Psoriasis

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

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.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Food and Drug Administration has approved the interleukin-17 inhibitor secukinumab (Cosentyx) for the treatment of moderate to severe plaque psoriasis in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.

Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.

The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”

The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.

At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.

Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.

The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.

“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”

Dr. Cordoro reported having no financial disclosures.

[email protected]

The Food and Drug Administration has approved the interleukin-17 inhibitor secukinumab (Cosentyx) for the treatment of moderate to severe plaque psoriasis in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.

Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.

The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”

The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.

At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.

Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.

The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.

“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”

Dr. Cordoro reported having no financial disclosures.

[email protected]

The Food and Drug Administration has approved the interleukin-17 inhibitor secukinumab (Cosentyx) for the treatment of moderate to severe plaque psoriasis in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.

Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.

The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”

The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.

At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.

Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.

The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.

“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”

Dr. Cordoro reported having no financial disclosures.

[email protected]

Tumor necrosis factor α (TNF-α) inhibitor–induced psoriasis is a known paradoxical adverse effect of this family of medications, which includes infliximab, adalimumab, etanercept, golimumab, and certolizumab. In the pediatric population, these therapies recently gained approval for nondermatologic conditions—meaning that this phenomenon is encountered more frequently.¹ In a systematic review of TNF-α inhibitor–induced psoriasis, severe scalp involvement was associated with alopecia in 7.5% of cases.² Onset of scalp psoriasis with alopecia in patients being treated with a TNF-α inhibitor should lead to consideration of this condition.

Psoriatic alopecia is an uncommon presentation of psoriasis. Although well described, alopecia as a clinical manifestation of scalp psoriasis is not a well-known concept among clinicians and has never been widely accepted. Adding to the diagnostic challenge is that psoriatic alopecia secondary to TNF-α inhibitor–induced psoriasis rarely has been reported in adults or children.^3-5 Including our case, our review of the literature yielded 7 pediatric cases (≤18 years) of TNF-α inhibitor–induced psoriatic alopecia.^6,7 A primary literature search of PubMed articles indexed for MEDLINE was conducted using the terms psoriatic alopecia, psoriasiform alopecia, TNF-α inhibitors, infliximab, adalimumab, etanercept, golimumab, and certolizumab.

We present the case of a pediatric patient with psoriatic alopecia secondary to treatment with adalimumab for Crohn disease (CD). We also provide a review of reported cases of psoriatic alopecia induced by a TNF-α inhibitor in the literature.

Case Report

A 12-year-old girl presented to our dermatology clinic with erythematous scaly plaques on the trunk, scalp, arms, and legs of 2 months’ duration. The lesions involved approximately 15% of the body surface area. The patient’s medical history was remarkable for CD diagnosed 4 years prior to presentation of the skin lesions. She had been treated for the past 2 years with adalimumab 40 mg once every 2 weeks and azathioprine 100 mg once daily. Because her CD was poorly controlled, the dosage of adalimumab was increased to 40 mg once weekly 6 months prior to the current presentation.

Our diagnosis was TNF-α inhibitor-induced psoriasis secondary to treatment with adalimumab.

The patient was treated with mometasone lotion 0.1% for the scalp lesions and triamcinolone cream 0.1% for the body lesions. Because of the extent of the psoriasis, we recommended changing adalimumab to ustekinumab, which is approved for CD in adults but is off label in children.

At 1-month follow-up, after receiving the induction dose of ustekinumab, the patient presented with partial improvement of the skin lesions but had developed a large, alopecic, erythematous plaque with thick yellowish scales on the scalp (Figure 1). She also had a positive hair pull test. The presumptive initial diagnosis of the alopecic scalp lesion was tinea capitis, for which multiple potassium hydroxide preparations of scales were performed, all yielding negative results. In addition, histopathologic examination with hematoxylin and eosin staining was performed (Figures 2A and 2B). Sterile tissue cultures for bacteria, fungi, and acid-fast bacilli were obtained and showed no growth. Periodic acid–Schiff staining was negative for fungal structures.

