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Real-world experience with dupilumab in AD mirrors clinical trial efficacy
MILAN – A retrospective, multicenter Maria Fargnoli, MD, reported at the World Congress of Dermatology.
By the end of 4 weeks of treatment, participants’ mean Eczema Area and Severity Index (EASI) score had dropped from 33.3 to 15.3, a 54.2% reduction. At 16 weeks, the mean EASI score was 9.2, a reduction of 72.5% from baseline (P less than .001 for both time points, compared with baseline). At 16 weeks, 87.2% of patients achieved EASI 50, 60.6% achieved EASI 75, and 32.4% achieved EASI 90.
“In a real-life context, dupilumab significantly improved disease severity, pruritus, sleep loss, and quality of life in adult moderate to severe atopic dermatitis patients,” said Dr. Fargnoli, presenting results of the study during a late-breaking abstract session at the meeting. “All measures improved at 4 weeks, and a further decline was seen at 16 weeks. … These results confirm data from clinical trials, and from other real-life experiences with dupilumab.”
The study, conducted in Italy, tracked outcomes for 109 patients treated for moderate to severe atopic dermatitis at 39 centers from June 2018 to February 2019. Adult patients with EASI scores of at least 24 with contraindications, failure, or intolerance of corticosteroid therapy were included and followed for at least 16 weeks. Those who had concomitant systemic anti-inflammatory or immunomodulator use were excluded, as were those with missing data, said Dr. Fargnoli, chair of the department of dermatology at the University of L’Aquila (Italy).
Patients were given a loading dose of two 300-mg subcutaneous injections of dupilumab, followed by 300-mg injections at 2-week intervals.
Patients were assessed at baseline and after 4 and 16 weeks of treatment. In addition to EASI score, itch and sleep were measured via numeric rating scales; mean itch scores dropped from 8.4 at baseline to 4.1 after 4 weeks, and to 2.5 at 16 weeks (P less than .001 for both time points, compared with baseline).
Sleep scores also improved, from a mean 6.9 at baseline to 3.3 at four weeks, and 1.9 at 16 weeks (P less than .001 for both time points, compared with baseline).
Patients also completed the Dermatology Life Quality Index. At the 4-week mark, patients saw a reduction to 8.3 points from the baseline score of 17.6 points (out of a possible 30, with higher scores indicating worse quality of life); scores dropped to 5.4 by week 16 (P less than .001 for both time points, compared with baseline).
Dupilumab was generally well tolerated, with conjunctivitis – seen in 11% of patients – being the most commonly reported adverse event. This falls in line with other recently published real-world studies of dupilumab, Dr. Fargnoli noted.
Efficacy, as measured by EASI reduction and improvement in itch and sleep, were also comparable between the Italian cohort and clinical trial results, as well as other real-life studies in Denmark, France, the Netherlands, and Spain, she said.
Patients, about one-third female, had a mean body mass index of about 24 kg/m2. Mean age was about 38 years (range, 19-80 years). The mean age of disease onset was about 14 years (range, 0-77 years).
Atopic dermatitis was characterized by phenotype for each patient; groupings included classic adult type (73%), nummular dermatitis (7%), prurigo (8%), and erythrodermic dermatitis (12%). About three in four patients (76.1%) had facial involvement; 61.5% had hand involvement, and 22.9% had genital involvement.
Allergic comorbidities were reported by many patients; 44.9% had rhinitis, 38.5% had asthma, 33% had conjunctivitis, and 15.6% reported food allergies. Other notable comorbidities included psychiatric or psychological conditions, present in 11% of patients, and hypertension or other cardiovascular disorders, seen in 9.1% of patients.
Most patients had tried treatment with both cyclosporine A and corticosteroids (88.9% and 88.1%, respectively). Almost half (45.8%) had tried UV-light therapy, and about a quarter had tried methotrexate.
“The results give real-life data on patterns of treatment response according to heterogeneous atopic dermatitis phenotypes, and on long-term efficacy and safety,” said Dr. Fargnoli.
The study was not funded by any company, according to Dr. Fargnoli. She has served on the advisory board for and has received honoraria for lectures and research grants from Sanofi-Genzyme.
MILAN – A retrospective, multicenter Maria Fargnoli, MD, reported at the World Congress of Dermatology.
By the end of 4 weeks of treatment, participants’ mean Eczema Area and Severity Index (EASI) score had dropped from 33.3 to 15.3, a 54.2% reduction. At 16 weeks, the mean EASI score was 9.2, a reduction of 72.5% from baseline (P less than .001 for both time points, compared with baseline). At 16 weeks, 87.2% of patients achieved EASI 50, 60.6% achieved EASI 75, and 32.4% achieved EASI 90.
“In a real-life context, dupilumab significantly improved disease severity, pruritus, sleep loss, and quality of life in adult moderate to severe atopic dermatitis patients,” said Dr. Fargnoli, presenting results of the study during a late-breaking abstract session at the meeting. “All measures improved at 4 weeks, and a further decline was seen at 16 weeks. … These results confirm data from clinical trials, and from other real-life experiences with dupilumab.”
The study, conducted in Italy, tracked outcomes for 109 patients treated for moderate to severe atopic dermatitis at 39 centers from June 2018 to February 2019. Adult patients with EASI scores of at least 24 with contraindications, failure, or intolerance of corticosteroid therapy were included and followed for at least 16 weeks. Those who had concomitant systemic anti-inflammatory or immunomodulator use were excluded, as were those with missing data, said Dr. Fargnoli, chair of the department of dermatology at the University of L’Aquila (Italy).
Patients were given a loading dose of two 300-mg subcutaneous injections of dupilumab, followed by 300-mg injections at 2-week intervals.
Patients were assessed at baseline and after 4 and 16 weeks of treatment. In addition to EASI score, itch and sleep were measured via numeric rating scales; mean itch scores dropped from 8.4 at baseline to 4.1 after 4 weeks, and to 2.5 at 16 weeks (P less than .001 for both time points, compared with baseline).
Sleep scores also improved, from a mean 6.9 at baseline to 3.3 at four weeks, and 1.9 at 16 weeks (P less than .001 for both time points, compared with baseline).
Patients also completed the Dermatology Life Quality Index. At the 4-week mark, patients saw a reduction to 8.3 points from the baseline score of 17.6 points (out of a possible 30, with higher scores indicating worse quality of life); scores dropped to 5.4 by week 16 (P less than .001 for both time points, compared with baseline).
Dupilumab was generally well tolerated, with conjunctivitis – seen in 11% of patients – being the most commonly reported adverse event. This falls in line with other recently published real-world studies of dupilumab, Dr. Fargnoli noted.
Efficacy, as measured by EASI reduction and improvement in itch and sleep, were also comparable between the Italian cohort and clinical trial results, as well as other real-life studies in Denmark, France, the Netherlands, and Spain, she said.
Patients, about one-third female, had a mean body mass index of about 24 kg/m2. Mean age was about 38 years (range, 19-80 years). The mean age of disease onset was about 14 years (range, 0-77 years).
Atopic dermatitis was characterized by phenotype for each patient; groupings included classic adult type (73%), nummular dermatitis (7%), prurigo (8%), and erythrodermic dermatitis (12%). About three in four patients (76.1%) had facial involvement; 61.5% had hand involvement, and 22.9% had genital involvement.
Allergic comorbidities were reported by many patients; 44.9% had rhinitis, 38.5% had asthma, 33% had conjunctivitis, and 15.6% reported food allergies. Other notable comorbidities included psychiatric or psychological conditions, present in 11% of patients, and hypertension or other cardiovascular disorders, seen in 9.1% of patients.
Most patients had tried treatment with both cyclosporine A and corticosteroids (88.9% and 88.1%, respectively). Almost half (45.8%) had tried UV-light therapy, and about a quarter had tried methotrexate.
“The results give real-life data on patterns of treatment response according to heterogeneous atopic dermatitis phenotypes, and on long-term efficacy and safety,” said Dr. Fargnoli.
The study was not funded by any company, according to Dr. Fargnoli. She has served on the advisory board for and has received honoraria for lectures and research grants from Sanofi-Genzyme.
MILAN – A retrospective, multicenter Maria Fargnoli, MD, reported at the World Congress of Dermatology.
By the end of 4 weeks of treatment, participants’ mean Eczema Area and Severity Index (EASI) score had dropped from 33.3 to 15.3, a 54.2% reduction. At 16 weeks, the mean EASI score was 9.2, a reduction of 72.5% from baseline (P less than .001 for both time points, compared with baseline). At 16 weeks, 87.2% of patients achieved EASI 50, 60.6% achieved EASI 75, and 32.4% achieved EASI 90.
“In a real-life context, dupilumab significantly improved disease severity, pruritus, sleep loss, and quality of life in adult moderate to severe atopic dermatitis patients,” said Dr. Fargnoli, presenting results of the study during a late-breaking abstract session at the meeting. “All measures improved at 4 weeks, and a further decline was seen at 16 weeks. … These results confirm data from clinical trials, and from other real-life experiences with dupilumab.”
The study, conducted in Italy, tracked outcomes for 109 patients treated for moderate to severe atopic dermatitis at 39 centers from June 2018 to February 2019. Adult patients with EASI scores of at least 24 with contraindications, failure, or intolerance of corticosteroid therapy were included and followed for at least 16 weeks. Those who had concomitant systemic anti-inflammatory or immunomodulator use were excluded, as were those with missing data, said Dr. Fargnoli, chair of the department of dermatology at the University of L’Aquila (Italy).
Patients were given a loading dose of two 300-mg subcutaneous injections of dupilumab, followed by 300-mg injections at 2-week intervals.
Patients were assessed at baseline and after 4 and 16 weeks of treatment. In addition to EASI score, itch and sleep were measured via numeric rating scales; mean itch scores dropped from 8.4 at baseline to 4.1 after 4 weeks, and to 2.5 at 16 weeks (P less than .001 for both time points, compared with baseline).
Sleep scores also improved, from a mean 6.9 at baseline to 3.3 at four weeks, and 1.9 at 16 weeks (P less than .001 for both time points, compared with baseline).
Patients also completed the Dermatology Life Quality Index. At the 4-week mark, patients saw a reduction to 8.3 points from the baseline score of 17.6 points (out of a possible 30, with higher scores indicating worse quality of life); scores dropped to 5.4 by week 16 (P less than .001 for both time points, compared with baseline).
Dupilumab was generally well tolerated, with conjunctivitis – seen in 11% of patients – being the most commonly reported adverse event. This falls in line with other recently published real-world studies of dupilumab, Dr. Fargnoli noted.
Efficacy, as measured by EASI reduction and improvement in itch and sleep, were also comparable between the Italian cohort and clinical trial results, as well as other real-life studies in Denmark, France, the Netherlands, and Spain, she said.
Patients, about one-third female, had a mean body mass index of about 24 kg/m2. Mean age was about 38 years (range, 19-80 years). The mean age of disease onset was about 14 years (range, 0-77 years).
Atopic dermatitis was characterized by phenotype for each patient; groupings included classic adult type (73%), nummular dermatitis (7%), prurigo (8%), and erythrodermic dermatitis (12%). About three in four patients (76.1%) had facial involvement; 61.5% had hand involvement, and 22.9% had genital involvement.
Allergic comorbidities were reported by many patients; 44.9% had rhinitis, 38.5% had asthma, 33% had conjunctivitis, and 15.6% reported food allergies. Other notable comorbidities included psychiatric or psychological conditions, present in 11% of patients, and hypertension or other cardiovascular disorders, seen in 9.1% of patients.
Most patients had tried treatment with both cyclosporine A and corticosteroids (88.9% and 88.1%, respectively). Almost half (45.8%) had tried UV-light therapy, and about a quarter had tried methotrexate.
“The results give real-life data on patterns of treatment response according to heterogeneous atopic dermatitis phenotypes, and on long-term efficacy and safety,” said Dr. Fargnoli.
The study was not funded by any company, according to Dr. Fargnoli. She has served on the advisory board for and has received honoraria for lectures and research grants from Sanofi-Genzyme.
REPORTING FROM WCD2019
Cyclosporine, methotrexate have lowest 6-month infection risk for AD patients
(AD) receiving systemic therapy in a real-world setting, according to a recently published population-based study.
When compared with methotrexate, there was a significant reduction in risk of serious infection at 6 months for patients with AD receiving cyclosporine. Prednisone, azathioprine, and mycophenolate carried higher risks of serious infections at 6 months than methotrexate or cyclosporine, researchers said in the study, which appeared in the Journal of the American Academy of Dermatology.
“Among non-biologic systemic agents, cyclosporine and methotrexate appear to have better safety profiles than mycophenolate, azathioprine, and systemic prednisone with regard to serious infections,” they concluded. “These findings may help inform clinicians in their selection of medications for patients requiring systemic therapy for atopic dermatitis,” Maria C. Schneeweiss, MD, from the departments of dermatology and medicine and Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital, Boston, and colleagues wrote in their study.
Using population-based claims data, the researchers evaluated rates of serious infection requiring hospitalization in 232,611 patients between January 2003 and January 2017 who received methotrexate, cyclosporine, azathioprine, prednisone or mycophenolate for treatment of AD. Patients first received the same level of corticosteroids before moving to systemic therapy or phototherapy. They also compared results with 23,908 patients in a second cohort who were new users of dupilumab (391 patients) or non-biologic systemic immunomodulators (23,517).
Overall, the rate of serious infections was 7.53 per 1,000 for patients receiving systemic non-biologic therapy at 6 months compared with 7.38 per 1,000 for patients receiving phototherapy, and 2.6 per 1,000 for patients receiving dupilumab.
When matching using propensity scores, the researchers found a significantly reduced risk at 6 months of serious infections from cyclosporine compared with methotrexate (relative risk, 0.87; 95% confidence interval, 0.59-1.28). Compared with methotrexate, there was an increased risk of serious infection at 6 months for azathioprine (RR, 1.78; 95% CI, 0.98-3.25), prednisone (RR, 1.89; 95% CI, 1.05-3.42) and mycophenolate (RR, 3.31; 95% CI, 1.94-5.64).
According to preliminary data, when compared with patients who received non-biologic systemic therapy, there was no increased risk for patients receiving dupilumab (RR, 0.33; 95% CI, 0.03-3.20). Dupilumab was approved in March 2017, and “with one year of data resulting in one event among 391 patients, this analysis is limited but does not show an obvious signal for increased risk” for dupilumab, they wrote.
Dr. Schneeweiss and colleagues noted some of their analyses had wide confidence intervals, they did not account for dosing schemes or cumulative dose exposure over the study period, and the data on dupilumab showing no increase were preliminary and not conclusive.
“Our findings on systemic non-biologics are highly plausible, given the known risk of systemic immunomodulators in patients treated for other indications, the meaningful effect size, and the methodologically robust approach with a new-user active-comparator design and propensity score matching,” the researchers said.
