Repositioning omalizumab in Dermatology: emerging indications and mechanism-based Therapeutic Insights

INTRODUCTION: Omalizumab, a humanized anti-immunoglobulin E (IgE) monoclonal antibody approved for chronic spontaneous urticaria (CSU), is increasingly used off-label across a range of dermatoses linked by IgE-mediated and mast cell-driven mechanisms, exemplifying the concept of mechanism-based drug repositioning. AREAS COVERED: This review examines the molecular pharmacology, pleiotropic mechanisms, and clinical evidence for omalizumab in established and emerging dermatologic indications, including CSU, chronic inducible urticarias, bullous pemphigoid, mastocytosis, prurigo nodularis, hyper-IgE syndrome, eosinophilic dermatoses, and other refractory conditions. A literature search of PubMed, Scopus, Embase, and Google Scholar through May 2026 informed the synthesis, with particular emphasis on therapeutic positioning relative to newer targeted biologics and oral agents. EXPERT OPINION: Bullous pemphigoid represents the most clinically compelling near-term indication, supported by a coherent autoreactive-IgE rationale and a candidate predictive biomarker (anti-BP180 IgE); biomarker-stratified trials are now essential to define its role alongside the recently FDA-approved dupilumab. Clinical response does not require elevated baseline IgE, arguing against serum IgE as a strict selection criterion. Biosimilar availability may reposition omalizumab as a cost-effective option, particularly in resource-limited settings, even as newer interleukin IL-4/IL-13, IL-31, and oral Bruton tyrosine kinase (BTK)-targeted therapies reshape treatment algorithms. Biomarker-stratified controlled trials remain the principal research priority.