AIP is frequent in elderly males. According to a nationwide survey [21] in Japan, the male-to-female ratio of AIP patients was 3.7, with a mean age of 63.0 years. In the USA, the mean age was 61 years, and 85 % was male [22]. Obstructive jaundice induced by sclerosing cholangitis is the predominant initial symptom (74 % in the Komagome Hospital series [23]), and the jaundice sometimes fluctuates. Other symptoms include abdominal or back pain, weight loss, and anorexia. Diabetes mellitus (DM), usually type 2, is found in about half of AIP patients. The diagnoses of DM and AIP are made simultaneously in most patients, but some patients show exacerbation of preexisting DM with the onset of AIP [24, 25]. Mild or moderate pancreatic exocrine dysfunction is frequently detected [24]. Signs of associated extrapancreatic lesions, such as swelling of the salivary glands, hydronephrosis, and lymphadenopathy, are sometimes seen.

Liver and biliary enzymes and total bilirubin are frequently increased. Elevation of serum pancreatic enzymes was sometimes detected, but their levels were rarely abnormally high. Peripheral eosinophilia (≥600 cells/mm³) and elevation of serum IgE levels were present in 11 and 34 %, respectively [26]. Elevation of serum IgG levels, positive antinuclear antibody (ANA), and positive rheumatoid factor (RF) were seen in 56.9, 33.6, and 27.3 %, respectively [21]. Serum IgG4 levels are frequently increased (77 % in the Komagome Hospital series [27], 81 % in the USA [22], and 68 % in Korea [28]). However, serum IgG4 levels are also elevated in some patients with pancreatic cancer (4 % (5/116) in the Komagome Hospital series [27] and 7 % (5/71) in the University of Pittsburgh Medical Center series [29]).

The typical pancreatic imaging of AIP is diffuse enlargement and effacement of the lobular contour of the pancreas, with enhancement of the enlarged pancreas in the delayed phase of dynamic CT and MRI. A capsule-like rim that surrounds the pancreas is rather specific to AIP patients [30, 31]. On diffusion-weighted magnetic resonance imaging, AIP and pancreatic cancer are seen as high signal intensity areas, which are frequently diffuse or multiple in AIP patients, while they are solitary in pancreatic cancer patients [32]_.

Ultrasound examination shows an enlarged hypoechoic pancreas with hyperechoic spots [4]. Irregular narrowing (<3 mm in diameter) of the main pancreatic duct is a characteristic pancreatographic finding of AIP. The degree of narrowing of the main pancreatic duct can sometimes differ in the same patient [33–35]. MRCP cannot demonstrate the narrowing of the main pancreatic duct in many cases, but AIP is suggested by the presence of less upstream dilatation of the main pancreatic duct [36]. On fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), both AIP and pancreatic cancer patients showed FDG uptake in the pancreas, but abnormal extrapancreatic FDG uptake, such as extensive lymphadenopathy or swollen salivary gland, is highly suggestive of AIP [37].

The histological findings in the pancreas of AIP (LPSP) are abundant infiltration of T lymphocytes and IgG4-positive plasma cells and fibrosis in a periductal and interlobular distribution. The epithelium of the narrowed pancreatic duct is usually well preserved. Obliterative phlebitis is frequently seen in the variably sized pancreatic veins [2, 38, 39].

Recently, the ICDC [18] for AIP were developed to diagnose AIP safely, avoid misdiagnosing pancreatic cancer as AIP, and diagnose AIP when it presents acutely. The criteria for type 1 and type 2 AIP were developed independently, and the diagnosis of AIP is made based on one or more of the following cardinal features: imaging characteristics of the pancreatic parenchyma and pancreatic duct, serology, other organ involvement, pancreatic histology, and the optional criterion of response to steroid therapy. Each feature has been categorized as either level 1 or 2 depending on its diagnostic reliability.

The most important disease to rule out when considering a diagnosis of AIP is pancreatic cancer. CT findings (a capsule-like rim, delayed enhancement of the swollen pancreas, and presence of extrapancreatic lesions) and ERP findings (≥3-cm-long narrowed main pancreatic duct, maximal upstream main pancreatic duct <5 mm, side branch derivation from the narrowed portion, and skipped lesions) suggest AIP rather than pancreatic cancer [33, 35, 40]. However, especially in segmental-type AIP, a histological approach with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) plays an important role in confirming the diagnosis and excluding malignancy [41]. IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla of AIP patients is useful to support the diagnosis of AIP [41–43].

Although a diagnostic trial of steroid therapy is useful in some cases to differentiate AIP from pancreatic cancer, it requires extreme caution and should be only be undertaken by pancreatologists in limited cases after a negative workup for pancreatic cancer, including EUS-FNA [18, 38].

Although spontaneous improvement of AIP is seen in some patients, the standard therapy for AIP is oral steroid [17, 44, 45]. It is vitally important to distinguish AIP from pancreatic cancer before steroid therapy is started. In the Japanese standard regimen [44, 45] of steroid therapy for AIP, the indications for steroid therapy are principally symptoms such as obstructive jaundice and hydronephrosis. Before steroid therapy, the blood glucose level should be controlled using insulin in patients with DM, and in patients with obstructive jaundice, the jaundice is usually managed by endoscopic or transhepatic biliary drainage. The recommended initial dose of oral prednisolone is 0.6 mg/kg/day. Morphological and serological evaluations of the effectiveness of steroid treatment are performed 2 weeks after its start. A poor response to steroid therapy should raise the possibility of pancreatic cancer and the need to reevaluate the diagnosis. When steroid therapy is effective, the steroid dose is tapered by 5 mg every 1–2 weeks to a maintenance dose over a period of 3–6 months, while the patient’s symptoms, as well as the biochemical, serological, and imaging findings, are carefully monitored. Relapses of AIP are frequent (around 30 %) [19, 20]. To prevent relapse, steroid maintenance therapy (5 mg/day) is recommended for at least about 6 months. Predictors of disease relapse include the presence of proximal bile duct involvement [20, 46] and persistent elevation of serum IgG4 levels [17]. In relapsed cases, re-administration or dose-up of steroid [17, 44, 45] and administration of immunosuppressive drugs such as azathioprine [47, 48] or rituximab [48, 49] are effective.