Answer: B

Granuloma Annulare

Granuloma Annulare (GA) is a benign, self-limited, idiopathic dermatosis with multiple clinical presentations and shared histologic features. It was described in 1895 and named in 1902.7-9 The most widely documented clinical phenotypes of GA include localized GA, generalized GA, and subcutaneous GA. Localized GA is the most common variant of GA and is characterized by singular or multiple annular erythematous plaques seen on the extremities. Subcutaneous GA (SGA) is a less common subtype that occurs almost exclusively in children aged 1 to 14 years.7 Synonymous names include deep GA, subcutaneous palisading granuloma, pseudorheumatoid nodule, and necrobiotic granuloma.10

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Patients typically have slow-growing pink, yellow, or tan nodules that can be solitary or multiple. Nodules are frequently pretibial but also may occur on hands, scalp, buttocks, and behind the ears.7,10 Despite SGA distribution, trauma is not a recognized cause. Nodules located superficial to bone have been reported to extend to periosteum. They are typically motile on the extremities and slightly motile or nonmotile on the scalp or forehead. They are reported to be painless or slightly tender on palpation. Atypical manifestations include pain, unusual location, and rapid enlargement.11 Patients with SGA are usually young (mean age, 4.3 years) and otherwise healthy.8 Lesions predominantly occur in girls, with a female-to-male ratio of 1 to 2:1. Familial cases of SGA have been reported, but a relative lack of data exist on the genetics of SGA. Although an association of SGA with diabetes mellitus is speculated, it has not yet been established. Lesions of SGA in patients with diabetes mellitus are not discernibly different from lesions in patients without diabetes mellitus.10

Excisional biopsy is diagnostic but not therapeutic, and recurrence after biopsy has been reported in up to 75% of children. Complications of excisional biopsy for diagnosis include scar formation and infection. Histologic examination shows that nodules occur in reticular dermis and subcutaneous layers. Lesions are characterized by degeneration of collagen as a result of ischemia, surrounded by palisading histiocytes and mononuclear inflammatory cells.7-10 Histologically, SGA resembles RN and necrobiosis lipoidica diabeticorum (NLD) in adults. The key differentiating feature between SGA and RNs is the presence or lack of mucin in necrobiotic areas. A hematoxylin and eosin stain of SGA results in a bluish appearance of central zones because of mucin, which is not typically found in RNs. Staining with colloidal iron can confirm the presence of mucin.10

Because adults with rheumatoid nodules, which are histologically similar to SGA, are at significant risk for rheumatoid arthritis, efforts have been made to determine whether children with SGA are at similar risk for connective tissue disease. Two studies reviewing more than 100 cases found no association between SGA and the development of rheumatoid arthritis.8,12

Clinically, SGA and NLD are distinct, but they share histologic features. NLD is a granulomatous skin disorder that occurs in 0.3% of people with diabetes. It most commonly occurs on the legs but can also involve other areas such as the scalp, upper extremities, and abdomen. The average age of onset is 30 years.13 Central zones of degenerated collagen surrounded by palisading histiocytes are present in both conditions. SGA is distinguished histologically by smaller, rounder lesions involving only the deeper dermis and subcutis with more abundant mucin.

Other potential diagnoses include neoplastic, infectious, or systemic disease. Hematomas, abscesses, and infectious granulomas are usually suspected on the basis of a history of trauma, laboratory abnormalities (elevated erythrocyte sedimentation rate, elevated rheumatoid factor level), and systemic symptoms such as fever.11 Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves the lymph nodes, skin, spleen, eyes, liver, and lungs. Twenty-five percent of cases of sarcoidosis involve the skin and may include subcutaneous nodules.14 Sarcoidosis is confirmed histologically by noncaseating granulomas with lymphocytic infiltrates in the periphery.15

Benign and malignant tumors can be considered in the initial differential diagnosis. Leukemia and precursor B-lymphoblastic lymphoma may include the presence of cutaneous nodules. Soft-tissue tumors, such as rhabdomyosarcomas, can include masses with indistinct borders on the arms and legs. These lesions are typically painful. SGA is typically firmer than lipomas or neurofibromas. SGA can be confused with a soft tissue tumor, especially when nodules are located in the scalp. Radiographs indicating only soft tissue growth and no underlying bony involvement suggest a benign nodule. Dermatofibromas warrant consideration but typically are more yellow than SGA. These tumors lack palisading histiocytes on histologic evaluation.9

Lesions of SGA are benign and do not require treatment or intervention. However, for patients who experience distress because of the cosmetic appearance of the nodules, certain therapies may be effective. These include topical and systemic steroids as well as surgical excision. However, there is limited evidence for the efficacy of these treatments.12 Recurrences locally or distally are common but do not warrant additional biopsy, which can result in scarring or infection.11 Fortunately for many patients, SGA typically regresses after 12 to 24 months but may recur again after months or years.16

After discussing the various therapies, the patient’s mother decided to wait and see whether the nodules would regress before trying topical or systemic steroids.

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Emily Burns, BA, is a medical student; Ariella Noorily, BA, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor School of Medicine in Houston, Texas.


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