Radiologic remission of type 1 AIP with induction of remission therapy. Before treatment, CT scan reveals diffuse swelling of pancreatic parenchyme with minimal peripancreatic haziness. The pancreatic duct visualized by ERCP shows multifocal narrowings in main pancreatic duct without remarkable poststenotic dilation. After induction of remission, pancreas on CT scan looks to have normal contour. The pancreatic duct obtained by ERCP shows normal caliber of main pancreatic duct and the multifocal stenotic segments of pancreatic duct disappeared
Definition of remission and relapse of autoimmune pancreatitis
Resolution of accompanying symptoms (i.e., obstructive jaundice and abdominal pain)
Normalization of elevated serum IgG or IgG4 level
Resolution of pancreatic enlargement and main pancreatic duct narrowing
Restitution of abnormal histologic changes to normal architecture
Normalization of exocrine and/or endocrine function of the pancreas (diabetes mellitus)
A + B + C
2 of 3 (A, B, C)
Occurrence of accompanying symptoms after remission
Elevation of serum IgG or IgG4 level after remission
Occurrence of pancreatic enlargement and/or main pancreatic duct narrowing at the same or different locations, compared with previous disease
Occurrence of abnormal histologic changes
In clinical setting, complete remission can be defined when symptomatic, serologic, and radiologic remissions are achieved with treatment. Incomplete remission can be defined when only 2 of the above 3 categories are satisfied.
Relapse of AIP
Even though AIP is extremely responsive to initial steroid treatment, relapse or recurrence of the disease is frequently encountered during follow-up of the patients. According to the subtypes of AIP, disease relapse is common in type 1 AIP, while type 2 AIP does not relapse [11, 15]. The exact rate of relapse for type 1 AIP has not been unveiled. In a recent international multicenter study, 31 % of patients with type 1 AIP experienced at least one disease relapse . More than half of patients who experienced multiple relapses have permanent histologic changes (pancreatic calcifications or stones and intensive fibrosis) in pancreas and do not show steroid responsiveness [17, 18].
Theoretically, relapse of AIP can be defined as recurrence of symptomatic, serologic, radiologic, or histologic abnormalities of AIP after complete or incomplete remission has been achieved. The definition of relapse can be also categorized as (1) symptomatic, (2) serologic, (3) radiologic, and (4) histologic relapse (Table 22.1). Serologic relapse is elevation of serum IgG or IgG4 after normalization. Sometimes, serologic relapse can be observed without any evidence of symptomatic and radiologic relapse. That may mean subclinical disease activity or undetected disease activity in other organs [11, 19].
Indication of Steroid Treatment
Patients with AIP who receive glucocorticoid treatment have significantly higher remission rates of all aspects of clinical, histopathological, and serologic findings than those who do not [20–22]. Glucocorticoid treatment has also been reported to reduce the time to remission and improve the exocrine function of the pancreas. Even though there is no consensus on the indication, steroid treatment for AIP patients can alleviate symptoms and improve radiologic and serologic abnormalities. And steroid therapy should be started when vital organs are affected for preventing severe organ dysfunction and failure. However, not all manifestations of AIP require immediate intervention, and implementation of steroid therapy should be decided based on the significance, functional status, and disease course of the organ affected. In practice, the generally accepted indications of steroid treatment include obstructive jaundice, abdominal pain, back pain, and symptomatic extrapancreatic diseases.
Induction of Remission and Withdrawal of Steroid
Steroid therapy for AIP consists of induction of remission, withdrawal of steroid, maintenance therapy, and off-steroid therapy (Fig. 22.2). For induction of remission, high dose of steroid is recommended. The exact dose of steroid and duration for remission induction have not been yet established. Most of the experts agree to use 30 mg or 40 mg of prednisolone or prednisone [3, 12, 13, 16, 20, 22–26]. Recently, ICDC defines the starting dose of steroid for induction of remission as 0.6–1 mg/kg per day for type 1 AIP . For the duration of induction of remission with high-dose steroid, the clinical protocols are quite different according to countries. In Korea and Japan, 30–40 mg of oral corticosteroid is usually prescribed for 1–2 months. On the contrary, 40 mg of oral steroid is used for 1 month in the USA. In general, 1 month of 30–40 mg oral corticosteroid can be used as a standard induction of remission regimen. However, the duration of high-dose steroid therapy should be tailored to each patient based on the disease activity of the involved organs.
Recommendation of steroid therapy for autoimmune pancreatitis
Before starting withdrawal of steroid, it should be preceded to confirm the responsiveness of disease to the drug. Usually, symptomatic response or remission can be observed within 2–3 weeks after installation of steroid therapy. However, it usually takes several weeks to months to achieve serologic and radiologic remission. Especially, extrapancreatic lesions such as bile duct stricture and retroperitoneal fibrosis take more time to be resolved. The protocols of tapering the steroid after induction of remission are also different from medical center to center. However, most of the protocols taper the drug by 5 mg/week.
Maintenance Treatment for AIP
The goal of maintenance therapy for AIP is to prevent relapse. Theoretical reasons for need of maintenance therapy are that the relapse rate of AIP has been reported to 30–50 % of all cases. And the serologic and radiologic remissions require more time of treatment in clinical setting. However, the issue of whether maintenance therapy should be used on all patients of AIP or confined to the patients who experienced relapse at least once remains unsolved. Furthermore, the duration of maintenance therapy is another issue to be solved.
Currently, Japanese group and several Korean groups favor the maintenance therapy after induction of remission. Japanese guidelines for AIP suggest maintenance therapy with low dose of steroid (2.5–5 mg/day) should be administered to all patients for 3 years. On the contrary, the US group recommends maintenance therapy only for the patients who experienced relapse. They recommend short course of high-dose steroid therapy for induction of remission and complete withdrawal of steroid by tapering out (5 mg/week).
Steroid-Induced Adverse Effect
As already well known, high-dose and long-term steroid treatment increases the risk of adverse effect. In one study, steroid therapy for AIP caused glucose intolerance, exacerbation of preexisting DM, osteoporosis, spinal compression fracture, avascular necrosis of femoral head, and pneumonia . In practice, the change of body shape such as moon face, dorsal hump formation, and weight gain with abdominal striae is the most common side effect during steroid treatment. However, when encountered serious side effects just like osteoporosis with compression fracture, avascular necrosis, and opportunistic infection, steroid therapy should be stopped and other therapy which can spare the requirement of steroid should be considered [22, 24].
Treatment of Relapse
The patients of AIP can experience the disease relapse either during withdrawal period or after off-steroid period. Overall rate of relapse in AIP has been 30–50 %. However, these studies have several flaws such as inconsistent definition of relapse, heterogeneity of study population, and incomplete differentiation of subtype. Currently, the relapse is common in type 1 AIP and rare in type 2 disease.