CASE #1: Granuloma annulare

Granuloma annulare (GA) is a common, usually benign condition that most often presents as an annular, brownish-red papule, nodule, or plaque seen on the dorsal aspects of extremities of young women (especially children). In this patient, the lesion’s appearance and circumstances were so classic that a confirmatory biopsy was not needed. Had that procedure been done, it would have demonstrated foci of degenerative collagen associated with palisaded granulomatous inflammation, all highly suggestive of a diagnosis of GA.

Theories as to the origin of GA abound and include possible type IV cell-mediated immune response or primary degeneration of connective tissue leading to granulomatous inflammation, lymphocyte-mediated immune reaction with macrophage activation, and cytokine-mediated degradation of connective tissue.

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GA was once thought to have a strong connection to type 2 diabetes, but this line of thinking has long since been disproven. Alhough the condition is seen more often in patients with type 1 diabetes, any possible relationship is still a matter of conjecture.1

Clinically, GA most often presents with a solitary lesion. However, in 9% to 15% of cases, it presents with multiple or even generalized lesions.2 Women are affected twice as often as men. The age distribution of GA is bimodal: Most cases are seen in children younger than age 10 years, but there is a significant increase in incidence in persons aged 30 to 60 years.2

The typical plaques of GA are often mistakenly thought to be of fungal origin, but unlike the basic epidermal nature of the latter, GA is an intradermal process with little, if any, epidermal component. The somewhat beady, annular border and central sunken appearance (known as delling) seen in this case are typical. However, GA can also present as a macular, discolored patch with no raised component. Such a situation often demands a biopsy.

Two additional diseases that should be included in the differential diagnosis include erythema annulare centrificum and subacute lupus, both of which also typically demonstrate a significant scaly component. Biopsy in atypical cases can help rule out such other conditions in the annular differential as acute neutrophilic dermatosis (Sweet’s syndrome), necrobiosis lipoidica diabeticorum, lichen planus (LP), erythema elevatum diutinum, sarcoidosis, and Hansen’s disease.

To the uninitiated eye, the appearance of classic GA practically shouts “fungal,” a misdiagnosis that can lead to months of frustration (not to mention multiple futile treatments). The condition is usually instantly recognizable in any dermatology office.

Generalized GA can involve large areas of the body with hundreds of smaller lesions. This condition can be symptomatic (pruritus) and often requires biopsy to rule out similar-appearing conditions (e.g., LP and secondary syphilis). Generalized GA can also be a challenge to treat. Phototherapy has been used with some success, as has isotretinoin, hydroxychloroquine (Plaquenil), dapsone, and potassium iodide.

Rare forms of GA include subcutaneous3 and perforating4 types that require biopsy to confirm and referral to dermatology for management. Besides the treatments noted above, etanercept and other biologic agents are being used in severe cases of these variants.

Solitary and generalized GA have been reported in association with such malignancies as solid tumors (breast, colon and others) and lymphomas and leukemias.

As illustrated by this case, localized GA is usually asymptomatic and self-limited and therefore does not require treatment. Treatments that have been used with varying degrees of success include cryotherapy, use of class 1 topical steroids, and intralesional class 4 steroids (e.g., triamcinolone). Treatment choices—including intralesional steroid injections, topical steroid application, and ablation by cryotherapy—were discussed with the patient. She opted to use topical fluocinolone cream 0.05% twice a day to flatten the lesion and decrease coloration. Regardless of treatment, GA is typically self-limiting and will usually clear completely in a matter of months.