A 74yearold male complained of dysphagia and abdominal pain. This igg4related sclerosing cholangitis is the most common extrapancreatic manifestation of type 1 aip igg4related, present in over 70 percent of such patients 4. Igg4related sclerosing cholangitis a form of sclerosing cholangitis that is clinically distinct from primary sclerosing cholangitis may occur as part of the igg4rd. Rd, a systemic fibroinflammatory condition that is characterized by mass lesions andor strictures with classical histopathological findings in involved organs. Consensus statement on the pathology of igg4 related disease. The disease is characterized by dense bile duct infiltration by igg4 positive plasma cells resulting in extensive fibrosis. However, to our knowledge, there has been only one reported case of igg4 related sclerosing disease that man. Case 1 uterine adenosarcoma with sarcomatous overgrowth had the highest igg4 positivity and igg. Presents a comprehensive overview of research on bile duct pathology, from basic understanding to practical aspects.
Igg4related systemic sclerosing disease of the ocular adnexa. However, a recent consensus statement on the pathology of igg4 rd 9 has recognized that a large number of conditions that are outside the igg4 rd spectrum. Consensus statement on the pathology of igg4related disease. Igg4 related sclerosing sialadenitis a retrospective analysis. Igg4 related diseases, but few criteria are known for igg4 related thyroiditis since few such patients have been identi. Keywords igg4 related sclerosing disease igg4 related pachymeningitis nonvasculitic autoimmune in.
A novel clinical entity, igg4related disease igg4rd. The pathology is very specific and looks similar in all organs. Igg4related dacryoadenitis and sialadenitis rare disease. Membranous glomerulopathy can be a manifestation of igg4 related renal disease. Recognition and management of common, rare, and novel serum protein. The same policy has been also adopted in the consensus statement on the pathology of igg4 related disease 3. It is a separate entity to primary sclerosing cholangitis pathology. Endoscopic retrograde cholangiography and magnetic resonance cholangiography. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung and prostate, in which tissue fibrosis with obliterative phlebitis is pathologically induced table table1. Igg4related sclerosing disease has been described in the orbit and. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung and prostate, in which tissue fibrosis with obliterative.
The histopathology of igg4related disease springerlink. The classic igg4 rd patient is a middleaged to elderly individual. American journal of clinical pathology, volume 7, issue 5, may 2012. Gastric mass gastritis and gastric ulcers can be associated with igg4 related sclerosing disease and aip 11, 12. Sclerosing peritonitis associated with gynecological. Idiopathic retroperitoneal fibrosis ormond disease. Igg4related disease igg4rd is a systemic autoimmune fibroinflammatory. Igg4 related disease is now considered a systemic disease that might affect every organ with progressively growing. Although possibly based on opinion rather than on objective assessments, symptoms, if any, are commonly described as mild in the medical literature. People are often described as being generally well at the time of diagnosis, although some may give a history of. Atypical manifestations of igg4related sclerosing disease. Consequently, th2 pathways are no longer believed to be central to disease pathophysiology. It is a chronic, systemic, inflammatory condition of unknown etiology.
Igg4 related sclerosing disease igg4 related systemic sclerosing disease. Igg4related disease is a recently recognized systemic syndrome characterized by massforming lesions with lymphoplasmacytic infiltration, increase in the number of igg4. Igg4 related disease igg4 rd is a rare fibroinflammatory condition that can affect almost any organ, characterized by swollen lesions and often by eosinophilia and elevated serum igg4 concentrations. Click on the link to view a sample search on this topic. Igg4related disease is a newlydescribed rare syndrome consisting of many disease entities. Igg4related disease is a protean condition that mimics many malignant, infectious, and inflammatory disorders. Masaki y, et al a novel clinical entity, igg4related disease igg4rd. Igg4related sclerosing disease, also known as igg4 related systemic disease igg4 rsd, hyper igg4 disease and igg4 related disease is an autoimmune disease in which inflammatory cells cause fibrosis, the deposition of connective tissue, in one or more organs.