This study was funded in part by Brigham and Women’s Hospital in Boston. One author reported being a consultant for multiple pharmaceutical companies. The other authors report no relevant conflicts of interest.
SOURCE: Schneeweiss M, et al. J Am Acad Dermatol. 2019. doi:10.1016/j.jaad.2019.05.073.
(AD) receiving systemic therapy in a real-world setting, according to a recently published population-based study.
When compared with methotrexate, there was a significant reduction in risk of serious infection at 6 months for patients with AD receiving cyclosporine. Prednisone, azathioprine, and mycophenolate carried higher risks of serious infections at 6 months than methotrexate or cyclosporine, researchers said in the study, which appeared in the Journal of the American Academy of Dermatology.
“Among non-biologic systemic agents, cyclosporine and methotrexate appear to have better safety profiles than mycophenolate, azathioprine, and systemic prednisone with regard to serious infections,” they concluded. “These findings may help inform clinicians in their selection of medications for patients requiring systemic therapy for atopic dermatitis,” Maria C. Schneeweiss, MD, from the departments of dermatology and medicine and Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital, Boston, and colleagues wrote in their study.
Using population-based claims data, the researchers evaluated rates of serious infection requiring hospitalization in 232,611 patients between January 2003 and January 2017 who received methotrexate, cyclosporine, azathioprine, prednisone or mycophenolate for treatment of AD. Patients first received the same level of corticosteroids before moving to systemic therapy or phototherapy. They also compared results with 23,908 patients in a second cohort who were new users of dupilumab (391 patients) or non-biologic systemic immunomodulators (23,517).
Overall, the rate of serious infections was 7.53 per 1,000 for patients receiving systemic non-biologic therapy at 6 months compared with 7.38 per 1,000 for patients receiving phototherapy, and 2.6 per 1,000 for patients receiving dupilumab.
When matching using propensity scores, the researchers found a significantly reduced risk at 6 months of serious infections from cyclosporine compared with methotrexate (relative risk, 0.87; 95% confidence interval, 0.59-1.28). Compared with methotrexate, there was an increased risk of serious infection at 6 months for azathioprine (RR, 1.78; 95% CI, 0.98-3.25), prednisone (RR, 1.89; 95% CI, 1.05-3.42) and mycophenolate (RR, 3.31; 95% CI, 1.94-5.64).
According to preliminary data, when compared with patients who received non-biologic systemic therapy, there was no increased risk for patients receiving dupilumab (RR, 0.33; 95% CI, 0.03-3.20). Dupilumab was approved in March 2017, and “with one year of data resulting in one event among 391 patients, this analysis is limited but does not show an obvious signal for increased risk” for dupilumab, they wrote.
Dr. Schneeweiss and colleagues noted some of their analyses had wide confidence intervals, they did not account for dosing schemes or cumulative dose exposure over the study period, and the data on dupilumab showing no increase were preliminary and not conclusive.
“Our findings on systemic non-biologics are highly plausible, given the known risk of systemic immunomodulators in patients treated for other indications, the meaningful effect size, and the methodologically robust approach with a new-user active-comparator design and propensity score matching,” the researchers said.
This study was funded in part by Brigham and Women’s Hospital in Boston. One author reported being a consultant for multiple pharmaceutical companies. The other authors report no relevant conflicts of interest.
SOURCE: Schneeweiss M, et al. J Am Acad Dermatol. 2019. doi:10.1016/j.jaad.2019.05.073.
(AD) receiving systemic therapy in a real-world setting, according to a recently published population-based study.
When compared with methotrexate, there was a significant reduction in risk of serious infection at 6 months for patients with AD receiving cyclosporine. Prednisone, azathioprine, and mycophenolate carried higher risks of serious infections at 6 months than methotrexate or cyclosporine, researchers said in the study, which appeared in the Journal of the American Academy of Dermatology.
“Among non-biologic systemic agents, cyclosporine and methotrexate appear to have better safety profiles than mycophenolate, azathioprine, and systemic prednisone with regard to serious infections,” they concluded. “These findings may help inform clinicians in their selection of medications for patients requiring systemic therapy for atopic dermatitis,” Maria C. Schneeweiss, MD, from the departments of dermatology and medicine and Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital, Boston, and colleagues wrote in their study.
Using population-based claims data, the researchers evaluated rates of serious infection requiring hospitalization in 232,611 patients between January 2003 and January 2017 who received methotrexate, cyclosporine, azathioprine, prednisone or mycophenolate for treatment of AD. Patients first received the same level of corticosteroids before moving to systemic therapy or phototherapy. They also compared results with 23,908 patients in a second cohort who were new users of dupilumab (391 patients) or non-biologic systemic immunomodulators (23,517).
Overall, the rate of serious infections was 7.53 per 1,000 for patients receiving systemic non-biologic therapy at 6 months compared with 7.38 per 1,000 for patients receiving phototherapy, and 2.6 per 1,000 for patients receiving dupilumab.
When matching using propensity scores, the researchers found a significantly reduced risk at 6 months of serious infections from cyclosporine compared with methotrexate (relative risk, 0.87; 95% confidence interval, 0.59-1.28). Compared with methotrexate, there was an increased risk of serious infection at 6 months for azathioprine (RR, 1.78; 95% CI, 0.98-3.25), prednisone (RR, 1.89; 95% CI, 1.05-3.42) and mycophenolate (RR, 3.31; 95% CI, 1.94-5.64).
According to preliminary data, when compared with patients who received non-biologic systemic therapy, there was no increased risk for patients receiving dupilumab (RR, 0.33; 95% CI, 0.03-3.20). Dupilumab was approved in March 2017, and “with one year of data resulting in one event among 391 patients, this analysis is limited but does not show an obvious signal for increased risk” for dupilumab, they wrote.
Dr. Schneeweiss and colleagues noted some of their analyses had wide confidence intervals, they did not account for dosing schemes or cumulative dose exposure over the study period, and the data on dupilumab showing no increase were preliminary and not conclusive.
“Our findings on systemic non-biologics are highly plausible, given the known risk of systemic immunomodulators in patients treated for other indications, the meaningful effect size, and the methodologically robust approach with a new-user active-comparator design and propensity score matching,” the researchers said.
This study was funded in part by Brigham and Women’s Hospital in Boston. One author reported being a consultant for multiple pharmaceutical companies. The other authors report no relevant conflicts of interest.
SOURCE: Schneeweiss M, et al. J Am Acad Dermatol. 2019. doi:10.1016/j.jaad.2019.05.073.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Severity, itch improvements remain steady with ruxolitinib for atopic dermatitis
MILAN – A in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.
Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.
Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.
“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.
Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.
The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.
After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.
The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.
In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.
The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.
The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.
Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.
Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.
Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.
The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.
Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.
The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.
Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.
MILAN – A in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.
Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.
Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.
“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.
Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.
The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.
After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.
The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.
In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.
The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.
The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.
Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.
Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.
Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.
The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.
Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.
The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.
Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.
MILAN – A in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.
Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.
Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.
“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.
Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.
The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.
After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.
The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.
In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.
The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.
The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.
Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.
Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.
Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.
The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.
Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.
The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.
Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.
REPORTING FROM WCD2019
Atopic dermatitis patients achieved freedom from itch on JAK inhibitor upadacitinib
MILAN – according to a report presented at the World Congress of Dermatology.
Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).
These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.
“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”
Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.
In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.
Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).
In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.
The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).
Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.
That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”
Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.
The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.
Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.
Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.
MILAN – according to a report presented at the World Congress of Dermatology.
Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).
These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.
“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”
Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.
In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.
Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).
In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.
The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).
Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.
That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”
Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.
The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.
Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.
Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.
MILAN – according to a report presented at the World Congress of Dermatology.
Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).
These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.
“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”
Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.
In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.
Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).
In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.
The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).
Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.
That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”
Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.
The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.
Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.
Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.
REPORTING FROM WCD2019
Phototherapy: Is It Still Important?
Phototherapy has been used to treat skin diseases for millennia. From the Incas to the ancient Greeks and Egyptians, nearly every major civilization has attempted to harness the sun, with some even worshipping it for its healing powers.1 Today, phototherapy remains as important as ever. Despite the technological advances that have brought about biologic medications, small molecule inhibitors, and elegant vehicle delivery systems, phototherapy continues to be a valuable tool in the dermatologist’s armamentarium.
Patient Access to Phototherapy
An important step in successfully managing any disease is access to treatment. In today’s health care landscape, therapeutic decisions frequently are dictated by a patient’s financial situation as well as by the discretion of payers. Costly medications such as biologics often are not accessible to patients on government insurance who fall into the Medicare “donut hole” and may be denied by insurance companies for a myriad of reasons. Luckily, phototherapy typically is well covered and is even a first-line treatment option for some conditions, such as mycosis fungoides.
Nevertheless, phototherapy also has its own unique accessibility hurdles. The time-consuming nature of office-based phototherapy treatment is the main barrier, and many patients find it difficult to incorporate treatments into their daily lives. Additionally, office-based phototherapy units often are clustered in major cities, making access more difficult for rural patients. Because light-responsive conditions often are chronic and may require a lifetime of treatment, home phototherapy units are now being recognized as cost-effective treatment options and are increasingly covered by insurance. In fact, one study comparing psoriasis patients treated with home narrowband UVB (NB-UVB) vs outpatient NB-UVB found that in-home treatment was equally as effective as office-based treatment at a similar cost.2 Because studies comparing the effectiveness of office-based vs home-based phototherapy treatment are underway for various other diseases, hopefully more patients will be able to receive home units, thus increasing access to safe and effective treatment.
Wide Range of Treatment Indications
Another merit of phototherapy is its ability to be used in almost all patient populations. It is one of the few modalities whose indications span the entire length of the human lifetime—from pediatric atopic dermatitis to chronic pruritus in elderly patients. Phototherapy also is one of the few treatment options that is safe to use in patients with an active malignancy or in patients who have multiple other medical conditions. Comorbidities including congestive heart failure, chronic infections, and demyelinating disorders often prevent the use of oral and injectable medications for immune-mediated disorders such as psoriasis or atopic dermatitis. In patients with multiple comorbidities whose disease remains uncontrolled despite an adequate topical regimen, phototherapy is one of the few effective treatment options that remain. Additionally, there is a considerable number of patients who prefer external treatments for cutaneous diseases. For these patients, phototherapy offers the opportunity to control skin conditions without the use of an internal medication.
Favorable Safety Profile
Phototherapy is a largely benign intervention with an excellent safety profile. Its main potential adverse events include erythema, pruritus, xerosis, recurrence of herpes simplex virus infection, and premature skin aging. The effects of phototherapy on skin carcinogenesis have long been controversial; however, data suggest a clear distinction in risk between treatment with NB-UVB and psoralen plus UVA (PUVA). A systematic review of psoriasis patients treated with phototherapy found no evidence to suggest an increased risk of melanoma or nonmelanoma skin cancer with NB-UVB treatment.3 The same cannot be said for psoriasis patients treated with PUVA, who were noted to have a higher incidence of nonmelanoma skin cancer than the general population. This increased risk was more substantial in American cohorts than in European cohorts, likely due to multiple factors including variable skin types and treatment regimens. Increased rates of melanoma also were noted in American PUVA cohorts, with no similar increase seen in their European counterparts.3
Broad vs Targeted Therapies
Targeted therapies have dominated the health care landscape over the last few years, with the majority of new medications being highly focused and only efficacious in a few conditions. One of phototherapy’s greatest strengths is its lack of specificity. Because the field of dermatology is filled with rare, overlapping, and often poorly understood diseases, nonspecific treatment options are needed to fill the gaps. Many generalized skin conditions may lack treatment options indicated by the US Food and Drug Administration. Phototherapy is the ultimate untargeted intervention and may be broadly used for a wide range of cutaneous conditions. Although classically utilized for atopic dermatitis and psoriasis, NB-UVB also can effectively treat generalized pruritus, vitiligo, urticaria, and seborrheic dermatitis.4 Not to be outdone, PUVA has shown success in treating more than 50 different dermatologic conditions including lichen planus, alopecia areata, and mycosis fungoides.
Final Thoughts
Phototherapy is a safe, accessible, and widely applicable treatment for a range of cutaneous disorders. Although more precisely engineered internal therapies have begun to replace UV light in psoriasis and atopic dermatitis, phototherapy likely will always remain an ideal treatment for a wide cohort of patients. Between increased access to home units and the continued validation of its excellent safety record, the future of phototherapy is looking bright.
- Grzybowski A, Sak J, Pawlikowski J. A brief report on the history of phototherapy. Clin Dermatol. 2016;34:532-537.
- Koek MB, Sigurdsson V, van Weelden H, et al. Cost effectiveness of home ultraviolet B phototherapy for psoriasis: economic evaluation of a randomised controlled trial (PLUTO study). BMJ. 2010;340:c1490.
- Archier E, Devaux S, Castela E, et al. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. 2012;26(suppl 3):22-31.
- Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52:660-670.
- Ledo E, Ledo A. Phototherapy, photochemotherapy, and photodynamic therapy: unapproved uses or indications. Clin Dermatol. 2000;18:77-86.
Phototherapy has been used to treat skin diseases for millennia. From the Incas to the ancient Greeks and Egyptians, nearly every major civilization has attempted to harness the sun, with some even worshipping it for its healing powers.1 Today, phototherapy remains as important as ever. Despite the technological advances that have brought about biologic medications, small molecule inhibitors, and elegant vehicle delivery systems, phototherapy continues to be a valuable tool in the dermatologist’s armamentarium.
Patient Access to Phototherapy
An important step in successfully managing any disease is access to treatment. In today’s health care landscape, therapeutic decisions frequently are dictated by a patient’s financial situation as well as by the discretion of payers. Costly medications such as biologics often are not accessible to patients on government insurance who fall into the Medicare “donut hole” and may be denied by insurance companies for a myriad of reasons. Luckily, phototherapy typically is well covered and is even a first-line treatment option for some conditions, such as mycosis fungoides.
Nevertheless, phototherapy also has its own unique accessibility hurdles. The time-consuming nature of office-based phototherapy treatment is the main barrier, and many patients find it difficult to incorporate treatments into their daily lives. Additionally, office-based phototherapy units often are clustered in major cities, making access more difficult for rural patients. Because light-responsive conditions often are chronic and may require a lifetime of treatment, home phototherapy units are now being recognized as cost-effective treatment options and are increasingly covered by insurance. In fact, one study comparing psoriasis patients treated with home narrowband UVB (NB-UVB) vs outpatient NB-UVB found that in-home treatment was equally as effective as office-based treatment at a similar cost.2 Because studies comparing the effectiveness of office-based vs home-based phototherapy treatment are underway for various other diseases, hopefully more patients will be able to receive home units, thus increasing access to safe and effective treatment.
