Atopic Dermatitis

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

dbrunk@mdedge.com

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

dbrunk@mdedge.com

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

dbrunk@mdedge.com

One in 15 patients who start dupilumab treatment may develop conjunctivitis during the first 6 months, most of which is manageable with ophthalmic treatments, results from large study of U.S. claims data showed.

“About 4 years after dupilumab’s approval, we’re interested in how conjunctivitis has played out in our daily clinical practice,” lead study investigator Maria C. Schneeweiss, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Drawing from two nationwide U.S. databases, MarketScan and Optum, Dr. Schneeweiss, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues sought to characterize the incidence of bacterial and nonbacterial conjunctivitis among 6,730 patients with AD who started treatment with either dupilumab, methotrexate, mycophenolate, or cyclosporine between March 2017 and January 2020. They also wanted to identify patient subgroups at increased or decreased risk of dupilumab-related conjunctivitis in clinical practice.

Of the 6,730 patients, 3,755 started treatment with dupilumab, while 2,010 started with methotrexate, 536 started with mycophenolate, and 429 started with cyclosporine. Using a new-user, active-comparator study design, the researchers identified patients with AD from both databases and selected three dupilumab cohorts: dupilumab versus methotrexate (MTX), dupilumab versus mycophenolate (MMF), and dupilumab versus cyclosporine (CsA). Follow-up lasted 6 months and 1:1 propensity score matching was used to account for conjunctivitis risk factor differences. Patients with a history of conjunctivitis were excluded from the study, except one subgroup limited to those with prior conjunctivitis.

Dr. Schneeweiss reported that the overall incidence rate of conjunctivitis within 6 months of treatment initiation was 6.6% in dupilumab users, or 1 in 15 patients, compared with 3.3% in MTX users, 4.2% in MMF users, and 2.8% in CsA users. The incidence rates for the different types of conjunctivitis were as follows:

• Bacterial conjunctivitis: 1.5% in dupilumab users versus 0.95% in MTX, 0.4% in MMF, and 0.7% in CsA users.
• Allergic conjunctivitis: 2.2% in dupilumab users versus 0.8% in MTX, 0.2% in MMF, and 1.6% in CsA users.
• Keratoconjunctivitis: 0.8% in dupilumab users versus 1.1% in MTX, 1.5% in MMF, and 0.5% in CsA users.

In addition, the rate of conjunctivitis requiring ophthalmic medication was 2.6% in dupilumab users versus 0.7% in MTX, 1% in MMF, and 0.5% in CsA users.

After the researchers applied 1:1 propensity score matching, they observed that the risk of conjunctivitis within 6 months of starting treatment was increased in dupilumab users versus MTX users (relative risk, 2.12), dupilumab versus MMF users (RR, 2.43), and dupilumab versus CsA users (RR, 1.83). Among dupilumab users, the risk of conjunctivitis requiring ophthalmic medication was increased six to eightfold, compared with those who used MTX, MMF or CsA. In addition, bacterial conjunctivitis was increased 1.6- to 4.0-fold, compared with those who used MTX, MMF or CsA, but the confidence intervals were wide and included the null, while allergic conjunctivitis was increased 2.7- to 7-fold when compared with those who used MTX and MMF.

In other findings, the risk of allergic conjunctivitis was similar between dupilumab and CsA users (RR, 1.14), and there was no increased risk of keratoconjunctivitis in dupilumab users, compared with those who used MTX, MMF, or CsA. The relative risk of conjunctivitis in those who used dupilumab was further increased when the analysis was limited to AD patients with comorbid asthma (RR, 2.86), those who used systemic glucocorticoids fewer than 30 days prior (RR, 2.88), and those age 65 and older (RR, 2.57), compared with those who used methotrexate.

“Compared to AD patients who received treatment with other systemic agents, dupilumab treatment doubled the risk of conjunctivitis in clinical practice,” Dr. Schneeweiss concluded. “Risk factors that further increase the risk include comorbid asthma, use of systemic corticosteroids, and older age. It should be noted that conjunctivitis does not require treatment discontinuation and is manageable with ophthalmic medications.”

Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, said that the work “verifies what we see clinically: that conjunctivitis is increased among dupilumab users even when it is compared to immunosuppressive agents used to treat other conditions. Because the study is retrospective, one cannot assume all diagnosis of types of conjunctivitis or even of skin disease is entirely accurate. But, with the large numbers of claims looked at and compared, one would think its conclusions are accurate.”

Dr. Schneeweiss reported having no relevant financial disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for Amgen, AbbVie, Arcutis, Brickell, Candescent, Cassiopeia, Dermavant, Galderma, Janssen, Forte, Incyte, MC-2, Lilly, Novartis, Novan, Ortho Dermatologics, Revance, Sun Pharma, UCB, and Vyne.

dbrunk@mdedge.com

One in 15 patients who start dupilumab treatment may develop conjunctivitis during the first 6 months, most of which is manageable with ophthalmic treatments, results from large study of U.S. claims data showed.

“About 4 years after dupilumab’s approval, we’re interested in how conjunctivitis has played out in our daily clinical practice,” lead study investigator Maria C. Schneeweiss, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Drawing from two nationwide U.S. databases, MarketScan and Optum, Dr. Schneeweiss, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues sought to characterize the incidence of bacterial and nonbacterial conjunctivitis among 6,730 patients with AD who started treatment with either dupilumab, methotrexate, mycophenolate, or cyclosporine between March 2017 and January 2020. They also wanted to identify patient subgroups at increased or decreased risk of dupilumab-related conjunctivitis in clinical practice.

Of the 6,730 patients, 3,755 started treatment with dupilumab, while 2,010 started with methotrexate, 536 started with mycophenolate, and 429 started with cyclosporine. Using a new-user, active-comparator study design, the researchers identified patients with AD from both databases and selected three dupilumab cohorts: dupilumab versus methotrexate (MTX), dupilumab versus mycophenolate (MMF), and dupilumab versus cyclosporine (CsA). Follow-up lasted 6 months and 1:1 propensity score matching was used to account for conjunctivitis risk factor differences. Patients with a history of conjunctivitis were excluded from the study, except one subgroup limited to those with prior conjunctivitis.

Dr. Schneeweiss reported that the overall incidence rate of conjunctivitis within 6 months of treatment initiation was 6.6% in dupilumab users, or 1 in 15 patients, compared with 3.3% in MTX users, 4.2% in MMF users, and 2.8% in CsA users. The incidence rates for the different types of conjunctivitis were as follows:

• Bacterial conjunctivitis: 1.5% in dupilumab users versus 0.95% in MTX, 0.4% in MMF, and 0.7% in CsA users.
• Allergic conjunctivitis: 2.2% in dupilumab users versus 0.8% in MTX, 0.2% in MMF, and 1.6% in CsA users.
• Keratoconjunctivitis: 0.8% in dupilumab users versus 1.1% in MTX, 1.5% in MMF, and 0.5% in CsA users.

In addition, the rate of conjunctivitis requiring ophthalmic medication was 2.6% in dupilumab users versus 0.7% in MTX, 1% in MMF, and 0.5% in CsA users.

After the researchers applied 1:1 propensity score matching, they observed that the risk of conjunctivitis within 6 months of starting treatment was increased in dupilumab users versus MTX users (relative risk, 2.12), dupilumab versus MMF users (RR, 2.43), and dupilumab versus CsA users (RR, 1.83). Among dupilumab users, the risk of conjunctivitis requiring ophthalmic medication was increased six to eightfold, compared with those who used MTX, MMF or CsA. In addition, bacterial conjunctivitis was increased 1.6- to 4.0-fold, compared with those who used MTX, MMF or CsA, but the confidence intervals were wide and included the null, while allergic conjunctivitis was increased 2.7- to 7-fold when compared with those who used MTX and MMF.

In other findings, the risk of allergic conjunctivitis was similar between dupilumab and CsA users (RR, 1.14), and there was no increased risk of keratoconjunctivitis in dupilumab users, compared with those who used MTX, MMF, or CsA. The relative risk of conjunctivitis in those who used dupilumab was further increased when the analysis was limited to AD patients with comorbid asthma (RR, 2.86), those who used systemic glucocorticoids fewer than 30 days prior (RR, 2.88), and those age 65 and older (RR, 2.57), compared with those who used methotrexate.

“Compared to AD patients who received treatment with other systemic agents, dupilumab treatment doubled the risk of conjunctivitis in clinical practice,” Dr. Schneeweiss concluded. “Risk factors that further increase the risk include comorbid asthma, use of systemic corticosteroids, and older age. It should be noted that conjunctivitis does not require treatment discontinuation and is manageable with ophthalmic medications.”

Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, said that the work “verifies what we see clinically: that conjunctivitis is increased among dupilumab users even when it is compared to immunosuppressive agents used to treat other conditions. Because the study is retrospective, one cannot assume all diagnosis of types of conjunctivitis or even of skin disease is entirely accurate. But, with the large numbers of claims looked at and compared, one would think its conclusions are accurate.”

Dr. Schneeweiss reported having no relevant financial disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for Amgen, AbbVie, Arcutis, Brickell, Candescent, Cassiopeia, Dermavant, Galderma, Janssen, Forte, Incyte, MC-2, Lilly, Novartis, Novan, Ortho Dermatologics, Revance, Sun Pharma, UCB, and Vyne.

dbrunk@mdedge.com

One in 15 patients who start dupilumab treatment may develop conjunctivitis during the first 6 months, most of which is manageable with ophthalmic treatments, results from large study of U.S. claims data showed.

“About 4 years after dupilumab’s approval, we’re interested in how conjunctivitis has played out in our daily clinical practice,” lead study investigator Maria C. Schneeweiss, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Drawing from two nationwide U.S. databases, MarketScan and Optum, Dr. Schneeweiss, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues sought to characterize the incidence of bacterial and nonbacterial conjunctivitis among 6,730 patients with AD who started treatment with either dupilumab, methotrexate, mycophenolate, or cyclosporine between March 2017 and January 2020. They also wanted to identify patient subgroups at increased or decreased risk of dupilumab-related conjunctivitis in clinical practice.

Of the 6,730 patients, 3,755 started treatment with dupilumab, while 2,010 started with methotrexate, 536 started with mycophenolate, and 429 started with cyclosporine. Using a new-user, active-comparator study design, the researchers identified patients with AD from both databases and selected three dupilumab cohorts: dupilumab versus methotrexate (MTX), dupilumab versus mycophenolate (MMF), and dupilumab versus cyclosporine (CsA). Follow-up lasted 6 months and 1:1 propensity score matching was used to account for conjunctivitis risk factor differences. Patients with a history of conjunctivitis were excluded from the study, except one subgroup limited to those with prior conjunctivitis.

Dr. Schneeweiss reported that the overall incidence rate of conjunctivitis within 6 months of treatment initiation was 6.6% in dupilumab users, or 1 in 15 patients, compared with 3.3% in MTX users, 4.2% in MMF users, and 2.8% in CsA users. The incidence rates for the different types of conjunctivitis were as follows:

• Bacterial conjunctivitis: 1.5% in dupilumab users versus 0.95% in MTX, 0.4% in MMF, and 0.7% in CsA users.
• Allergic conjunctivitis: 2.2% in dupilumab users versus 0.8% in MTX, 0.2% in MMF, and 1.6% in CsA users.
• Keratoconjunctivitis: 0.8% in dupilumab users versus 1.1% in MTX, 1.5% in MMF, and 0.5% in CsA users.

In addition, the rate of conjunctivitis requiring ophthalmic medication was 2.6% in dupilumab users versus 0.7% in MTX, 1% in MMF, and 0.5% in CsA users.

After the researchers applied 1:1 propensity score matching, they observed that the risk of conjunctivitis within 6 months of starting treatment was increased in dupilumab users versus MTX users (relative risk, 2.12), dupilumab versus MMF users (RR, 2.43), and dupilumab versus CsA users (RR, 1.83). Among dupilumab users, the risk of conjunctivitis requiring ophthalmic medication was increased six to eightfold, compared with those who used MTX, MMF or CsA. In addition, bacterial conjunctivitis was increased 1.6- to 4.0-fold, compared with those who used MTX, MMF or CsA, but the confidence intervals were wide and included the null, while allergic conjunctivitis was increased 2.7- to 7-fold when compared with those who used MTX and MMF.

