A 61-year-old man presents with a 7-month history of lesions on his hands and arms. His medical history includes depression, hypertension, and hyperlipidemia. He has no personal or family history of skin problems. His skin lesions are not painful or itchy, and he is not bothered by their appearance. He has not tried any treatments for the lesions. Physical examination reveals a number of pink, annular plaques with smooth raised borders on the patient’s dorsal forearms and hands. On close inspection, small discrete papules are seen within the plaques.
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Localized granuloma annulare (GA) is a common granulomatous skin condition that presents as skin-colored to erythematous papules and plaques.1 The first case of GA was described in 1895 by English dermatologist Thomas Calcott Fox as a ringed eruption, and the term granuloma annulare was coined in 1902 by Henry Radcliffe Crocker.2
GA is twice as common in women as in men, occurs most commonly in patients younger than 30 years, and displays no racial predilection.1,3 Localized GA is the most common form of GA, accounting for approximately 75% of cases.1 Generalized GA, defined by the presence of 10 or more lesions or widespread plaques, accounts for 8% to 15% of cases.1 Macular/patch, subcutaneous, and perforating variants of GA also have been described in the literature.1
Although the etiology of GA is unknown, the inciting event is thought to be a type IV delayed hypersensitivity response to an unknown antigen. The granulomatous response is caused by type 1 helper (TH1) cells, which mediate an inflammatory reaction leading to increased levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-2, and IL-12.4 In addition, increased macrophage activity releases lysozymes that cause matrix degradation.3,4 Generalized GA may be associated with human leukocyte antigen-BW35, although no genetic etiology of localized GA has been reported.3,5
Although the majority of patients with GA are healthy,1 the condition has been linked to several systemic diseases, including thyroid disease, dyslipidemia, and hematologic and solid malignancies.1,3,4,6 Infectious agents (hepatitis B and C viruses, HIV), trauma, insect bites, and vaccinations also have been implicated as inciting factors for GA.1,3
Classically, the lesions of localized GA are arranged in an annular configuration on the dorsal hands or feet.7 Lesions are limited to the arms and dorsal hands in 60% of GA cases and to the legs and dorsal feet in 20% of cases. Involvement of both the upper and lower extremities, trunk, and other body areas is less common.3 The lesions present as papules or plaques with smooth, raised borders up to 5 cm in diameter.7 Upon closer inspection, these lesions are made up of individual small papules several millimeters in diameter.3 GA generally is asymptomatic, but mild pruritus is present in some cases.7
Histologically, GA is characterized by palisading granulomas around a focal region of collagen degradation as well as perivascular and interstitial lymphocytes and histiocytes. The presence of mucin is an important hallmark of GA.3,8
GA is diagnosed clinically and histologically; no laboratory test aids in diagnosis.3 Dermoscopic findings of GA are variable but commonly there are whitish regions, which reflect the collagen degradation and mucin deposition seen in GA, as well as yellowish-orange regions and unfocused vascular structures.9
The differential diagnosis for GA includes sarcoidosis, necrobiosis lipoidica, tinea corporis, leprosy, mycosis fungoides, and annular elastolytic giant cell granuloma (AEGCG).3,7 The presence of mucin on histologic examination will rule out sarcoidosis and necrobiosis lipoidica because mucin is absent in these pathologies.1 Biopsy is also required to definitively rule out mycosis fungoides.3 GA lesions do not display scaling and are not accompanied by vesicles or pustules, which helps distinguish GA from tinea corporis.7 In addition, hyphae will be visualized in a potassium hydroxide preparation of a suspected tinea corporis lesion and not in a GA lesion. Leprosy can be differentiated from GA by the presence of scaling and anesthesia, which are not characteristic of GA.7 If lesions have central hypopigmentation and/or atrophy, the diagnosis of AEGCG is favored.3
Localized GA is a benign, self-limited disease with approximately 50% of cases resolving within 2 years.1 However, up to 40% of cases recur. Reassuring patients about the benign nature of the disease and monitoring them is an appropriate management strategy for many mild cases of localized GA. Patients may seek treatment if lesions are symptomatic or for cosmetic reasons.2,3 Most of the data on treatment of GA is limited to case reports, retrospective studies, and small case series. A lack of conclusive data may be due, in part, to the self-limited nature of the disease, which may make some treatments appear more efficacious than they truly are.6 High-potency topical steroids with or without occlusion are considered first-line therapy for localized disease. Lesions that do not respond to topical steroids can be treated with intralesional corticosteroids.4 Additional local treatment options include cryotherapy and topical tacrolimus.1,3 More extensive disease may be treated with phototherapy or systemic medications (eg, antimalarials, retinoids, biologics, niacinamide).1,3
Our patient was prescribed topical clobetasol, which helped the lesions fade, but he returned a year later with a recurrence. He declined treatment for the recurrence because the lesions did not bother him.
1. Thornsberry LA, English JC. Etiology, diagnosis, and therapeutic management of granuloma annulare: an update. Am J Clin Dermatol. 2013;14(4):279-290. doi:10.1007/s40257-013-0029-5
2. Wang J, Khachemoune A. Granuloma annulare: a focused review of therapeutic options. Am J Clin Dermatol. 2018;19(3):333-344. doi:10.1007/s40257-017-0334-5
3. Rosenbach MA, Wanat KA, Reisenauer A, White KP, Korcheva V, White CR. Non-infectious granulomas. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. Elsevier; 2018:1644-1663.
4. Keimig EL. Granuloma annulare. Dermatol Clin. 2015;33(3):315-329. doi:10.1016/j.det.2015.03.001
5. Piette EW, Rosenbach M. Granuloma annulare: clinical and histologic variants, epidemiology, and genetics. J Am Acad Dermatol. 2016;75(3):457-465. doi:10.1016/j.jaad.2015.03.054
6. Wu W, Robinson-Bostom L, Kokkotou E, Jung HY, Kroumpouzos G. Dyslipidemia in granuloma annulare. Arch Dermatol. 2012;148(10):1131-1136. doi:10.1001/archdermatol.2012.1381
7. Hsu S, Le EH, Khoshevis MR. Differential diagnosis of annular lesions. Am Fam Physician. 2001;64(2):289-296.
8. Umbert P, Winkelmann RK. Histologic, ultrastructural and histochemical studies of granuloma annulare. Arch Dermatol. 1977;113(12):1681-1686. doi:10.1001/archderm.1977.01640120049007
9. Errichetti E, Lallas A, Apalla Z, Di Stefani A, Stinco G. Dermoscopy of granuloma annulare: a clinical and histological correlation study. Dermatology. 2017;233(1):74-79. doi:10.1159/000454857