IgG4-related disease for the hematologist

Area of Science:

• Immunology
• Pathology
• Rheumatology

Background:

• Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition affecting multiple organs, notably hematopoietic and lymphoid tissues.
• Key diagnostic features include increased IgG4-positive plasma cells in tissues, elevated serum IgG and IgG4, storiform fibrosis, lymphoplasmacytic infiltrate, eosinophilia, and obliterative phlebitis.
• IgG4-RD can manifest as proliferative diseases (e.g., autoimmune pancreatitis) or fibrotic conditions (e.g., retroperitoneal fibrosis).

Purpose of the Study:

• To review the four main hematological manifestations of IgG4-RD: polyclonal hypergammaglobulinemia (PHGG), IgG4-positive plasma cell enriched lymphadenopathy (LAD), eosinophilia, and retroperitoneal fibrosis (RPF).
• To provide an organized approach for distinguishing IgG4-RD from its hematological mimics.
• To highlight the importance of accurate diagnosis for appropriate treatment strategies.

Main Methods:

• Review of literature focusing on the hematological manifestations of IgG4-RD.
• Analysis of key diagnostic criteria, including histological findings and serological markers.
• Comparison of IgG4-RD with its common hematological mimics such as Castleman disease, eosinophilic vasculitis, hypereosinophilic syndromes, and histiocyte disorders.

Main Results:

• PHGG, LAD, eosinophilia, and RPF are present in 70%, 60%, 40%, and 25% of IgG4-RD patients, respectively.
• These hematological features can also mimic IgG4-RD, presenting diagnostic challenges.
• An organized diagnostic approach is essential to differentiate IgG4-RD from conditions like Castleman disease and hypereosinophilic syndromes.

Conclusions:

• Hematological manifestations are common in IgG4-RD and can also mimic the disease, necessitating careful evaluation.
• Distinguishing IgG4-RD from its mimics is critical for guiding treatment decisions.
• Proliferative IgG4-RD forms respond well to immunosuppressive therapy, while fibrotic changes may be irreversible.