Etiology, diagnosis, and therapeutic management of granuloma annulare: an update

Granuloma annulare (GA) is a common cutaneous disorder classically presenting as annular groups of skin-colored to erythematous papules without epidermal change localized to the dorsal hands and/or feet. In addition to the localized form, there are variants including generalized (including generalized annular GA, disseminated papular GA, and atypical generalized GA), subcutaneous, and perforating GA, providing for a wide spectrum of clinical lesions. The etiology of GA remains unknown and several systemic associations have been proposed but not proven, including diabetes mellitus, malignancy, thyroid disease, and dyslipidemia. The diagnosis of GA relies on clinicopathological correlation, with a skin biopsy confirming the histological features of the disease, including palisading granulomas, collagen degeneration, mucin, and a lymphohistiocytic infiltrate. Localized GA is often asymptomatic and self-limited within 2 years; however, the patient may desire treatment for cosmetic reasons, with topical and intralesional corticosteroids as the mainstays of therapy. When GA is generalized, disseminated, or atypical, a more thorough medical workup for underlying diseases may be considered depending on the physical examination, a thorough review of systems, comorbidities, and clinical suspicion. Treatment is often challenging for generalized GA, especially because of its recalcitrant nature and a lack of evidence-based therapy. Over 30 different treatments have been described for GA with variable results; however, the majority of these have been single case reports, small case series, or retrospective studies. Reported treatments for GA include topical, intralesional, intramuscular, and oral medications (steroidal vs. non-steroidal); biologic agents; surgical interventions; phototherapy; and laser treatments. When selecting a systemic therapy for a patient with GA, multiple variables must be considered, such as baseline blood evaluations, comorbidities, drug interactions, compliance, adverse effect profiles, prior treatments, and reproductive status. This evidence-based review will focus on the advances made in the twenty-first century regarding the etiology, diagnosis, and therapeutic management of GA.