Dermatology

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Certain opioids are proving to be effective in treating a variety of itch conditions, according to Brian S. Kim, MD.

“We know that opioids or opiates do cause itch in a significant number of patients,” Dr. Kim, a dermatologist who is codirector of the Center for the Study of Itch & Sensory Disorders at Washington University, St. Louis, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “It’s thought to do this by way of acting as a pruritogen at times and stimulating sensory neurons [that] then activate the itch cascade. But it’s also been well known that endogenous kappa opioids can activate sensory neurons that can then suppress itch and gate out signals from these opiates, but perhaps other pruritogens as well.”

Multiple drugs differentially target kappa-opioid receptor (KOR) and mu-opioid receptor (MOR) pathways, he continued. For example, oral naltrexone is a MOR antagonist, oral nalfurafine and intravenous difelikefalin are KOR agonists, while intranasal butorphanol and oral nalbuphine have a dual mechanism.

Difelikefalin is the first Food and Drug Administration–approved treatment for uremic pruritus associated with dialysis, approved in August 2021 for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis; it is administered intravenously. During the 2021 annual congress of the European Academy of Dermatology and Venereology, Dr. Kim and colleagues presented findings from a phase 2 trial of 401 people with atopic dermatitis (AD) and moderate to severe pruritus, who were randomized to receive oral difelikefalin at a dose of 0.25 mg, 0.5 mg, or 1.0 mg, or placebo over a 12-week treatment period. The primary endpoint, change from baseline in Itch Numerical Rating Scale score, was not met in any of the difelikefalin dose groups in the overall study population, but patients with a body surface area of less than 10% experienced a significant improvement in itch at week 12 in the combined difelikefalin dose group in (P = .039). A significant reduction in itch with difelikefalin was seen in this group of patients with itch-dominant AD, as early as the second day of treatment.

In another trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg, 60 mg, or placebo and treated for 8 weeks. The researchers found that nalbuphine 120 mg significantly reduced the itching intensity. Specifically, from a baseline numerical rate scale (NRS) of 6.9, the mean NRS declined by 3.5 and by 2.8 in the nalbuphine 120-mg and the placebo groups, respectively (P = .017).

In a separate, unpublished multicenter, randomized, phase 2/3 trial, researchers evaluated the safety and antipruritic efficacy of nalbuphine extended-release tablets dosed twice daily at 90 mg and 180 mg in 62 patients in the United States and Europe. The proportion of patients in the nalbuphine 180-mg arm who met 50% responder criteria at week 10 or last observed visit approached statistical significance (P = .083), and this arm met statistical significance for patients who completed treatment (P = .028).

Dr. Kim disclosed that he has served as a consultant for AbbVie, AstraZeneca, Cara Therapeutics, Galderma, GlaxoSmithKline, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, Trevi Therapeutics. He also has conducted contracted research for Cara Therapeutics and LEO Pharma.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

Certain opioids are proving to be effective in treating a variety of itch conditions, according to Brian S. Kim, MD.

“We know that opioids or opiates do cause itch in a significant number of patients,” Dr. Kim, a dermatologist who is codirector of the Center for the Study of Itch & Sensory Disorders at Washington University, St. Louis, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “It’s thought to do this by way of acting as a pruritogen at times and stimulating sensory neurons [that] then activate the itch cascade. But it’s also been well known that endogenous kappa opioids can activate sensory neurons that can then suppress itch and gate out signals from these opiates, but perhaps other pruritogens as well.”

Multiple drugs differentially target kappa-opioid receptor (KOR) and mu-opioid receptor (MOR) pathways, he continued. For example, oral naltrexone is a MOR antagonist, oral nalfurafine and intravenous difelikefalin are KOR agonists, while intranasal butorphanol and oral nalbuphine have a dual mechanism.

Difelikefalin is the first Food and Drug Administration–approved treatment for uremic pruritus associated with dialysis, approved in August 2021 for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis; it is administered intravenously. During the 2021 annual congress of the European Academy of Dermatology and Venereology, Dr. Kim and colleagues presented findings from a phase 2 trial of 401 people with atopic dermatitis (AD) and moderate to severe pruritus, who were randomized to receive oral difelikefalin at a dose of 0.25 mg, 0.5 mg, or 1.0 mg, or placebo over a 12-week treatment period. The primary endpoint, change from baseline in Itch Numerical Rating Scale score, was not met in any of the difelikefalin dose groups in the overall study population, but patients with a body surface area of less than 10% experienced a significant improvement in itch at week 12 in the combined difelikefalin dose group in (P = .039). A significant reduction in itch with difelikefalin was seen in this group of patients with itch-dominant AD, as early as the second day of treatment.

In another trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg, 60 mg, or placebo and treated for 8 weeks. The researchers found that nalbuphine 120 mg significantly reduced the itching intensity. Specifically, from a baseline numerical rate scale (NRS) of 6.9, the mean NRS declined by 3.5 and by 2.8 in the nalbuphine 120-mg and the placebo groups, respectively (P = .017).

In a separate, unpublished multicenter, randomized, phase 2/3 trial, researchers evaluated the safety and antipruritic efficacy of nalbuphine extended-release tablets dosed twice daily at 90 mg and 180 mg in 62 patients in the United States and Europe. The proportion of patients in the nalbuphine 180-mg arm who met 50% responder criteria at week 10 or last observed visit approached statistical significance (P = .083), and this arm met statistical significance for patients who completed treatment (P = .028).

Dr. Kim disclosed that he has served as a consultant for AbbVie, AstraZeneca, Cara Therapeutics, Galderma, GlaxoSmithKline, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, Trevi Therapeutics. He also has conducted contracted research for Cara Therapeutics and LEO Pharma.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

Certain opioids are proving to be effective in treating a variety of itch conditions, according to Brian S. Kim, MD.

“We know that opioids or opiates do cause itch in a significant number of patients,” Dr. Kim, a dermatologist who is codirector of the Center for the Study of Itch & Sensory Disorders at Washington University, St. Louis, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “It’s thought to do this by way of acting as a pruritogen at times and stimulating sensory neurons [that] then activate the itch cascade. But it’s also been well known that endogenous kappa opioids can activate sensory neurons that can then suppress itch and gate out signals from these opiates, but perhaps other pruritogens as well.”

Multiple drugs differentially target kappa-opioid receptor (KOR) and mu-opioid receptor (MOR) pathways, he continued. For example, oral naltrexone is a MOR antagonist, oral nalfurafine and intravenous difelikefalin are KOR agonists, while intranasal butorphanol and oral nalbuphine have a dual mechanism.

Difelikefalin is the first Food and Drug Administration–approved treatment for uremic pruritus associated with dialysis, approved in August 2021 for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis; it is administered intravenously. During the 2021 annual congress of the European Academy of Dermatology and Venereology, Dr. Kim and colleagues presented findings from a phase 2 trial of 401 people with atopic dermatitis (AD) and moderate to severe pruritus, who were randomized to receive oral difelikefalin at a dose of 0.25 mg, 0.5 mg, or 1.0 mg, or placebo over a 12-week treatment period. The primary endpoint, change from baseline in Itch Numerical Rating Scale score, was not met in any of the difelikefalin dose groups in the overall study population, but patients with a body surface area of less than 10% experienced a significant improvement in itch at week 12 in the combined difelikefalin dose group in (P = .039). A significant reduction in itch with difelikefalin was seen in this group of patients with itch-dominant AD, as early as the second day of treatment.

In another trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg, 60 mg, or placebo and treated for 8 weeks. The researchers found that nalbuphine 120 mg significantly reduced the itching intensity. Specifically, from a baseline numerical rate scale (NRS) of 6.9, the mean NRS declined by 3.5 and by 2.8 in the nalbuphine 120-mg and the placebo groups, respectively (P = .017).

In a separate, unpublished multicenter, randomized, phase 2/3 trial, researchers evaluated the safety and antipruritic efficacy of nalbuphine extended-release tablets dosed twice daily at 90 mg and 180 mg in 62 patients in the United States and Europe. The proportion of patients in the nalbuphine 180-mg arm who met 50% responder criteria at week 10 or last observed visit approached statistical significance (P = .083), and this arm met statistical significance for patients who completed treatment (P = .028).

Dr. Kim disclosed that he has served as a consultant for AbbVie, AstraZeneca, Cara Therapeutics, Galderma, GlaxoSmithKline, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, Trevi Therapeutics. He also has conducted contracted research for Cara Therapeutics and LEO Pharma.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

Clinical assessment for pulmonary disease and malignancy in patients with dermatomyositis should not be replaced with serologic tests at this time, according to Jeffrey P. Callen, MD.

That’s because the validity and reproducibility of testing in commercial laboratories remain questionable, Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville, Ky., said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “The testing in research laboratories is not widely available and the results are often delayed by weeks to months,” he said.

In addition, while the associations between antibody results and risks of malignancy or pulmonary disease are “statistically valid,” he said, “there are patients with disease in whom antibodies are not present and those without associated disease in whom the testing was positive.” For example, there are patients positive for anti–transition initiation factor (TIF)-1gamma but don’t have a malignancy, “and the ones with anti-MDA-5 tend to have pulmonary disease, but there are patients with anti-MDA-5 who don’t have pulmonary disease.”

Compared with patients with systemic lupus erythematosus, patients with dermatomyositis tend to have more itching and they tend of have fewer serologic abnormalities, such as anti-Ro/SS-A antibody, “but there is overlap,” Dr. Callen said. “The reason to differentiate cutaneous lupus erythematosus from dermatomyositis is because we think that patients who have amyopathic dermatomyositis still have an increased risk of having or developing an internal malignancy,” he added. Another differentiating point that is substantive is the presence of Gottron papules.

In a recent development related to antibody testing, researchers demonstrated that the IgG2 isotype of anti-TIF-1gamma antibodies is a biomarker of cancer and mortality in adult dermatomyositis.

According to population-based studies, about 20%-25% of dermatomyositis patients have had, have, or will develop a cancer (Lancet 2001;357: 96-100). Amyopathic dermatomyositis patients may also have cancer. Polymyositis patients generally have lower rates and their risk of subsequent malignancy is much closer to that of the general population, suggesting that the presence of the association is due to a “diagnostic suspicion bias,” Dr. Callen said.

