Miscellaneous Pancreatitis

Etiology

Autoimmune pancreatitis (AIP) is a peculiar form of chronic pancreatitis characterized by a fibroinflammatory process involving multiple organs with characteristic histopathologic and serologic features, association with other autoimmune disorders, and a propensity to respond to corticosteroid therapy (CST). Two subtypes of disease have recently been described: type I, also known as lymphoplasmacytic sclerosing pancreatitis, is considered a spectrum of immunoglobulin G4 (IgG4)-related systemic disease and represents the predominant form in the United States, Japan, and Korea and is characterized by seropositivity, whereas type II, also known as idiopathic duct-centric pancreatitis, is more commonly seen in Europe and is characterized by seronegativity. The occurrence of AIP in concordance with other autoimmune disease processes ( Box 50-1 ) as well as pathologic findings have led to acceptance of its immune-mediated causes, possibly in genetically susceptible patients. For example, 16% to 30% of patients with type II AIP carry or will subsequently be diagnosed with inflammatory bowel disease (IBD). Absence of prior attacks of acute pancreatitis or alcohol abuse is a notable feature of this form of pancreatitis. Although a benign disease, it often mimics pancreatic malignancy clinically and radiologically.

Prevalence and Epidemiology

Although there has been an increasing trend in diagnosis of AIP since it was first described in 1961, this trend is thought to be due to increasing awareness of the disease process and prevalence rate of AIP is still unclear. However, certain differences have been observed in the Western and Japanese populations. Type I predominantly arises in men over 50 years of age, typically in the sixth and seventh decades, whereas type II predominantly arises in a slightly younger population in the fifth decade without a gender predilection. However, disease can affect a wide age range, with documented cases even in pediatric populations.

Clinical Presentation

Clinical presentation of AIP is generally nonspecific. Symptoms related to pancreatic involvement include vague upper abdominal pain, jaundice, nausea, vomiting, weight loss, steatorrhea, back pain, and exocrine and endocrine dysfunction with type 2 diabetes mellitus arising at or before the onset of AIP. Patients may present with acute pancreatitis, type II more commonly than type I, although obstructing jaundice is a more common presentation. Often, up to 75% of older patients will present with obstructive jaundice, making differentiation of pancreatic malignancy difficult. However, most will present with nonspecific or mild symptoms that are overlooked, which results in delay in diagnosis, some to the stage at which changes of chronicity such as atrophy or strictures have set in.

Extrapancreatic manifestations involving the biliary tree, liver, kidney, retroperitoneum, bowel, lungs, lymph nodes, orbits, and salivary glands may occur in 60% of patients, with incidental detection of pancreatic involvement. Aside from known associations with IBD, extrapancreatic manifestations are considered rare in type II AIP and are commonly seen in type I AIP.

Depending on the subtype, the disease may relapse or persist in a milder form for a time before it is diagnosed. Type I AIP has a relapse rate of up to 59%, with most occurring within first 3 years, whereas type II AIP does not appear to relapse.

Pathophysiology

Although the pathophysiology is still largely unknown, it is thought there is an aberrant response to self-antigens that induces cellular and humoral response with resultant chronic inflammation maintained by the complement cascade and IgG4. Nearly half of the patients also demonstrate elevated IgE levels and eosinophils, which are typically seen in allergic reactions, and it is unclear if allergic cascade also may be involved in pathogenesis of AIP.

Pathology