INTRODUCTION
Granuloma annulare (GA), initially identified as a "ringed eruption of the fingers," is a benign and self-limiting inflammatory skin disorder characterized by granuloma formation in the dermis.1 Its incidence is estimated at 0.04%, with a higher prevalence among women and adults over thirty years old.1 The most common form of GA is the localized variant, which typically manifests as annular erythematous plaques or papules, primarily on the dorsal surfaces of the hands or feet.2,3 Generalized GA is characterized by the presence of 10 or more widespread annular plaques and involves both the upper and lower extremities.3,4 This study focuses on the localized and generalized forms of GA, as they represent the most frequently encountered clinical variants.
The pathophysiology of GA is hypothesized to involve a delayed-type hypersensitivity reaction, with CD4+ Th1-mediated macrophage activation followed by a Th2-driven cytokine response, culminating in connective tissue degradation.1 Both M1 and M2 macrophages appear upregulated in GA, supporting a biphasic mechanism of tissue breakdown and remodeling.1 While the disease is histologically characterized by necrobiotic granulomas surrounded by palisading histiocytes, eosinophils, lymphocytes, and mucin deposition, its etiology remains poorly understood.1,5 GA has been linked to systemic conditions including hyperlipidemia, autoimmune disease, and type 2 diabetes mellitus, though the latter association remains unclear.1,3,6
Topical and intralesional corticosteroids are considered first-line therapies, often yielding partial or complete resolution.1 For recalcitrant or generalized disease, additional agents such as phototherapy, hydroxychloroquine, pentoxifylline, and dapsone have been explored, though response rates vary considerably.1,7,8 More recently, systemic and targeted agents such as methotrexate, TNF-α inhibitors, and JAK inhibitors have shown promise in small case series.9,10,11,12 However, variability in treatment efficacy, limited high-quality data, and long disease
The pathophysiology of GA is hypothesized to involve a delayed-type hypersensitivity reaction, with CD4+ Th1-mediated macrophage activation followed by a Th2-driven cytokine response, culminating in connective tissue degradation.1 Both M1 and M2 macrophages appear upregulated in GA, supporting a biphasic mechanism of tissue breakdown and remodeling.1 While the disease is histologically characterized by necrobiotic granulomas surrounded by palisading histiocytes, eosinophils, lymphocytes, and mucin deposition, its etiology remains poorly understood.1,5 GA has been linked to systemic conditions including hyperlipidemia, autoimmune disease, and type 2 diabetes mellitus, though the latter association remains unclear.1,3,6
Topical and intralesional corticosteroids are considered first-line therapies, often yielding partial or complete resolution.1 For recalcitrant or generalized disease, additional agents such as phototherapy, hydroxychloroquine, pentoxifylline, and dapsone have been explored, though response rates vary considerably.1,7,8 More recently, systemic and targeted agents such as methotrexate, TNF-α inhibitors, and JAK inhibitors have shown promise in small case series.9,10,11,12 However, variability in treatment efficacy, limited high-quality data, and long disease