A large-scale multicenter cohort study that set out to identify the risk factors and prognosis of patients with cancer-associated myositis found that ovarian cancer seems to be overrepresented. The only serologic abnormality that was statistically significant was anti-TIF-1gamma antibody (P less than .001). Patients with cancer-associated myositis also have less overall survival compared with those with non–cancer-associated myositis (P = .004), with malignancy being the primary cause of death (P less than .001).

In what is believed to be the largest study of its kind, Dr. Callen and colleagues retrospectively examined the prevalence of malignancy and screening practices in 400 dermatomyositis patients. Of the 400 patients, 48 (12%) had malignancies, and 21 cancers (40%) were diagnosed within 1 year of the dermatomyositis diagnosis. Both classic dermatomyositis and amyopathic dermatomyositis were associated with cancer, and 27 patients (6.8%) had a cancer at the time of diagnosis. Of those, 59% were asymptomatic; their cancers were discovered with CT scans, suggesting that “blind” screening is effective in identifying cancers in DM patients.

Dr. Callen’s malignancy evaluation includes chest x-ray, CT of the chest and abdomen, stool Hematest in all dermatomyositis patients; a mammogram, pelvic ultrasound and/or CT of the pelvis in women; and age, race or ethnicity-related testing. “I generally reevaluate patients annually for 3 years, because data from epidemiologic studies suggest that after 3 years [from the initial diagnosis], the rates of malignancy return toward normal,” he said. “I also evaluate any new symptom that might be suggestive of malignancy. The remaining issue is how to handle a patient in remission for several years, but who develops a relapse. What I do is perform another malignancy assessment.”

According to results from a meta-analysis of risk factors and systematic review of screening approaches, factors that increase malignancy risk include dermatomyositis subtype (risk ratio, 2.21), older age (weighted mean difference 11.19), male gender (RR, 1.53), dysphagia (RR, 2.09), cutaneous necrosis (RR, 2.73), and positive anti-TIF-1gamma (RR, 4.41).

Factors associated with a decreased risk of malignancy include polymyositis (RR, 0.49), clinically amyopathic dermatomyositis subtypes (RR, 0.44), Raynaud’s phenomenon (RR, 0.61), interstitial lung disease (RR, 0.49), very high serum creatine kinase (WMD –1189.96) or lactate dehydrogenase levels (WMD –336.53), and anti-Jo1 (RR, 0.45) or anti-EJ (RR, 0.17) positivity.

The analysis also found that CT scanning of the thorax, abdomen and pelvis appeared to yield a high proportion of underlying asymptomatic cancers. Limited evidence relating to the utility of tumor markers and 18F-FDG PET/CT was available.

As for treatment, the use of tofacitinib for cutaneous lesions of dermatomyositis has been suggested in various studies. In a recent open-label study of 10 patients with dermatomyositis who took extended release the JAK inhibitor tofacitinib 11 mg daily for 12 weeks, half experienced moderate improvement in disease activity, and the other half experienced minimal improvement. JAK inhibitors have been used in patients with juvenile dermatomyositis.

Dr. Callen’s treatment approach with dermatomyositis patients includes recommendations for sunscreens and protective clothing, plus assessment of vitamin D levels. “I will use topical emollients, corticosteroids, and calcineurin inhibitors,” he said. “Antimalarials might be used. I generally reach for methotrexate or mycophenolate mofetil relatively early. IVIG has also been studied.” Off-label therapies that have been used include dapsone, thalidomide, leflunomide, sirolimus, chlorambucil, etanercept, infliximab, rituximab, apremilast, tofacitinib, lenabasum, and low-dose naltrexone.

Dr. Callen disclosed that he is a consultant to Genentech and is a member of the safety monitoring committee for Principia Biopharma. He holds equity in Celgene, Pfizer, 3M, Johnson & Johnson, Merck, Abbott Laboratories, AbbVie, Procter & Gamble, Gilead, Allergen, and Amgen.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

Clinical assessment for pulmonary disease and malignancy in patients with dermatomyositis should not be replaced with serologic tests at this time, according to Jeffrey P. Callen, MD.

That’s because the validity and reproducibility of testing in commercial laboratories remain questionable, Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville, Ky., said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “The testing in research laboratories is not widely available and the results are often delayed by weeks to months,” he said.

In addition, while the associations between antibody results and risks of malignancy or pulmonary disease are “statistically valid,” he said, “there are patients with disease in whom antibodies are not present and those without associated disease in whom the testing was positive.” For example, there are patients positive for anti–transition initiation factor (TIF)-1gamma but don’t have a malignancy, “and the ones with anti-MDA-5 tend to have pulmonary disease, but there are patients with anti-MDA-5 who don’t have pulmonary disease.”

Compared with patients with systemic lupus erythematosus, patients with dermatomyositis tend to have more itching and they tend of have fewer serologic abnormalities, such as anti-Ro/SS-A antibody, “but there is overlap,” Dr. Callen said. “The reason to differentiate cutaneous lupus erythematosus from dermatomyositis is because we think that patients who have amyopathic dermatomyositis still have an increased risk of having or developing an internal malignancy,” he added. Another differentiating point that is substantive is the presence of Gottron papules.

In a recent development related to antibody testing, researchers demonstrated that the IgG2 isotype of anti-TIF-1gamma antibodies is a biomarker of cancer and mortality in adult dermatomyositis.

According to population-based studies, about 20%-25% of dermatomyositis patients have had, have, or will develop a cancer (Lancet 2001;357: 96-100). Amyopathic dermatomyositis patients may also have cancer. Polymyositis patients generally have lower rates and their risk of subsequent malignancy is much closer to that of the general population, suggesting that the presence of the association is due to a “diagnostic suspicion bias,” Dr. Callen said.

A large-scale multicenter cohort study that set out to identify the risk factors and prognosis of patients with cancer-associated myositis found that ovarian cancer seems to be overrepresented. The only serologic abnormality that was statistically significant was anti-TIF-1gamma antibody (P less than .001). Patients with cancer-associated myositis also have less overall survival compared with those with non–cancer-associated myositis (P = .004), with malignancy being the primary cause of death (P less than .001).

In what is believed to be the largest study of its kind, Dr. Callen and colleagues retrospectively examined the prevalence of malignancy and screening practices in 400 dermatomyositis patients. Of the 400 patients, 48 (12%) had malignancies, and 21 cancers (40%) were diagnosed within 1 year of the dermatomyositis diagnosis. Both classic dermatomyositis and amyopathic dermatomyositis were associated with cancer, and 27 patients (6.8%) had a cancer at the time of diagnosis. Of those, 59% were asymptomatic; their cancers were discovered with CT scans, suggesting that “blind” screening is effective in identifying cancers in DM patients.

Dr. Callen’s malignancy evaluation includes chest x-ray, CT of the chest and abdomen, stool Hematest in all dermatomyositis patients; a mammogram, pelvic ultrasound and/or CT of the pelvis in women; and age, race or ethnicity-related testing. “I generally reevaluate patients annually for 3 years, because data from epidemiologic studies suggest that after 3 years [from the initial diagnosis], the rates of malignancy return toward normal,” he said. “I also evaluate any new symptom that might be suggestive of malignancy. The remaining issue is how to handle a patient in remission for several years, but who develops a relapse. What I do is perform another malignancy assessment.”

According to results from a meta-analysis of risk factors and systematic review of screening approaches, factors that increase malignancy risk include dermatomyositis subtype (risk ratio, 2.21), older age (weighted mean difference 11.19), male gender (RR, 1.53), dysphagia (RR, 2.09), cutaneous necrosis (RR, 2.73), and positive anti-TIF-1gamma (RR, 4.41).

Factors associated with a decreased risk of malignancy include polymyositis (RR, 0.49), clinically amyopathic dermatomyositis subtypes (RR, 0.44), Raynaud’s phenomenon (RR, 0.61), interstitial lung disease (RR, 0.49), very high serum creatine kinase (WMD –1189.96) or lactate dehydrogenase levels (WMD –336.53), and anti-Jo1 (RR, 0.45) or anti-EJ (RR, 0.17) positivity.

The analysis also found that CT scanning of the thorax, abdomen and pelvis appeared to yield a high proportion of underlying asymptomatic cancers. Limited evidence relating to the utility of tumor markers and 18F-FDG PET/CT was available.

As for treatment, the use of tofacitinib for cutaneous lesions of dermatomyositis has been suggested in various studies. In a recent open-label study of 10 patients with dermatomyositis who took extended release the JAK inhibitor tofacitinib 11 mg daily for 12 weeks, half experienced moderate improvement in disease activity, and the other half experienced minimal improvement. JAK inhibitors have been used in patients with juvenile dermatomyositis.

Dr. Callen’s treatment approach with dermatomyositis patients includes recommendations for sunscreens and protective clothing, plus assessment of vitamin D levels. “I will use topical emollients, corticosteroids, and calcineurin inhibitors,” he said. “Antimalarials might be used. I generally reach for methotrexate or mycophenolate mofetil relatively early. IVIG has also been studied.” Off-label therapies that have been used include dapsone, thalidomide, leflunomide, sirolimus, chlorambucil, etanercept, infliximab, rituximab, apremilast, tofacitinib, lenabasum, and low-dose naltrexone.

Dr. Callen disclosed that he is a consultant to Genentech and is a member of the safety monitoring committee for Principia Biopharma. He holds equity in Celgene, Pfizer, 3M, Johnson & Johnson, Merck, Abbott Laboratories, AbbVie, Procter & Gamble, Gilead, Allergen, and Amgen.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

Clinical assessment for pulmonary disease and malignancy in patients with dermatomyositis should not be replaced with serologic tests at this time, according to Jeffrey P. Callen, MD.

That’s because the validity and reproducibility of testing in commercial laboratories remain questionable, Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville, Ky., said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “The testing in research laboratories is not widely available and the results are often delayed by weeks to months,” he said.