Wide Range of Treatment Indications
Another merit of phototherapy is its ability to be used in almost all patient populations. It is one of the few modalities whose indications span the entire length of the human lifetime—from pediatric atopic dermatitis to chronic pruritus in elderly patients. Phototherapy also is one of the few treatment options that is safe to use in patients with an active malignancy or in patients who have multiple other medical conditions. Comorbidities including congestive heart failure, chronic infections, and demyelinating disorders often prevent the use of oral and injectable medications for immune-mediated disorders such as psoriasis or atopic dermatitis. In patients with multiple comorbidities whose disease remains uncontrolled despite an adequate topical regimen, phototherapy is one of the few effective treatment options that remain. Additionally, there is a considerable number of patients who prefer external treatments for cutaneous diseases. For these patients, phototherapy offers the opportunity to control skin conditions without the use of an internal medication.
Favorable Safety Profile
Phototherapy is a largely benign intervention with an excellent safety profile. Its main potential adverse events include erythema, pruritus, xerosis, recurrence of herpes simplex virus infection, and premature skin aging. The effects of phototherapy on skin carcinogenesis have long been controversial; however, data suggest a clear distinction in risk between treatment with NB-UVB and psoralen plus UVA (PUVA). A systematic review of psoriasis patients treated with phototherapy found no evidence to suggest an increased risk of melanoma or nonmelanoma skin cancer with NB-UVB treatment.3 The same cannot be said for psoriasis patients treated with PUVA, who were noted to have a higher incidence of nonmelanoma skin cancer than the general population. This increased risk was more substantial in American cohorts than in European cohorts, likely due to multiple factors including variable skin types and treatment regimens. Increased rates of melanoma also were noted in American PUVA cohorts, with no similar increase seen in their European counterparts.3
Broad vs Targeted Therapies
Targeted therapies have dominated the health care landscape over the last few years, with the majority of new medications being highly focused and only efficacious in a few conditions. One of phototherapy’s greatest strengths is its lack of specificity. Because the field of dermatology is filled with rare, overlapping, and often poorly understood diseases, nonspecific treatment options are needed to fill the gaps. Many generalized skin conditions may lack treatment options indicated by the US Food and Drug Administration. Phototherapy is the ultimate untargeted intervention and may be broadly used for a wide range of cutaneous conditions. Although classically utilized for atopic dermatitis and psoriasis, NB-UVB also can effectively treat generalized pruritus, vitiligo, urticaria, and seborrheic dermatitis.4 Not to be outdone, PUVA has shown success in treating more than 50 different dermatologic conditions including lichen planus, alopecia areata, and mycosis fungoides.
Final Thoughts
Phototherapy is a safe, accessible, and widely applicable treatment for a range of cutaneous disorders. Although more precisely engineered internal therapies have begun to replace UV light in psoriasis and atopic dermatitis, phototherapy likely will always remain an ideal treatment for a wide cohort of patients. Between increased access to home units and the continued validation of its excellent safety record, the future of phototherapy is looking bright.
Phototherapy has been used to treat skin diseases for millennia. From the Incas to the ancient Greeks and Egyptians, nearly every major civilization has attempted to harness the sun, with some even worshipping it for its healing powers.1 Today, phototherapy remains as important as ever. Despite the technological advances that have brought about biologic medications, small molecule inhibitors, and elegant vehicle delivery systems, phototherapy continues to be a valuable tool in the dermatologist’s armamentarium.
Patient Access to Phototherapy
An important step in successfully managing any disease is access to treatment. In today’s health care landscape, therapeutic decisions frequently are dictated by a patient’s financial situation as well as by the discretion of payers. Costly medications such as biologics often are not accessible to patients on government insurance who fall into the Medicare “donut hole” and may be denied by insurance companies for a myriad of reasons. Luckily, phototherapy typically is well covered and is even a first-line treatment option for some conditions, such as mycosis fungoides.
Nevertheless, phototherapy also has its own unique accessibility hurdles. The time-consuming nature of office-based phototherapy treatment is the main barrier, and many patients find it difficult to incorporate treatments into their daily lives. Additionally, office-based phototherapy units often are clustered in major cities, making access more difficult for rural patients. Because light-responsive conditions often are chronic and may require a lifetime of treatment, home phototherapy units are now being recognized as cost-effective treatment options and are increasingly covered by insurance. In fact, one study comparing psoriasis patients treated with home narrowband UVB (NB-UVB) vs outpatient NB-UVB found that in-home treatment was equally as effective as office-based treatment at a similar cost.2 Because studies comparing the effectiveness of office-based vs home-based phototherapy treatment are underway for various other diseases, hopefully more patients will be able to receive home units, thus increasing access to safe and effective treatment.
Wide Range of Treatment Indications
Another merit of phototherapy is its ability to be used in almost all patient populations. It is one of the few modalities whose indications span the entire length of the human lifetime—from pediatric atopic dermatitis to chronic pruritus in elderly patients. Phototherapy also is one of the few treatment options that is safe to use in patients with an active malignancy or in patients who have multiple other medical conditions. Comorbidities including congestive heart failure, chronic infections, and demyelinating disorders often prevent the use of oral and injectable medications for immune-mediated disorders such as psoriasis or atopic dermatitis. In patients with multiple comorbidities whose disease remains uncontrolled despite an adequate topical regimen, phototherapy is one of the few effective treatment options that remain. Additionally, there is a considerable number of patients who prefer external treatments for cutaneous diseases. For these patients, phototherapy offers the opportunity to control skin conditions without the use of an internal medication.
Favorable Safety Profile
Phototherapy is a largely benign intervention with an excellent safety profile. Its main potential adverse events include erythema, pruritus, xerosis, recurrence of herpes simplex virus infection, and premature skin aging. The effects of phototherapy on skin carcinogenesis have long been controversial; however, data suggest a clear distinction in risk between treatment with NB-UVB and psoralen plus UVA (PUVA). A systematic review of psoriasis patients treated with phototherapy found no evidence to suggest an increased risk of melanoma or nonmelanoma skin cancer with NB-UVB treatment.3 The same cannot be said for psoriasis patients treated with PUVA, who were noted to have a higher incidence of nonmelanoma skin cancer than the general population. This increased risk was more substantial in American cohorts than in European cohorts, likely due to multiple factors including variable skin types and treatment regimens. Increased rates of melanoma also were noted in American PUVA cohorts, with no similar increase seen in their European counterparts.3
Broad vs Targeted Therapies
Targeted therapies have dominated the health care landscape over the last few years, with the majority of new medications being highly focused and only efficacious in a few conditions. One of phototherapy’s greatest strengths is its lack of specificity. Because the field of dermatology is filled with rare, overlapping, and often poorly understood diseases, nonspecific treatment options are needed to fill the gaps. Many generalized skin conditions may lack treatment options indicated by the US Food and Drug Administration. Phototherapy is the ultimate untargeted intervention and may be broadly used for a wide range of cutaneous conditions. Although classically utilized for atopic dermatitis and psoriasis, NB-UVB also can effectively treat generalized pruritus, vitiligo, urticaria, and seborrheic dermatitis.4 Not to be outdone, PUVA has shown success in treating more than 50 different dermatologic conditions including lichen planus, alopecia areata, and mycosis fungoides.
Final Thoughts
Phototherapy is a safe, accessible, and widely applicable treatment for a range of cutaneous disorders. Although more precisely engineered internal therapies have begun to replace UV light in psoriasis and atopic dermatitis, phototherapy likely will always remain an ideal treatment for a wide cohort of patients. Between increased access to home units and the continued validation of its excellent safety record, the future of phototherapy is looking bright.
- Grzybowski A, Sak J, Pawlikowski J. A brief report on the history of phototherapy. Clin Dermatol. 2016;34:532-537.
- Koek MB, Sigurdsson V, van Weelden H, et al. Cost effectiveness of home ultraviolet B phototherapy for psoriasis: economic evaluation of a randomised controlled trial (PLUTO study). BMJ. 2010;340:c1490.
- Archier E, Devaux S, Castela E, et al. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. 2012;26(suppl 3):22-31.
- Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52:660-670.
- Ledo E, Ledo A. Phototherapy, photochemotherapy, and photodynamic therapy: unapproved uses or indications. Clin Dermatol. 2000;18:77-86.
- Grzybowski A, Sak J, Pawlikowski J. A brief report on the history of phototherapy. Clin Dermatol. 2016;34:532-537.
- Koek MB, Sigurdsson V, van Weelden H, et al. Cost effectiveness of home ultraviolet B phototherapy for psoriasis: economic evaluation of a randomised controlled trial (PLUTO study). BMJ. 2010;340:c1490.
- Archier E, Devaux S, Castela E, et al. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. 2012;26(suppl 3):22-31.
- Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52:660-670.
- Ledo E, Ledo A. Phototherapy, photochemotherapy, and photodynamic therapy: unapproved uses or indications. Clin Dermatol. 2000;18:77-86.
Treatment Consideration for US Military Members With Skin Disease
The National Defense Authorization Act for Fiscal Year 20171 has changed military medicine, including substantial reduction in military medical personnel as positions are converted to combat functions. As a result, there will be fewer military dermatologists, which means many US soldiers, sailors, airmen, and marines will seek medical care outside of military treatment facilities. This article highlights some unique treatment considerations in this patient population for our civilian dermatology colleagues.
Medical Readiness
In 2015, General Joseph F. Dunford Jr, 19th Chairman of the Joint Chiefs of Staff, made readiness his top priority for the US Armed Forces.2 Readiness refers to service members’ ability to deploy to locations across the globe and perform their military duties with little advanced notice, which requires personnel to be medically prepared at all times to leave home and perform their duties in locations with limited medical support.
Medical readiness is maintaining a unit that is medically able to perform its military function both at home and in a deployed environment. Military members’ medical readiness status is carefully tracked and determined via annual physical, dental, hearing, and vision examinations, as well as human immunodeficiency virus status and immunizations. The readiness status of the unit (ie, the number of troops ready to deploy at any given time) is available to commanders at all levels at any time. Each military branch has tracking systems that allow commanders to know when a member is past due for an examination or if a member’s medical status has changed, making them nondeployable. When a member is nondeployable, it affects the unit’s ability to perform its mission and degrades its readiness. If readiness is suboptimal, the military cannot deploy and complete its missions, which is why readiness is a top priority. The primary function of military medicine is to support the medical readiness of the force.
Deployment Eligibility
A unique aspect of military medicine that can be foreign to civilian physicians is the unit commanders’ authority to request and receive information on military members’ medical conditions as they relate to readiness. Under most circumstances, an individual’s medical information is his/her private information; however, that is not always the case in the military. If a member’s medical status changes and he/she becomes nondeployable, by regulation the commander can be privy to pertinent aspects of that member’s medical condition as it affects unit readiness, including the diagnosis, treatment plan, and prognosis. Commanders need this information to aid in the member’s recovery, ensure training does not impact his/her care, and identify possible need of replacement.
Published accession guidelines are used to determine medical eligibility for service.3 These instructions are organized by major organ systems and broad disease categories. They provide guidance on medically disqualifying conditions. The Table outlines those conditions that apply to the skin.3 Individual military branches may have additional regulations with guidance on medically disqualifying conditions that are job specific. Additional regulations also are available based on an area of military operation that can be more restrictive and specific to those locations.4
Similarly, each military branch has its own retention standards.5,6 Previously healthy individuals can develop new medical conditions, and commanders are notified if a service member becomes medically nondeployable. If a medical condition limits a service member’s ability to deploy, he/she will be evaluated for retention by a medical evaluation board (MEB). Three outcomes are possible: return in current function, retain the service member but retrain in another military occupation, or separate from military service.7 Rarely, waivers are provided so that the service member can return to duty.
Readiness and Patient Care
Importantly, readiness should not be seen as a roadblock to appropriate patient care. Patients should receive treatment that is appropriate for their medical condition. Much of the difficulty within military medicine is understanding and communicating how the natural disease history, prognosis, and treatment of their respective medical conditions will impact members’ service.
In some cases, the condition and/or treatment is incompatible with military service. Consider the following scenario: A 23-year-old active-duty soldier with a history of psoriasis developed widespread disease of 1 year’s duration and was referred to a civilian dermatologist due to nonavailability of a military dermatologist. After topical and light-based therapies failed, he was started on ustekinumab, which cleared the psoriasis. He wanted to continue on ustekinumab due to its good efficacy, but his unit was set to deploy in the coming year, and the drug made him medically nondeployable due to its immunosuppressive nature.
This real-life example was a difficult case to disposition. The service member was unsure if he could perform his military duties and deploy without continuing treatment with ustekinumab. His prior dermatology notes were requested to better assess the severity of his baseline disease, followed by a candid discussion between the military dermatologist and the patient about treatment options and their respective ramifications to his military career. One option included continuing ustekinumab, which would initiate an MEB evaluation and likely result in separation. Another option was UV therapy, which would not prompt an MEB evaluation but would not be available in deployed environments. Apremilast was offered as a third treatment option and could be used in place of UV therapy during deployment along with topical medications. This patient opted to continue treatment with ustekinumab, resulting in MEB review and separation from military service.
Dermatology Treatment Considerations
Civilian dermatologists should be aware of specific considerations when treating active US service members with common cutaneous diagnoses such as acne, atopic dermatitis (AD), psoriasis, dissecting cellulitis of the scalp (DCS), and lupus erythematosus (LE). This discussion is not meant to be all-inclusive but provides information and examples related to common treatment challenges in this patient population.
Acne
Acne is common in the active-duty military population. Typically, acne should be treated per recommended guidelines based on type and severity.8 Medical evaluation board review is warranted in cases of severe acne that is unresponsive to treatment and interferes with a service member’s performance.5,6 Unique situations in the active-duty military population include the following:
• Use of minocycline. Aircrew members have unique restrictions on many medications,6 including minocycline, which is restricted in this population due to vestibular side effects. Doxycycline is an acceptable alternative for aircrew members; however, even this medication may require a ground trial to ensure there are no idiosyncratic effects.
• Use of isotretinoin, which is not permitted in aircrew members, submariners, or divers. If they take this medication, they will be temporarily removed from duty for the duration of treatment and for a period of time after completion (1–3 months, depending on service). Isotretinoin also is not used during deployment due to potential side effects, the need for laboratory monitoring, and iPLEDGE system requirements.
Atopic Dermatitis
A history of AD after the 12th birthday is considered a disqualifying condition with regard to military service,3 though mild and well-controlled disease can easily be overlooked during entrance physical examinations. Members frequently present with eczema flares following field training exercises where they are outdoors for many hours and have been exposed to grass or other environmental triggers while wearing military gear that is heavy and occlusive, which is further exacerbated by being unable to bathe or care for their skin as they would at home.
Separation from the military is considered when AD is moderate to severe, is unresponsive to treatment, and/or interferes with performance of duty. Severity often can be evaluated based on the impact of AD on performance of duties in addition to clinical appearance. A pilot who is distracted by itching presents a potentially dangerous situation. A soldier whose AD flares every time he/she goes to the field, requiring him/her to return home early to control symptoms, can be considered moderate to severe due to lack of ability to do his/her job away from home base.
