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

Ann Rheum Dis. 2009 Aug;68(8):1310-5. doi: 10.1136/ard.2008.089169. Epub 2008 Aug 13.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Diagnosis, Differential
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulin G / analysis*
  • Lacrimal Apparatus / pathology
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / drug therapy
  • Lymphoproliferative Disorders / immunology*
  • Lymphoproliferative Disorders / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mikulicz' Disease / diagnosis
  • Mikulicz' Disease / drug therapy
  • Mikulicz' Disease / immunology*
  • Mikulicz' Disease / pathology
  • Prednisolone / therapeutic use
  • Retrospective Studies
  • Salivary Glands, Minor / pathology
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology
  • Syndrome
  • Young Adult

Substances

  • Glucocorticoids
  • Immunoglobulin G
  • Prednisolone