Tools
Autoimmune Pancreatitis
Introduction
Autoimmune pancreatitis (AIP), also referred to as non-alcoholic destructive pancreatitis and sclerosing pancreatitis, is a chronic inflammatory condition characterized histologically by chronic inflammation of the pancreas and clinically by various symptoms related to biliary and pancreatic pathologies.[1] It is increasingly being recognized as an uncommon but important cause of recurrent acute pancreatitis or painless jaundice.[2] In addition to primarily being a pancreatic disorder, it is also being suggested as a systemic autoimmune disease that can be present along with other autoimmune conditions or as a part of the spectrum of immunoglobin G subclass 4 (IgG4) related disorders.[3][4]
AIP has been classified into two clinical subtypes
- Type 1: IgG4 related pancreatitis, associated with high serum IgG4 concentration and IgG4 bearing plasma cell infiltration of the pancreas with a background of lymphoplasmacytic sclerosing pancreatitis. IgG4 related pancreatitis is associated with high serum IgG4 concentration and IgG4 bearing plasma cell infiltration of the pancreas with a background of lymphoplasmacytic sclerosing pancreatitis.
- Type 2: Idiopathic duct centric pancreatitis, granulocytic epithelial lesions in pancreatic duct without IgG4 positive cells or systemic involvement
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The etiology of autoimmune pancreatitis is considered to be autoimmune, as demonstrated by the presence of lymphocytic infiltration on histology.[3] As an IgG4 related disease, various immune-mediated mechanisms have been suggested that could initiate the inflammatory response.[5] Some potential initiating mechanisms include bacterial infection and molecular mimicry in the setting of genetic risk factors and autoimmunity. T-regulatory cells mediated immune reaction and the shift of peripheral blood T lymphocytes towards T helper 2 response could also contribute to the recruitment of cytokines and interleukins that subsequently induce inflammation and fibrosis.[5] The IgG4 antibodies are thought to behave as tissue-destructive immunoglobulins both locally and systemically, but there remains a gap in the understanding of the etiology of many IgG4-related diseases.[6]
Epidemiology
Autoimmune pancreatitis is an uncommon cause of chronic and recurrent pancreatitis and is likely an underdiagnosed condition. It is reported to account for up to 2% of all cases of chronic pancreatitis, with a prevalence of less than 1 per 100,000 population. Most of the initial reports in the literature are from Asian countries, including Japan, where the prevalence is speculated to be higher; however, this may partly have been because of increased recognition.[7] In recent years, it has increasingly been reported in Western countries, making it a worldwide entity.[8]
Most of the epidemiological data about AIP has been based on estimates from small case series and study groups. It has been seen more in males with a ratio of 3:1, and the age of onset is reported to be greater than 45 years.[9]
Histopathology
A histopathologic examination can help and is usually necessary to distinguish autoimmune pancreatitis from pancreatic cancer.[10][11] The autoimmune nature of AIP is supported by the presence of lymphoproliferative inflammation demonstrated on histology. On biopsy, dense lymphoplasmacytic infiltrates can be seen, especially in and around pancreatic ducts with associated fibrosis.[12] Fibrosis may be similar to chronic obstructive pancreatitis, with the presence of both interlobular and intralobular fibrosis along with acinar atrophy.
A histopathologic picture of sclerosing pancreatitis or a presence of IgG4 positive cells along with periductal lymphoplasmacytic infiltration, acinar fibrosis, or obliterative phlebitis can establish a diagnosis of AIP type 1. AIP type 2 is characterized by the lack of IgG4 positive cells in pancreatic parenchyma and granulocytic epithelial lesions in the pancreatic duct.[10]
History and Physical
Clinically, autoimmune pancreatitis can manifest with symptoms related to biliary or pancreatic involvement. Patients can present with recurrent episodes of abdominal pain, with or without attacks of pancreatitis. Obstructive jaundice is a common presentation that can be accompanied by non-specific symptoms such as nausea, vomiting, loss of appetite, or weight loss, depending on the degree of biliary or pancreatic strictures and involvement.[13] A physical examination can be non-revealing, except for mild jaundice, but it can help in ruling out an alternate diagnosis, causing abdominal pain.
Patients can also have other organ system involvement manifestations, such as salivary glands, thyroid, and renal involvement, associated with autoimmune pancreatitis. This is usually part of systemic IgG4-related disorders.
