Cholinergic Urticaria (CholU) is as a subtype of CIndU caused by an increase in the core body temperature, such as to activate the sweating reflex. It can occur in response to physical exercise, hot bathing and/or emotional stress. Clinically it appears as pinpointing and highly pruritic wheals with surrounding erythema, CholU can be accompanied by severe symptoms such as angioedema, respiratory symptoms or anaphylaxi CholU is frequently associated with atopic dermatitis (AD) The JAK-STAT is a mast cell (MC) signaling pathway activated downstream of IgE and IL-3 with important roles in MC homeostasis via regulation of proliferation, survival, and release of mediators. JAK-STAT activation is associated with polarization toward Th2, B cell isotype switching to IgE production, and IgE-dependent degranulation and cytokine release . Because both IL-4 and IL-13 use the IL-4Rα as a receptor component, these cytokines activate any common signaling pathways. Both of these cytokines use Janus kinases (JAKs) to initiate signaling and activate signal transducer and activator of transcription-6 (STAT6), which is a transcription factor required for many of their biologic functions. The non-receptor protein tyrosine kinases JAK1 and JAK3 associate with the IL-4Rα and γC, respectively. The binding of IL-4 to its receptor induces the transphosphorylation of JAK1 and JAK3, an event that activates these kinases and thereby initiates the early events of signal transduction .