Autoimmune pancreatitis

　　First, etiology

　　All autoimmune pathogenic mechanisms may become causes of autoimmune pancreatitis. For example, sjgren syndrome, primary biliary cholangitis, and other autoimmune diseases complicated with pancreatitis.

　　Second, pathogenesis

　　1, Classification

　　(1) Pancreatic duct stenosis type chronic pancreatitis: The entire pancreas duct through which the main pancreatic duct passes becomes thin, irregular, and is accompanied by significant pancreatic enlargement and diffuse inflammation. There is hypergammaglobulinemia and positive autoantibodies, with lymphocytic infiltration in the pancreas accompanied by significant fibrosis. Steroid hormone treatment has significant efficacy. It is also known as duct stenosis type autoimmune-associated pancreatitis.

　　(2) Localized pancreatic duct stenosis type chronic pancreatitis: Corresponding to diffuse stenotic pancreatitis, it is irregular inflammatory changes in the non-stenotic parts or branches of the pancreatic duct. Pancreatic duct stenosis type chronic pancreatitis and localized pancreatic duct stenosis type chronic pancreatitis are interrelated. The localized type may be the initial stage of the diffuse type or a stage in the healing process, while the diffuse type is the lesion stage of the localized type. Therefore, a duct stenosis length of more than 2/3 is considered to be diffuse stenosis, and less than 2/3 is considered localized. This is the basis for diagnosing diffuse stenotic pancreatitis, and it is necessary to exclude localized lesions and tumor lesions shown by short stenosis images.

　　2, Pathology

　　(1) Pancreas: The pancreas is enlarged and hardened without clear tumor formation. On cross-section, fibrosis can be seen, with the glands maintaining their original lobular structure. The pancreatic capsule becomes fibrously hypertrophic, especially on the portal vein side, with thicker fibrosis.

　　Histologically, there is significant lymphocytic infiltration and fibrosis, and the interlobular stroma of the pancreas expands, with lymphoid follicles forming. Fibrosis can extend into the acinar parenchyma, with possible atrophy of the glands. The fibrosis around the pancreatic ducts is more pronounced than the glandular inflammation. The original elastic fibers around the ducts become relaxed and hyperplastic, with lymphocytes and inflammatory cells infiltrating or collagen fibers hyperplastic near the lumen, resulting in a smaller lumen. Lymph nodes are enlarged, with significant lymphoid follicle hyperplasia, and epithelioid cells form small clusters of nests.

　　The infiltration of T cells around the ducts is more significant than that of B cells. The T cell subset is mainly CD4 positive, with some CD8 positive as well.

　　Eosinophilic cell infiltration in cholangitis and peripancreatic fibrosis can be clearly seen. Fibrosis and inflammatory cell infiltration affect the adipose tissue and connective tissue surrounding the pancreatic parenchyma. The ventral side extends beyond the elastic fibers, while the dorsal side involves the portal vein, reaching a wide range from the pancreatic papilla to the distal end of the pancreas.

　　Veins around the pancreas become occluded due to inflammatory cell infiltration, presenting as obliterative phlebitis changes. Arteries show no specific changes, with small arteries surrounded by fibrosis, and the lumen becomes narrow due to intimal thickening.

　　(2) Biliary and gallbladder lesions: The bile duct wall inside the pancreas becomes thickened and narrowed, the mucosal surface of the narrowed bile duct is smooth, the original covering bile duct mucosa is diffusely hyperplastic, the upper part of the common bile duct wall becomes thickened, and the changes in the extrapancreatic bile duct are more obvious than those inside the pancreas. The entire bile duct wall is infiltrated by lymphocytes and fibrosis, edema with thickening, involving bile ducts, ducts, and gland ducts as well as the duodenal wall. The gallbladder wall becomes thickened, but there is no change in the histology of the bile duct wall.

