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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    • "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.
    Journal of Clinical Medicine Research 08/2014; 6(4):295-8. DOI:10.14740/jocmr1845w
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    • "Hamano et al. [1] first reported the association of elevated serum immunoglobulin G4 (IgG4) levels in patients with autoimmune pancreatitis in 2001. A syndrome comprising, in addition to sclerosing pancreatitis, sclerosing sialadenitis and/or retroperitoneal fibrosis was subsequently described [2, 3]. Other clinical manifestations including autoimmune hepatitis [4], inflammatory pseudotumour [5], nonspecific interstitial pneumonia [6] and inflammatory abdominal aortic aneurysm [7] have also been linked with elevated serum levels of IgG4. "
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    ABSTRACT: BackgroundImmunoglobulin G4 (IgG4)-related sclerosing disease is a recently described clinicopathological entity with diverse manifestations including, amongst others, autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis and retroperitoneal fibrosis. Elevated serum IgG4 concentration has been described as the hallmark of this condition with reported good sensitivity and specificity.ObjectiveWe sought to establish the utility of serum IgG4 concentrations in the diagnosis of IgG4-related sclerosing disease by determining how many serum samples with elevated IgG4 from an unselected population would originate from patients who fulfilled criteria for this diagnosis.MethodsThe clinical features and laboratory characteristics of patients whose serum IgG4 concentration was greater than 1.30 g/L were analysed retrospectively from a total of 1,258 IgG subclass measurements performed in a tertiary hospital diagnostic laboratory.ResultsEighty patients (6.4%) had elevated IgG4 concentrations greater than 1.30 g/L. Nine of 61 patients had the diagnosis of IgG4-related sclerosing disease, giving a poor positive predictive value of 15%. The median serum IgG4 concentrations of those with and without IgG4-related sclerosing disease were 2.16 g/L and 1.86 g/L, respectively (p = 0.22).ConclusionSerum IgG4 concentration has poor positive predictive value in the diagnosis of IgG4-related sclerosing disease and, therefore, the clinical significance of elevated serum IgG4 concentration alone must be interpreted with caution.
    07/2014; 4(3):172-6. DOI:10.5415/apallergy.2014.4.3.172
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    • "Involvement of the heart in IgG4-related sclerosing disease is rare.3 The clinical presentation depends on the involved tissues; however, the histopathologic findings seem to be similar regardless of location.4 We report a case of IgG4-related sclerosing disease involving cardiac conduction system, that induced recurrent syncope in a middle aged female patient. "
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    ABSTRACT: A 55-year-old woman presented with frequent episodes of syncope due to sinus pauses. During ambulatory Holter monitoring, atrial fibrillation and first-degree atrioventricular nodal block were observed. Magnetic resonance imaging and CT scans showed a tumor-like mass from the superior vena cava to the right atrial septum. Open chest cardiac biopsy was performed. The tumor was composed of proliferating IgG4-positive plasma cells and lymphocytes with surrounding sclerosis. The patient was diagnosed with IgG4-related sclerosing disease. Because of frequent sinus pauses and syncope, a permanent pacemaker was implanted. The cardiac mass was inoperable, but it did not progress during the one-year follow-up.
    Yonsei medical journal 09/2013; 54(5):1285-8. DOI:10.3349/ymj.2013.54.5.1285 · 1.29 Impact Factor
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