In other findings, the risk of allergic conjunctivitis was similar between dupilumab and CsA users (RR, 1.14), and there was no increased risk of keratoconjunctivitis in dupilumab users, compared with those who used MTX, MMF, or CsA. The relative risk of conjunctivitis in those who used dupilumab was further increased when the analysis was limited to AD patients with comorbid asthma (RR, 2.86), those who used systemic glucocorticoids fewer than 30 days prior (RR, 2.88), and those age 65 and older (RR, 2.57), compared with those who used methotrexate.

“Compared to AD patients who received treatment with other systemic agents, dupilumab treatment doubled the risk of conjunctivitis in clinical practice,” Dr. Schneeweiss concluded. “Risk factors that further increase the risk include comorbid asthma, use of systemic corticosteroids, and older age. It should be noted that conjunctivitis does not require treatment discontinuation and is manageable with ophthalmic medications.”

Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, said that the work “verifies what we see clinically: that conjunctivitis is increased among dupilumab users even when it is compared to immunosuppressive agents used to treat other conditions. Because the study is retrospective, one cannot assume all diagnosis of types of conjunctivitis or even of skin disease is entirely accurate. But, with the large numbers of claims looked at and compared, one would think its conclusions are accurate.”

Dr. Schneeweiss reported having no relevant financial disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for Amgen, AbbVie, Arcutis, Brickell, Candescent, Cassiopeia, Dermavant, Galderma, Janssen, Forte, Incyte, MC-2, Lilly, Novartis, Novan, Ortho Dermatologics, Revance, Sun Pharma, UCB, and Vyne.

dbrunk@mdedge.com

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

dbrunk@mdedge.com

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

dbrunk@mdedge.com

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

dbrunk@mdedge.com

This patient has atopic dermatitis (AD), but on the basis of the image and description above, by no means would this be an intuitive diagnosis; the findings are not characteristic of those in younger patients with AD. Further, clinicians might find it difficult to diagnose AD in an older patient because older patients generally tend to have more comorbidities and medication side effects, including chronic pruritus of unknown origin and xerosis, which could confound the diagnosis. 

Finally, specific guidelines are lacking for clinicians to distinguish AD from other pruritic skin conditions in the older patient. Currently, according to one report, older patients are diagnosed with AD after at least 6 months of symptom assessment and exclusion of other conditions, including cutaneous T-cell lymphoma, allergic contact dermatitis, psoriasis, drug reactions, and chronic idiopathic or secondary erythroderma.

AD arising de novo in older persons is a discrete form of the disease that characteristically involves the face, neck, trunk, and hands, while sparing the flexural areas, which are prominently involved in younger patients. The eczema can become erythrodermic. Older men are affected threefold more often than older women. 

Skin manifestations in older patients with AD generally match those of adolescents and young adults with AD, but the reverse sign of lichenified eczema around unaffected folds of the elbows and knees is more common than the classic sign of localized lichenified eczema at those folds. 

Factors rendering older people susceptible to AD include innate physiologic changes of aging, notably a decline in skin barrier function, dysregulation of innate immune cells, and skewing of adaptive immunity to a Th2 response.

Much about how to best treat AD in older patients remains unclear. It is a challenge to treat older patients according to standardized guidelines for general AD treatment because dermatologists and others need to consider comorbidities and the medications that these patients might already be taking. Some examples: Dermatologists might limit cyclosporine use in patients with hypertension and reduced kidney function, or limit systemic steroid use in patients with osteoporosis. Older patients have a greater propensity for infection, which might cause dermatologists to limit systemic immunosuppressant drugs. And skin thinning and diffuse photoaging might cause doctors to limit even topical steroid treatment in these patients.

As in other age groups, regular application of moisturizers in combination with calcineurin inhibitors, adjunctive administration of oral antihistamines and avoidance of exacerbating factors comprise basic treatments for AD in older patients. 

Although antihistamines such as hydroxyzine can work for itching in some individuals, they are generally lacking in efficacy in most patients with AD.

Brian S. Kim, MD, is Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

This patient has atopic dermatitis (AD), but on the basis of the image and description above, by no means would this be an intuitive diagnosis; the findings are not characteristic of those in younger patients with AD. Further, clinicians might find it difficult to diagnose AD in an older patient because older patients generally tend to have more comorbidities and medication side effects, including chronic pruritus of unknown origin and xerosis, which could confound the diagnosis. 

Finally, specific guidelines are lacking for clinicians to distinguish AD from other pruritic skin conditions in the older patient. Currently, according to one report, older patients are diagnosed with AD after at least 6 months of symptom assessment and exclusion of other conditions, including cutaneous T-cell lymphoma, allergic contact dermatitis, psoriasis, drug reactions, and chronic idiopathic or secondary erythroderma.

AD arising de novo in older persons is a discrete form of the disease that characteristically involves the face, neck, trunk, and hands, while sparing the flexural areas, which are prominently involved in younger patients. The eczema can become erythrodermic. Older men are affected threefold more often than older women. 

Skin manifestations in older patients with AD generally match those of adolescents and young adults with AD, but the reverse sign of lichenified eczema around unaffected folds of the elbows and knees is more common than the classic sign of localized lichenified eczema at those folds. 

Factors rendering older people susceptible to AD include innate physiologic changes of aging, notably a decline in skin barrier function, dysregulation of innate immune cells, and skewing of adaptive immunity to a Th2 response.

Much about how to best treat AD in older patients remains unclear. It is a challenge to treat older patients according to standardized guidelines for general AD treatment because dermatologists and others need to consider comorbidities and the medications that these patients might already be taking. Some examples: Dermatologists might limit cyclosporine use in patients with hypertension and reduced kidney function, or limit systemic steroid use in patients with osteoporosis. Older patients have a greater propensity for infection, which might cause dermatologists to limit systemic immunosuppressant drugs. And skin thinning and diffuse photoaging might cause doctors to limit even topical steroid treatment in these patients.

As in other age groups, regular application of moisturizers in combination with calcineurin inhibitors, adjunctive administration of oral antihistamines and avoidance of exacerbating factors comprise basic treatments for AD in older patients. 

Although antihistamines such as hydroxyzine can work for itching in some individuals, they are generally lacking in efficacy in most patients with AD.

Brian S. Kim, MD, is Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

This patient has atopic dermatitis (AD), but on the basis of the image and description above, by no means would this be an intuitive diagnosis; the findings are not characteristic of those in younger patients with AD. Further, clinicians might find it difficult to diagnose AD in an older patient because older patients generally tend to have more comorbidities and medication side effects, including chronic pruritus of unknown origin and xerosis, which could confound the diagnosis. 

Finally, specific guidelines are lacking for clinicians to distinguish AD from other pruritic skin conditions in the older patient. Currently, according to one report, older patients are diagnosed with AD after at least 6 months of symptom assessment and exclusion of other conditions, including cutaneous T-cell lymphoma, allergic contact dermatitis, psoriasis, drug reactions, and chronic idiopathic or secondary erythroderma.

AD arising de novo in older persons is a discrete form of the disease that characteristically involves the face, neck, trunk, and hands, while sparing the flexural areas, which are prominently involved in younger patients. The eczema can become erythrodermic. Older men are affected threefold more often than older women. 

Skin manifestations in older patients with AD generally match those of adolescents and young adults with AD, but the reverse sign of lichenified eczema around unaffected folds of the elbows and knees is more common than the classic sign of localized lichenified eczema at those folds. 

Factors rendering older people susceptible to AD include innate physiologic changes of aging, notably a decline in skin barrier function, dysregulation of innate immune cells, and skewing of adaptive immunity to a Th2 response.

Much about how to best treat AD in older patients remains unclear. It is a challenge to treat older patients according to standardized guidelines for general AD treatment because dermatologists and others need to consider comorbidities and the medications that these patients might already be taking. Some examples: Dermatologists might limit cyclosporine use in patients with hypertension and reduced kidney function, or limit systemic steroid use in patients with osteoporosis. Older patients have a greater propensity for infection, which might cause dermatologists to limit systemic immunosuppressant drugs. And skin thinning and diffuse photoaging might cause doctors to limit even topical steroid treatment in these patients.

As in other age groups, regular application of moisturizers in combination with calcineurin inhibitors, adjunctive administration of oral antihistamines and avoidance of exacerbating factors comprise basic treatments for AD in older patients. 

Although antihistamines such as hydroxyzine can work for itching in some individuals, they are generally lacking in efficacy in most patients with AD.

Brian S. Kim, MD, is Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

The Comparison

A Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy.

B Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl.

C Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

Epidemiology

People of African descent have the highest atopic dermatitis prevalence and severity.

Key clinical features in people with darker skin tones include:

• follicular prominence
• papular morphology
• prurigo nodules
• hyperpigmented, violaceous-brown or gray plaques instead of erythematous plaques
• lichenification
• treatment resistant.^1,2

Worth noting
Postinflammatory hyperpigmentation and postinflammatory hypopigmentation may be more distressing to the patient/family than the atopic dermatitis itself.

Health disparity highlight
In the United States, patients with skin of color are more likely to be hospitalized with severe atopic dermatitis, have more substantial out-ofpocket costs, be underinsured, and have an increased number of missed days of work. Limited access to outpatient health care plays a role in exacerbating this health disparity.^3,4

The Comparison

A Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy.

B Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl.

C Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

Epidemiology

People of African descent have the highest atopic dermatitis prevalence and severity.

Key clinical features in people with darker skin tones include:

• follicular prominence
• papular morphology
• prurigo nodules
• hyperpigmented, violaceous-brown or gray plaques instead of erythematous plaques
• lichenification
• treatment resistant.^1,2

Worth noting
Postinflammatory hyperpigmentation and postinflammatory hypopigmentation may be more distressing to the patient/family than the atopic dermatitis itself.

Health disparity highlight
In the United States, patients with skin of color are more likely to be hospitalized with severe atopic dermatitis, have more substantial out-ofpocket costs, be underinsured, and have an increased number of missed days of work. Limited access to outpatient health care plays a role in exacerbating this health disparity.^3,4

The Comparison

A Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy.

B Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl.

C Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

Epidemiology

People of African descent have the highest atopic dermatitis prevalence and severity.

Key clinical features in people with darker skin tones include:

• follicular prominence
• papular morphology
• prurigo nodules
• hyperpigmented, violaceous-brown or gray plaques instead of erythematous plaques
• lichenification
• treatment resistant.^1,2

Worth noting
Postinflammatory hyperpigmentation and postinflammatory hypopigmentation may be more distressing to the patient/family than the atopic dermatitis itself.

Health disparity highlight
In the United States, patients with skin of color are more likely to be hospitalized with severe atopic dermatitis, have more substantial out-ofpocket costs, be underinsured, and have an increased number of missed days of work. Limited access to outpatient health care plays a role in exacerbating this health disparity.^3,4

Within the last decade, almost 3000 articles have been published on the role of diet in the prevention and management of dermatologic conditions. Patients are increasingly interested in—and employing—dietary modifications that may influence skin appearance and aid in the treatment of cutaneous disease.¹ It is essential that dermatologists are familiar with existing evidence on the role of diet in dermatology to counsel patients appropriately. Herein, we discuss the compositions of several popular diets and their proposed utility for dermatologic purposes. We highlight the limited literature that exists surrounding this topic and emphasize the need for future, well-designed clinical trials that study the impact of diet on skin disease.

Ketogenic Diet

The ketogenic diet has a macronutrient profile composed of high fat, low to moderate protein, and very low carbohydrates. Nutritional ketosis occurs as the body begins to use free fatty acids (via beta oxidation) as the primary metabolite driving cellular metabolism. It has been suggested that the ketogenic diet may impart beneficial effects on skin disease; however, limited literature exists on the role of nutritional ketosis in the treatment of dermatologic conditions.

