皮膚白斑病之臨床免疫和治療的反應評估

Evaluation of immunological profiles and clinical characteristics in patients with vitiligo

目的：評估白斑病人免疫調控異常以及低劑量azathioprine合併使用類固醇之臨床療效。方法：在這一個open-label的研究當中，針對190白斑病病人在一般的外用塗抹皮質類固醇和光化學治療的反應皆失敗後收案作治療前後評估。所有本研究的病人皆有詳盡的記錄，包括：臨床特徵、疾病進程、以及血清資料（全血球計數、尿液分析、免疫功能分析（ANA、ENA、RF、C3、C4、IgA、IgG、IgM、CIC、cryoglobulin）、甲狀腺功能（anti-thyroid antibody、T3、free T4、TSH、antithyroglobulin、antimicrosomal antibody））。病人每天接受低劑量的25 mg azathioprine（硫唑嘌呤）合併5 mg prednisolone。治療後每月皆有仔細記錄，包括白斑進展（skin lesion progression），新白斑病變（new skin lesions development），白斑週邊淡化（less distinct vitiligo margin），以及新色素形成（pigment regeneration）。結果：在此研究當中，145位病人（76.32%）患有單純皮膚白斑病，並沒有血清實驗數據異常。相反地，45位病人（23.68%） 合併有免疫疾病異常；其中的9位病人有甲狀腺疾病，有22位病人符合系統性的風濕免疫疾病診斷的要素，包括5位系統性紅斑性狼瘡，4位乾癬，4位脊椎關節病變，4位冷凝球蛋白血症，2位類風濕性關節炎，1位皮肌炎，1位Behcet's disease，1位過敏性血管炎。另有14位病人有血清檢查上的數據異常但尚未有足夠條件診斷出特定的疾病。進一步分析，主要的抽血實驗檢查異常包括：補體低下、甲狀腺功能異常、ANA自體免疫抗體、持續的白血球過低、淋巴球過低、免疫球蛋白增多症和其他的異常（包括RF類風溼因子、ENA、anti-dsDNA抗體、cryoglobulin冷凝蛋白、CIC免疫複合體、蛋白尿）。分析治療反應得知大部分病人（共174位，91.58%）於低劑量的25 mg azathioprine/天和5 mg prednisolone/天治療後其皮膚的病灶不再惡化進行，也不再產生新的病灶，平均治療反應時間約2.3 ± 1.1個月；64位病人（33.68%）皮膚白斑有持續縮小，平均持續治療時間約5.4 ± 1.6個月；52位病患（27.37%）皮膚病灶的邊緣變得不明顯；33位病人（17.37%）皮膚病灶有色素再生現象。沒有病人對於此項治療產生副作用。結論：我們的研究顯示皮膚白斑病是一種免疫調控異常疾病，而且常合併其他自體免疫疾病。我們的研究結果也顯示低劑量的azathioprine 和prednisolone治療此疾病有顯著療效。

Objective: Assess the presence of immune disorders in patients with vitiligo and the effects of low dose azathioprine and steroid as treatment. Methods: We enrolled 190 Taiwanese vitiligo patients at a rheumatology out-patient clinic, all of whom had previously failed to respond to topical corticosteroids and photochemotherapy. We recorded clinical features, disease course, and serological data commonly used in the diagnosis of autoimmune diseases. The response to low dose of azathioprine 25 mg qd and prednisolone 5 mg qd were assessed in each of four dimenions, including skin lesion progression, new skin lesions development, less distinct vitiligo margin and pigment regeneration by physician and patient visual analog scale. Results: 145 patients (76.32%) had simple vitiligo (no serological abnormality) and 45 patients (23.68%) had at least one serological abnormality. Of these 45 patients, 22 patients (11.58%) had systemic rheumatic disease (5 patients with systemic lupus erythematosus, 4 patients in each of psoriasis, spondyloarthropathy, and cryoglobulnemia, 2 patients with rheumatoid arthritis, and 1 patients in each of dermatomyositis, Behcet’s disease, and hypersensitive angitis), 9 patients (4.74%) had thyroid disease, and 14 patients (7.37%) had serology abnormalities without diagnosis of specific disease. Most patients (174 patients, 91.58%) showed no more vitiligo progression and no development of new skin lesions within 2.3 ± 1.1 months. Furthermore, 64 patients (33.68%) experienced a regression of skin lesions in 5.4 ± 1.6 months, 52 patients (27.37%) experiencing a less distinct margin and 33 patients (17.37%) experiencing pigment regeneration. None of the patients reacted adversely to the treatment. Conclusion: Our study showed a possible immune dysregulation in patients with vitiligo as evidenced by presence of abnormal immune prfiles and association with other autoimmune diseases. Our data also disclosed that low dose systemic azathioprine and steroid were effective in treating this disorder.