Every body is different. People react to illness in their own ways, with symptoms that can look and feel different from person to person — even with the same diagnosis. This is especially true with systemic amyloidosis, a rare disease that can affect many parts of the body.

Systemic amyloidosis happens when abnormal protein material, called amyloid, builds up in organs and tissues. These protein deposits can appear in different places and cause a wide range of symptoms, making the condition hard to diagnose. The symptoms can also look like those of other conditions.

Below, we’ll explore some of the organs and organ systems that can be affected by systemic amyloidosis.

What Is Systemic Amyloidosis?

In systemic amyloidosis, amyloid builds up in more than one part of the body, making it difficult for affected organs to work properly. The different types of systemic amyloidosis are named for the kind of protein that forms the amyloid deposits. The three most common types are:

• Amyloid light-chain amyloidosis (AL amyloidosis) — Often linked to a bone marrow disorder, AL amyloidosis commonly affects the heart and kidneys.
• Reactive amyloidosis (AA amyloidosis) — Usually occurring due to chronic inflammation from another condition, AA amyloidosis typically affects the kidneys, liver, and gastrointestinal (GI) tract.
• Transthyretin amyloidosis (ATTR amyloidosis) — Caused by a mutation (change) in the transthyretin protein or by age-related changes, ATTR amyloidosis most often involves the heart and the nervous system.

Other parts of the body, such as muscles and skin, can also be affected by systemic amyloidosis.

Not everyone experiences symptoms the same way, so it’s important to tell your healthcare provider if you notice anything new or unusual. Early diagnosis is important — the sooner the condition is diagnosed and treated, the better the chance of avoiding long-term organ damage from amyloid deposits.

1. Heart

When amyloid builds up in the heart muscle, it’s called cardiac amyloidosis. These protein deposits make the heart muscle stiff and less able to stretch or relax, so the heart can’t fill and pump blood the way it should. Over time, this weakens the heart muscle and can lead to heart failure.

Cardiac amyloidosis is most often linked to AL and ATTR amyloidosis. About 50 percent to 70 percent of people with AL amyloidosis have amyloid deposits in their heart. Common symptoms of cardiac amyloidosis include:

• Shortness of breath, even during light movement or at rest
• Heart palpitations (feeling your heart is racing or pounding)
• Swelling in the feet, ankles, legs, and belly due to fluid buildup
• Fatigue (persistent exhaustion that doesn’t improve with rest) that may get worse over time
• Enlarged neck veins, which are a sign of fluid overload from heart failure

Your healthcare provider may check for cardiac amyloidosis using tests such as the following:

• Blood tests and urine tests to look for amyloid protein
• Echocardiogram, which uses ultrasound to take a picture that shows how well your heart is moving and pumping
• Electrocardiogram to measure the heart’s electrical signals
• Cardiac MRI, which uses magnets and radio waves to create detailed pictures of the heart
• Heart biopsy (taking a small sample of tissue to look at under a microscope) to confirm amyloid deposits

2. Kidneys

The kidneys are another common site of amyloid protein deposits. These deposits can interfere with the kidneys’ ability to remove fluid and waste from the blood and may lead to kidney failure if left untreated. About two-thirds of people with AL amyloidosis have kidney involvement. The kidneys are also commonly affected in AA amyloidosis.

The main sign of kidney amyloidosis is nephrotic syndrome, a group of symptoms that include:

• Proteinuria (high levels of protein in the urine)
• Low levels of protein in the blood
• Swelling, often in the legs or ankles or around the eyes
• High levels of cholesterol and other fats in the blood
• Abnormal lab results, such as low albumin and high creatinine or blood urea nitrogen

To check for amyloid in the kidneys, your healthcare provider may order blood and urine tests. A kidney biopsy may be needed to confirm the diagnosis.

3. Liver

Amyloid protein can also build up in the liver — one study found that 70 percent of people with primary systemic amyloidosis had amyloid deposits in this organ. However, in most cases, liver-related symptoms are mild or go unnoticed. When symptoms do occur, they often include an enlarged liver or abnormal liver function tests.

