Unravelling IgG4-Related Disease: A Case of Systemic Inflammation and Autoimmune Overlap
5 affiliations
- 1Internal Medicine, Dubai Health Authority, Dubai, ARE
- 2Medicine, Dubai Health, Dubai, ARE
- 3Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, ARE
- 4Department of Clinical Sciences, Dubai Medical College for Girls, Dubai, ARE
- 5Internal Medicine, Dubai Hospital, Dubai Health, Dubai, ARE
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a rare, chronic, immune-mediated disorder characterized by fibroinflammatory changes and infiltration of IgG4-positive plasma cells; its clinical spectrum overlaps with malignancies, infections, and autoimmune conditions, often complicating diagnosis. We report a 47-year-old woman with a history of seronegative rheumatoid arthritis, antiphospholipid syndrome, and diabetes mellitus who presented with low-grade fever, left flank pain, and generalized lymphadenopathy. Laboratory findings revealed markedly elevated CRP and IgG4, and imaging demonstrated pulmonary infiltrates and widespread lymphadenopathy concerning for malignancy. Excisional lymph node biopsy showed plasma cell-rich hyperplasia with increased IgG4-positive plasma cells, and Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serologies suggested recent or reactivated infection. The patient was diagnosed with IgG4-RD and treated with corticosteroids followed by rituximab, resulting in clinical improvement. This case illustrates the diagnostic complexity of IgG4-RD in the presence of systemic inflammation, autoimmune background, and viral reactivation; its pathogenesis involves atypical immune regulation between B cells and CD4+ cytotoxic T cells that drives cytokine-mediated fibroblast activation, leading to storiform fibrosis and lymphoplasmacytic infiltration. EBV infection may have acted as a trigger for IgG4 class switching, though its role remains uncertain, and early histopathological confirmation with prompt treatment is critical to prevent irreversible organ damage. IgG4-RD should be considered in patients with unexplained systemic lymphadenopathy and elevated inflammatory markers after exclusion of infection and malignancy; a multidisciplinary approach is essential for diagnosis and management, and this case underscores the potential contribution of viral triggers, particularly EBV, warranting further research.
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BibTeX
@article{atef2026unravelling,
title = {{Unravelling IgG4-Related Disease: A Case of Systemic Inflammation and Autoimmune Overlap}},
author = {Radwa Atef and Ayesha Banu and Mohammad Kais A Jawish and Raabeah F Jafri and Namra F Jafri and Yazan Y Rabah and Leena Abdelrahman},
journal = {Cureus},
year = {2026},
month = oct,
doi = {10.7759/cureus.117463},
url = {https://doi.org/10.7759/cureus.117463},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unravelling IgG4-Related Disease: A Case of Systemic Inflammation and Autoimmune Overlap
AU - Radwa Atef
AU - Ayesha Banu
AU - Mohammad Kais A Jawish
AU - Raabeah F Jafri
AU - Namra F Jafri
AU - Yazan Y Rabah
AU - Leena Abdelrahman
PY - 2026
DA - 2026/10/05
JO - Cureus
DO - 10.7759/cureus.117463
UR - https://doi.org/10.7759/cureus.117463
AB - Immunoglobulin G4-related disease (IgG4-RD) is a rare, chronic, immune-mediated disorder characterized by fibroinflammatory changes and infiltration of IgG4-positive plasma cells; its clinical spectrum overlaps with malignancies, infections, and autoimmune conditions, often complicating diagnosis. We report a 47-year-old woman with a history of seronegative rheumatoid arthritis, antiphospholipid syndrome, and diabetes mellitus who presented with low-grade fever, left flank pain, and generalized lymphadenopathy. Laboratory findings revealed markedly elevated CRP and IgG4, and imaging demonstrated pulmonary infiltrates and widespread lymphadenopathy concerning for malignancy. Excisional lymph node biopsy showed plasma cell-rich hyperplasia with increased IgG4-positive plasma cells, and Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serologies suggested recent or reactivated infection. The patient was diagnosed with IgG4-RD and treated with corticosteroids followed by rituximab, resulting in clinical improvement. This case illustrates the diagnostic complexity of IgG4-RD in the presence of systemic inflammation, autoimmune background, and viral reactivation; its pathogenesis involves atypical immune regulation between B cells and CD4+ cytotoxic T cells that drives cytokine-mediated fibroblast activation, leading to storiform fibrosis and lymphoplasmacytic infiltration. EBV infection may have acted as a trigger for IgG4 class switching, though its role remains uncertain, and early histopathological confirmation with prompt treatment is critical to prevent irreversible organ damage. IgG4-RD should be considered in patients with unexplained systemic lymphadenopathy and elevated inflammatory markers after exclusion of infection and malignancy; a multidisciplinary approach is essential for diagnosis and management, and this case underscores the potential contribution of viral triggers, particularly EBV, warranting further research.
SN - 2168-8184
ER -