Management Strategies for Generalised Granuloma Annulare: A Systematic Review of Current and Emerging Therapies

Generalised Granuloma Annulare (GGA) is a chronic inflammatory skin disorder with no standard treatment. Since the last review in 2013, new treatments and varied responses have highlighted the need for an updated synthesis to guide clinical decisions. This systematic review aimed to evaluate the epidemiology, comorbidities and treatment outcomes in patients with GGA, synthesising evidence from published studies to provide insights into both conventional and emerging therapeutic strategies. A systematic literature search was conducted in CENTRAL, Embase and PubMed, following PRISMA guidelines. Studies published in English, French or Spanish up to January 15, 2024, were included. Data extraction focused on patient demographics, comorbidities, treatment regimens and therapeutic outcomes. A total of 689 patients were included. The mean age of patients was 52.8 years, with a female predominance (72.6%). Based on this systematic review, we propose a stepwise approach: first-line treatment includes hydroxychloroquine and phototherapy (PUVA > UVA1 > nb-UVB). Oral corticosteroids along with high-potency topical steroids or calcineurin inhibitors may be used in extensive or rapidly progressive disease or as bridging therapy pending slower-acting agents. Sulfones are second-line, with oral retinoids (e.g., isotretinoin) as alternatives if contraindicated. For refractory cases, off-label anti-TNF-alpha agents or JAK inhibitors are recommended, with methotrexate or cyclosporine as valid alternatives. This largest systematic review of GGA treatments offers an evidence-based clinical framework. While steroids and phototherapy remain standard, emerging options like JAK inhibitors and biologics show promise for refractory cases. Tailored, multimodal strategies may improve outcomes, though further trials are needed to standardise guidelines.