Igg4 related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to massforming lesions in different organs. Igg4related sclerosing cholangitis radiology reference. The criteria for a diagnosis of igg4 related sclerosing disease of the orbit have not been well established. Although autoimmune pancreatitis is present in most patients with igg4related sclerosing disease, the latter has been reported in patients with no pancreatic involvement 20,28. Patients with igg4 related sclerosing disease usually demonstrate a dramatic response to corticosteroid therapy, often within a few weeks, although spontaneous resolution may occur 3,29,30. Pubmed is a searchable database of medical literature and lists journal articles that discuss igg4related dacryoadenitis and sialadenitis. Described initially as a form of sclerosing autoimmune pancreatitis now designated as type i autoimmune pancreatitis. Necrosis, discrete granulomata, and xanthogranulomatous changes are atypical and, when present, suggest other diagnoses.
Igg4related disease igg4 rd is a multiorgan fibroinflammatory condition of unknown aetiology that is defined by its unique histopathological features, that are fairly similar regardless of the affected organ. This book is distributed under the terms of the creative commons attribution 4. Suggested diagnostic criteria for igg4 related ht include. Requires additional clinical, serological or radiological evidence to confirm the diagnosis of igg4 related disease. Diagnostic guidelines for igg4related disease with a focus on. Biopsy diagnosis of type 1 autoimmune pancreatitis.
Discrepancies, if any, must be resolved in an interdisciplinary setting and with further evaluation, including a rebiopsy if necessary. The distinction between aip and pancreas cancer is vital, but is hard to make in some cases, for example in lesions with focal pancreatic enlargement andor negative serological tests. Igg4related disease igg4 rd, formerly known as igg4 related systemic disease, is a chronic inflammatory condition characterized by tissue infiltration with lymphocytes and igg4 secreting plasma cells, various degrees of fibrosis scarring and a usually prompt response to oral steroids. Immunoglobulin g4 igg4 related disease igg4 rd is an immunemediated condition that can affect almost any organ. Pseudotumor formation is the most common and characteristic clinical symptom. Igg4 related sclerosing disease is a syndrome affecting various sites with elevated serum. Described initially as a form of sclerosing autoimmune pancreatitis now.
The exact etiology of igg4related disease remains unclear with no known role of the igg4 molecule itself being identified. The histopathology of igg4related disease was a specific focus of the. Relatively rare in occurrence, this condition is benign, but presents as hard, indurated and enlarged masses that are clinically indistinguishable from salivary gland neoplasms or tumors. Igg4 rd is a fascinating clinical entity including a wide variety of diseases, formerly diagnosed as mikuliczs disease, autoimmune pancreatitis aip, interstitial nephritis, prostatitis and retroperitoneal fibrosis. Igg4 ratio of approximately 5% with moderate intensity staining while the other cases were 01% and weak to negative. Diagnostic guidelines for igg4related disease with a. In approximately 5170% of people with this disease, serum igg4 concentrations are elevated during an. It was first described as a systemic condition in 2003 when extrapancreatic manifestations were identified in patients with autoimmune. When igg4related disease is suspected, serum protein electrophoresis and igg. The contributing authors extensively discuss the topic from different perspectives, including the pathogenesis of conditions such as cellular senescence and innate immunity as well as diseases such as igg4 related sclerosing cholangitis and intraductal papillary neoplasm. Pulmonary manifestations of immunoglobulin g4related.
Igg4 associated disease is a relatively newly discovered entity characterized by sclerosing inflammation, a lymphoplasmacytic infiltration full of igg4 positive plasma cells and frequently associated with elevated serum igg4 concentrations. The purpose of this article is to present the pathologic and clinical features of igg4 related sclerosing cholangitis isc, illustrate the associated imaging findings, and discuss treatment of the disorder. An elevated serum titer of immunoglobulin g4 igg4, the least common 3% to 6% of the 4 subclasses of igg, is a surrogate marker for the recently characterized igg4 related sclerosing disease. Seminars in diagnostic pathology the pathology of igg4 related. Pathology of the bile duct yasuni nakanuma springer. Immunoglobulin igg4 related sclerosing disease isd also called igg4 related systemic disease, igg4 related disease or hyper igg4 disease is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of igg4. Increasing evidence suggests that igg4 rd is an autoimmune condition, much like rheumatoid arthritis and lupus. This multiorgan immunemediated condition links many disorders previously regarded as isolated, singleorgan diseases without any known underlying systemic condition.
