What role does desloratadine or levocetirizine play when added to oral isotretinoin in the treatment of acne vulgaris?

Isotretinoin is the gold-standard systemic therapy for severe acne, but its use is limited by dose-dependent mucocutaneous adverse events such as cheilitis, pruritus, xerosis, and early acne flare-ups. Second-generation H1-antihistamines (desloratadine 5 mg/day or levocetirizine 5 mg/day) have anti-inflammatory, mast-cell-stabilizing, and sebum-modulating properties that could theoretically enhance isotretinoin efficacy and tolerability.

Meta-analysis of 10 randomized controlled trials (675 patients, predominantly Asian and Middle-Eastern) showed that adding desloratadine—but not levocetirizine—to isotretinoin significantly improved outcomes:
Global Acne Grading Scale (GAGS) scores were reduced by an additional 2.68 points at week 12 (95 % CI 1.60–3.75, p < 0.00001, I² = 0 %).
Inflammatory lesion counts decreased significantly at weeks 4, 8 and 12 after exclusion of a low-baseline outlier (mean difference 7.96 lesions, 95 % CI 3.42–12.50, p = 0.0006).
Non-inflammatory lesions showed a delayed but significant reduction at week 12 (OR 2.77, p < 0.0001).
Mucocutaneous tolerability improved: desloratadine reduced acne flare-ups (OR 0.36, 95 % CI 0.17–0.76), cheilitis (OR 0.37, 95 % CI 0.17–0.81), and pruritus (OR 0.13, 95 % CI 0.06–0.27); no consistent benefit was observed for xerosis. Levocetirizine lacked clear efficacy and introduced heterogeneity.