Response to treatment is more often where trouble lies for military members with AD, as patients are only permitted to take emollients, preferred cleansers, and topical medications to field training exercises and deployments. UV therapy is used to control disease in the military population but is not an option in deployed environments. Classic immunosuppressants (eg, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine) may result in a good response to treatment; however, due to their side-effect profiles, need for laboratory monitoring, and immunosuppressive nature, long-term use of those medications will result in a nondeployable status. Dupilumab does not appear to have the immunosuppressive effects of other biologics; however, the medication requires refrigeration,9 which currently precludes its use in the deployed environment, as it would be difficult to ensure supply and storage in remote areas.
Service members with a history of AD are exempt from the smallpox vaccine due to concerns about eczema vaccinatum.10
Psoriasis
Psoriasis is another dermatologic condition that does not meet military admission standards,3 and mild undiagnosed cases may be overlooked during the entrance physical examination. Because psoriasis commonly affects young adults, it may manifest in service members after entering service. If psoriasis is extensive or refractory to treatment, an MEB evaluation may be required.5,6 Widespread psoriasis can result in considerable discomfort when wearing body armor and other military gear. Severe localized disease can have duty implications; service members with treatment-resistant scalp psoriasis or pustular psoriasis of the feet may have difficulty wearing helmets or military boots, respectively.
Most service members with limited psoriasis vulgaris can be managed with topical steroids and steroid-sparing agents such as calcipotriene. Some service members opt not to aggressively treat their psoriasis if it is limited in nature and not symptomatic.
When discussing systemic treatments beyond light therapy in those with refractory disease, apremilast can be a good first-line treatment option.11 It is an oral medication, has minimal monitoring requirements, and lacks immunosuppressive side effects; therefore, it does not adversely impact deployability. If patients do not improve in 4 months with apremilast, biologics should then be considered; however, biologics have service implications, the most important being inability to deploy while taking the medication. In rare circumstances, military dermatologists may discuss utilizing biologic therapy only in the nondeployed setting. In these cases, service members are counseled that biologic therapy will be discontinued if they deploy in the future and treatment will be sustained with topicals and/or apremilast through the deployment. The treatment plan also should be communicated to the patient’s primary care provider to ensure that he/she is in agreement.
Dissecting Cellulitis of the Scalp
Dissecting cellulitis of the scalp may result in separation if the condition is unresponsive to treatment and/or interferes with satisfactory performance of duty.5 In addition to causing considerable pain, this condition can prevent service members from wearing combat helmets, which limits their ability to train and deploy. One of the authors (S.C.) has had more service members undergo an MEB evaluation for DCS than any of the other conditions mentioned.
Topical tretinoin and topical antibiotics can be used in conjunction with either doxycycline or minocycline to treat DCS, with the addition of intralesional corticosteroids for painful nodules. Fluctuant lesions are treated with incision and drainage. If there is inadequate response to treatment after 2 to 3 months, oral clindamycin and rifampin can be tried for 3 months. As an alternative measure or if the condition is refractory to oral clindamycin and rifampin, isotretinoin can then be used. One of the authors (S.C.) typically recommends a temporary no-helmet profile to the patient’s primary care provider until his/her next dermatology appointment. If the patient still has substantial disease despite these treatment options, it is recommended that the patient be issued a permanent profile for no helmet wear, which will prompt an MEB evaluation. Although tumor necrosis factor α inhibitors can work well in patients with DCS, the use of biologics is not conducive to continued service.
Lupus Erythematosus
A history of LE is disqualifying from military service. Patients who develop LE while on active duty will be referred for MEB evaluation if their disease is unresponsive to treatment and/or interferes with the satisfactory performance of duty.5,6 In general, connective tissue diseases have an array of physical implications that can affect military service, including photosensitivity, joint inflammation, and internal organ involvement. Similar to the other dermatologic conditions described, treatment of connective tissue diseases also can present challenges to continued military service. Considerations in the case of LE that are unique to military service members include the following:
• Sun exposure. Most military service members are required to work outside in all manners of conditions, which include hot, sunny, humid, and/or dry climates. Often physicians might counsel sun-sensitive patients with LE to avoid being outside during daylight hours, limit window exposure at work, and avoid daytime driving when possible; however, these recommendations are not possible for many, if not most, service members.
• Immunosuppressive therapies are incompatible with military deployment; therefore, prescribing methotrexate, cyclosporine, mycophenolate mofetil, rituximab, or belimumab for treatment of LE would prompt an MEB evaluation if the treatment is necessary to control the disease.
Final Thoughts
The recent changes to military medicine are needed to meet our country’s defense requirements and will ultimately result in civilian specialists playing a larger role in the care of our military population. This article highlights unique factors civilian dermatologists must consider when treating active-duty military patients to ensure they remain deployable during treatment.
- National Defense Authorization Act for Fiscal Year 2017, S 2943, 114th Congress, 2nd Sess (2016).
- Garamone J. Dunford sends message to joint force, stresses readiness, warfighting, education [news release]. Washington, DC: US Department of Defense; October 2, 2015. https://dod.defense.gov/News/Article/Article/621725/dunford-sends-message-to-joint-force-stresses-readiness-warfighting-education/. Accessed May 17, 2019.
- Medical Standards for Appointment, Enlistment, or Induction Into the Military Services (DoD Instruction 6130.03). Washington, DC: Department of Defense; March 30, 2018. https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003p.pdf?ver=2018-05-04-113917-883. Accessed May 17, 2019.
- Force health protection guidance for deployment in USSOUTHCOM as of 7 December 2017. US Southern Command website. https://www.southcom.mil/Portals/7/Documents/Operational%20Contract%20Support/USSOUTHCOM_Force_Health_Protection_Guidance_AS_OF_7_DEC_2017.pdf?ver=2018-01-29-100603-957. Published December 7, 2017. Accessed May 28, 2019.
- US Department of the Army. Standards of medical fitness. http://www.au.af.mil/au/awc/awcgate/army/r40_501.pdf. Published August 26, 2003. Accessed May 17, 2019.
- US Department of the Air Force. Medical examinations and standards. https://static.e-publishing.af.mil/production/1/af_sg/publication/afi48-123/afi48-123.pdf. Published November 5, 2013. Accessed May 17, 2019.
- Medical and physical evaluation boards (MEB/PEB). US Army Warrior Care and Transition website. https://wct.army.mil/modules/soldier/s6-medicalBoards.html. Accessed May 28, 2019.
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.
- Dupixent [package insert]. Tarrytown, NY: Regeneron, Inc; 2017.
- Departments of the Army, the Navy, the Air Force, and the Coast Guard. Immunizations and chemoprophylaxis for the prevention of infectious diseases. https://health.mil/Reference-Center/Policies/2013/10/07/Immunizations-and-Chemoprophylaxis-for-the-Prevention-of-Infectious-Diseases. Published October 7, 2013. Accessed May 28, 2019.
- Rosenberg A, Meyerle J. The use of apremilast to treat psoriasis during deployment. Mil Med. 2017;182:1628-1631.
The National Defense Authorization Act for Fiscal Year 20171 has changed military medicine, including substantial reduction in military medical personnel as positions are converted to combat functions. As a result, there will be fewer military dermatologists, which means many US soldiers, sailors, airmen, and marines will seek medical care outside of military treatment facilities. This article highlights some unique treatment considerations in this patient population for our civilian dermatology colleagues.
Medical Readiness
In 2015, General Joseph F. Dunford Jr, 19th Chairman of the Joint Chiefs of Staff, made readiness his top priority for the US Armed Forces.2 Readiness refers to service members’ ability to deploy to locations across the globe and perform their military duties with little advanced notice, which requires personnel to be medically prepared at all times to leave home and perform their duties in locations with limited medical support.
Medical readiness is maintaining a unit that is medically able to perform its military function both at home and in a deployed environment. Military members’ medical readiness status is carefully tracked and determined via annual physical, dental, hearing, and vision examinations, as well as human immunodeficiency virus status and immunizations. The readiness status of the unit (ie, the number of troops ready to deploy at any given time) is available to commanders at all levels at any time. Each military branch has tracking systems that allow commanders to know when a member is past due for an examination or if a member’s medical status has changed, making them nondeployable. When a member is nondeployable, it affects the unit’s ability to perform its mission and degrades its readiness. If readiness is suboptimal, the military cannot deploy and complete its missions, which is why readiness is a top priority. The primary function of military medicine is to support the medical readiness of the force.
Deployment Eligibility
A unique aspect of military medicine that can be foreign to civilian physicians is the unit commanders’ authority to request and receive information on military members’ medical conditions as they relate to readiness. Under most circumstances, an individual’s medical information is his/her private information; however, that is not always the case in the military. If a member’s medical status changes and he/she becomes nondeployable, by regulation the commander can be privy to pertinent aspects of that member’s medical condition as it affects unit readiness, including the diagnosis, treatment plan, and prognosis. Commanders need this information to aid in the member’s recovery, ensure training does not impact his/her care, and identify possible need of replacement.
Published accession guidelines are used to determine medical eligibility for service.3 These instructions are organized by major organ systems and broad disease categories. They provide guidance on medically disqualifying conditions. The Table outlines those conditions that apply to the skin.3 Individual military branches may have additional regulations with guidance on medically disqualifying conditions that are job specific. Additional regulations also are available based on an area of military operation that can be more restrictive and specific to those locations.4
Similarly, each military branch has its own retention standards.5,6 Previously healthy individuals can develop new medical conditions, and commanders are notified if a service member becomes medically nondeployable. If a medical condition limits a service member’s ability to deploy, he/she will be evaluated for retention by a medical evaluation board (MEB). Three outcomes are possible: return in current function, retain the service member but retrain in another military occupation, or separate from military service.7 Rarely, waivers are provided so that the service member can return to duty.
Readiness and Patient Care
Importantly, readiness should not be seen as a roadblock to appropriate patient care. Patients should receive treatment that is appropriate for their medical condition. Much of the difficulty within military medicine is understanding and communicating how the natural disease history, prognosis, and treatment of their respective medical conditions will impact members’ service.
In some cases, the condition and/or treatment is incompatible with military service. Consider the following scenario: A 23-year-old active-duty soldier with a history of psoriasis developed widespread disease of 1 year’s duration and was referred to a civilian dermatologist due to nonavailability of a military dermatologist. After topical and light-based therapies failed, he was started on ustekinumab, which cleared the psoriasis. He wanted to continue on ustekinumab due to its good efficacy, but his unit was set to deploy in the coming year, and the drug made him medically nondeployable due to its immunosuppressive nature.
This real-life example was a difficult case to disposition. The service member was unsure if he could perform his military duties and deploy without continuing treatment with ustekinumab. His prior dermatology notes were requested to better assess the severity of his baseline disease, followed by a candid discussion between the military dermatologist and the patient about treatment options and their respective ramifications to his military career. One option included continuing ustekinumab, which would initiate an MEB evaluation and likely result in separation. Another option was UV therapy, which would not prompt an MEB evaluation but would not be available in deployed environments. Apremilast was offered as a third treatment option and could be used in place of UV therapy during deployment along with topical medications. This patient opted to continue treatment with ustekinumab, resulting in MEB review and separation from military service.
Dermatology Treatment Considerations
Civilian dermatologists should be aware of specific considerations when treating active US service members with common cutaneous diagnoses such as acne, atopic dermatitis (AD), psoriasis, dissecting cellulitis of the scalp (DCS), and lupus erythematosus (LE). This discussion is not meant to be all-inclusive but provides information and examples related to common treatment challenges in this patient population.
Acne
Acne is common in the active-duty military population. Typically, acne should be treated per recommended guidelines based on type and severity.8 Medical evaluation board review is warranted in cases of severe acne that is unresponsive to treatment and interferes with a service member’s performance.5,6 Unique situations in the active-duty military population include the following:
• Use of minocycline. Aircrew members have unique restrictions on many medications,6 including minocycline, which is restricted in this population due to vestibular side effects. Doxycycline is an acceptable alternative for aircrew members; however, even this medication may require a ground trial to ensure there are no idiosyncratic effects.
• Use of isotretinoin, which is not permitted in aircrew members, submariners, or divers. If they take this medication, they will be temporarily removed from duty for the duration of treatment and for a period of time after completion (1–3 months, depending on service). Isotretinoin also is not used during deployment due to potential side effects, the need for laboratory monitoring, and iPLEDGE system requirements.
Atopic Dermatitis
A history of AD after the 12th birthday is considered a disqualifying condition with regard to military service,3 though mild and well-controlled disease can easily be overlooked during entrance physical examinations. Members frequently present with eczema flares following field training exercises where they are outdoors for many hours and have been exposed to grass or other environmental triggers while wearing military gear that is heavy and occlusive, which is further exacerbated by being unable to bathe or care for their skin as they would at home.
Separation from the military is considered when AD is moderate to severe, is unresponsive to treatment, and/or interferes with performance of duty. Severity often can be evaluated based on the impact of AD on performance of duties in addition to clinical appearance. A pilot who is distracted by itching presents a potentially dangerous situation. A soldier whose AD flares every time he/she goes to the field, requiring him/her to return home early to control symptoms, can be considered moderate to severe due to lack of ability to do his/her job away from home base.
Response to treatment is more often where trouble lies for military members with AD, as patients are only permitted to take emollients, preferred cleansers, and topical medications to field training exercises and deployments. UV therapy is used to control disease in the military population but is not an option in deployed environments. Classic immunosuppressants (eg, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine) may result in a good response to treatment; however, due to their side-effect profiles, need for laboratory monitoring, and immunosuppressive nature, long-term use of those medications will result in a nondeployable status. Dupilumab does not appear to have the immunosuppressive effects of other biologics; however, the medication requires refrigeration,9 which currently precludes its use in the deployed environment, as it would be difficult to ensure supply and storage in remote areas.
Service members with a history of AD are exempt from the smallpox vaccine due to concerns about eczema vaccinatum.10
Psoriasis
Psoriasis is another dermatologic condition that does not meet military admission standards,3 and mild undiagnosed cases may be overlooked during the entrance physical examination. Because psoriasis commonly affects young adults, it may manifest in service members after entering service. If psoriasis is extensive or refractory to treatment, an MEB evaluation may be required.5,6 Widespread psoriasis can result in considerable discomfort when wearing body armor and other military gear. Severe localized disease can have duty implications; service members with treatment-resistant scalp psoriasis or pustular psoriasis of the feet may have difficulty wearing helmets or military boots, respectively.
Most service members with limited psoriasis vulgaris can be managed with topical steroids and steroid-sparing agents such as calcipotriene. Some service members opt not to aggressively treat their psoriasis if it is limited in nature and not symptomatic.
