complex 1 (mTORC1), a major promoter of cellular growth and proliferation that primarily is regulated through nutrient availability. ⁵ This article will review our understanding of the impact of the Western diet on acne pathogenesis and highlight the existing evidence behind the contributions of the mTORC1 pathway in this process. Although quality randomized controlled trials analyzing these effects are limited, dermatologists should understand the existing evidence supporting the potential impacts of diet on acne.

The Western Diet

Glycemic Index—To assess the impact of a high glycemic index diet on acne, Kwon et al⁶ evaluated 32 patients with mild to moderate acne and placed them on a low or high glycemic index diet for 10 weeks. The low glycemic index diet group was found to have a 70% reduction in the mean number of inflammatory acne lesions from baseline (P<.05), while the high glycemic index diet group had no significant reduction. Noninflammatory lesion counts remained statistically unchanged.⁶ Smith et al⁷ studied 43 male patients with acne on either a low glycemic index diet or a self-directed high glycemic diet that was carbohydrate dense. The low glycemic index group showed greater improvement in lesion count as well as improved insulin sensitivity at 12 weeks. Specifically, the mean lesion count (SEM) decreased by 23.5 (3.9) in the low glycemic index group and by only 12.0 (3.5) in the control group (P=.03).⁷ Observational studies also have supported this hypothesis. After adjustment, an analysis of 24,452 participants in the NutriNet-Santé cohort found significant associations between current acne and the consumption of sugary beverages (adjusted OR, 1.18; 95% CI, 1.01-1.38) and the consumption of fatty and sugary products (adjusted OR, 1.54; 95% CI, 1.09-2.16).⁸ A Cochrane review that included only 2 studies (Kwon et al⁶ and Smith et al⁷) did not find evidence to suggest a low glycemic index diet for noninflammatory lesion count reduction but did note possible benefit for a reduction in inflammatory and total lesion counts; however, Kwon et al⁶ had incomplete data.⁹

Dairy—A large retrospective study including 47,355 nurses noted the frequency of milk intake was significantly associated with increased prevalence of acne in adolescence (prevalence ratio, 1.22; 95% CI, 1.03-1.44; P=.002).¹⁰ A 2019 meta-analysis further suggested a significant relationship between acne and milk in highest vs lowest intake groups (OR, 1.48; 95% CI, 1.31-1.66) with no significant heterogeneity between the studies (I²=23.6%, P=.24 for heterogeneity), as well as a positive relationship between the highest vs lowest intake of low-fat milk (OR, 1.25; 95% CI, 1.10-1.43) and skim milk (OR, 1.82; 95% CI, 1.34-2.47). In this meta-analysis, yogurt and cheese consumption were not significantly associated with acne (OR, 0.90; 95% CI, 0.73-1.11).¹¹ One non–evidence-based explanation for this may be that fermented dairy products have different biological actions. Pasteurized milk allows microRNAs that directly activate mTORC1 to persist, whereas the bacteria present in the fermentation process may augment this.¹² A separate meta-analysis from 2018 did find that yogurt consumption was positively associated with acne (OR, 1.36; 95% CI, 1.05-1.77; P=.022), highlighting the need for larger, more rigorous studies on this topic.¹³

Insulin and IGF-1—As reviewed above, acne has been considered a disease of Western society, with the Western diet at the center of this association.¹⁴ A typical Western diet consists of high glycemic index foods, carbohydrates, and dairy, all of which enhance the production of insulin and IGF-1. Insulin levels increase secondary to high blood glucose and to a lesser degree by protein intake.¹⁵ Insulinlike growth factor 1 production is most influenced by age and peaks during puberty; however, high protein diets also increase liver IGF-1 production and release.¹⁶ When present in excess, insulin can function as a growth factor. Insulin exerts its anabolic effects through the IGF-1 pathway; however, insulin and IGF-1 are produced in response to different signals.¹⁷ Endocrine production of IGF-1 represents 70% of blood levels, peaks at puberty, and rapidly declines in the third decade of life.¹⁸ Insulin is produced by the pancreas, and levels correspond to lifestyle and genetically induced insulin resistance.¹⁹

Adolescents have elevated levels of IGF-1 as a major driver of puberty-associated growth.²⁰ Despite the natural decrease in IGF-1 following puberty, acne persists in many patients and can even develop for the first time in adulthood in a subset of patients. A study of 40 acne patients and 20 controls found that patients with acne who consumed a high glycemic–load diet was significantly higher than the number of controls consuming a similar diet (P=.008). Additionally, significantly higher levels of mean (SD) serum IGF-1 on quantitative sandwich enzyme-linked immunosorbent assay in acne patients vs controls (543.2 [174.7] ng/mL vs 316.9 [95.7] ng/mL; P<.001) was identified, and these levels correlated significantly with high glycemic–load diet consumption.²¹ In another study, Kartal et al²² found that basal and fasting insulin levels and homeostasis model assessment scores evaluating for insulin resistance were significantly higher in 36 women compared with 24 age/sex-matched controls (P<.05). This finding remained significant even after excluding women with hyperandrogenemia (P<.05).²²

Highlighting the importance of IGF-1 in the pathogenesis of acne, patients with genetic disorders characterized by IGF-1 deficiency, such as Laron syndrome, do not develop acne despite having a functional androgen receptor. Treatment with IGF-1 in these patients induces acne, further supporting the role of IGF-1 in the pathogenesis of this condition.²³

