Laryngeal involvement in chronic spontaneous urticaria–associated angioedema

Background: Chronic spontaneous urticaria (CSU) affects up to 1% of the population, and 40% of patients develop concomitant angioedema (CSU-AE). While clinically significant laryngeal involvement in mast cell–mediated CSU-AE is considered rare, and large cohorts report no fatal airway compromise, patients frequently present to emergency departments with symptoms perceived as potentially airway affecting. Objective: To describe retrospective clinical observations of CSU-AE patients presenting with symptoms suggestive of upper airway involvement and to contextualize these findings within the existing literature. Methods: We performed a retrospective descriptive review of consecutive CSU patients evaluated between October 2017 and July 2018 at two tertiary referral centers (Milan, Italy and Sofia, Bulgaria). Medical records were screened for angioedema localization, history of physician-documented laryngeal involvement during emergency evaluations, history of airway interventions, medication exposure, and acute treatment response. Results: Among 1,098 patients, 530 (48%) experienced angioedema and wheals in the context of CSU-AE. Thirteen patients (2%) had objectively documented laryngeal involvement prompting emergency assessment; three patients (all female) underwent endotracheal intubation. No fatalities or loss of consciousness occurred. None had concurrent wheals during the reported laryngeal episodes. History of NSAID exposure preceded some laryngeal exacerbations, though not in intubated cases. None of the patients was receiving ACE inhibitor treatment, all had normal C1 inhibitor (antigen and function) and normal C4. Laryngeal symptoms resolved within hours following standard acute therapy with corticosteroids and/or antihistamines (AHs). Due to the retrospective design, diagnostic work-up for alternative angioedema mechanisms (genetic testing) was incomplete. Conclusions: These observations do not indicate an increased intrinsic airway risk in CSU-AE. Rather, they illustrate diagnostic and management challenges in emergency settings and highlight the importance of mechanism-aware clinical assessment to avoid unnecessary invasive airway interventions. Laryngeal angioedema in CSU-AE is rare and presents with a mild clinical phenotype that does not typically require airway intervention.