CLINICAL AND EPIDEMIOLOGICAL RESEARCH

Proposal for a new clinical entity, IgG₄-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG₄-related disorders

Y Masaki¹, L Dong^1,2, N Kurose³, K Kitagawa⁴, Y Morikawa⁵, M Yamamoto⁷, H Takahashi⁷, Y Shinomura⁷, K Imai⁸, T Saeki⁹, A Azumi¹⁰, S Nakada¹¹, E Sugiyama¹², S Matsui¹², T Origuchi¹³, S Nishiyama¹⁴, I Nishimori¹⁵, T Nojima³, K Yamada¹⁶, M Kawano¹⁶, Y Zen¹⁷, M Kaneko¹⁸, K Miyazaki¹⁹, K Tsubota²⁰, K Eguchi²¹, K Tomoda⁶, T Sawaki¹, T Kawanami¹, M Tanaka¹, T Fukushima¹, S Sugai¹, H Umehara¹

¹ Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan
² Department of Hematology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
³ Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
⁴ Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan
⁵ Department of Epidemiology and Public Health (School of Nursing), Kanazawa Medical University, Ishikawa, Japan
⁶ Department of Otolaryngology, Kanazawa Medical University, Ishikawa, Japan
⁷ First Department of Internal Medicine, Sapporo Medical University School of Medicine, Hokkaido, Japan
⁸ Sapporo Medical University, Hokkaido, Japan
⁹ Department of Internal Medicine, Nagaoka Red-Cross Hospital, Niigata, Japan
¹⁰ Department of Ophthalmology, Department of Surgery Related, Kobe University Graduate School of Medicine, Hyogo, Japan
¹¹ Department of Japanese Oriental Medicine, University of Toyama, Toyama, Japan
¹² First Department of Internal Medicine, University of Toyama, Toyama, Japan
¹³ Nagasaki Graduate School of Health Sciences, Nagasaki, Japan
¹⁴ Department of Internal Medicine, Kurashiki Medical Center, Okayama, Japan
¹⁵ Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
¹⁶ Division of Rheumatology, Department of Internal Medicine, Kanazawa University, Ishikawa, Japan
¹⁷ Department of Human Pathology, Kanazawa University, Ishikawa, Japan
¹⁸ Department of Internal Medicine, Uwajima Hospital, Ehime, Japan
¹⁹ Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan
²⁰ Department of Ophthalmology, Keio University, Tokyo, Japan
²¹ First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Dr Y Masaki, Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan; yasum{at}kanazawa-med.ac.jp

Background: Mikulicz’s disease (MD) has been considered as one manifestation of Sjögren’s syndrome (SS). Recently, it has also been considered as an IgG₄-related disorder.

Objective: To determine the differences between IgG₄-related disorders including MD and SS.

Methods: A study was undertaken to investigate patients with MD and IgG₄-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG₄-positive multiorgan lymphoproliferative syndrome (IgG₄+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG₄ (>135 mg/dl) and infiltration of IgG₄⁺ plasma cells in the tissue (IgG₄+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG₄+MOLPS and 31 patients with typical SS were compared.

Results: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG₄+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG₂, IgG₄ and IgE levels were significantly increased in IgG₄+MOLPS. Histological specimens from patients with IgG₄+MOLPS revealed marked IgG₄+ plasma cell infiltration. Many patients with IgG₄+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG₄+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG₄+MOLPS treated with glucocorticoids showed marked clinical improvement.

Conclusion: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG₄+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG₄+MOLPS.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?