Non-Annular Granuloma Annulare Reports and Review

Granuloma annulare (GA) is a benign, inflammatory skin disease named for its histology of lymphohistiocytic granulomas and its morphology of annular lesions.^1,2 However, GA has other morphologic and histologic variants, including nodular, interstitial, and papular.^1-4 Here, we present two case reports illustrating two morphological presentations of interstitial GA, as well as a review of the possible morphologies.

CASE REPORT ONE

A 62-year-old woman presented with complaints of a non-painful, non-pruritic rash on her chest and abdomen. Physical examination showed several non-scaly, erythematous patches (Figure 1). Biopsy revealed mild spongiosis and mild acanthosis, as well as collagen degeneration, mucin deposition, histiocytic, neutrophilic, eosinophilic, and fibroblastic infiltrates, consistent with generalized interstitial generalized GA. The patient tried treatment with triamcinolone 0.1% ointment and then clobetasol 0.05% ointment. The patient experienced only minor improvement with the clobetasol ointment.

Figure 1: Interstitial GA on the patient’s right anterior thigh and abdomen. 

CASE REPORT TWO

A 25-year-old man with a history of type 2 diabetes presented with complaints of bilateral bumps on his knees, developing over the course of 4 months. The patient had tried topical salicylic acid without improvement. The physical exam showed hyperpigmented papules and nodules on both knees (Figure 2), as well as excoriated, hyperpigmented brown and erythematous papules on the bilateral posterior arms. The biopsy showed superficial and deep histiocytic infiltrate and collagen bundles that are separated by mild interstitial mucin deposits. No well-formed granulomas or collagen degeneration were identified. These findings were consistent with interstitial granuloma annulare. The patient started 0.1% triamcinolone ointment but did not experience any improvement.

Figure 2: Image of hyperpigmented papules and nodules on the knees of the patient.

DISCUSSION

GA has substantial morphological and histological variations, especially when considering comorbidities, and it can have more than first reported in the literature. However, commonalities also exist, such as their prevalence in patients and their comorbidities. The most common comorbidity associated with GA is type 2 diabetes. The validity of GA’s association with lipid abnormalities, malignant diseases, and thyroid disorders remains under investigation. Aside from prevalence and comorbidities, clinical manifestations of GA tend to be variable.^2,5-14

GA is a disease that has a few morphologic and histologic looks, although self-limited, benign, and often asymptomatic. Visible lesions, while asymptomatic, may be a source of psychosocial pain.

Treatments for GA can be frustrating as there are few controlled studies. For localized GA, whether annular, nodular, or papular, treatment options consist of intralesional corticosteroid injections, topical steroids with occlusion, or cryosurgery.^1-3,15-17 These treatment options can pose some risks, such as scarring or atrophy of the treated area. Treatment options for disseminated GA typically are systemic treatments, including dapsone, isotretinoin, tumor necrosis factor (TNF) inhibitors, antimalarial agents, or phototherapy. Risks for such courses of treatment are fatigue, muscle weakness, elevated cholesterol, or infections that are either viral, bacterial, or fungal.^2,18

Annular

The annular morphology of GA presents as papules or plaques that are red or flesh-colored and in the shape of rings, partial rings, or circles (Figure 3). The dorsal aspects of the hands, feet, and limbs are most commonly affected, and symptoms are less frequently present on the trunk. The annular form of GA frequently presents in females and adolescents. Histologically, annular GA is characterized by the deterioration of collagen, presence of mucin, and inflammatory mononuclear cells.^1-4,9,15

Figure 3: Annular GA on the right leg of a young child. 

Nodular

Nodular GA typically shows small, non-annular nodules on the limbs and dorsal hands, and near joints (Figure 2). It can be mistaken for rheumatoid nodules. Nodular GA, however, lacks the same inflammatory response that is commonly seen in patients suffering from rheumatoid nodules. Histologically, nodular GA shows necrobiosis with palisading granulomas as well as lymphocytes, T-cells, and lysozymes. Nodular GA is commonly associated with subcutaneous (pseudo-rheumatoid) GA.^7,10,19,20

Interstitial

Interstitial GA lesions (Figure 1 and Figure 4) are frequently pink patches or plaques that lack a distinct annular shape. These lesions are capable of covering a large body surface area of the limbs and trunk. Palisading granulomas, degradation of collagen, giant cells, and histiocytes are histological features of interstitial GA. Interstitial GA is frequently found in adults above the age of 40.^{1-5,8-12,14,21}

Figure 4: Interstitial GA presenting on the right arm of a patient. 

Papular

Papular GA shows papules most commonly on the hands and limbs (Figure 5 and Figure 6). Some lesions may have a crust and be umbilicated. Rarely, the lesions perforate. The usual histological signs of granuloma annulare are present in papular GA; however, in perforating papular GA, necrobiotic granulomas are seen. The necrobiotic granuloma localizes superficially within the epidermis, resulting in perforations. Perforating papules are typically classified as perforating GA, which typically afflicts young adults and children. The comorbidities of perforating granuloma annulare do not appear to differ from the other variants of GA.^1,4,6,22-25

Figure 5: Papular GA on the left elbow and forearm.

Figure 6: Papular GA on a patient’s back.

CONCLUSION

While GA is benign, the condition is taxing on patients psychosocially. The current literature lacks robust and systemic studies of GA, limiting treatment and management. The available literature consists of small studies and case reports, leaving much to be desired in way of statistical significance.

Regardless, this review may help clinicians recognize GA more readily, including non-annular variants, thereby facilitating earlier diagnosis, treatment discussions, and patient counseling. 

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Zebulon A. Thorsen, MA

North Shore Center for Medical Aesthetics
Northbrook, IL

Francisco P. Gomez, MD

University of Illinois College of Medicine, Department of Dermatology
Chicago, IL

Joshua Gilon Burshtein, MD

University of Illinois College of Medicine, Department of Dermatology
Chicago, IL

Michelle Bain, MD

University of Illinois College of Medicine, Department of Dermatology
Chicago, IL

Sheryl Hoyer, MD

University of Illinois College of Medicine, Department of Dermatology