Comment

Psoriatic alopecia induced by a TNF-α inhibitor was first reported in 2007 in a 30-year-old woman with ankylosing spondylitis who was being treated with adalimumab.⁸ She had erythematous, scaly, alopecic plaques on the scalp and palmoplantar pustulosis. Findings on skin biopsy were compatible with psoriasis. The patient’s severe scalp psoriasis failed to respond to topical steroid treatment and adalimumab cessation. The extensive hair loss responded to cyclosporine 3 mg/kg daily.⁸

After conducting an extensive literature review, we found 26 cases of TNF-α–induced psoriatic alopecia, including the current case (Table).^6-16 The mean age at diagnosis was 27.8 years (SD, 13.6 years; range, 7–60 years). The female-to-male ratio was 3.3:1. The most common underlying condition for which TNF-α inhibitors were prescribed was CD (77% [20/26]). Psoriatic alopecia most commonly was reported secondary to treatment with infliximab (54% [14/26]), followed by adalimumab (42% [11/26]). Golimumab was the causative drug in 1 (4%) case. We did not find reports of etanercept or certolizumab having induced this manifestation. The onset of the scalp lesions occurred 2 to 46 months after starting treatment with the causative medication.

Previously reported cases have demonstrated various treatment options that yielded improvement or resolution of TNF-α inhibitor–induced psoriatic alopecia. These include either continuation or discontinuation of the TNF-α inhibitor combined with topical or intralesional steroids, methotrexate, or cyclosporine. Another option is to switch the TNF-α inhibitor to another biologic. Outcomes vary from patient to patient, making the physician’s clinical judgment crucial in deciding which treatment route to take. Our patient showed notable improvement when she was switched from adalimumab to ustekinumab as well as the combination of ustekinumab and clobetasol lotion 0.05%.

Conclusion

We recommend an individualized approach that provides patients with the safest and least invasive treatment option for TNF-α inhibitor–induced psoriatic alopecia. In most reported cases, the problem resolved with treatment, thereby classifying this form of alopecia as noncicatricial alopecia.

Tumor necrosis factor α (TNF-α) inhibitor–induced psoriasis is a known paradoxical adverse effect of this family of medications, which includes infliximab, adalimumab, etanercept, golimumab, and certolizumab. In the pediatric population, these therapies recently gained approval for nondermatologic conditions—meaning that this phenomenon is encountered more frequently.¹ In a systematic review of TNF-α inhibitor–induced psoriasis, severe scalp involvement was associated with alopecia in 7.5% of cases.² Onset of scalp psoriasis with alopecia in patients being treated with a TNF-α inhibitor should lead to consideration of this condition.

Psoriatic alopecia is an uncommon presentation of psoriasis. Although well described, alopecia as a clinical manifestation of scalp psoriasis is not a well-known concept among clinicians and has never been widely accepted. Adding to the diagnostic challenge is that psoriatic alopecia secondary to TNF-α inhibitor–induced psoriasis rarely has been reported in adults or children.^3-5 Including our case, our review of the literature yielded 7 pediatric cases (≤18 years) of TNF-α inhibitor–induced psoriatic alopecia.^6,7 A primary literature search of PubMed articles indexed for MEDLINE was conducted using the terms psoriatic alopecia, psoriasiform alopecia, TNF-α inhibitors, infliximab, adalimumab, etanercept, golimumab, and certolizumab.

We present the case of a pediatric patient with psoriatic alopecia secondary to treatment with adalimumab for Crohn disease (CD). We also provide a review of reported cases of psoriatic alopecia induced by a TNF-α inhibitor in the literature.

Case Report

A 12-year-old girl presented to our dermatology clinic with erythematous scaly plaques on the trunk, scalp, arms, and legs of 2 months’ duration. The lesions involved approximately 15% of the body surface area. The patient’s medical history was remarkable for CD diagnosed 4 years prior to presentation of the skin lesions. She had been treated for the past 2 years with adalimumab 40 mg once every 2 weeks and azathioprine 100 mg once daily. Because her CD was poorly controlled, the dosage of adalimumab was increased to 40 mg once weekly 6 months prior to the current presentation.

Our diagnosis was TNF-α inhibitor-induced psoriasis secondary to treatment with adalimumab.

The patient was treated with mometasone lotion 0.1% for the scalp lesions and triamcinolone cream 0.1% for the body lesions. Because of the extent of the psoriasis, we recommended changing adalimumab to ustekinumab, which is approved for CD in adults but is off label in children.

At 1-month follow-up, after receiving the induction dose of ustekinumab, the patient presented with partial improvement of the skin lesions but had developed a large, alopecic, erythematous plaque with thick yellowish scales on the scalp (Figure 1). She also had a positive hair pull test. The presumptive initial diagnosis of the alopecic scalp lesion was tinea capitis, for which multiple potassium hydroxide preparations of scales were performed, all yielding negative results. In addition, histopathologic examination with hematoxylin and eosin staining was performed (Figures 2A and 2B). Sterile tissue cultures for bacteria, fungi, and acid-fast bacilli were obtained and showed no growth. Periodic acid–Schiff staining was negative for fungal structures.

