Department of Clinical Sciences, Section of Rheumatology, Lund University , Sweden.
Scand J Rheumatol. 2014;43(3):242-5. doi: 10.3109/03009742.2013.846405. Epub 2013 Dec 9.
To study the clinical characteristics and epidemiology of the combination of primary systemic vasculitis (PSV) and severe alpha-1 antitrypsin (α1-AT) deficiency.
Patients with PSV [granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss), and polyarteritis nodosa] were identified through diagnosis registries and serological databases. Clinical and laboratory data, including the presence of severe α1-AT deficiency, were collected from the time of diagnosis. During follow-up, data on relapses and permanent organ damage were collected. Using the county of Skåne as the denominator population, we estimated the annual incidence rate and point prevalence of PSV in people with severe α1-AT deficiency.
Five patients (three women, median age 49 years) with PSV diagnosed between 1996 and 2008 were found to have α1-AT deficiency, all of them carrying the protease inhibitor ZZ (PiZZ) phenotype. During follow-up (median time 166 months, range 53-208), four patients experienced a total of 13 relapses. The median Vasculitis Damage Index (VDI) score for all patients was 3 (range 1-4) at year 1, and 7 (range 3-9) at the last follow-up. The incidence rate of PSV among PiZZ carriers was estimated to be 397/million [95% confidence interval (CI) 8-787]. The point prevalence on 1 January 2013 was estimated to be 4689/million (95% CI 94-9285).
In this study both the incidence and prevalence of PSV were elevated nearly 10-fold for individuals with severe α1-AT deficiency compared with the general population. Combined with previous publications, this indicates a dose-response relationship for the genetic risk and suggests a causal relationship between the PiZ allele and vasculitis.
研究原发性系统性血管炎（PSV）与严重α-1 抗胰蛋白酶（α1-AT）缺乏症合并的临床特征和流行病学。
通过诊断登记和血清学数据库确定 PSV 患者（肉芽肿性多血管炎（GPA）（韦格纳）、显微镜下多血管炎、嗜酸性肉芽肿性多血管炎（EGPA）（Churg-Strauss）和多发性动脉炎）。从诊断时起收集临床和实验室数据，包括严重 α1-AT 缺乏的存在。在随访期间，收集复发和永久性器官损伤的数据。以斯科讷县为分母人群，估计严重 α1-AT 缺乏症患者中 PSV 的年发病率和时点患病率。
发现 5 例（3 名女性，中位年龄 49 岁）于 1996 年至 2008 年间诊断为 PSV 的患者存在 α1-AT 缺乏症，均携带蛋白酶抑制剂 ZZ（PiZZ）表型。在随访期间（中位时间 166 个月，范围 53-208），4 名患者共经历了 13 次复发。所有患者在第 1 年的血管炎损伤指数（VDI）中位数为 3（范围 1-4），在最后一次随访时为 7（范围 3-9）。PiZZ 携带者中 PSV 的发病率估计为 397/百万[95%置信区间（CI）8-787]。2013 年 1 月 1 日的时点患病率估计为 4689/百万（95%CI 94-9285）。
在这项研究中，与普通人群相比，严重 α1-AT 缺乏症个体的 PSV 发病率和患病率分别升高了近 10 倍。结合以前的出版物，这表明遗传风险存在剂量反应关系，并表明 PiZ 等位基因与血管炎之间存在因果关系。