Mechanistically, the ketogenic diet decreases the secretion of insulin and insulinlike growth factor 1, resulting in a reduction of circulating androgens and increased activity of the retinoid X receptor.² In acne vulgaris, it has been suggested that the ketogenic diet may be beneficial in decreasing androgen-induced sebum production and the overproliferation of keratinocytes.^2-7 The ketogenic diet is one of the most rapidly effective dietary strategies for normalizing both insulin and androgens, thus it may theoretically be useful for other metabolic and hormone-dependent skin diseases, such as hidradenitis suppurativa.^8,9

The cutaneous manifestations associated with chronic hyperinsulinemia and hyperglycemia are numerous and include acanthosis nigricans, acrochordons, diabetic dermopathy, scleredema diabeticorum, bullosis diabeticorum, keratosis pilaris, and generalized granuloma annulare. There also is an increased risk for bacterial and fungal skin infections associated with hyperglycemic states.¹⁰ The ketogenic diet is an effective nonpharmacologic tool for normalizing serum insulin and glucose levels in most patients and may have utility in the aforementioned conditions.^11,12 In addition to improving insulin sensitivity, it has been used as a dietary strategy for weight loss.^11-15 Because obesity and metabolic syndrome are highly correlated with common skin conditions such as psoriasis, hidradenitis suppurativa, and androgenetic alopecia, there may be a role for employing the ketogenic diet in these patient populations.^16,17

Although robust clinical studies on ketogenic diets in skin disease are lacking, a recent single-arm, open-label clinical trial observed benefit in all 37 drug-naïve, overweight patients with chronic plaque psoriasis who underwent a ketogenic weight loss protocol. Significant reductions in psoriasis area and severity index (PASI) score and dermatology life quality index score were reported (P<.001).¹⁸ Another study of 30 patients with psoriasis found that a 4-week, low-calorie, ketogenic diet resulted in 50% improvement of PASI scores, 10% weight loss, and a reduction in the proinflammatory cytokines IL-1β and IL-2.¹⁹ Despite these results, it is a challenge to tease out if the specific dietary intervention or its associated weight loss was the main driver in these reported improvements in skin disease.

There is mixed evidence on the anti-inflammatory nature of the ketogenic diet, likely due to wide variation in the composition of foods included in individual diets. In many instances, the ketogenic diet is thought to possess considerable antioxidant and anti-inflammatory capabilities. Ketones are known activators of the nuclear factor erythroid 2–related factor 2 pathway, which upregulates the production of glutathione, a major endogenous intracellular antioxidant.²⁰ Additionally, dietary compounds from foods that are encouraged while on the ketogenic diet, such as sulforaphane from broccoli, also are independent activators of nuclear factor erythroid 2–related factor 2.²¹ Ketones are efficiently utilized by mitochondria, which also may result in the decreased production of reactive oxygen species and lower oxidative stress.²² Moreover, the ketone body β-hydroxybutyrate has demonstrated the ability to reduce proinflammatory IL-1β levels via suppression of nucleotide-binding domain-like receptor protein 3 inflammasome activity.^23,24 The activity of IL-1β is known to be elevated in many dermatologic conditions, including juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, hidradenitis suppurativa, Behçet disease, and other autoinflammatory syndromes.²⁵ Ketones also have been shown to inhibit the nuclear factor–κB proinflammatory signaling pathway.^22,26,27 Overexpression of IL-1β and aberrant activation of nuclear factor–κB are implicated in a variety of inflammatory, autoimmune, and oncologic cutaneous pathologies. The ketogenic diet may prove to be an effective adjunctive treatment for dermatologists to consider in select patient populations.^23,24,28-30

For patients with keratinocyte carcinomas, the ketogenic diet may offer the aforementioned anti-inflammatory and antioxidant effects, as well as suppression of the mechanistic target of rapamycin, a major regulator of cell metabolism and proliferation.^31,32 Inhibition of mechanistic target of rapamycin activity has been shown to slow tumor growth and reduce the development of squamous cell carcinoma.^25,33,34 The ketogenic diet also may exploit the preferential utilization of glucose exhibited by many types of cancer cells, thereby “starving” the tumor of its primary fuel source.^35,36 In vitro and animal studies in a variety of cancer types have demonstrated that a ketogenic metabolic state—achieved through the ketogenic diet or fasting—can sensitize tumor cells to chemotherapy and radiation while conferring a protective effect to normal cells.^37-40 This recently described phenomenon is known as differential stress resistance, but it has not been studied in keratinocyte malignancies or melanoma to date. Importantly, some basal cell carcinomas and BRAF V600E–mutated melanomas have worsened while on the ketogenic diet, suggesting more data is needed before it can be recommended for all cancer patients.^41,42 Furthermore, other skin conditions such as prurigo pigmentosa have been associated with initiation of the ketogenic diet.⁴³

Low FODMAP Diet

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that are poorly absorbed, osmotically active, and rapidly fermented by intestinal bacteria.⁴⁴ The low FODMAP diet has been shown to be efficacious for treatment of irritable bowel syndrome, small intestinal bacterial overgrowth (SIBO), and some cases of inflammatory bowel disease (IBD).^44-49 A low FODMAP diet may have potential implications for several dermatologic conditions.

Rosacea has been associated with various gastrointestinal tract disorders including irritable bowel syndrome, SIBO, and IBD.^50-54 A single study found that patients with rosacea had a 13-fold increased risk for SIBO.^55,56 Treatment of 40 patients with SIBO using rifaximin resulted in complete resolution of rosacea in all patients, with no relapse after a 3-year follow-up period.⁵⁵ Psoriasis also has been associated with SIBO and IBD.^57,58 One small study found that eradication of SIBO in psoriatic patients resulted in improved PASI scores and colorimetric values.⁵⁹

Although the long-term health consequences of the low FODMAP diet are unknown, further research on such dietary interventions for inflammatory skin conditions is warranted given the mounting evidence of a gut-skin connection and the role of the intestinal microbiome in skin health.^50,51

Gluten-Free Diet

Gluten is a protein found in a variety of grains. Although the role of gluten in the pathogenesis of celiac disease and dermatitis herpetiformis is indisputable, the deleterious effects of gluten outside of the context of these diseases remain controversial. There may be a compelling case for eliminating gluten in psoriasis patients with seropositivity for celiac disease. A recent systematic review found a 2.2-fold increased risk for celiac disease in psoriasis patients.⁶⁰ Antigliadin antibody titers also were found to be positively correlated with psoriatic disease severity.⁶¹ In addition, one open-label study found a reduction in PASI scores in 73% of patients with antigliadin antibodies after 3 months on a gluten-free diet compared to those without antibodies; however, the study only included 22 patients.⁶² Several other small studies have yielded similar results^63,64; however, antigliadin antibodies are neither the most sensitive nor specific markers of celiac disease, and additional testing should be completed in any patient who may carry this diagnosis. A survey study by the National Psoriasis Foundation found that the dietary change associated with the greatest skin improvement was removal of gluten and nightshade vegetables in approximately 50% of the 1200 psoriasis patients that responded.⁶⁵ Case reports of various dermatologic conditions including sarcoidosis, vitiligo, alopecia areata, lichen planus, dermatomyositis, pyoderma gangrenosum, erythema nodosum, leukocytoclastic vasculitis, linear IgA bullous dermatosis, and aphthous ulcerations have reportedly improved with a gluten-free diet; however, this should not be used as primary therapy in patients without celiac disease.^66-71 Because gluten-free diets can be expensive and challenging to follow, a formal assessment for celiac disease should be considered before recommendation of this dietary intervention.

Low Histamine Diet

Histamine is a biogenic amine produced by the decarboxylation of the amino acid histidine.⁷² It is found in several foods in varying amounts. Because bacteria can convert histidine into histamine, many fermented and aged foods such as kimchi, sauerkraut, cheese, and red wine contain high levels of histamine. Individuals who have decreased activity of diamine oxidase (DAO), an enzyme that degrades histamine, may be more susceptible to histamine intolerance.⁷² The symptoms of histamine intolerance are numerous and include gastrointestinal tract distress, rhinorrhea and nasal congestion, headache, urticaria, flushing, and pruritus. Histamine intolerance can mimic an IgE-mediated food allergy; however, allergy testing is negative in these patients. Unfortunately, there is no laboratory test for histamine intolerance; a double-blind, placebo-controlled food challenge is considered the gold-standard test.⁷²

As it pertains to dermatology, a low histamine diet may play a role in the treatment of certain patients with atopic dermatitis and chronic spontaneous urticaria. One study reported that 17 of 54 (31.5%) atopic patients had higher basal levels of serum histamine compared to controls.⁷³ Another study found that a histamine-free diet led to improvement in both histamine intolerance symptoms and atopic dermatitis disease severity (SCORing atopic dermatitis) in patients with low DAO activity.⁷⁴ In chronic spontaneous urticaria, a recent systematic review found that in 223 patients placed on a low histamine diet for 3 to 4 weeks, 12% and 44% achieved complete and partial remission, respectively.⁷⁵ Although treatment response based on a patient’s DAO activity level has not been correlated, a diet low in histamine may prove useful for patients with persistent atopic dermatitis and chronic spontaneous urticaria who have negative food allergy tests and report exacerbation of symptoms after ingestion of histamine-rich foods.^76,77

Mediterranean Diet

The Mediterranean diet has been touted as one of the healthiest diets to date, and large randomized clinical trials have demonstrated its effectiveness in weight loss, improving insulin sensitivity, and reducing inflammatory cytokine profiles.^78,79 A major criticism of the Mediterranean diet is that it has considerable ambiguity and lacks a precise definition due to the variability of what is consumed in different Mediterranean regions. Generally, the diet emphasizes high consumption of colorful fruits and vegetables, aromatic herbs and spices, olive oil, nuts, and seafood, as well as modest amounts of dairy, eggs, and red meat.⁸⁰ The anti-inflammatory effects of this diet largely have been attributed to its abundance of polyphenols, carotenoids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids (PUFAs).^80,81 Examples of polyphenols include resveratrol in red grapes, quercetin in apples and red onions, and curcumin in turmeric, while examples of carotenoids include lycopene in tomatoes and zeaxanthin in dark leafy greens. Oleic acid is a monounsaturated fatty acid present in high concentrations in olive oil, while eicosapentaenoic acid and docosahexaenoic acid are omega-3 PUFAs predominantly found in fish.⁸²

Unfortunately, rigorous clinical trials regarding the Mediterranean diet as it pertains to dermatology have not been undertaken. Numerous observational studies in patients with psoriasis have suggested that close adherence to the Mediterranean diet was associated with improvement in PASI scores.^83-86 The National Psoriasis Foundation now recommends a trial of the Mediterranean diet in some patients with psoriasis, emphasizing increased dietary intake of olive oil, fish, and vegetables.⁸⁷ Adherence to a Mediterranean diet also has been inversely correlated to the severity of acne vulgaris and hidradenitis suppurativa^88,89; however, these studies failed to account for the multifactorial risk factors associated with these conditions. Mediterranean diets also may impart a chemopreventive effect, supported by a number of in vivo and in vitro studies demonstrating the inhibition and/or reversal of cutaneous DNA damage induced by UV radiation through supplementation with various phytonutrients and omega-3 PUFAs.^81,90-92 Although small case-control studies have found a decreased risk of basal cell carcinoma in those who closely adhered to a Mediterranean diet, more rigorous clinical research is needed.⁹³

Whole-Food, Plant-Based Diet

A whole-food, plant-based (WFPB) diet is another popular dietary approach that consists of eating fruits, vegetables, legumes, nuts, seeds, and grains in their whole natural form.⁹⁴ This diet discourages all animal products, including red meat, seafood, dairy, and eggs. It is similar to a vegan diet except that it eliminates all highly refined carbohydrates, vegetable oils, and other processed foods.⁹⁴ Randomized clinical studies have demonstrated the WFPB diet to be effective in the treatment of obesity and metabolic syndrome.^95,96

A WFPB diet has been shown to increase the antioxidant capacity of cells, lengthen telomeres, and reduce formation of advanced glycation end products.^94,97,98 These benefits may help combat accelerated skin aging, including increased skin permeability, reduced elasticity and hydration, decreased angiogenesis, impaired immune function, and decreased vitamin D synthesis. Accelerated skin aging can result in delayed wound healing and susceptibility to skin tears and ecchymoses and also may promote the development of cutaneous malignancies.⁹⁹ There remains a lack of clinical data studying a properly formulated WFPB diet in the dermatologic setting.