Comment

Psoriatic alopecia induced by a TNF-α inhibitor was first reported in 2007 in a 30-year-old woman with ankylosing spondylitis who was being treated with adalimumab.⁸ She had erythematous, scaly, alopecic plaques on the scalp and palmoplantar pustulosis. Findings on skin biopsy were compatible with psoriasis. The patient’s severe scalp psoriasis failed to respond to topical steroid treatment and adalimumab cessation. The extensive hair loss responded to cyclosporine 3 mg/kg daily.⁸

After conducting an extensive literature review, we found 26 cases of TNF-α–induced psoriatic alopecia, including the current case (Table).^6-16 The mean age at diagnosis was 27.8 years (SD, 13.6 years; range, 7–60 years). The female-to-male ratio was 3.3:1. The most common underlying condition for which TNF-α inhibitors were prescribed was CD (77% [20/26]). Psoriatic alopecia most commonly was reported secondary to treatment with infliximab (54% [14/26]), followed by adalimumab (42% [11/26]). Golimumab was the causative drug in 1 (4%) case. We did not find reports of etanercept or certolizumab having induced this manifestation. The onset of the scalp lesions occurred 2 to 46 months after starting treatment with the causative medication.

Previously reported cases have demonstrated various treatment options that yielded improvement or resolution of TNF-α inhibitor–induced psoriatic alopecia. These include either continuation or discontinuation of the TNF-α inhibitor combined with topical or intralesional steroids, methotrexate, or cyclosporine. Another option is to switch the TNF-α inhibitor to another biologic. Outcomes vary from patient to patient, making the physician’s clinical judgment crucial in deciding which treatment route to take. Our patient showed notable improvement when she was switched from adalimumab to ustekinumab as well as the combination of ustekinumab and clobetasol lotion 0.05%.

Conclusion

We recommend an individualized approach that provides patients with the safest and least invasive treatment option for TNF-α inhibitor–induced psoriatic alopecia. In most reported cases, the problem resolved with treatment, thereby classifying this form of alopecia as noncicatricial alopecia.

Tumor necrosis factor α (TNF-α) inhibitor–induced psoriasis is a known paradoxical adverse effect of this family of medications, which includes infliximab, adalimumab, etanercept, golimumab, and certolizumab. In the pediatric population, these therapies recently gained approval for nondermatologic conditions—meaning that this phenomenon is encountered more frequently.¹ In a systematic review of TNF-α inhibitor–induced psoriasis, severe scalp involvement was associated with alopecia in 7.5% of cases.² Onset of scalp psoriasis with alopecia in patients being treated with a TNF-α inhibitor should lead to consideration of this condition.

Psoriatic alopecia is an uncommon presentation of psoriasis. Although well described, alopecia as a clinical manifestation of scalp psoriasis is not a well-known concept among clinicians and has never been widely accepted. Adding to the diagnostic challenge is that psoriatic alopecia secondary to TNF-α inhibitor–induced psoriasis rarely has been reported in adults or children.^3-5 Including our case, our review of the literature yielded 7 pediatric cases (≤18 years) of TNF-α inhibitor–induced psoriatic alopecia.^6,7 A primary literature search of PubMed articles indexed for MEDLINE was conducted using the terms psoriatic alopecia, psoriasiform alopecia, TNF-α inhibitors, infliximab, adalimumab, etanercept, golimumab, and certolizumab.

We present the case of a pediatric patient with psoriatic alopecia secondary to treatment with adalimumab for Crohn disease (CD). We also provide a review of reported cases of psoriatic alopecia induced by a TNF-α inhibitor in the literature.

Case Report

A 12-year-old girl presented to our dermatology clinic with erythematous scaly plaques on the trunk, scalp, arms, and legs of 2 months’ duration. The lesions involved approximately 15% of the body surface area. The patient’s medical history was remarkable for CD diagnosed 4 years prior to presentation of the skin lesions. She had been treated for the past 2 years with adalimumab 40 mg once every 2 weeks and azathioprine 100 mg once daily. Because her CD was poorly controlled, the dosage of adalimumab was increased to 40 mg once weekly 6 months prior to the current presentation.

