Autoimmune pancreatitis is a rare systemic disease of the pancreas and other organs caused by damage to connective tissue by G4 immunoglobulins. It is manifested by abdominal pain, jaundice syndrome, dyspepsia, changes in stool and signs of malnutrition. It is diagnosed by ultrasound, MRI of the pancreatic gland, coprogram, determination of the level of immunoglobulins and histological analysis. Corticosteroids and monoclonal antibodies are used for therapy. If conservative treatment is ineffective, drainage, stenting, and stomy of the pancreatic and biliary ducts are performed.
K86.1 Other chronic pancreatitis
Although autoimmune pancreatitis is considered a rare disease, its share in the structure of chronic inflammation of the pancreas reaches 4-6%. The prevalence of the disease does not exceed 0.0008%. The pathology was first described by the French clinician G. Sarles in 1961. The disease was recognized as a separate nosological unit in 2001 after the development of the etiological classification of pancreatitis TIGAR-O. Autoimmune pancreatic lesion in men is detected 2-5 times more often than in women. Up to 85% of patients become ill after the age of 50. The disease is often combined with rheumatoid arthritis, retroperitoneal fibrosis, sclerosing cholangitis and other autoimmune processes.
Causes of autoimmune pancreatitis
The etiology of autoimmune pancreatitis has not been established. Usually, the disease is diagnosed by exclusion when G4 type immunoglobulins are detected and there are no other possible causes of pancreatic damage. Specialists in the field of clinical gastroenterology admit the leading role of hereditary burden, in the course of medical and genetic studies, an association of the autoimmune process with the serotypes HLA DRß1-0405, DQß1-0401, DQß1-57 has been established. Serum protein weighing 13.1 kDa was isolated from the patients’ blood, which is considered a specific antigen.
Carbonic anhydrase present in the tissues of the digestive organs, bronchial tree and distal renal tubules, lactoferrin detected in pancreatic acinuses, glands of the bronchi and stomach, components of cell nuclei and smooth muscle fibers, pancreatic inhibitor of trypsinogen and trypsin are considered as probable autoantigens. Cross–sensitization with infectious agents is not excluded – molecular mimicry between antibodies to the proteins of the causative agent of helicobacteriosis and plasminogen-binding protein has been detected.
The trigger mechanism of changes in the pancreatic gland and other sensitive organs is the connection of serum Ig G4 with autoantigens of acinar cells, normal epithelial cells of pancreatic, bile, salivary ducts, etc. Antigenic damage is accompanied by a violation of apoptosis of cellular elements of the immune system. The key link in the pathogenesis of autoimmune pancreatitis is the accumulation of persistent activated T- and B-lymphocytes, neutrophils and eosinophils in the connective tissue, provoking fibrotic-sclerotic processes.
Cytological examination in the pancreatic stroma reveals signs of fibrosis and sclerosis in the absence of pseudocysts and concretions. Due to lymphoplasmocytic, neutrophilic and eosinophilic infiltration, the duct walls are compacted, narrowed, fragmented during the prolonged course of the autoimmune process. The spread of inflammatory infiltration to the lobules of the pancreas leads to the loss of the lobular structure of the organ and is often combined with phlebitis. As with other variants of chronic pancreatitis, calcification of the parenchyma and stroma is possible.
When systematizing the forms of autoimmune pancreatitis, the prevalence of the fibrotic-sclerotic process, the presence of concomitant lesions of other organs, morphological features of inflammation are taken into account. In the focal variant of the disease, certain areas of the pancreatic parenchyma are damaged, mainly the head of the organ. Usually at least 1/3 of the gland is affected (segmental form of pancreatitis). The diffuse form of pathology is characterized by the involvement of the entire organ.
In the absence of other autoimmune diseases, pancreatitis is called isolated. In the case of systemic damage to several organs, they speak of syndromic autoimmune pancreatic inflammation. Taking into account the histological picture, there are two main variants of the disease, each of which differs in characteristic clinical features:
Lymphoplasmocyte-sclerosing form of pancreatitis. Infiltration by immunoglobulin-producing cells, pronounced fibrosis of the organ stroma and obliterating phlebitis prevail. It is combined with IgG4-associated autoimmune pathology. It is often characterized by a recurrent course with the progression of sclerotic changes.
Ductal-concentric idiopathic pancreatitis. Morphologically, it is manifested by neutrophil infiltration with cell clusters resembling microabsesses. Phlebitis and fibrosis are less pronounced. Serum IgG4 levels are usually normal. In 30% of cases it is associated with ulcerative colitis. It proceeds without relapses. It occurs 3.5-4 times less often.
Autoimmune pancreatitis symptoms
The clinical picture of the disease differs from the typical inflammation of the pancreas. In the autoimmune variant of organ damage, the pain is less intense, dull, and not associated with errors in the diet. Pain syndrome develops only in half of patients. Another important symptom of autoimmune pancreatitis is mechanical jaundice, which occurs on average in 60-80% of patients and is manifested by jaundice staining of the skin and sclera, skin itching, fecal discoloration.
Autoimmune pancreatic pathology is often accompanied by dyspeptic disorders: nausea, changes in the nature of the stool (abundant fetid feces of a grayish color), bloating. With the progression of the disease, there is a violation of absorption and a deficiency of nutrients, which is manifested by a decrease in the body weight of patients, protein-free edema of the face and lower extremities. In the later stages of pancreatitis, constant thirst develops, polyuria (symptoms of glucose metabolism disorders).
