Types of Amyloidosis Symptoms

Relief for Different Types of Amyloidosis Pain

Medically reviewed by Renee Nilan, MD

"Amyloidosis" is the name for a rare group of diseases in which amyloid protein builds up in the organs. That buildup affects the way organs and body tissues work. Amyloidosis can affect the heart, kidneys, spleen, liver, gastrointestinal (GI) tract, and nervous system.

Amyloidosis is often classified into subtypes based on the body areas it affects, and symptoms are specific to those areas. The disease is often overlooked in its earliest stages because it does not cause symptoms. When there are symptoms, they are often mistaken for those caused by other conditions.

Risk factors for amyloidosis include family history and genetics, inflammatory conditions, long-term kidney dialysis, and older age. Early diagnosis might prevent organ damage, and while there is no cure for the condition, amyloidosis is manageable and treatable.

Amyloidosis is not a type of cancer. However, one form is associated with some types of blood cancer, including multiple myeloma.

This article covers the various body area symptoms caused by amyloidosis, diagnosis, treatment, and more.

Amyloidosis Skin Symptoms

Amyloidosis that affects the skin is called cutaneous amyloidosis. It causes amyloid proteins to be deposited in the two layers of skin (the dermis and epidermis). It is considered localized amyloidosis because it mainly affects the skin and does not invade the organs.

Cutaneous amyloidosis causes patches of skin that may appear in abnormal textures and colors. The reason for the different appearance is that there are three forms of the condition: lichen amyloidosis, macular amyloidosis, and nodular amyloidosis.

Lichen amyloidosis causes very itchy, bumpy skin patches. These patches might also be scaly, red-brown, and primarily appear on the shins but may occur on other leg areas, the forearms, and other body areas. 

With macular amyloidosis, skin patches are dark brown and flat, although they may have a lacy or rippled appearance. These lesions can be found on the upper back, torso, and limbs. Patches might be itchy.

Nodular amyloidosis causes firm, raised nodules (bumps) that may appear pink, red, or brown. Nodules might appear on the face, torso, limbs, or genitals. Nodular amyloidosis isn't typically itchy or painful.

Some people experience a combined type of cutaneous amyloidosis that includes skin symptoms of both lichen and macular amyloidosis. This is called biphasic amyloidosis. 

Cutaneous amyloidosis typically isn't life-threatening, but it can lead to cosmetic changes and cause severe itching that diminishes your quality of life. Like other skin diseases (i.e., psoriasis and vitiligo), it can cause psychosocial stress and emotional challenges.

Additional symptoms of amyloidosis that may affect skin cells are easy bruising, patches around the eyes, and hair loss. Amyloidosis may also cause tongue and muscle enlargement.

Amyloidosis Respiratory Symptoms

Respiratory involvement occurs in 50% of people with amyloidosis. Respiratory symptoms might mimic those seen in people with interstitial lung disease—a lung condition that causes progressive lung scarring.

Respiratory symptoms of amyloidosis include shortness of breath, cough, mucus that contains blood, wheezing, and recurrent respiratory tract infections.

Amyloidosis that affects the lungs can also cause shortness of breath. This symptom will make everyday activities like climbing stairs harder, and you may need to rest after little physical exertion.

Amyloidosis Cardiac Symptoms

Amyloidosis that affects the heart is caused by amyloid deposits on heart tissue that make it harder for the heart to function. Cardiac amyloidosis will not cause symptoms early on. 

When symptoms do present, they may include:

• Nocturia (frequent nighttime urination)

• Heart palpitations (sensation of feeling your heartbeat)

• Fatigue and reduced exercise ability

• Swelling of the legs, ankles, abdomen, and other body areas

• Breathing troubles

If amyloidosis affects the heart, it may cause shortness of breath. This happens because amyloid deposits affect the heart's ability to fill up with blood between heartbeats, which means less blood is pumped. Cardiac amyloidosis might make it harder to take deep breaths, especially when lying flat on your back.

Amyloidosis Weight Symptoms

Amyloid protein loss from the blood can lead to loss of appetite and weight loss. Swallowing and chewing difficulties from an enlarged tongue can lead to discomfort and cause you to eat less, so you lose weight. 

