Autoimmune pancreatitis: what is it, symptoms, treatment, prognosis

What is autoimmune pancreatitis?

Autoimmune pancreatitis (AIP), also called non-alcoholic destructive pancreatitis, sclerosing pancreatitis, is a chronic inflammatory condition, histologically characterized by chronic inflammation pancreas and clinically different symptoms associated with pathologies of the biliary tract and pancreas glands. AIP is increasingly recognized as an unusual but important cause of recurrent acute pancreatitis or painless jaundice. In addition to being primarily a disease pancreas, it also refers to the system autoimmune disease, which may be present in conjunction with other autoimmune conditions or as part of a spectrum of diseases associated with immunoglobin subclass G4 (IgG4).

Autoimmune pancreatitis is classified into two clinical subtypes.

• Type 1: IgG4-associated pancreatitis associated with high serum IgG4 concentration and infiltration of plasma cells of the pancreas carrying IgG4, against the background of lymphoplasmacytic sclerosing pancreatitis.
• Type 2: idiopathic ductocentric pancreatitis, granulocytic epithelial lesions of the pancreatic duct without IgG4-positive cells or systemic lesions.

Signs and symptoms

Autoimmune pancreatitis can cause many symptoms and signs, including pancreatic and bile duct manifestations, and systemic disease. Two-thirds of patients have either painless jaundice due to obstruction of the bile ducts or a "mass" in the head of the pancreas that mimics carcinoma. Thus, a careful assessment to exclude pancreatic cancer important in cases of suspicion of AIP.

Autoimmune pancreatitis usually occurs in men in their 60s and 70s with painless jaundice. In some cases, imaging reveals a mass in the pancreas or diffuse enlargement of an organ. A narrowing of the pancreatic duct called strictures may occur. In rare cases, AIP is manifested by acute pancreatitis. AIP type 1 manifests itself autoimmune diseases (associated with IgG4) in at least half of the cases. The most common form of systemic injury is cholangitis, which occurs in almost 80% of AIP cases. Additional manifestations include inflammation of the salivary glands (Sjogren's syndrome), lungs, leading to scarring (pulmonary fibrosis) and nodules, scars in the chest cavity (mediastinal fibrosis) or in the anatomical space behind the abdominal cavity (retroperitoneal fibrosis (Ormond's disease)) and inflammation in the kidneys (tubulointerstitial nephritis).

Causes and risk factors

The etiology of autoimmune pancreatitis is considered autoimmune, as evidenced by the presence of lymphocytic infiltration on histological examination. As an IgG4-associated disease, various immune-mediated mechanisms have been proposed that can initiate an inflammatory response. Some potential initiation mechanisms include bacterial infection and molecular mimicry in the setting of genetic risk factors and autoimmunity. T-regulatory cells, mediated by the immune response, and the shift of T-lymphocytes of peripheral blood towards the T-helper response 2 can also promote the recruitment of cytokines and interleukins, which subsequently cause inflammation and fibrosis. IgG4 antibodies are believed to act as tissue-degrading immunoglobulins, both locally and systemically, but a gap remains in understanding the etiology of many IgG4-associated diseases.

Epidemiology

Autoimmune pancreatitis is a rare cause of chronic and recurrent pancreatitis. AIP is reported to account for up to 2% of all cases chronic pancreatitis with a prevalence of less than 1 per 100,000 population. Most of the initial reports in the literature come from Asian countries, including Japan, where prevalence is believed to be higher; however, part of this may be due to the wider acceptance of the disease. In recent years, it has been increasingly reported in Western countries.

Most of the epidemiological data on AIP are based on small case series and study group estimates. The disease was seen more often in men than in women in a 3: 1 ratio, and the age of onset was reported to be over 45 years.

Diagnostics

- History and physical examination.