As with other organs, a biopsy is the only way to confirm amyloidosis in the liver. Imaging tests such as CT and MRI scans can help detect signs of amyloid deposits, such as an enlarged or nodular (bumpy-looking) liver.

4. Peripheral Nervous System

Systemic amyloidosis can affect the peripheral nervous system, which is the network of nerves outside the brain and spinal cord. Sensory and motor nerves control sensations and movement, while autonomic nerves manage automatic body functions like blood pressure, digestion, and heart rate.

When amyloid deposits interfere with these nerves, the condition is called peripheral neuropathy. About 15 percent to 35 percent of people with AL amyloidosis have peripheral neuropathy. In addition, one form of ATTR amyloidosis is defined by the neuropathy it causes, and nervous system symptoms are the main or earliest signs.

Peripheral neuropathy symptoms depend on which nerves are involved. Damage to sensory or motor nerves may cause:

• Numbness
• Pins-and-needles (tingling) sensations
• Burning or shooting pain
• A feeling of an electric shock
• Weakness in affected muscles

For example, carpal tunnel syndrome occurs when amyloid deposits press on a nerve in the wrist. If both wrists are affected and typical treatments don’t help, that may be an early sign of amyloidosis, especially in ATTR amyloidosis.

Damage to autonomic nerves can lead to more systemic symptoms, including:

• Orthostatic hypotension (a drop in blood pressure when standing), often causing dizziness, lightheadedness, or fainting
• Diarrhea and constipation
• Erectile dysfunction (trouble getting or keeping an erection)
• Dry eyes or dry mouth

A nerve biopsy can help confirm the diagnosis. Other tools such as nerve conduction studies and electromyography can help determine the type and severity of nerve damage. In cases of small fiber neuropathy, which affects pain and temperature sensation, a skin biopsy with nerve fiber density testing may be needed.

5. Gastrointestinal Tract

Your gastrointestinal tract includes your mouth, throat, stomach, small intestine, rectum, and anus. When amyloid deposits build up in the GI tract, symptoms can vary widely depending on which areas are affected. The symptoms are often general, which means they overlap with those of many other conditions, so GI involvement in amyloidosis can be hard to diagnose.

A rare but notable symptom is macroglossia (an enlarged tongue), which may occur in both AL and ATTR amyloidosis. More common GI symptoms include:

• Abdominal (belly) pain
• Nausea
• Diarrhea
• Difficulty swallowing
• Bloating or feeling full quickly
• Unexplained weight loss

If your doctor suspects amyloidosis is affecting your GI tract, they may recommend different types of tests to better understand what’s happening and how much of the tract is involved. These tests may include:

• Endoscopy, which uses a long, flexible tube to look at your digestive tract
• Colonoscopy, which looks at your colon and rectum using a similar tube
• MRI and CT scans to help detect changes in the size or shape of organs

6. Skin

Amyloidosis that affects the skin is called cutaneous amyloidosis. In some cases, people may have only skin symptoms, a condition known as primary cutaneous amyloidosis. This is different from systemic amyloidosis, in which skin changes — reported in 30 percent to 40 percent of cases — can happen along with symptoms in other organs.

The type of skin symptoms depends on where amyloid buildup occurs. Amyloid deposits that stick to blood vessels in the skin can cause purpura — purplish or dark-colored spots or patches that may look like pinpoint dots, bruises, or blotchy areas.

Abnormal proteins from amyloidosis can also build up near the surface of the skin, causing small bumps that may contain fluid. These bumps often appear in areas with creased skin, such as the eyelids, neck, and armpits. Skin amyloidosis can be confirmed by taking a biopsy of the affected area.

Communicate With Your Doctor

Systemic amyloidosis can affect the body in ways that mimic other conditions, so getting the right diagnosis early is key. If something doesn’t feel right or your symptoms don’t improve with treatment, speak up — sharing details with your doctor can help guide the right tests and care.

Talk With Others Who Understand

MyAmyloidosisTeam is the social network for people with amyloidosis and their loved ones. On MyAmyloidosisTeam, members come together to ask questions, give advice, and share their stories with others who understand life with amyloidosis.

Are you living with systemic amyloidosis? Do you want to know more about how it affects different organs? Share your experiences in the comments below, or start a conversation by posting on your Activities page.