# Symptoms and stages of systemic amyloidosis
Systemic amyloidosis does not progress in clearly defined stages like some other diseases. Instead, complaints develop gradually as more amyloid protein accumulates in organs, and they vary greatly depending on which organs are involved. This tab describes how the disease typically manifests and which symptoms can occur at what times.
Early stage: few or no symptoms
In the very beginning, amyloidosis is often "silent" — amyloid protein deposits in tissues, but this does not yet cause noticeable problems. The disease is sometimes discovered by chance because a doctor sees an abnormality during examination (for example, enlargement of the spleen or liver, or unexplained weight loss) or because blood is tested due to other complaints.
**What can occur:**
- No complaints at all
- Slight weight loss that cannot be easily explained
- Tiredness that does not match what you are doing
- Weak sensations in hands or feet
In many cases, people only realize something is wrong when organs are already quite damaged. This makes early detection difficult.
Stage with heart complaints (cardiac involvement)
The heart is damaged more often in amyloidosis than many people realize. Amyloid accumulates in the heart muscle tissue, causing the heart to stiffen and pump less effectively.
**Symptoms:**
- Shortness of breath, especially during exertion or when you sit still for a long time and then stand up
- Tiredness and lack of energy even during light activities
- Swelling of feet and legs (due to fluid accumulation)
- Irregular heartbeat (palpitations) — sensation of heartbeat or 'fluttering' in the chest
- Dizziness or fainting when standing up or during exertion
- Pressure or pain in the chest (may occur)
- Difficulty sleeping, especially when lying down
**Impact on daily life:**
Many patients have to adjust their activities significantly. Climbing stairs, shopping, or working longer can suddenly become much more difficult. Waking up at night with shortness of breath is distressing. Swelling in the legs can make shoes difficult to wear and walking distances painful.
**What is known about this stage:**
For patients with AL amyloidosis with cardiac involvement: in studies from the 2010-2020 period, median survival (without treatment or with standard treatment) was several months to about 1-2 years, depending on how severely the heart was damaged. This has changed dramatically with newer treatments: recent data (2026) suggests that modern therapies significantly extend survival, but exact median figures vary greatly between research groups. Individual differences are enormous — much depends on age, how well your body responds to treatment, and whether other organs are also involved.
With hereditary ATTR amyloidosis with cardiac involvement, progression is slower — often several years before serious problems develop, depending on genotype and age.
Stage with kidney complaints (renal involvement)
The kidneys can be seriously damaged by amyloid. This leads to proteinuria (high protein in urine) and eventually kidney failure.
**Symptoms:**
- Foamy or cloudy urine
- Swelling of feet, legs, face (due to protein loss)
- Tiredness and pallor (due to anemia)
- Nausea and poor appetite (if kidneys are working very poorly)
- Itching (sometimes only late, if kidney function is much worse)
- Frequent need to urinate at night
**Impact on daily life:**
The swelling can be quite troublesome and make many socks and shoes uncomfortable. Frequent trips to the bathroom at night disrupt sleep. As the kidneys work worse, everything feels more tiring and eating can become more difficult (bad taste, nausea). If dialysis becomes necessary, it takes up much time and means a significant lifestyle change.
**What is known about this stage:**
Many patients with AL amyloidosis have kidney problems at the time of diagnosis already. The progression varies enormously: some maintain reasonable kidney function for years with treatment, others worsen faster. In hereditary ATTR amyloidosis, kidney failure is less frequent and usually progresses more slowly. Exact median survival times for the kidney-related phase are difficult to establish because many patients are already in a multi-organ phase.
Phase with nerve problems (peripheral and autonomic neuropathy)
The nerves can be severely affected by amyloid, especially in hereditary forms (ATTR) but also in AL amyloidosis.
**Symptoms:**
- Tingling, prickling, pain or numbness in feet (later also hands)
- Muscle weakness, especially in legs — walking becomes difficult
- Loss of balance or instability: risk of falling increases
- Pain in legs and feet (can be stabbing, burning or dull)
- Autonomic symptoms (from damage to nerve cells that regulate automatic functions):
- Constipation or diarrhea
- Erectile dysfunction (men)
- Blood pressure drop upon standing (dizziness)
- Poor sweating or excessive sweating
**Impact on daily life:**
Walking becomes increasingly difficult and dangerous. Many patients need a walker or cane, and eventually a wheelchair. Fine manual work becomes difficult (buttons, writing). Diarrhea or constipation can be seriously disruptive and socially uncomfortable. Autonomic nervous system involvement also makes many everyday things more difficult (standing for long is hard, heart rate stays slow, sweating doesn't work well).
