Background IgG4 related disease (IgG4RD) is a multi-organ affecting disease characterized by fibro-sclerosing lesions with IgG4+ cell infiltration. Serum IgG4 elevation is a critical clue for diagnosis of IgG4RD. However, there are patients of non-IgG4RDs whose IgG4 levels are elevated. Clinical features of these patients have not been fully elucidated.
Objectives To clarify clinical features of patients with serumIgG4 elevation, particularly, to determine whether IgG4 RD is a distinctive disease in patients with IgG4 elevation and whether there is a subset of non-IgG4RDs which have strong similarity to IgG4RD.
Methods For determination of the prevalence of patients with serum IgG4 elevation, consecutive 185 patients who admitted our department during 2 months were enrolled. For clarification of clinical features of patients with IgG4 elevation (IgG4>135mg/dl), 68 cases with IgG4 elevation were selected from consecutive 350 patients receiving IgG4 test in clinical practice at our hospital and their medical records were reviewed retrospectively. IgG4RD was diagnosed by comprehensive diagnostic criteria for IgG4-related disease (Mod Rheumatol.22:21-30; 2012). Cluster analysis according to organ involvements was performed through Ward's method.
Results Prevalence of serum IgG4 elevation in general inpatients was 9/1850 (4.9%). Only 1 of 9 was IgG4RD. Among 68 cases with IgG4 elevation who received IgG4 test in clinical practice, IgG4RD was 41%. Cluster analysis according to organ involvements revealed 5 clusters; cluster1: multiple sclerosing lesions with salivary, orbital and retroperitoneal lesions, 2: sclerosing lesions with autoimmune pancreatitis, 3: pulmonary inflammation, 4 varieties of inflammatory diseases including connective tissue diseases, and 5: pleuritis. Cluster 1 and 2 were divided from other ones at 1st node. IgG4RD existed only cluster 1 and 2.
In addition to sclerosing lesions, non-sclerosing lesions were found in 13% of cluster 1, 43% of cluster 2, 33% of IgG4RD and 70% of non-IgG4RDs. Non-sclerosing lesions were developed as organ limited inflammation in most cases of IgG4RD and non-IgG4RDs, which was contrast to sclerosing lesions in IgG4RD affecting multi-organs.
Among non-sclerosing lesions, IgG4+ cells were observed. Pathological examination of non-sclerosing lesions revealed IgG4+ cell inflammation in 4/5 in IgG4RD and 8/21 in I non-IgG4RDs. The lesions in non-IgG4RDs were indistinguishable from those in IgG4RD. Patients of non-IgG4RDs with IgG4+ cells had similar clinical features to IgG4RD including high IgG4 levels, low CRP levels and good response to glucocorticoid in addition to pathological findings.
Conclusions IgG4RD is a minor, but a distinctive disease in patients with serum IgG4elevation, characterized by sclerosing lesions affecting multiple organs. IgG4RD causes non-sclerosing lesions with IgG4+ cells as well as sclerosing ones. Among non-IgG4RDs, there are patients with IgG4 + non-sclerosing lesions indistinguishable from those of IgG4RD and they had similar clinical features to IgG4RD. It might be necessary to provide a position to these cases in “the extended spectrum of IgG4RD” defined as having IgG4+ cell inflammation and serum IgG4 elevation.
Disclosure of Interest : None declared
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