When discussing systemic treatments beyond light therapy in those with refractory disease, apremilast can be a good first-line treatment option.11 It is an oral medication, has minimal monitoring requirements, and lacks immunosuppressive side effects; therefore, it does not adversely impact deployability. If patients do not improve in 4 months with apremilast, biologics should then be considered; however, biologics have service implications, the most important being inability to deploy while taking the medication. In rare circumstances, military dermatologists may discuss utilizing biologic therapy only in the nondeployed setting. In these cases, service members are counseled that biologic therapy will be discontinued if they deploy in the future and treatment will be sustained with topicals and/or apremilast through the deployment. The treatment plan also should be communicated to the patient’s primary care provider to ensure that he/she is in agreement.
Dissecting Cellulitis of the Scalp
Dissecting cellulitis of the scalp may result in separation if the condition is unresponsive to treatment and/or interferes with satisfactory performance of duty.5 In addition to causing considerable pain, this condition can prevent service members from wearing combat helmets, which limits their ability to train and deploy. One of the authors (S.C.) has had more service members undergo an MEB evaluation for DCS than any of the other conditions mentioned.
Topical tretinoin and topical antibiotics can be used in conjunction with either doxycycline or minocycline to treat DCS, with the addition of intralesional corticosteroids for painful nodules. Fluctuant lesions are treated with incision and drainage. If there is inadequate response to treatment after 2 to 3 months, oral clindamycin and rifampin can be tried for 3 months. As an alternative measure or if the condition is refractory to oral clindamycin and rifampin, isotretinoin can then be used. One of the authors (S.C.) typically recommends a temporary no-helmet profile to the patient’s primary care provider until his/her next dermatology appointment. If the patient still has substantial disease despite these treatment options, it is recommended that the patient be issued a permanent profile for no helmet wear, which will prompt an MEB evaluation. Although tumor necrosis factor α inhibitors can work well in patients with DCS, the use of biologics is not conducive to continued service.
Lupus Erythematosus
A history of LE is disqualifying from military service. Patients who develop LE while on active duty will be referred for MEB evaluation if their disease is unresponsive to treatment and/or interferes with the satisfactory performance of duty.5,6 In general, connective tissue diseases have an array of physical implications that can affect military service, including photosensitivity, joint inflammation, and internal organ involvement. Similar to the other dermatologic conditions described, treatment of connective tissue diseases also can present challenges to continued military service. Considerations in the case of LE that are unique to military service members include the following:
• Sun exposure. Most military service members are required to work outside in all manners of conditions, which include hot, sunny, humid, and/or dry climates. Often physicians might counsel sun-sensitive patients with LE to avoid being outside during daylight hours, limit window exposure at work, and avoid daytime driving when possible; however, these recommendations are not possible for many, if not most, service members.
• Immunosuppressive therapies are incompatible with military deployment; therefore, prescribing methotrexate, cyclosporine, mycophenolate mofetil, rituximab, or belimumab for treatment of LE would prompt an MEB evaluation if the treatment is necessary to control the disease.
Final Thoughts
The recent changes to military medicine are needed to meet our country’s defense requirements and will ultimately result in civilian specialists playing a larger role in the care of our military population. This article highlights unique factors civilian dermatologists must consider when treating active-duty military patients to ensure they remain deployable during treatment.
The National Defense Authorization Act for Fiscal Year 20171 has changed military medicine, including substantial reduction in military medical personnel as positions are converted to combat functions. As a result, there will be fewer military dermatologists, which means many US soldiers, sailors, airmen, and marines will seek medical care outside of military treatment facilities. This article highlights some unique treatment considerations in this patient population for our civilian dermatology colleagues.
Medical Readiness
In 2015, General Joseph F. Dunford Jr, 19th Chairman of the Joint Chiefs of Staff, made readiness his top priority for the US Armed Forces.2 Readiness refers to service members’ ability to deploy to locations across the globe and perform their military duties with little advanced notice, which requires personnel to be medically prepared at all times to leave home and perform their duties in locations with limited medical support.
Medical readiness is maintaining a unit that is medically able to perform its military function both at home and in a deployed environment. Military members’ medical readiness status is carefully tracked and determined via annual physical, dental, hearing, and vision examinations, as well as human immunodeficiency virus status and immunizations. The readiness status of the unit (ie, the number of troops ready to deploy at any given time) is available to commanders at all levels at any time. Each military branch has tracking systems that allow commanders to know when a member is past due for an examination or if a member’s medical status has changed, making them nondeployable. When a member is nondeployable, it affects the unit’s ability to perform its mission and degrades its readiness. If readiness is suboptimal, the military cannot deploy and complete its missions, which is why readiness is a top priority. The primary function of military medicine is to support the medical readiness of the force.
Deployment Eligibility
A unique aspect of military medicine that can be foreign to civilian physicians is the unit commanders’ authority to request and receive information on military members’ medical conditions as they relate to readiness. Under most circumstances, an individual’s medical information is his/her private information; however, that is not always the case in the military. If a member’s medical status changes and he/she becomes nondeployable, by regulation the commander can be privy to pertinent aspects of that member’s medical condition as it affects unit readiness, including the diagnosis, treatment plan, and prognosis. Commanders need this information to aid in the member’s recovery, ensure training does not impact his/her care, and identify possible need of replacement.
Published accession guidelines are used to determine medical eligibility for service.3 These instructions are organized by major organ systems and broad disease categories. They provide guidance on medically disqualifying conditions. The Table outlines those conditions that apply to the skin.3 Individual military branches may have additional regulations with guidance on medically disqualifying conditions that are job specific. Additional regulations also are available based on an area of military operation that can be more restrictive and specific to those locations.4
Similarly, each military branch has its own retention standards.5,6 Previously healthy individuals can develop new medical conditions, and commanders are notified if a service member becomes medically nondeployable. If a medical condition limits a service member’s ability to deploy, he/she will be evaluated for retention by a medical evaluation board (MEB). Three outcomes are possible: return in current function, retain the service member but retrain in another military occupation, or separate from military service.7 Rarely, waivers are provided so that the service member can return to duty.
Readiness and Patient Care
Importantly, readiness should not be seen as a roadblock to appropriate patient care. Patients should receive treatment that is appropriate for their medical condition. Much of the difficulty within military medicine is understanding and communicating how the natural disease history, prognosis, and treatment of their respective medical conditions will impact members’ service.
In some cases, the condition and/or treatment is incompatible with military service. Consider the following scenario: A 23-year-old active-duty soldier with a history of psoriasis developed widespread disease of 1 year’s duration and was referred to a civilian dermatologist due to nonavailability of a military dermatologist. After topical and light-based therapies failed, he was started on ustekinumab, which cleared the psoriasis. He wanted to continue on ustekinumab due to its good efficacy, but his unit was set to deploy in the coming year, and the drug made him medically nondeployable due to its immunosuppressive nature.
This real-life example was a difficult case to disposition. The service member was unsure if he could perform his military duties and deploy without continuing treatment with ustekinumab. His prior dermatology notes were requested to better assess the severity of his baseline disease, followed by a candid discussion between the military dermatologist and the patient about treatment options and their respective ramifications to his military career. One option included continuing ustekinumab, which would initiate an MEB evaluation and likely result in separation. Another option was UV therapy, which would not prompt an MEB evaluation but would not be available in deployed environments. Apremilast was offered as a third treatment option and could be used in place of UV therapy during deployment along with topical medications. This patient opted to continue treatment with ustekinumab, resulting in MEB review and separation from military service.
Dermatology Treatment Considerations
Civilian dermatologists should be aware of specific considerations when treating active US service members with common cutaneous diagnoses such as acne, atopic dermatitis (AD), psoriasis, dissecting cellulitis of the scalp (DCS), and lupus erythematosus (LE). This discussion is not meant to be all-inclusive but provides information and examples related to common treatment challenges in this patient population.
Acne
Acne is common in the active-duty military population. Typically, acne should be treated per recommended guidelines based on type and severity.8 Medical evaluation board review is warranted in cases of severe acne that is unresponsive to treatment and interferes with a service member’s performance.5,6 Unique situations in the active-duty military population include the following:
• Use of minocycline. Aircrew members have unique restrictions on many medications,6 including minocycline, which is restricted in this population due to vestibular side effects. Doxycycline is an acceptable alternative for aircrew members; however, even this medication may require a ground trial to ensure there are no idiosyncratic effects.
• Use of isotretinoin, which is not permitted in aircrew members, submariners, or divers. If they take this medication, they will be temporarily removed from duty for the duration of treatment and for a period of time after completion (1–3 months, depending on service). Isotretinoin also is not used during deployment due to potential side effects, the need for laboratory monitoring, and iPLEDGE system requirements.
Atopic Dermatitis
A history of AD after the 12th birthday is considered a disqualifying condition with regard to military service,3 though mild and well-controlled disease can easily be overlooked during entrance physical examinations. Members frequently present with eczema flares following field training exercises where they are outdoors for many hours and have been exposed to grass or other environmental triggers while wearing military gear that is heavy and occlusive, which is further exacerbated by being unable to bathe or care for their skin as they would at home.
Separation from the military is considered when AD is moderate to severe, is unresponsive to treatment, and/or interferes with performance of duty. Severity often can be evaluated based on the impact of AD on performance of duties in addition to clinical appearance. A pilot who is distracted by itching presents a potentially dangerous situation. A soldier whose AD flares every time he/she goes to the field, requiring him/her to return home early to control symptoms, can be considered moderate to severe due to lack of ability to do his/her job away from home base.
Response to treatment is more often where trouble lies for military members with AD, as patients are only permitted to take emollients, preferred cleansers, and topical medications to field training exercises and deployments. UV therapy is used to control disease in the military population but is not an option in deployed environments. Classic immunosuppressants (eg, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine) may result in a good response to treatment; however, due to their side-effect profiles, need for laboratory monitoring, and immunosuppressive nature, long-term use of those medications will result in a nondeployable status. Dupilumab does not appear to have the immunosuppressive effects of other biologics; however, the medication requires refrigeration,9 which currently precludes its use in the deployed environment, as it would be difficult to ensure supply and storage in remote areas.
Service members with a history of AD are exempt from the smallpox vaccine due to concerns about eczema vaccinatum.10
Psoriasis
Psoriasis is another dermatologic condition that does not meet military admission standards,3 and mild undiagnosed cases may be overlooked during the entrance physical examination. Because psoriasis commonly affects young adults, it may manifest in service members after entering service. If psoriasis is extensive or refractory to treatment, an MEB evaluation may be required.5,6 Widespread psoriasis can result in considerable discomfort when wearing body armor and other military gear. Severe localized disease can have duty implications; service members with treatment-resistant scalp psoriasis or pustular psoriasis of the feet may have difficulty wearing helmets or military boots, respectively.
Most service members with limited psoriasis vulgaris can be managed with topical steroids and steroid-sparing agents such as calcipotriene. Some service members opt not to aggressively treat their psoriasis if it is limited in nature and not symptomatic.
When discussing systemic treatments beyond light therapy in those with refractory disease, apremilast can be a good first-line treatment option.11 It is an oral medication, has minimal monitoring requirements, and lacks immunosuppressive side effects; therefore, it does not adversely impact deployability. If patients do not improve in 4 months with apremilast, biologics should then be considered; however, biologics have service implications, the most important being inability to deploy while taking the medication. In rare circumstances, military dermatologists may discuss utilizing biologic therapy only in the nondeployed setting. In these cases, service members are counseled that biologic therapy will be discontinued if they deploy in the future and treatment will be sustained with topicals and/or apremilast through the deployment. The treatment plan also should be communicated to the patient’s primary care provider to ensure that he/she is in agreement.
Dissecting Cellulitis of the Scalp
Dissecting cellulitis of the scalp may result in separation if the condition is unresponsive to treatment and/or interferes with satisfactory performance of duty.5 In addition to causing considerable pain, this condition can prevent service members from wearing combat helmets, which limits their ability to train and deploy. One of the authors (S.C.) has had more service members undergo an MEB evaluation for DCS than any of the other conditions mentioned.
Topical tretinoin and topical antibiotics can be used in conjunction with either doxycycline or minocycline to treat DCS, with the addition of intralesional corticosteroids for painful nodules. Fluctuant lesions are treated with incision and drainage. If there is inadequate response to treatment after 2 to 3 months, oral clindamycin and rifampin can be tried for 3 months. As an alternative measure or if the condition is refractory to oral clindamycin and rifampin, isotretinoin can then be used. One of the authors (S.C.) typically recommends a temporary no-helmet profile to the patient’s primary care provider until his/her next dermatology appointment. If the patient still has substantial disease despite these treatment options, it is recommended that the patient be issued a permanent profile for no helmet wear, which will prompt an MEB evaluation. Although tumor necrosis factor α inhibitors can work well in patients with DCS, the use of biologics is not conducive to continued service.
Lupus Erythematosus
A history of LE is disqualifying from military service. Patients who develop LE while on active duty will be referred for MEB evaluation if their disease is unresponsive to treatment and/or interferes with the satisfactory performance of duty.5,6 In general, connective tissue diseases have an array of physical implications that can affect military service, including photosensitivity, joint inflammation, and internal organ involvement. Similar to the other dermatologic conditions described, treatment of connective tissue diseases also can present challenges to continued military service. Considerations in the case of LE that are unique to military service members include the following:
• Sun exposure. Most military service members are required to work outside in all manners of conditions, which include hot, sunny, humid, and/or dry climates. Often physicians might counsel sun-sensitive patients with LE to avoid being outside during daylight hours, limit window exposure at work, and avoid daytime driving when possible; however, these recommendations are not possible for many, if not most, service members.
• Immunosuppressive therapies are incompatible with military deployment; therefore, prescribing methotrexate, cyclosporine, mycophenolate mofetil, rituximab, or belimumab for treatment of LE would prompt an MEB evaluation if the treatment is necessary to control the disease.
Final Thoughts
The recent changes to military medicine are needed to meet our country’s defense requirements and will ultimately result in civilian specialists playing a larger role in the care of our military population. This article highlights unique factors civilian dermatologists must consider when treating active-duty military patients to ensure they remain deployable during treatment.
- National Defense Authorization Act for Fiscal Year 2017, S 2943, 114th Congress, 2nd Sess (2016).
- Garamone J. Dunford sends message to joint force, stresses readiness, warfighting, education [news release]. Washington, DC: US Department of Defense; October 2, 2015. https://dod.defense.gov/News/Article/Article/621725/dunford-sends-message-to-joint-force-stresses-readiness-warfighting-education/. Accessed May 17, 2019.
- Medical Standards for Appointment, Enlistment, or Induction Into the Military Services (DoD Instruction 6130.03). Washington, DC: Department of Defense; March 30, 2018. https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003p.pdf?ver=2018-05-04-113917-883. Accessed May 17, 2019.
- Force health protection guidance for deployment in USSOUTHCOM as of 7 December 2017. US Southern Command website. https://www.southcom.mil/Portals/7/Documents/Operational%20Contract%20Support/USSOUTHCOM_Force_Health_Protection_Guidance_AS_OF_7_DEC_2017.pdf?ver=2018-01-29-100603-957. Published December 7, 2017. Accessed May 28, 2019.
