Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria.

Background: Treatment with second-generation antihistamines is recommended in patients with chronic spontaneous urticaria (CSU). Some patients remain unresponsive even after up-dosing up to fourfold. Many third line treatment options have limited availability and/or give rise to significant side effects. We investigated effectiveness and safety of antihistamine treatment with dosages up to fourfold and higher.

Methods: This retrospective analysis of patients' records was performed in adult CSU patients suffering wheals and/or angioedema (AE). Demographic, clinical, and therapeutic data was extracted from their medical records. We recorded the type, maximum prescribed dosage, effectiveness, and reported side effects of antihistamine treatment.

Results: Of 200 screened patients, 178 were included. Treatment was commenced with a once daily dose of antihistamines. Persisting symptoms meant that up-dosing up to fourfold occurred in 138 (78%) of patients, yielding sufficient response in 41 (23%). Up-dosing antihistamines was necessary in 110 (80%) patient with weals alone or weals with angioedema and 28 (64%) with AE only (p = 0.039). Of the remaining 97 patients with insufficient response, 59 were treated with dosages higher than fourfold (median dosage 8, range 5-12). This was sufficient in 29 patients (49%). Side effects were reported in 36 patients (20%), whereof 30 (17%) experienced somnolence. Side effects after up-dosing higher than fourfold were reported in six out of 59 patients (10%).

Conclusion: Up-dosing antihistamines higher than fourfold dosage seems a feasible therapeutic option with regards to effectiveness and safety. The need for third line therapies could be decreased by 49%, with a very limited increase of reported side effects.