Paleolithic Diet

The paleolithic (Paleo) diet is an increasingly popular way of eating that attempts to mirror what our ancestors may have consumed between 10,000 and 2.5 million years ago.¹⁰⁰ It is similar to the Mediterranean diet but excludes grains, dairy, legumes, and nightshade vegetables. It also calls for elimination of highly processed sugars and oils as well as chemical food additives and preservatives. There is a strict variation of the diet for individuals with autoimmune disease that also excludes eggs, nuts, and seeds, as these can be inflammatory or immunogenic in some patients.^100-106 Other variations of the diet exist, including the ketogenic Paleo diet, pegan (Paleo vegan) diet, and lacto-Paleo diet.¹⁰⁰ An often cited criticism of the Paleo diet is the low intake of calcium and risk for osteoporosis; however, consumption of calcium-rich foods or a calcium supplement can address this concern.¹⁰⁷

Although small clinical studies have found the Paleo diet to be beneficial for various autoimmune diseases, clinical data evaluating the utility of the diet for cutaneous disease is lacking.^108,109 Numerous randomized trials have demonstrated the Paleo diet to be effective for weight loss and improving insulin sensitivity and lipid levels.^110-116 Thus, the Paleo diet may theoretically serve as a viable adjunct dietary approach to the treatment of cutaneous diseases associated with obesity and metabolic derangement.¹¹⁷

Carnivore Diet

Arguably the most controversial and radical diet is the carnivore diet. As the name implies, the carnivore diet is based on consuming solely animal products. A properly structured carnivore diet emphasizes a “nose-to-tail” eating approach where all parts of the animal including the muscle meats, organs, and fat are consumed. Proponents of the diet cite anthropologic evidence from fossil-stable carbon-13/carbon-12 isotope analyses, craniodental features, and numerous other adaptations that indicate increased consumption of meat during human evolution.^118-122 Notably, many early humans ate a carnivore diet, but life span was very short at this time, suggesting the diet may not be as beneficial as has been suggested.

Despite the abundance of anecdotal evidence supporting its use for a variety of chronic conditions, including cutaneous autoimmune disease, there is a virtual absence of high-quality research on the carnivore diet.^123-125

The purported benefits of the carnivore diet may be attributed to the consumption of organ meats that contain highly bioavailable essential vitamins and minerals, such as iron, zinc, copper, selenium, thiamine, niacin, folate, vitamin B₆, vitamin B₁₂, vitamin A, vitamin D, vitamin K, and choline.^126-128 Other dietary compounds that have demonstrated benefit for skin health and are predominantly found in animal foods include carnosine, carnitine, creatine, taurine, coenzyme Q10, and collagen.^129-134 Nevertheless, there is no data to recommend the elimination of antioxidant- and micronutrient-dense plant-based foods. Rigorous clinical research evaluating the efficacy and safety of the carnivore diet in dermatologic patients is needed. A carnivore diet should not be undertaken without the assistance of a dietician who can ensure adequate micronutrient and macronutrient support.

Final Thoughts

The adjunctive role of diet in the treatment of skin disease is expanding and becoming more widely accepted among dermatologists. Unfortunately, there remains a lack of randomized controlled trials confirming the efficacy of various dietary interventions in the dermatologic setting. Although evidence-based dietary recommendations currently are limited, it is important for dermatologists to be aware of the varied and nuanced dietary interventions employed by patients.

Ultimately, dietary recommendations must be personalized, considering a patient’s comorbidities, personal beliefs and preferences, and nutrigenetics. The emerging field of dermatonutrigenomics—the study of how dietary compounds interact with one’s genes to influence skin health—may allow for precise dietary recommendations to be made in dermatologic practice. Direct-to-consumer genetic tests targeted toward dermatology patients are already on the market, but their clinical utility awaits validation.¹ Because nutritional science is a constantly evolving field, becoming familiar with these popular diets will serve both dermatologists and their patients well.

Within the last decade, almost 3000 articles have been published on the role of diet in the prevention and management of dermatologic conditions. Patients are increasingly interested in—and employing—dietary modifications that may influence skin appearance and aid in the treatment of cutaneous disease.¹ It is essential that dermatologists are familiar with existing evidence on the role of diet in dermatology to counsel patients appropriately. Herein, we discuss the compositions of several popular diets and their proposed utility for dermatologic purposes. We highlight the limited literature that exists surrounding this topic and emphasize the need for future, well-designed clinical trials that study the impact of diet on skin disease.

Ketogenic Diet

The ketogenic diet has a macronutrient profile composed of high fat, low to moderate protein, and very low carbohydrates. Nutritional ketosis occurs as the body begins to use free fatty acids (via beta oxidation) as the primary metabolite driving cellular metabolism. It has been suggested that the ketogenic diet may impart beneficial effects on skin disease; however, limited literature exists on the role of nutritional ketosis in the treatment of dermatologic conditions.

Mechanistically, the ketogenic diet decreases the secretion of insulin and insulinlike growth factor 1, resulting in a reduction of circulating androgens and increased activity of the retinoid X receptor.² In acne vulgaris, it has been suggested that the ketogenic diet may be beneficial in decreasing androgen-induced sebum production and the overproliferation of keratinocytes.^2-7 The ketogenic diet is one of the most rapidly effective dietary strategies for normalizing both insulin and androgens, thus it may theoretically be useful for other metabolic and hormone-dependent skin diseases, such as hidradenitis suppurativa.^8,9

The cutaneous manifestations associated with chronic hyperinsulinemia and hyperglycemia are numerous and include acanthosis nigricans, acrochordons, diabetic dermopathy, scleredema diabeticorum, bullosis diabeticorum, keratosis pilaris, and generalized granuloma annulare. There also is an increased risk for bacterial and fungal skin infections associated with hyperglycemic states.¹⁰ The ketogenic diet is an effective nonpharmacologic tool for normalizing serum insulin and glucose levels in most patients and may have utility in the aforementioned conditions.^11,12 In addition to improving insulin sensitivity, it has been used as a dietary strategy for weight loss.^11-15 Because obesity and metabolic syndrome are highly correlated with common skin conditions such as psoriasis, hidradenitis suppurativa, and androgenetic alopecia, there may be a role for employing the ketogenic diet in these patient populations.^16,17

Although robust clinical studies on ketogenic diets in skin disease are lacking, a recent single-arm, open-label clinical trial observed benefit in all 37 drug-naïve, overweight patients with chronic plaque psoriasis who underwent a ketogenic weight loss protocol. Significant reductions in psoriasis area and severity index (PASI) score and dermatology life quality index score were reported (P<.001).¹⁸ Another study of 30 patients with psoriasis found that a 4-week, low-calorie, ketogenic diet resulted in 50% improvement of PASI scores, 10% weight loss, and a reduction in the proinflammatory cytokines IL-1β and IL-2.¹⁹ Despite these results, it is a challenge to tease out if the specific dietary intervention or its associated weight loss was the main driver in these reported improvements in skin disease.

There is mixed evidence on the anti-inflammatory nature of the ketogenic diet, likely due to wide variation in the composition of foods included in individual diets. In many instances, the ketogenic diet is thought to possess considerable antioxidant and anti-inflammatory capabilities. Ketones are known activators of the nuclear factor erythroid 2–related factor 2 pathway, which upregulates the production of glutathione, a major endogenous intracellular antioxidant.²⁰ Additionally, dietary compounds from foods that are encouraged while on the ketogenic diet, such as sulforaphane from broccoli, also are independent activators of nuclear factor erythroid 2–related factor 2.²¹ Ketones are efficiently utilized by mitochondria, which also may result in the decreased production of reactive oxygen species and lower oxidative stress.²² Moreover, the ketone body β-hydroxybutyrate has demonstrated the ability to reduce proinflammatory IL-1β levels via suppression of nucleotide-binding domain-like receptor protein 3 inflammasome activity.^23,24 The activity of IL-1β is known to be elevated in many dermatologic conditions, including juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, hidradenitis suppurativa, Behçet disease, and other autoinflammatory syndromes.²⁵ Ketones also have been shown to inhibit the nuclear factor–κB proinflammatory signaling pathway.^22,26,27 Overexpression of IL-1β and aberrant activation of nuclear factor–κB are implicated in a variety of inflammatory, autoimmune, and oncologic cutaneous pathologies. The ketogenic diet may prove to be an effective adjunctive treatment for dermatologists to consider in select patient populations.^23,24,28-30

For patients with keratinocyte carcinomas, the ketogenic diet may offer the aforementioned anti-inflammatory and antioxidant effects, as well as suppression of the mechanistic target of rapamycin, a major regulator of cell metabolism and proliferation.^31,32 Inhibition of mechanistic target of rapamycin activity has been shown to slow tumor growth and reduce the development of squamous cell carcinoma.^25,33,34 The ketogenic diet also may exploit the preferential utilization of glucose exhibited by many types of cancer cells, thereby “starving” the tumor of its primary fuel source.^35,36 In vitro and animal studies in a variety of cancer types have demonstrated that a ketogenic metabolic state—achieved through the ketogenic diet or fasting—can sensitize tumor cells to chemotherapy and radiation while conferring a protective effect to normal cells.^37-40 This recently described phenomenon is known as differential stress resistance, but it has not been studied in keratinocyte malignancies or melanoma to date. Importantly, some basal cell carcinomas and BRAF V600E–mutated melanomas have worsened while on the ketogenic diet, suggesting more data is needed before it can be recommended for all cancer patients.^41,42 Furthermore, other skin conditions such as prurigo pigmentosa have been associated with initiation of the ketogenic diet.⁴³

Low FODMAP Diet

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that are poorly absorbed, osmotically active, and rapidly fermented by intestinal bacteria.⁴⁴ The low FODMAP diet has been shown to be efficacious for treatment of irritable bowel syndrome, small intestinal bacterial overgrowth (SIBO), and some cases of inflammatory bowel disease (IBD).^44-49 A low FODMAP diet may have potential implications for several dermatologic conditions.

Rosacea has been associated with various gastrointestinal tract disorders including irritable bowel syndrome, SIBO, and IBD.^50-54 A single study found that patients with rosacea had a 13-fold increased risk for SIBO.^55,56 Treatment of 40 patients with SIBO using rifaximin resulted in complete resolution of rosacea in all patients, with no relapse after a 3-year follow-up period.⁵⁵ Psoriasis also has been associated with SIBO and IBD.^57,58 One small study found that eradication of SIBO in psoriatic patients resulted in improved PASI scores and colorimetric values.⁵⁹

Although the long-term health consequences of the low FODMAP diet are unknown, further research on such dietary interventions for inflammatory skin conditions is warranted given the mounting evidence of a gut-skin connection and the role of the intestinal microbiome in skin health.^50,51

Gluten-Free Diet

Gluten is a protein found in a variety of grains. Although the role of gluten in the pathogenesis of celiac disease and dermatitis herpetiformis is indisputable, the deleterious effects of gluten outside of the context of these diseases remain controversial. There may be a compelling case for eliminating gluten in psoriasis patients with seropositivity for celiac disease. A recent systematic review found a 2.2-fold increased risk for celiac disease in psoriasis patients.⁶⁰ Antigliadin antibody titers also were found to be positively correlated with psoriatic disease severity.⁶¹ In addition, one open-label study found a reduction in PASI scores in 73% of patients with antigliadin antibodies after 3 months on a gluten-free diet compared to those without antibodies; however, the study only included 22 patients.⁶² Several other small studies have yielded similar results^63,64; however, antigliadin antibodies are neither the most sensitive nor specific markers of celiac disease, and additional testing should be completed in any patient who may carry this diagnosis. A survey study by the National Psoriasis Foundation found that the dietary change associated with the greatest skin improvement was removal of gluten and nightshade vegetables in approximately 50% of the 1200 psoriasis patients that responded.⁶⁵ Case reports of various dermatologic conditions including sarcoidosis, vitiligo, alopecia areata, lichen planus, dermatomyositis, pyoderma gangrenosum, erythema nodosum, leukocytoclastic vasculitis, linear IgA bullous dermatosis, and aphthous ulcerations have reportedly improved with a gluten-free diet; however, this should not be used as primary therapy in patients without celiac disease.^66-71 Because gluten-free diets can be expensive and challenging to follow, a formal assessment for celiac disease should be considered before recommendation of this dietary intervention.