- US Department of the Army. Standards of medical fitness. http://www.au.af.mil/au/awc/awcgate/army/r40_501.pdf. Published August 26, 2003. Accessed May 17, 2019.
- US Department of the Air Force. Medical examinations and standards. https://static.e-publishing.af.mil/production/1/af_sg/publication/afi48-123/afi48-123.pdf. Published November 5, 2013. Accessed May 17, 2019.
- Medical and physical evaluation boards (MEB/PEB). US Army Warrior Care and Transition website. https://wct.army.mil/modules/soldier/s6-medicalBoards.html. Accessed May 28, 2019.
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.
- Dupixent [package insert]. Tarrytown, NY: Regeneron, Inc; 2017.
- Departments of the Army, the Navy, the Air Force, and the Coast Guard. Immunizations and chemoprophylaxis for the prevention of infectious diseases. https://health.mil/Reference-Center/Policies/2013/10/07/Immunizations-and-Chemoprophylaxis-for-the-Prevention-of-Infectious-Diseases. Published October 7, 2013. Accessed May 28, 2019.
- Rosenberg A, Meyerle J. The use of apremilast to treat psoriasis during deployment. Mil Med. 2017;182:1628-1631.
- National Defense Authorization Act for Fiscal Year 2017, S 2943, 114th Congress, 2nd Sess (2016).
- Garamone J. Dunford sends message to joint force, stresses readiness, warfighting, education [news release]. Washington, DC: US Department of Defense; October 2, 2015. https://dod.defense.gov/News/Article/Article/621725/dunford-sends-message-to-joint-force-stresses-readiness-warfighting-education/. Accessed May 17, 2019.
- Medical Standards for Appointment, Enlistment, or Induction Into the Military Services (DoD Instruction 6130.03). Washington, DC: Department of Defense; March 30, 2018. https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003p.pdf?ver=2018-05-04-113917-883. Accessed May 17, 2019.
- Force health protection guidance for deployment in USSOUTHCOM as of 7 December 2017. US Southern Command website. https://www.southcom.mil/Portals/7/Documents/Operational%20Contract%20Support/USSOUTHCOM_Force_Health_Protection_Guidance_AS_OF_7_DEC_2017.pdf?ver=2018-01-29-100603-957. Published December 7, 2017. Accessed May 28, 2019.
- US Department of the Army. Standards of medical fitness. http://www.au.af.mil/au/awc/awcgate/army/r40_501.pdf. Published August 26, 2003. Accessed May 17, 2019.
- US Department of the Air Force. Medical examinations and standards. https://static.e-publishing.af.mil/production/1/af_sg/publication/afi48-123/afi48-123.pdf. Published November 5, 2013. Accessed May 17, 2019.
- Medical and physical evaluation boards (MEB/PEB). US Army Warrior Care and Transition website. https://wct.army.mil/modules/soldier/s6-medicalBoards.html. Accessed May 28, 2019.
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.
- Dupixent [package insert]. Tarrytown, NY: Regeneron, Inc; 2017.
- Departments of the Army, the Navy, the Air Force, and the Coast Guard. Immunizations and chemoprophylaxis for the prevention of infectious diseases. https://health.mil/Reference-Center/Policies/2013/10/07/Immunizations-and-Chemoprophylaxis-for-the-Prevention-of-Infectious-Diseases. Published October 7, 2013. Accessed May 28, 2019.
- Rosenberg A, Meyerle J. The use of apremilast to treat psoriasis during deployment. Mil Med. 2017;182:1628-1631.
Practice Points
- Certain conditions and treatments are incompatible with military service and may result in separation.
- Dermatologists must consider a patient’s profession when choosing a treatment modality.
Pustular Tinea Id Reaction
To the Editor:
A 17-year-old adolescent girl presented to the dermatology clinic with a tender pruritic rash on the left wrist that was spreading to the bilateral arms and legs of several years’ duration. An area of a prior biopsy on the left wrist was healing well with use of petroleum jelly and halcinonide cream. The patient denied any constitutional symptoms.
Physical examination revealed numerous erythematous papules coalescing into plaques on the bilateral anterior and posterior arms and legs, including some erythematous macules and papules on the palms and soles. The original area of involvement on the left dorsal medial wrist demonstrated a background of erythema with overlying peripheral scaling and resolving violaceous to erythematous papules with signs of serosanguineous crusting (Figure 1). Scattered perifollicular erythema was present on the posterior aspects of the bilateral thighs and arms (Figure 2). Baseline complete blood cell count and complete metabolic panel were within reference range.
Clinical histopathology showed evidence of a pustular superficial dermatophyte infection, and Grocott-Gomori methenamine-silver stain demonstrated numerous fungal hyphae within subcorneal pustules, indicating pustular tinea. Based on the clinicopathologic correlation, the initial presentation was diagnosed as pustular tinea of the entire left wrist, followed by a generalized id reaction 1 week later.
The patient was prescribed oral terbinafine 250 mg once daily to treat the diffuse involvement of the pustular tinea as well as once-daily oral cetirizine, once-daily oral diphenhydramine, a topical emollient, and a topical nonsteroidal antipruritic gel.
Tinea is a superficial fungal infection commonly caused by the dermatophytes Epidermophyton, Trichophyton, and Microsporum. It has a variety of clinical presentations based on the anatomic location, including tinea capitis (hair/scalp), tinea pedis (feet), tinea corporis (face/trunk/extremities), tinea cruris (groin), and tinea unguium (nails).1 Tinea infections occur in the stratum corneum, hair, and nails, thriving on dead keratin in these areas.2 Tinea corporis usually appears as an erythematous ring-shaped lesion with a scaly border, but atypical cases presenting with vesicles, pustules, and bullae also have been reported.3 Additionally, secondary eruptions called id reactions, or autoeczematization, can present in the setting of dermatophyte infections. Such outbreaks may be due to a delayed hypersensitivity reaction to the fungal antigens. Id reactions can manifest in many forms of tinea with patients generally exhibiting pruritic papulovesicular lesions that can present far from the site of origin.4
Patients with id reactions can have atypical and varied presentations. In a case of id reaction due to tinea corporis, a patient presented with vesicles and pustules that grew in number and coalesced to form annular lesions.5 A case of an id reaction caused by tinea pedis also noted the presence of pustules, which are atypical in this form of tinea.6 In another case of tinea pedis, a generalized id reaction was noted, illustrating that such eruptions do not necessarily appear at the original site of infection.7 Additionally, in a rare presentation of tinea invading the nares, a patient developed an erythema multiforme id reaction.8 Id reactions also were noted in 14 patients with refractory otitis externa, illustrating the ability of this fungal infection to persist and infect distant locations.9
Because the differential diagnoses for tinea infection are extensive, pathology or laboratory confirmation is necessary for diagnosis, and potassium hydroxide preparation often is used to diagnose dermatophyte infections.1,2 Additionally, the possibility of a hypersensitivity drug rash should remain in the differential if the patient received allergy-inducing medications prior to the outbreak, which may in turn complicate the diagnosis.
Tinea infections typically can be treated with topical antifungals such as terbinafine, butenafine,1 and luliconazole10; however, more involved cases may require oral antifungal treatment.1 Systemic treatment of tinea corporis includes itraconazole, terbinafine, and fluconazole,11 all of which exhibit fewer side effects and greater efficacy when compared to griseofulvin.12-15
Treatment of id reactions centers on the proper clearance of the dermatophyte infection, and treatment with oral antifungals generally is sufficient. In the cases of id reaction in patients with refractory otitis, some success was achieved with treatment involving immunotherapy with dermatophyte and dust mite allergen extracts coupled with a yeast elimination diet.9 In acute id reactions, topical corticosteroids and antipruritic agents can be applied.4 Rarely, systemic glucocorticoids are required, such as in cases in which the id reaction persists despite proper treatment of the primary infection.16
- Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. Am Fam Physician. 2014;90:702-710.
- Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 5th ed. Hanover, NH: Elsevier, Inc; 2010.
- Ziemer M, Seyfarth F, Elsner P, et al. Atypical manifestations of tinea corporis. Mycoses. 2007;50(suppl 2):31-35.
- Cheng N, Rucker Wright D, Cohen BA. Dermatophytid in tinea capitis: rarely reported common phenomenon with clinical implications [published online July 4, 2011]. Pediatrics. 2011;128:e453-e457.
- Ohno S, Tanabe H, Kawasaki M, et al. Tinea corporis with acute inflammation caused by Trichophyton tonsurans. J Dermatol. 2008;35:590-593.
- Hirschmann JV, Raugi GJ. Pustular tinea pedis. J Am Acad Dermatol. 2000;42:132-133.
- Iglesias ME, España A, Idoate MA, et al. Generalized skin reaction following tinea pedis (dermatophytids). J Dermatol. 1994;21:31-34.
- Atzori L, Pau M, Aste M. Erythema multiforme ID reaction in atypical dermatophytosis: a case report. J Eur Acad Dermatol Venereol. 2003;17:699-701.
- Derebery J, Berliner KI. Foot and ear disease—the dermatophytid reaction in otology. Laryngoscope. 1996;106(2 Pt 1):181-186.
- Khanna D, Bharti S. Luliconazole for the treatment of fungal infections: an evidence-based review. Core Evid. 2014;9:113-124.
- Korting HC, Schöllmann C. The significance of itraconazole for treatment of fungal infections of skin, nails and mucous membranes. J Dtsch Dermatol Ges. 2009;7:11-20.
- Goldstein AO, Goldstein BG. Dermatophyte (tinea) infections. UpToDate website. https://www.uptodate.com/contents/dermatophyte-tinea-infections. Updated December 28, 2018. Accessed April 24, 2019.
- Cole GW, Stricklin G. A comparison of a new oral antifungal, terbinafine, with griseofulvin as therapy for tinea corporis. Arch Dermatol. 1989;125:1537.
- Panagiotidou D, Kousidou T, Chaidemenos G, et al. A comparison of itraconazole and griseofulvin in the treatment of tinea corporis and tinea cruris: a double-blind study. J Int Med Res. 1992;20:392-400.
- Faergemann J, Mörk NJ, Haglund A, et al. A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol. 1997;136:575-577.
- Ilkit M, Durdu M, Karakas M. Cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management. Crit Rev Microbiol. 2012;38:191-202.
To the Editor:
A 17-year-old adolescent girl presented to the dermatology clinic with a tender pruritic rash on the left wrist that was spreading to the bilateral arms and legs of several years’ duration. An area of a prior biopsy on the left wrist was healing well with use of petroleum jelly and halcinonide cream. The patient denied any constitutional symptoms.
Physical examination revealed numerous erythematous papules coalescing into plaques on the bilateral anterior and posterior arms and legs, including some erythematous macules and papules on the palms and soles. The original area of involvement on the left dorsal medial wrist demonstrated a background of erythema with overlying peripheral scaling and resolving violaceous to erythematous papules with signs of serosanguineous crusting (Figure 1). Scattered perifollicular erythema was present on the posterior aspects of the bilateral thighs and arms (Figure 2). Baseline complete blood cell count and complete metabolic panel were within reference range.
Clinical histopathology showed evidence of a pustular superficial dermatophyte infection, and Grocott-Gomori methenamine-silver stain demonstrated numerous fungal hyphae within subcorneal pustules, indicating pustular tinea. Based on the clinicopathologic correlation, the initial presentation was diagnosed as pustular tinea of the entire left wrist, followed by a generalized id reaction 1 week later.
The patient was prescribed oral terbinafine 250 mg once daily to treat the diffuse involvement of the pustular tinea as well as once-daily oral cetirizine, once-daily oral diphenhydramine, a topical emollient, and a topical nonsteroidal antipruritic gel.
Tinea is a superficial fungal infection commonly caused by the dermatophytes Epidermophyton, Trichophyton, and Microsporum. It has a variety of clinical presentations based on the anatomic location, including tinea capitis (hair/scalp), tinea pedis (feet), tinea corporis (face/trunk/extremities), tinea cruris (groin), and tinea unguium (nails).1 Tinea infections occur in the stratum corneum, hair, and nails, thriving on dead keratin in these areas.2 Tinea corporis usually appears as an erythematous ring-shaped lesion with a scaly border, but atypical cases presenting with vesicles, pustules, and bullae also have been reported.3 Additionally, secondary eruptions called id reactions, or autoeczematization, can present in the setting of dermatophyte infections. Such outbreaks may be due to a delayed hypersensitivity reaction to the fungal antigens. Id reactions can manifest in many forms of tinea with patients generally exhibiting pruritic papulovesicular lesions that can present far from the site of origin.4
Patients with id reactions can have atypical and varied presentations. In a case of id reaction due to tinea corporis, a patient presented with vesicles and pustules that grew in number and coalesced to form annular lesions.5 A case of an id reaction caused by tinea pedis also noted the presence of pustules, which are atypical in this form of tinea.6 In another case of tinea pedis, a generalized id reaction was noted, illustrating that such eruptions do not necessarily appear at the original site of infection.7 Additionally, in a rare presentation of tinea invading the nares, a patient developed an erythema multiforme id reaction.8 Id reactions also were noted in 14 patients with refractory otitis externa, illustrating the ability of this fungal infection to persist and infect distant locations.9
Because the differential diagnoses for tinea infection are extensive, pathology or laboratory confirmation is necessary for diagnosis, and potassium hydroxide preparation often is used to diagnose dermatophyte infections.1,2 Additionally, the possibility of a hypersensitivity drug rash should remain in the differential if the patient received allergy-inducing medications prior to the outbreak, which may in turn complicate the diagnosis.
Tinea infections typically can be treated with topical antifungals such as terbinafine, butenafine,1 and luliconazole10; however, more involved cases may require oral antifungal treatment.1 Systemic treatment of tinea corporis includes itraconazole, terbinafine, and fluconazole,11 all of which exhibit fewer side effects and greater efficacy when compared to griseofulvin.12-15
Treatment of id reactions centers on the proper clearance of the dermatophyte infection, and treatment with oral antifungals generally is sufficient. In the cases of id reaction in patients with refractory otitis, some success was achieved with treatment involving immunotherapy with dermatophyte and dust mite allergen extracts coupled with a yeast elimination diet.9 In acute id reactions, topical corticosteroids and antipruritic agents can be applied.4 Rarely, systemic glucocorticoids are required, such as in cases in which the id reaction persists despite proper treatment of the primary infection.16
To the Editor:
A 17-year-old adolescent girl presented to the dermatology clinic with a tender pruritic rash on the left wrist that was spreading to the bilateral arms and legs of several years’ duration. An area of a prior biopsy on the left wrist was healing well with use of petroleum jelly and halcinonide cream. The patient denied any constitutional symptoms.