In addition, while the associations between antibody results and risks of malignancy or pulmonary disease are “statistically valid,” he said, “there are patients with disease in whom antibodies are not present and those without associated disease in whom the testing was positive.” For example, there are patients positive for anti–transition initiation factor (TIF)-1gamma but don’t have a malignancy, “and the ones with anti-MDA-5 tend to have pulmonary disease, but there are patients with anti-MDA-5 who don’t have pulmonary disease.”

Compared with patients with systemic lupus erythematosus, patients with dermatomyositis tend to have more itching and they tend of have fewer serologic abnormalities, such as anti-Ro/SS-A antibody, “but there is overlap,” Dr. Callen said. “The reason to differentiate cutaneous lupus erythematosus from dermatomyositis is because we think that patients who have amyopathic dermatomyositis still have an increased risk of having or developing an internal malignancy,” he added. Another differentiating point that is substantive is the presence of Gottron papules.

In a recent development related to antibody testing, researchers demonstrated that the IgG2 isotype of anti-TIF-1gamma antibodies is a biomarker of cancer and mortality in adult dermatomyositis.

According to population-based studies, about 20%-25% of dermatomyositis patients have had, have, or will develop a cancer (Lancet 2001;357: 96-100). Amyopathic dermatomyositis patients may also have cancer. Polymyositis patients generally have lower rates and their risk of subsequent malignancy is much closer to that of the general population, suggesting that the presence of the association is due to a “diagnostic suspicion bias,” Dr. Callen said.

A large-scale multicenter cohort study that set out to identify the risk factors and prognosis of patients with cancer-associated myositis found that ovarian cancer seems to be overrepresented. The only serologic abnormality that was statistically significant was anti-TIF-1gamma antibody (P less than .001). Patients with cancer-associated myositis also have less overall survival compared with those with non–cancer-associated myositis (P = .004), with malignancy being the primary cause of death (P less than .001).

In what is believed to be the largest study of its kind, Dr. Callen and colleagues retrospectively examined the prevalence of malignancy and screening practices in 400 dermatomyositis patients. Of the 400 patients, 48 (12%) had malignancies, and 21 cancers (40%) were diagnosed within 1 year of the dermatomyositis diagnosis. Both classic dermatomyositis and amyopathic dermatomyositis were associated with cancer, and 27 patients (6.8%) had a cancer at the time of diagnosis. Of those, 59% were asymptomatic; their cancers were discovered with CT scans, suggesting that “blind” screening is effective in identifying cancers in DM patients.

Dr. Callen’s malignancy evaluation includes chest x-ray, CT of the chest and abdomen, stool Hematest in all dermatomyositis patients; a mammogram, pelvic ultrasound and/or CT of the pelvis in women; and age, race or ethnicity-related testing. “I generally reevaluate patients annually for 3 years, because data from epidemiologic studies suggest that after 3 years [from the initial diagnosis], the rates of malignancy return toward normal,” he said. “I also evaluate any new symptom that might be suggestive of malignancy. The remaining issue is how to handle a patient in remission for several years, but who develops a relapse. What I do is perform another malignancy assessment.”

According to results from a meta-analysis of risk factors and systematic review of screening approaches, factors that increase malignancy risk include dermatomyositis subtype (risk ratio, 2.21), older age (weighted mean difference 11.19), male gender (RR, 1.53), dysphagia (RR, 2.09), cutaneous necrosis (RR, 2.73), and positive anti-TIF-1gamma (RR, 4.41).

Factors associated with a decreased risk of malignancy include polymyositis (RR, 0.49), clinically amyopathic dermatomyositis subtypes (RR, 0.44), Raynaud’s phenomenon (RR, 0.61), interstitial lung disease (RR, 0.49), very high serum creatine kinase (WMD –1189.96) or lactate dehydrogenase levels (WMD –336.53), and anti-Jo1 (RR, 0.45) or anti-EJ (RR, 0.17) positivity.

The analysis also found that CT scanning of the thorax, abdomen and pelvis appeared to yield a high proportion of underlying asymptomatic cancers. Limited evidence relating to the utility of tumor markers and 18F-FDG PET/CT was available.

As for treatment, the use of tofacitinib for cutaneous lesions of dermatomyositis has been suggested in various studies. In a recent open-label study of 10 patients with dermatomyositis who took extended release the JAK inhibitor tofacitinib 11 mg daily for 12 weeks, half experienced moderate improvement in disease activity, and the other half experienced minimal improvement. JAK inhibitors have been used in patients with juvenile dermatomyositis.

Dr. Callen’s treatment approach with dermatomyositis patients includes recommendations for sunscreens and protective clothing, plus assessment of vitamin D levels. “I will use topical emollients, corticosteroids, and calcineurin inhibitors,” he said. “Antimalarials might be used. I generally reach for methotrexate or mycophenolate mofetil relatively early. IVIG has also been studied.” Off-label therapies that have been used include dapsone, thalidomide, leflunomide, sirolimus, chlorambucil, etanercept, infliximab, rituximab, apremilast, tofacitinib, lenabasum, and low-dose naltrexone.

Dr. Callen disclosed that he is a consultant to Genentech and is a member of the safety monitoring committee for Principia Biopharma. He holds equity in Celgene, Pfizer, 3M, Johnson & Johnson, Merck, Abbott Laboratories, AbbVie, Procter & Gamble, Gilead, Allergen, and Amgen.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

A new survey-based estimate puts the prevalence of vitiligo somewhere between 0.76% and 1.11% in the United States and suggests that 40% of adults with the autoimmune disorder may be undiagnosed.

“The remarkably high number of participants with undiagnosed vitiligo” indicates a need for “the development and validation of teledermatology apps that allow for potential diagnosis,” Kavita Gandhi, MS, of the patient and health impact group at Pfizer in Collegeville, Pa., and associates said in JAMA Dermatology.

The estimated range of 0.76%-1.11% prevalence represents 1.9 million to 2.8 million adults with vitiligo in the general population, based on responses from 40,888 participants surveyed between Dec. 30, 2019, and March 11, 2020, and further physician evaluation of photos uploaded by 113 respondents, they explained. The investigators used a representative sample of the U.S. population, of people ages 18-85 years.

A prior vitiligo diagnosis was reported by 314 participants, and another 249 screened positive through the survey, for a self-reported overall prevalence of 1.38% in the adult population and a previously undiagnosed prevalence of 0.61%. The physician adjudication brought the overall prevalence down to 0.76% and the undiagnosed prevalence to 0.29%. “These findings suggest that up to 40% of adults with vitiligo in the U.S. may be undiagnosed,” the investigators wrote.

Survey questions covering the laterality of lesions broke the 1.38% overall prevalence down to 0.77% nonsegmental vitiligo (self-reported as bilateral) and 0.61% segmental (unilateral). The 0.76% overall prevalence provided by the three dermatologist reviewers worked out to 0.58% classified as nonsegmental and 0.18% as segmental, Ms. Gandhi and associates said.

“The distinction between segmental and nonsegmental vitiligo is of prime importance [since] patients are usually concerned by the spreading of the disease and its unpredictable course, which is the hallmark of nonsegmental vitiligo,” the researchers noted.

The analysis was the first, to the authors’ knowledge, to identify several trends among the undiagnosed population. The proportion of nonwhite adults was higher in the undiagnosed group (40.2%) than among those with a diagnosis (31.5%), as was Hispanic, Latino, or Spanish origin (21.3% vs. 15.3%). Unilateral presentation was seen in 54.2% of the undiagnosed adults and 37.3% of those with diagnosed vitiligo, they reported.

The study was sponsored by Pfizer, which employs several of the investigators. Two of the investigators disclosed multiple conflicts of interest involving other companies.

rfranki@mdedge.com

A new survey-based estimate puts the prevalence of vitiligo somewhere between 0.76% and 1.11% in the United States and suggests that 40% of adults with the autoimmune disorder may be undiagnosed.

“The remarkably high number of participants with undiagnosed vitiligo” indicates a need for “the development and validation of teledermatology apps that allow for potential diagnosis,” Kavita Gandhi, MS, of the patient and health impact group at Pfizer in Collegeville, Pa., and associates said in JAMA Dermatology.

The estimated range of 0.76%-1.11% prevalence represents 1.9 million to 2.8 million adults with vitiligo in the general population, based on responses from 40,888 participants surveyed between Dec. 30, 2019, and March 11, 2020, and further physician evaluation of photos uploaded by 113 respondents, they explained. The investigators used a representative sample of the U.S. population, of people ages 18-85 years.

A prior vitiligo diagnosis was reported by 314 participants, and another 249 screened positive through the survey, for a self-reported overall prevalence of 1.38% in the adult population and a previously undiagnosed prevalence of 0.61%. The physician adjudication brought the overall prevalence down to 0.76% and the undiagnosed prevalence to 0.29%. “These findings suggest that up to 40% of adults with vitiligo in the U.S. may be undiagnosed,” the investigators wrote.

Survey questions covering the laterality of lesions broke the 1.38% overall prevalence down to 0.77% nonsegmental vitiligo (self-reported as bilateral) and 0.61% segmental (unilateral). The 0.76% overall prevalence provided by the three dermatologist reviewers worked out to 0.58% classified as nonsegmental and 0.18% as segmental, Ms. Gandhi and associates said.

“The distinction between segmental and nonsegmental vitiligo is of prime importance [since] patients are usually concerned by the spreading of the disease and its unpredictable course, which is the hallmark of nonsegmental vitiligo,” the researchers noted.

The analysis was the first, to the authors’ knowledge, to identify several trends among the undiagnosed population. The proportion of nonwhite adults was higher in the undiagnosed group (40.2%) than among those with a diagnosis (31.5%), as was Hispanic, Latino, or Spanish origin (21.3% vs. 15.3%). Unilateral presentation was seen in 54.2% of the undiagnosed adults and 37.3% of those with diagnosed vitiligo, they reported.

The study was sponsored by Pfizer, which employs several of the investigators. Two of the investigators disclosed multiple conflicts of interest involving other companies.

rfranki@mdedge.com

A new survey-based estimate puts the prevalence of vitiligo somewhere between 0.76% and 1.11% in the United States and suggests that 40% of adults with the autoimmune disorder may be undiagnosed.

“The remarkably high number of participants with undiagnosed vitiligo” indicates a need for “the development and validation of teledermatology apps that allow for potential diagnosis,” Kavita Gandhi, MS, of the patient and health impact group at Pfizer in Collegeville, Pa., and associates said in JAMA Dermatology.