Clinically, autoimmune pancreatitis can present with biliary or pancreatic symptoms. Patients may have recurrent episodes of abdominal pain with or without pancreatitis. Obstructive jaundice is a common manifestation that may be accompanied by nonspecific symptoms such as nausea, vomiting, loss of appetite, or weight loss, depending on the degree of biliary or pancreatic strictures, and defeat. Physical examination may not reveal, except for mild jaundice, but may help rule out an alternative diagnosis causing abdominal pain.

Patients may also have manifestations of damage to other organ systems, such as salivary glands, thyroid gland, kidney damage in combination with autoimmune pancreatitis, usually as part of systemic diseases associated with IgG4.

- Analyzes and imaging studies.

Internationally agreed diagnostic criteria for autoimmune pancreatitis include imaging of the pancreas gland and duct, serologic tests, including IgG4 levels, histopathology, and the presence of other related states. Evaluation of patients with suspected AIP includes laboratory tests, including a complete blood count and a comprehensive metabolic panel, including tests of liver and kidney function. Obstructive transaminitis with increased levels of alkaline phosphatase and bilirubin can be noted.

Imaging of the biliary tract and pancreas can be done with computed tomography or MRI, which can also help evaluate an alternative diagnosis. MRI along with cholangiopancreatography (MRCP) is generally considered the best method for assessing size, texture, contrast enhancement, and presence of strictures. When available, endoscopic ultrasound of the pancreas is preferred due to its imaging usefulness, image enhancement techniques, and the ability to obtain tissue with fine needle aspiration, or biopsy.

Differential diagnosis

One of the important differences that must be ruled out before starting treatment for autoimmune pancreatitis is pancreas cancer. It can be difficult to distinguish between the two on the basis of clinical presentation or imaging findings alone. Histopathological examination may be useful and preferred as part of the diagnostic criteria before starting AIP treatment.

Other differential diagnoses to consider are other causes of biliary obstruction such as choledocholithiasis, cholangiocarcinoma, pancreatic cysts, scars or other pathologies that can contribute to the obstruction of the pancreatic ducts.

Treatment

Data on the treatment of autoimmune pancreatitis are limited, and most are based on observational studies. Most patients have been observed to respond to therapy corticosteroids, which leads to an improvement in symptoms as well as a decrease in AIP complications. In patients with obstructive jaundice and sclerosing cholangitis early initiation of corticosteroids is recommended. It has been suggested that lack of improvement with corticosteroids may indicate the possibility of an alternative diagnosis, such as malignant tumor (cancer) of the pancreas glands.

AIP recurrence or inability to wean from steroids can occur in up to half of patients, especially when IgG4-linked AIP requiring long-term corticosteroid use or steroid-sparing use funds. Azathioprine has been shown to be effective in patients with discontinuation of steroid therapy. Patients with biliary strictures also have a high risk of relapse after discontinuation of steroid therapy. The role of other immunomodulators in the treatment of frequent relapses of AIP, which is more common in type 1 AIP, all is still under discussion, and due to the lack of established guidelines, therapy is selected individually for each the patient.

Forecast

Autoimmune pancreatitis usually responds well to corticosteroid treatment and has a good prognosis. In most cases, remission is observed with steroid use, and the incidence of complications has been reported to improve significantly with treatment. AIP cases with concomitant pancreatic tumor are difficult to treat and have a poorer prognosis, which may be associated with the need for pancreatic resection.

Complications

Recurrent attacks of pancreatitis may manifest as recurrent pancreatic disease in some patients. There have been reports of the incidence of pancreatic cancer in the follow-up of AIP patients; however, the relationship between AIP and malignant neoplasms has not been established. If treatment is ineffective or if an underlying malignant neoplasm is suspected, surgical resection remains one of the options for solving the problem, and surgical intervention is associated with significant morbidity and mortality.

Other complications of AIP are associated with exacerbation of biliary strictures and, if left untreated, significant obstructive jaundice. There may also be complications associated with long-term treatment with corticosteroids, the inability weaning from corticosteroids or other complications secondary to immunomodulatory therapy.