免疫介導發炎性疾病中的淋巴增殖性疾病

Lymphoproliferative disorders arising in immune-mediated inflammatory diseases related immune deficiency and dysregulation, a single center experience

目的：我們分析了免疫缺陷和失調患者中的淋巴增殖性疾病（LPDs），旨在提醒醫師關於免疫介導發炎性疾病（IMID）患者潛在的LPDs風險，並探討監測策略。
方法：對免疫缺陷和失調患者中發展LPDs的一組患者進行了回顧性審查。采用2022年修訂的《血液淋巴瘤分型分類（WHO-HAEM5）》第五版對LPD進行分類。分析了患者的人口統計學特徵、臨床特徵、治療和預後。評估了Epstein-Barr病毒（EBV）狀態在治療和預測結果中的作用。
結果：共鑑定了12例病例，其中包括5例類風濕性關節炎患者、2例潰瘍性結腸炎（UC）患者、2例腎移植後患者、1例系統性紅斑狼瘡患者、1例多發性肌炎患者和1例乾癬患者。LPD診斷時的平均年齡為52.8歲（範圍33-76歲）。潛在疾病發病與LPD診斷之間的平均持續時間為13.6年（範圍3-30.6年）。六名患者使用甲氨蝶呤（平均劑量11.25毫克/週，平均持續時間10.1年），其中6名中有2名同時使用阿達木單抗。三名患者接受了硫唑嘌呤治療（平均持續時間8.5年），其中1名UC患者合併使用了英夫利昔單抗。超過半數（58%）的病例觀察到乳酸脫氫酶（LDH）升高，並且在11例中的7例中發現了EBV陽性。
結論：LPDs可以在免疫缺陷和失調的任何階段發展，強調了對此需提高警覺。特定治療藥物與LPDs風險之間的關聯尚無定論。在接受免疫抑制劑治療的IMID患者中，LPDs的監測策略尚不足夠，但定期測量LDH和理學檢查注意淋巴結腫大可能有助於早期發現。

Objectives: We analyzed lymphoproliferative disorders (LPDs) in patients with immune deficiency and dysregulation, aiming to raise awareness among physicians regarding the potential risk of LPDs in patients with immune-mediated inflammatory diseases (IMID) and to explore monitoring strategies.
Methods: A retrospective review was conducted on a cohort of patients with immune deficiency and dysregulation who developed LPDs. The fifth edition of the Classification of Haematolymphoid Tumours (WHO-HAEM5), revised in 2022, was applied to classify LPD. Patient demographics, clinical characteristics, treatments, and outcomes were analyzed. Epstein-Barr virus (EBV) status was evaluated for its role in guiding therapies and predicting outcomes.
Results: Twelve cases were identified, including 5 patients with rheumatoid arthritis, 2 with ulcerative colitis (UC), 2 post-renal transplant, 1 systemic lupus erythematosus, 1 polymyositis, and 1 psoriasis. The mean age at LPD diagnosis was 52.8 years (ranged 33-76 years). Mean duration between the onset of underlying diseases and LPD diagnosis was 13.6 years (ranged 3-30.6 years). Six patients were methotrexate users (mean dose 11.25 mg/week, mean duration 10.1 years) and 2 out of 6 were combining adalimumab. Three patients received azathioprine (mean duration 8.5 years), with 1 UC patient combined with infliximab. Elevated lactate dehydrogenase (LDH) levels were observed in more than half (58%) of the cases, and EBV positivity was found in seven out of eleven (64%) tested samples.
Conclusion: LPDs can develop at any stage of immune deficiency and dysregulation, emphasizing the need for awareness. The association between specific therapeutic agents and the risk of LPDs remains inconclusive. Monitoring strategies for LPDs in IMID patients receiving immunosuppressants are lacking, but regular follow-up with LDH measurements and physical examinations for lymphadenopathy may aid in early detection.