Steroid therapy is clinically, morphologically, and serologically effective in AIP patients, and as a result, it has become the standard current therapy for AIP. From the international survey of AIP (Kamisawa et al., 2011
), steroid therapy is standard for AIP in all countries. According to the Japanese consensus guideline for the management of AIP (Kamisawa et al., 2010b
), the indications for steroid therapy in AIP include symptoms such as obstructive jaundice and the presence of symptomatic extrapancreatic lesions. Before steroid therapy, obstructive jaundice should be controlled by biliary drainage and blood glucose levels should be regulated, usually by administration of insulin in diabetes mellitus patients. The initial recommended dose of oral prednisolone for induction of remission is 0.6 mg/kg/day, administered for 2–4 weeks. Biochemical and serological blood tests, such as liver enzyme and IgG4 levels, as well as imaging tests, such as CT, MRCP, and ERCP, are performed periodically after the start of steroid therapy. Pancreatic size usually normalizes within a few weeks, and biliary drainage becomes unnecessary within about 1 month. Rapid response to steroids is reassuring and confirms the diagnosis of AIP. If steroid effectiveness is reduced, the patient should be re-evaluated on suspicion of pancreatic cancer. The dose is gradually tapered to a maintenance dose of 2.5–5 mg/day over a period of 2–3 months.
Remission is defined as, the disappearance of clinical symptoms and resolution of the pancreatic and/or extrapancreatic manifestations on imaging studies. In the Japanese multicenter survey of steroid therapy for AIP (Kamisawa et al., 2009
), the remission rate of AIP patients treated with steroid was 98% (451/459). At remission, the enlarged pancreas returned to near-normal size in 239 (80%) of 300 patients and became atrophic in 58 patients (20%). Elevated serum IgG4 levels decreased in all patients after the start of steroid therapy, but they failed to normalize in 115 (63%) of 182 patients. HbA1c and impaired pancreatic exocrine function improved and normalized in half of them.
Relapse of AIP is defined as reappearance of symptoms accompanied by the reappearance of pancreatic and/or extrapancreatic, including bile duct, salivary gland, and retroperitoneal abnormalities on imaging and/or elevation of serum IgG4 levels. In a multicenter survey (Kamisawa et al., 2009
), the relapse rate of AIP patients treated with steroid was 24% (110/451). Relapse occurred in the pancreas (n
= 57, 52%), bile duct (n
= 37, 34%), and extrapancreatic lesions (n
= 19). Maintenance steroid therapy was given after remission in 377 (82%) of 459 patients treated with steroid. The maintenance oral prednisolone dose was 10 mg/day (n
= 27, 7%), 7.5 mg/day (n
= 13, 3%), 5 mg/day (n
= 238, 63%), 2.5 mg/day (n
= 78, 21%), and others. The relapse rate with maintenance therapy was 23% (63/273), which was significantly lower than that of patients who stopped maintenance therapy (34%, 35/104; p
< 0.05). In the USA and UK, where no maintenance therapy was given, relapse rates of patients treated with steroid were reportedly 38% (Sandanayake et al., 2009
) and 53% (Ghazale et al., 2008
). Whether maintenance therapy benefits AIP patients remains unconfirmed, but given these findings, maintenance therapy with low dose prednisolone (2.5–5 mg/day) was recommended to prevent relapse (Kamisawa et al., 2009
). In a multicenter study (Kamisawa et al., 2009
), of the 377 patients who underwent maintenance therapy, maintenance therapy was stopped in 104 (28%) in whom complete radiological and serological improvement was achieved. As to the period from the start of steroid therapy to relapse, 32% (32/99) relapsed within 6 months, 56% (55/99) relapsed within 1 year, 76% (75/99) relapsed within 2 years, and 92% (91/99) relapsed within 3 years after starting medication. Maintenance therapy should be stopped within 1–3 years in cases with radiological and serological improvement to prevent steroid-related complications such as osteoporosis, diabetes, and infection (Kamisawa et al., 2009
) (Figure ).
Regimen of Japanese standard steroid treatment for AIP.
For relapsed AIP, re-administration or dose-up of steroid was effective. In the USA and UK, immunomodulatory drugs such as azathioprine were used in addition to re-administered steroid for relapsed patients, and remission was again achieved and maintained on long-term azathioprine (Ghazale et al., 2008
; Sandanayake et al., 2009
It has been reported that the predictors for relapse are the presence of proximal bile duct stenosis and elevated serum IgG4 levels (Ghazale et al., 2008
; Kamisawa et al., 2009
; Sah et al., 2010
; Takuma et al., 2011
). Pancreatic stones are formed in relapsing AIP patients, which might be induced by pancreatic juice stasis from intensified incomplete obstruction of the pancreatic duct system (Takuma et al., 2011
; Maruyama et al., 2012
). Since, AIP might transform into ordinary chronic pancreatitis after several relapses, relapses of AIP should be avoided as much as possible.
It is necessary to verify the validity of the Japanese regimen of steroid therapy for AIP: the necessity, drugs, and duration of maintenance therapy need to be clarified by prospective studies.