In most patients, autoimmune pancreatitis occurs with the involvement of other organs and tissues in the pathological process. Most often, the disease spreads to the biliary system with the development of sclerosing cholangitis and stone-free cholecystitis. The connection of these nosological forms with pancreatitis is indicated by a typical lymphohistiocytic infiltration of the walls of the biliary tract and a good response to hormone therapy. Sometimes the liver is affected with the formation of pseudotumor or cirrhosis.
A frequent complication of pancreatic autoimmune inflammation is diabetes mellitus, which occurs due to the gradual necrosis of the cells of the islets of Langerhans, accompanied by a sharp decrease in insulin production. More rare consequences of the disease are immunocomplex damage of the renal parenchyma by the type of tubulointerstitial nephritis, interstitial pneumonia. The circulation of IgG antibodies in the blood leads to sclerosis of salivary gland tissues.
The correct diagnosis is difficult, which is explained by the rare occurrence of pathology and the variety of its clinical manifestations. In most cases, the diagnostic search for autoimmune pancreatitis is aimed at excluding other forms of pancreatic inflammation. The most informative are such research methods as:
- Fecal examination. The coprogram identifies typical signs of malabsorption and maldigestion: a large number of undigested food particles and muscle fibers, an increased content of fatty acids. Additionally, an analysis is performed for fecal elastase, which allows you to confirm the presence of pancreatitis.
- Serological reactions. A blood test for specific antibodies reveals hypergammaglobulinemia — an increase in IgG and IgG4 levels several times, which is a pathognomonic symptom of type 1 autoimmune lesion. Antimitochondrial and antinuclear antibodies are also detected.
- Sonography. A standard study confirms the disease only in the advanced stage. With endoscopic ultrasound of the pancreas, focal or diffuse tissue compaction is visualized, alternating areas of expansion and narrowing of the pancreatic duct (“sausage-shaped” pancreas).
- Tomography. The autoimmune type of pancreatitis is characterized by a diffuse increase in the size of the organ or the presence of a limited tumor-like formation, deformation of the contours of the ducts. Pancreatic MRI is also used to monitor the effectiveness of glucocorticosteroid therapy.
- Histological examination. Cytological analysis is the “gold standard” in the diagnosis of autoimmune inflammation. Morphological examination reveals lymphoplasmocytic infiltration around the pancreatic ducts, areas of destruction of the parenchyma, involvement of the vascular network in the process.
The indicators of the blood test for autoimmune pancreatitis are usually unchanged. In the biochemical analysis of blood, nonspecific signs of damage to the biliary tract and liver are detected: an increase in the level of liver enzymes, lipase and amylase, an increase in the concentration of bilirubin due to the conjugated fraction. If an autoimmune lesion of the lungs is suspected, radiography is performed, if kidney function is impaired, urine analysis according to Zimnitsky.
First of all, the disease must be differentiated from pancreatic cancer, especially in patients over 60 years of age. In favor of autoimmune inflammation is indicated by an increase in specific antibodies in the blood, typical ultrasound signs, inflammatory infiltration of pancreatic tissue according to histology results. Differential diagnosis is also carried out with primary sclerosing cholangitis, cancer of the biliary tract. To examine a patient with an autoimmune variant of pancreatitis, a gastroenterologist, oncologist, and immunologist are involved.
Autoimmune pancreatitis treatment
Since spontaneous healing is possible in some patients with complete restoration of exocrine and endocrine pancreatic functions, drug therapy is carried out only if there are appropriate indications. With an asymptomatic course, the prescription of medications is justified in the case of persistent pancreatic gland formation, persistent changes in liver parameters in combination with signs of sclerosing cholangitis. Recommended treatment regimens for the autoimmune variant of pancreatitis usually include:
- Glucocorticosteroids. Steroid hormones are first-line drugs and often have a long-term therapeutic effect for 2-3 weeks. In the absence of obvious fibrosis, the size and structure of the pancreas can fully recover. The appointment of steroids is effective not only for signs of pancreatitis, but also for autoimmune damage to other organs.
- Monoclonal antibodies. They are indicated for the resistant course of the disease or the presence of contraindications to steroid therapy. Synthetic immunoglobulins Ig G1-k are used to bind B-lymphocytic CD antigen. A rapid decrease in the number of B-lymphocytes is accompanied by a drop in the level of Ig G4 and the induction of remission of autoimmune pancreatic inflammation.
In symptomatic therapy, taking into account clinical manifestations, pancreatic enzymes, hypoglycemic agents and proton pump blockers are used. Nonsteroidal anti-inflammatory drugs, myotropic antispasmodics are recommended for the relief of pain syndrome. Patients with persistent compression undergo stenting of the main pancreatic duct, percutaneous transhepatic drainage of the bile ducts, nasobiliary drainage in ERCP. If minimally invasive techniques are unsuccessful, pancreatoejunostomy and cholecystoenterostomy are performed.
Prognosis and prevention
The outcome of the disease depends on the degree of tissue damage, the severity of complications. Although steroid therapy can achieve remission in more than 90% of patients, the prognosis of autoimmune pancreatitis is relatively unfavorable, in some patients there is an irreversible decrease in the endocrine and exocrine functions of the organ. Due to the insufficiently studied etiopathogenetic mechanism, specific prevention measures have not been developed. To prevent complications, it is important to detect and treat autoimmune diseases of the digestive tract in a timely manner.
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