IgG4-related Orbital Inflammation Research Articles

IgG4-related orbital inflammation presenting as bilateral proptosis in a child

Sir, IgG4-related orbital disease is an immune-mediated fibro-inflammatory disease with systemic associations1, 2 and predominantly affects middle-aged and elderly patients,2 presentation of IgG4-related orbital disease in children is very rare.3, 4

IgG4-Related Orbital Inflammation Presenting as Unilateral Pseudotumor

IgG4 related systemic disease (IgG4-RSD) has been recognised in the last few years. Orbital pseudotumor as a presentation of IgG4-RSD is one of the rare complaints encountered in pediatric population. It is an inflammatory condition of unknown etiology characterized by tumorous swelling of the organs, characteristic histopathologic changes and elevated IgG4: IgG plasma cells ratio. The disease is also characterized by involvement of varied organ systems. The authors describe a seven-year-old boy with orbital pseudotumor after two years of initial onset with waxing and waning course, steroid responsive lesion and biopsy suggestive of IgG4-RSD involving the extraocular soft tissue. Treatment with oral corticosteroids and Azathioprine produced a significant decline in the pseudotumor size. It is important for pediatricians to be aware of this condition as appropriate recognition and management is important to prevent long-term damage of the tissue involved. This is the first case of IgG4 related orbital pseudotumor reported from India.

Clinicopathological features of IgG4-related disease complicated with orbital involvement

Objective. IgG4-related disease (IgG4-RD) is characterized by IgG4-positive plasmacytic infiltration and fibrosis in various organs. Orbital involvement in IgG4-RD includes lacrimal glands, extra-ocular muscles, trigeminal nerve and other parts of the orbit. Immunohistochemical staining is used to diagnose IgG4-RD in patients with orbital inflammation. The purpose of this retrospective study was to clarify the clinicopathological features of IgG4-RD complicated with orbital involvement.Methods. We examined the clinical features, pathological findings and response to treatment in nine patients with IgG4-RD who underwent orbital tissue biopsy between April 2010 and August 2012 at the University of Tsukuba Hospital.Results. Among the nine patients, eight had dacryoadenitis, one had infraorbital nerve swelling, and another one had IgG4-related orbital inflammation. Involvement of other organs was identified in all patients, including involvement of the salivary glands, lymph nodes, lung, kidney and para-aorta. In all patients, biopsy samples from orbital tissues showed lymphoplasmacytic infiltration and fibrosis, and IgG4-positive/IgG-positive plasmacyte ratio of > 40%. All patients were treated with prednisolone (0.6 mg/kg/day) and responded well in early phase, although relapse was noted in two patients following tapering of prednisolone, evident by swelling of lacrimal glands.Conclusion. Patients with IgG4-RD complicated with orbital involvement often present with involvement of other organs. The histopathological findings of orbital tissue match the characteristic features of IgG4-RD. Corticosteroid is effective for orbital and systemic involvement in IgG4-RD.

A prevalence study of IgG4-related ophthalmic disease in Japan

Immunoglobulin (Ig)G4-related ophthalmic disease belongs to a category of ocular adnexal lymphoproliferative disorders, the most frequent group of orbital tumors and simulating lesions. The aim of this study was to elucidate the number of IgG4-related diseases of orbital lymphoproliferative disorders and correlate ages and sex of such patients from 18 centers in Japan. One thousand and fourteen patients with orbital lymphoproliferative disorders were enrolled in this study. All had pathologically diagnosed lymphoproliferative disorders with surgical samples of ocular adnexal tissue. Patients with conjunctival lesions and intraocular lymphoma were excluded. Of the 1,014 cases of orbital lymphoproliferative disorders 404 (39.8%) had extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, 156 (15.4%) had other malignant lymphomas, 191 (18.8%) had non-IgG4 orbital inflammation, 219 (21.6%) had IgG4-related orbital inflammation, and 44 (4.3%) had IgG4-positive MALT lymphoma. Median age of the IgG4-related orbital inflammation group was 62years, which is significantly lower than that of the MALT lymphoma group (median 66years) and higher than the non-IgG4 orbital inflammation group (median 57years). The male/female ratio was 105/114 in the IgG4-related orbital inflammation group. Nearly a quarter of orbital lymphoproliferative disorders in Japan are related to IgG4.

