Epstein-Barr病毒陽性之滅殺除炎相關淋巴增生性疾病：類風濕性關節炎病例系列與文獻回顧

Epstein-Barr Virus–Positive Methotrexate-Associated Lymphoproliferative Disorders in Rheumatoid Arthritis: A Case Series and Literature Review

目的：本研究旨在探討類風濕性關節炎（RA）患者中，Epstein-Barr病毒（EBV）陽性的滅殺除炎（methotrexate, MTX）相關淋巴增生性疾病（MTX-LPD）之臨床特徵、危險因子、組織學亞型與預後，並依據2022年修訂之《世界衛生組織第五版血液與淋巴造血腫瘤分類》（WHO-HAEM5）進行分析。
方法：回顧雙和醫院2009年1月至2025年3月間病理資料，篩選出9位合併RA診斷且罹患MTX-LPD之患者。分析其臨床資料、實驗室檢查、治療歷程與預後，並與既有文獻進行比較。
結果：共納入9位RA患者，平均MTX使用時間為8.7年。多數患者出現乳酸脫氫酶（LDH）升高及淋巴球減少。組織學亞型包括多型性LPD、淋巴瘤、EBV黏膜皮膚潰瘍及反應性增生。三位患者於停用MTX後病灶緩解，其餘患者則需進一步治療或預後不佳。
結論：RA患者所發生之EBV陽性MTX-LPD在停用MTX後可能出現病灶消退。WHO-HAEM5分類有助於亞型鑑別與預後評估。對高風險患者進行密切監測並適時停用MTX，對改善預後至關重要。

Objective: To investigate the clinical characteristics, risk factors, histological subtypes, and outcomes of Epstein-Barr Virus–Positive methotrexate-associated lymphoproliferative disorders (EBV positive MTXLPDs) in rheumatoid arthritis (RA) patients using the fifth edition of the Classification of Hematolymphoid Tumors (WHO-HAEM5), revised in 2022, framework.
Methods: A retrospective review of pathology records from January 2009 to March 2025 was conducted at Shuang-Ho Hospital. Clinical data, laboratory findings, treatment histories, and outcomes were analyzed and compared with existing literature.
Results: Nine RA patients with EBV-positive MTX-LPD were identified, with a mean exposure of 8.7 years. Most patients exhibited elevated lactate dehydrogenase (LDH), and lymphopenia. Histological subtypes included polymorphic LPD, lymphoma, EBV mucocutaneous ulcer and reactive hyperplasia. Three patients achieved remission after MTX withdrawal, while others required further treatment or had poor outcomes.
Conclusions: EBV-positive MTX-LPDs in RA patients may regress after MTX withdrawal. The WHOHAEM5 classification aids in subtype identification and prognostication. Careful monitoring of high-risk patients and timely MTX discontinuation are critical for favorable outcomes.