IgG4-Related Lymphadenopathy

Abstract EN

Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease.

The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes.

Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder.

The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells (IgG4+/IgG+ plasma cell ratio >40%).

However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD.

Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone.

Laboratory analyses are crucial to differentiate between the 2 diseases.

Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia.

In contrast, IgG4-RD does not share any of these characteristics.

Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.