Evaluation
The international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis include imaging of the pancreas and pancreatic duct, serologic studies including IgG4 levels, histopathology, and other associated conditions.[14] Evaluating patients with suspected AIP involves laboratory tests, including a complete blood count and a comprehensive metabolic panel, with liver and kidney function tests. An obstructive pattern of transaminitis with elevated alkaline phosphatase and bilirubin levels may be noted.
Imaging of biliary and pancreatic systems can be done with a computed tomography (CT) scan or magnetic resonance imaging (MRI), which also helps to evaluate for alternate diagnoses. MRI scans, along with cholangiopancreatogram (MRCP), are generally considered superior to evaluate for size, textures, enhancement with contrast as well as the presence of strictures.[15] When expertise is available, endoscopic ultrasound of the pancreas is favored because of its utility in imaging, image-enhancing techniques, and the ability to acquire tissue through fine needle aspiration or biopsy.[16][17]
Treatment / Management
There is limited data on the treatment of autoimmune pancreatitis, and most of it is based on observational studies. Most patients are seen to respond to corticosteroid therapy, which leads to improvement of symptoms as well as a reduction in complications of AIP.[18] In patients presenting with obstructive jaundice and sclerosing cholangitis, early initiation of corticosteroids is recommended.[18] It has been suggested that a lack of improvement with corticosteroids could hint towards the possibility of alternate diagnoses such as pancreatic malignancy.[19]
Relapse of AIP or failure to wean steroids may occur in up to half of the patients, especially in IgG4-related AIP requiring long-term steroids or use of steroid-sparing agents. Azathioprine has been shown to be effective in patients to help in weaning steroid therapy.[20] Patients with biliary strictures are also at high risk for relapse after withdrawal of steroid therapy.[13] The role of other immunomodulators in treating frequent relapses of AIP, which is more common in type I AIP, is still being debated. Because of the lack of established guidelines, therapy needs to be tailored in individual patients.[21](B2)
Differential Diagnosis
One of the important differentials that need to be ruled out before initiating treatment of autoimmune pancreatitis is pancreatic cancer. It may be difficult to differentiate the two based on clinical presentation or imaging findings alone.[22] Histopathological examination can be of yield and is preferred as a part of diagnostic criteria before initiating treatment of AIP.
Other differential diagnoses that need to be considered are other causes of biliary tract obstruction, such as choledocholithiasis, cholangiocarcinoma, pancreatic cysts, scarring, or other pathologies that can contribute to the obstruction of pancreatic ducts.
Prognosis
Autoimmune pancreatitis responds generally well to treatment with corticosteroids and has a favorable prognosis. A majority of cases exhibit remission with steroids, and the rate of complications is also reported to improve significantly with treatment. The cases of AIP that have a concurrent pancreatic tumor are challenging to treat and carry a worse prognosis that can be associated with the need for pancreatic resection.[22]
Complications
Recurrent attacks of pancreatitis may present as pancreatic relapse in a few patients. There have been reports of the incidence of pancreatic cancer on the surveillance of patients with AIP; however, the association of AIP with malignancies is not established.[23] In cases that fail treatment or if there is suspicion of concurrent malignancy, surgical resection remains an option, and surgery can be associated with significant morbidity and mortality.[24]
The other complications of AIP are related to the worsening of biliary strictures and, if untreated, cause significant obstructive jaundice. There can also be complications related to long-term treatment with steroids, failure to wean steroids, or other complications secondary to immunomodulatory therapy.
Deterrence and Patient Education
Patients with autoimmune pancreatitis should be thoroughly educated regarding the treatment options for their condition. The importance of medication adherence and the consequences of inadequate treatment should be explained in detail. They should also be made aware of the potential side effects of long-term corticosteroid use, including adrenal insufficiency, osteoporosis, weight gain, osteonecrosis, and hyperglycemia.
Enhancing Healthcare Team Outcomes
Autoimmune pancreatitis can present with a diagnostic challenge because of nonspecific presentation with symptoms of abdominal pain and frequent episodes similar to acute pancreatitis. Patients can present to their primary care providers or in an emergency setting with these complaints. Diagnostic workup involves an interprofessional approach including gastroenterologists for possible endoscopic intervention, radiologists for imaging as well as rheumatologists for evaluation of other associated autoimmune conditions. The role of nursing is also vital as a member of the interprofessional group with monitoring vital signs and educating patients and their family members.
