Type 1 Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis Is Associated With Extrapancreatic Organ Failure, Malignancy, and Mortality in a Prospective UK Cohort

Abstract

OBJECTIVES Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1–107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P < 0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio = 2.25, CI = 1.12–3.94, P = 0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio = 2.07, CI = 1.07–3.55, P = 0.02). CONCLUSIONS Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort

“…Th e disease has been described in Asia, United States, and throughout Europe, with geographical variations in its clinical presentation, the utility of serum IgG4 in diagnosis, the presence of extra-pancreatic manifestations, and treatment regimens and outcome ( 5 ). Although originally considered a relatively benign disease, we recently provided evidence for high rates of relapse, organ dysfunction and failure, malignancy, and mortality in the largest prospective cohort of AIP and IgG4-SC patients reported from Europe ( 6 ).…”

Cerebral involvement in IgG4-related disease

“…[5][6][7][8] IgG4-RD is associated with signifi cant patient morbidity and mortality. 9 A number of diagnostic criteria have been used for IgG4-RD, including the recent International Consensus Diagnostic Criteria (ICDC). 10 During the period of this study, the HISORt criteria proposed by the Mayo Clinic were used in the diagnosis of AIP 11 and its extra-pancreatic manifestations.…”

IgG4 Sclerosing Cholangitis and Post Infantile Giant Cell Hepatitis: A Case Report of an Extraordinary Co-presentation

“…Type 1 auto-immune pancreatitis (AIP) is part of the IgG4-RD that often affects multiple organs including the pancreas, bile ducts, salivary glands, kidneys and lymph nodes [22]. The isolated IgG4-SC without the mutually described AIP has been reported in a small number of cases.…”