Hyper-IgG4 disease: report and characterisation of a new disease

Guy H Neild,John O Connolly,Manuel Rodriguez-Justo,Catherine Wall

doi:10.1186/1741-7015-4-23

Guy H Neild, John O Connolly + Show 2 more

Open Access

https://doi.org/10.1186/1741-7015-4-23

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Abstract

BackgroundWe highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis.MethodsWe report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis.ResultsHistology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment.ConclusionWe believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good.

Highlights

We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report
The principal synonyms that we found for these fibrosing conditions are: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis (Table 1)
We believe that hyper-IgG4 disease is an important condition to recognise as the diagnosis can be verified by histology and simple blood tests, and the outcome with treatment during the acute phase is very good

Summary

Introduction

We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. While investigating a patient who had an uncharacterised multisystem disease with evidence of a severe acute-phase response, we found that similar rare cases had been described, usually as single reports [1], under an alarming list of synonyms [2] (Table 1) These conditions are all characterised by chronic inflammation leading to dense fibrosis, and retroperitoneal fibrosis (RPF) is a typical example. We observed the rare behaviour of idiopathic RPF behaving like a tumour, in which the inflammatory mass was invading both the kidney and liver and presented as a progressive cholangitis This case was one of a series of patients seen in our gastroenterological department, who had sclerosing pancreatitis and chronic inflammation associated with immunoglobulin (Ig)G4expressing plasma cells [3,4]. In biopsies from both these cases, we found typical fibrosis with lymphoplasmacytic inflammation and IgG4-bearing plasma cells [5]

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