Our diagnosis was TNF-α inhibitor-induced psoriasis secondary to treatment with adalimumab.

The patient was treated with mometasone lotion 0.1% for the scalp lesions and triamcinolone cream 0.1% for the body lesions. Because of the extent of the psoriasis, we recommended changing adalimumab to ustekinumab, which is approved for CD in adults but is off label in children.

At 1-month follow-up, after receiving the induction dose of ustekinumab, the patient presented with partial improvement of the skin lesions but had developed a large, alopecic, erythematous plaque with thick yellowish scales on the scalp (Figure 1). She also had a positive hair pull test. The presumptive initial diagnosis of the alopecic scalp lesion was tinea capitis, for which multiple potassium hydroxide preparations of scales were performed, all yielding negative results. In addition, histopathologic examination with hematoxylin and eosin staining was performed (Figures 2A and 2B). Sterile tissue cultures for bacteria, fungi, and acid-fast bacilli were obtained and showed no growth. Periodic acid–Schiff staining was negative for fungal structures.

Comment

Psoriatic alopecia induced by a TNF-α inhibitor was first reported in 2007 in a 30-year-old woman with ankylosing spondylitis who was being treated with adalimumab.⁸ She had erythematous, scaly, alopecic plaques on the scalp and palmoplantar pustulosis. Findings on skin biopsy were compatible with psoriasis. The patient’s severe scalp psoriasis failed to respond to topical steroid treatment and adalimumab cessation. The extensive hair loss responded to cyclosporine 3 mg/kg daily.⁸

After conducting an extensive literature review, we found 26 cases of TNF-α–induced psoriatic alopecia, including the current case (Table).^6-16 The mean age at diagnosis was 27.8 years (SD, 13.6 years; range, 7–60 years). The female-to-male ratio was 3.3:1. The most common underlying condition for which TNF-α inhibitors were prescribed was CD (77% [20/26]). Psoriatic alopecia most commonly was reported secondary to treatment with infliximab (54% [14/26]), followed by adalimumab (42% [11/26]). Golimumab was the causative drug in 1 (4%) case. We did not find reports of etanercept or certolizumab having induced this manifestation. The onset of the scalp lesions occurred 2 to 46 months after starting treatment with the causative medication.

Previously reported cases have demonstrated various treatment options that yielded improvement or resolution of TNF-α inhibitor–induced psoriatic alopecia. These include either continuation or discontinuation of the TNF-α inhibitor combined with topical or intralesional steroids, methotrexate, or cyclosporine. Another option is to switch the TNF-α inhibitor to another biologic. Outcomes vary from patient to patient, making the physician’s clinical judgment crucial in deciding which treatment route to take. Our patient showed notable improvement when she was switched from adalimumab to ustekinumab as well as the combination of ustekinumab and clobetasol lotion 0.05%.

Conclusion

We recommend an individualized approach that provides patients with the safest and least invasive treatment option for TNF-α inhibitor–induced psoriatic alopecia. In most reported cases, the problem resolved with treatment, thereby classifying this form of alopecia as noncicatricial alopecia.

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

The Diagnosis: Demodicosis 

A clinical diagnosis of facial demodicosis triggered by topical corticosteroid therapy was suspected in our patient. A 3-mm punch biopsy of the right forehead demonstrated a follicular infundibulum rich in Demodex folliculorum with a discrete mononuclear infiltrate in the dermis (Figure 1), confirming the diagnosis. The patient was prescribed metronidazole gel 2% twice daily. Complete clearance of the facial rash was observed at 1-week follow-up (Figure 2). 

Demodex folliculorum is a mite that parasitizes the pilosebaceous follicles of human skin, becoming pathogenic with excessive colonization.^1-3 Facial demodicosis presents as pruritic papules and pustules in a pilosebaceous distribution on the face.^2,3 The diagnosis of facial demodicosis can be difficult due to similarities with many other common facial rashes such as acne, rosacea, contact dermatitis, and folliculitis.  

Similar to facial demodicosis, rosacea can present with erythema, papules, and pustules on the face. Patients with rosacea also have a higher prevalence and degree of Demodex mite infestation.⁴ However, these facial rashes can be differentiated when symptom acuity and personal and family histories are considered. In patients with a long-standing personal and/or family history of erythema, papules, and pustules, the chronicity of disease implies a diagnosis of rosacea. The acute onset of symptomatology and absence of personal or family history of rosacea in our patient favored a diagnosis of demodicosis. 