The estimated range of 0.76%-1.11% prevalence represents 1.9 million to 2.8 million adults with vitiligo in the general population, based on responses from 40,888 participants surveyed between Dec. 30, 2019, and March 11, 2020, and further physician evaluation of photos uploaded by 113 respondents, they explained. The investigators used a representative sample of the U.S. population, of people ages 18-85 years.

A prior vitiligo diagnosis was reported by 314 participants, and another 249 screened positive through the survey, for a self-reported overall prevalence of 1.38% in the adult population and a previously undiagnosed prevalence of 0.61%. The physician adjudication brought the overall prevalence down to 0.76% and the undiagnosed prevalence to 0.29%. “These findings suggest that up to 40% of adults with vitiligo in the U.S. may be undiagnosed,” the investigators wrote.

Survey questions covering the laterality of lesions broke the 1.38% overall prevalence down to 0.77% nonsegmental vitiligo (self-reported as bilateral) and 0.61% segmental (unilateral). The 0.76% overall prevalence provided by the three dermatologist reviewers worked out to 0.58% classified as nonsegmental and 0.18% as segmental, Ms. Gandhi and associates said.

“The distinction between segmental and nonsegmental vitiligo is of prime importance [since] patients are usually concerned by the spreading of the disease and its unpredictable course, which is the hallmark of nonsegmental vitiligo,” the researchers noted.

The analysis was the first, to the authors’ knowledge, to identify several trends among the undiagnosed population. The proportion of nonwhite adults was higher in the undiagnosed group (40.2%) than among those with a diagnosis (31.5%), as was Hispanic, Latino, or Spanish origin (21.3% vs. 15.3%). Unilateral presentation was seen in 54.2% of the undiagnosed adults and 37.3% of those with diagnosed vitiligo, they reported.

The study was sponsored by Pfizer, which employs several of the investigators. Two of the investigators disclosed multiple conflicts of interest involving other companies.

rfranki@mdedge.com

 

In the clinical experience of Emmy Graber, MD, MBA, rosacea is in the eye of the beholder.

“It’s not really up to us as the providers as to what’s important to the patient or how bad their rosacea is,” she said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “It really is up to the patient,” added Dr. Graber, president of The Dermatology Institute of Boston, who recommends asking patients about how severe they consider their rosacea to be, and what about rosacea bothers them most. Their responses may be surprising.

A study published in 2017 showed that complete resolution of even mild rosacea prolongs remission of rosacea, and most importantly, improves the quality of life for patients. “So, don’t discount what you consider to be mild rosacea in patients,” she said.

Skin care recommendations

“And don’t forget about basic skin care,” she advised. A recently published Chinese study of 999 rosacea patients and 1,010 controls with healthy skin found that a high frequency of cleansing and expansive use of cleansers were positively correlated with rosacea occurrence, suggesting that overcleansing can be a risk factor for rosacea. “Ask your patient, ‘how often are you cleaning your face?’ ” Dr. Graber suggested. “You might find that they’re overdoing it by washing three or four times a day. Several studies have shown that basic skin care alone improves rosacea.”

Skin care recommendations for patients with rosacea include avoiding chemical or physical exfoliants and alcohol-based topical products, and moisturizing and washing their faces with mild, synthetic detergent-based products rather than traditional soaps, which may further alkalinize and irritate the skin. “Patients should also be counseled to use physical-based sunscreens rather than chemical-based sunscreens,” she said.
 

Treating erythema

For treating erythema with topicals, a systematic review published in 2019 found the most evidence for brimonidine 0.33% gel, an alpha2-adrenergic agonist, and oxymetazoline 1% cream, an alpha1-adrenergic agonist. “Both of these products functionally constrict facial blood vessels,” and are Food and Drug Administration approved for treating persistent erythema, Dr. Graber said. “These products improve erythema within 3 hours of and up to 12 hours after application and overall, they are well tolerated.”

Rosacea.org

Based on clinical trial results, about 15% of patients on brimonidine report adverse reactions such as dermatitis, burning, pruritus, and erythema, compared with 8% of patients on oxymetazoline. At the same time, up to 20% of individuals on brimonidine report rebound erythema, compared with fewer than 1% of those using oxymetazoline. Laser and light therapies such as pulse-dye lasers, potassium-titanyl-phosphate lasers, and intense-pulse light devices are also effective in treating persistent erythema but are less effective for transient flushing.
 

 

Treatment of papules and pustules

For treating papules and pustules, the 2019 systemic review also found high-certainty evidence for using azelaic acid and topical ivermectin, and moderate-certainty evidence for using topical metronidazole and topical minocycline. “Topical ivermectin was demonstrated to be the most effective topical treatment for papulopustular rosacea and to provide the greatest psychological benefit to these patients,” Dr. Graber said.

In a double-blind, multicenter 15-week trial comparing azelaic acid 15% gel with metronidazole 0.75% gel in patients with papulopustular rosacea, both agents were found to be effective. But those treated with azelaic acid 15% gel had a greater reduction in lesion counts and erythema, and improvement in global assessments, compared with metronidazole 0.75% gel. However, the azelaic acid 15% gel was associated with more stinging compared with metronidazole 0.75% gel, although it was usually transient.

Another study, a double-blind, single-center, 15-week trial, compared the efficacy of azelaic acid 20% cream with metronidazole 0.75% cream. Both agents were found to be effective and had similar levels of reductions in papules and pustules. However, patients in the azelaic acid 20% cream arm had significantly higher physician ratings of global improvement, as well as overall higher patient satisfaction.

More recently, a phase 3 study of 962 patients found that ivermectin 1% cream once daily improved quality of life slightly more than metronidazole 0.75% cream twice daily. No difference in adverse events were noted between the two agents.

Other options for treating papules and pustules include topical minocycline 1.5% foam, which is FDA approved for rosacea, as well as second-line agents topical sodium sulfacetamide with sulfur cleanser (cream or lotion), and permethrin, Dr. Graber said.

As for treating papules and pustules with oral agents, the strongest evidence favors oral tetracyclines and isotretinoin, she noted.

Doxycycline, minocycline, tetracycline, and sarecycline can be used as monotherapy or coadministered with topical agents. “The addition of topical agents may also help to shorten the duration of antibiotic use, which is very important,” Dr. Graber said.

She noted that oral beta-blockers might be useful to treat persistent erythema and flushing because they antagonize the effects of sympathetic nerve stimulation and circulating catecholamines at b-adrenoceptors. Carvedilol and propranolol have been the most studied. The most common potential side effects are hypotension and bradycardia.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

 

In the clinical experience of Emmy Graber, MD, MBA, rosacea is in the eye of the beholder.

“It’s not really up to us as the providers as to what’s important to the patient or how bad their rosacea is,” she said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “It really is up to the patient,” added Dr. Graber, president of The Dermatology Institute of Boston, who recommends asking patients about how severe they consider their rosacea to be, and what about rosacea bothers them most. Their responses may be surprising.

A study published in 2017 showed that complete resolution of even mild rosacea prolongs remission of rosacea, and most importantly, improves the quality of life for patients. “So, don’t discount what you consider to be mild rosacea in patients,” she said.

Skin care recommendations

“And don’t forget about basic skin care,” she advised. A recently published Chinese study of 999 rosacea patients and 1,010 controls with healthy skin found that a high frequency of cleansing and expansive use of cleansers were positively correlated with rosacea occurrence, suggesting that overcleansing can be a risk factor for rosacea. “Ask your patient, ‘how often are you cleaning your face?’ ” Dr. Graber suggested. “You might find that they’re overdoing it by washing three or four times a day. Several studies have shown that basic skin care alone improves rosacea.”

Skin care recommendations for patients with rosacea include avoiding chemical or physical exfoliants and alcohol-based topical products, and moisturizing and washing their faces with mild, synthetic detergent-based products rather than traditional soaps, which may further alkalinize and irritate the skin. “Patients should also be counseled to use physical-based sunscreens rather than chemical-based sunscreens,” she said.
 

Treating erythema

For treating erythema with topicals, a systematic review published in 2019 found the most evidence for brimonidine 0.33% gel, an alpha2-adrenergic agonist, and oxymetazoline 1% cream, an alpha1-adrenergic agonist. “Both of these products functionally constrict facial blood vessels,” and are Food and Drug Administration approved for treating persistent erythema, Dr. Graber said. “These products improve erythema within 3 hours of and up to 12 hours after application and overall, they are well tolerated.”

Rosacea.org

Based on clinical trial results, about 15% of patients on brimonidine report adverse reactions such as dermatitis, burning, pruritus, and erythema, compared with 8% of patients on oxymetazoline. At the same time, up to 20% of individuals on brimonidine report rebound erythema, compared with fewer than 1% of those using oxymetazoline. Laser and light therapies such as pulse-dye lasers, potassium-titanyl-phosphate lasers, and intense-pulse light devices are also effective in treating persistent erythema but are less effective for transient flushing.
 

 

Treatment of papules and pustules

For treating papules and pustules, the 2019 systemic review also found high-certainty evidence for using azelaic acid and topical ivermectin, and moderate-certainty evidence for using topical metronidazole and topical minocycline. “Topical ivermectin was demonstrated to be the most effective topical treatment for papulopustular rosacea and to provide the greatest psychological benefit to these patients,” Dr. Graber said.

In a double-blind, multicenter 15-week trial comparing azelaic acid 15% gel with metronidazole 0.75% gel in patients with papulopustular rosacea, both agents were found to be effective. But those treated with azelaic acid 15% gel had a greater reduction in lesion counts and erythema, and improvement in global assessments, compared with metronidazole 0.75% gel. However, the azelaic acid 15% gel was associated with more stinging compared with metronidazole 0.75% gel, although it was usually transient.

Another study, a double-blind, single-center, 15-week trial, compared the efficacy of azelaic acid 20% cream with metronidazole 0.75% cream. Both agents were found to be effective and had similar levels of reductions in papules and pustules. However, patients in the azelaic acid 20% cream arm had significantly higher physician ratings of global improvement, as well as overall higher patient satisfaction.

