Argininosuccinic Aciduria

 Argininosuccinic Aciduria

Overview

Autoimmune pancreatitis (AIP) is a chronic inflammation that is thought to be caused by the body's immune system attacking the pancreas and that responds to steroid therapy. Two subtypes of AIP are now recognized, type 1 and type 2.

Type 1 AIP is the pancreatic manifestation of a disease called IgG4-related disease (IgG4-RD). This disease often affects multiple organs including the pancreas, bile ducts in the liver, salivary glands, kidneys and lymph nodes.

Type 2 AIP seems to affect only the pancreas, although about one-third of people with type 2 AIP have associated inflammatory bowel disease.

Type 1 AIP can be mistakenly diagnosed as pancreatic cancer. The two conditions have overlapping signs and symptoms, but very different treatments, so it is very important to distinguish one from the other.

Symptoms

Autoimmune pancreatitis (AIP) is difficult to diagnose. Often, it doesn't cause any symptoms. Symptoms and signs of type 1 AIP are similar to those of pancreatic cancer.

Pancreatic cancer signs and symptoms can include:

Dark urine

Pale stools or stools that float in the toilet

Yellow skin and eyes (jaundice)

Pain in your upper abdomen or middle part of your back

Nausea and vomiting

Weakness or extreme tiredness

Loss of appetite or feelings of fullness

Weight loss for no known reason

The most common sign of type 1 AIP, present in about 80% of people, is painless jaundice, caused by blocked bile ducts. Type 2 AIP can present with recurrent episodes of acute pancreatitis. Pain in the upper abdomen, a common symptom of pancreatic cancer, is frequently absent in autoimmune pancreatitis.

Differences between type 1 and type 2 AIP are:

In type 1 AIP, the disease may affect other organs in addition to the pancreas. Type 2 AIP affects only the pancreas, although the disease is associated with another autoimmune condition, inflammatory bowel disease.

Type 1 AIP predominantly affects men in the sixth to seventh decade of life.

Type 2 AIP affects both men and women equally and has a younger age of onset compared with type 1 AIP.

Type 1 AIP is more likely to relapse after treatment is discontinued.

When to see a doctor

Autoimmune pancreatitis often doesn't cause any symptoms. See your doctor, however, if you experience unexplained weight loss, abdominal pain, jaundice, or other signs and symptoms that bother you.

Causes

Doctors don't know what causes autoimmune pancreatitis, but as in other autoimmune diseases, it is thought to be caused by the body's immune system attacking healthy body tissue.

Risk factors

The two types of AIP occur with different frequency in different parts of the world. In the United States, about 80 percent of people with autoimmune pancreatitis have type 1.

People with type 1 autoimmune pancreatitis often:

Are over age 60

Are male

People with type 2 autoimmune pancreatitis:

Are often over age 40 (one or two decades younger than those with type 1)

Are as likely to be female as male

Are more likely to have inflammatory bowel disease, such as ulcerative colitis

Complications

Autoimmune pancreatitis can cause a variety of complications.

Pancreatic exocrine insufficiency. AIP may affect the ability of your pancreas to make enough enzymes. Signs and symptoms may include diarrhea, weight loss, metabolic bone disease, and vitamin or mineral deficiency.

Diabetes. Because the pancreas is the organ that produces insulin, damage to it may cause diabetes and you may need treatment with oral medication or insulin.

Pancreatic and bile duct stricture.

Pancreatic calcifications or stones.

Treatments for autoimmune pancreatitis, such as long-term steroid use, also can cause complications. However, even with these complications, people who are treated for autoimmune pancreatitis have a normal life expectancy.

There is no established association between AIP and pancreatic cancer.

Diagnosis

Autoimmune pancreatitis is difficult to diagnose, because its signs and symptoms are very similar to those of pancreatic cancer. However, an accurate diagnosis is extremely important. Undiagnosed cancer may result in delaying or not receiving necessary treatment.

People with AIP tend to have a general enlargement of the pancreas, but they may also have a mass in the pancreas. To pinpoint the diagnosis and determine which type of AIP you have, blood and imaging tests are necessary.

Tests

No single test or characteristic feature identifies autoimmune pancreatitis. Consensus guidelines for diagnosis use a combination of imaging, blood tests and biopsy results.

Specific tests may include:

Imaging tests. Tests of your pancreas and other organs may include CT, MRI, endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP).

Blood tests. You will be tested for elevated levels of an immunoglobulin called IgG4, produced by your immune system. People with type 1 AIP, but usually not with type 2 AIP, will have highly elevated blood levels of IgG4.

However a positive test doesn't necessarily mean that you have the disease. A small number of people who don't have autoimmune pancreatitis, including some with pancreatic cancer, also have high blood levels of IgG4.

Endoscopic core biopsy. In this test, pathologists analyze a sample of pancreatic tissue in the laboratory. AIP has a distinctive appearance that can be easily recognized under a microscope by an expert pathologist. Doctors insert a small tube (endoscope) through the mouth into the stomach and, guided by ultrasound, remove some tissue from the pancreas using a special needle.

The challenge is obtaining a sample of tissue large enough to analyze, rather than just a few cells. This procedure is not widely available, and results may not be conclusive.

Steroid trial. Autoimmune pancreatitis generally responds to steroids; doctors sometimes use a trial course of this drug to confirm a diagnosis. However, this strategy should ideally be under expert guidance, be used sparingly and only be done when there is strong evidence to support a diagnosis of autoimmune pancreatitis. Response to corticosteroids is measured by CT and improvement in serum IgG4 levels.

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Treatment

Biliary stenting. Before starting medication, sometimes doctors will insert a tube to drain the biliary ducts (biliary stenting) in people with symptoms of obstructive jaundice. Often, though, jaundice improves with steroid treatment alone. Sometimes drainage is recommended if the diagnosis is uncertain. Tissue samples and cells from the bile duct may be obtained at the time of stent placement.

Steroids. Symptoms of autoimmune pancreatitis often improve after a short course of prednisolone or prednisone. Many people respond quickly, even dramatically. Sometimes people get better without any treatment.

Immunosuppressants and immunomodulators. About 30% to 50% of the time in type 1 AIP and less than 10% of the time in type 2 AIP, the disease relapses, requiring additional treatment, sometimes long term.

To help reduce the serious side effects associated with extended steroid use, doctors often add drugs that suppress or modify the immune system, sometimes called steroid-sparing medications, to the treatment. You may be able to stop taking steroids altogether depending on your response to steroid-sparing medication.

Immunosuppressants and immunomodulators include mycophenolate (CellCept), mercaptopurine (Purinethol, Purixan), azathioprine (Imuran, Azasan) and rituximab (Rituxan). In general, they have been used in small sample groups and long-term benefits are still being studied.

Monitoring of other organ involvement. Type 1 AIP often is associated with other organ involvement, including enlarged lymph nodes and salivary glands, scarring of the bile ducts, liver inflammation, and kidney disease. Although these signs may lessen or disappear completely with steroid therapy, your doctor will continue to monitor you.

TYPE OF DOCTOR AND DEPARTMENT: Gastroenterology and Hepatology SPECIALIST CAN DIAGNOSE THIS DISEASE.