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

UCL Centre for Nephrology, Royal Free Hospital, London NW3 2QG, UK.
BMC Medicine (Impact Factor: 7.25). 02/2006; 4(1):23. DOI: 10.1186/1741-7015-4-23
Source: PubMed


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. 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.
We 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.
Histology 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.
We 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.

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Available from: Manuel Rodriguez-Justo
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    • "Histological examination revealed a collagen-rich background and fibroblasts admixed with an inflammatory infiltrate consisting of lymphocytes, plasma cells, macrophages, and eosinophils[2]. RPF has many causes; however, in approximately 70% of cases, the cause is un- known[3]. Several reports have described the association between RPF and spondyloarthritis[4], whereas other types of arthritis appear to be rare. "
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    ABSTRACT: A 54-year-old male diagnosed with rheumatoid arthritis (RA) was effectively treated with methotrexate and adalimumab. He was admitted with fatigue and right lower back pain which had persisted for 1 month. An enhanced abdominal computed tomography scan showed an ill-defined mass with soft tissue attenuation surrounding the right common iliac artery involving the right middle portion of the ureter. Laparoscopic ureterolysis and biopsy were performed. Microscopic evaluation confirmed the presence of fibroblastic proliferation, with a pleomorphic inflammatory cell infiltrate consisting predominantly of lymphocytes, macrophages, and vascular endothelial cells, without granuloma or neoplastic cells. Therefore, our diagnosis was retroperitoneal fibrosis (RPF)-associated RA. Clinicians should consider the possibility of RPF in patients with RA who experience lower back pain, abdominal pain, or dysuria, and order suitable imaging studies.
    Full-text · Article · Jan 2015
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    • "Accumulating recent evidences revealed that similar pathological change also occurs in multiple organs, including the lungs [10] . Lung lesions in the IgG4-RD have been usually recognized for manifesting as interstitial pneumonia or inflammatory pseudo-tumor [2] [3] [4] . "

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    • "The disease can also be associated with mass-like lesions that may be mistaken for cancerous lesions [3]. Many organs can be involved by the disease such as the pancreas, biliary tract, salivary glands, lymph nodes, thyroid, kidneys, lung, skin, prostate and aorta [4]. Involvement of the upper gastrointestinal (GI) tract is rare and there has only been two case reports describing IgG4-related esophageal disease [5, 6]. "
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    ABSTRACT: IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform fibrosis and can be associated with tumefactive lesions. IgG4-related disease involving the upper gastrointestinal tract is rare and only two previous case reports have reported IgG4-related esophageal disease. We report the case of a 63-year-old female patient with a long-standing history of severe dysphagia and odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed endoscopic images consistent with esophagitis dissecans superficialis (sloughing esophagitis). An underlying autoimmune process was suspected and immunosuppressant agents were tried to control her disease. The patient eventually developed disabling dysphagia secondary to multiple chronic esophageal strictures. A diagnosis of IgG4-related disease was eventually made after reviewing esophageal biopsies and performing an immunohistochemical study with an anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. Our case report describes this unique case of IgG4-related esophageal disease presenting as chronic esophagitis dissecans with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease.
    Full-text · Article · Aug 2014 · Journal of Clinical Medicine Research
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