The mTORC1 Pathway

Comprised of mTOR in addition to other proteins, mTORC1 is a nutrient-sensitive regulator of cellular growth, proliferation, lipid synthesis, and protein translation.⁵ Increased activity of mTORC1 has been described in diabetes, neurodegenerative disease, and cancer,^14,24 while decreased activity may promote longevity.²⁵ Regulation of mTORC1 occurs through several mechanisms. Growth factors such as insulin and IGF-1 promote mTORC1 activation through the PI3K/Akt pathway. Several amino acids—specifically branched chain amino acids such as alanine, arginine, asparagine, glutamine, histidine, leucine, methionine, serine, threonine, and valine—also can activate mTORC1 independently.²⁶ Excess glucose leads to decreased adenosine monophosphate–activated protein kinase and increased activity of mTORC1, which occurs separately from insulin or IGF-1.²⁷ Starvation blocks mTORC1 via increased adenosine monophosphate–activated protein kinase and starvation-induced hypoxia.^26,28 To activate mTORC1, both the IGF-1 or insulin signal and amino acid excess must be present.²⁹ Although not studied in acne, altering the dietary protein content in obese mice has been shown to perturb the mTORC1 pathway, leading to pathologic changes in the mTORC1-autophagy signaling axis, increased amino acid release into the blood, and an acute elevation in mTORC1 signaling.³⁰

Another major regulator of mTORC1 is Forkhead box protein O1 (FOXO1), which is a transcription factor that regulates mTORC1 through sestrin 3.^31,32 Sestrin 3 is a stress-induced protein that helps regulate blood glucose and promote insulin sensitivity.³³ When FOXO1 is translocated to the cell nucleus, it upregulates the expression of sestrin 3, resulting in mTORC1 inhibition.^31,32 Insulin, IGF-1, and nutrient excess lead to FOXO1 translocation to the cell cytoplasm where it can no longer mitigate mTORC1 activity, while the fasted state leads to translocation to the nucleus.³⁴ A single study evaluated the association between FOXO1, mTORC1, a high glycemic–load diet, and acne development. Immunohistochemical detection of mTORC1 assessed by digital image analysis revealed significantly greater expression in inflamed pilosebaceous units found in acne patients (P<.001). Immunohistochemical cytoplasmic expression of FOXO1 and mTOR (used as a proxy for mTORC1) was significantly higher in patients on a high glycemic–load diet (P=.021 and P=.009, respectively) as well as in patients with more severe forms of acne (P=.005 and P=.015, respectively) and elevated IGF-1 levels (P=.004 and P=.003, respectively).²¹

mTORC1 contributes to the proliferation of keratinocytes and excess sebum production, both independently and through androgen-mediated processes.^35-40 Insulinlike growth factor 1 binding the IGF-1 receptor leads to proliferation of keratinocytes lining the sebaceous gland and hair follicle in vivo.³⁵ In mice with epidermis-specific deletion of mTOR, keratinocyte proliferation was decreased and hair follicles were diminished both in number and development. Genetic loss of mTOR in the epidermis led to attenuated signaling pathways of mTORC1 and mTORC2.³⁶

Androgen function is augmented by mTORC1, FOXO1, and IGF-1 through several mechanisms, which may partially explain the hormonal relationship to acne. Androgens increase IGF-1 within the hair follicle.³⁷ In prostate cancer cells, IGF-1 then facilitates movement of FOXO1 to the cytoplasm, preventing it from blocking mTORC1. This effective inactivation of FOXO1 thus further augments the impact of androgens by both allowing unchecked mTORC1 pathway activity and increasing translocation of the androgen receptor (AR) to the nucleus where it exerts its effects.³⁸ Interestingly, genetic polymorphisms of the AR have been shown to cause variable affinity of FOXO1 for the AR; specifically, shorter CAG (cytosine, adenine, guanine) repeat length may lead to decreased FOXO1 binding and is associated with an increased risk for acne.^41-43 In addition to its effects on the hair follicle, IGF-1 stimulates production of testosterone and dehydroepiandrosterone as well as activates 5α-reductase, leading to higher dihydrotestosterone levels, which activate the AR with higher affinity than testosterone.⁴⁴ In some tissues, androgens help regulate the mTORC1 pathway through positive feedback loops.^45,46 At this time, we do not know if this occurs in the pathogenesis of acne.

Isotretinoin is the treatment of choice for refractory acne. It has been hypothesized that isotretinoin induces sebocyte apoptosis via the upregulation of FOXO transcription factors and p53.⁴⁷ Elevated levels of nuclear FOXO1 have been found in the sebaceous glands of patients following initiation of treatment with isotretinoin and are hypothesized to play a major role in the drug’s effectiveness. Specifically, biopsies from 14 acne patients before and after 6 weeks of isotretinoin therapy were analyzed with immunohistochemical staining and found to have a significantly improved nuclear to cytoplasmic ratio of nonphosphorylated FOXO1 (P<.001).⁴⁷

Practical Recommendations

Given the available evidence, it is important for dermatologists to address dietary recommendations in acne patients. Although large randomized controlled trials on diet and acne severity are challenging to conduct in this population, the existing literature suggests that patients should avoid high glycemic index simple sugars and processed grains, and patients should focus on eating more complex carbohydrates in the form of legumes, vegetables, fruits, and tubers.^6-8 With regard to dairy, milk (especially skim) has been associated with increased risks for acne.^11,13 Fermented dairy products may have less impact on acne severity and include cheese, yogurt (unsweetened to keep glycemic index low), and sour cream.¹² Additionally, dermatologists can consider evaluating acne patients for insulin resistance with a hemoglobin A_1c or oral glucose tolerance test; however, these are not perfect markers of insulin sensitivity. This should be considered in patients with clinical features suggesting metabolic derangement such as acanthosis nigricans; elevated nonfasting triglycerides; or symptoms of polycystic ovarian syndrome, which include irregular menstruation, hirsutism, and early-onset androgenetic alopecia (also an independent sign of insulin resistance in men).^48-51