More recently, a phase 3 study of 962 patients found that ivermectin 1% cream once daily improved quality of life slightly more than metronidazole 0.75% cream twice daily. No difference in adverse events were noted between the two agents.

Other options for treating papules and pustules include topical minocycline 1.5% foam, which is FDA approved for rosacea, as well as second-line agents topical sodium sulfacetamide with sulfur cleanser (cream or lotion), and permethrin, Dr. Graber said.

As for treating papules and pustules with oral agents, the strongest evidence favors oral tetracyclines and isotretinoin, she noted.

Doxycycline, minocycline, tetracycline, and sarecycline can be used as monotherapy or coadministered with topical agents. “The addition of topical agents may also help to shorten the duration of antibiotic use, which is very important,” Dr. Graber said.

She noted that oral beta-blockers might be useful to treat persistent erythema and flushing because they antagonize the effects of sympathetic nerve stimulation and circulating catecholamines at b-adrenoceptors. Carvedilol and propranolol have been the most studied. The most common potential side effects are hypotension and bradycardia.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

 

In the clinical experience of Emmy Graber, MD, MBA, rosacea is in the eye of the beholder.

“It’s not really up to us as the providers as to what’s important to the patient or how bad their rosacea is,” she said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “It really is up to the patient,” added Dr. Graber, president of The Dermatology Institute of Boston, who recommends asking patients about how severe they consider their rosacea to be, and what about rosacea bothers them most. Their responses may be surprising.

A study published in 2017 showed that complete resolution of even mild rosacea prolongs remission of rosacea, and most importantly, improves the quality of life for patients. “So, don’t discount what you consider to be mild rosacea in patients,” she said.

Skin care recommendations

“And don’t forget about basic skin care,” she advised. A recently published Chinese study of 999 rosacea patients and 1,010 controls with healthy skin found that a high frequency of cleansing and expansive use of cleansers were positively correlated with rosacea occurrence, suggesting that overcleansing can be a risk factor for rosacea. “Ask your patient, ‘how often are you cleaning your face?’ ” Dr. Graber suggested. “You might find that they’re overdoing it by washing three or four times a day. Several studies have shown that basic skin care alone improves rosacea.”

Skin care recommendations for patients with rosacea include avoiding chemical or physical exfoliants and alcohol-based topical products, and moisturizing and washing their faces with mild, synthetic detergent-based products rather than traditional soaps, which may further alkalinize and irritate the skin. “Patients should also be counseled to use physical-based sunscreens rather than chemical-based sunscreens,” she said.
 

Treating erythema

For treating erythema with topicals, a systematic review published in 2019 found the most evidence for brimonidine 0.33% gel, an alpha2-adrenergic agonist, and oxymetazoline 1% cream, an alpha1-adrenergic agonist. “Both of these products functionally constrict facial blood vessels,” and are Food and Drug Administration approved for treating persistent erythema, Dr. Graber said. “These products improve erythema within 3 hours of and up to 12 hours after application and overall, they are well tolerated.”

Rosacea.org

Based on clinical trial results, about 15% of patients on brimonidine report adverse reactions such as dermatitis, burning, pruritus, and erythema, compared with 8% of patients on oxymetazoline. At the same time, up to 20% of individuals on brimonidine report rebound erythema, compared with fewer than 1% of those using oxymetazoline. Laser and light therapies such as pulse-dye lasers, potassium-titanyl-phosphate lasers, and intense-pulse light devices are also effective in treating persistent erythema but are less effective for transient flushing.
 

 

Treatment of papules and pustules

For treating papules and pustules, the 2019 systemic review also found high-certainty evidence for using azelaic acid and topical ivermectin, and moderate-certainty evidence for using topical metronidazole and topical minocycline. “Topical ivermectin was demonstrated to be the most effective topical treatment for papulopustular rosacea and to provide the greatest psychological benefit to these patients,” Dr. Graber said.

In a double-blind, multicenter 15-week trial comparing azelaic acid 15% gel with metronidazole 0.75% gel in patients with papulopustular rosacea, both agents were found to be effective. But those treated with azelaic acid 15% gel had a greater reduction in lesion counts and erythema, and improvement in global assessments, compared with metronidazole 0.75% gel. However, the azelaic acid 15% gel was associated with more stinging compared with metronidazole 0.75% gel, although it was usually transient.

Another study, a double-blind, single-center, 15-week trial, compared the efficacy of azelaic acid 20% cream with metronidazole 0.75% cream. Both agents were found to be effective and had similar levels of reductions in papules and pustules. However, patients in the azelaic acid 20% cream arm had significantly higher physician ratings of global improvement, as well as overall higher patient satisfaction.

More recently, a phase 3 study of 962 patients found that ivermectin 1% cream once daily improved quality of life slightly more than metronidazole 0.75% cream twice daily. No difference in adverse events were noted between the two agents.

Other options for treating papules and pustules include topical minocycline 1.5% foam, which is FDA approved for rosacea, as well as second-line agents topical sodium sulfacetamide with sulfur cleanser (cream or lotion), and permethrin, Dr. Graber said.

As for treating papules and pustules with oral agents, the strongest evidence favors oral tetracyclines and isotretinoin, she noted.

Doxycycline, minocycline, tetracycline, and sarecycline can be used as monotherapy or coadministered with topical agents. “The addition of topical agents may also help to shorten the duration of antibiotic use, which is very important,” Dr. Graber said.

She noted that oral beta-blockers might be useful to treat persistent erythema and flushing because they antagonize the effects of sympathetic nerve stimulation and circulating catecholamines at b-adrenoceptors. Carvedilol and propranolol have been the most studied. The most common potential side effects are hypotension and bradycardia.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

 

A study on the role of the ocular surface microbiome in rosacea pathogenesis and an investigation of elevated intracellular signals in rosacea lesions earned new research funding from the National Rosacea Society (NRS) this year, as part of the organization’s research grants program.

National Rosacea Society

The NRS research grants program was created to increase knowledge and understanding of not only the potential causes of rosacea, but other aspects of the disease that may inform prevention, treatment, or a potential cure, according to the press release announcing the recipients.

New research grant recipient Sezen Karakus, MD, of the Johns Hopkins Wilmer Eye Institute, Baltimore, received $15,000 for a study on the contribution of the ocular surface microbiome to the development of rosacea. Ocular rosacea can result in corneal complications severe enough to affect vision, and identifying the microorganisms on the ocular surface may lead to new treatment strategies, Dr. Karakus said in the release. He will collaborate on this research with dermatologist Noori Kim, MD, of Johns Hopkins University, Baltimore.

A second new research grant went to Emmanuel Contassot, MD, project leader in the dermatology department at of the University Hospital of Basel, Switzerland, who received $5,000 to investigate whether certain elevated intracellular signals in rosacea lesions may promote the skin inflammation that may be a root cause of the condition.

The NRS also renewed its support of a pair of ongoing studies. Michelle Trautwein, MD, of the Institute for Biodiversity Science and Sustainability at the California Academy of Sciences, continues her work on the first study to sequence the genome of Demodex mites; the study also identifies associated bacteria that may play a role in rosacea.

National Rosacea Society

A second ongoing study by Tissa Hata, MD, of the University of California, San Diego, focuses on the normalization of the microbiome in people with rosacea. Dr. Hata’s work identifies types of bacteria associated with rosacea, as well as bacteria that may be associated with healthy skin after successful treatment of rosacea, including Cutibacterium acnes and Staphylococcus epidermidis.

The deadline to submit research proposals for next year’s grants is June 17, 2022. Researchers can find forms and instructions at the research grants section of the NRS website or by contacting the National Rosacea Society at 111 Lions Dr., Suite 216, Barrington, Ill., 60010, by telephone at 1-888-662-5874, or by email at info@rosacea.org.

 

A study on the role of the ocular surface microbiome in rosacea pathogenesis and an investigation of elevated intracellular signals in rosacea lesions earned new research funding from the National Rosacea Society (NRS) this year, as part of the organization’s research grants program.

National Rosacea Society

The NRS research grants program was created to increase knowledge and understanding of not only the potential causes of rosacea, but other aspects of the disease that may inform prevention, treatment, or a potential cure, according to the press release announcing the recipients.

New research grant recipient Sezen Karakus, MD, of the Johns Hopkins Wilmer Eye Institute, Baltimore, received $15,000 for a study on the contribution of the ocular surface microbiome to the development of rosacea. Ocular rosacea can result in corneal complications severe enough to affect vision, and identifying the microorganisms on the ocular surface may lead to new treatment strategies, Dr. Karakus said in the release. He will collaborate on this research with dermatologist Noori Kim, MD, of Johns Hopkins University, Baltimore.

A second new research grant went to Emmanuel Contassot, MD, project leader in the dermatology department at of the University Hospital of Basel, Switzerland, who received $5,000 to investigate whether certain elevated intracellular signals in rosacea lesions may promote the skin inflammation that may be a root cause of the condition.

The NRS also renewed its support of a pair of ongoing studies. Michelle Trautwein, MD, of the Institute for Biodiversity Science and Sustainability at the California Academy of Sciences, continues her work on the first study to sequence the genome of Demodex mites; the study also identifies associated bacteria that may play a role in rosacea.

National Rosacea Society

A second ongoing study by Tissa Hata, MD, of the University of California, San Diego, focuses on the normalization of the microbiome in people with rosacea. Dr. Hata’s work identifies types of bacteria associated with rosacea, as well as bacteria that may be associated with healthy skin after successful treatment of rosacea, including Cutibacterium acnes and Staphylococcus epidermidis.

The deadline to submit research proposals for next year’s grants is June 17, 2022. Researchers can find forms and instructions at the research grants section of the NRS website or by contacting the National Rosacea Society at 111 Lions Dr., Suite 216, Barrington, Ill., 60010, by telephone at 1-888-662-5874, or by email at info@rosacea.org.

 

A study on the role of the ocular surface microbiome in rosacea pathogenesis and an investigation of elevated intracellular signals in rosacea lesions earned new research funding from the National Rosacea Society (NRS) this year, as part of the organization’s research grants program.

National Rosacea Society

The NRS research grants program was created to increase knowledge and understanding of not only the potential causes of rosacea, but other aspects of the disease that may inform prevention, treatment, or a potential cure, according to the press release announcing the recipients.