　　80% of patients with autoimmune pancreatitis have abnormal glucose tolerance. The symptoms of diabetes that existed before treatment may worsen or improve during steroid hormone treatment. 80% of exocrine function is low, and half of them normalize after treatment with steroid hormones. The mechanism of abnormal glucose tolerance is considered to be acute infiltration of inflammatory cells and fibrosis accompanied by extrapancreatic secretion blood flow disorders, causing islet blood flow disorders.

　　There are no specific symptoms. Abdominal symptoms may manifest as mild abdominal pain and back pain, obstructive jaundice is also common, and autoimmune diseases represented by Sjögren's syndrome are more common. Other conditions such as membranous nephritis, abnormal glucose tolerance, sclerosing cholangitis, chronic rheumatoid arthritis, and chronic thyroiditis can also be associated with autoimmune pancreatitis. Among them, the incidence rate of diabetes is the highest, and latent diabetes can occur with islet inflammation related to diabetes, but type 2 diabetes is more common. Steroid hormone treatment improves, on the one hand, the pancreatitis improves, but there may also be a tendency for diabetes to worsen. This is not only true for pancreatitis but also for cases of sclerosing cholangitis and similar lesions, where steroid hormones are also effective.

　　Autoimmune pancreatitis has a tendency to recur. Preventive measures include eliminating the cause and avoiding triggers, such as abstaining from alcohol, not overeating, and treating hyperlipidemia, etc. Gallstones play an important role in the pathogenesis of autoimmune pancreatitis. Therefore, patients with gallstones and a history of autoimmune pancreatitis should be scheduled for cholecystectomy and common bile duct exploration. For patients with existing autoimmune diseases such as Graves' disease and SLE who have pain in the left upper abdomen, the possibility of this disease should be suspected. Early detection and treatment are the key to prevention.

　　1. Eosinophils

　　Increased, activated CD4, CD8 positive, hypergammaglobulinemia, increased IgG and IgG4, and the presence of autoimmune antibodies (antinuclear antibodies, anti-mitochondrial antibodies, anti-CA-Ⅱ antibodies, rheumatoid factors, anti-α-fodrin antibodies, anti-smooth muscle antibodies).

　　2. Blood and urine amylase

　　It may be elevated, normal, or low, with 40% to 50% elevated, and 60% to 70% of liver and biliary system enzymes and bilirubin elevated.

　　3. Pancreatic function examination

　　The 3-factor half-value of chymotrypsinogen test is low, the BT-PABA excretion test is 81%, diabetes type is 68%, critical type is 13%, and endocrine abnormalities account for 84%.

　　4. US

　　In ultrasound examination, autoimmune pancreatitis is characterized by low echo, mainly diffuse pancreatic enlargement, with 69% diffuse enlargement and 31% localized enlargement (24% in the pancreatic head and 7% in the tail), without cases of pancreatic atrophy, 9% pancreatic calculi, and 7% pancreatic cysts. When there is localized pancreatic enlargement, it should be differentiated from pancreatic cancer, as the internal echo of the pancreatic cancer lesion is inhomogeneous, with a high echo in the central part, and the pancreatic tail duct is highly expanded, smooth, and presents as bead-like changes. Autoimmune pancreatitis has no ductal expansion or very slight expansion, and smooth shape is more common.

　　5. CT

　　Diffuse pancreatic enlargement is a characteristic finding, and the dynamic CT early phase enhancement effect is insufficient at the lesion site, while the late phase enhancement shows characteristic changes of delayed enhancement.

　　6. EUS

　　Compared with extracorporeal US, there are fewer blind spots in the pancreatic head and tail, and the application of high-frequency ultrasound (7.5-20MHz) can obtain the fine structure of the lesion site, and it is also manifested as diffuse pancreatic enlargement with low echo as the main feature and localized enlargement.

　　7. ERCP

　　The image of pancreatic duct stenosis displayed by ERCP is a characteristic of autoimmune pancreatitis. Periductal inflammatory cell infiltration and fibrosis are the causes of lumen stenosis. The main pancreatic duct usually becomes thinner, the wall is irregular, and there is no significant expansion of the upper segment of the pancreatic duct. The length of the stenotic image accounts for more than 2/3 of the main pancreatic duct in the diffuse type, and more than 1/3 but less than 2/3 in the localized type.

