Allergic contact dermatitis to Compositae: A possible cause of dupilumab‐associated facial and neck dermatitis in atopic dermatitis patients?

Abstract

Dupilumab inhibits interleukin (IL)-4 and IL-13 and downregulates the T helper (Th)2 pathway. It is approved for atopic dermatitis (AD) and is currently undergoing trials for other skin diseases, including allergic contact dermatitis (ACD). The development of face and neck dermatitis during dupilumab AD treatment is an emerging adverse event whose cause and diagnosis are still debated. Compositae is a family of plants containing sesquiterpene lactones (SLs) allergens and being a cause of ACD to Compositae, usually affecting exposed skin areas. We report three cases of Compositae ACD affecting the face and neck in AD patients during dupilumab treatment (Table 1). They were three males aged 56 (patient 1), 50 (patient 2), and 24 (patient 3) years. Patient 1 had the hobby of gardening, while patients 2 and patient 3 worked as an agricultural mechanic and a greengrocer, respectively. They had severe AD unresponsive to traditional systemic immunosuppressants. Dupilumab treatment was started at label dosage with a dramatic improvement after 16 weeks. However, after an average of 24 weeks the patients all showed erythemato-oedematus, scaly dermatitis of the face and neck (Figure 1). Patch tests were performed with the Società Italiana di Dermatologia Allergologica Professionale e Ambientale (SIDAPA) baseline series and plant series. At day (D) 2, D3, and D4 a positive reaction to SLs mix (++) was recorded in all the patients, and in patient 1 also to Compositae mix (+) (Figure 1). Dupilumab treatment was continued. Prednisone 25 mg once-a-day for 7 days while patient 1 avoided gardening avoidance (patient 1) or job duty change and patients 2 and 3) changed job duty. This was followed by persistent healing. Dupilumab does not interfere with most patch test responses, since ACD is a predominantly Th1/Th17 driven disease, including ACD to some SLs. Furthermore, the dupilumab-induced block of Th2 axis might shunt immune response to the Th1/Th17 pathway. However, the attenuated response found for some allergens led us to consider a selective, allergen-specific effect. Indeed, keratinocyte transcriptome analysis in nickelor fragrance-sensitized patients rev-