Bettolini Luca, Maione Vincenzo, Carugno Andrea, Stabile Giorgio, Podo Brunetti Antonio, Fratton Zeno, Errichetti Enzo, Zerbinati Nicola, Rongioletti Franco, Calzavara-Pinton Piergiacomo, Rossi Mariateresa, Bighetti Stefano
Dermatology Department, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Australas J Dermatol. 2025 Sep;66(6):329-337. doi: 10.1111/ajd.14560. Epub 2025 Jun 30.
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-α 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.
泛发性环状肉芽肿（GGA）是一种慢性炎症性皮肤病，尚无标准治疗方法。自2013年上次综述以来，新的治疗方法和不同的反应凸显了更新综述以指导临床决策的必要性。本系统综述旨在评估GGA患者的流行病学、合并症和治疗结果，综合已发表研究的证据，以深入了解传统和新兴治疗策略。按照PRISMA指南，在CENTRAL、Embase和PubMed中进行了系统的文献检索。纳入截至2024年1月15日以英文、法文或西班牙文发表的研究。数据提取集中在患者人口统计学、合并症、治疗方案和治疗结果。共纳入689例患者。患者的平均年龄为52.8岁，女性占优势（72.6%）。基于本系统综述，我们提出一种逐步治疗方法：一线治疗包括羟氯喹和光疗（补骨脂素加长波紫外线照射>UVA1>窄谱中波紫外线）。口服糖皮质激素联合强效外用糖皮质激素或钙调神经磷酸酶抑制剂可用于广泛性或快速进展性疾病，或作为在起效较慢的药物起效前的过渡治疗。砜类药物为二线治疗药物，若有禁忌，可选用口服维甲酸类药物（如异维甲酸）。对于难治性病例，推荐使用非标签抗TNF-α药物或JAK抑制剂，甲氨蝶呤或环孢素为有效的替代药物。这项关于GGA治疗的最大规模系统综述提供了一个基于证据的临床框架。虽然类固醇和光疗仍然是标准治疗方法，但JAK抑制剂和生物制剂等新兴选择为难治性病例带来了希望。量身定制的多模式策略可能会改善治疗结果，不过还需要进一步试验来规范指南。
