Refractory chronic urticaria in adults: clinical characterization and predictors of severity

BACKGROUND: Chronic urticaria (CU) is defined as recurrent urticaria lasting for more than 6 weeks. OBJECTIVES: We aimed to characterize the phenotypes of patients with CU refractory to standard dose anti-H1 antihistamine treatment and search for clinical predictors of poor disease control. METHODS: Retrospective collection of data regarding clinical characteristics, comorbidities, treatment, and disease control of all adult refractory CU patients presenting to the Allergy and Immunology Department during 1 year. RESULTS: Sixty-one adult patients were included, 74% females, average age 44.5 years (18 to 84 years old). Most patients (78.7%) had initiated CU less than 1 year before enrolment. Chronic spontaneous urticaria (CSU) accounted for 55.7% of the patients, CSU associated with chronic inducible urticaria (CIndU) as a comorbidity for 44.3%, and angioedema was present in 55.7%. Medically-confirmed psychiatric disorders were present in 78.7%. Complementary diagnostic tests were performed in cases with more severe presentation (UAS7 ≥ 28 and/or UCT < 12) or with longer evolution (> 1 year), corresponding to 42 tested patient. Evidence for autoimmunity (positive anti-thyroid peroxidase antibodies, anti-nuclear antibodies or autologous serum test) was found in 45.2% (n = 19/42), and high C-reactive protein was present in 14.3% (n = 6/42), half of these also had positive antinuclear antibodies. Forty-six patients (75.4%) had at least one significant exacerbation, requiring medical appointment, emergency room, hospitalization or job absenteeism. The number of exacerbations correlated with the presence of angioedema (p = 0.022), with a recent diagnosis (< 1 year), and with higher UAS7 severity (p = 0.006). Although ClndU was associated with poor symptom control (p = 0.022), it was also associated with less exacerbations requiring medical observation or hospitalization (p = 0.015). All patients were using antihistamines and 21.3% (n = 13) of them were also under treatment with omalizumab, ciclosporine or montelukast for disease control. CONCLUSIONS: Autoimmunity can affect about half of the patients with severe or long-term CU. UAS7 and angioedema are associated with disease exacerbations. UAS7 and UCT presented unequal accuracy, with UAS7 better associating with the occurrence of exacerbations and treatment doses. Patients with refractory CU frequently present psychiatric disorders. Accurate diagnostic tests, namely autoimmune parameters and inflammatory markers, should be recommended in some individual cases.