Supplementary Material for: A Monocentric, Retrospective Analysis of 61 Patients with Generalized Granuloma Annulare

<b><i>Background:</i></b> Granuloma annulare is a chronic noninfectious granulomatous skin condition with variable clinical presentations. Generalized granuloma annulare, defined as widespread disease with &gt;10 skin lesions, accounts for 15% of all cases. Numerous associated diseases have been controversially discussed, most importantly diabetes mellitus, dyslipidemia, thyroid disease, malignancy and systemic infections. <b><i>Objectives:</i></b> The objective of our study is to describe disease characteristics, treatment outcome and associated diseases in patients treated at the Department of Dermatology of the University Hospital Zurich during the last 20 years. <b><i>Methods:</i></b> The hospital database was searched for patients with generalized granuloma annulare in the last 20 years (January 1, 1998, to December 31, 2017). Overall, 61 patients, 14 males and 47 females, were included in our study. The mean age was 58 years at first consultation. The diagnosis was verified clinically and histologically. <b><i>Results:</i></b> Generalized granuloma annulare occurred at a mean age of 55 years, more commonly in females. Pruritus was absent in 51% of all patients. Metabolic diseases including diabetes mellitus, hypercholesterinemia and hypertriglyceridemia were present in 10.5, 8.2 and 4.9%, respectively. Thyroid disease was present in 9.8% and malignant disease in 23%, including colorectal cancer, lymphoproliferative disease, squamous cell carcinoma of the esophagus, basal cell carcinoma and gynecological malignancy. Therapy was initiated in 92%, while second- and third-line therapy was performed in 70 and 39%, respectively. Benefit during therapy (e.g., full and partial remission) was achieved in 39.3% during first-line, in 39.4% during second-line and in 33.8% during third-line treatment. Topical corticosteroids were the most commonly prescribed treatment, mostly leading to stable disease (46.6%). Combined full and partial remission occurred in a large proportion of patients receiving UVA1 (45%), PUVA (63.6%) and intralesional triamcinolone acetonide (100%). <b><i>Conclusions:</i></b> Generalized granuloma annulare is a mostly asymptomatic and benign disease with a strong tendency for treatment resistance. We suggest to screen all patients for dyslipidemia, thyroid disease and malignant disease. While randomized trials are needed, we suggest topical corticosteroids as the first-line treatment, intralesional triamcinolone acetonide for persistent solitary lesions and, if further treatment is needed, UVA1 or PUVA.

<b><i>背景：</i></b> 环状肉芽肿（Granuloma annulare）是一种慢性非感染性肉芽肿性皮肤病，临床表现多样。泛发性环状肉芽肿（Generalized granuloma annulare）定义为皮损数量超过10个的广泛性病变，占所有病例的15%。学界对其关联疾病存在诸多争议，其中以糖尿病、血脂异常、甲状腺疾病、恶性肿瘤及全身性感染最为受关注。
<b><i>研究目的：</i></b> 本研究旨在回顾20年间苏黎世大学医院皮肤科接诊的泛发性环状肉芽肿患者的疾病特征、治疗结局及关联疾病情况。
<b><i>研究方法：</i></b> 检索1998年1月1日至2017年12月31日20年间的医院数据库，筛选确诊泛发性环状肉芽肿的患者。最终纳入61例患者，其中男性14例，女性47例，首次就诊时的平均年龄为58岁。所有病例均经临床及组织病理学确诊。
<b><i>研究结果：</i></b> 泛发性环状肉芽肿的平均发病年龄为55岁，女性患者更为多见。51%的患者无瘙痒症状。代谢性疾病中，糖尿病、高胆固醇血症及高甘油三酯血症的患病率分别为10.5%、8.2%及4.9%。甲状腺疾病患病率为9.8%，恶性肿瘤患病率为23%，包括结直肠癌、淋巴增殖性疾病、食管鳞状细胞癌、基底细胞癌及妇科恶性肿瘤。92%的患者接受了治疗，其中70%及39%的患者分别接受了二线及三线治疗。一线治疗、二线治疗及三线治疗的获益（如完全或部分缓解）率分别为39.3%、39.4%及33.8%。外用糖皮质激素是最常用的治疗方案，多数患者可达到病情稳定（46.6%）。接受UVA1、PUVA及皮损内注射曲安奈德（triamcinolone acetonide）的患者中，分别有45%、63.6%及100%达到完全或部分缓解。
<b><i>研究结论：</i></b> 泛发性环状肉芽肿多为无症状的良性疾病，但具有较强的治疗抵抗性。我们建议对所有患者筛查血脂异常、甲状腺疾病及恶性肿瘤。尽管尚需开展随机对照试验，我们仍推荐外用糖皮质激素作为一线治疗方案，对于持续性孤立性皮损可采用皮损内注射曲安奈德，若需进一步治疗则可选用UVA1或PUVA。