Sina Sokol, Bonisoli Giulio Luigi, Vitale Sofia, Marzano Luigi, Crinò Stefano Francesco, Conti Bellocchi Maria Cristina, Boninsegna Sara, Conci Simone, Maiolini Federica, Nocini Riccardo, Sacchetto Luca, Barbera Giorgio, Fior Andrea, Kalaja Nikela, Malloggi Elena, Brighenti Antonietta, Parisi Alice, Cardobi Nicolò, Scarpa Aldo, Friso Simonetta, Tinazzi Elisa
Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
Section of Internal Medicine B, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
Diagnostics (Basel). 2025 Sep 10;15(18):2299. doi: 10.3390/diagnostics15182299.
IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Classic forms, such as pancreaticobiliary or retroperitoneal involvement, are often recognized early, whereas atypical manifestations mimic malignancy or inflammatory conditions, leading to delayed or inappropriate treatment. : A 30-year-old man presented with hyperemesis, proptosis, and gait instability. He was found to have colonic stenosis, stomach thickening, pachymeningitis, and polyserositis. Gastroenteric histology and serology confirmed IgG4-RD. Steroids were ineffective, but rituximab produced sustained clinical and radiologic improvement. A 35-year-old woman developed jaundice and cholestasis with a perihilar mass highly suggestive of cholangiocarcinoma. Histopathology revealed IgG4-RD, and rituximab therapy led to marked clinical and serological improvement. A 64-year-old woman with a submandibular mass underwent sialoadenectomy, with histology confirming IgG4-RD; she remained asymptomatic without systemic treatment. : A literature review highlighted the diagnostic challenges of atypical IgG4-RD. Gastrointestinal involvement is rare and often misclassified as inflammatory bowel disease. Isolated biliary disease frequently mimics cholangiocarcinoma, while salivary gland involvement may be misdiagnosed as neoplasia. Serum IgG4 levels >135 mg/dL and IgG4/IgG ratio >0.21 may support clinical suspicion, but histopathology remains indispensable for definitive diagnosis and for excluding malignancy. Steroid responsiveness is a hallmark, though relapses after tapering are common, often necessitating B-cell-directed therapy. : IgG4-RD should be considered in patients with unexplained, relapsing, or steroid-responsive conditions. Early recognition, multidisciplinary collaboration, and integration of histopathology with clinical features are essential to avoid misdiagnosis and optimize management.
IgG4相关性疾病（IgG4-RD）是一种慢性免疫介导的纤维炎性疾病，其特征为富含IgG4阳性浆细胞的淋巴浆细胞浸润、席纹状纤维化，且血清IgG4水平常升高。胰腺胆管或腹膜后受累等典型形式通常能早期识别，而非典型表现则类似恶性肿瘤或炎症性疾病，导致治疗延迟或不当。一名30岁男性出现剧烈呕吐、眼球突出和步态不稳。他被发现患有结肠狭窄、胃增厚、硬脑膜炎和多浆膜炎。胃肠组织学和血清学检查确诊为IgG4-RD。类固醇治疗无效，但利妥昔单抗使临床和影像学得到持续改善。一名35岁女性出现黄疸和胆汁淤积，肝门周围有一肿块，高度提示胆管癌。组织病理学显示为IgG4-RD，利妥昔单抗治疗使临床和血清学得到显著改善。一名64岁女性因下颌下肿块接受了涎腺切除术，组织学检查确诊为IgG4-RD；未经全身治疗，她仍无症状。文献综述强调了非典型IgG4-RD的诊断挑战。胃肠道受累罕见，常被误诊为炎症性肠病。孤立性胆管疾病常类似胆管癌，而涎腺受累可能被误诊为肿瘤。血清IgG4水平>135mg/dL且IgG4/IgG比值>0.21可能支持临床怀疑，但组织病理学对于明确诊断和排除恶性肿瘤仍然不可或缺。类固醇反应性是一个标志，尽管减量后复发很常见，通常需要进行B细胞靶向治疗。对于患有无法解释的、复发性或类固醇反应性疾病的患者，应考虑IgG4-RD。早期识别、多学科协作以及将组织病理学与临床特征相结合对于避免误诊和优化管理至关重要。
