Granuloma annulare is a relatively common, self-limited, and benign skin disorder that presents in both children and adults. The condition was first described as a “ringed eruption of the fingers” by Thomas Colcott Fox in 1895.1 Today, there exist multiple classifications of granuloma annular, including localized and generalized forms, as well as subcutaneous, patch and perforating granuloma annular. The various types differ in clinical presentation and appearance, but they share a similar histopathology.
Granuloma annulare most frequently presents in female patients, with a female-to-male ratio of 2:1.2 It is also more common in children and young adults; two-thirds of those affected are younger than 30 years of age.2 The overall incidence and prevalence of granuloma annular has not been studied on a large scale; however, one review article estimates that granuloma annulare was diagnosed in 0.1% to 0.4% of new patients presenting to dermatologists.3 The pathogenesis of the condition is not entirely understood. Proposed triggers include trauma, vaccinations, insect bites, and various viral infections including hepatitis B and C, Epstein-Barr virus, and HIV.4 Although research has been conducted to assess a potential association between granuloma annular and diabetes mellitus, the association is controversial due to lack of large-scale epidemiologic studies.2
Granuloma annulare may present with a variety of clinical characteristics. The localized form usually presents as an annular or arciform asymptomatic plaque without scale. The plaque may be erythematous, violaceous, or skin colored and often has an area of central clearing. Some lesions may present with discrete 1- to 2-mm papules at the outer edge of the lesion; other lesions develop a firm, continuous border, which upon careful inspection is composed of individual small, 1- to 3-mm papules that coalesce into a larger annular plaque, usually <6 cm.2 Localized granuloma annular most often presents in the wrists, ankles, and on the dorsal aspect of the hands and feet. More than half of patients will have more than one lesion. In generalized granuloma annular, papules and plaques present in widespread areas of the trunk and extremities. The lesions are most commonly distributed symmetrically. Generalized granuloma annulare usually presents at a later age than the localized subtype.
Subcutaneous granuloma annulare presents as deep dermal or subcutaneous asymptomatic nodules with no overlying skin changes. Lesions are most commonly located on the anterior tibial surfaces, buttocks, hands, and scalp of children.5 Perforating granuloma annular consists of small papules with central umbilication, crust, or ulceration. These lesions occur most frequently on the dorsal aspects of the fingers and hands. Patch granuloma annulare presents as symmetric erythematous patches on the extremities and trunk.2
With so many different variants of granuloma annulare, the diagnosis often must be made microscopically. Histologic examination of granuloma annulare demonstrates a dermal lymphohistiocytic infiltrate with degenerated collagen and mucin deposition. The cells most commonly organize in an interstitial or palisading granulomatous pattern. The interstitial histologic pattern demonstrates histiocytes scattered between collagen fibers, with basophilic mucin deposits among the collagen bundles. The palisading granulomatous pattern demonstrates a central core of degenerating collagen, elastic fibers, and mucin, with histiocytes and lymphocytes at the circumference. In subcutaneous granuloma annular, the palisaded granulomatous pattern can be seen in the deep dermis and subcutaneous fat.2
Due to the variety of clinical presentations, the differential diagnosis for granuloma annulare is broad. Localized granuloma annulare simulates other annulare entities including tinea corporis, annular elastolytic giant cell granuloma (AEGCG), and sarcoidosis. Granuloma annulare can be differentiated from tinea corporis clinically by lack of scale in in the former. Definitive diagnosis of tinea corporis can be confirmed by performing a potassium hydroxide preparation or fungal culture. AEGCG appears clinically as a pink annular plaque with central atrophy and hypopigmentation; these lesions most commonly occur in sun-exposed areas. Histologically, both AEGCG and granuloma annulare may contain palisading granulomas. However, the two are set apart by loss of dermal elastic fibers and absent mucin in AEGCG. Cutaneous sarcoidosis may present as red-brown annular plaques and papules, with a predilection for the face. Sarcoidosis is often associated with systemic symptoms. Histologically, sarcoidosis may be distinguished from granuloma annulare by the presence of noncaseating sarcoidal granulomas in the former.6
Generalized papular granuloma annulare may appear similar to flat warts, insect bites, eruptive xanthomas, or secondary syphilis. Clinical correlation and biopsy should be used to distinguish the different entities.2 Subcutaneous granuloma annulare must be distinguished from rheumatoid nodules, the nodules of rheumatic fever, and deep granulomatous infections. Rheumatoid nodules simulate subcutaneous granuloma annulare both clinically and in histopathology; subcutaneous granuloma annulare lesions are also known as pseudorheumatoid nodules. Classic rheumatoid nodules occur in individuals with severe, seropositive arthritis.7 Therefore, nodules appearing in young children are more likely to be subcutaneous granuloma annulare, while lesions occurring in older individuals with rheumatoid arthritis are more likely rheumatoid nodules.
Oftentimes, the diagnosis of granuloma annulare can be made clinically. No serologic test exists for this condition. One must carefully rule out the other conditions in the differential diagnosis including the annular, papular, and nodular lesions previously described. Biopsy can confirm the presence of granuloma annulare.
In localized and asymptomatic disease, reassurance and clinical observation are recommended, as granuloma annulare is a self-limited condition. Half of cases of localized granuloma annulare will completely resolve in 2 years without intervention.2 For individuals with localized disease that persists, first-line therapy consists of topical or intralesional corticosteroids. Response to this treatment is variable; however, some studies have found intralesional therapy to be greatly effective.8 Topical steroid should be applied once or twice daily for 2 to 4 weeks. Intralesional steroid, usually triamcinolone, should be injected at the border of the lesions every 6 to 8 weeks.9 Topical tacrolimus may also be effective. For more extensive disease, phototherapy or systemic medications including hydroxychloroquine, isotretinoin, and dapsone may be used. Granuloma annulare often recurs in the same area as the original lesions, and the majority of recurrences resolve spontaneously.2
For the patient in our case, biopsy of the lesion confirmed the diagnosis of localized granuloma annulare. She was reassured as to the benign nature of the condition and elected not to pursue treatment. She followed up in the clinic every 3 months and the lesion resolved after approximately 15 months.
Click to the next page for Case 2.