If amyloidosis affects the digestive system, it might impair food digestion and nutrient absorption, affecting weight and causing nutritional deficiencies. Symptoms like diarrhea and esophageal reflux may also contribute to weight loss.

Amyloidosis Gastrointestinal Symptoms

Amyloidosis that causes amyloid proteins to accumulate in the GI tract is called GI amyloidosis. This type of amyloidosis can be genetic or acquired.

GI amyloidosis causes weight loss, bleeding, diarrhea, constipation, malabsorption, esophageal reflux, and obstruction. Symptoms will vary based on the type and location of amyloid deposits.

Amyloidosis Neurological Symptoms

Amyloidosis can cause neurological symptoms that affect peripheral sensory, motor, and autonomic nerves. Amyloid deposits can also lead to problems in these nerves. 

The most common neurological symptoms of amyloidosis include:

• Painful paresthesia (tingling, burning, or numbness in your skin) in your hands or feet

• Balance troubles

• Ongoing nausea and vomiting

• Diarrhea, constipation, and incontinence if amyloidosis affects the nerves that control these processes

• Sweating abnormalities

• Sexual dysfunction 
  

Amyloidosis Musculoskeletal Symptoms

Amyloidosis can affect bones, joints, and muscles. It can cause the muscles to be enlarged and bone and joint pain and swelling. It can also increase your risk for fractures (bone breaks).

Amyloid proteins might even affect the spine and cause neurological symptoms and muscle weakness. Protein buildup has also been linked to bone erosion and destruction, bone cysts, and carpal tunnel syndrome.

Amyloidosis Kidney Symptoms

Amyloidosis can limit the kidneys' filtering system causing proteins in the blood to leak into the urine. This causes the kidneys to become sluggish in removing waste products, eventually leading to kidney failure and the need for dialysis.

If you have kidney damage, you might experience nephrotic syndrome. Symptoms of nephrotic syndrome include: 

• Swelling in multiple body areas

• Increased risk for blood clots

Amyloidosis Systemic Symptoms

Amyloidosis can cause systemic symptoms that affect the whole body or an entire body system. Such symptoms include:

• Fatigue or extreme tiredness

• Inflammation (swelling)

• Edema (fluid buildup) that leads to painful swelling

• Low blood pressure

• Appetite loss

• Nausea

• Skin rash

• Dizziness 
  

Types of Amyloidosis

Determining the type of amyloidosis can be helpful to your healthcare provider in offering treatments and determining prognosis. 

Primary Amyloidosis

Light-chain amyloidosis—also called primary amyloidosis—is the most common type and accounts for 70% of amyloidosis cases. It causes amyloid proteins to be overproduced in the bone marrow by plasma cells, a type of white blood cell that produces antibodies. In this type, the amyloid protein is a misshapen subunit of antibodies called light chains.

These proteins circulate into the bloodstream and deposit in various body areas, including the heart, kidneys, spleen, nerves, and skin. This type is sometimes linked to multiple myeloma, a type of blood cancer affecting the plasma cells.

Secondary Amyloidosis

Autoimmune amyloidosis—also called secondary amyloidosis—occurs because of a reaction from a chronic inflammatory condition or an infection. AA amyloidosis is caused by serum amyloid A protein produced in response to inflammation.

Conditions that might lead to AA amyloidosis include:

• Autoimmune diseases like rheumatoid arthritis (RA)

• Inflammatory bowel diseases like Crohn's disease and ulcerative colitis

• Periodic fever syndromes such as familial Mediterranean fever

• Chronic infections, including tuberculosis and osteomyelitis

• Malignancies, such as Hodgkin's disease and renal cell carcinoma
  

Transthyretin Amyloidosis

Transthyretin amyloidosis is caused by a mutation in the transthyretin gene leading to a production of abnormal transthyretin protein. It is an inherited amyloidosis type that can lead to neuropathy (nerve damage) and cardiomyopathy (enlarged and stiffened heart muscle) in mid to late life.

Beta-2 Microglobulin Amyloidosis

Beta-2 microglobulin amyloidosis is caused by chronic renal failure and occurs in people on long-term dialysis. With this type of amyloidosis, beta-2 microglobulin amyloid deposits will build up in body tissues, especially the joints. This happens because the kidneys cannot rid the body of the proteins due to the kidneys failing. 

