Ophthalmic manifestations of IgG4-related disease: single-center experience and literature review

Semin Arthritis Rheum. 2014 Jun;43(6):806-17. doi: 10.1016/j.semarthrit.2013.11.008. Epub 2013 Nov 15.


Objectives: IgG4-related disease (IgG4-RD) is an inflammatory disorder responsible for fibrosing, tumefactive lesions that can involve the lacrimal gland as well as the extraocular muscles, orbital soft tissues, sclera, and local nerves. We reviewed IgG4-related ophthalmic disease (IgG4-ROD), including the natural history, pathology, and treatment, based on our center's experience and that reported in the literature.

Methods: We identified 27 patients with orbital manifestations from our IgG4-RD registry; six were excluded because no pathology was available for review. All 21 cases included had histopathologically confirmed diagnoses of IgG4-RD, 11 of which were of the orbital tissue. Other data were obtained by a retrospective medical records review. MEDLINE and PubMed literature searches in English were conducted to identify articles for a literature review on the topic.

Results: Patients with IgG4-ROD were predominantly male (57%) and had an average age at symptom onset of 50 years (range: 21-79 years). The lacrimal gland was the most commonly involved structure (62%). Most patients (71%) had bilateral disease and extra-orbital involvement (71%); these patients also had elevated serum IgG4 concentrations compared to those with unilateral disease and no extra-orbital disease. Ten patients improved following rituximab treatment.

Conclusions: Ophthalmic involvement is a common manifestation of IgG4-RD and can affect nearly every orbital structure. Consideration of IgG4-RD and accurate diagnosis by biopsy have important implications for prognosis and treatment following the distinction of this condition from the Sjögren syndrome (SjS), granulomatosis with polyangiitis (GPA, formerly Wegener's), sarcoidosis, lymphoma, infection, and other disorders. Rituximab holds promise as an effective steroid-sparing agent or therapy for steroid-resistant cases.

Keywords: Dacryoadenitis; Idiopathic inflammation; IgG4-related disease; Myositis; Orbital pseudotumor; Rituximab.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Cohort Studies
  • Dacryocystitis / etiology
  • Dacryocystitis / immunology
  • Eye Diseases / drug therapy
  • Eye Diseases / etiology
  • Eye Diseases / immunology*
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Immunologic Factors / therapeutic use
  • Male
  • Middle Aged
  • Orbital Myositis / etiology
  • Orbital Myositis / immunology
  • Orbital Pseudotumor / etiology
  • Orbital Pseudotumor / immunology
  • Rituximab
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin G
  • Immunologic Factors
  • Rituximab