　　8. FDG-PET examination

　　At the most severe stage of inflammation, FDG is highly accumulated in the lesions of autoimmune pancreatitis, with SUV values all above 3.5. After inflammation subsides or corticosteroid hormone treatment is effective, FDG accumulation decreases, and FDG accumulation disappears during remission. When autoimmune pancreatitis affects the entire pancreas, FDG accumulation in the entire pancreas is a characteristic. However, when there is pancreatic head cancer and pancreatic tail tumors accompanied by pancreatitis, FDG is also accumulated in the entire pancreas. Relying solely on this point, it is difficult to differentiate from other diseases, and it is not possible to perform differential diagnosis between autoimmune pancreatitis and malignant tumors.

　　Dietary care for patients with autoimmune pancreatitis: Generally, fasting should be observed during the acute phase of the disease, and gradual intake can be started during the recovery period. It is important to start from small to large and from thin to thick. Begin with soft, easily digestible foods such as congee, noodle soup, egg custard vegetables, fresh fruit juice, etc., and pay attention to small and frequent meals. Subsequently, it can gradually return to normal diet. Pay attention to monitor blood sugar and observe the condition of feces.

　　1. Surgical Treatment:Surgical treatment is performed for cases of pancreatic calculi, refractory pain, and pseudocysts, as well as for differential diagnosis of tumor-forming pancreatitis and pancreatic cancer. Tumor-forming pancreatitis includes autoimmune pancreatitis, which is more common, with significant bile duct stenosis, uncontrolled jaundice, and when the pancreas cannot be resected, biliary jejunostomy can be performed.

　　2. Endoscopic Treatment:During the acute phase, due to the narrowing of the terminal bile duct of the pancreas due to inflammation, bile excretion is not smooth, and endoscopic endoscopic stenting and external stenting are performed under endoscopy to improve the enlarged pancreas.

　　3. Drug Treatment:Treatment should be given to acute pancreatitis during the acute phase, including fasting, high-calorie intravenous infusion, and antiproteinase agent therapy. In the remission phase, drugs can be alternately administered intravenously and orally, and sedatives can be used if clinical symptoms such as abdominal pain occur. When the pancreas is progressively atrophic, the exocrine function of the pancreas is low, and digestive enzyme therapy can be given.

　　Chronic pancreatitis generally does not require steroid hormone therapy, but when there are other autoimmune diseases and autoimmune pancreatitis, steroid therapy is effective. It is usually administered orally, starting with 30 to 40mg per day, observing the treatment response, and gradually reducing the dose to 5mg per day after about 2 weeks, which is appropriate. When starting with 40mg, the initial reduction can be 10mg. The efficacy is the relief of abdominal pain and the reduction of pancreatic enzymes, and the gradual reduction and maintenance of low dose are to prevent recurrence and relapse.

　　In the morphological changes of AIP, considering the high lymphocytic infiltration, if diagnosed, it is often given steroid hormone therapy at the same time as antiproteinase therapy. There are also cases that improve spontaneously without using steroid hormones. Therefore, not all cases are treated uniformly with steroid hormones, and short-term treatment with symptoms is effective. There are also cases with normal pancreatic function for a long time, but clinical experience is more common in cases of pancreatic atrophy.

　　AIP is characterized by high lymphocytic infiltration and fibrosis. In the acute phase, pancreas enlargement can be seen, and eventually, the progressive destruction of pancreatic cells leads to atrophy and concavity, which can occur in a relatively short period of time. The cases that do not atrophy are related to the duration and severity of the disease. Therefore, preventive measures should be taken during the non-atrophy period. Steroid hormones are continuously used to suppress the immune response within the pancreas. Whether it can prevent atrophy needs more accumulated cases to make a correct evaluation.