<h3>Background:</h3> Mikulicz’s disease (MD) has been considered as one manifestation of Sjögren’s syndrome (SS). Recently, it has also been considered as an IgG<sub>4</sub>-related disorder. <h3>Objective:</h3> To determine the differences between IgG<sub>4</sub>-related disorders including MD and SS. <h3>Methods:</h3> A study was undertaken to investigate patients with MD and IgG<sub>4</sub>-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG<sub>4</sub>-positive multiorgan lymphoproliferative syndrome (IgG<sub>4</sub>+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG<sub>4</sub> (&gt;135 mg/dl) and infiltration of IgG<sub>4</sub><sup>+</sup> plasma cells in the tissue (IgG<sub>4</sub>+/IgG+ plasma cells &gt;50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG<sub>4</sub>+MOLPS and 31 patients with typical SS were compared. <h3>Results:</h3> 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<sub>4</sub>+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG<sub>2</sub>, IgG<sub>4</sub> and IgE levels were significantly increased in IgG<sub>4</sub>+MOLPS. Histological specimens from patients with IgG<sub>4</sub>+MOLPS revealed marked IgG<sub>4</sub>+ plasma cell infiltration. Many patients with IgG<sub>4</sub>+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG<sub>4</sub>+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG<sub>4</sub>+MOLPS treated with glucocorticoids showed marked clinical improvement. <h3>Conclusion:</h3> Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG<sub>4</sub>+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG<sub>4</sub>+MOLPS.

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