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）被归类为一种罕见的非朗格汉斯细胞组织细胞增生症（non-Langerhans cell histiocytosis），好发于40~50岁年龄段的女性群体。该全身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患者体内发现各类潜在恶性肿瘤，包括乳腺、胃、胸腺、肝脏来源的恶性肿瘤以及黑色素瘤；此前仅报道过1例合并肾细胞癌的MRH患者病例。目前文献中尚未确立公认的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增添了难度。本文报告1例存在广泛关节与皮肤受累的MRH患者，该患者接受英夫利昔单抗联合甲氨蝶呤治疗后获得了临床症状改善，后续被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，加之二者不良反应谱较低，在MRH治疗中展现出良好的应用前景；本例患者经该方案治疗后症状与皮肤表现均得到缓解。我们认为此联合疗法是一种有效的治疗方案。我们强调，即便患者初始诊断时临床症状有所改善、或恶性肿瘤筛查结果为阴性，也应针对MRH相关的潜在恶性肿瘤开展全面且持续的筛查。