**What is known about this stage:**
In hereditary ATTR amyloidosis (especially the Portuguese and Swedish-American forms), neuropathy occurs early and is often progressive over many years — many patients have 5-10+ years disease duration. AL amyloidosis with neuropathy is less frequent but can also be progressive. Exact survival figures per phase are not well established because neuropathy-affected patients deteriorate at different speeds.
Phase with digestion problems (gastrointestinal involvement)
The entire gastrointestinal tract can accumulate amyloid, causing many different problems.
**Symptoms:**
- Nausea and retching
- Pain or discomfort in stomach or abdomen
- Feeling full quickly, even with small amounts of food
- Diarrhea (can be severe and dropsy-like)
- Constipation (verstopping) — can alternate with diarrhea
- Difficulty swallowing (rarely, but can occur)
- Weight loss from poor absorption or being unable to eat
- Internal bleeding (rarely, but possible) — sign: blood in stool or vomit
**Impact on daily life:**
Many patients must drastically change their diet — small meals, food that is easy to digest, avoidance of certain foods. Weight loss can happen quickly and fatigue can worsen. Frequent diarrhea ties you to home and toilet. Malnutrition and electrolyte disturbances can seriously weaken overall condition.
**What is known:**
Gastrointestinal involvement is quite common in AL amyloidosis and hereditary ATTR. It progresses very variably — some have mild symptoms, others have severe diarrhea and weight loss. Median survival figures specifically for this phase are largely absent from the literature.
Phase with liver problems (hepatic involvement)
Liver amyloidosis is often asymptomatic for a long time, but can eventually lead to liver failure.
**Symptoms:**
- Enlarged liver (not always felt by the patient themselves)
- Nausea and loss of appetite
- Abdominal pain (especially upper right)
- Yellowing of skin and eyes (jaundice) — sign of serious liver damage
- Dark urine, pale stool
- Abdominal fluid (ascites) — abdomen swells up
- General fatigue, unexplained weight loss
**Impact on daily life:**
When the liver is seriously damaged, this can cause overall fatigue, nutrition problems and swelling. Failure of liver functions (such as metabolism of medicines) also makes treatment more complicated.
**What is known:**
Hepatic involvement is less frequent than cardiac or renal involvement in AL amyloidosis. It progresses variably and progressive liver failure is relatively rare. Exact survival figures for hepatic amyloidosis are lacking.
Phase with ocular involvement
Amyloid can accumulate in and around the eye, causing vision problems.
**Symptoms:**
- Blurred vision
- Sensation of eye pressure or eye pain
- Elevated intraocular pressure (glaucoma risk)
- Disturbed eye movements (rare)
- Visual field defects
- In some cases: swelling around the eye, thickened eyelids
**Impact on daily life:**
Reduced vision makes reading, driving and everyday tasks more difficult. Eye pressure complaints can be painful. Adjusted glasses sometimes help but not always.
**What is known:**
Ocular amyloidosis is relatively rare systemically. It progresses variably and does not always need to be progressive.
Phase with other involvement (skin, joints, blood)
Amyloid can also accumulate in:
- **Skin**: dark spots, bruises (purpura), especially around eyes or on sensitive areas; skin thickening
- **Joints**: pain, stiffness, especially in hands and wrists
- **Carpal tunnel syndrome (CTS)**: tingling in hands, especially at night — can be bilateral
- **Blood**: increased bleeding tendency (susceptibility to bruising, nosebleeds, slow wound healing)
**Impact on daily life:**
Skin changes are mainly cosmetically bothersome or psychologically burdensome. CTS can significantly disrupt work and night rest. Increased bleeding tendency raises the risk of serious bleeding from trauma or medical procedures.
**What is known:**
This involvement is more downplayed in many guidelines but is nonetheless relatively frequently observed in practice. Carpal tunnel syndrome can occur earlier than systemic symptoms and is sometimes the first warning sign.
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When to contact your doctor
Make sure you have regular contact with your amyloidosis team (cardiologist, nephrologist, hematologist, internist — whoever is involved in your amyloidosis). Contact immediately or go to the emergency department if you:
- Suddenly become much more short of breath, especially at rest
- Faint or feel extremely dizzy
- Experience chest pain or notice an unusual heartbeat
- Lose a lot of blood (from mouth, nose, stool)
- Cannot urinate or have very dark urine
- Experience severe abdominal pain
- Have a high fever
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