Division of Hematology, Department of Medicine, University of British Columbia
Department of Pathology and Laboratory Medicine, St. Paul's Hospital.
Haematologica. 2019 Mar;104(3):444-455. doi: 10.3324/haematol.2018.205526. Epub 2019 Jan 31.
IgG4-related disease is a fibro-inflammatory condition that can affect nearly any organ system. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. This review focuses on the hematologic manifestations of IgG4-related disease, including lymphadenopathy, eosinophilia, and polyclonal hypergammaglobulinemia. The disease can easily be missed by unsuspecting hematologists, as patients may present with clinical problems that mimic disorders such as multicentric Castleman disease, lymphoma, plasma cell neoplasms and hypereosinophilic syndromes. When IgG4-related disease is suspected, serum protein electrophoresis and IgG subclasses are helpful as initial tests but a firm histological diagnosis is essential both to confirm the diagnosis and to rule out mimickers. The central histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells (with an IgG4/IgG ratio >40%), storiform fibrosis, and obliterative phlebitis. Importantly for hematologists, the latter two features are seen in all tissues except bone marrow and lymph nodes, making these two sites suboptimal for histological confirmation. Many patients follow an indolent course and respond well to treatment, but a significant proportion may have highly morbid or fatal complications such as periaortitis, severe retroperitoneal fibrosis or pachymeningitis. Corticosteroids are effective but cause new or worsening diabetes in about 40% of patients. Initial response rates to rituximab are high but durable remissions are rare. More intensive lymphoma chemotherapy regimens may be required in rare cases of severe, refractory disease, and targeted therapy against plasmablasts, IgE and other disease biomarkers warrant further exploration.
IgG4 相关疾病是一种纤维炎症性疾病，可影响几乎任何器官系统。常见表现包括大唾液腺和泪腺肿大、眼眶疾病、自身免疫性胰腺炎、腹膜后纤维化和肾小管间质性肾炎。本文重点介绍 IgG4 相关疾病的血液学表现，包括淋巴结病、嗜酸性粒细胞增多和多克隆高丙种球蛋白血症。由于患者可能出现类似于多种 Castleman 病、淋巴瘤、浆细胞瘤病和嗜酸性粒细胞增多综合征等疾病的临床问题，因此未被怀疑的血液科医生可能会轻易错过这种疾病。当怀疑 IgG4 相关疾病时，血清蛋白电泳和 IgG 亚类检查有助于作为初始检查，但明确的组织学诊断对于确诊和排除类似疾病都是必不可少的。中心组织病理学特征是密集的多克隆淋巴浆细胞浸润，富含 IgG4 阳性浆细胞（IgG4/IgG 比值>40%）、席纹状纤维化和闭塞性静脉炎。对血液科医生而言，重要的是后两种特征可见于除骨髓和淋巴结以外的所有组织，这使得这两个部位不适合进行组织学确认。许多患者呈惰性病程且对治疗反应良好，但相当一部分患者可能会出现严重的或致命的并发症，如大动脉炎、严重的腹膜后纤维化或硬脑膜炎。皮质类固醇有效，但约 40%的患者会出现新发或恶化的糖尿病。利妥昔单抗的初始缓解率较高，但缓解持久者罕见。在罕见的严重、难治性疾病中，可能需要更强化的淋巴瘤化疗方案，针对浆母细胞、IgE 和其他疾病生物标志物的靶向治疗值得进一步探索。
