Steroid Therapy and Steroid Response in Autoimmune Pancreatitis

Abstract

Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33–78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24–52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.

Steroid-responsive pancreatitides

“…Serum IgG4, IgE, eosinophils and IL-2 soluble receptor have been reported as biomarkers of disease activity and, consequently, potential predictors of therapy response and relapse. A high risk of relapse has been associated with high pretreatment serum IgG4 (> × 4 upper limit of normal) persistent high serum IgG4 or minor decrease after steroid initiation, proximal biliary involvement and multiorgan involvement (> 2 organs)[ 78 , 79 ].…”

United European Gastroenterology guideline: How to manage immunoglobulin G4‐related digestive diseases

“…6,9 Endoscopic ultrasonography-guided fine-needle aspiration biopsy is fairly important in cases suspected to be autoimmune pancreatitis (AIP), both to exclude malignancies and to achieve a conclusive histological diagnosis. 4,9 Similarly, transpapillary biliary biopsy is effective in cases of IgG4-related sclerosing cholangitis (IgG4-SC). 6 Although the histological items for IgG4-SC cannot be fully obtained by bile-duct biopsy (0-88%), 6 exclusion of biliary cancer is feasible to some extent.…”

“…Corticosteroid is the standard AIP treatment and has an initial response rate of 97-100%. 9 Rituximab and immunomodulators (azathioprine) can be applied in steroid-refractory or repeatedly relapsed cases. Corticosteroid is generally associated with aggravation of glycemic control and can induce diabetes.…”

“…9 One therapeutic issue is the high relapse rate (24-52%) in type 1 AIP during the long clinical course. 9,10 The relapse rate tends to differ among countries, depending on the use of low-dose maintenance steroids. 10 A prolonged steroid dosage increases the risk of side effects, such as infection, vertebral fracture, femoral head necrosis, and myopathy.…”

“…However, whether the standardized incidence ratio is significantly increasing in the cohort of AIP remains controversial. 9 The increase may reflect a bias due to intensive systemic examinations at the initial diagnosis, as malignancies are predominantly discovered shortly after diagnosis of AIP. The concept of paraneoplastic syndrome has also been reported, whereby IgG4-related lesions may develop as responses to subclinical malignancies.…”