IgG4‐related disease in patients with idiopathic orbital inflammation syndrome: data from the French SIOI prospective cohort

Abstract

Purpose To better characterize IgG4‐related disease (RD) in the setting of idiopathic orbital inflammation syndrome (IOIS). Methods National, multicentre, prospective, observational cohort study. Among the patients consecutively included in the French multicentre SIOI cohort, we selected those who underwent orbital and/or adnexal biopsy. Clinical, morphological and pathological findings at diagnosis were blindly analysed. Serum IgG4 levels at inclusion were measured and all available biopsy specimens were immunostained for IgG4 and IgG. Biopsy samples with more than 10 IgG4‐positive plasma cells per high‐power field and a IgG4+/IgG+ plasma cell ratio above 40% were scored as positive. IgG4‐positive patients were then screened for comprehensive diagnostic criteria for IgG4‐RD. Results Of the 87 patients included, 35 had histologically documented IOIS. Thirteen patients (37%) with a mean age at onset of 27 years (range 21–78) had IgG4‐positive biopsies, among which 10 patients (77%) and 3 (23%, with IgG4 serum levels >1.35 g/L) were considered as having probable and definite IgG4‐RD, respectively. The latter 13 patients more frequently fulfilled histological criteria for IgG4‐RD (including plasmacytic infiltrate (p = 0.006), fibrosis (p = 0.0025) and periphlebitis (p = 0.075)) than IgG4‐negative patients. Storiform fibrosis was exclusively found in orbital tissues from IgG4‐positive patients (n = 3, 23%). Eosinophilia associated with recurrent sinusitis or asthma was a prominent feature in patients with definite IgG4‐RD. Conclusions More than one‐third of patients with biopsy‐proven IOIS satisfied criteria for IgG4‐RD, but only a few had a definite type.

IgG4-related disease in patients with idiopathic orbital inflammation

“…We observed that bilateral ocular adnexal disease and an enlargement of the infraorbital nerve were more frequent in IgG4-RD than in non-IgG4-RD patients. In agreement with previous studies, IgG4-RD showed similarities with several of the clinical characteristics of IOI, which, in general, tends to affect men more than women [3,14,17]. Our study revealed that non-IgG4-RD patients were mostly female, which is similar to the findings in published studies [1,18].…”

“…Data were reviewed, including age, sex, affected eye, visual acuity (VA), signs and symptoms, the location and extent of the disease, radiologic data, histopathologic features, and treatment outcome. Blood eosinophilia was defined as a percentage of eosinophils > 10 [14].…”

Immunoglobulin G4-Related Orbital Disease with Bilateral Optic Perineuritis and Maxillary Nerves Involvement: A Case Report

“…Tiegs-Heiden et al reported that among the patients with IgG4-ROD in their study, sinusitis was present in 89% [10]. Eosinophilia associated with recurrent sinusitis or asthma has been found to be a prominent feature in patients with definite IgG4-RD [11]. The inflammatory mucosal thickening noted in the paranasal sinuses has an unknown association with IgG4-ROD, with a potential link between IgG4 positivity and Th2 immune response being one possibility presented [11].…”

“…Eosinophilia associated with recurrent sinusitis or asthma has been found to be a prominent feature in patients with definite IgG4-RD [11]. The inflammatory mucosal thickening noted in the paranasal sinuses has an unknown association with IgG4-ROD, with a potential link between IgG4 positivity and Th2 immune response being one possibility presented [11]. The presence of sinusitis may offer an additional clue when the diagnosis of IgG4-RD is considered.…”

Elevated Immunoglobulin G4 Levels in Patients with Thyroid Eye Disease and Their Clinical Implications

“…In fact, similar to our study, other studies have found that the serum level of IgG4 is often but not always elevated in patients with IgG4-RD, 26 approximately only two-thirds of patients with IgG4-RD have elevated serum IgG4 levels, 27 and only 23% of pathologically identified patients with IgG4-positive IgG4-RD had elevated serum IgG4 levels. 28 The relative dys-synchrony of serum and pathologic IgG4 may provide two possible explanations for the overabundance of IgG4 antibodies: tissue-destructive immunoglobulins and the response to an unknown primary inflammatory stimulus. 1 However, we found that patients with either histopathological or serum IgG4 positivity still presented a series of unique clinicopathologic features compared with IgG4-negative patients with TED, indicating a more active and severe subtype.…”