Hives in autonomic disorders: a cutaneous marker of a distinct symptom phenotype

Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined. Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance. Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all  < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54-7.77,  = 0.002) and tingling (OR 5.73, CI 2.15-15.26,  < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment. Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.