Low Histamine Diet

Histamine is a biogenic amine produced by the decarboxylation of the amino acid histidine.⁷² It is found in several foods in varying amounts. Because bacteria can convert histidine into histamine, many fermented and aged foods such as kimchi, sauerkraut, cheese, and red wine contain high levels of histamine. Individuals who have decreased activity of diamine oxidase (DAO), an enzyme that degrades histamine, may be more susceptible to histamine intolerance.⁷² The symptoms of histamine intolerance are numerous and include gastrointestinal tract distress, rhinorrhea and nasal congestion, headache, urticaria, flushing, and pruritus. Histamine intolerance can mimic an IgE-mediated food allergy; however, allergy testing is negative in these patients. Unfortunately, there is no laboratory test for histamine intolerance; a double-blind, placebo-controlled food challenge is considered the gold-standard test.⁷²

As it pertains to dermatology, a low histamine diet may play a role in the treatment of certain patients with atopic dermatitis and chronic spontaneous urticaria. One study reported that 17 of 54 (31.5%) atopic patients had higher basal levels of serum histamine compared to controls.⁷³ Another study found that a histamine-free diet led to improvement in both histamine intolerance symptoms and atopic dermatitis disease severity (SCORing atopic dermatitis) in patients with low DAO activity.⁷⁴ In chronic spontaneous urticaria, a recent systematic review found that in 223 patients placed on a low histamine diet for 3 to 4 weeks, 12% and 44% achieved complete and partial remission, respectively.⁷⁵ Although treatment response based on a patient’s DAO activity level has not been correlated, a diet low in histamine may prove useful for patients with persistent atopic dermatitis and chronic spontaneous urticaria who have negative food allergy tests and report exacerbation of symptoms after ingestion of histamine-rich foods.^76,77

Mediterranean Diet

The Mediterranean diet has been touted as one of the healthiest diets to date, and large randomized clinical trials have demonstrated its effectiveness in weight loss, improving insulin sensitivity, and reducing inflammatory cytokine profiles.^78,79 A major criticism of the Mediterranean diet is that it has considerable ambiguity and lacks a precise definition due to the variability of what is consumed in different Mediterranean regions. Generally, the diet emphasizes high consumption of colorful fruits and vegetables, aromatic herbs and spices, olive oil, nuts, and seafood, as well as modest amounts of dairy, eggs, and red meat.⁸⁰ The anti-inflammatory effects of this diet largely have been attributed to its abundance of polyphenols, carotenoids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids (PUFAs).^80,81 Examples of polyphenols include resveratrol in red grapes, quercetin in apples and red onions, and curcumin in turmeric, while examples of carotenoids include lycopene in tomatoes and zeaxanthin in dark leafy greens. Oleic acid is a monounsaturated fatty acid present in high concentrations in olive oil, while eicosapentaenoic acid and docosahexaenoic acid are omega-3 PUFAs predominantly found in fish.⁸²

Unfortunately, rigorous clinical trials regarding the Mediterranean diet as it pertains to dermatology have not been undertaken. Numerous observational studies in patients with psoriasis have suggested that close adherence to the Mediterranean diet was associated with improvement in PASI scores.^83-86 The National Psoriasis Foundation now recommends a trial of the Mediterranean diet in some patients with psoriasis, emphasizing increased dietary intake of olive oil, fish, and vegetables.⁸⁷ Adherence to a Mediterranean diet also has been inversely correlated to the severity of acne vulgaris and hidradenitis suppurativa^88,89; however, these studies failed to account for the multifactorial risk factors associated with these conditions. Mediterranean diets also may impart a chemopreventive effect, supported by a number of in vivo and in vitro studies demonstrating the inhibition and/or reversal of cutaneous DNA damage induced by UV radiation through supplementation with various phytonutrients and omega-3 PUFAs.^81,90-92 Although small case-control studies have found a decreased risk of basal cell carcinoma in those who closely adhered to a Mediterranean diet, more rigorous clinical research is needed.⁹³

Whole-Food, Plant-Based Diet

A whole-food, plant-based (WFPB) diet is another popular dietary approach that consists of eating fruits, vegetables, legumes, nuts, seeds, and grains in their whole natural form.⁹⁴ This diet discourages all animal products, including red meat, seafood, dairy, and eggs. It is similar to a vegan diet except that it eliminates all highly refined carbohydrates, vegetable oils, and other processed foods.⁹⁴ Randomized clinical studies have demonstrated the WFPB diet to be effective in the treatment of obesity and metabolic syndrome.^95,96

A WFPB diet has been shown to increase the antioxidant capacity of cells, lengthen telomeres, and reduce formation of advanced glycation end products.^94,97,98 These benefits may help combat accelerated skin aging, including increased skin permeability, reduced elasticity and hydration, decreased angiogenesis, impaired immune function, and decreased vitamin D synthesis. Accelerated skin aging can result in delayed wound healing and susceptibility to skin tears and ecchymoses and also may promote the development of cutaneous malignancies.⁹⁹ There remains a lack of clinical data studying a properly formulated WFPB diet in the dermatologic setting.

Paleolithic Diet

The paleolithic (Paleo) diet is an increasingly popular way of eating that attempts to mirror what our ancestors may have consumed between 10,000 and 2.5 million years ago.¹⁰⁰ It is similar to the Mediterranean diet but excludes grains, dairy, legumes, and nightshade vegetables. It also calls for elimination of highly processed sugars and oils as well as chemical food additives and preservatives. There is a strict variation of the diet for individuals with autoimmune disease that also excludes eggs, nuts, and seeds, as these can be inflammatory or immunogenic in some patients.^100-106 Other variations of the diet exist, including the ketogenic Paleo diet, pegan (Paleo vegan) diet, and lacto-Paleo diet.¹⁰⁰ An often cited criticism of the Paleo diet is the low intake of calcium and risk for osteoporosis; however, consumption of calcium-rich foods or a calcium supplement can address this concern.¹⁰⁷

Although small clinical studies have found the Paleo diet to be beneficial for various autoimmune diseases, clinical data evaluating the utility of the diet for cutaneous disease is lacking.^108,109 Numerous randomized trials have demonstrated the Paleo diet to be effective for weight loss and improving insulin sensitivity and lipid levels.^110-116 Thus, the Paleo diet may theoretically serve as a viable adjunct dietary approach to the treatment of cutaneous diseases associated with obesity and metabolic derangement.¹¹⁷

Carnivore Diet

Arguably the most controversial and radical diet is the carnivore diet. As the name implies, the carnivore diet is based on consuming solely animal products. A properly structured carnivore diet emphasizes a “nose-to-tail” eating approach where all parts of the animal including the muscle meats, organs, and fat are consumed. Proponents of the diet cite anthropologic evidence from fossil-stable carbon-13/carbon-12 isotope analyses, craniodental features, and numerous other adaptations that indicate increased consumption of meat during human evolution.^118-122 Notably, many early humans ate a carnivore diet, but life span was very short at this time, suggesting the diet may not be as beneficial as has been suggested.

Despite the abundance of anecdotal evidence supporting its use for a variety of chronic conditions, including cutaneous autoimmune disease, there is a virtual absence of high-quality research on the carnivore diet.^123-125

The purported benefits of the carnivore diet may be attributed to the consumption of organ meats that contain highly bioavailable essential vitamins and minerals, such as iron, zinc, copper, selenium, thiamine, niacin, folate, vitamin B₆, vitamin B₁₂, vitamin A, vitamin D, vitamin K, and choline.^126-128 Other dietary compounds that have demonstrated benefit for skin health and are predominantly found in animal foods include carnosine, carnitine, creatine, taurine, coenzyme Q10, and collagen.^129-134 Nevertheless, there is no data to recommend the elimination of antioxidant- and micronutrient-dense plant-based foods. Rigorous clinical research evaluating the efficacy and safety of the carnivore diet in dermatologic patients is needed. A carnivore diet should not be undertaken without the assistance of a dietician who can ensure adequate micronutrient and macronutrient support.

Final Thoughts

The adjunctive role of diet in the treatment of skin disease is expanding and becoming more widely accepted among dermatologists. Unfortunately, there remains a lack of randomized controlled trials confirming the efficacy of various dietary interventions in the dermatologic setting. Although evidence-based dietary recommendations currently are limited, it is important for dermatologists to be aware of the varied and nuanced dietary interventions employed by patients.

Ultimately, dietary recommendations must be personalized, considering a patient’s comorbidities, personal beliefs and preferences, and nutrigenetics. The emerging field of dermatonutrigenomics—the study of how dietary compounds interact with one’s genes to influence skin health—may allow for precise dietary recommendations to be made in dermatologic practice. Direct-to-consumer genetic tests targeted toward dermatology patients are already on the market, but their clinical utility awaits validation.¹ Because nutritional science is a constantly evolving field, becoming familiar with these popular diets will serve both dermatologists and their patients well.

Within the last decade, almost 3000 articles have been published on the role of diet in the prevention and management of dermatologic conditions. Patients are increasingly interested in—and employing—dietary modifications that may influence skin appearance and aid in the treatment of cutaneous disease.¹ It is essential that dermatologists are familiar with existing evidence on the role of diet in dermatology to counsel patients appropriately. Herein, we discuss the compositions of several popular diets and their proposed utility for dermatologic purposes. We highlight the limited literature that exists surrounding this topic and emphasize the need for future, well-designed clinical trials that study the impact of diet on skin disease.

Ketogenic Diet

The ketogenic diet has a macronutrient profile composed of high fat, low to moderate protein, and very low carbohydrates. Nutritional ketosis occurs as the body begins to use free fatty acids (via beta oxidation) as the primary metabolite driving cellular metabolism. It has been suggested that the ketogenic diet may impart beneficial effects on skin disease; however, limited literature exists on the role of nutritional ketosis in the treatment of dermatologic conditions.

Mechanistically, the ketogenic diet decreases the secretion of insulin and insulinlike growth factor 1, resulting in a reduction of circulating androgens and increased activity of the retinoid X receptor.² In acne vulgaris, it has been suggested that the ketogenic diet may be beneficial in decreasing androgen-induced sebum production and the overproliferation of keratinocytes.^2-7 The ketogenic diet is one of the most rapidly effective dietary strategies for normalizing both insulin and androgens, thus it may theoretically be useful for other metabolic and hormone-dependent skin diseases, such as hidradenitis suppurativa.^8,9

The cutaneous manifestations associated with chronic hyperinsulinemia and hyperglycemia are numerous and include acanthosis nigricans, acrochordons, diabetic dermopathy, scleredema diabeticorum, bullosis diabeticorum, keratosis pilaris, and generalized granuloma annulare. There also is an increased risk for bacterial and fungal skin infections associated with hyperglycemic states.¹⁰ The ketogenic diet is an effective nonpharmacologic tool for normalizing serum insulin and glucose levels in most patients and may have utility in the aforementioned conditions.^11,12 In addition to improving insulin sensitivity, it has been used as a dietary strategy for weight loss.^11-15 Because obesity and metabolic syndrome are highly correlated with common skin conditions such as psoriasis, hidradenitis suppurativa, and androgenetic alopecia, there may be a role for employing the ketogenic diet in these patient populations.^16,17

Although robust clinical studies on ketogenic diets in skin disease are lacking, a recent single-arm, open-label clinical trial observed benefit in all 37 drug-naïve, overweight patients with chronic plaque psoriasis who underwent a ketogenic weight loss protocol. Significant reductions in psoriasis area and severity index (PASI) score and dermatology life quality index score were reported (P<.001).¹⁸ Another study of 30 patients with psoriasis found that a 4-week, low-calorie, ketogenic diet resulted in 50% improvement of PASI scores, 10% weight loss, and a reduction in the proinflammatory cytokines IL-1β and IL-2.¹⁹ Despite these results, it is a challenge to tease out if the specific dietary intervention or its associated weight loss was the main driver in these reported improvements in skin disease.

