Amyloidosis

Amyloidosis is not one disease but several different ones that end the same way. A misfolded protein settles in the tissues: instead of doing its job and breaking down, it clumps into dense, insoluble fibres and stays in the organ. Over time these deposits push normal tissue aside and the organ stops coping. The heart, the kidneys, the nerves and the gut are affected most often. The condition is rare, and its main difficulty lies not in treatment but in how long it takes to be recognised.

Why a protein stops dissolving

Every protein in the body has its own shape and works only while it holds that shape. If the molecule folds wrongly it turns sticky and latches on to others like it, and that is how amyloid fibres grow. The body has almost no way of taking them apart, so the deposits only build up.

What matters is which protein went wrong, because that decides which organs suffer, how fast, and what will help. This is why the word «amyloidosis» without a type is not yet a diagnosis, only half of one.

Different diseases under one name

• AL amyloidosis. The commonest systemic form. A group of plasma cells in the bone marrow turns out the same antibody fragment over and over — a light chain — and that fragment is what is deposited. Sometimes myeloma is found alongside it.
• AA amyloidosis. The result of inflammation running for years: rheumatoid arthritis, Crohn's disease, ulcerative colitis, familial Mediterranean fever, or a long-standing infection such as tuberculosis or chronic bone inflammation. It strikes the kidneys first.
• Hereditary ATTR. A change in the gene for transthyretin, a carrier protein made by the liver. It is passed on to children and shows itself through damage to the nerves, the heart, or both at once, often in middle age.
• Wild-type ATTR. The gene is normal; the protein simply degrades with age. It almost always means the heart, most often in men past seventy.
• Amyloidosis of long-term dialysis. Beta-2 microglobulin that the kidneys no longer clear settles over years into joints, tendons and bone.

There is also localised amyloidosis, in the skin, the larynx or the bladder. It does not spread to other organs and is usually not life-threatening.

What shows on the outside

The first complaints are deceptively ordinary: tiredness that rest does not fix, weight loss for no reason, breathlessness on exertion, swollen ankles and lower legs. After that the picture depends on which organ is occupied.

• Kidneys. Frothy urine, and swelling that climbs higher — thighs, abdomen, face.
• Heart. Breathlessness lying flat, waking at night short of air, an irregular beat, vision greying out on standing.
• Nerves. Numbness, burning and pins and needles in the feet that creep upwards, weak legs, dizziness on getting up, disturbed sweating.
• Gut. Feeling full very early, nausea, diarrhoea alternating with constipation, weight falling away.

Two signs barely occur in anything else and are therefore worth a great deal: bruising around the eyes appearing with no blow behind it, sometimes after coughing or bending, and an enlarged tongue with tooth marks along its edges. Both belong to the AL type.

The clue that usually gets missed

Cardiac ATTR amyloidosis has a warning that runs years ahead of the breathlessness: carpal tunnel syndrome in both hands at once. The same group includes narrowing of the lumbar spinal canal and rupture of the biceps tendon without any effort to explain it. Deposits of the same protein reach the tendons before they reach the heart muscle.

Nocturnal tingling in the fingers on its own is an extremely common complaint and almost always harmless. But if it affected both hands and breathlessness arrived some years later, that combination is worth saying out loud to a doctor: it changes the direction of the search.

What should not wait

• swollen legs persisting for weeks and urine that froths;
• breathlessness that keeps growing, sleep possible only propped up on pillows;
• fainting, or vision greying out on standing;
• weight coming off by itself;
• numbness and burning in the feet worsening month by month.

Seek emergency help for chest pain, severe breathlessness at rest, a faint with a fall, or a fast irregular heartbeat.

How the diagnosis is confirmed, and the trap inside it

The starting point is blood and urine testing: protein in the urine, kidney function, markers of cardiac strain and, where the AL type is suspected, free light chains and protein electrophoresis with immunofixation. Then come the electrocardiogram, the echocardiogram and cardiac magnetic resonance imaging. One mismatch is a strong pointer: thickened heart walls together with low voltages on the electrocardiogram.

Confirmation comes from a biopsy stained with Congo red — under polarised light amyloid throws off a characteristic green glow. But finding amyloid is not enough; its type has to be established, by immunohistochemistry or mass spectrometry.

And here sits the trap worth knowing about. A small excess of light chains in the blood occurs in older people on its own, with no amyloidosis at all. If that incidental finding turns up in someone who actually has cardiac ATTR amyloidosis, the type can be assigned wrongly and chemotherapy prescribed where it is neither needed nor useful. Typing the tissue settles the question, and it is not worth skipping for the sake of speed.

For the cardiac ATTR form there is a route that avoids biopsy: scintigraphy with a labelled bone-seeking tracer, which under a few defined conditions confirms the diagnosis on its own. Hereditary variants are pinned down by genetic testing, and if one is confirmed it makes sense to test blood relatives as well.

What treatment achieves

Removing amyloid that has already built up is, for the most part, beyond current medicine. The aim is different: shut off the source of the faulty protein so the deposits stop growing, and support the organs that have already taken damage. How well this works depends on the type.

• AL. The bone marrow clone is treated with regimens built around monoclonal antibodies and drugs that suppress plasma cells; some patients undergo a transplant of their own stem cells.
• AA. The essential move is to put out the inflammation feeding it. When the underlying disease is brought under control, deposits can shrink and kidney function can partly recover.
• ATTR. There are now drugs that hold transthyretin together and others that reduce how much of it the liver makes. They do not give back what has been lost, but they slow the disease appreciably, which is exactly why an early diagnosis is worth something here.
• Dialysis-related. Modern membranes and a kidney transplant help.

The supportive side means diuretics for swelling, limiting salt, treating rhythm disturbances and, where needed, dialysis or an organ transplant. One more thing is worth knowing: in cardiac amyloidosis several of the usual heart failure medicines are tolerated badly and have to be chosen with care. Taking «the standard heart tablets» on someone else's advice with this diagnosis is dangerous.

Online consultation

In an online consultation the doctor goes through the history in order: when the swelling, the breathlessness or the numbness began, what earlier tests showed, whether anything similar has happened in the family. They explain which investigations make sense and in what order, help you read the reports you already hold, and point you to the right specialist to see in person.

This material is for information only and does not replace medical advice.