Cholinergic Urticaria, an Effective and Safe “Off Label” Use of Dupilumab: A Case Report with Literature Review

Cholinergic Urticaria (CholU) is a form of generalized urticaria induced by an increase in core body temperature that activates the sweat reflex. Clinically it is characterized by localized and highly itchy wheals with surrounding erythema and can occur in response to exercise, hot baths and/or emotional stress. Dupilumab is a fully human monoclonal antibody specifically designed to simultaneously inhibit the activity of interleukin-4 (IL-4) and interleukin-13 (IL-13), which play a key role in the inflammation cascade of type 2. We report the case of a 26-year-old man suffering from CholU for 3 years, unresponsive to standard treatment in which off-label therapy was undertaken with Dupilumab, 600 mg subcutaneous as a loading dose and then 300 mg every 15 days. The daily Visual Analogue Scale (VAS) score was used to assess the efficacy of the therapy. Already after the first two administrations, the patient no longer had CholU episodes and resumed regular sporting activity, with a marked improvement in the quality of life. A possible mechanism of Dupilumab in reducing the manifestations of CholU is the blocking of the IL-4 pathway and the expression of the high-affinity IgE receptor (FcϵR1) on B cells, mast cells (MCs) and basophils. By decreasing the production of FcϵR1, the adhesion of IgE to the surface of MCs decreases with consequent reduction of MCs activation and histamine release. Further experience and large-scale studies may be needed to establish whether Dupilumab can be a therapeutic alternative in CholU, especially in patients who do not respond to standard treatment.