The pancreas is an organ positioned behind the stomach that performs two major functions: digestion and blood sugar regulation. Its exocrine function produces digestive enzymes, while its endocrine function releases hormones like insulin to control glucose levels. When the pancreas becomes inflamed, the condition is known as pancreatitis. Immunoglobulin G4-related pancreatitis (IgG4-RP) is a specific, chronic inflammatory form of pancreatitis often overlooked due to its rarity and unusual presentation.
The Autoimmune Basis of IgG4 Pancreatitis
IgG4-RP is the manifestation of a larger systemic disorder called Immunoglobulin G4-Related Disease (IgG4-RD). Classified as Type 1 Autoimmune Pancreatitis (AIP), this condition is characterized by the immune system mistakenly attacking its own tissues. The underlying mechanism involves the Immunoglobulin G4 (IgG4) antibody, a specific subclass normally present in low concentrations in the blood.
In IgG4-RD, plasma cells excessively proliferate and produce the IgG4 antibody. These IgG4-positive plasma cells infiltrate the pancreas, causing chronic inflammation and leading to the formation of dense, swirling scar tissue known as storiform fibrosis. This progressive scarring causes the pancreas to become enlarged and hardened, ultimately impairing its function.
A defining feature of this disease is its systemic nature, meaning it commonly affects organs beyond the pancreas. Most patients with IgG4-RD have multi-organ involvement. Other common sites include the bile ducts, salivary glands, kidneys, lungs, and the tissue behind the abdominal cavity (retroperitoneum).
Recognizing Symptoms and Distinguishing from Cancer
The clinical presentation of IgG4-RP poses a significant challenge because its symptoms often mimic those of pancreatic cancer. Both conditions can cause obstructive jaundice, which is a yellowing of the skin and eyes due to bile duct blockage. Jaundice is the most common symptom of Type 1 AIP, occurring in about 80% of cases, often accompanied by non-specific symptoms like weight loss and mild abdominal discomfort.
Diagnosis is difficult because IgG4-RP can present as a focal or mass-like lesion on imaging, indistinguishable from a cancerous tumor. Notably, 5% to 21% of pancreatic masses removed surgically for suspected cancer turn out to be IgG4-RP. The primary distinguishing symptom is the nature of the pain: unlike typical pancreatitis or pancreatic cancer, abdominal pain in IgG4-RP is often mild or entirely absent.
Another clue is the course of jaundice, which can sometimes fluctuate or resolve spontaneously in IgG4-RP, a pattern rarely seen in the progressive obstruction of pancreatic cancer. This distinction is important because misdiagnosis can lead to unnecessary, major surgery, such as a Whipple procedure, which carries substantial risks. Accurately identifying IgG4-RP avoids high-risk surgery and directs the patient toward highly effective medical treatment.
Diagnostic Procedures and Key Findings
Diagnosing IgG4-RP requires a comprehensive approach integrating clinical, serological, radiological, and histopathological findings, as no single test is definitive. Serological testing measures the level of Immunoglobulin G4 in the blood. An elevated serum IgG4 level is a hallmark finding in most patients. However, this alone is not conclusive, as 20% to 30% of patients may have normal levels, and some pancreatic cancer patients show mild elevations.
Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), visualize the pancreas. A characteristic finding in diffuse disease is the “sausage-shaped” pancreas, where the organ is symmetrically enlarged with a featureless border. Another distinct feature on contrast-enhanced imaging is the “capsule-like rim,” which appears as a low-attenuation halo surrounding the enlarged gland.
When a mass-like lesion makes cancer difficult to exclude, definitive diagnosis relies on obtaining a tissue sample through a biopsy. This is typically performed using Endoscopic Ultrasound-guided Fine Needle Biopsy (EUS-FNB) for accurate sampling. Histopathological examination confirms the diagnosis by revealing characteristic features: lymphoplasmacytic infiltration, storiform fibrosis, and abundant IgG4-positive plasma cells.
Effective Treatment Strategies
The treatment approach for IgG4-RP differs significantly from pancreatic cancer, as the condition is highly responsive to immunosuppressive therapy. Corticosteroids, such as oral prednisolone, are the established first-line treatment for inducing remission. The initial, or induction, phase typically involves a relatively high dose, such as 0.6 mg/kg per day of prednisolone, administered for two to four weeks.
Patients often show a rapid clinical and radiological response within a few weeks, which further helps distinguish the condition from pancreatic malignancy. Following remission induction, the corticosteroid dose is gradually tapered over several months to a low-dose maintenance therapy (often 2.5 to 7.5 mg per day). This maintenance treatment is important because Type 1 AIP has a significant risk of relapse, which can be as high as 45.7% after cessation.
Maintenance therapy with low-dose steroids or alternative immunosuppressants (such as azathioprine or rituximab) prevents the recurrence of inflammation and fibrosis. High serum IgG4 levels or extensive multi-organ involvement are risk factors for relapse, often requiring a longer duration of maintenance therapy. If relapse occurs, re-treatment with the initial corticosteroid regimen is usually effective in achieving a second remission.