Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders
- Y Masaki1,
- L Dong1,2,
- 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
- 1Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan
- 2Department of Hematology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
- 3Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
- 4Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan
- 5Department of Epidemiology and Public Health (School of Nursing), Kanazawa Medical University, Ishikawa, Japan
- 6Department of Otolaryngology, Kanazawa Medical University, Ishikawa, Japan
- 7First Department of Internal Medicine, Sapporo Medical University School of Medicine, Hokkaido, Japan
- 8Sapporo Medical University, Hokkaido, Japan
- 9Department of Internal Medicine, Nagaoka Red-Cross Hospital, Niigata, Japan
- 10Department of Ophthalmology, Department of Surgery Related, Kobe University Graduate School of Medicine, Hyogo, Japan
- 11Department of Japanese Oriental Medicine, University of Toyama, Toyama, Japan
- 12First Department of Internal Medicine, University of Toyama, Toyama, Japan
- 13Nagasaki Graduate School of Health Sciences, Nagasaki, Japan
- 14Department of Internal Medicine, Kurashiki Medical Center, Okayama, Japan
- 15Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
- 16Division of Rheumatology, Department of Internal Medicine, Kanazawa University, Ishikawa, Japan
- 17Department of Human Pathology, Kanazawa University, Ishikawa, Japan
- 18Department of Internal Medicine, Uwajima Hospital, Ehime, Japan
- 19Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan
- 20Department of Ophthalmology, Keio University, Tokyo, Japan
- 21First 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;
- Accepted 26 July 2008
- Published Online First 13 August 2008
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.
Competing interests: None.
Patient consent: Obtained.
Ethics approval: The study was approved by the review board of Kanazawa Medical University and those of each collaborating institute. All data and samples from patients were collected with their informed consent.
▸ Additional data are published online only at http://ard.bmj.com/content/vol68/issue8