Cohen Philip R, Nikanjam Mina, Kato Shumei, Goodman Aaron M, Kurzrock Razelle
Dermatology, San Diego Family Dermatology, National City, USA.
Division of Hematology and Oncology, University of California San Diego, La Jolla, USA.
Cureus. 2020 Jul 2;12(7):e8967. doi: 10.7759/cureus.8967.
Castleman disease is a lymphoproliferative disorder characterized by atypical lymph node hyperplasia and systemic symptoms; it can also affect the skin and blood counts. The condition is categorized by the extent of involvement (unicentric or multicentric) and the observed lymph node pathology (hyaline-vascular, plasma cell or mixed cellularity). Pathogenesis also has a role in the classification and treatment of multicentric Castleman disease; this variant can either be related to the presence of human herpesvirus-8 (HHV-8) infection or associated with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins and skin changes) syndrome, or idiopathic. The principal cytokine responsible for causing idiopathic multicentric Castleman disease (IMCD) is interleukin-6 (IL-6). Therefore, treatment with agents that bind to IL-6 (such as siltuximab) or block the IL-6 receptor (such as tocilizumab) has been used. We report a woman with IMCD who was successfully being treated with siltuximab; her cutaneous manifestations and systemic disease (lung and lymph nodes) improved within three months. However, nine months after starting siltuximab, she developed a worsening cough and new infiltrates in the right lung on positron emission tomography/computed tomography (PET/CT) scan; there were no other constitutional symptoms such as fever, night sweats or fatigue. Differential diagnosis included Castleman disease recurrence, lung neoplasm and infection. Her pulmonary symptoms and infiltrates on scan resolved after treatment with systemic levofloxacin, indicating that she had an antibiotic-sensitive afebrile pneumonia. We postulate that her siltuximab therapy blocked the IL-6-associated fever and constitutional symptoms that normally are a hallmark of pneumonia. Therefore, patients who are receiving medications such as siltuximab and tocilizumab that block the IL-6 pathway and impair the acute phase inflammatory response may fail to manifest constitutional symptoms such as fever when infected.
卡斯特曼病是一种以非典型淋巴结增生和全身症状为特征的淋巴增殖性疾病；它也可影响皮肤和血细胞计数。该疾病根据受累范围（单中心或多中心）以及观察到的淋巴结病理（透明血管型、浆细胞型或混合细胞型）进行分类。发病机制在多中心卡斯特曼病的分类和治疗中也起作用；这种变体要么与人类疱疹病毒8型（HHV - 8）感染有关，要么与POEMS（多发性神经病变、器官肿大、内分泌病、单克隆蛋白和皮肤改变）综合征相关，或者是特发性的。导致特发性多中心卡斯特曼病（IMCD）的主要细胞因子是白细胞介素 - 6（IL - 6）。因此，已使用与IL - 6结合的药物（如西妥昔单抗）或阻断IL - 6受体的药物（如托珠单抗）进行治疗。我们报告了一名接受西妥昔单抗成功治疗的IMCD女性患者；她的皮肤表现和全身疾病（肺部和淋巴结）在三个月内得到改善。然而，在开始使用西妥昔单抗九个月后，她出现咳嗽加重，正电子发射断层扫描/计算机断层扫描（PET/CT）显示右肺有新的浸润影；没有发热、盗汗或疲劳等其他全身症状。鉴别诊断包括卡斯特曼病复发、肺部肿瘤和感染。经全身使用左氧氟沙星治疗后，她的肺部症状和扫描显示的浸润影消失，表明她患有对抗生素敏感的无热肺炎。我们推测，她的西妥昔单抗治疗阻断了通常是肺炎特征的与IL - 6相关的发热和全身症状。因此，接受阻断IL - 6途径并损害急性期炎症反应的药物（如西妥昔单抗和托珠单抗）治疗的患者在感染时可能不会出现发热等全身症状。
