What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloidosis of Digestive Tract
• Gastrointestinal Tract Amyloidosis
• GI Tract Amyloidosis

What is Gastrointestinal Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins)
• These protein aggregates are abnormally-formed and arranged into fibrils (slender fibers). An amyloid build-up can occur locally in only one organ, or may occur throughout the body. The deposition of amyloid proteins in the organs of the gastrointestinal system leads to Gastrointestinal (GI) Amyloidosis
• There are 5 major types of amyloidosis. The subtypes that lead to Amyloidosis of Gastrointestinal Tract may include:
  • AL amyloidosis that occurs when bone marrow produces too much amyloid protein creating light (L) chains
  • AA amyloidosis, when amyloid proteins build up secondary to a chronic disease
  • Hereditary amyloidosis: It is an inherited form of the disease; the amyloid build-up primarily affects the kidneys and nerves
  • Dialysis-related amyloidosis: This occurs in individuals who have undergone dialysis for a long time. The amyloid protein tends to get deposited in the tendons and joints
• Gastrointestinal Amyloidosis is generally associated with AA, AL, hereditary, and dialysis-related subtypes of amyloidosis. The condition usually occurs in older men and women, with men being more susceptible to the condition than women
• Gastrointestinal Amyloidosis may cause nausea, diarrhea or constipation, abdominal pain and bloating. Over time, it may cause weight loss and malnutrition. The treatment involves symptomatic therapy and effective management of the underlying amyloidosis
• The outcome of Gastrointestinal Amyloidosis depends on the underlying condition causing it, the severity of symptoms, and the response of the affected individual to treatment

Who gets Gastrointestinal Amyloidosis? (Age and Sex Distribution)

• Gastrointestinal Amyloidosis is more frequent in adults over 40 years of age. It may occur worldwide in any individual with systemic amyloidosis
• Although GI Amyloidosis can occur in both genders, more cases are observed in men than women
• In a small study of individuals with different subtypes of amyloidosis, approximately 3.6% showed GI Amyloidosis

What are the Risk Factors for Gastrointestinal Amyloidosis? (Predisposing Factors)

The following are some known risk factors for developing Gastrointestinal Amyloidosis:

• Advancing age
• Male gender
• A family history of amyloidosis
• Any condition that affects the antibody-producing cells in the body, including benign monoclonal gammopathy, malignant lymphoma, and multiple myeloma
• Chronic inflammatory conditions such as:
  • Arthritis, including rheumatoid arthritis, juvenile inflammatory arthritis, psoriatic arthritis, and ankylosing spondylitis
  • Inflammatory bowel disease (IBD) such as ulcerative colitis
• Chronic infections, including
  • Tuberculosis
  • Leprosy
  • Bronchiectasis
  • Osteomyelitis
  • Skin infections (especially in drug abusers, who use needles to inject themselves)
  • Chronic infection in skin with burns
  • Chronic kidney infections (pyelonephritis)
  • Whipple’s disease
• Poorly-controlled diabetes
• Infectious diseases such as HIV infection and AIDS
• Cystic fibrosis; individuals with this condition are prone to repeat infections
• Certain cancers such as Hodgkin’s lymphoma and renal cell carcinoma
• Family history of certain hereditary disorders that may include:
  • Familial Mediterranean fever (FMF)
  • Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)
  • Hyperimmunoglobulin D syndrome and periodic fever syndrome (HIDS)
  • Cryopyrin-associated periodic syndrome (CAPS)
  • Majeed syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Gastrointestinal Amyloidosis? (Etiology)

• Gastrointestinal Amyloidosis is a rare condition that is caused consequent to AA, AL, hereditary or dialysis-related subtypes of amyloidosis. Irrespective of the subtype of amyloidosis, abnormal proteins are generated that undergo misfolding to form amyloid proteins
• The amyloid protein fibrils circulate in the bloodstream and get deposited in the gastrointestinal tract. The following parts of the GI tract may be involved:
  • Mouth and tongue
  • Pharynx
  • Esophagus
  • Duodenum
  • Stomach
  • Small intestine
  • Colon
  • Rectum
  • Anus

What are the Signs and Symptoms of Gastrointestinal Amyloidosis?

The signs and symptoms of Gastrointestinal Amyloidosis may vary among the individuals, depending on the subtype of amyloidosis. However, individuals with the same subtype may also have varying symptoms.

