IgG4-Related Disease: The Great Pretender

[Featured image of solid pseudopapillary tumor (SPT) of the pancreas.]

By Martina M. McGrath, MD
March 24, 2017

Retroperitoneal fibrosis, autoimmune pancreatitis, Reidel’s thyroiditis, sclerosing cholangitis and Mikulicz’s disease, sclerosing aortitis and periaortitis – what do all of these conditions have in common?

IgG4-related disease (IgG4-RD) is a chronic, fibro-inflammatory condition with a characteristic histological appearance including dense lymphoplasmacytic infiltration with large numbers of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis,and eosinophil infiltration. 1 It is now recognized as the cause of a large number of chronic inflammatory conditions, previously considered idiopathic, including those listed above. IgG4-RD is the most common cause of Type I autoimmune pancreatitis. 2

Contrary to most immune-mediated diseases, IgG4-RD is more common in men than women and most frequently presents after the age of 50. Almost any organ can be involved; including sinuses, lacrimal glands, pancreas, aorta, biliary tree, kidney, meninges, thyroid, and breast. Patients can present with a variety of clinical manifestations including end-organ dysfunction, signs of systemic inflammation such as lymphadenopathy, weight loss, or with masses/tumors of affected organs. Masses can occur in any affected organ but most frequently occur in the pancreas, lacrimal or salivary glands. It is estimated that 60-80% of patients have multi-organ involvement at the time of diagnosis.1 Up to 40% may have allergic conditions such as asthma or sinusitis. 3

Laboratory testing is frequently nonspecific. Only ~60% of patients have an elevated IgG4 level at the time of diagnosis. While this may fall in response to therapy, in a subset of patients IgG4 remains elevated despite successful treatment, rendering this an unreliable marker of treatment response. Hypocomplementemia and peripheral eosinophilia are also commonly seen at the time of diagnosis.

As the clinical presentation may be nonspecific, and there are no pathognomic laboratory tests abnormalities; histological examination of affected tissues is necessary to confirm the diagnosis. Specific histological criteria have been proposed for accurate diagnosis and the exact findings may vary slightly according to the organ involved. Masses are a common presenting feature of IgG4-RD, and lymphoma is often an important differential diagnosis. Therefore, accurate exclusion of underlying malignancy is a key concern in caring for these patients.

Glucocorticoids are first-line therapy, and many patients will rapidly respond to moderate-dose therapy, including with tumor shrinkage. In relapsing or refractory cases, rituximab has also been reported to be effective. 1 However, response to treatment is often dependent on initial histology, where those with prolonged history of disease and extensive fibrosis at the time of diagnosis likely to experience poorer treatment response.

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  1. Stone J, et al. IgG4-Related Disease. N Engl J Med 2012; 366:539-551
  2. Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003;38:982-984
  3. Kamisawa T, Anjiki H, Egawa N, Kubota N. Allergic manifestations in autoimmune pancreatitis. Eur J Gastroenterol Hepatol 2009;21:1136-1139

Headshot of Dr. McGrathDr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.

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