Igg4related disease is a multiorgan immunemediated chronic fibroinflammatory condition characterized by elevated serum igg4 concentrations, tumefaction, and tissue infiltration by igg4 positive plasma cells. Patients with igg4related sclerosing disease usually demonstrate a dramatic response to corticosteroid therapy, often within a few weeks, although spontaneous resolution may occur 3,29,30. Igg4 related chronic sclerosing sialadenitis patients may show an elevated serum igg4 levels. Orphanet is a european reference portal for information on rare diseases and orphan drugs. Igg4related disease has been described as an indolent condition. Identification of a novel antibody associated with autoimmune pancreatitis. It was recognised as a unified entity only 10 years ago. The contributing authors extensively discuss the topics from different perspectives, including the pathogenesis of conditions such as cellular senescence and innate immunity as well as diseases such as igg4 related sclerosing cholangitis and intraductal papillary neoplasm. We read with great interest the editorial by fox and fox1 describing the use of serum immunoglobulin g4 igg4 concentrations as a marker for igg4 related disease igg4 rd. Igg4related hashimotos thyroiditis of the thyroid gland.
Igg4related sclerosing disease, an emerging entity. Igg4related sclerosing disease is a systemic disease characterized by extensive igg4 positive plasma cells and tlymphocyte infiltration of various organs. Since 2001, when a possible link between igg4 and sclerosing lesions was identified, 1 idiopathic fibro. The variable organ dysfunction reflects the clinical presentation. Igg4related disease is an immunemediated condition, meaning that it involves the occurrence of disease in organs as the result of a dysregulated immune system. Increased numbers of igg4 expressing plasma cells and an increased ratio 30% of igg4 iggexpressing plasma cells have been suggested as possible criteria. When igg4 related disease affects the bile ducts, it is called igg4 related sclerosing cholangitis. This condition has been known by many other names in the past, such as igg4 related sclerosing disease, igg4 related systemic disease, igg4 related systemic sclerosing disease, igg4 syndrome, and igg4 associated disease, however a consensus in 2012 agreed upon the use of igg4related disease. Igg4related systemic sclerosing disease of the ocular. Rare diagnosis of igg4 related systemic disease by lip. The disease is so named because the antibody subtype igg4 can be detected on tissue samples and often at elevated levels in the.
Relationship between rosaidorfman disease and igg4. Clinicopathologic analysis of igg4related skin disease. Provides extensive discussions on issues including recent emerging pathogenesis such as cellular senescence and innate immunity, and new diseases such as igg4 related sclerosing cholangitis and intraductal papillary neoplasm. Pathology, jackson memorial hospital, holtz 2042c, 1611 nw 12th ave, miami, fl 336 email. Igg4 related systemic disease is now recognized as a systemic disease that may affect various organs. Vol 385 april 11, 2015 1461 rare in igg4related disease.
Because there are not specific antibodies for this disease. Chronic sclerosing sialadenitis is a chronic longlasting inflammatory condition affecting the salivary gland. Sclerosing mesenteritis is a rare inflammatory and fibrosing disorder of unknown etiology, while igg4. Common features include igg4 related autoimmune pancreatitis, swelling of or within an organ system an inflammatory pseudotumor, salivary gland disease which can lead to enlargement of the salivary glands, swollen lymph nodes lymphadenopathy, skin manifestations, and symptoms consistent with allergies or asthma. Sc can mimic primary sclerosing cholangitis psc, cholangiocarcinoma cca, and pancreatic.
Igg4related sclerosing cholangitis, also known as autoimmune cholangiopathy, is part of the spectrum of igg4 related disease but can also occur in isolation. Igg4related disease igg4rd is known as an igg4related systemic disease, hyperigg4. Igg4related sclerosing disease is a systemic disease characterized by extensive igg4positive plasma cells and tlymphocyte infiltration of various organs. Igg4 related disease igg4rd statpearls ncbi bookshelf. Igg4 ratio indicated sclerosing peritonitis was an igg4 related disease. Igg4 related disease igg4 rd is a multiorgan system disease that has been recognized in the last 10 years. Health, general autoimmune diseases causes of development and progression diagnosis b cells epidemiology histochemistry histology, pathological methods immunoglobulin g health aspects physiological aspects pancreatitis. Few years later, igg4 positive cells were found in other organs and the term igg4 related systemic disease was suggested. Lymphoplasmacytic sclerosing pancreatitis, a prototypal histological type of aip, is now recognized as a systemic igg4. In our study on further follow up of 2436 months, none of the cases showed other manifestations of igg4 related systemic disease. The syndrome affects predominantly middleaged and elderly patients, with male predominance.
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