After a thorough evaluation and after ruling out differential diagnoses such as pancreatic malignancy, patients need continuous follow-up with their providers to assess their response to immunosuppressant therapy. Care coordination in both inpatient and outpatient settings remains critical to enhancing healthcare outcomes for the condition, reducing associated morbidity, and improving patient quality of life.
References
Matsubayashi H, Kakushima N, Takizawa K, Tanaka M, Imai K, Hotta K, Ono H. Diagnosis of autoimmune pancreatitis. World journal of gastroenterology. 2014 Nov 28:20(44):16559-69. doi: 10.3748/wjg.v20.i44.16559. Epub [PubMed PMID: 25469024]
Level 3 (low-level) evidenceNagpal SJS, Sharma A, Chari ST. Autoimmune Pancreatitis. The American journal of gastroenterology. 2018 Sep:113(9):1301. doi: 10.1038/s41395-018-0146-0. Epub 2018 Jun 18 [PubMed PMID: 29910463]
Kamisawa T, Egawa N, Nakajima H. Autoimmune pancreatitis is a systemic autoimmune disease. The American journal of gastroenterology. 2003 Dec:98(12):2811-2 [PubMed PMID: 14687846]
Level 3 (low-level) evidenceOta M, Umemura T, Kawa S. Immunogenetics of IgG4-Related AIP. Current topics in microbiology and immunology. 2017:401():35-44. doi: 10.1007/82_2016_37. Epub [PubMed PMID: 27832379]
Stone JH, Zen Y, Deshpande V. IgG4-related disease. The New England journal of medicine. 2012 Feb 9:366(6):539-51. doi: 10.1056/NEJMra1104650. Epub [PubMed PMID: 22316447]
Kubo K, Yamamoto K. IgG4-related disease. International journal of rheumatic diseases. 2016 Aug:19(8):747-62. doi: 10.1111/1756-185X.12586. Epub 2015 Aug 10 [PubMed PMID: 26259069]
Nishimori I, Tamakoshi A, Otsuki M, Research Committee on Intractable Diseases of the Pancreas, Ministry of Health, Labour, and Welfare of Japan. Prevalence of autoimmune pancreatitis in Japan from a nationwide survey in 2002. Journal of gastroenterology. 2007 May:42 Suppl 18():6-8 [PubMed PMID: 17520216]
Level 3 (low-level) evidenceKim KP, Kim MH, Lee SS, Seo DW, Lee SK. Autoimmune pancreatitis: it may be a worldwide entity. Gastroenterology. 2004 Apr:126(4):1214 [PubMed PMID: 15057766]
Level 3 (low-level) evidenceRasch S, Phillip V, Schmid RM, Algül H. Epidemiology, clinical presentation, diagnosis and treatment of autoimmune pancreatitis: A retrospective analysis of 53 patients. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2016 Jan-Feb:16(1):73-7. doi: 10.1016/j.pan.2015.11.006. Epub 2015 Nov 27 [PubMed PMID: 26694138]
Level 2 (mid-level) evidenceChari ST, Takahashi N, Levy MJ, Smyrk TC, Clain JE, Pearson RK, Petersen BT, Topazian MA, Vege SS. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2009 Oct:7(10):1097-103. doi: 10.1016/j.cgh.2009.04.020. Epub 2009 May 4 [PubMed PMID: 19410017]
Suda K, Takase M, Fukumura Y, Kashiwagi S. Pathology of autoimmune pancreatitis and tumor-forming pancreatitis. Journal of gastroenterology. 2007 May:42 Suppl 18():22-7 [PubMed PMID: 17520219]
Suda K, Takase M, Fukumura Y, Ogura K, Ueda A, Matsuda T, Suzuki F. Histopathologic characteristics of autoimmune pancreatitis based on comparison with chronic pancreatitis. Pancreas. 2005 May:30(4):355-8 [PubMed PMID: 15841047]
Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, Topazian MD, Clain JE, Pearson RK, Petersen BT, Vege SS, Lindor K, Farnell MB. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008 Mar:134(3):706-15. doi: 10.1053/j.gastro.2007.12.009. Epub 2007 Dec 7 [PubMed PMID: 18222442]
