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    • Introduction Granuloma annulare GA is a benign and usually

    2018-11-15

    Introduction Granuloma annulare (GA) is a benign, and usually self-limited, inflammatory GDC-0994 disease. The disease incidence is estimated to be between 0.1% and 0.4%. The clinical manifestations vary, from localized, erythematous to flesh-colored papules with annular arrangement to the more generalized form. GA can develop in any skin areas, but it tends to occur on the lateral or dorsal surfaces of the hands and feet. GA is usually self-limited. The pathogenesis of GA remains unclear although abnormal repair in vascular injury or aberrant responses in delayed-type hypersensitivity may be involved. The diagnosis is made clinically or by skin biopsy with the typical histological findings of eosinophilic necrobiosis and palisading lymphohistiocytic infiltrates. GA was reported to commonly affect children and young adults with a female preponderance based on hospital based studies performed in USA, Singapore, Switzerland, and UK. However, a recent study in Korea reported a bimodal distribution of onset age and a slight male predominance among patients with generalized GA. The mixed clinical and epidemiological pattern of GA might depend on the variations in clinical categorizations, races, and associated triggering factors. In Taiwan, several individual cases of GA have been reported; however, a comprehensive study to delineate the clinical categorizations, treatment outcome, associated disease, and histopathological features of GA is lacking. Therefore, we herein aimed to evaluate the clinical findings, histopathological features, associated diseases, and treatment outcomes in Taiwanese patients of GA.
    Method Based on clinical manifestations, the disease was classified into localized, generalized, subcutaneous, and perforating types. Solitary or a few lesions on a single anatomical site were defined as localized form. Generalized GA was defined as affecting at least the trunk and either upper, lower, or both limbs, based on the criteria initially stated by Dabski and Winkeiann. Subcutaneous GA was characterized by granuloma predominantly affecting subcutaneous tissue while perforating GA was featured by superficial umbilicated papules and transepidermal elimination of necrobiotic collagen. Representative clinical features for subtypes of GA are shown in Figure 1.
    Results
    Discussion GA is a chronic, benign inflammatory skin disease that usually presents as annular plaques located on the extremities of young people. Age onset of GA was reported mostly in the first 3 decades in the previous literature. Majority of previous studies demonstrate female preponderance. However, in our study, it has a bimodal age distribution (one peak below 20 years and the other above 50 years) with slight male preponderance (male: female = 1.09: 1). Most patients were older than 50 years. In this study, consistent with previous literature, localized GA is the most frequent clinical variant in either children or adults. However, in this study, the prevalence of generalized GA in our patients (36.4%) is higher than that reported in other previous studies (range, 5–25.8%). Dabski and Winkeiann divided the clinical appearance of generalized GA into two forms. In the present study, the predominantly annular form accounted for 45.5%, whereas the predominant papular form accounted for 38.6%. Subcutaneous GA occurs most often in children and young adults. Perforating GA was the rarest subtype and exclusively seen in children. The pathogenesis of GA has not been fully elucidated. Most patients cannot identify any precipitating factors. Reported precipitating factors in the literature were trauma, sunburn, insect bite, Bacillus Calmette–Guérin vaccination, drugs, upper respiratory infection, reaction to intravenous contrast medium, phlebitis, sepsis after surgery, and stress. Many investigators have attempted to demonstrate a relationship between GA and other systemic diseases, with DM most noteworthy. The association of GA with DM remains controversial. Studer et al noted that 10 of 84 adult patients (12%) with GA (localized or generalized) had DM, as opposed to the 5% prevalence of DM among the regional population. However, other studies that looked for carbohydrate intolerance by performing glucose tolerance testing or assessing the hemoglobin A1c values failed to find an increased prevalence of altered carbohydrate metabolism in the patients with GA. Our study showed that the prevalence of DM in GA patient is 13.6% (5 generalized GA and 1 localized GA), which is higher than general adult population in Taiwan (6.38%). In our study, patients with generalized GA were more likely to develop DM than those with localized disease, although the difference was not statistically significance (p = 0.0691). Although the association between GA and DM is not settled, we recommended DM workup for the GA patients, especially for those who presented generalized typed GA and age over 50 years.