Localized Amyloidosis

Localized amyloidosis leads to localized amyloid proteins in the airways, eyes, bladder, skin, heart, and other body areas. Multiple subtypes exist but usually do not become systemic.

How Are Amyloidosis Symptoms Diagnosed?

Early diagnosis of amyloidosis can prevent organ and tissue damage. Unfortunately, the disease is often overlooked because the symptoms it causes are seen in various conditions. It is also possible for the condition to be asymptomatic (having no disease symptoms) at first. 

Your healthcare provider will start with a physical exam. This looks for physical signs of the condition, including skin symptoms like easy bruising, nodules, skin plaques, brittle nails, and swelling throughout the body.

Your healthcare provider will also want to know about your family history and medical history, along with the symptoms you are experiencing. 

Immunohistochemistry (IHC) testing can be used to determine the subtype of amyloidosis. It involves a tissue collection to look for amyloid proteins on the cell surfaces. The IHC test is typically done with a protein electrophoresis test, which can help detect amyloidosis.

Additional testing for amyloidosis includes laboratory testing and imaging, such as:

• Laboratory testing: Both blood work and a urinalysis can be used to check for amyloid protein levels. Blood work might also be used to check kidney and liver function.

• Biopsy: A small tissue sample is removed from an area affected by amyloid proteins and analyzed to determine the type of amyloidosis.

• Bone marrow aspiration: The bone marrow aspiration test takes a small amount of fluid from inside the bone. A bone marrow biopsy can remove tissue from inside the bone. Samples are taken to a lab to look for abnormal cells.

• Imaging studies: Imaging tests, including echocardiogram, can produce images of the heart to see if amyloid proteins have caused heart damage. Nuclear imaging might also be done to look for signs of amyloidosis and help your healthcare provider determine the type.
  

What Helps With Amyloidosis Pain Symptoms?

Some of the symptoms of amyloidosis can be painful, including neuropathy and joint and muscle pain. Severe organ damage might also cause pain and discomfort. 

Amyloidosis nerve pain can be managed with anti-seizure drugs, antidepressants, and analgesics such as Advil (ibuprofen), Indocin (indomethacin), and opioids. Medicines like corticosteroids can reduce bone, muscle, and joint inflammation and swelling. Diuretics can reduce fluid to decrease pain in edema-affected body areas.

Treatment Options for Amyloidosis Symptoms

Treatment for amyloidosis aims to reduce symptoms and prevent complications like kidney, liver, or heart failure. Treatment may vary based on the type of amyloidosis and the symptoms it causes.

For example, primary amyloidosis treatment includes chemotherapy, corticosteroids, and Velcade (bortezomib), a targeted therapy for amyloidosis. These medicines can slow down organ damage and improve quality of life. Velcade works by targeting processes that lead to the development of abnormal amyloid proteins. 

Autoimmune amyloidosis is treated by managing the underlying cause. For example, if the cause is an inflammatory arthritis disease, it can be treated with biologics and other disease-modifying antirheumatic drugs (DMARDs).

A person whose amyloidosis has damaged their liver will need a liver transplant. The new liver will not produce abnormal amyloid proteins. A person whose kidneys have been damaged by amyloidosis may need dialysis to filter their blood regularly. 

Researchers are looking at new therapies to prevent amyloid proteins from depositing in the organs. They have also looked at high-dose chemotherapy with autologous stem cell transplantation to treat primary amyloidosis and improve life expectancy.

Summary

Amyloidosis is a group of diseases that causes abnormal amyloid protein buildup in various body areas, including the skin, heart, lungs, kidneys, and liver. Left untreated, this buildup can be dangerous and cause organ damage. There are different types of amyloidosis, but the two most common are primary and secondary amyloidosis. 

Symptoms of amyloidosis can affect various body areas and include skin patches and nodules, neurological symptoms, weight loss, shortness of breath, muscle, bone, and joint pain, muscle weakness and enlargement, kidney filtering problems, and systemic symptoms like dizziness and severe fatigue. 

Secondary amyloidosis is typically treated by managing its underlying cause, while other types are treated with chemotherapy, corticosteroids, and drugs designed to reduce abnormal amyloid protein buildup. There is no cure for amyloidosis, but managing symptoms and preventing complications like organ failure is possible.