Brief overview
- What is amyloidosis? Amyloidosis is a disease caused by protein deposits. Different organs are affected.
- Prognosis: No general statement can be made about this. Besides the subtype, it mainly depends on how many organs are affected.
- Symptoms: Different symptoms, depending on the organs affected.
- Diagnosis: blood count, urinalysis; collection of tissue samples for laboratory examination, imaging techniques such as scintigraphy
- Treatment: treatment of the triggering underlying disease; drugs that may slow down protein deposition
What is amyloidosis?
Scientists have now identified more than 30 of these proteins. Triggers are, for example, certain diseases or changes in the genetic material that lead to an increased deposition of poorly soluble proteins. Amyloidosis affects various organs.
Amyloidosis is not a uniform clinical picture. There are localized amyloidoses with deposits in one region of the body or impairments in the entire body (systemic amyloidoses).
Frequency
There are no reliable figures on the frequency. Researchers cite one case per 100,000 population for systemic amyloidoses in the United Kingdom. Other research groups found five to 13 cases per 100,000 people for Western industrialized nations.
Common forms
AL amyloidosis
This is the most common form, accounting for 68 percent of all amyloidoses. “AL” means “amyloid consisting of light chains”. Affected are special cells in the bone marrow (plasma cells) that produce antibodies. Antibodies consist of two light and two heavy chains, i.e. large and small protein chains.
AA amyloidosis
AA amyloidosis follows in second place with a frequency of about twelve percent. It is triggered by the so-called acute phase protein. This is a protein that is formed in the body after injuries or infections.
Some viruses, bacteria, chronic inflammatory bowel diseases or cancer lead to this form. Symptoms usually occur in the kidney, spleen, liver, adrenal glands and gastrointestinal tract.
ATTR amyloidosis
In the rarer hereditary form, the symptoms appear between the ages of 20 and 80. In this case, the peripheral and autonomic nerves are also often affected, and more rarely the eyes and kidneys.
A-Beta2-M amyloidosis
However, due to its size, beta2-microgobulin gets caught on filter membranes of a dialysis and remains in the blood. As a result, it accumulates in the body and is deposited. Affected patients report pain in the joints in particular. In many cases, carpal tunnel syndrome also occurs.
AFib amyloidosis
AFib amyloidosis is similarly rare (1.7 percent). Doctors also refer to it as hereditary fibrinogen Aα-chain amyloidosis because the deposits can be traced back to changes in the gene for fibrinogen. Fibrinogen is a protein that plays a central role in blood clotting.
Clumping occurs primarily in the kidneys. Consequences range from needing dialysis to a kidney transplant.
Can you die from it?
Is amyloidosis hereditary?
There are different amyloidoses. The two most common forms are not hereditary. AA amyloidosis is triggered by some inflammations, infections or cancers; hereditary factors do not play a role here. AL amyloidosis is due to certain blood disorders and is not directly inherited. Patients who require long-term dialysis occasionally develop AB amyloidosis. It is due to the treatment.
Whether inherited or acquired, all amyloidoses are affected by the formation of too many poorly soluble proteins, which are deposited and ultimately cause illness. Many of these proteins are dissolved in the blood or organs. Various metabolic diseases, chronic inflammations or chronic infections cause their concentration to rise sharply until they can no longer be dissolved.
The deposits disrupt the architecture of tissues and are toxic to cells. This leads to restrictions in organ function, for example in the heart, kidney or central nervous system.
What are the symptoms of amyloidosis?
Symptoms with involvement of the kidneys
Poorly soluble proteins form either on capillary vessels of the renal corpuscles or on inflow and outflow vessels of the kidneys. Patients often notice that their urine is very foamy. The kidney no longer functions properly, and water accumulation (edema) occurs.
Symptoms with involvement of the heart
Patients are short of breath, have low blood pressure and suffer from general weakness. Doctors then speak of cardiac amyloidosis.
Symptoms with involvement of the brain and central nervous system
Symptoms with involvement of the peripheral nervous system
If the deposits form on the nerves outside the brain and spinal cord, many affected people develop movement disorders or insensations. Depending on the location of the deposit, people with amyloidosis have problems emptying their stomach, bowels and/or bladder properly. Erectile dysfunction is also common. Doctors refer to these cases as a polyneuropathy.
