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

Abstract

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.