Background/Purpose: IgG4-related disease is a recently described systemic inflammatory and fibrosing condition that may mimic various other systemic rheumatic diseases. We studied the occurrence of IgG4-related disease over a one year period at a university hospital serving a population of 1.5 million, and assessed the diagnostic significance of a serum IgG4 concentration higher than the upper level of the reference interval.

Methods: Files were scrutinized for a diagnosis of IgG4-related disease over a one year period (May 2010 to May 2011). The diagnosis rested on the combination of a clinical picture consistent with IgG4-related disease and histopathological features showing a characteristic appearance with a dense lymphoplasmacytic infiltration, a pattern of fibrosis, and variable numbers of IgG4 positive plasma cells. In addition, the files of all patients with a serum IgG4 concentration higher than 1.40 g/l, determined for various reasons during the same time period, were examined and the diagnoses were recorded. IgG subclasses in serum were analysed with a BN II nephelometer using N AS IgG1, N AS IgG2, N Latex IgG3, and N Latex IgG4 reagents (Siemens, Marburg, Germany). The reference interval for IgG4 at our laboratory is 0.08–1.4 g/l.

Results: 14 patients (12 men and 2 women, mean age 61 years, range 40–78 years) were diagnosed with IgG4-related disease during the one-year study period. In 3 patients the disease was confined to a single organ, whereas the other 11 had multiorgan involvement. The presenting features and major manifestations were autoimmune pancreatitis in 10, autoimmune cholangitis in 10, Mikulicz disease in 3, Riedel’s thyroiditis in 2, retroperitoneal fibrosis in 1, and mediastinal fibrosis in 1. Three had a diagnosis of bronchial asthma. Median serum IgG4 concentration at diagnosis was 7.75 g/l with a range of 1.66–18.20 g/l. No patients with a diagnosis of IgG4-related disease and normal serum IgG4 concentrations were identified. Major diagnoses suspected at referral included pancreatic carcinoma, liver disease, primary Sjögren’s syndrome, sarcoidosis, lymphoma, and vasculitis. Over the same time period no less than 238 additional patients with a serum IgG4 concentration higher than 1.40 g/l (median 2.22 g/l, range 1.41–11.50 g/l) were recorded. The most common diagnoses among these patients were bronchial asthma, chronic sinusitis and various allergic conditions, but high values were observed in a wide range of other diseases including sclerosing cholangitis, inflammatory bowel disease, and vasculitis.

Conclusion: We confirmed previous observations that IgG4-related disease occurs predominantly in middle aged or elderly men. Awareness of this newly recognized condition is essential since it constitutes a major differential diagnosis against various systemic inflammatory diseases and other diseases including lymphoma and other neoplasia. In our series a high serum IgG4 concentration was a regular finding among patients with IgG4-related disease. However, serum IgG4 concentrations higher than normal also occurred in a great variety of other diseases.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/spectrum-of-igg4-related-disease-and-diagnostic-value-of-serum-igg4-determinations/