台北一醫學中心幼年型硬皮症病患之臨床經驗

Juvenile scleroderma in Taiwanese children - experience of one institution in Taipei

前言：幼年型硬皮症在孩童時期是一極罕見的疾病，局部型硬皮症孩童較全身系統型硬皮症孩童為多。在本研究，我們回溯性分析十一位診斷為幼年型硬皮症之孩童（包括全身系統性及局部性），並對其臨床特徵及實驗結果作整理。研究材料與方法：自西元1993年3月至西元2006年6月於台北馬偕紀念醫院小兒部過敏免疫風濕科門診，我們回顧十一位幼年型硬皮症之孩童。他們皆為符合美國風濕病醫學會的診斷條件或者硬皮範圍及臨床表現所診斷。記錄並探討其性別、發病年齡、診斷年齡、臨床表徵、實驗室資料、家族史、過去受傷病史、治療和預後等資料之關聯性。研究結果：整體病童之平均診斷年齡為9.2歲（範圍從3歲至12歲）；平均發病年齡為6.5歲（範圍從出生至11.7歲）。兩位孩童（1位男孩，1位女孩）為全身系統性（兩者皆有肺功能異常，1位女孩腎臟有受影響）；其餘6位女孩、3位男孩為局部性硬皮症，不是硬斑病就是線狀硬皮病或者兩者合併存在。十位孩童其血清抗核抗體為陽性，濃度為40倍至640倍不等；於免疫螢光染色下，6位為斑點狀分布，2位為均勻分布，2位為均勻狀至斑點狀分布。血清抗硬皮症抗體（anti-Scl-70 antibodies）檢查皆不存在。血清類風濕因子濃度由<20 IU/mL至60.2 IU/mL不等，僅3位孩童有上升情形（1位全身系統型硬皮症女孩其血清類風濕因子濃度高達60.2 IU/mL；局部性硬皮症孩童中，1位女孩及1位男孩其血清類風濕因子濃度分別為45.6 IU/mL及58.2 IU/mL）。所有病患皆有皮膚緊繃變硬但是沒有任何一位病患有皮下鈣化之症狀。雷諾氏現象合併指尖點狀凹陷於兩位全身系統性硬皮症孩童身上皆可見。兩位男孩及一位女童有做皮膚切片顯示真皮層膠原纖維束增厚，合併皮膚附屬器或腺體萎縮與淋巴細胞浸潤增多。所有病患皆接受D-青黴胺（D-penicillamine）口服治療，合併或未合併口服類固醇與口服滅殺除癌錠（methotrexate）治療。僅有一位局部性硬皮症男孩完全痊癒，但是其餘局部型硬皮症孩童皆有明顯皮膚軟化之改善，臨床進程為良性。追蹤這九位局部性硬皮症孩童，沒有一位轉變為全身系統性硬皮症之病患。結論：幼年型硬皮症多以局部性硬皮症型式存在。雖然可能不會痊癒，但是局部性硬皮症並不會轉變為全身系統性硬皮症。

Objective. Scleroderma is rare in children who are more likely to have localized cutaneous scleroderma. In this study, we retrospectively reviewed the cases of eleven children with systemic and localized scleroderma. Materials and Methods. We reviewed the records of eleven children with systemic or localized scleroderma seen from March 1993 to June 2006 in the Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan. They were diagnosed according to American College of Rheumatology criteria and clinical manifestations of hard skin involvement. Data extracted from the records included gender, age at onset, age at diagnosis, clinical manifestations, laboratory data, family history, trauma history, treatment, and outcome. Results. The mean age at diagnosis was 9.2 years (range, 3 to 12 years). The mean age at onset was 6.5 years (range, birth to 11.7 years). Two children (1 girl and 1 boy) had systemic scleroderma (both with pulmonary involvement and 1 with renal involvement) and the other 6 girls and 3 boys bad localized scleroderma, either morphea or a linear pattern. Antinuclear antibodies were positive in 10 at titers of 40x to 640x; 6 had a speckled pattern, 2 had a homogenous pattern, and 2 had a speckled-to-homogenous pattern. Tests for anti-Scl-70 antibodies were all negative. Serum levels of rheumatoid factor ranged from <20 to 60.2 IU/ml with only 3 children having positive levels (60.2 IU/ml in 1 girl with systemic scleroderma; 45.6 and 58.2 IU/ml in I girl and 1 boy with localized scleroderma, respectively). All patients had skin tightening but none had subcutaneous calcification. Raynaud's phenomenon with digital pitting was present only in the 2 patients with systemic scleroderma. Skin biopsy specimens from 2 boys and 1 girl showed hypertrophic collagen bundles with atrophic skin appendages and lymphocytic infiltration. All patients were treated with 0-penicillamine with or without steroids and methotrexate. Only 1 boy with localized scleroderma recovered completely while the others with localized disease had a benign course with some skin softening. None of those 9 children with localized scleroderma progressed to systemic disease. Conclusion. Childhood scleroderma is more likely to be a localized cutaneous disease which, while it may not resolve, does not appear to progress to systemic disease.