Treatment of Generalized Granuloma Annulare with JAK Inhibitors: Systematic Review.

Background: Granuloma annulare (GA) is a rare granulomatous skin condition characterized by well-demarcated, annular, erythematous to skin-colored plaques. Treating GA, particularly generalized GA (GGA), remains challenging due to the lack of FDA-approved therapies and limited large-scale studies. Traditional treatments, including corticosteroids, phototherapy, and systemic agents such as antimalarials and antibiotics, have shown variable efficacy. Recent research highlights the role of the JAK-STAT pathway in GA pathogenesis, leading to interest in JAK inhibitors as a potential treatment. Emerging evidence suggests that JAK inhibitors may reduce inflammation and lesion burden in GGA. This manuscript evaluates the efficacy and safety of JAK inhibitors in the treatment of GGA. Results: Twenty-two studies were included, encompassing 50 patients with GGA. Agents included tofacitinib (n=27), baricitinib (n=11), upadacitinib (n=10), abrocitinib (n=1), and ruxolitinib (n=1). Across reports, most patients had recalcitrant disease with multiple prior treatment failures. Clinical improvement was observed in all patients, with complete response reported in 58.0% (29/50) and partial or near complete response in 42.0% (21/50). Median time to initial response was 5 weeks (IQR 2.75-8 weeks). Relapse occurred in a subset after discontinuation, but lesions often resolved with re-initiation. Adverse events were generally mild and consistent with known JAK inhibitor safety profiles (eg, hyperlipidemia, infections, herpes zoster). Conclusion: JAK inhibitors show promise as a targeted therapy for GGA, offering a novel approach for patients with refractory disease. Further studies, including clinical trials, are needed to establish long-term efficacy and safety.