There is mixed evidence on the anti-inflammatory nature of the ketogenic diet, likely due to wide variation in the composition of foods included in individual diets. In many instances, the ketogenic diet is thought to possess considerable antioxidant and anti-inflammatory capabilities. Ketones are known activators of the nuclear factor erythroid 2–related factor 2 pathway, which upregulates the production of glutathione, a major endogenous intracellular antioxidant.²⁰ Additionally, dietary compounds from foods that are encouraged while on the ketogenic diet, such as sulforaphane from broccoli, also are independent activators of nuclear factor erythroid 2–related factor 2.²¹ Ketones are efficiently utilized by mitochondria, which also may result in the decreased production of reactive oxygen species and lower oxidative stress.²² Moreover, the ketone body β-hydroxybutyrate has demonstrated the ability to reduce proinflammatory IL-1β levels via suppression of nucleotide-binding domain-like receptor protein 3 inflammasome activity.^23,24 The activity of IL-1β is known to be elevated in many dermatologic conditions, including juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, hidradenitis suppurativa, Behçet disease, and other autoinflammatory syndromes.²⁵ Ketones also have been shown to inhibit the nuclear factor–κB proinflammatory signaling pathway.^22,26,27 Overexpression of IL-1β and aberrant activation of nuclear factor–κB are implicated in a variety of inflammatory, autoimmune, and oncologic cutaneous pathologies. The ketogenic diet may prove to be an effective adjunctive treatment for dermatologists to consider in select patient populations.^23,24,28-30

For patients with keratinocyte carcinomas, the ketogenic diet may offer the aforementioned anti-inflammatory and antioxidant effects, as well as suppression of the mechanistic target of rapamycin, a major regulator of cell metabolism and proliferation.^31,32 Inhibition of mechanistic target of rapamycin activity has been shown to slow tumor growth and reduce the development of squamous cell carcinoma.^25,33,34 The ketogenic diet also may exploit the preferential utilization of glucose exhibited by many types of cancer cells, thereby “starving” the tumor of its primary fuel source.^35,36 In vitro and animal studies in a variety of cancer types have demonstrated that a ketogenic metabolic state—achieved through the ketogenic diet or fasting—can sensitize tumor cells to chemotherapy and radiation while conferring a protective effect to normal cells.^37-40 This recently described phenomenon is known as differential stress resistance, but it has not been studied in keratinocyte malignancies or melanoma to date. Importantly, some basal cell carcinomas and BRAF V600E–mutated melanomas have worsened while on the ketogenic diet, suggesting more data is needed before it can be recommended for all cancer patients.^41,42 Furthermore, other skin conditions such as prurigo pigmentosa have been associated with initiation of the ketogenic diet.⁴³

Low FODMAP Diet

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that are poorly absorbed, osmotically active, and rapidly fermented by intestinal bacteria.⁴⁴ The low FODMAP diet has been shown to be efficacious for treatment of irritable bowel syndrome, small intestinal bacterial overgrowth (SIBO), and some cases of inflammatory bowel disease (IBD).^44-49 A low FODMAP diet may have potential implications for several dermatologic conditions.

Rosacea has been associated with various gastrointestinal tract disorders including irritable bowel syndrome, SIBO, and IBD.^50-54 A single study found that patients with rosacea had a 13-fold increased risk for SIBO.^55,56 Treatment of 40 patients with SIBO using rifaximin resulted in complete resolution of rosacea in all patients, with no relapse after a 3-year follow-up period.⁵⁵ Psoriasis also has been associated with SIBO and IBD.^57,58 One small study found that eradication of SIBO in psoriatic patients resulted in improved PASI scores and colorimetric values.⁵⁹

Although the long-term health consequences of the low FODMAP diet are unknown, further research on such dietary interventions for inflammatory skin conditions is warranted given the mounting evidence of a gut-skin connection and the role of the intestinal microbiome in skin health.^50,51

Gluten-Free Diet

Gluten is a protein found in a variety of grains. Although the role of gluten in the pathogenesis of celiac disease and dermatitis herpetiformis is indisputable, the deleterious effects of gluten outside of the context of these diseases remain controversial. There may be a compelling case for eliminating gluten in psoriasis patients with seropositivity for celiac disease. A recent systematic review found a 2.2-fold increased risk for celiac disease in psoriasis patients.⁶⁰ Antigliadin antibody titers also were found to be positively correlated with psoriatic disease severity.⁶¹ In addition, one open-label study found a reduction in PASI scores in 73% of patients with antigliadin antibodies after 3 months on a gluten-free diet compared to those without antibodies; however, the study only included 22 patients.⁶² Several other small studies have yielded similar results^63,64; however, antigliadin antibodies are neither the most sensitive nor specific markers of celiac disease, and additional testing should be completed in any patient who may carry this diagnosis. A survey study by the National Psoriasis Foundation found that the dietary change associated with the greatest skin improvement was removal of gluten and nightshade vegetables in approximately 50% of the 1200 psoriasis patients that responded.⁶⁵ Case reports of various dermatologic conditions including sarcoidosis, vitiligo, alopecia areata, lichen planus, dermatomyositis, pyoderma gangrenosum, erythema nodosum, leukocytoclastic vasculitis, linear IgA bullous dermatosis, and aphthous ulcerations have reportedly improved with a gluten-free diet; however, this should not be used as primary therapy in patients without celiac disease.^66-71 Because gluten-free diets can be expensive and challenging to follow, a formal assessment for celiac disease should be considered before recommendation of this dietary intervention.

Low Histamine Diet

Histamine is a biogenic amine produced by the decarboxylation of the amino acid histidine.⁷² It is found in several foods in varying amounts. Because bacteria can convert histidine into histamine, many fermented and aged foods such as kimchi, sauerkraut, cheese, and red wine contain high levels of histamine. Individuals who have decreased activity of diamine oxidase (DAO), an enzyme that degrades histamine, may be more susceptible to histamine intolerance.⁷² The symptoms of histamine intolerance are numerous and include gastrointestinal tract distress, rhinorrhea and nasal congestion, headache, urticaria, flushing, and pruritus. Histamine intolerance can mimic an IgE-mediated food allergy; however, allergy testing is negative in these patients. Unfortunately, there is no laboratory test for histamine intolerance; a double-blind, placebo-controlled food challenge is considered the gold-standard test.⁷²

As it pertains to dermatology, a low histamine diet may play a role in the treatment of certain patients with atopic dermatitis and chronic spontaneous urticaria. One study reported that 17 of 54 (31.5%) atopic patients had higher basal levels of serum histamine compared to controls.⁷³ Another study found that a histamine-free diet led to improvement in both histamine intolerance symptoms and atopic dermatitis disease severity (SCORing atopic dermatitis) in patients with low DAO activity.⁷⁴ In chronic spontaneous urticaria, a recent systematic review found that in 223 patients placed on a low histamine diet for 3 to 4 weeks, 12% and 44% achieved complete and partial remission, respectively.⁷⁵ Although treatment response based on a patient’s DAO activity level has not been correlated, a diet low in histamine may prove useful for patients with persistent atopic dermatitis and chronic spontaneous urticaria who have negative food allergy tests and report exacerbation of symptoms after ingestion of histamine-rich foods.^76,77

Mediterranean Diet

The Mediterranean diet has been touted as one of the healthiest diets to date, and large randomized clinical trials have demonstrated its effectiveness in weight loss, improving insulin sensitivity, and reducing inflammatory cytokine profiles.^78,79 A major criticism of the Mediterranean diet is that it has considerable ambiguity and lacks a precise definition due to the variability of what is consumed in different Mediterranean regions. Generally, the diet emphasizes high consumption of colorful fruits and vegetables, aromatic herbs and spices, olive oil, nuts, and seafood, as well as modest amounts of dairy, eggs, and red meat.⁸⁰ The anti-inflammatory effects of this diet largely have been attributed to its abundance of polyphenols, carotenoids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids (PUFAs).^80,81 Examples of polyphenols include resveratrol in red grapes, quercetin in apples and red onions, and curcumin in turmeric, while examples of carotenoids include lycopene in tomatoes and zeaxanthin in dark leafy greens. Oleic acid is a monounsaturated fatty acid present in high concentrations in olive oil, while eicosapentaenoic acid and docosahexaenoic acid are omega-3 PUFAs predominantly found in fish.⁸²

Unfortunately, rigorous clinical trials regarding the Mediterranean diet as it pertains to dermatology have not been undertaken. Numerous observational studies in patients with psoriasis have suggested that close adherence to the Mediterranean diet was associated with improvement in PASI scores.^83-86 The National Psoriasis Foundation now recommends a trial of the Mediterranean diet in some patients with psoriasis, emphasizing increased dietary intake of olive oil, fish, and vegetables.⁸⁷ Adherence to a Mediterranean diet also has been inversely correlated to the severity of acne vulgaris and hidradenitis suppurativa^88,89; however, these studies failed to account for the multifactorial risk factors associated with these conditions. Mediterranean diets also may impart a chemopreventive effect, supported by a number of in vivo and in vitro studies demonstrating the inhibition and/or reversal of cutaneous DNA damage induced by UV radiation through supplementation with various phytonutrients and omega-3 PUFAs.^81,90-92 Although small case-control studies have found a decreased risk of basal cell carcinoma in those who closely adhered to a Mediterranean diet, more rigorous clinical research is needed.⁹³

Whole-Food, Plant-Based Diet

A whole-food, plant-based (WFPB) diet is another popular dietary approach that consists of eating fruits, vegetables, legumes, nuts, seeds, and grains in their whole natural form.⁹⁴ This diet discourages all animal products, including red meat, seafood, dairy, and eggs. It is similar to a vegan diet except that it eliminates all highly refined carbohydrates, vegetable oils, and other processed foods.⁹⁴ Randomized clinical studies have demonstrated the WFPB diet to be effective in the treatment of obesity and metabolic syndrome.^95,96

A WFPB diet has been shown to increase the antioxidant capacity of cells, lengthen telomeres, and reduce formation of advanced glycation end products.^94,97,98 These benefits may help combat accelerated skin aging, including increased skin permeability, reduced elasticity and hydration, decreased angiogenesis, impaired immune function, and decreased vitamin D synthesis. Accelerated skin aging can result in delayed wound healing and susceptibility to skin tears and ecchymoses and also may promote the development of cutaneous malignancies.⁹⁹ There remains a lack of clinical data studying a properly formulated WFPB diet in the dermatologic setting.

Paleolithic Diet

The paleolithic (Paleo) diet is an increasingly popular way of eating that attempts to mirror what our ancestors may have consumed between 10,000 and 2.5 million years ago.¹⁰⁰ It is similar to the Mediterranean diet but excludes grains, dairy, legumes, and nightshade vegetables. It also calls for elimination of highly processed sugars and oils as well as chemical food additives and preservatives. There is a strict variation of the diet for individuals with autoimmune disease that also excludes eggs, nuts, and seeds, as these can be inflammatory or immunogenic in some patients.^100-106 Other variations of the diet exist, including the ketogenic Paleo diet, pegan (Paleo vegan) diet, and lacto-Paleo diet.¹⁰⁰ An often cited criticism of the Paleo diet is the low intake of calcium and risk for osteoporosis; however, consumption of calcium-rich foods or a calcium supplement can address this concern.¹⁰⁷

Although small clinical studies have found the Paleo diet to be beneficial for various autoimmune diseases, clinical data evaluating the utility of the diet for cutaneous disease is lacking.^108,109 Numerous randomized trials have demonstrated the Paleo diet to be effective for weight loss and improving insulin sensitivity and lipid levels.^110-116 Thus, the Paleo diet may theoretically serve as a viable adjunct dietary approach to the treatment of cutaneous diseases associated with obesity and metabolic derangement.¹¹⁷

Carnivore Diet

Arguably the most controversial and radical diet is the carnivore diet. As the name implies, the carnivore diet is based on consuming solely animal products. A properly structured carnivore diet emphasizes a “nose-to-tail” eating approach where all parts of the animal including the muscle meats, organs, and fat are consumed. Proponents of the diet cite anthropologic evidence from fossil-stable carbon-13/carbon-12 isotope analyses, craniodental features, and numerous other adaptations that indicate increased consumption of meat during human evolution.^118-122 Notably, many early humans ate a carnivore diet, but life span was very short at this time, suggesting the diet may not be as beneficial as has been suggested.