Pityrosporum folliculitis is an eruption caused by Malassezia furfur, the organism implicated in tinea versicolor. It can present similarly to Demodex folliculitis with follicular papules and pustules on the forehead and back. Features that help to differentiate Pityrosporum folliculitis from Demodex folliculitis include involvement of the upper trunk and onset after antibiotic usage.⁵ Diagnosis of Pityrosporum folliculitis can be confirmed by potassium hydroxide preparation, which demonstrates spaghetti-and-meatball-like hyphae and spores. 

Eosinophilic folliculitis is a chronic sterile folliculitis that usually presents as intensely pruritic papules and pustules on the face with an eruptive onset. There are 3 variants of disease: the classic form (also known as Ofuji disease), immunosuppression-associated disease, and infancy-associated disease.⁶ Eosinophilic folliculitis also may present with annular plaques and peripheral blood eosinophilia, and it is more prevalent in patients of Japanese descent. Differentiation from Demodex folliculitis can be done by histologic examination, which demonstrates spongiosis with exocytosis of eosinophils into the epithelium and a clear deficiency of infiltrating mites.⁶ 

Miliaria, also known as sweat rash, is a common condition that occurs due to occlusion of eccrine sweat glands.⁷ Clinically, miliaria is characterized by erythematous papules ranging from 2 to 4 mm in size that may be vesicular or pustular. Miliaria and demodicosis may have similar clinical presentations; however, several characteristic differences can be noted. Based on the pathophysiology, miliaria will not be folliculocentric, which differs from demodicosis. Additionally, miliaria most commonly occurs in areas of occlusion, such as in skin folds or on the trunk under tight clothing. Miliaria rarely can appear confluent and sunburnlike.⁸ Furthermore, miliaria is less common on the face, while demodicosis almost exclusively is found on the face. 

We present the case of an otherwise healthy patient with acute onset of pruritic papules and pustules involving the superior face following topical corticosteroid use. Similar cases frequently are encountered by dermatologists and require broad differential diagnoses. 

The Diagnosis: Demodicosis 

A clinical diagnosis of facial demodicosis triggered by topical corticosteroid therapy was suspected in our patient. A 3-mm punch biopsy of the right forehead demonstrated a follicular infundibulum rich in Demodex folliculorum with a discrete mononuclear infiltrate in the dermis (Figure 1), confirming the diagnosis. The patient was prescribed metronidazole gel 2% twice daily. Complete clearance of the facial rash was observed at 1-week follow-up (Figure 2). 

Demodex folliculorum is a mite that parasitizes the pilosebaceous follicles of human skin, becoming pathogenic with excessive colonization.^1-3 Facial demodicosis presents as pruritic papules and pustules in a pilosebaceous distribution on the face.^2,3 The diagnosis of facial demodicosis can be difficult due to similarities with many other common facial rashes such as acne, rosacea, contact dermatitis, and folliculitis.  

Similar to facial demodicosis, rosacea can present with erythema, papules, and pustules on the face. Patients with rosacea also have a higher prevalence and degree of Demodex mite infestation.⁴ However, these facial rashes can be differentiated when symptom acuity and personal and family histories are considered. In patients with a long-standing personal and/or family history of erythema, papules, and pustules, the chronicity of disease implies a diagnosis of rosacea. The acute onset of symptomatology and absence of personal or family history of rosacea in our patient favored a diagnosis of demodicosis. 

Pityrosporum folliculitis is an eruption caused by Malassezia furfur, the organism implicated in tinea versicolor. It can present similarly to Demodex folliculitis with follicular papules and pustules on the forehead and back. Features that help to differentiate Pityrosporum folliculitis from Demodex folliculitis include involvement of the upper trunk and onset after antibiotic usage.⁵ Diagnosis of Pityrosporum folliculitis can be confirmed by potassium hydroxide preparation, which demonstrates spaghetti-and-meatball-like hyphae and spores. 

