Supplementary Material for: A Novel Case of Multicentric Reticulohistiocytosis Associated with Renal Cell Carcinoma Successfully Treated with Infliximab and Methotrexate

Multicentric reticulohistiocytosis (MRH) is categorized as a rare non-Langerhans cell histiocytosis most commonly seen in women in the fourth to fifth decade of life. This systemic inflammatory condition affects multiple organ systems and can result in severe joint destruction which can progress to arthritis mutilans. To date, various underlying malignancies have been discovered in patients with MRH including breast, gastric, thymic, hepatic, and melanoma. There has been 1 case of underlying renal cell carcinoma reported in a patient diagnosed with MRH. Additionally, there is no consistently recognized treatment for MRH described in the literature. The rarity of the disease contributes to the difficulty in defining a standardized treatment. We present the case of a patient with extensive joint and skin involvement who was successfully treated with infliximab and methotrexate, experienced clinical improvement, and was later diagnosed with clear cell renal cell carcinoma. The synergistic effects of infliximab and methotrexate, in combination with the low side-effect profile, appear to be promising in the setting of MRH and in our patient resulted in the resolution of symptoms and cutaneous manifestations. We suggest this regimen as an effective combination therapy. We emphasize thorough and continuous screening for underlying malignancy associated with MRH, despite clinical improvement or negative malignancy work-up upon initial diagnosis.

多中心网状组织细胞增生症（Multicentric reticulohistiocytosis, MRH）属于罕见的非朗格汉斯细胞组织细胞增生症（non-Langerhans cell histiocytosis），好发于40至50岁的女性群体。该系统性炎症性疾病可累及多器官系统，可引发严重的关节破坏，甚至进展为毁形性关节炎（arthritis mutilans）。截至目前，临床已在MRH患者中发现多种潜在恶性肿瘤，包括乳腺癌、胃癌、胸腺癌、肝癌及黑色素瘤，目前已有1例合并肾细胞癌的MRH患者的病例报道。此外，目前文献中尚无公认的MRH标准化治疗方案，该病的罕见性也为标准化治疗方案的制定带来了极大挑战。本文报告1例出现广泛关节与皮肤受累的MRH患者：该患者接受英夫利昔单抗（infliximab）与甲氨蝶呤（methotrexate）治疗后获得了良好的临床应答，后续确诊为透明细胞肾细胞癌（clear cell renal cell carcinoma）。英夫利昔单抗与甲氨蝶呤的协同作用，加之其较低的不良反应发生率，在MRH的治疗中展现出良好的应用前景；本病例中该联合方案成功缓解了患者的临床症状与皮肤损害。我们认为该联合方案是一种有效的治疗选择。同时我们强调，即便患者初始诊断时的恶性肿瘤筛查结果为阴性且临床症状得到改善，仍需对其进行全面且持续的潜在恶性肿瘤筛查。