Despite the abundance of anecdotal evidence supporting its use for a variety of chronic conditions, including cutaneous autoimmune disease, there is a virtual absence of high-quality research on the carnivore diet.^123-125

The purported benefits of the carnivore diet may be attributed to the consumption of organ meats that contain highly bioavailable essential vitamins and minerals, such as iron, zinc, copper, selenium, thiamine, niacin, folate, vitamin B₆, vitamin B₁₂, vitamin A, vitamin D, vitamin K, and choline.^126-128 Other dietary compounds that have demonstrated benefit for skin health and are predominantly found in animal foods include carnosine, carnitine, creatine, taurine, coenzyme Q10, and collagen.^129-134 Nevertheless, there is no data to recommend the elimination of antioxidant- and micronutrient-dense plant-based foods. Rigorous clinical research evaluating the efficacy and safety of the carnivore diet in dermatologic patients is needed. A carnivore diet should not be undertaken without the assistance of a dietician who can ensure adequate micronutrient and macronutrient support.

Final Thoughts

The adjunctive role of diet in the treatment of skin disease is expanding and becoming more widely accepted among dermatologists. Unfortunately, there remains a lack of randomized controlled trials confirming the efficacy of various dietary interventions in the dermatologic setting. Although evidence-based dietary recommendations currently are limited, it is important for dermatologists to be aware of the varied and nuanced dietary interventions employed by patients.

Ultimately, dietary recommendations must be personalized, considering a patient’s comorbidities, personal beliefs and preferences, and nutrigenetics. The emerging field of dermatonutrigenomics—the study of how dietary compounds interact with one’s genes to influence skin health—may allow for precise dietary recommendations to be made in dermatologic practice. Direct-to-consumer genetic tests targeted toward dermatology patients are already on the market, but their clinical utility awaits validation.¹ Because nutritional science is a constantly evolving field, becoming familiar with these popular diets will serve both dermatologists and their patients well.

Genetic biomarkers for atopic dermatitis (AD) vary from one ethnic group to another, with a mutation in the interleukin-17 receptor A (IL-17RA) gene particularly important in Korean patients, researchers say.

The finding moves researchers another step forward in the effort to figure out which patients are most at risk for the disease and who will respond best to which treatments.

“Because atopic dermatitis is considered a complex trait, we think if there is any method to detect AD gene variations simultaneously, it could be possible to prevent the development of AD and then the atopic march,” said Eung Ho Choi, MD, PhD, a dermatology professor at Yonsei University, Wonju, South Korea.

He presented the finding at the International Society of Atopic Dermatitis (ISAD) 2021 Annual Meeting.

Atopic dermatitis is not caused by a single genetic mutation. But genetic factors play an important role, with about 75% concordance between monozygotic twins versus only 23% for dizygotic twins.

“Genetic biomarkers are needed in predicting the occurrence, severity, and treatment response,” as well as determining the prognosis of atopic dermatitis “and applying it to precision medicine,” Dr. Choi said.

Researchers have identified multiple genetic variations related to atopic dermatitis. One of the most significant genetic contributions found so far is the filaggrin gene variation, which can produce a defective skin barrier, Dr. Choi said. Others are involved in the immune response.

Although variations in the filaggrin gene (FLG ) are the most reliable genetic predictor of atopic dermatitis in Korean patients, they are less common in Korean patients than in Northwestern Europeans, Chinese, and Japanese patients. In Korean patients, the most common reported mutations of this gene are 3321delA and K4022X, Dr. Choi said.

To find out what other gene variants are important in Korean patients with atopic dermatitis, Dr. Choi and his colleagues developed the reverse blot hybridization assay (REBA) to detect skin barrier variations in the FLG, SPINK5 and KLK7 genes, and genes involved in immune response variations, KDR, IL-5RA, IL-9, DEFB1 (Defensin Beta 1), IL-12RB1 (interleukin-12 receptor subunit beta 1), and IL-12RB2.

They compared the prevalence of these variations in 279 Koreans with atopic dermatitis to the prevalence in 224 healthy people without atopic dermatitis and found that the odds ratio for atopic dermatitis increased with the number of these variants: People with three or four variants had a 3.75 times greater risk of AD, and those with 5 or more variants had a 10.3 times greater risk. The number of variants did not correlate to the severity of the disease, however.

The filaggrin variation was present in 13.9% of those with atopic dermatitis. About a quarter (28%) of the patients with AD who had this variation had impetigo, 15% had eczema herpeticum, and 5% had prurigo nodularis. By comparison, 14% of the patients with AD who did not have this variation had impetigo, and 5% had eczema herpeticum, but 19% had prurigo nodularis.

In a separate study, Dr. Choi and his colleagues identified a mutation in IL-17RA, present in 8.1% of 332 patients with AD compared with 3.3% of 245 controls. The patients with IL-17RA mutations all had extrinsic AD.

The variation was associated with longer disease duration, more frequent keratosis pilaris, higher blood eosinophil counts, higher serum total immunoglobulin E (IgE) levels, higher house dust mite allergen-specific IgE levels, and a greater need for systemic treatment than patients without the IL-17RA mutation.

Such findings are important for progress in treating atopic dermatitis because the mechanism differs among patients, said Emma Guttman-Yassky, MD, PhD, director of the Center for Excellence in Eczema and professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

“It’s not one size fits all in atopic dermatitis, and we need better biomarkers that will be able to tell us which treatment will work best for each patient,” she said in an interview.

In addition to genetic biomarkers, she and her colleagues are analyzing proteins involved in inflammation. They are using adhesive tape strips to harvest these markers, a less invasive approach than skin biopsies.

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

Genetic biomarkers for atopic dermatitis (AD) vary from one ethnic group to another, with a mutation in the interleukin-17 receptor A (IL-17RA) gene particularly important in Korean patients, researchers say.

The finding moves researchers another step forward in the effort to figure out which patients are most at risk for the disease and who will respond best to which treatments.

“Because atopic dermatitis is considered a complex trait, we think if there is any method to detect AD gene variations simultaneously, it could be possible to prevent the development of AD and then the atopic march,” said Eung Ho Choi, MD, PhD, a dermatology professor at Yonsei University, Wonju, South Korea.

He presented the finding at the International Society of Atopic Dermatitis (ISAD) 2021 Annual Meeting.

Atopic dermatitis is not caused by a single genetic mutation. But genetic factors play an important role, with about 75% concordance between monozygotic twins versus only 23% for dizygotic twins.

“Genetic biomarkers are needed in predicting the occurrence, severity, and treatment response,” as well as determining the prognosis of atopic dermatitis “and applying it to precision medicine,” Dr. Choi said.

Researchers have identified multiple genetic variations related to atopic dermatitis. One of the most significant genetic contributions found so far is the filaggrin gene variation, which can produce a defective skin barrier, Dr. Choi said. Others are involved in the immune response.

Although variations in the filaggrin gene (FLG ) are the most reliable genetic predictor of atopic dermatitis in Korean patients, they are less common in Korean patients than in Northwestern Europeans, Chinese, and Japanese patients. In Korean patients, the most common reported mutations of this gene are 3321delA and K4022X, Dr. Choi said.

To find out what other gene variants are important in Korean patients with atopic dermatitis, Dr. Choi and his colleagues developed the reverse blot hybridization assay (REBA) to detect skin barrier variations in the FLG, SPINK5 and KLK7 genes, and genes involved in immune response variations, KDR, IL-5RA, IL-9, DEFB1 (Defensin Beta 1), IL-12RB1 (interleukin-12 receptor subunit beta 1), and IL-12RB2.

They compared the prevalence of these variations in 279 Koreans with atopic dermatitis to the prevalence in 224 healthy people without atopic dermatitis and found that the odds ratio for atopic dermatitis increased with the number of these variants: People with three or four variants had a 3.75 times greater risk of AD, and those with 5 or more variants had a 10.3 times greater risk. The number of variants did not correlate to the severity of the disease, however.

The filaggrin variation was present in 13.9% of those with atopic dermatitis. About a quarter (28%) of the patients with AD who had this variation had impetigo, 15% had eczema herpeticum, and 5% had prurigo nodularis. By comparison, 14% of the patients with AD who did not have this variation had impetigo, and 5% had eczema herpeticum, but 19% had prurigo nodularis.

In a separate study, Dr. Choi and his colleagues identified a mutation in IL-17RA, present in 8.1% of 332 patients with AD compared with 3.3% of 245 controls. The patients with IL-17RA mutations all had extrinsic AD.

The variation was associated with longer disease duration, more frequent keratosis pilaris, higher blood eosinophil counts, higher serum total immunoglobulin E (IgE) levels, higher house dust mite allergen-specific IgE levels, and a greater need for systemic treatment than patients without the IL-17RA mutation.

Such findings are important for progress in treating atopic dermatitis because the mechanism differs among patients, said Emma Guttman-Yassky, MD, PhD, director of the Center for Excellence in Eczema and professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

“It’s not one size fits all in atopic dermatitis, and we need better biomarkers that will be able to tell us which treatment will work best for each patient,” she said in an interview.

In addition to genetic biomarkers, she and her colleagues are analyzing proteins involved in inflammation. They are using adhesive tape strips to harvest these markers, a less invasive approach than skin biopsies.

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

Genetic biomarkers for atopic dermatitis (AD) vary from one ethnic group to another, with a mutation in the interleukin-17 receptor A (IL-17RA) gene particularly important in Korean patients, researchers say.

The finding moves researchers another step forward in the effort to figure out which patients are most at risk for the disease and who will respond best to which treatments.

“Because atopic dermatitis is considered a complex trait, we think if there is any method to detect AD gene variations simultaneously, it could be possible to prevent the development of AD and then the atopic march,” said Eung Ho Choi, MD, PhD, a dermatology professor at Yonsei University, Wonju, South Korea.

He presented the finding at the International Society of Atopic Dermatitis (ISAD) 2021 Annual Meeting.

Atopic dermatitis is not caused by a single genetic mutation. But genetic factors play an important role, with about 75% concordance between monozygotic twins versus only 23% for dizygotic twins.

“Genetic biomarkers are needed in predicting the occurrence, severity, and treatment response,” as well as determining the prognosis of atopic dermatitis “and applying it to precision medicine,” Dr. Choi said.

Researchers have identified multiple genetic variations related to atopic dermatitis. One of the most significant genetic contributions found so far is the filaggrin gene variation, which can produce a defective skin barrier, Dr. Choi said. Others are involved in the immune response.

Although variations in the filaggrin gene (FLG ) are the most reliable genetic predictor of atopic dermatitis in Korean patients, they are less common in Korean patients than in Northwestern Europeans, Chinese, and Japanese patients. In Korean patients, the most common reported mutations of this gene are 3321delA and K4022X, Dr. Choi said.

To find out what other gene variants are important in Korean patients with atopic dermatitis, Dr. Choi and his colleagues developed the reverse blot hybridization assay (REBA) to detect skin barrier variations in the FLG, SPINK5 and KLK7 genes, and genes involved in immune response variations, KDR, IL-5RA, IL-9, DEFB1 (Defensin Beta 1), IL-12RB1 (interleukin-12 receptor subunit beta 1), and IL-12RB2.

They compared the prevalence of these variations in 279 Koreans with atopic dermatitis to the prevalence in 224 healthy people without atopic dermatitis and found that the odds ratio for atopic dermatitis increased with the number of these variants: People with three or four variants had a 3.75 times greater risk of AD, and those with 5 or more variants had a 10.3 times greater risk. The number of variants did not correlate to the severity of the disease, however.

The filaggrin variation was present in 13.9% of those with atopic dermatitis. About a quarter (28%) of the patients with AD who had this variation had impetigo, 15% had eczema herpeticum, and 5% had prurigo nodularis. By comparison, 14% of the patients with AD who did not have this variation had impetigo, and 5% had eczema herpeticum, but 19% had prurigo nodularis.

In a separate study, Dr. Choi and his colleagues identified a mutation in IL-17RA, present in 8.1% of 332 patients with AD compared with 3.3% of 245 controls. The patients with IL-17RA mutations all had extrinsic AD.

