What is IgG4 (Immunoglobulin G4) related pancreatitis?

From the Guidelines

IgG4-related pancreatitis should be treated with corticosteroids as first-line treatment, typically starting with prednisone at 40mg daily for 2-4 weeks, followed by a gradual taper over 3-6 months, as recommended by the British Society of Gastroenterology and UK-PSC guidelines 1. The diagnosis of IgG4-related pancreatitis is supported by elevated serum IgG4 levels, but a confirmatory histological diagnosis is recommended to distinguish it from other conditions like primary sclerosing cholangitis (PSC) 1. Some key points to consider in the diagnosis and management of IgG4-related pancreatitis include:

• Elevated serum IgG4 levels support the diagnosis, but cannot be relied on for making a definite diagnosis 1
• A confirmatory histological diagnosis is recommended, which can be obtained through endoscopic ultrasound-guided fine-needle aspiration cytology or core biopsy 1
• Other organ involvement, such as pancreatic manifestations of IgG4-RD, may provide important information to distinguish IgG4-SC from PSC 1
• Patients with active IgG4-SC should be given corticosteroids as first-line treatment, and all patients with IgG4-SC should be considered for continued immunosuppressive therapy 1
• Patients with complex IgG4-SC and those with suspected malignancy should be referred to a specialist multidisciplinary team (MDM) for review 1 The treatment of IgG4-related pancreatitis involves:
• Corticosteroids as first-line treatment, with a typical starting dose of prednisone at 40mg daily for 2-4 weeks, followed by a gradual taper over 3-6 months 1
• Immunomodulators like azathioprine (2mg/kg/day), mycophenolate mofetil (1000-2000mg/day), or rituximab (typically two 1000mg infusions given two weeks apart) may be used for patients who relapse or cannot tolerate steroids 1
• Monitoring response involves tracking symptoms, IgG4 levels, and imaging studies 1

From the Research

Definition and Classification of IgG4 Pancreatitis

• IgG4 pancreatitis, also known as autoimmune pancreatitis (AIP), is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) 2.
• AIP is classified into two distinct subtypes: type 1 and type 2, with type 1 being the most common manifestation of IgG4-related disease 3.
• Type 1 AIP is characterized by elevated IgG4 levels in the serum and affected tissues, while type 2 AIP is a pancreas-specific disorder that frequently occurs in the context of inflammatory bowel diseases 3.

Clinical Presentation and Diagnosis

• Patients with IgG4 pancreatitis often present with obstructive jaundice, and the disease can mimic hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer 4.
• Accurate diagnosis is challenging due to the absence of pathognomonic findings, but can be achieved using the HISORt criteria (histology, imaging, serology, other organ involvement, and response to immunosuppressive therapy) 4.
• Serum IgG4 levels are often elevated in type 1 AIP, while histological findings include lymphoplasmacytic acinar inflammation and storiform fibrosis 2, 5.

Treatment and Management

• The standard therapy for IgG4 pancreatitis is oral corticosteroid administration, with more than 90% of patients responding to steroid treatment within 1 month 6.
• Steroid treatment can result in normalization of serological markers, including IgG4, but may also induce adverse events, such as chronic glycometabolism, obesity, and osteoporosis 6.
• Maintenance treatment is often employed in type 1 AIP due to the higher relapse rate compared to type 2 AIP, and may include immunosuppressive drugs, such as azathioprine, and B-cell depletion therapies, such as rituximab 4, 3.