Drugs & Aging

, Volume 35, Issue 4, pp 275–287 | Cite as

IgG4-Related Disease: Beyond Glucocorticoids

  • Mitsuhiro Akiyama
  • Tsutomu Takeuchi
Review Article


IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission. However, the toxic effects of glucocorticoids are problematic because IgG4-related disease is more prevalent in patients above 60 years of age, a population with frequent comorbid conditions and polypharmacy. Immunosuppressants (cyclophosphamide, methotrexate, leflunomide, and tacrolimus) and targeted immunomodulators (rituximab, XmAb5871, and abatacept) are appealing to overcome potential toxic effects of glucocorticoids and as emerging glucocorticoid-sparing and/or maintenance treatments. In this review, we provide an overview of our understanding of the pathophysiology of the disease (T follicular helper cells, CD4+ cytotoxic T cells, plasmablasts, and alternatively activated M2 macrophages) and clinical characteristics, and highlight the potential targets for treatment intervention.


Compliance with Ethical Standards


No funding was received for the preparation of this article.

Conflict of interest

Mitsuhiro Akiyama has received consulting fees, speaking fees, and honoraria from Asahi Kasei Co., Cure Grades Co., and Eisai Co., Ltd, and a research grant from Mitsubishi Tanabe Pharma Co and Keio Medical Association. Tsutomu Takeuchi has received consulting fees, speaking fees and/or honoraria from Pfizer Japan, Mitsubishi Tanabe Pharma, Eisai, Astellas Pharma, and UCB (less than $10,000 each) and Chugai Pharmaceutical, Bristol-Myers K.K., Daiichi Sankyo, AbbVie, Janssen Pharmaceutical K.K., Pfizer Japan, Asahi Kasei Pharma, Takeda Pharmaceutical, AstraZeneca K.K., Eli Lilly Japan K.K., and Novartis Pharma K.K. (more than $10,000 each).


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan

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