New research grant recipient Sezen Karakus, MD, of the Johns Hopkins Wilmer Eye Institute, Baltimore, received $15,000 for a study on the contribution of the ocular surface microbiome to the development of rosacea. Ocular rosacea can result in corneal complications severe enough to affect vision, and identifying the microorganisms on the ocular surface may lead to new treatment strategies, Dr. Karakus said in the release. He will collaborate on this research with dermatologist Noori Kim, MD, of Johns Hopkins University, Baltimore.

A second new research grant went to Emmanuel Contassot, MD, project leader in the dermatology department at of the University Hospital of Basel, Switzerland, who received $5,000 to investigate whether certain elevated intracellular signals in rosacea lesions may promote the skin inflammation that may be a root cause of the condition.

The NRS also renewed its support of a pair of ongoing studies. Michelle Trautwein, MD, of the Institute for Biodiversity Science and Sustainability at the California Academy of Sciences, continues her work on the first study to sequence the genome of Demodex mites; the study also identifies associated bacteria that may play a role in rosacea.

National Rosacea Society

A second ongoing study by Tissa Hata, MD, of the University of California, San Diego, focuses on the normalization of the microbiome in people with rosacea. Dr. Hata’s work identifies types of bacteria associated with rosacea, as well as bacteria that may be associated with healthy skin after successful treatment of rosacea, including Cutibacterium acnes and Staphylococcus epidermidis.

The deadline to submit research proposals for next year’s grants is June 17, 2022. Researchers can find forms and instructions at the research grants section of the NRS website or by contacting the National Rosacea Society at 111 Lions Dr., Suite 216, Barrington, Ill., 60010, by telephone at 1-888-662-5874, or by email at info@rosacea.org.

Topical retinoids are a staple first-line treatment option cited in the American Academy of Dermatology’s most recent guidelines for the care of patients with acne, yet they are likely underused in today’s clinical practice.

A study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids for just 58.8% of acne cases, while nondermatologists prescribed them for only 32.4% of cases. “If the guidelines are telling us that we should use topical retinoids for almost all of our acne patients, why are we using them for half of the patients?” Emmy Graber, MD, MBA, asked during MedscapeLive’s annual Las Vegas Dermatology Seminar. “We have a lot of options today for topical retinoids,” she added, noting that, in the past few years, trifarotene cream 0.005% and new formulations of tazarotene lotion (0.045%) and tretinoin lotion (0.05%) have become available.

According to Dr. Graber, president of The Dermatology Institute of Boston, tazarotene has been considered the most efficacious topical retinoid but is generally the least well tolerated, while adapalene has often been considered to be one of the better-tolerated topical retinoids. “This is a broad generalization,” she said. “One should also take into account the concentration and formulation of the retinoid. Cutaneous adverse events increase in severity as the concentration increases regardless of the vehicle.” There are no studies comparing trifarotene with other topical retinoids, she added.

In two phase 2, double-blind, vehicle-controlled studies (PERFECT 1 and PERFECT 2), researchers randomized more than 2,400 patients with moderate facial or truncal acne to receive trifarotene cream or a vehicle for 12 weeks. The mean percent change from baseline in facial inflammatory lesions in the trifarotene-treated group was –54.4% and –66.2% in PERFECT 1, and PERFECT 2, respectively, while the mean percent change from baseline in facial noninflammatory lesions was –49.7% and –57.7%, respectively.

In addition, the mean percent change from baseline in truncal inflammatory lesions in the trifarotene-treated groups was –57.4% and –65.4%, respectively, while the mean percent change from baseline in truncal noninflammatory lesions was –49.1% and –55.2%, respectively.

The choice of vehicle may affect absorption of topical retinoids, and some formulations may increase skin hydration and decrease transepidermal water loss, “which is a good thing,” Dr. Graber said. “Also, vehicles aim to slow drug delivery over time while also making sure that the drug penetrates into the pilosebaceous unit.”

One recent advance is the honeycomb-like polymeric emulsion technology found in tretinoin 0.05% lotion and tazarotene 0.045% lotion. These formulations contain droplets of the tretinoin and tazarotene embedded in a honeycomb matrix with hydrating agents. “I think this is exciting and could enhance our patient compliance and tolerability,” she said. Another unique feature about these two products, especially the tretinoin product, is the very small particle size with this new formulation. “It’s small enough that it can penetrate down into the pilosebaceous unit,” which is different than with older formulations, in which the tretinoin “largely just sat on the surface of the skin and didn’t penetrate into the pilosebaceous unit.” In addition, she said, “there’s only 9% degradation of the tretinoin in UV light, compared to 72% degradation of standard tretinoin 0.025% gel, and with the new tretinoin formulation, there’s no degradation when used with benzoyl peroxide.”

Another new topical retinoid to consider is a fixed-dose combination of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% cream (Twyneo), which was approved by the Food and Drug Administration in July 2021 for the treatment of acne in adults and children aged 9 years and older. “Typically, benzoyl peroxide and tretinoin cannot be mixed in the same tube to stability issues,” she said. “Here, each product is individually encapsulated in a silica shell so that they can be applied together.”

The approval was supported by positive results from two phase 3, randomized, double-blind, vehicle-controlled, multicenter studies (NCT03761784 and NCT03761810), in which Twyneo demonstrated efficacy and a favorable tolerability profile in patients aged 9 years and older with facial acne.

Another topical treatment option, dapsone, is now FDA approved for ages 9 and up, expanded from its initial indication for ages 12 and up. The new indication is based on a phase 4, multicenter, open-label study in which acne patients aged 9-11 years applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. After 12 weeks, facial acne was clear or almost clear in about 47% of patients. “Inflammatory, noninflammatory, and total lesions decreased from baseline, but there was a greater reduction in noninflammatory lesions, so if you have a very young patient with acne, now you can consider dapsone gel,” Dr. Graber said.

In August 2020, clascoterone cream became the first topical androgen receptor inhibitor approved for the treatment of acne in patients 12 years of age and older. It is a drug believed to address sebum and inflammation directly in the sebaceous gland and is structurally similar to dihydrotestosterone and spironolactone.

“This is a completely new drug category in acne,” she said. “Unlike all oral antiandrogen therapies, clascoterone cream can be used in both males and females with acne. It’s the first acne drug to have a new mechanism of action in almost 40 years, since isotretinoin was approved in 1982.”

In vitro, she continued, clascoterone competes with dihydrotestosterone for binding to the androgen receptor, inhibiting downstream signaling and leading to inhibited sebum production, reduced secretion of inflammatory cytokines, and inhibition of inflammatory pathways. Two phase 3 studies that led to its approval involved 1,440 patients with moderate to severe facial acne aged 9-58 years. The cream was applied twice a day for 12 weeks and treatment adherence was approximately 90%. The researchers found that clascoterone cream was significantly more effective than vehicle cream at achieving Investigator’s Global Assessment scores of 0 (clear) or 1 (almost clear), the definition of treatment success in the study, and reducing noninflammatory lesion and inflammatory lesion counts at week 12. “There were no safety issues noted during these studies, and clascoterone cream was well tolerated,” Dr. Graber said.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

Commentary by Lawrence W. Eichenfield, MD

Acne vulgaris remains an issue of tremendous importance to preteens, teens, and young adults, with approximately 85% of individuals aged 12-24 being affected. Expanding options for topical treatments may help bring effective disease control. Dr. Graber pointed out that historically, pediatricians and other primary care practitioners utilize topical retinoids less often for acne care as compared with dermatologists or guidelines recommendations (either the AAP’s or AAD’s). There are now expanded options, including over-the-counter retinoids (adapalene 0.1% gel), generic and trade brand topical tretinoin products, prescription adapalene medications, older and recently approved tazarotene products, and a newer type of topical retinoid, trifarotene. Novel formulations and emulsion technology, as well as retinoid developed in combination products, give more options in patients down to 9 years of age. A novel topical anti-androgen, clascoterone, is in its own category, as the first topical “hormonal agent,” allowing hormonal therapy to be used for males as well as females (aged 12 years and up). A recent review in JAMA (2021 Nov 23;326[20]:2055-67) incorporates many of these newer medications into management suggestions, emphasizing that first-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals, whereas in more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Topical retinoids are a staple first-line treatment option cited in the American Academy of Dermatology’s most recent guidelines for the care of patients with acne, yet they are likely underused in today’s clinical practice.

A study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids for just 58.8% of acne cases, while nondermatologists prescribed them for only 32.4% of cases. “If the guidelines are telling us that we should use topical retinoids for almost all of our acne patients, why are we using them for half of the patients?” Emmy Graber, MD, MBA, asked during MedscapeLive’s annual Las Vegas Dermatology Seminar. “We have a lot of options today for topical retinoids,” she added, noting that, in the past few years, trifarotene cream 0.005% and new formulations of tazarotene lotion (0.045%) and tretinoin lotion (0.05%) have become available.

According to Dr. Graber, president of The Dermatology Institute of Boston, tazarotene has been considered the most efficacious topical retinoid but is generally the least well tolerated, while adapalene has often been considered to be one of the better-tolerated topical retinoids. “This is a broad generalization,” she said. “One should also take into account the concentration and formulation of the retinoid. Cutaneous adverse events increase in severity as the concentration increases regardless of the vehicle.” There are no studies comparing trifarotene with other topical retinoids, she added.

In two phase 2, double-blind, vehicle-controlled studies (PERFECT 1 and PERFECT 2), researchers randomized more than 2,400 patients with moderate facial or truncal acne to receive trifarotene cream or a vehicle for 12 weeks. The mean percent change from baseline in facial inflammatory lesions in the trifarotene-treated group was –54.4% and –66.2% in PERFECT 1, and PERFECT 2, respectively, while the mean percent change from baseline in facial noninflammatory lesions was –49.7% and –57.7%, respectively.

In addition, the mean percent change from baseline in truncal inflammatory lesions in the trifarotene-treated groups was –57.4% and –65.4%, respectively, while the mean percent change from baseline in truncal noninflammatory lesions was –49.1% and –55.2%, respectively.

