LAUSR

Dear Editor, A 35-year-old gentleman of Arabic origin, skin type 4, presented to dermatology department at Sheikh Khalifa Medical City, Abu Dhabi, UAE, with flare up of long-lasting atopic dermatitis (AD) in July 2019. At the time of presentation, themost visible areas such as face, neck, and hand were severely affected with erythema-scaly lesions. Lichenification, excoriations, and postinflammatory hyperpigmentation were also noticed all over the skin. The patient reported severe itching that restricted his daily activity and prevented from normal sleep. Previously the patient was treated with topical corticosteroids, moisturizers, and oral antihistamines. No other health problems. No intake of medications and supplements. Dupilumab was initiated at 600 mg starting dose and consecutively 300 mg every 2 weeks. During the follow-up September, he reported “excellent result” with prominent improvement, no erythematous changes, mainly postinflammatory hyperpigmentation and mild lichenification. The itching sensation reduced 80% to 90%. In December 2019, the patient present with new flare up, since he missed the last month treatment. Exacerbation was noticed mostly over the face and extremities. In addition, skin changes with clinical characteristic of psoriasis were noticed on his forehead, arms, and lower leg. Detailed history revealed they were present since a year but much smaller in size. According to the patient, the lesion on the forehead was presented on the hairline as a small dark erythematous papule before initiation of dupilumab and recently increased in size. Biopsy was performed and revealed the changes characteristic of psoriasis. Psoriasis and AD are both T-cell-mediated inflammatory diseases that exist on opposing ends of the spectrum: TH1-mediated cytokines driving psoriasis and TH2 cytokines driving AD cases of either a new presentation or exacerbation of psoriasis following treatment with dupilumab has been reported. Also development of eczema after TNFα treatment for psoriasis has been reported. The abovementioned supports the hypothesis that patients may be capable of shifting between divergent TH responses. Tracey et al. proposed the theory that blocking TH2 cell signaling with dupilumab shifts the immune profile toward TH1 response and subsequent psoriasiform dermatitis. Dupilumab is a fully human monoclonal antibody, an interleukin 4 receptor α (IL-4Rα) antagonist that inhibits IL-4 and IL-13 signaling by targeting the shared alpha subunit of IL-4 and IL-13 receptors. It is known that IL-4 enhances TH2 response and abrogates TH17 response acting directly on T-cell and suppressing IL-23 production mediated by dendritic cell. Consequently, blocking IL-4 may induce an overexpression of IL-17 that may represent a triggering factor for psoriasis onset in patient with genetic predisposition or to exacerbate already existing one. Only one report mentioned about ethnicity of the patients. We would like to raise the question regarding relationship between ethnicity, genes, and certain pathway? Shall we expect a similar response in all patients, independently of their ethnicity and genetic background? The existence of both conditions is well known. A common genetic background for these diseases was shown by recent linkage and GWAS studies. The importance of proper clinical examination cannot be overemphasized. The exiguous psoriatic skin changes in our patient were overlooked on account of severely demonstrated and widespread AD. To the best of our knowledge, this is the first report describing exacerbation of psoriasis in patient of Arabic origin treated with dupilumab. Further research will be needed to clarify if the ethnicity and genetic background play role not only in dupilumab triggered and exacerbated psoriasis but also in entire interplay of TH1 and TH2 immunity.