Igg4-associated autoimmune pancreatitis K86.1

Rare autoimmunologically induced chronic pancreatitis associated with IgG4-associated autoimmune diseases Often associated with other autoimmune diseases (Kazaki K et al. 2018).

Type 1: lymphoplasmocytic type 1 (LPSP = lymphoplasmocytic sclerosing pancreatitis); in 30% of cases association with other autoimmune diseases and with retroperitoneal fibrosis. Ig4 i.S. often elevated. Only this type belongs to IgG4-associated diseases. Good response to glucocorticoids.

Type 2: (IDCP = idiopathic duct-centric chronic pancreatitis; less common); type 2 is a separate entity with a different pathophysiology. Association with inflammatory bowel disease in 30% of cases. Good response to glucocorticoids.

Approximately 2% of cases of chronic pancreatitis; AIP is found in about 2.6% of patients who have undergone surgery for suspected carcinoma

Currently still unclear. It is possible that"molecular mimicry" plays a role, i.e. cross-reactivity of bacterial peptide sequences, e.g. ubiquitin ligase from Helicobacter pylori with endogenous proteins, which induces a Th1 response. Persistence of the triggering pathogens could then lead to a Th2- and Treg-mediated immune response and IgG4-associated disease.

Plasmacytoid dendritic cells (pDC) play a crucial role in this process. These are capable of producing large amounts of type 1 interferons (IFN-I). They take on a useful role in the defense against viral infections. Excessive activation of pDC leads to (eosinophilic) inflammation followed by severe fibrosis.

The cytokines released in this process (e.g., interleukin-4, TGF-beta1) probably cause the organ fibrosis typical of IgG4-associated diseases.

Recently, antibodies against laminin 511-E8 were detected in about 50% of patients with AIP (Shiokawa M et al. 2018).

Predominantly occurring in Asia.

AIP1 paitents were older than AIP2 paitents (54.4 versus 40.8 years) in a larger cohort study. Furthermore, 85.0% of AIP1 patients had IgG4-associated autoimmune cholangitis (AIC). 18.8% of AIP2 patients suffered from an "overlap" with ulcerative colitis (Buechter M et al. 2017).

Clinical signs of chronic pancreatitis:

• Chronic recurrent pain that is not colicky (DD biliary colic) and may last hours to days.
• food intolerance (nausea and vomiting)
• Maldigestion with weight loss, fatty stools, meteorism, diarrhea (symptoms do not appear until exocrine pancreatic function is reduced to 10% of normal.

In the acute phase, the pancreas is diffuse, sausage-shaped enlarged in transabdominal ultrasound or endosonography (EUS) in 40 % of patients (MRI in figure the same in CT) with reduced echogenicity and a very narrow pancreatic duct.

In 60 % a focal finding (up to 50 mm) is shown. In these focus areas, the differentiation from pancreatic carcinoma can be difficult. The pancreatic duct can also be long or segmentally stenosed.

If AIP is suspected, endoscopic retrograde pancreatic capture (ERP) can be used for primary diagnosis.

4 core criteria in ERP have been developed for the diagnosis of autoimmune pancreatitis:

1. stricture or narrowing of the pancreatic duct over more than one third of its course
2. no gait dilatation > 5 mm proximal to the structure
3. multiple strictures/constrictions
4. secondary corridors with contrast medium filling that lead off the stenosed main corridor at right angles.

Possibly ANA+, AK against Carboanhydrase II.

Elevated serum IgG4 levels are found in 63 % of patients with AIP type 1 and 23 % of patients with AIP type 2.

Acute pancreatitis without apparent cause,

Association with other autoimmune phenomena(arthritides, autoimmune hepatitis, autoimmune thyroiditis, etc.), broad-based gamma-globulin peak on electrophoresis, serum IgG4 level: elevated in type 1, not elevated in type 2; antibodies to carbonic anhydrase II and lactoferrin.

Sonography: "sausage-shaped" thickening of the organ with homogeneous, relatively echo-poor parenchyma.

Histopathological examination of pancreatic tissue is diagnostically crucial: histologically in type 1 lymphoplasmocytic infiltration with tendency to fibrosis, IgG4-positive plasma cell infiltration., in type 2 granulomatous inflammation and epithelial cell defects of the excretory ducts.

Good response to glucocorticosteroids (Rana SS et al. 2018). In type 1 - in contrast to type 2 - recurrences occur frequently.

In this case additive immunomodulators (e.g. azathioprine, 6-mercaptopurine or mycophenolate mofetil) are used.

Alternative: Rituximab for type 1 relapses.

IgG4-associated diseases include the following:

• Primary sclerosing cholangitis
• Mikulicz syndrome (sialadenitis)
• Sjögren's syndrome
• Riedel's stroma
• Retroperitoneal fibrosis (Ormond's disease)
• Granuloma faciale
• Eosinophilic angiocentric fibrosis

1. Buechter M et al (2017) Outcome and Genetic Factors in IgG4-Associated Autoimmune Pancreatitis and Cholangitis: A Single Center Experience. Gastroenterol Res Pract 2017:6126707.
2. Kazaki K et al (2018) Current concept of autoimmune pancreatitis and IgG4-related disease. Am J Gastroenterol doi:10.1038/s41395-018-0184-7.
3. Minaga K et al (2021) Plasmacytoid Dendritic Cells as a New Therapeutic Target for Autoimmune Pancreatitis and IgG4-Related Disease. Front Immunol 12:713779.
4. Shiokawa M et al (2018) Laminin 511 is a target antigen in autoimmune pancreatitis. Sci Transl Med 10(453).
5. Sulieman I et al (2018) IgG4-related disease mimicking pancreatic cancer: Case report and review of the literature. Int J Surg Case Rep 50:100-105.
6. Tahir M et al (2018) Type-1 seronegative autoimmune pancreatitis: A Rare Case of Autoimmune Pancreatitis with Sclerosing Cholangitis and Hashimoto's Disease. Cureus 10:e2624.
7. Rana SS et al (2018) . Clinical profile and treatment outcomes in autoimmune pancreatitis: a report from North India. Ann Gastroenterol 31:506-512.