The signs and symptoms related to the gastrointestinal system may include:

• Thickening of tongue (macroglossia)
• Difficulty in swallowing
• Acid reflux (gastroesophageal reflux disease or GERD)
• Sluggish peristaltic movement (process that moves food in the GI tract by involuntary muscle contractions)
• Nausea
• Loss of appetite; feeling of fullness after eating a small amount of food
• Gastric polyps (nodules on the stomach wall)
• Slowing of stomach emptying (gastrointestinal atony)
• Pseudo-obstruction of intestines; a sense of blocked intestines without any actual physical blockage
• Abdominal bloating and distension; abdominal pain
• Constipation or diarrhea that may even contain blood
• Clay-colored stools; or fatty and foul-smelling stools (steatorrhea)

GI Amyloidosis is generally a manifestation of systemic amyloidosis, affecting many different body tissues and organs. Therefore, the following additional signs and symptoms may be present:

• Fatigue
• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Joint pain
• Skin rashes, which may be purple or red spots
• Rash around eyes
• Eyes that appear puffy
• Tingling sensation and numbness
• Anemia
• Carpal tunnel syndrome (resulting in a weak grip)
• Bleeding disorders; problems with proper clotting of blood

How is Gastrointestinal Amyloidosis Diagnosed?

The diagnosis of Gastrointestinal Tract Amyloidosis may include general tests to ascertain the subtype of amyloidosis (and its underlying cause), as well as specific tests to assess damage to the structure and function of the gastrointestinal system.

The following methods may be employed for an accurate diagnosis of GI Amyloidosis:

• A thorough physical examination
• Evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood tests:
  • To perform “Freelite assay”, a measurement of light chain immunoglobulins
  • For measuring immunoglobulin by immunofixation electrophoresis
  • For measuring liver enzymes
• Urine tests to check function of kidneys
• Imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Endoscopy and colonoscopy to assess damage to the GI tract through:
  • Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the upper GI tract
  • Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area
  • Virtual colonoscopy, which is a combination of analysis methods, relying on computer technology and X-rays
  • Flexible sigmoidoscopy, which is a testing protocol utilizing a small camera with an attached light, to examine the rectum and lower colon
• Manometry: In this procedure, a device is inserted into the GI tract to check muscle pressure and movement in an individual who is sedated. The apparatus is connected to a computer. Upon standing up, the movement of food is monitored through the images on computer. This procedure is generally performed to assess obstruction in the digestive tract
• Tissue biopsy: A biopsy of an affected organ or tissue is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In GI Tract Amyloidosis,
  • Immunohistochemical analysis of tissue samples using anti-AA serum may be performed, to identify the type of amyloidosis an individual has
  • Amyloid deposit from affected tissue is detected using a staining procedure. When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)
• Bone marrow aspiration for checking the type of abnormal immunoglobulin light chains
• Molecular genetic testing to check for mutation(s) in genes known to cause various types of amyloidosis
• Molecular testing to check the type of proteins in amyloid deposits through mass spectrophotometry

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Gastrointestinal Amyloidosis?

The potential complications of Gastrointestinal Amyloidosis may include:

• Inability to eat food
• Weight loss and malnutrition
• Bacterial infection in the intestines

How is Gastrointestinal Amyloidosis Treated?

The following are some treatment options for Gastrointestinal Amyloidosis:

• Placement of feeding tube to prevent malnutrition
• Administration of medications for the following:
  • Pain, if necessary
  • Acid reflux
  • Diarrhea
  • Constipation
  • Improving muscle movement in the intestine
  • Treating infection (antibiotics)
• Decompression procedure to remove gas from colon and ease abdominal bloating
• If the patient is able to swallow, small and frequent meals may be recommended
• Surgery, if there is intestinal pseudo-obstruction that is not treatable by medications

GI Amyloidosis generally does not occur in isolation; it is often associated with involvement of many other organs as part of systemic amyloidosis. Therefore, additional treatments pertaining to the subtype of amyloidosis and its underlying cause are often necessary.

How can Gastrointestinal Amyloidosis be Prevented?

Currently, there are no specific methods or guidelines to prevent Gastrointestinal Amyloidosis.

• Seeking prompt medical attention for pre-existing conditions that can lead to amyloidosis, which consequently causes GI Amyloidosis is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Gastrointestinal Amyloidosis? (Outcomes/Resolutions)

• The prognosis for Gastrointestinal Amyloidosis is determined by a number of factors, such as the extent of the condition, overall health of the affected individual, and his/her response to treatment
• With timely and appropriate treatment, it is possible to delay progression of the condition and have an improved quality of life. However, if complications develop, the prognosis may be guarded

Additional and relevant Useful information for Gastrointestinal Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum