Amyloidosis

Amyloidosis refers to a group of diseases caused by the accumulation of the protein amyloid in different organs and tissues. Amyloid protein is produced by plasma cells in bone marrow and is deposited in and around tissues, nerves, and organs.

Buildup of amyloid protein affects the structure and function of tissues and organs. The pattern of deposit varies with each individual.

Symptoms of amyloidosis result from abnormal functioning of the organ or tissue due to the protein buildup.

Diagnosis of amyloidosis is based on a biopsy of the tissue. Severe amyloidosis is potentially life-threatening due to multiple organ failure.

Treatment depends on the type of amyloidosis and focuses on treating the underlying condition and controlling production of amyloid protein. 

Symptoms of amyloidosis depend on the organ affected by the protein accumulation. In most cases, symptoms appear only after the condition has reached an advanced stage. They are also very subtle and often may go unnoticed or are mistaken for another medical condition with similar symptoms.

Some of the general symptoms of amyloidosis include:

• Fatigue
• Shortness of breath
• Swelling of tongue
• Anemia
• Tingling and numbness in the legs and feet
• Joint pain
• Clay-colored stools
• Weakness
• Weight loss
• Change in skin color

Amyloid deposits in the heart wall make it stiff and affect heart rhythm. This condition causes excessive pressure on the heart, which could impact its functioning, including pumping blood. Heart amyloidosis is characterized by:

• Shortness of breath
• Irregular heartbeat
• Swelling of the feet and ankles
• Weakness and fatigue
• Nausea

Kidneys are largely responsible for filtering out wastes from the body. Protein buildup in the kidneys makes it hard for the body to detoxify. It results in the accumulation of fluid and toxins, leading to kidney failure. Symptoms of kidney amyloidosis are:

• Swelling of the feet and ankles
• Swelling around the eyes
• Increased levels of protein in urine

Accumulation of protein in the gastrointestinal tract leads to gastrointestinal amyloidosis. An excessive buildup of proteins in the gastrointestinal tract can cause difficulty in food digestion, which results in indigestion and is characterized by lack of appetite, diarrhea, nausea, stomach pain, and weight loss.

Amyloid deposits in the liver lead to its enlargement, fluid buildup, and abnormalities in liver function tests.

Amyloid deposits in nerves result in amyloid neuropathy characterized by:

• Difficulty balancing
• Problems controlling bladder and bowel movements
• Excessive sweating
• Tingling
• Weakness
• Light-headedness

Amyloidosis is caused by the accumulation of the abnormal protein amyloid in and around tissues and organs.

There are different types of amyloidosis, and the cause depends on the specific type of amyloidosis:

• AL amyloidosis: Also known as primary or immunoglobulin light chain amyloidosis, this type is caused by amyloid light chains (AL), a kind of protein produced by the bone marrow that is hard to break. These proteins are normally deposited around the kidney, liver, heart, nerves, and intestines.
• AA amyloidosis: Also known as secondary amyloidosis, this type is associated with chronic inflammatory conditions like rheumatoid arthritis and inflammatory bowel disease. AA stands for amyloid protein A, which accumulates around the tissues. It mostly affects the kidneys, liver, and adrenal glands.
• Familial amyloidosis: Also called hereditary amyloidosis, this is a rare form of amyloidosis that runs in families. The abnormal protein accumulates in the liver, nerves, heart, and kidneys and is caused by the buildup of the protein amyloid transthyretin. It is commonly seen in African-Americans.
• Dialysis-related amyloidosis: This type is commonly seen in people who have been on dialysis for several years. It is caused by the buildup of beta-2 microglobulin protein in the blood and most commonly affects joints, bones, and tendons. 

Deposits may also happen in specific organs like the skin, resulting in different symptoms.
The major risk factors for amyloidosis are:

• Age
• Gender
• Other medical conditions
• Family history
• Dialysis

It is most commonly seen in men above the age of fifty. 

Types of Amyloidosis

Various proteins could result in amyloid deposits in the body, however, only some of these are associated with health issues. The kind of protein accumulation and where it occurs in the affected person’s body is used to determine the type of amyloidosis. Amyloid deposits can happen in the entire body or may concentrate in one or two parts.

There are several types of amyloidosis, including:

• Primary (systemic AL) amyloidosis: This condition manifests without a specific cause, but it is most commonly seen in people with a form of blood cancer known as multiple myeloma. Primary amyloidosis is also one of the most common forms of amyloidosis. “Systemic” is a term used when a condition impacts the entire body. This condition most commonly affects the kidney, liver, heart, and central nervous system.
• Secondary (systemic AA) amyloidosis: This condition normally occurs due to another secondary medical condition like a chronic inflammatory disease, such as lupus, rheumatoid arthritis, tuberculosis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), and certain cancers. The condition is known to usually impact the functioning of various organs like the spleen, kidneys, liver, adrenal gland, and lymph nodes.
• Dialysis-related amyloidosis (DRA): This condition is more commonly seen in older adults and patients who have undergone dialysis treatment for over five years. The condition normally results due to deposits of beta-2 microglobulin, which often builds up in the blood stream. The deposits can happen in various tissues, but the impact is largely seen in bones, joints, and tendons.
• Familial, or hereditary, amyloidosis (AF): This is a rather rare condition that is normally genetic and seen in family lines. It occurs due to an abnormal amyloid transthyretin (TTR) protein, which is created in the liver. This form of protein is known to trigger most common forms of hereditary or genetic amyloidosis.
• Senile systemic amyloidosis (SSA): This condition occurs due to deposits of proteins or TTR in the heart. The deposits could also occur in various other tissues and are most commonly observed in older men.
• Organ-specific amyloidosis: This condition triggers protein deposits in various organs. The deposits can also occur in the skin; this is known as cutaneous amyloidosis.

Although many researches have shown a linkage between amyloid deposits and Alzheimer’s disease, the brain is not often responsible for systemic amyloidosis.

Symptoms of amyloidosis resemble those of many other medical conditions, making diagnosis difficult. Since amyloidosis is often the result of another underlying condition, it is more important to first identify this condition, followed by amyloidosis.

The diagnostic procedure begins with a detailed physical exam and an analysis of the patient’s medical history.

When it comes to lab tests, there are no specific blood tests that can detect amyloidosis. However, there are certain detailed and advanced laboratory tests, known as electrophoresis or free light chain assays, that can help identify amyloid proteins in the blood stream.

In certain cases, doctors may also recommend a biopsy, which is required to identify the protein responsible for triggering the disease. A tissue sample is extracted from the body and sent for biopsy. The sample may be obtained from the abdomen, mouth, rectal region, or other organ. It is not necessary for the sample to be obtained only from the affected organ; traces of amyloid deposit can be found even in other organs of the body.

If the doctor suspects the disease to be genetic, a genetic screening may be conducted. It is important to identify the correct cause of the disease, as treatment differs for each type of amyloidosis.

Other forms of sample testing, like blood, urine, or scans, may be recommended to test the functioning capacity of various organs that are suspected to be affected by the disease.

There is no definitive cure for amyloidosis, but treatment strategies help alleviate the signs and symptoms of protein buildup.

Timely treatment also helps limit the production of abnormal proteins. Treatment methods depend on the type of amyloidosis:

• Chemotherapy and stem cell transplant are the treatment options for AL amyloidosis. Chemotherapy limits the growth of cells that produce the abnormal protein. Patients with early stages of amyloidosis benefit from peripheral blood stem cell transplant. In this procedure, stem cells are collected from the peripheral blood. These stem cells are then reintroduced into the patient after high-dose chemotherapy.
• Anti-inflammatory medications are suggested to control the underlying conditions that result in AA amyloidosis. 
• Liver transplant is an option for treating hereditary amyloidosis, as the abnormal proteins are produced in the liver. 
• Kidney transplant or changing the type of dialysis helps control dialysis-related amyloidosis. 
• Medications are suggested to control symptoms like pain and fluid retention. Pain killers, diuretics, and blood-thinning medications are commonly recommended.

There is no standard prevention method for amyloidosis, as the actual cause of the condition is not known.

Preventing inflammatory diseases like rheumatoid arthritis helps block secondary amyloidosis. 

A few alternative and homeopathic remedies exist for amyloidosis.

Natural remedies help reduce the progression of amyloidosis.

Antioxidants like lipoic acid, carnosine, acetyl-l-carnitine, and vitamins C and E are suggested to control protein buildup. 

There are different ways to adapt your lifestyle to cope with amyloidosis:

• Having a balanced diet helps improve energy levels
• A low-salt diet is usually recommended to control fluid buildup. Avoiding strenuous activities prevents shortness of breath
• Having a support group allows individuals to discuss feelings and experiences. Supportive family and friends are equally important in coping with the disease
• Framing achievable goals and working towards them gives ample confidence 

Risks and complications of amyloidosis depend on the organ affected by the protein buildup.

It can lead to kidney failure, shortness of breath, change in heart rhythm, pain and numbness in the fingers, sudden drop of blood pressure, and fainting.

Men are more susceptible to amyloidosis compared to women. The risks are known to increase with age. People suffering from other diseases, such as cancer, are more prone to getting amyloidosis due to other factors. 15% of patients who suffer from multiple myeloma stand at a high risk of acquiring amyloidosis.

People with renal failure or kidney disease and who are undergoing dialysis treatment on a long-term basis are also very likely to suffer from amyloidosis.

Coming to Terms

Accepting a condition like amyloidosis can be hard for patients since it affects the functioning of major organs like the heart, kidneys, and liver. Early diagnosis is the first step towards stopping the disease’s progression, which in most cases develops very quickly. Diagnosis should be promptly followed by the required treatment, as many people die within two years of being diagnosed with this condition without the right treatment. Although much research is being done in this field, it is still difficult for patients to come to terms with the fact that they are suffering from a life-threatening disease. Having a positive outlook is very important, and it is also crucial to keep in touch with your doctor and participate in any follow-up treatment.