Physical examination revealed numerous erythematous papules coalescing into plaques on the bilateral anterior and posterior arms and legs, including some erythematous macules and papules on the palms and soles. The original area of involvement on the left dorsal medial wrist demonstrated a background of erythema with overlying peripheral scaling and resolving violaceous to erythematous papules with signs of serosanguineous crusting (Figure 1). Scattered perifollicular erythema was present on the posterior aspects of the bilateral thighs and arms (Figure 2). Baseline complete blood cell count and complete metabolic panel were within reference range.
Clinical histopathology showed evidence of a pustular superficial dermatophyte infection, and Grocott-Gomori methenamine-silver stain demonstrated numerous fungal hyphae within subcorneal pustules, indicating pustular tinea. Based on the clinicopathologic correlation, the initial presentation was diagnosed as pustular tinea of the entire left wrist, followed by a generalized id reaction 1 week later.
The patient was prescribed oral terbinafine 250 mg once daily to treat the diffuse involvement of the pustular tinea as well as once-daily oral cetirizine, once-daily oral diphenhydramine, a topical emollient, and a topical nonsteroidal antipruritic gel.
Tinea is a superficial fungal infection commonly caused by the dermatophytes Epidermophyton, Trichophyton, and Microsporum. It has a variety of clinical presentations based on the anatomic location, including tinea capitis (hair/scalp), tinea pedis (feet), tinea corporis (face/trunk/extremities), tinea cruris (groin), and tinea unguium (nails).1 Tinea infections occur in the stratum corneum, hair, and nails, thriving on dead keratin in these areas.2 Tinea corporis usually appears as an erythematous ring-shaped lesion with a scaly border, but atypical cases presenting with vesicles, pustules, and bullae also have been reported.3 Additionally, secondary eruptions called id reactions, or autoeczematization, can present in the setting of dermatophyte infections. Such outbreaks may be due to a delayed hypersensitivity reaction to the fungal antigens. Id reactions can manifest in many forms of tinea with patients generally exhibiting pruritic papulovesicular lesions that can present far from the site of origin.4
Patients with id reactions can have atypical and varied presentations. In a case of id reaction due to tinea corporis, a patient presented with vesicles and pustules that grew in number and coalesced to form annular lesions.5 A case of an id reaction caused by tinea pedis also noted the presence of pustules, which are atypical in this form of tinea.6 In another case of tinea pedis, a generalized id reaction was noted, illustrating that such eruptions do not necessarily appear at the original site of infection.7 Additionally, in a rare presentation of tinea invading the nares, a patient developed an erythema multiforme id reaction.8 Id reactions also were noted in 14 patients with refractory otitis externa, illustrating the ability of this fungal infection to persist and infect distant locations.9
Because the differential diagnoses for tinea infection are extensive, pathology or laboratory confirmation is necessary for diagnosis, and potassium hydroxide preparation often is used to diagnose dermatophyte infections.1,2 Additionally, the possibility of a hypersensitivity drug rash should remain in the differential if the patient received allergy-inducing medications prior to the outbreak, which may in turn complicate the diagnosis.
Tinea infections typically can be treated with topical antifungals such as terbinafine, butenafine,1 and luliconazole10; however, more involved cases may require oral antifungal treatment.1 Systemic treatment of tinea corporis includes itraconazole, terbinafine, and fluconazole,11 all of which exhibit fewer side effects and greater efficacy when compared to griseofulvin.12-15
Treatment of id reactions centers on the proper clearance of the dermatophyte infection, and treatment with oral antifungals generally is sufficient. In the cases of id reaction in patients with refractory otitis, some success was achieved with treatment involving immunotherapy with dermatophyte and dust mite allergen extracts coupled with a yeast elimination diet.9 In acute id reactions, topical corticosteroids and antipruritic agents can be applied.4 Rarely, systemic glucocorticoids are required, such as in cases in which the id reaction persists despite proper treatment of the primary infection.16
- Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. Am Fam Physician. 2014;90:702-710.
- Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 5th ed. Hanover, NH: Elsevier, Inc; 2010.
- Ziemer M, Seyfarth F, Elsner P, et al. Atypical manifestations of tinea corporis. Mycoses. 2007;50(suppl 2):31-35.
- Cheng N, Rucker Wright D, Cohen BA. Dermatophytid in tinea capitis: rarely reported common phenomenon with clinical implications [published online July 4, 2011]. Pediatrics. 2011;128:e453-e457.
- Ohno S, Tanabe H, Kawasaki M, et al. Tinea corporis with acute inflammation caused by Trichophyton tonsurans. J Dermatol. 2008;35:590-593.
- Hirschmann JV, Raugi GJ. Pustular tinea pedis. J Am Acad Dermatol. 2000;42:132-133.
- Iglesias ME, España A, Idoate MA, et al. Generalized skin reaction following tinea pedis (dermatophytids). J Dermatol. 1994;21:31-34.
- Atzori L, Pau M, Aste M. Erythema multiforme ID reaction in atypical dermatophytosis: a case report. J Eur Acad Dermatol Venereol. 2003;17:699-701.
- Derebery J, Berliner KI. Foot and ear disease—the dermatophytid reaction in otology. Laryngoscope. 1996;106(2 Pt 1):181-186.
- Khanna D, Bharti S. Luliconazole for the treatment of fungal infections: an evidence-based review. Core Evid. 2014;9:113-124.
- Korting HC, Schöllmann C. The significance of itraconazole for treatment of fungal infections of skin, nails and mucous membranes. J Dtsch Dermatol Ges. 2009;7:11-20.
- Goldstein AO, Goldstein BG. Dermatophyte (tinea) infections. UpToDate website. https://www.uptodate.com/contents/dermatophyte-tinea-infections. Updated December 28, 2018. Accessed April 24, 2019.
- Cole GW, Stricklin G. A comparison of a new oral antifungal, terbinafine, with griseofulvin as therapy for tinea corporis. Arch Dermatol. 1989;125:1537.
- Panagiotidou D, Kousidou T, Chaidemenos G, et al. A comparison of itraconazole and griseofulvin in the treatment of tinea corporis and tinea cruris: a double-blind study. J Int Med Res. 1992;20:392-400.
- Faergemann J, Mörk NJ, Haglund A, et al. A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol. 1997;136:575-577.
- Ilkit M, Durdu M, Karakas M. Cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management. Crit Rev Microbiol. 2012;38:191-202.
- Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. Am Fam Physician. 2014;90:702-710.
- Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 5th ed. Hanover, NH: Elsevier, Inc; 2010.
- Ziemer M, Seyfarth F, Elsner P, et al. Atypical manifestations of tinea corporis. Mycoses. 2007;50(suppl 2):31-35.
- Cheng N, Rucker Wright D, Cohen BA. Dermatophytid in tinea capitis: rarely reported common phenomenon with clinical implications [published online July 4, 2011]. Pediatrics. 2011;128:e453-e457.
- Ohno S, Tanabe H, Kawasaki M, et al. Tinea corporis with acute inflammation caused by Trichophyton tonsurans. J Dermatol. 2008;35:590-593.
- Hirschmann JV, Raugi GJ. Pustular tinea pedis. J Am Acad Dermatol. 2000;42:132-133.
- Iglesias ME, España A, Idoate MA, et al. Generalized skin reaction following tinea pedis (dermatophytids). J Dermatol. 1994;21:31-34.
- Atzori L, Pau M, Aste M. Erythema multiforme ID reaction in atypical dermatophytosis: a case report. J Eur Acad Dermatol Venereol. 2003;17:699-701.
- Derebery J, Berliner KI. Foot and ear disease—the dermatophytid reaction in otology. Laryngoscope. 1996;106(2 Pt 1):181-186.
- Khanna D, Bharti S. Luliconazole for the treatment of fungal infections: an evidence-based review. Core Evid. 2014;9:113-124.
- Korting HC, Schöllmann C. The significance of itraconazole for treatment of fungal infections of skin, nails and mucous membranes. J Dtsch Dermatol Ges. 2009;7:11-20.
- Goldstein AO, Goldstein BG. Dermatophyte (tinea) infections. UpToDate website. https://www.uptodate.com/contents/dermatophyte-tinea-infections. Updated December 28, 2018. Accessed April 24, 2019.
- Cole GW, Stricklin G. A comparison of a new oral antifungal, terbinafine, with griseofulvin as therapy for tinea corporis. Arch Dermatol. 1989;125:1537.
- Panagiotidou D, Kousidou T, Chaidemenos G, et al. A comparison of itraconazole and griseofulvin in the treatment of tinea corporis and tinea cruris: a double-blind study. J Int Med Res. 1992;20:392-400.
- Faergemann J, Mörk NJ, Haglund A, et al. A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol. 1997;136:575-577.
- Ilkit M, Durdu M, Karakas M. Cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management. Crit Rev Microbiol. 2012;38:191-202.
Practice Points
• Id reactions, or autoeczematization, can occur secondary to dermatophyte infections, possibly due to a hypersensitivity reaction to the fungus. These eruptions can occur in many forms of tinea and in a variety of clinical presentations.
• Treatment is based on clearance of the original dermatophyte infection.
Dupilumab for Treatment of Severe Atopic Dermatitis in a Heart Transplant Recipient
To the Editor:
Solid-organ transplant recipients can develop a range of dermatologic consequences due to chronic immunosuppression, including frequent skin infections and malignancies. Atopic dermatitis (AD) and psoriasis are relatively rare in this population because many immunosuppressive therapies, such as mycophenolate mofetil and tacrolimus, also are used to treat inflammatory dermatoses.1 In a large renal transplant population, the prevalence of AD was 1.3%.2 The pathogenesis of posttransplantation AD is poorly understood, and standard treatment regimens have not been defined. Dupilumab is a novel biologic medication that has demonstrated efficacy in the treatment of AD.3 Reports of dupilumab use for AD management in solid-organ transplant recipients are limited in the literature.
A 29-year-old woman with a history of a heart transplant 4 years prior presented to our dermatology clinic with an itchy rash over the entire body. Since the transplant, she had been on long-term immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. The rash appeared after she switched from brand-name to generic versions of the medications. Physical examination revealed erythematous scaly plaques on the lateral face, back, chest, arms, and legs covering approximately 10% of the body surface area. The patient’s total serum IgE level was elevated at 711,500 µg/L (reference range, 0–1500 µg/L). Outside biopsies revealed changes consistent with spongiotic dermatitis, and patch testing performed by an outside physician was positive for sensitivity to the preservative bronopol.
The patient was switched back to brand-name tacrolimus, but the rash did not improve. Topical steroids, phototherapy, and omalizumab were ineffective. The itching was primarily managed with desoximetasone spray, mometasone cream, and loratidine. With approval from the patient’s transplant team outside of our hospital system, she was started on dupilumab 300 mg once every 14 days. Complete clearance of the rash was noted within 3 months of treatment. Besides bilateral conjunctivitis, which was treated with ophthalmic prednisolone and moxifloxacin solutions, dupilumab was well tolerated. No issues related to immunosuppressant levels or graft-related issues, including rejection, were reported at 6-, 12-, and 18-month follow-up visits.
Atopic dermatitis is characterized by activation of type 2 immune responses, skin barrier defects, and increased Staphylococcus aureus colonization.4 A potential mechanism for the development of AD in transplant recipients relates to their use of tacrolimus for chronic immunosuppression. Tacrolimus increases intestinal permeability and therefore allows greater absorption of allergens. This influx of allergens promotes hypersensitivity reactions, resulting in elevated IgE levels and eosinophilia. Tacrolimus also facilitates predominance of helper T cells (TH2 cytokines) through selective inhibition of the TH1 cytokine IL-2.5
Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of TH2-mediated inflammation. In addition to downregulation of inflammatory mediators, dupilumab also increases production of epidermal barrier proteins, resulting in skin repair. It has demonstrated rapid, dose-dependent efficacy in patients with moderate to severe AD.6 Dupilumab boasts a good safety profile with no increase in risk for skin infections compared to placebo6; however, its safety has not yet been verified in transplant recipients.
Our case is notable for the severity of the patient’s AD despite considerable immunosuppression with transplant medications. Development of AD was associated with a switch from brand-name to generic drugs, which is not commonly reported. Her condition was refractory to a litany of treatments prior to a trial of dupilumab. The rapid clearance observed with this novel biologic medication highlights its potential to provide relief to patients who have particularly tenacious cases of AD. Prior to starting dupilumab, we do recommend more extensive laboratory testing in immunosuppressed patients including transplant recipients and patients with human immunodeficiency virus. We illustrate that a history of solid-organ transplant need not exclude patients from consideration for dupilumab therapy.
- Savoia P, Cavaliere G, Zavattaro E, et al. Inflammatory cutaneous diseases in renal transplant recipients [published online August 19, 2016]. Int J Mol Sci. doi:10.3390/ijms17081362.
- Lally A, Casabonne D, Imko-Walczuk B, et al. Prevalence of benign cutaneous disease among Oxford renal transplant recipients. J Eur Acad Dermatol Venereol. 2011;25:462-470.
- Beck L, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
- Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335-2348.
- Machura E, Chodór B, Kleszyk M, et al. Atopic allergy and chronic inflammation of the oral mucosa in a 3-year-old boy after heart transplantation—diagnostic and therapeutic difficulties. Kardiochir Torakochirurgia Pol. 2015;12:176-180.
- Beck L, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
To the Editor:
Solid-organ transplant recipients can develop a range of dermatologic consequences due to chronic immunosuppression, including frequent skin infections and malignancies. Atopic dermatitis (AD) and psoriasis are relatively rare in this population because many immunosuppressive therapies, such as mycophenolate mofetil and tacrolimus, also are used to treat inflammatory dermatoses.1 In a large renal transplant population, the prevalence of AD was 1.3%.2 The pathogenesis of posttransplantation AD is poorly understood, and standard treatment regimens have not been defined. Dupilumab is a novel biologic medication that has demonstrated efficacy in the treatment of AD.3 Reports of dupilumab use for AD management in solid-organ transplant recipients are limited in the literature.
A 29-year-old woman with a history of a heart transplant 4 years prior presented to our dermatology clinic with an itchy rash over the entire body. Since the transplant, she had been on long-term immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. The rash appeared after she switched from brand-name to generic versions of the medications. Physical examination revealed erythematous scaly plaques on the lateral face, back, chest, arms, and legs covering approximately 10% of the body surface area. The patient’s total serum IgE level was elevated at 711,500 µg/L (reference range, 0–1500 µg/L). Outside biopsies revealed changes consistent with spongiotic dermatitis, and patch testing performed by an outside physician was positive for sensitivity to the preservative bronopol.
The patient was switched back to brand-name tacrolimus, but the rash did not improve. Topical steroids, phototherapy, and omalizumab were ineffective. The itching was primarily managed with desoximetasone spray, mometasone cream, and loratidine. With approval from the patient’s transplant team outside of our hospital system, she was started on dupilumab 300 mg once every 14 days. Complete clearance of the rash was noted within 3 months of treatment. Besides bilateral conjunctivitis, which was treated with ophthalmic prednisolone and moxifloxacin solutions, dupilumab was well tolerated. No issues related to immunosuppressant levels or graft-related issues, including rejection, were reported at 6-, 12-, and 18-month follow-up visits.