Eosinophilic folliculitis is a chronic sterile folliculitis that usually presents as intensely pruritic papules and pustules on the face with an eruptive onset. There are 3 variants of disease: the classic form (also known as Ofuji disease), immunosuppression-associated disease, and infancy-associated disease.⁶ Eosinophilic folliculitis also may present with annular plaques and peripheral blood eosinophilia, and it is more prevalent in patients of Japanese descent. Differentiation from Demodex folliculitis can be done by histologic examination, which demonstrates spongiosis with exocytosis of eosinophils into the epithelium and a clear deficiency of infiltrating mites.⁶ 

Miliaria, also known as sweat rash, is a common condition that occurs due to occlusion of eccrine sweat glands.⁷ Clinically, miliaria is characterized by erythematous papules ranging from 2 to 4 mm in size that may be vesicular or pustular. Miliaria and demodicosis may have similar clinical presentations; however, several characteristic differences can be noted. Based on the pathophysiology, miliaria will not be folliculocentric, which differs from demodicosis. Additionally, miliaria most commonly occurs in areas of occlusion, such as in skin folds or on the trunk under tight clothing. Miliaria rarely can appear confluent and sunburnlike.⁸ Furthermore, miliaria is less common on the face, while demodicosis almost exclusively is found on the face. 

We present the case of an otherwise healthy patient with acute onset of pruritic papules and pustules involving the superior face following topical corticosteroid use. Similar cases frequently are encountered by dermatologists and require broad differential diagnoses. 

The Diagnosis: Demodicosis 

A clinical diagnosis of facial demodicosis triggered by topical corticosteroid therapy was suspected in our patient. A 3-mm punch biopsy of the right forehead demonstrated a follicular infundibulum rich in Demodex folliculorum with a discrete mononuclear infiltrate in the dermis (Figure 1), confirming the diagnosis. The patient was prescribed metronidazole gel 2% twice daily. Complete clearance of the facial rash was observed at 1-week follow-up (Figure 2). 

Demodex folliculorum is a mite that parasitizes the pilosebaceous follicles of human skin, becoming pathogenic with excessive colonization.^1-3 Facial demodicosis presents as pruritic papules and pustules in a pilosebaceous distribution on the face.^2,3 The diagnosis of facial demodicosis can be difficult due to similarities with many other common facial rashes such as acne, rosacea, contact dermatitis, and folliculitis.  

Similar to facial demodicosis, rosacea can present with erythema, papules, and pustules on the face. Patients with rosacea also have a higher prevalence and degree of Demodex mite infestation.⁴ However, these facial rashes can be differentiated when symptom acuity and personal and family histories are considered. In patients with a long-standing personal and/or family history of erythema, papules, and pustules, the chronicity of disease implies a diagnosis of rosacea. The acute onset of symptomatology and absence of personal or family history of rosacea in our patient favored a diagnosis of demodicosis. 

Pityrosporum folliculitis is an eruption caused by Malassezia furfur, the organism implicated in tinea versicolor. It can present similarly to Demodex folliculitis with follicular papules and pustules on the forehead and back. Features that help to differentiate Pityrosporum folliculitis from Demodex folliculitis include involvement of the upper trunk and onset after antibiotic usage.⁵ Diagnosis of Pityrosporum folliculitis can be confirmed by potassium hydroxide preparation, which demonstrates spaghetti-and-meatball-like hyphae and spores. 

Eosinophilic folliculitis is a chronic sterile folliculitis that usually presents as intensely pruritic papules and pustules on the face with an eruptive onset. There are 3 variants of disease: the classic form (also known as Ofuji disease), immunosuppression-associated disease, and infancy-associated disease.⁶ Eosinophilic folliculitis also may present with annular plaques and peripheral blood eosinophilia, and it is more prevalent in patients of Japanese descent. Differentiation from Demodex folliculitis can be done by histologic examination, which demonstrates spongiosis with exocytosis of eosinophils into the epithelium and a clear deficiency of infiltrating mites.⁶ 

Miliaria, also known as sweat rash, is a common condition that occurs due to occlusion of eccrine sweat glands.⁷ Clinically, miliaria is characterized by erythematous papules ranging from 2 to 4 mm in size that may be vesicular or pustular. Miliaria and demodicosis may have similar clinical presentations; however, several characteristic differences can be noted. Based on the pathophysiology, miliaria will not be folliculocentric, which differs from demodicosis. Additionally, miliaria most commonly occurs in areas of occlusion, such as in skin folds or on the trunk under tight clothing. Miliaria rarely can appear confluent and sunburnlike.⁸ Furthermore, miliaria is less common on the face, while demodicosis almost exclusively is found on the face. 

We present the case of an otherwise healthy patient with acute onset of pruritic papules and pustules involving the superior face following topical corticosteroid use. Similar cases frequently are encountered by dermatologists and require broad differential diagnoses. 

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.