The variation was associated with longer disease duration, more frequent keratosis pilaris, higher blood eosinophil counts, higher serum total immunoglobulin E (IgE) levels, higher house dust mite allergen-specific IgE levels, and a greater need for systemic treatment than patients without the IL-17RA mutation.

Such findings are important for progress in treating atopic dermatitis because the mechanism differs among patients, said Emma Guttman-Yassky, MD, PhD, director of the Center for Excellence in Eczema and professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

“It’s not one size fits all in atopic dermatitis, and we need better biomarkers that will be able to tell us which treatment will work best for each patient,” she said in an interview.

In addition to genetic biomarkers, she and her colleagues are analyzing proteins involved in inflammation. They are using adhesive tape strips to harvest these markers, a less invasive approach than skin biopsies.

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

Bringing pharmacists, allergists, and dermatologists together to discuss patient care can improve outcomes for children with atopic dermatitis, researchers say.

“I think we really gained insight to how a more holistic approach benefited the patient,” Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said in an interview.

At the 2021 annual meeting of the International Society of Atopic Dermatitis, he and his colleagues described a pilot program to bring the specialists together at UCSD and Rady Children’s Hospital, San Diego.

Typically, children seeking care for atopic dermatitis see allergists and dermatologists separately for 10- to 15-minute appointments. The specialists sometimes prescribe treatments that conflict or are redundant with each other and may give contradictory instructions.

Instead, Dr. Eichenfield and colleagues designed a program bringing patients in for initial assessments lasting 1-1.5 hours. Patients typically started with visits to a clinical pharmacist, who assessed what medications had been prescribed and how much the patients were actually taking.

The patients then proceeded to separate appointments with an allergist and a dermatologist for evaluations. These specialists then met face to face to develop a treatment plan. At least one of the specialists would then present the plan to the patient and the patient’s family.

“We had a rich set of educational materials that were developed and put online that helped with shared decision-making and increased comfort level with appropriate skin care and medication,” Dr. Eichenfield said.

He and his colleagues assigned a physician assistant trained in both pediatric dermatology and pediatric allergy to coordinate the clinic. They designed combined pediatric dermatology and pediatric allergy fellowships for two fellows. “So, part of this program ended up allowing specially trained individuals who overlapped in fields that traditionally were separate,” said Dr. Eichenfield.

To see how well the approach worked, the researchers followed the progress of 23 patients who were already receiving treatment at one or both of the institutions.

• Eczema Area and Severity Index (EASI) scores decreased from visit 1 to visit 2 by a mean of 15.36 (P < .001), which correlates to a 56.36% average decrease.
• In 20 patients (89.96%), in EASI scores improved 50%.
• Thirteen patients (56.54%) achieved 75% improvement in EASI scores.
• Body surface area scores improved by a mean of 23.21% (P = .002).
• Validated Investigator Global Assessment scores decreased in 56.52% of patients to a clinically significant level.

The study did not include any control group, nor did the researchers report any details on how long the patients had been treated before the multidisciplinary program started or how their prescriptions changed.

Patients benefited from the comprehensive assessment of their symptoms, said Dr. Eichenfield, also chief of pediatric and adolescent dermatology at Rady Children’s Hospital. “Some had significant environmental allergies that might not have been a contributing factor to their atopic dermatitis,” he explained. “The complexities of comorbidities and atopic dermatitis influence the patient, even if one disease state isn’t necessarily directly causative of the other.”

In surveys, patients said they especially appreciated the increased time spent with their specialists. “No one’s ever spent an hour teaching us about eczema,” some commented. The approach motivated patients to take their home treatment more effectively, Dr. Eichenfield believed.

Primary care physicians did not participate in the multidisciplinary program, but the specialists communicated with them and shared electronic medical records with them, he said.

Without a control group, it is hard to say how much difference the multidisciplinary approach made, Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at George Washington University, Washington, said in an interview.

“What it does show is that there is significant improvement in a variety of endpoints within this multidisciplinary approach,” Dr. Silverberg said in an interview. “And so I have no doubt that this is valid and that a multidisciplinary approach would really improve, holistically, many aspects of patient care.”

Dr. Silverberg ran a multidisciplinary program at Northwestern University, Chicago, which included sleep medicine, endocrinology, gastroenterology, and other specialties as well as dermatology, allergy, and pharmacy.

However, Dr. Silverberg pointed out, a multidisciplinary approach is more expensive than standard care because when specialists spend more time with each patient, they see fewer patients per day. “So many health care systems or academic institutions are not as open as they should be to this kind of interdisciplinary care, which is why it’s so important to have outcome measures showing that this approach actually works.”

Dr. Eichenfield and Dr. Silverberg had no relevant disclosures.

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

Bringing pharmacists, allergists, and dermatologists together to discuss patient care can improve outcomes for children with atopic dermatitis, researchers say.

“I think we really gained insight to how a more holistic approach benefited the patient,” Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said in an interview.

At the 2021 annual meeting of the International Society of Atopic Dermatitis, he and his colleagues described a pilot program to bring the specialists together at UCSD and Rady Children’s Hospital, San Diego.

Typically, children seeking care for atopic dermatitis see allergists and dermatologists separately for 10- to 15-minute appointments. The specialists sometimes prescribe treatments that conflict or are redundant with each other and may give contradictory instructions.

Instead, Dr. Eichenfield and colleagues designed a program bringing patients in for initial assessments lasting 1-1.5 hours. Patients typically started with visits to a clinical pharmacist, who assessed what medications had been prescribed and how much the patients were actually taking.

The patients then proceeded to separate appointments with an allergist and a dermatologist for evaluations. These specialists then met face to face to develop a treatment plan. At least one of the specialists would then present the plan to the patient and the patient’s family.

“We had a rich set of educational materials that were developed and put online that helped with shared decision-making and increased comfort level with appropriate skin care and medication,” Dr. Eichenfield said.

He and his colleagues assigned a physician assistant trained in both pediatric dermatology and pediatric allergy to coordinate the clinic. They designed combined pediatric dermatology and pediatric allergy fellowships for two fellows. “So, part of this program ended up allowing specially trained individuals who overlapped in fields that traditionally were separate,” said Dr. Eichenfield.

To see how well the approach worked, the researchers followed the progress of 23 patients who were already receiving treatment at one or both of the institutions.

• Eczema Area and Severity Index (EASI) scores decreased from visit 1 to visit 2 by a mean of 15.36 (P < .001), which correlates to a 56.36% average decrease.
• In 20 patients (89.96%), in EASI scores improved 50%.
• Thirteen patients (56.54%) achieved 75% improvement in EASI scores.
• Body surface area scores improved by a mean of 23.21% (P = .002).
• Validated Investigator Global Assessment scores decreased in 56.52% of patients to a clinically significant level.

The study did not include any control group, nor did the researchers report any details on how long the patients had been treated before the multidisciplinary program started or how their prescriptions changed.

Patients benefited from the comprehensive assessment of their symptoms, said Dr. Eichenfield, also chief of pediatric and adolescent dermatology at Rady Children’s Hospital. “Some had significant environmental allergies that might not have been a contributing factor to their atopic dermatitis,” he explained. “The complexities of comorbidities and atopic dermatitis influence the patient, even if one disease state isn’t necessarily directly causative of the other.”

In surveys, patients said they especially appreciated the increased time spent with their specialists. “No one’s ever spent an hour teaching us about eczema,” some commented. The approach motivated patients to take their home treatment more effectively, Dr. Eichenfield believed.

Primary care physicians did not participate in the multidisciplinary program, but the specialists communicated with them and shared electronic medical records with them, he said.

Without a control group, it is hard to say how much difference the multidisciplinary approach made, Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at George Washington University, Washington, said in an interview.

“What it does show is that there is significant improvement in a variety of endpoints within this multidisciplinary approach,” Dr. Silverberg said in an interview. “And so I have no doubt that this is valid and that a multidisciplinary approach would really improve, holistically, many aspects of patient care.”

Dr. Silverberg ran a multidisciplinary program at Northwestern University, Chicago, which included sleep medicine, endocrinology, gastroenterology, and other specialties as well as dermatology, allergy, and pharmacy.

However, Dr. Silverberg pointed out, a multidisciplinary approach is more expensive than standard care because when specialists spend more time with each patient, they see fewer patients per day. “So many health care systems or academic institutions are not as open as they should be to this kind of interdisciplinary care, which is why it’s so important to have outcome measures showing that this approach actually works.”

Dr. Eichenfield and Dr. Silverberg had no relevant disclosures.

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

Bringing pharmacists, allergists, and dermatologists together to discuss patient care can improve outcomes for children with atopic dermatitis, researchers say.

“I think we really gained insight to how a more holistic approach benefited the patient,” Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said in an interview.

At the 2021 annual meeting of the International Society of Atopic Dermatitis, he and his colleagues described a pilot program to bring the specialists together at UCSD and Rady Children’s Hospital, San Diego.

Typically, children seeking care for atopic dermatitis see allergists and dermatologists separately for 10- to 15-minute appointments. The specialists sometimes prescribe treatments that conflict or are redundant with each other and may give contradictory instructions.

Instead, Dr. Eichenfield and colleagues designed a program bringing patients in for initial assessments lasting 1-1.5 hours. Patients typically started with visits to a clinical pharmacist, who assessed what medications had been prescribed and how much the patients were actually taking.

The patients then proceeded to separate appointments with an allergist and a dermatologist for evaluations. These specialists then met face to face to develop a treatment plan. At least one of the specialists would then present the plan to the patient and the patient’s family.

“We had a rich set of educational materials that were developed and put online that helped with shared decision-making and increased comfort level with appropriate skin care and medication,” Dr. Eichenfield said.

He and his colleagues assigned a physician assistant trained in both pediatric dermatology and pediatric allergy to coordinate the clinic. They designed combined pediatric dermatology and pediatric allergy fellowships for two fellows. “So, part of this program ended up allowing specially trained individuals who overlapped in fields that traditionally were separate,” said Dr. Eichenfield.

To see how well the approach worked, the researchers followed the progress of 23 patients who were already receiving treatment at one or both of the institutions.

• Eczema Area and Severity Index (EASI) scores decreased from visit 1 to visit 2 by a mean of 15.36 (P < .001), which correlates to a 56.36% average decrease.
• In 20 patients (89.96%), in EASI scores improved 50%.
• Thirteen patients (56.54%) achieved 75% improvement in EASI scores.
• Body surface area scores improved by a mean of 23.21% (P = .002).
• Validated Investigator Global Assessment scores decreased in 56.52% of patients to a clinically significant level.

The study did not include any control group, nor did the researchers report any details on how long the patients had been treated before the multidisciplinary program started or how their prescriptions changed.

Patients benefited from the comprehensive assessment of their symptoms, said Dr. Eichenfield, also chief of pediatric and adolescent dermatology at Rady Children’s Hospital. “Some had significant environmental allergies that might not have been a contributing factor to their atopic dermatitis,” he explained. “The complexities of comorbidities and atopic dermatitis influence the patient, even if one disease state isn’t necessarily directly causative of the other.”

In surveys, patients said they especially appreciated the increased time spent with their specialists. “No one’s ever spent an hour teaching us about eczema,” some commented. The approach motivated patients to take their home treatment more effectively, Dr. Eichenfield believed.

Primary care physicians did not participate in the multidisciplinary program, but the specialists communicated with them and shared electronic medical records with them, he said.

Without a control group, it is hard to say how much difference the multidisciplinary approach made, Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at George Washington University, Washington, said in an interview.

“What it does show is that there is significant improvement in a variety of endpoints within this multidisciplinary approach,” Dr. Silverberg said in an interview. “And so I have no doubt that this is valid and that a multidisciplinary approach would really improve, holistically, many aspects of patient care.”

Dr. Silverberg ran a multidisciplinary program at Northwestern University, Chicago, which included sleep medicine, endocrinology, gastroenterology, and other specialties as well as dermatology, allergy, and pharmacy.

However, Dr. Silverberg pointed out, a multidisciplinary approach is more expensive than standard care because when specialists spend more time with each patient, they see fewer patients per day. “So many health care systems or academic institutions are not as open as they should be to this kind of interdisciplinary care, which is why it’s so important to have outcome measures showing that this approach actually works.”

Dr. Eichenfield and Dr. Silverberg had no relevant disclosures.

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