Level 2 (mid-level) evidenceShimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Klöppel G, Lerch MM, Löhr M, Notohara K, Okazaki K, Schneider A, Zhang L, International Association of Pancreatology. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011 Apr:40(3):352-8. doi: 10.1097/MPA.0b013e3182142fd2. Epub [PubMed PMID: 21412117]
Level 3 (low-level) evidenceLee S, Kim JH, Kim SY, Byun JH, Kim HJ, Kim MH, Lee MG, Lee SS. Comparison of diagnostic performance between CT and MRI in differentiating non-diffuse-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma. European radiology. 2018 Dec:28(12):5267-5274. doi: 10.1007/s00330-018-5565-1. Epub 2018 Jun 12 [PubMed PMID: 29948075]
Fujii-Lau LL, Levy MJ. The Role of Endoscopic Ultrasound in the Diagnosis of Autoimmune Pancreatitis. Gastrointestinal endoscopy clinics of North America. 2017 Oct:27(4):643-655. doi: 10.1016/j.giec.2017.06.005. Epub 2017 Jul 8 [PubMed PMID: 28918803]
Bhattacharya A, Cruise M, Chahal P. Endoscopic ultrasound guided 22 gauge core needle biopsy for the diagnosis of Autoimmune pancreatitis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2018 Mar:18(2):168-169. doi: 10.1016/j.pan.2018.01.003. Epub 2018 Jan 10 [PubMed PMID: 29338920]
Hirano K, Tada M, Isayama H, Yagioka H, Sasaki T, Kogure H, Nakai Y, Sasahira N, Tsujino T, Yoshida H, Kawabe T, Omata M. Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment. Gut. 2007 Dec:56(12):1719-24 [PubMed PMID: 17525092]
Moon SH, Kim MH, Park DH, Hwang CY, Park SJ, Lee SS, Seo DW, Lee SK. Is a 2-week steroid trial after initial negative investigation for malignancy useful in differentiating autoimmune pancreatitis from pancreatic cancer? A prospective outcome study. Gut. 2008 Dec:57(12):1704-12. doi: 10.1136/gut.2008.150979. Epub 2008 Jun 26 [PubMed PMID: 18583399]
Sandanayake NS, Church NI, Chapman MH, Johnson GJ, Dhar DK, Amin Z, Deheragoda MG, Novelli M, Winstanley A, Rodriguez-Justo M, Hatfield AR, Pereira SP, Webster GJ. Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2009 Oct:7(10):1089-96. doi: 10.1016/j.cgh.2009.03.021. Epub 2009 Apr 1 [PubMed PMID: 19345283]
Okazaki K, Chari ST, Frulloni L, Lerch MM, Kamisawa T, Kawa S, Kim MH, Lévy P, Masamune A, Webster G, Shimosegawa T. International consensus for the treatment of autoimmune pancreatitis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2017 Jan-Feb:17(1):1-6. doi: 10.1016/j.pan.2016.12.003. Epub 2016 Dec 12 [PubMed PMID: 28027896]
Level 3 (low-level) evidenceXiang P, Zhang X, Wang C, Lang Y, Xu L, Huang L, Shen J, Feng ST. Pancreatic tumor in type 1 autoimmune pancreatitis: a diagnostic challenge. BMC cancer. 2019 Aug 16:19(1):814. doi: 10.1186/s12885-019-6027-0. Epub 2019 Aug 16 [PubMed PMID: 31419961]
Ishikawa T, Kawashima H, Ohno E, Iida T, Suzuki H, Uetsuki K, Yamada K, Yashika J, Yoshikawa M, Gibo N, Aoki T, Kataoka K, Mori H, Fujishiro M. Risks and characteristics of pancreatic cancer and pancreatic relapse in autoimmune pancreatitis patients. Journal of gastroenterology and hepatology. 2020 Dec:35(12):2281-2288. doi: 10.1111/jgh.15163. Epub 2020 Jul 6 [PubMed PMID: 32583452]
Dickerson LD, Farooq A, Bano F, Kleeff J, Baron R, Raraty M, Ghaneh P, Sutton R, Whelan P, Campbell F, Healey P, Neoptolemos JP, Yip VS. Differentiation of Autoimmune Pancreatitis from Pancreatic Cancer Remains Challenging. World journal of surgery. 2019 Jun:43(6):1604-1611. doi: 10.1007/s00268-019-04928-w. Epub [PubMed PMID: 30815742]