IgG4-assoziierte orbitale Entzündungen

Serum immunoglobulin G4 (IgG4)-related systemic disease is a newly found entity and should be considered as a further differential diagnosis to the big pool of unspecific orbital inflammation. We describe clinical appearance and treatment options. We retrospectively analyzed all patients with the diagnosis IgG4-related orbital inflammation who were examined in our outpatient clinic. We compared symptoms, clinical and histological findings and therapy. In the last 17 months five patients were diagnosed with IgG4-related orbital disease. Biopsies were performed of most affected areas as seen in the computerised tomography scan. Histology revealed marked infiltration with IgG4-positive plasma cells. Serum IgG4-levels were partly significantly elevated. Based on these findings diagnosis of an IgG4-related disease was agreed and treatment with oral prednisone installed. In one patient a therapy with Rituximab was successfully started. Extended unspecific orbital inflammation, especially when bilateral and associated with systemic disease should be considered to be IgG4-related. Histological proof of IgG4-positive plasma cells and elevated IgG4 serum levels do confirm this diagnosis. Strict follow-up and interdisciplinary work-up is recommended.

Three cases of IgG4-related orbital inflammation presented as unilateral pseudotumor and review of the literature

IgG4-related disease is an emerging disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. In IgG4-related disease, tumor-like lesions develop in multiple organs, such as the lacrimal gland, salivary gland, lung, pancreas, kidney, and lymph nodes. We report here three cases of IgG4-related orbital inflammation that presented as unilateral pseudotumors. The patients all were men, with an age range of 65-75 years. The patients had been pointed out unilateral intra-orbital masses, and histopathological examinations revealed marked accumulation of IgG4-positive plasma cells (IgG4/IgG ratio: 51.1-71.6%) with fibrosis. But storiform fibrosis was seen in only one case, and no obliterative phlebitis was seen. The serum levels of IgG4 were increased to 178-670 mg/dL. The masses had well-defined homogeneous signal intensities, and they were hypo-intense on T1-weighted MR images and iso-intense on T2-weighted MR images. Gadolinium enhanced mass lesions in two cases. All orbital mass lesions responded well to corticosteroid treatment.

Serologic Factors in Early Relapse of IgG4-Related Orbital Inflammation After Steroid Treatment

To determine whether serologic factors correlate with early relapse in cases of IgG4-related orbital inflammation, a lymphoproliferative disorder. Retrospective cohort study. We examined the orbital images and serum data of 30 patients with (n=24) or without (n=6) corticosteroid treatment before and after corticosteroid treatment and 6months after discontinuation of corticosteroid treatment. Seven patients (23%) (all with corticosteroid treatment) had elevated serum levels of rheumatoid factor. Of the 24 patients with corticosteroid treatment, 24 (100%) showed regression of the lesion, but 8 of the24 (33%) showed relapse. The serum IgG4 levels before and after corticosteroid treatment were not significantly different between the relapsed and nonrelapsed groups (P=.5 and P=.2, respectively). However, the incidence of patients who were rheumatoid factor-positive was significantly higher in the relapsed group (P=.02). The 6 patients without corticosteroid treatment showed minor proliferation or regression of the lesion at the 6-month follow-up. The serum rheumatoid factor level may correlate with proliferative activity in IgG4-related orbital inflammation.

Clinical Aspects of IgG4-Related Orbital Inflammation in a Case Series of Ocular Adnexal Lymphoproliferative Disorders

The most frequent ocular adnexal tumors and simulating lesions are lymphoproliferative disorders (LPDs), including malignant lymphomas and orbital inflammation with lymphoid hyperplasia or infiltration. IgG4-related orbital inflammation (IgG4-ROI) often involves lacrimal glands and other orbital tissues and is an important differential diagnosis. The present study evaluated clinical aspects of IgG4-ROI in a case series of orbital LPD. Sixty-two consecutive cases of orbital LPD, pathologically diagnosed from November, 2004, through March, 2011, were investigated. Histological types were 22 cases with MALT lymphoma, 11 cases with diffuse large B-cell lymphoma (DLBCL), 3 cases with other malignant lymphomas, 16 cases with IgG4-ROI, and 10 cases with non-IgG4-ROI. Ages of the IgG4-ROI group (56 ± 10 yrs) were significantly lower than the MALT lymphoma (71 ± 12 yrs) and DLBCL (75 ± 14 yrs) groups. Orbital lesions other than lacrimal glands were present in six cases including extraocular muscle swelling, mass lesions surrounding the optic nerve, and supraorbital and infraorbital nerves enlargements. Although none of the malignant lymphomas were related to IgG4, previous evidence suggested that malignant lymphomas can arise from IgG4-ROI. Based on this study (26%) and another report (33%), it is likely that nearly a quarter of orbital LPD are IgG4-ROI.