What’s Really Behind Those Symptoms

“Defined about 30 years ago, autoimmune pancreatitis [AIP] remains a diagnostic challenge,” said Vinciane Rebours, MD, PhD, professor and head of the Pancreatology and Digestive Oncology Department, Beaujon Hospital in Clichy, France. She spoke at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology 2025, held in Paris. The challenge lies in the fact that AIP includes two distinct clinical entities, neither of which is truly autoimmune. However, much remains unknown, including its natural history, cancer risk, and optimal treatment strategies. However, some aspects are now better understood.

Autoimmune Pancreatitis

AIP has two forms of involvement: Type 1 AIP, linked to immunoglobulin G4–related disease (IgG4-RD), and type 2 AIP, primarily associated with inflammatory bowel disease (IBD). These forms differ in their histological characteristics. Type 1 exhibits lymphoplasmacytic infiltration, extensive fibrosis, and IgG4-positive plasma cells. Type 2 presents with granulocytic lesions similar to those in Crohn’s disease.

Type 1 AIP typically affects men aged 50 years or older and is often associated with jaundice, pseudotumor formation, diabetes, and exocrine pancreatic insufficiency. “It is a systemic disease where lymphoplasmacytic infiltration can affect multiple organs, with the pancreas and lymph nodes most commonly involved,” said Rebours.

A definitive diagnosis of type 1 AIP requires three criteria: Organ involvement, serum IgG4 levels more than twice the normal level, and histological abnormalities on biopsy. If one of these criteria is missing, the diagnosis is considered probable or possible.

Diagnosing type 1 AIP is challenging because it can affect multiple organs, often with few symptoms, leading to significant clinical variability. Type 2 AIP, in contrast, generally affects younger individuals, with no gender preference. It is pathophysiologically distinct and is linked to IBD in 87% of cases. Diagnosis relies on clinical criteria, imaging abnormalities (parenchymal or ductal changes identifiable on scans), response to corticosteroids in symptomatic patients, and the presence of IBD. The absence of IgG4 can also aid in the diagnosis. However, gathering all these elements can be difficult.

Evolving Treatment

Symptomatic patients and those at risk for organ failure, particularly lung and kidney failure, are eligible for induction treatment. This involves the administration of full-dose corticosteroids for 4 weeks, followed by a tapering regimen. Remission was achieved in 99% of type 1 and 92% of type 2 cases. Corticosteroids can also be used as a “trial treatment” to assess corticosteroid sensitivity in patients with type 2 AIP.

The risk for recurrence (in case of nonresponse or recurrence before 12 months posttreatment) is higher in type 1 (one third of cases) than in type 2 (15%). In such cases, immunomodulators, primarily rituximab, are recommended for type 1 AIP. Rituximab can also be used as an induction treatment, either alone or in combination, or as maintenance therapy. Alternatives include mycophenolate mofetil or inebilizumab, which showed an 87% reduction in relapse risk according to data published in 2024.

Maintenance treatment for type 2 AIP is not yet fully standardized. The disease is often managed in a manner similar to that of IBD treatment. Rebours cautioned, “Management cannot stop at the pancreas; it is essential to detect all other paucisymptomatic manifestations through comprehensive annual imaging and biannual biological and functional screenings.”

Monitoring IgG4

Monitoring IgG4 levels is important for therapeutic follow-up but is not the “holy grail” for diagnosis, Rebours acknowledged. For instance, 20% of IgG4-RD cases have normal IgG4 levels, 20% of pancreatic cancers show elevated IgG4 levels, and some patients achieve clinical remission despite persistently abnormal IgG4 levels. Without strong suspicion of type 1 AIP, measuring IgG4 levels is “zero cost-effective.”

This disease, which is associated with the risk for underlying cancer, requires extensive imaging (CT, MRI, and endoscopic ultrasound) to differentiate between AIP and cancer. This step is essential to avoid unnecessary surgery on organs affected by IgG4-RD or for treating cancer with corticosteroids.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.