Symptoms with involvement of various soft tissues
It is also possible that the canal in the spinal column through which the spinal cord runs narrows (spinal canal stenosis). In addition, some amyloidosis sufferers rupture a biceps tendon (biceps tendon rupture).
Symptoms with involvement of stomach and intestine
In addition, amyloidosis in the digestive tract leads to nausea, flatulence or constipation, and even intestinal obstruction. Affected persons lose weight unintentionally because components of the food are no longer sufficiently utilized. They are often tired and quickly exhausted. Pain in the abdominal area sometimes indicates abnormal enlargement of the liver.
What does the doctor do?
Initial examinations by the general practitioner
In a consultation with the patient, the physician records possible pre-existing conditions and listens to respiratory, cardiac, vascular and bowel sounds. A large blood count and urinalysis are also appropriate. Indications of amyloidosis include high protein levels in the urine, diseases of the heart muscle (cardiomyopathies), diseases of the nervous system (neuropathies), cancers of the hematopoietic system (multiple myelomas) or an enlarged liver.
To confirm amyloidosis as a diagnosis, specialists remove a tissue sample from the affected organ or subcutaneous fatty tissue using a special needle. They send this sample to the laboratory for further examination. There, specialists examine the tissue by staining it with Congo red, a special chemical, and viewing it under a microscope.
Scintigraphy is also suitable for diagnosing ATTR amyloidosis with cardiac involvement. The prerequisite for this is that AL amyloidosis has previously been ruled out by means of blood and urine tests.
How is amyloidosis treated?
Supportive treatment
Some therapies from general medicine have proven effective in amyloidosis. For example, doctors recommend a low-salt diet, diuretics and special cardiac medications for heart failure.
If symptoms are more severe, additional medications, a pacemaker or an implantable cardioverter defibrillator are used. This is a device that helps prevent sudden cardiac death in the event of life-threatening cardiac arrhythmias.
Therapy of AL amyloidosis
Doctors treat AL amyloidosis with drugs known from cancer therapy. These include classic cancer drugs (chemotherapeutics/cytostatics), special antibodies and cortisone. The exact form of therapy depends on various factors, such as age and stage of disease.
High-dose chemotherapy with stem cell transplantation
Patients who are candidates for stem cell transplantation first receive what is known as induction therapy. Doctors usually use the active ingredients bortezomib and dexamethasone, sometimes in combination with cyclosphamide (“CyBorD”). This is followed by high-dose chemotherapy with the active ingredient melphalan. Both therapies aim to destroy the causative plasma cells.
Conventional chemotherapy or combination therapy
If the organ damage in AL amyloidosis is already advanced, high-dose therapy followed by stem cell transplantation is no longer an option. The same applies to patients who are no longer fit enough for this (for example, due to age and previous illnesses). This is the case in about three quarters of all patients. Doctors then give conventional chemotherapy, often combined with other active substances.
- Melphalan and dexamethasone
- Bortezomib with cyclophosphamide and dexamethasone
- Lenalidomide, melphalan and dexamethasone
Therapy of AA amyloidosis
AA amyloidosis is associated with inflammatory diseases. To reduce the level of serum amyloid A, physicians will always try to find the cause and treat it with appropriate drugs. If it is familial Mediterranean fever, a hereditary disease with episodes of fever and pain, the drug colchicine is the agent of first choice.
Therapy of ATTR amyloidosis
Patients suffering from hereditary ATTR amyloidosis develop an altered form of the protein transthyretin due to mutations in their genetic material – more than 99 percent of which occur in the liver. Whereas liver transplantation used to be the only therapeutic approach, there are now drugs that slow down or prevent the progression of the disease.
In adult ATTR amyloidosis patients with heart muscle disease (cardiomyopathy), the active ingredient tafamidis slows further deposition in the heart muscle.
Prevention
There are no preventive measures against hereditary forms of amyloidosis. To prevent other forms, chronic infections and chronic inflammatory diseases must be treated quickly.