The choice of vehicle may affect absorption of topical retinoids, and some formulations may increase skin hydration and decrease transepidermal water loss, “which is a good thing,” Dr. Graber said. “Also, vehicles aim to slow drug delivery over time while also making sure that the drug penetrates into the pilosebaceous unit.”

One recent advance is the honeycomb-like polymeric emulsion technology found in tretinoin 0.05% lotion and tazarotene 0.045% lotion. These formulations contain droplets of the tretinoin and tazarotene embedded in a honeycomb matrix with hydrating agents. “I think this is exciting and could enhance our patient compliance and tolerability,” she said. Another unique feature about these two products, especially the tretinoin product, is the very small particle size with this new formulation. “It’s small enough that it can penetrate down into the pilosebaceous unit,” which is different than with older formulations, in which the tretinoin “largely just sat on the surface of the skin and didn’t penetrate into the pilosebaceous unit.” In addition, she said, “there’s only 9% degradation of the tretinoin in UV light, compared to 72% degradation of standard tretinoin 0.025% gel, and with the new tretinoin formulation, there’s no degradation when used with benzoyl peroxide.”

Another new topical retinoid to consider is a fixed-dose combination of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% cream (Twyneo), which was approved by the Food and Drug Administration in July 2021 for the treatment of acne in adults and children aged 9 years and older. “Typically, benzoyl peroxide and tretinoin cannot be mixed in the same tube to stability issues,” she said. “Here, each product is individually encapsulated in a silica shell so that they can be applied together.”

The approval was supported by positive results from two phase 3, randomized, double-blind, vehicle-controlled, multicenter studies (NCT03761784 and NCT03761810), in which Twyneo demonstrated efficacy and a favorable tolerability profile in patients aged 9 years and older with facial acne.

Another topical treatment option, dapsone, is now FDA approved for ages 9 and up, expanded from its initial indication for ages 12 and up. The new indication is based on a phase 4, multicenter, open-label study in which acne patients aged 9-11 years applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. After 12 weeks, facial acne was clear or almost clear in about 47% of patients. “Inflammatory, noninflammatory, and total lesions decreased from baseline, but there was a greater reduction in noninflammatory lesions, so if you have a very young patient with acne, now you can consider dapsone gel,” Dr. Graber said.

In August 2020, clascoterone cream became the first topical androgen receptor inhibitor approved for the treatment of acne in patients 12 years of age and older. It is a drug believed to address sebum and inflammation directly in the sebaceous gland and is structurally similar to dihydrotestosterone and spironolactone.

“This is a completely new drug category in acne,” she said. “Unlike all oral antiandrogen therapies, clascoterone cream can be used in both males and females with acne. It’s the first acne drug to have a new mechanism of action in almost 40 years, since isotretinoin was approved in 1982.”

In vitro, she continued, clascoterone competes with dihydrotestosterone for binding to the androgen receptor, inhibiting downstream signaling and leading to inhibited sebum production, reduced secretion of inflammatory cytokines, and inhibition of inflammatory pathways. Two phase 3 studies that led to its approval involved 1,440 patients with moderate to severe facial acne aged 9-58 years. The cream was applied twice a day for 12 weeks and treatment adherence was approximately 90%. The researchers found that clascoterone cream was significantly more effective than vehicle cream at achieving Investigator’s Global Assessment scores of 0 (clear) or 1 (almost clear), the definition of treatment success in the study, and reducing noninflammatory lesion and inflammatory lesion counts at week 12. “There were no safety issues noted during these studies, and clascoterone cream was well tolerated,” Dr. Graber said.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

Commentary by Lawrence W. Eichenfield, MD

Acne vulgaris remains an issue of tremendous importance to preteens, teens, and young adults, with approximately 85% of individuals aged 12-24 being affected. Expanding options for topical treatments may help bring effective disease control. Dr. Graber pointed out that historically, pediatricians and other primary care practitioners utilize topical retinoids less often for acne care as compared with dermatologists or guidelines recommendations (either the AAP’s or AAD’s). There are now expanded options, including over-the-counter retinoids (adapalene 0.1% gel), generic and trade brand topical tretinoin products, prescription adapalene medications, older and recently approved tazarotene products, and a newer type of topical retinoid, trifarotene. Novel formulations and emulsion technology, as well as retinoid developed in combination products, give more options in patients down to 9 years of age. A novel topical anti-androgen, clascoterone, is in its own category, as the first topical “hormonal agent,” allowing hormonal therapy to be used for males as well as females (aged 12 years and up). A recent review in JAMA (2021 Nov 23;326[20]:2055-67) incorporates many of these newer medications into management suggestions, emphasizing that first-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals, whereas in more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Topical retinoids are a staple first-line treatment option cited in the American Academy of Dermatology’s most recent guidelines for the care of patients with acne, yet they are likely underused in today’s clinical practice.

A study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids for just 58.8% of acne cases, while nondermatologists prescribed them for only 32.4% of cases. “If the guidelines are telling us that we should use topical retinoids for almost all of our acne patients, why are we using them for half of the patients?” Emmy Graber, MD, MBA, asked during MedscapeLive’s annual Las Vegas Dermatology Seminar. “We have a lot of options today for topical retinoids,” she added, noting that, in the past few years, trifarotene cream 0.005% and new formulations of tazarotene lotion (0.045%) and tretinoin lotion (0.05%) have become available.

According to Dr. Graber, president of The Dermatology Institute of Boston, tazarotene has been considered the most efficacious topical retinoid but is generally the least well tolerated, while adapalene has often been considered to be one of the better-tolerated topical retinoids. “This is a broad generalization,” she said. “One should also take into account the concentration and formulation of the retinoid. Cutaneous adverse events increase in severity as the concentration increases regardless of the vehicle.” There are no studies comparing trifarotene with other topical retinoids, she added.

In two phase 2, double-blind, vehicle-controlled studies (PERFECT 1 and PERFECT 2), researchers randomized more than 2,400 patients with moderate facial or truncal acne to receive trifarotene cream or a vehicle for 12 weeks. The mean percent change from baseline in facial inflammatory lesions in the trifarotene-treated group was –54.4% and –66.2% in PERFECT 1, and PERFECT 2, respectively, while the mean percent change from baseline in facial noninflammatory lesions was –49.7% and –57.7%, respectively.

In addition, the mean percent change from baseline in truncal inflammatory lesions in the trifarotene-treated groups was –57.4% and –65.4%, respectively, while the mean percent change from baseline in truncal noninflammatory lesions was –49.1% and –55.2%, respectively.

The choice of vehicle may affect absorption of topical retinoids, and some formulations may increase skin hydration and decrease transepidermal water loss, “which is a good thing,” Dr. Graber said. “Also, vehicles aim to slow drug delivery over time while also making sure that the drug penetrates into the pilosebaceous unit.”

One recent advance is the honeycomb-like polymeric emulsion technology found in tretinoin 0.05% lotion and tazarotene 0.045% lotion. These formulations contain droplets of the tretinoin and tazarotene embedded in a honeycomb matrix with hydrating agents. “I think this is exciting and could enhance our patient compliance and tolerability,” she said. Another unique feature about these two products, especially the tretinoin product, is the very small particle size with this new formulation. “It’s small enough that it can penetrate down into the pilosebaceous unit,” which is different than with older formulations, in which the tretinoin “largely just sat on the surface of the skin and didn’t penetrate into the pilosebaceous unit.” In addition, she said, “there’s only 9% degradation of the tretinoin in UV light, compared to 72% degradation of standard tretinoin 0.025% gel, and with the new tretinoin formulation, there’s no degradation when used with benzoyl peroxide.”

Another new topical retinoid to consider is a fixed-dose combination of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% cream (Twyneo), which was approved by the Food and Drug Administration in July 2021 for the treatment of acne in adults and children aged 9 years and older. “Typically, benzoyl peroxide and tretinoin cannot be mixed in the same tube to stability issues,” she said. “Here, each product is individually encapsulated in a silica shell so that they can be applied together.”

The approval was supported by positive results from two phase 3, randomized, double-blind, vehicle-controlled, multicenter studies (NCT03761784 and NCT03761810), in which Twyneo demonstrated efficacy and a favorable tolerability profile in patients aged 9 years and older with facial acne.

Another topical treatment option, dapsone, is now FDA approved for ages 9 and up, expanded from its initial indication for ages 12 and up. The new indication is based on a phase 4, multicenter, open-label study in which acne patients aged 9-11 years applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. After 12 weeks, facial acne was clear or almost clear in about 47% of patients. “Inflammatory, noninflammatory, and total lesions decreased from baseline, but there was a greater reduction in noninflammatory lesions, so if you have a very young patient with acne, now you can consider dapsone gel,” Dr. Graber said.

In August 2020, clascoterone cream became the first topical androgen receptor inhibitor approved for the treatment of acne in patients 12 years of age and older. It is a drug believed to address sebum and inflammation directly in the sebaceous gland and is structurally similar to dihydrotestosterone and spironolactone.

“This is a completely new drug category in acne,” she said. “Unlike all oral antiandrogen therapies, clascoterone cream can be used in both males and females with acne. It’s the first acne drug to have a new mechanism of action in almost 40 years, since isotretinoin was approved in 1982.”

