Chronic Urticaria-Associated Syndromes: Is Andersen–Tawil Syndrome One of Them?

The spectrum of syndromes associated with chronic urticaria (CU) is broad, ranging from monogenic autoinflammatory diseases (a single gene defect drives disease through dysregulated innate immunity) to multifactorial and acquired conditions (urticaria arises as part of a broader, polygenic or immune-mediated systemic process). Monogenic autoinflammatory conditions presenting with urticaria include cryopyrin-associated periodic syndromes (CAPS)—encompassing familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID/CINCA) and the broader group of familial cold urticarias. Monogenic conditions with well-characterized gain-of-function NLR family pyrin domain containing 3 (NLRP3) variants present with recurrent hives, a cardinal feature associated with recurrent fevers. Multifactorial and acquired autoinflammatory or immune-mediated conditions include Schnitzler syndrome, adult-onset Still’s disease, hypereosinophilic syndrome, Gleich syndrome, Wells syndrome, and Sjögren syndrome. Multifactorial conditions, including Schnitzler syndrome and Still’s disease, manifest similarly, with CU as an initial sign and a shared pathogenic mechanism of innate immune dysregulation, with interleukin-1β playing a central, pro-inflammatory role as a major pyrogen. Here, we also present a female patient with clinically established Andersen–Tawil syndrome (ATS) who developed recurrent hives on her extremities within minutes after vigorous exercise. To our knowledge, this is the first report of a co-occurrence of CU and ATS. The hives were successfully attenuated by oral intake of effervescent potassium chloride during physical activity. This observation raises the possibility that chronic inducible urticaria may represent a previously unrecognized cutaneous ATS manifestation and suggests a potential pathophysiological link between potassium-channel dysfunction and mast cell activation. Distinguishing whether hives are an isolated symptom or part of a broader syndrome is critically important, as it might be crucial for the patient outcome.