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Granuloma annulare (GA) is a benign skin condition characterized by groups of skin-colored to erythematous papules that are usually in an annular (ring-like) pattern and typically located on the dorsal aspects of the hands and feet. There are five types of GA: localized, generalized, subcutaneous, patch, and perforating.
- GA is a relatively common, noninfectious granulomatous disease. Population-based studies to determine the incidence and/or prevalence of GA are lacking. A single study in 1980 demonstrated that 0.1–0.4% of new patients presenting to dermatologists have GA but did not report similar descriptive statistics in the primary care arena (1).
- Although most lesions resolve spontaneously within 2 years, some persist for 10 years or more.
- Predominant sex: female > male (1 to 2.5:1)
- Onset of symptoms occurs at <30 years old in 2/3 of all patients. Typical ages for onset of each subtype are:
- Localized: <30 years old
- Generalized: bimodal: <10 years old, 30 to 60 years old
- Subcutaneous: 2 to 14 years old
- Patch: >30 years old
- Perforating: children and young adults
- Distribution of subtypes is as follows:
- Localized: 75%
- Generalized: 10–15%
- Subcutaneous: <5%
- Patch type: <5%
- Perforating: <5%
Etiology and Pathophysiology
The etiology of GA remains unknown. It is hypothesized to be a dermatologic manifestation of a delayed-type hypersensitivity reaction to an unknown antigen in the dermis that is mediated by tumor necrosis factor alpha (TNF-α) and interleukin factors 1 and 2 (IL-1 and IL-2) (2). Characteristic histopathologic features include lymphohistiocytic infiltrates, degeneration of collagen, palisading or interstitial granulomatous inflammation, and mucin deposition.
There is some evidence for a genetic predisposition. Two studies reported an increased frequency of HLA-Bw35 in patients with generalized GA. Of note, HLA-Bw35 has also been associated with thyroid disease (1).
No definite risk factors have been identified. There are reported associations between GA and diabetes mellitus (DM), autoimmune thyroid disease, dyslipidemia, human immunodeficiency virus, Epstein-Barr virus, herpes simplex virus, systemic lupus erythematosus, tuberculosis, and hepatitis B and C, among others. There have also been associations with interferon-α therapy, trauma, sun exposure, insect bites, borreliosis, and malignancies (most commonly lymphoma) (2,3).
There are no known preventive measures for GA.
Commonly Associated Conditions
- DM: The association between GA and DM is controversial. Early studies from the 1980s showed a possible link, but recent case-controlled studies have shown no statistically significant association between GA and DM (3).
- Autoimmune thyroid disease: Multiple case reports have linked thyroid disease with both generalized and localized GA. In one case-control study, 24 women with localized GA were compared to 100 age-matched women with non-GA dermatologic disease. A statistically significant increase in the incidence of autoimmune thyroid disease among those with localized GA as compared with those with other non-GA cutaneous disease was identified (12% vs. 1%, p = .022) (2,3).
- Malignancy: There is no definitive relationship between GA and malignancy. A review of the literature found 14 case reports and two correlation studies in which patients who had one or more malignancies also had GA. In a majority of these cases, the malignancies were hematologic, primarily lymphoma (2,3).
- Dyslipidemia: Dyslipidemia may be associated with GA. A single case-control study (n = 140) demonstrated a statistically significant increase in hyperlipidemia among patients with GA compared to controls (79.3% vs. 51.9%, p <.001) (4).
- HIV: Among patients with GA, those who also have HIV appear more likely to have the generalized subtype. In one study of 34 patients with GA and HIV, 20 (59%) had generalized GA (2).
- Note: Conclusions regarding associations between GA and various diseases, including those listed above, are limited by both design and power. Consequently, in the absence of new research, definitive associations between GA and other diseases cannot be made.