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

Published on Aug 1, 2009in Annals of the Rheumatic Diseases16.102
· DOI :10.1136/ARD.2008.089169
Yasufumi Masaki28
Estimated H-index: 28
(Kanazawa Medical University),
Lingli Dong16
Estimated H-index: 16
(Kanazawa Medical University)
+ 29 AuthorsHisanori Umehara43
Estimated H-index: 43
(Kanazawa Medical University)
Sources
Abstract
Background: Mikulicz’s disease (MD) has been considered as one manifestation of Sjogren’s syndrome (SS). Recently, it has also been considered as an IgG 4 -related disorder. Objective: To determine the differences between IgG 4 -related disorders including MD and SS. Methods: A study was undertaken to investigate patients with MD and IgG 4 -related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG 4 -positive multiorgan lymphoproliferative syndrome (IgG 4 +MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG 4 (>135 mg/dl) and infiltration of IgG 4 + plasma cells in the tissue (IgG 4 +/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG 4 +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 IgG 4 +MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG 2 , IgG 4 and IgE levels were significantly increased in IgG 4 +MOLPS. Histological specimens from patients with IgG 4 +MOLPS revealed marked IgG 4 + plasma cell infiltration. Many patients with IgG 4 +MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG 4 + cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG 4 +MOLPS treated with glucocorticoids showed marked clinical improvement. Conclusion: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG 4 +MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG 4 +MOLPS.
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Mikulicz's disease (MD) has been included within the diagnosis of primary Sjogren's syndrome (SS), but it represents a unique condition involving persistent enlargement of the lacrimal and salivary glands characterized by few autoimmune reactions and good responsiveness to glucocorticoids, leading to the recovery of gland function. Mikulicz's disease was recently reported to be associated with elevated immunoglobulin G4 (IgG4) concentrations in the serum and prominent infiltration of plasmacytes...
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