Etiology, Diagnosis, and Therapeutic Management of Granuloma Annulare: An Update

Abstract

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.

Necrobiosis lipoidica

“…2 Historically, they have been considered to be closely associated with diabetes mellitus; more recently the strength of the association has been questioned. [3][4][5] …”

Necrobiosis lipoidica and granuloma annulare: Part 2- Granuloma annulare

“…3,4 A variety of infectious agents have been implicated, including tuberculosis, Borrelia, varicella, EBV, hepatitis B and C and HIV. 4,5 Sun exposure and phototherapy with psoralen combined with ultraviolet A are also reported to precipitate GA. 4,6 Reported drug causes of GA included amlodipine, gold, allopurinol, diclofenac, quinidine, intra-nasal calcitonin and anti-tumour necrosis factor (TNF) agents. 6,7 In one study 15% of patients attributed onset of GA to psychological stress.…”

“…4,5 Sun exposure and phototherapy with psoralen combined with ultraviolet A are also reported to precipitate GA. 4,6 Reported drug causes of GA included amlodipine, gold, allopurinol, diclofenac, quinidine, intra-nasal calcitonin and anti-tumour necrosis factor (TNF) agents. 6,7 In one study 15% of patients attributed onset of GA to psychological stress. 5 It has been suggested that GA is due to a delayed type hypersensitivity reaction, 5 but other theories have also been proposed.…”

“…6 There have been numerous descriptions of GA occurring in patients with malignancies, but larger studies revealed conflicting results. Several of the patients in the study by Studer et al had malignant disease, but incidence was not different to the general population and onset of GA not temporally related.…”

“…Several of the patients in the study by Studer et al had malignant disease, but incidence was not different to the general population and onset of GA not temporally related. 6 Hawryluk et al reviewed the evidence for the association of GA and malignant disease: although they concluded there was no causative relationship between malignancy and GA, atypical presentations or GA occurring in an elderly patient should prompt age-appropriate screening for malignancy and evaluation of immune state. 15 GA has also been reported in association with thyroid abnormalities and dyslipidaemia.…”