Atopic Dermatitis

MILAN – A cream-based formulation of the Janus kinase (JAK) inhibitor ruxolitinib maintained its efficacy 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 cream-based formulation of the Janus kinase (JAK) inhibitor ruxolitinib maintained its efficacy 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 cream-based formulation of the Janus kinase (JAK) inhibitor ruxolitinib maintained its efficacy 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 – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, 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 – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, 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 – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, 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.

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.⁵ Although highly specific and targeted medications will continue to dominate the innovative dermatology treatment landscape, broadly effective treatments such as phototherapy will remain effective when disease states stray from their textbook pathophysiology.

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.⁵ Although highly specific and targeted medications will continue to dominate the innovative dermatology treatment landscape, broadly effective treatments such as phototherapy will remain effective when disease states stray from their textbook pathophysiology.

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.⁵ Although highly specific and targeted medications will continue to dominate the innovative dermatology treatment landscape, broadly effective treatments such as phototherapy will remain effective when disease states stray from their textbook pathophysiology.

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.

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

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

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

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.

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.

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.

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.

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 (T_H2 cytokines) through selective inhibition of the T_H1 cytokine IL-2.⁵

Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of T_H2-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 (T_H2 cytokines) through selective inhibition of the T_H1 cytokine IL-2.⁵

Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of T_H2-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 (T_H2 cytokines) through selective inhibition of the T_H1 cytokine IL-2.⁵

Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of T_H2-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.

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.

Ted Bosworth/MDedge News

“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.

Ted Bosworth/MDedge News

“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.

Ted Bosworth/MDedge News

“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.

WAIKOLOA, HAWAII – The prevalence of allergic contact dermatitis is elevated among patients with atopic dermatitis – and it pays to know their major sources of risk, according to Jonathan I. Silverberg, MD, PhD.

photorobot/Getty Images

“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).

Bruce Jancin/MDedge News

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.

bjancin@mdedge.com

WAIKOLOA, HAWAII – The prevalence of allergic contact dermatitis is elevated among patients with atopic dermatitis – and it pays to know their major sources of risk, according to Jonathan I. Silverberg, MD, PhD.

photorobot/Getty Images

“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).

Bruce Jancin/MDedge News

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.

bjancin@mdedge.com

WAIKOLOA, HAWAII – The prevalence of allergic contact dermatitis is elevated among patients with atopic dermatitis – and it pays to know their major sources of risk, according to Jonathan I. Silverberg, MD, PhD.

photorobot/Getty Images

“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).

Bruce Jancin/MDedge News

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.

bjancin@mdedge.com

Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.¹ Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.

Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.

General Observations Pertaining to Patients and Nature-Based Products

Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).^2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.

For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.^21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.²³ Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.^24-26

Nature-Based Products in Skin Health and Dermatologic Conditions

Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.

Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.

Physician Perceptions of Nature-Based Products

Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.²⁷ Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.^28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.³⁰

It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes³¹; coconut oil exhibits anti-inflammatory properties^32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.^34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.^42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.

Physician Recommendations

Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.⁴⁴ Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.

A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.⁴⁵ For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.

We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.

We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.

Conclusion

Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.



Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).

Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.¹ Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.

Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.

General Observations Pertaining to Patients and Nature-Based Products

Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).^2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.

For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.^21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.²³ Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.^24-26

Nature-Based Products in Skin Health and Dermatologic Conditions

Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.

Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.

Physician Perceptions of Nature-Based Products

Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.²⁷ Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.^28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.³⁰

It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes³¹; coconut oil exhibits anti-inflammatory properties^32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.^34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.^42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.

Physician Recommendations

Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.⁴⁴ Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.

A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.⁴⁵ For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.

We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.

We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.

Conclusion

Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.



Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).

Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.¹ Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.

Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.

General Observations Pertaining to Patients and Nature-Based Products

Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).^2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.

For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.^21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.²³ Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.^24-26

Nature-Based Products in Skin Health and Dermatologic Conditions

Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.

Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.

Physician Perceptions of Nature-Based Products

Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.²⁷ Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.^28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.³⁰

It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes³¹; coconut oil exhibits anti-inflammatory properties^32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.^34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.^42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.

Physician Recommendations

Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.⁴⁴ Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.

A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.⁴⁵ For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.

We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.

We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.

Conclusion

Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.



Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).