IgG4-related disease: A relatively new concept for clinicians

Abstract

IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy.The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression.About 30-50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a "capsule-like rim" surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD.This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD. 3Highlights Ø IgG4-related disease is a chronic fibrotic inflammation.Ø The disease affects multiple organs, is progressive, and impairs function.Ø The disorder has an allergic background and is immune-mediated.Ø Compatible clinical signs and typical pathology are the basis for the diagnosis.Ø Glucocorticoids and/or B-cell depletion induces prompt clinical response.Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibrotic inflammation, characterized by tissue infiltration by lymphocytes, IgG4-positive plasma cells, simultaneous development of fibrosis, and often, but not always, elevated serum levels of IgG4 (1, 2). The disease can affect multiple organs. Early diagnosis of IgG4-RD is not easy because of the indolent course of the disease with vague, nonspecific symptoms. It may first come to clinical attention as visible organ swelling or detected organ dysfunction due to fibrosis, or is identified incidentally by imaging and specific biopsy when the patient undergoes investigation of suspected tumor disease. Most forms of organ involvement in IgG4-RD, even in the advanced fibrotic stages, respond well to glucocorticoids (3, 4). 4A comprehensive search for all articles in E...

An Unexpected IgG4-Related Enteropathy Masquerading as a Stricturing Malignancy

“…2 A definitive diagnosis requires 2 out of 3 histologic criteria to be met, and there are differing opinions regarding whether an IgG4 to IgG plasma cell ratio greater than 0.4 is supportive of the diagnosis or mandatory for the diagnosis. 1,2 This IgG4 related enteropathy presentation continues the trend of being suspicious for a malignant process given the rarity of IgG4 related enteropathy involving the bowel wall. Clinicians rarely encounter this disease, so it remains low on the differential diagnosis.…”

“…2 A cutoff of more than 50 per high power field is highly specific, but different values are proposed for different tissues and surgical specimens. 2 A definitive diagnosis requires 2 out of 3 histologic criteria to be met, and there are differing opinions regarding whether an IgG4 to IgG plasma cell ratio greater than 0.4 is supportive of the diagnosis or mandatory for the diagnosis. 1,2 This IgG4 related enteropathy presentation continues the trend of being suspicious for a malignant process given the rarity of IgG4 related enteropathy involving the bowel wall.…”

IgG4-related disease presenting with headache and papilloedema

“…The patient improved with spinal taps evacuation and methylprednisolone treatment. Intracranial hypertrophic pachymeningitis is a severe and rare manifestation in the spectrum of IgG4-related diseases 1 2. Biopsy of meninges is the gold standard for the diagnosis 3.…”

“…Biopsy of meninges is the gold standard for the diagnosis 3. Exclusion of systemic inflammatory disorders and demonstration elevated serum IgG4 can support the diagnosis in patients with typical diffuse dural thickening 1 3. The disease responds to immunosuppressive drugs such as corticosteroids, methotrexate, azathioprine, mycophenolate or cyclophosphamide 1 2.…”

Diseases of the Pancreas

“…The most common form, type 1 AIP, is associated with IgG4-related diseases. Type 2 AIP is a different, even rarer entity and may be associated to chronic inflammatory bowel disease [31,32]. Both diseases have a similar clinical presentation with unspecific upper abdominal pain, obstructive jaundice, furthermore weight loss, and endo-and/or exocrine pancreatic insufficiency.…”