Atopic dermatitis is characterized by activation of type 2 immune responses, skin barrier defects, and increased Staphylococcus aureus colonization.4 A potential mechanism for the development of AD in transplant recipients relates to their use of tacrolimus for chronic immunosuppression. Tacrolimus increases intestinal permeability and therefore allows greater absorption of allergens. This influx of allergens promotes hypersensitivity reactions, resulting in elevated IgE levels and eosinophilia. Tacrolimus also facilitates predominance of helper T cells (TH2 cytokines) through selective inhibition of the TH1 cytokine IL-2.5
Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of TH2-mediated inflammation. In addition to downregulation of inflammatory mediators, dupilumab also increases production of epidermal barrier proteins, resulting in skin repair. It has demonstrated rapid, dose-dependent efficacy in patients with moderate to severe AD.6 Dupilumab boasts a good safety profile with no increase in risk for skin infections compared to placebo6; however, its safety has not yet been verified in transplant recipients.
Our case is notable for the severity of the patient’s AD despite considerable immunosuppression with transplant medications. Development of AD was associated with a switch from brand-name to generic drugs, which is not commonly reported. Her condition was refractory to a litany of treatments prior to a trial of dupilumab. The rapid clearance observed with this novel biologic medication highlights its potential to provide relief to patients who have particularly tenacious cases of AD. Prior to starting dupilumab, we do recommend more extensive laboratory testing in immunosuppressed patients including transplant recipients and patients with human immunodeficiency virus. We illustrate that a history of solid-organ transplant need not exclude patients from consideration for dupilumab therapy.
To the Editor:
Solid-organ transplant recipients can develop a range of dermatologic consequences due to chronic immunosuppression, including frequent skin infections and malignancies. Atopic dermatitis (AD) and psoriasis are relatively rare in this population because many immunosuppressive therapies, such as mycophenolate mofetil and tacrolimus, also are used to treat inflammatory dermatoses.1 In a large renal transplant population, the prevalence of AD was 1.3%.2 The pathogenesis of posttransplantation AD is poorly understood, and standard treatment regimens have not been defined. Dupilumab is a novel biologic medication that has demonstrated efficacy in the treatment of AD.3 Reports of dupilumab use for AD management in solid-organ transplant recipients are limited in the literature.
A 29-year-old woman with a history of a heart transplant 4 years prior presented to our dermatology clinic with an itchy rash over the entire body. Since the transplant, she had been on long-term immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. The rash appeared after she switched from brand-name to generic versions of the medications. Physical examination revealed erythematous scaly plaques on the lateral face, back, chest, arms, and legs covering approximately 10% of the body surface area. The patient’s total serum IgE level was elevated at 711,500 µg/L (reference range, 0–1500 µg/L). Outside biopsies revealed changes consistent with spongiotic dermatitis, and patch testing performed by an outside physician was positive for sensitivity to the preservative bronopol.
The patient was switched back to brand-name tacrolimus, but the rash did not improve. Topical steroids, phototherapy, and omalizumab were ineffective. The itching was primarily managed with desoximetasone spray, mometasone cream, and loratidine. With approval from the patient’s transplant team outside of our hospital system, she was started on dupilumab 300 mg once every 14 days. Complete clearance of the rash was noted within 3 months of treatment. Besides bilateral conjunctivitis, which was treated with ophthalmic prednisolone and moxifloxacin solutions, dupilumab was well tolerated. No issues related to immunosuppressant levels or graft-related issues, including rejection, were reported at 6-, 12-, and 18-month follow-up visits.
Atopic dermatitis is characterized by activation of type 2 immune responses, skin barrier defects, and increased Staphylococcus aureus colonization.4 A potential mechanism for the development of AD in transplant recipients relates to their use of tacrolimus for chronic immunosuppression. Tacrolimus increases intestinal permeability and therefore allows greater absorption of allergens. This influx of allergens promotes hypersensitivity reactions, resulting in elevated IgE levels and eosinophilia. Tacrolimus also facilitates predominance of helper T cells (TH2 cytokines) through selective inhibition of the TH1 cytokine IL-2.5
Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of TH2-mediated inflammation. In addition to downregulation of inflammatory mediators, dupilumab also increases production of epidermal barrier proteins, resulting in skin repair. It has demonstrated rapid, dose-dependent efficacy in patients with moderate to severe AD.6 Dupilumab boasts a good safety profile with no increase in risk for skin infections compared to placebo6; however, its safety has not yet been verified in transplant recipients.
Our case is notable for the severity of the patient’s AD despite considerable immunosuppression with transplant medications. Development of AD was associated with a switch from brand-name to generic drugs, which is not commonly reported. Her condition was refractory to a litany of treatments prior to a trial of dupilumab. The rapid clearance observed with this novel biologic medication highlights its potential to provide relief to patients who have particularly tenacious cases of AD. Prior to starting dupilumab, we do recommend more extensive laboratory testing in immunosuppressed patients including transplant recipients and patients with human immunodeficiency virus. We illustrate that a history of solid-organ transplant need not exclude patients from consideration for dupilumab therapy.
- Savoia P, Cavaliere G, Zavattaro E, et al. Inflammatory cutaneous diseases in renal transplant recipients [published online August 19, 2016]. Int J Mol Sci. doi:10.3390/ijms17081362.
- Lally A, Casabonne D, Imko-Walczuk B, et al. Prevalence of benign cutaneous disease among Oxford renal transplant recipients. J Eur Acad Dermatol Venereol. 2011;25:462-470.
- Beck L, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
- Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335-2348.
- Machura E, Chodór B, Kleszyk M, et al. Atopic allergy and chronic inflammation of the oral mucosa in a 3-year-old boy after heart transplantation—diagnostic and therapeutic difficulties. Kardiochir Torakochirurgia Pol. 2015;12:176-180.
- Beck L, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
- Savoia P, Cavaliere G, Zavattaro E, et al. Inflammatory cutaneous diseases in renal transplant recipients [published online August 19, 2016]. Int J Mol Sci. doi:10.3390/ijms17081362.
- Lally A, Casabonne D, Imko-Walczuk B, et al. Prevalence of benign cutaneous disease among Oxford renal transplant recipients. J Eur Acad Dermatol Venereol. 2011;25:462-470.
- Beck L, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
- Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335-2348.
- Machura E, Chodór B, Kleszyk M, et al. Atopic allergy and chronic inflammation of the oral mucosa in a 3-year-old boy after heart transplantation—diagnostic and therapeutic difficulties. Kardiochir Torakochirurgia Pol. 2015;12:176-180.
- Beck L, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
Practice Points
- Chronic tacrolimus use in solid-organ transplant recipients may increase intestinal permeability to allergens and is a potential cause for development of atopic dermatitis (AD).
- Dupilumab has the potential to provide relief from particularly tenacious cases of AD.
- History of solid-organ transplant should not be cause for exclusion from consideration for dupilumab therapy.
Atopic dermatitis in adults associated with increased risk of dementia
CHICAGO – Atopic dermatitis in adulthood was associated with a twofold increase in the risk of developing dementia late in life, based on results from a large longitudinal cohort study presented at the annual meeting of the Society for Investigative Dermatology.
“After adjusting for potential mediators such as smoking status, depression, cardiovascular disease, and asthma or rhinitis, the effect was decreased slightly but still remained strongly statistically significant,” reported Katrina Abuabara, MD, of the University of California, San Francisco.
Atopic dermatitis is the latest in growing list of chronic inflammatory conditions that have been associated with an increased risk of dementia, according to Dr. Abuabara, who cited a body of evidence suggesting that inflammation triggers or exacerbates the processes that drive risk of developing dementia late in life.
Interest in the potential association of atopic dermatitis and dementia has been triggered “by a paradigm shift in which we now think of atopic dermatitis as a systemic inflammatory condition.” Dr. Abuabara reported.
In a primary care database of more than 1 million patients, both atopic dermatitis and dementia were common in those aged 60 years or older. The two disorders were identified in 6.75% and 6.49% of patients, respectively.
Cox proportional hazard ratios were employed to determine the relationship between the presence of atopic dermatitis and subsequent development of dementia. The median follow-up was 8 years. Atopic dermatitis was classified as mild, moderate, or severe involvement based on treatment records.
Patients with dementia associated with infectious diseases such as HIV, alcoholism, and other exogenous toxins were excluded from the analysis.
For those with atopic dermatitis relative to those without, the unadjusted hazard ratios were 1.91 for dementia of any type, 2.14 for Alzheimer’s dementia, and 2.25 for vascular-related dementia. After adjustment for confounders such as age, sex, and socioeconomic status, these hazard ratios, respectively, were only somewhat lower and remained statistically significant.
There was a trend for greater dementia risk with greater atopic dermatitis severity, rising from 2.07 in those with mild atopic dermatitis to 2.72 to those with severe disease, according to Dr. Abuabara.
“The important next step is to determine if better control of atopic dermatitis results in a lower risk of dementia,” she said.
According to Dr. Abuabara, some experimental studies have supported the hypothesis that downregulation of systemic markers of inflammation may be protective.
“Even if you reduced risk by a small amount, it would translate into a large health impact because of the large and growing prevalence of dementia,” she said.
Dr. Abuabara is a consultant for the TARGET-DERM study, sponsored by Target PharmaSolutions.
CHICAGO – Atopic dermatitis in adulthood was associated with a twofold increase in the risk of developing dementia late in life, based on results from a large longitudinal cohort study presented at the annual meeting of the Society for Investigative Dermatology.
“After adjusting for potential mediators such as smoking status, depression, cardiovascular disease, and asthma or rhinitis, the effect was decreased slightly but still remained strongly statistically significant,” reported Katrina Abuabara, MD, of the University of California, San Francisco.
Atopic dermatitis is the latest in growing list of chronic inflammatory conditions that have been associated with an increased risk of dementia, according to Dr. Abuabara, who cited a body of evidence suggesting that inflammation triggers or exacerbates the processes that drive risk of developing dementia late in life.
Interest in the potential association of atopic dermatitis and dementia has been triggered “by a paradigm shift in which we now think of atopic dermatitis as a systemic inflammatory condition.” Dr. Abuabara reported.
In a primary care database of more than 1 million patients, both atopic dermatitis and dementia were common in those aged 60 years or older. The two disorders were identified in 6.75% and 6.49% of patients, respectively.
Cox proportional hazard ratios were employed to determine the relationship between the presence of atopic dermatitis and subsequent development of dementia. The median follow-up was 8 years. Atopic dermatitis was classified as mild, moderate, or severe involvement based on treatment records.
Patients with dementia associated with infectious diseases such as HIV, alcoholism, and other exogenous toxins were excluded from the analysis.
For those with atopic dermatitis relative to those without, the unadjusted hazard ratios were 1.91 for dementia of any type, 2.14 for Alzheimer’s dementia, and 2.25 for vascular-related dementia. After adjustment for confounders such as age, sex, and socioeconomic status, these hazard ratios, respectively, were only somewhat lower and remained statistically significant.
There was a trend for greater dementia risk with greater atopic dermatitis severity, rising from 2.07 in those with mild atopic dermatitis to 2.72 to those with severe disease, according to Dr. Abuabara.
“The important next step is to determine if better control of atopic dermatitis results in a lower risk of dementia,” she said.
According to Dr. Abuabara, some experimental studies have supported the hypothesis that downregulation of systemic markers of inflammation may be protective.
“Even if you reduced risk by a small amount, it would translate into a large health impact because of the large and growing prevalence of dementia,” she said.
Dr. Abuabara is a consultant for the TARGET-DERM study, sponsored by Target PharmaSolutions.
CHICAGO – Atopic dermatitis in adulthood was associated with a twofold increase in the risk of developing dementia late in life, based on results from a large longitudinal cohort study presented at the annual meeting of the Society for Investigative Dermatology.
“After adjusting for potential mediators such as smoking status, depression, cardiovascular disease, and asthma or rhinitis, the effect was decreased slightly but still remained strongly statistically significant,” reported Katrina Abuabara, MD, of the University of California, San Francisco.
Atopic dermatitis is the latest in growing list of chronic inflammatory conditions that have been associated with an increased risk of dementia, according to Dr. Abuabara, who cited a body of evidence suggesting that inflammation triggers or exacerbates the processes that drive risk of developing dementia late in life.
Interest in the potential association of atopic dermatitis and dementia has been triggered “by a paradigm shift in which we now think of atopic dermatitis as a systemic inflammatory condition.” Dr. Abuabara reported.
In a primary care database of more than 1 million patients, both atopic dermatitis and dementia were common in those aged 60 years or older. The two disorders were identified in 6.75% and 6.49% of patients, respectively.
Cox proportional hazard ratios were employed to determine the relationship between the presence of atopic dermatitis and subsequent development of dementia. The median follow-up was 8 years. Atopic dermatitis was classified as mild, moderate, or severe involvement based on treatment records.
Patients with dementia associated with infectious diseases such as HIV, alcoholism, and other exogenous toxins were excluded from the analysis.
For those with atopic dermatitis relative to those without, the unadjusted hazard ratios were 1.91 for dementia of any type, 2.14 for Alzheimer’s dementia, and 2.25 for vascular-related dementia. After adjustment for confounders such as age, sex, and socioeconomic status, these hazard ratios, respectively, were only somewhat lower and remained statistically significant.
There was a trend for greater dementia risk with greater atopic dermatitis severity, rising from 2.07 in those with mild atopic dermatitis to 2.72 to those with severe disease, according to Dr. Abuabara.
“The important next step is to determine if better control of atopic dermatitis results in a lower risk of dementia,” she said.
According to Dr. Abuabara, some experimental studies have supported the hypothesis that downregulation of systemic markers of inflammation may be protective.
“Even if you reduced risk by a small amount, it would translate into a large health impact because of the large and growing prevalence of dementia,” she said.
Dr. Abuabara is a consultant for the TARGET-DERM study, sponsored by Target PharmaSolutions.
REPORTING FROM SID 2019
Patch testing in atopic dermatitis: when and how
WAIKOLOA, HAWAII – The according to Jonathan I. Silverberg, MD, PhD.
“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).
This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.
“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.
The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).
Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.
Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.
“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.
When to patch test atopic dermatitis patients
Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.
Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.
“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.
Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
How to patch test atopic dermatitis patients
Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.
Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.
“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – The according to Jonathan I. Silverberg, MD, PhD.
“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).
This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.
“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.
The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).
Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.
Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.
“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.
When to patch test atopic dermatitis patients
Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.
Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.
“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.
Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
How to patch test atopic dermatitis patients
Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.
Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.
“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – The according to Jonathan I. Silverberg, MD, PhD.
“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).
This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.
“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.
The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).
Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.
Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.
“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.
When to patch test atopic dermatitis patients
Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.
Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.
“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.
Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
How to patch test atopic dermatitis patients
Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.
Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.
“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
