CASE #1: Granuloma annulare

Granuloma annulare (GA) was first described in 1895 as a ringed eruption of fingers. It was not until 1902 that Radcliffe-Crocker gave the official medical name for the disease.1

Presently, the etiology of GA is unknown. A delayed-type hypersensitivity reaction has been found to be the cause based on the T-cell subpopulations identified in the lesions, but to an unknown antigen.1 Some have associated GA with trauma, sun exposure, vaccinations, and insect bites. Given the similarity in morphology to TB, it has been suggested that GA is caused by a Th1 inflammatory reaction, with interferon-γ-producing lymphocytes, causing matrix degradation.1 These lymphocytes release various cytokines (e.g., macrophage inhibitor factor) that cause monocytes to gather in the dermis and release lysosomal enzymes that lead to the degradation of connective tissue. One study found that GA is primarily a disorder of elastic-tissue injury.1 Genetic factors have not been ruled out as a potential cause of the disease, as familial studies have reported GA in identical twins.1

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Classic GA most commonly appears as localized, benign, arciform-to-annular plaques on the extremities of young people. The female-to-male ratio is approximately 2:1. The plaques are asymptomatic and composed of small, individual papules that are erythematous, violaceous, or skin-colored. Lesions tend to enlarge centrifugally, however rarely are the rings more than 5 cm in diameter. In about 60% of cases, GA is found on the upper extremities.1 Lower extremities account for 20%, and 7% involve upper and lower extremities simultaneously.1 The torso accounts for 5% of all cases, and facial lesions are uncommon.1

While classic GA is the most common, other forms of the disease include generalized, perforating, subcutaneous, and patch GA. Generalized GA is distinguished by numerous small papules found on the trunk and extremities that may coalesce to form small annular plaques. This type of GA occurs in approximately 15% of patients,1 often at a later age. Generalized GA has a poorer response to therapy. There may be an association between generalized GA and diabetes mellitus, but this hypothesis remains controversial.2,3 Perforating GA is found on the dorsal hands and fingers, and the papules have distinct central umbilications, ulcerations, or keratotic plugs. Deep or subcutaneous GA tends to occur in young children and manifests as large, painless, skin-colored nodules located most commonly on the feet, anterior tibial surfaces, fingers, hands, and scalp. Patches of erythema on the trunk and extremities characterize patch GA. Oftentimes, the diagnosis of patch GA is made microscopically, as the clinical presentation lacks the classic annular plaques.

Histologically, in 70% of cases, GA is characterized by an infiltrative or interstitial pattern in which scattered histiocytes are distributed between collagen fibers. Necrobiosis is rarely seen; however, mucin deposition between collagen bundles can easily be highlighted with Alcian blue and colloidal iron stains. The second pattern is easier to recognize and consists of palisading granulomas around focal areas of collagen and elastin degeneration along with mucin accumulation.4,5 The epidermis is normal, and within the dermis, perivascular lymphocytes and eosinophils are sometimes seen. Vessel walls variably contain deposits of C3, immunoglobulin M, and fibrin, leading to occlusion of vascular lumina.

Currently laboratory tests can differentiate GA from diseases with similar clinical features. The diagnosis is mostly based on clinical observation and histopathologic features. Patients with GA very rarely show changes in the epidermal region. However, if changes such as scale are observed, annular lichen planus and tinea corporis should be taken into consideration. The former is characterized by violaceous, flat-topped papules or plaques with Wickham’s striae overlaying on top. The latter may be excluded by KOH examination of the associated scale.

Other diseases that imitate GA would require a definitive biopsy to differentiate between them. These include borderline leprosy, necrobiosis lipoidica diabeticorum, mycosis fungosides, and sarcoidosis.

GA is a noninfectious granuloma. Because of its benign, localized, and asymptomatic character, clinical observation and reassurance from the clinician is the best treatment. However, if clinically indicated, high-potency topical steroids or intralesional corticosteroids may be applied as first-line therapies. Topical steroids may also be used under occlusion; however, the risk of skin atrophy must be addressed. Cryosurgery, UVA1 therapy, psoralen UVA, and carbon dioxide laser treatment may also be used to alleviate the disease.1 Systemic agents are reserved for severe cases and include such medications as niacinamide, isotretinoin, hydroxychloroquine, dapsone, and pentoxifylline.1,3 One study reported six cases of GA, resistant to the standard modalities of treatment, that resolved after three months with monthly rifampin, ofloxacin, and minocycline hydrochloride combination therapy.6

GA is a self-limited disease in which 50% of cases spontaneously resolve within two years after onset.1 However, the duration of untreated lesions can range from a couple of weeks to several decades. There is a 40% reccurrence rate, and lesions often reappear at the original sites.2 Recurrent lesions tend to resolve more rapidly, with 80% clearing within two years.1 On healing, the lesions tend to turn brown in color and slowly fade without scarring.

This patient was treated with clinical observation and reassurance, as the lesions were asymptomatic.