Continuing Education Activity

Autoimmune pancreatitis is a clinical condition characterized by inflammation of the pancreas from an autoimmune etiology. It is an uncommon cause of pancreatitis but can present with significant morbidity and mortality because of repeated episodes of acute pancreatitis. It can be associated with other autoimmune conditions, and timely diagnosis and management are important to achieve good patient outcomes. This activity reviews the evaluation and management of autoimmune pancreatitis and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Describe the pathophysiology of autoimmune pancreatitis as an autoimmune process and associations of the entity with other diseases.
• Identify the clinical presentation of autoimmune pancreatitis.
• Review the management of autoimmune pancreatitis including corticosteroids and the choice of immunomodulators in managing the condition.
• Outline the importance of collaboration and coordination among the interprofessional team to improve recognition and treatment of patients with 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
• Type 2: Idiopathic duct centric pancreatitis, granulocytic epithelial lesions in pancreatic duct without IgG4 positive cells or systemic involvement

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 under-diagnosed 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 is increasingly being 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 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 can help in ruling out an alternate diagnosis, causing abdominal pain. 

Patients can also have manifestations of other organ system involvement such as salivary glands, thyroid, and renal involvement in association with autoimmune pancreatitis. This is usually as a 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, as well as the presence of other associated conditions.[14] The evaluation of patients with suspected AIP involves laboratory tests, including 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 to treat frequent relapses of AIP, which is more common in type I AIP, is still being debated, and because of the lack of established guidelines, therapy needs to be tailored in individual patients.[21]

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 which 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 of 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 education of patients and their family members.

With a thorough evaluation and after ruling out differential diagnoses such as pancreatic malignancy, patients need continuous follow-up with their providers to assess response to immunosuppressant therapy. Care coordination in both inpatient and outpatient settings remains critical to enhance healthcare outcomes of the condition and to reduce associated morbidity and improve patient quality of life.