In vitro, she continued, clascoterone competes with dihydrotestosterone for binding to the androgen receptor, inhibiting downstream signaling and leading to inhibited sebum production, reduced secretion of inflammatory cytokines, and inhibition of inflammatory pathways. Two phase 3 studies that led to its approval involved 1,440 patients with moderate to severe facial acne aged 9-58 years. The cream was applied twice a day for 12 weeks and treatment adherence was approximately 90%. The researchers found that clascoterone cream was significantly more effective than vehicle cream at achieving Investigator’s Global Assessment scores of 0 (clear) or 1 (almost clear), the definition of treatment success in the study, and reducing noninflammatory lesion and inflammatory lesion counts at week 12. “There were no safety issues noted during these studies, and clascoterone cream was well tolerated,” Dr. Graber said.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

Commentary by Lawrence W. Eichenfield, MD

Acne vulgaris remains an issue of tremendous importance to preteens, teens, and young adults, with approximately 85% of individuals aged 12-24 being affected. Expanding options for topical treatments may help bring effective disease control. Dr. Graber pointed out that historically, pediatricians and other primary care practitioners utilize topical retinoids less often for acne care as compared with dermatologists or guidelines recommendations (either the AAP’s or AAD’s). There are now expanded options, including over-the-counter retinoids (adapalene 0.1% gel), generic and trade brand topical tretinoin products, prescription adapalene medications, older and recently approved tazarotene products, and a newer type of topical retinoid, trifarotene. Novel formulations and emulsion technology, as well as retinoid developed in combination products, give more options in patients down to 9 years of age. A novel topical anti-androgen, clascoterone, is in its own category, as the first topical “hormonal agent,” allowing hormonal therapy to be used for males as well as females (aged 12 years and up). A recent review in JAMA (2021 Nov 23;326[20]:2055-67) incorporates many of these newer medications into management suggestions, emphasizing that first-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals, whereas in more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

While a squamous cell carcinoma presenting this way is perhaps more common, this nonhealing draining papule over a sternal scar was actually a sternocutaneous fistula (SCF). Examination revealed multiple bound down pits along the sternotomy scar. Very gentle probing of the papule in consideration of biopsy revealed a wire foreign body—the end of a sternotomy wire. A culture of yellow discharge ultimately grew Staphylococcus aureus.

SCF is a rare, and sometimes devastating, complication of cardiac surgery that occurred in 0.23% of cases at 1-year in a single center study of 12,297 patients over 9 years.¹ As in this case, it may also present distantly from the time of surgery. The risk of SCF increases with smoking, previous sternal wound infection, renal failure, and use of bone wax during surgery.¹

As soon as there was concern for SCF as a possible diagnosis, the patient was referred to, and quickly evaluated by, Cardiothoracic Surgery. Ultrasound and computed tomography imaging did not reveal any osteomyelitis or deep mediastinal disease. He was treated with debridement and removal of the sternotomy wire. At the 1-year follow-up, he had no further episodes of skin infection in the area.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

While a squamous cell carcinoma presenting this way is perhaps more common, this nonhealing draining papule over a sternal scar was actually a sternocutaneous fistula (SCF). Examination revealed multiple bound down pits along the sternotomy scar. Very gentle probing of the papule in consideration of biopsy revealed a wire foreign body—the end of a sternotomy wire. A culture of yellow discharge ultimately grew Staphylococcus aureus.

SCF is a rare, and sometimes devastating, complication of cardiac surgery that occurred in 0.23% of cases at 1-year in a single center study of 12,297 patients over 9 years.¹ As in this case, it may also present distantly from the time of surgery. The risk of SCF increases with smoking, previous sternal wound infection, renal failure, and use of bone wax during surgery.¹

As soon as there was concern for SCF as a possible diagnosis, the patient was referred to, and quickly evaluated by, Cardiothoracic Surgery. Ultrasound and computed tomography imaging did not reveal any osteomyelitis or deep mediastinal disease. He was treated with debridement and removal of the sternotomy wire. At the 1-year follow-up, he had no further episodes of skin infection in the area.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

While a squamous cell carcinoma presenting this way is perhaps more common, this nonhealing draining papule over a sternal scar was actually a sternocutaneous fistula (SCF). Examination revealed multiple bound down pits along the sternotomy scar. Very gentle probing of the papule in consideration of biopsy revealed a wire foreign body—the end of a sternotomy wire. A culture of yellow discharge ultimately grew Staphylococcus aureus.

SCF is a rare, and sometimes devastating, complication of cardiac surgery that occurred in 0.23% of cases at 1-year in a single center study of 12,297 patients over 9 years.¹ As in this case, it may also present distantly from the time of surgery. The risk of SCF increases with smoking, previous sternal wound infection, renal failure, and use of bone wax during surgery.¹

As soon as there was concern for SCF as a possible diagnosis, the patient was referred to, and quickly evaluated by, Cardiothoracic Surgery. Ultrasound and computed tomography imaging did not reveal any osteomyelitis or deep mediastinal disease. He was treated with debridement and removal of the sternotomy wire. At the 1-year follow-up, he had no further episodes of skin infection in the area.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Medications may cause a variety of cutaneous reactions. The most common type of reaction is an exanthematous (morbilliform or scarlatiniform) drug reaction. Reactions can occur anytime from within the first 2 weeks of treatment up to 10 days after the treatment has been discontinued. If a drug is rechallenged, eruptions may occur sooner. Pruritus is commonly seen. Clinically, erythematous papules and macules present symmetrically on the trunk and upper extremities and then become more generalized. A low-grade fever may be present.

Courtesy Dr. Donna Bilu Martin

Antibiotics are the most common causes of exanthematous drug eruptions. Penicillins and trimethoprim-sulfamethoxazole are common offenders. Cephalosporins, anticonvulsants, and allopurinol may also induce a reaction. As this condition is diagnosed clinically, skin biopsy is often not necessary. Histology is nonspecific and shows a mild perivascular lymphocytic infiltrate and few epidermal necrotic keratinocytes.

In drug reaction with eosinophilia and systemic symptoms (DRESS), symptoms present 2-6 weeks after the offending medication has been started. The cutaneous rash appears similar to an exanthematous drug eruption; however, lesions will also present on the face, and facial edema may occur. Fever is often present. Laboratory findings include a marked peripheral blood hypereosinophilia. Elevated liver function tests may be seen. Viruses such as Epstein-Barr virus, enteroviruses, adenovirus, early HIV, human herpesvirus 6, and parvovirus B19 have a similar clinical appearance to an exanthematous drug eruption. A mild eosinophilia, as seen in a drug eruption, helps to distinguish between a drug eruption and viral exanthem. In Stevens-Johnson Syndrome, mucosal membranes are involved and skin is often painful or appears dusky.

Treatment of exanthematous drug eruptions is largely supportive. Discontinuing the drug will help speed resolution and topical steroids may alleviate pruritus.

This case and photo were submitted by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Bolognia J et al. “Dermatology” (St. Louis: Mosby/Elsevier, 2008).

2. James W et al. “Andrews’ Diseases of the Skin,” 13th ed. (Philadelphia: Saunders Elsevier, 2006).

Medications may cause a variety of cutaneous reactions. The most common type of reaction is an exanthematous (morbilliform or scarlatiniform) drug reaction. Reactions can occur anytime from within the first 2 weeks of treatment up to 10 days after the treatment has been discontinued. If a drug is rechallenged, eruptions may occur sooner. Pruritus is commonly seen. Clinically, erythematous papules and macules present symmetrically on the trunk and upper extremities and then become more generalized. A low-grade fever may be present.

Courtesy Dr. Donna Bilu Martin

Antibiotics are the most common causes of exanthematous drug eruptions. Penicillins and trimethoprim-sulfamethoxazole are common offenders. Cephalosporins, anticonvulsants, and allopurinol may also induce a reaction. As this condition is diagnosed clinically, skin biopsy is often not necessary. Histology is nonspecific and shows a mild perivascular lymphocytic infiltrate and few epidermal necrotic keratinocytes.

In drug reaction with eosinophilia and systemic symptoms (DRESS), symptoms present 2-6 weeks after the offending medication has been started. The cutaneous rash appears similar to an exanthematous drug eruption; however, lesions will also present on the face, and facial edema may occur. Fever is often present. Laboratory findings include a marked peripheral blood hypereosinophilia. Elevated liver function tests may be seen. Viruses such as Epstein-Barr virus, enteroviruses, adenovirus, early HIV, human herpesvirus 6, and parvovirus B19 have a similar clinical appearance to an exanthematous drug eruption. A mild eosinophilia, as seen in a drug eruption, helps to distinguish between a drug eruption and viral exanthem. In Stevens-Johnson Syndrome, mucosal membranes are involved and skin is often painful or appears dusky.

Treatment of exanthematous drug eruptions is largely supportive. Discontinuing the drug will help speed resolution and topical steroids may alleviate pruritus.

This case and photo were submitted by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Bolognia J et al. “Dermatology” (St. Louis: Mosby/Elsevier, 2008).

2. James W et al. “Andrews’ Diseases of the Skin,” 13th ed. (Philadelphia: Saunders Elsevier, 2006).

Medications may cause a variety of cutaneous reactions. The most common type of reaction is an exanthematous (morbilliform or scarlatiniform) drug reaction. Reactions can occur anytime from within the first 2 weeks of treatment up to 10 days after the treatment has been discontinued. If a drug is rechallenged, eruptions may occur sooner. Pruritus is commonly seen. Clinically, erythematous papules and macules present symmetrically on the trunk and upper extremities and then become more generalized. A low-grade fever may be present.

Courtesy Dr. Donna Bilu Martin

Antibiotics are the most common causes of exanthematous drug eruptions. Penicillins and trimethoprim-sulfamethoxazole are common offenders. Cephalosporins, anticonvulsants, and allopurinol may also induce a reaction. As this condition is diagnosed clinically, skin biopsy is often not necessary. Histology is nonspecific and shows a mild perivascular lymphocytic infiltrate and few epidermal necrotic keratinocytes.

In drug reaction with eosinophilia and systemic symptoms (DRESS), symptoms present 2-6 weeks after the offending medication has been started. The cutaneous rash appears similar to an exanthematous drug eruption; however, lesions will also present on the face, and facial edema may occur. Fever is often present. Laboratory findings include a marked peripheral blood hypereosinophilia. Elevated liver function tests may be seen. Viruses such as Epstein-Barr virus, enteroviruses, adenovirus, early HIV, human herpesvirus 6, and parvovirus B19 have a similar clinical appearance to an exanthematous drug eruption. A mild eosinophilia, as seen in a drug eruption, helps to distinguish between a drug eruption and viral exanthem. In Stevens-Johnson Syndrome, mucosal membranes are involved and skin is often painful or appears dusky.

Treatment of exanthematous drug eruptions is largely supportive. Discontinuing the drug will help speed resolution and topical steroids may alleviate pruritus.

This case and photo were submitted by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Bolognia J et al. “Dermatology” (St. Louis: Mosby/Elsevier, 2008).

2. James W et al. “Andrews’ Diseases of the Skin,” 13th ed. (Philadelphia: Saunders Elsevier, 2006).