Amyloidosis are diseases in which proteins form poorly soluble, pathogenic deposits. This leads to functional failures and various symptoms. In some cases they are limited to certain organs or body regions – in others they affect the entire organism. Read here how the disease progresses, what signs point to amyloidosis and how it is treated!
ICD codes for amyloidosis disease: E85
Quick overview
• What is amyloidosis? Amyloidosis is a disease caused by protein deposits. Different organs are affected.
• Prognosis: It is not possible to make a general statement on this. In addition to the subtype, what matters most is how many organs are affected.
• Symptoms: Different symptoms depending on the organs affected.
• Risk factors: In addition to genetic risk factors, chronic inflammatory diseases, chronic infections and blood disorders increase the likelihood of amyloidosis.
• Diagnosis: blood count, urine test; Removal of tissue samples to be examined in the laboratory.
• Treatment: Treatment of the triggering underlying disease; Drugs that may slow down protein deposition.
• Prevention: Rapid treatment of chronic inflammatory diseases and chronic infections.
What is amyloidosis?
In amyloidosis, proteins accumulate in the spaces between cells. They form microscopically small fiber structures, so-called fibrils. The name “amyloidosis” indicates a special feature. In Greek, “ámylon” means strength. Because the deposits react in the laboratory in a similar way to starch granules: they turn blue in an iodine solution.
Strictly speaking, the term amyloidosis does not describe a specific disease, but a deposit of different proteins that leads to symptoms. Scientists have now found more than 30 of these proteins. Triggers are, for example, certain diseases or changes in the genetic material that lead to the accumulation of poorly soluble proteins. Amyloidosis affects different organs.
Causes of amyloidosis
Background: Proteins consist of individual amino acids. They are stringed together in a thread-like manner during protein production. Many of these proteins are dissolved in the blood or organs. In the case of amyloidosis, their concentration rises sharply for various reasons and the proteins are deposited. Certain changes in the genome lead to altered proteins with different properties that are deposited. In addition, the natural aging process sometimes favors the development.
Classification, distribution and frequency
Amyloidosis is not a uniform clinical picture. There are localized amyloidoses with deposits in one region of the body or impairments throughout the body (systemic amyloidoses). There are no reliable figures on the frequency for Germany. Scientists name one case per 100,000 inhabitants for systemic amyloidosis in Great Britain. Other research groups found five to 13 cases per 100,000 people in western industrialized nations.
Amyloidosis are divided into the following groups (subtypes) according to frequency, type and cause:
AL amyloidosis: This is the most common form, accounting for 68 percent of all amyloidosis. “AL” means “amyloid composed of light chains”. Special cells in the bone marrow (plasma cells) that produce antibodies are affected. Antibodies consist of two light and two heavy chains, i.e. large and small protein chains.
In AL amyloidosis, plasma cells produce large quantities of altered light chains, which are deposited. A tumor in the lymphatic tissue (lymphoma) is often behind the changes in the protein of the light chains. This form of amyloidosis usually occurs locally. The heart or kidneys are often affected.
AA amyloidosis follows in second place with a frequency of around twelve percent. It is triggered by the so-called acute phase protein. This is a protein that is produced in the body after injury or infection. Some viruses, bacteria, chronic inflammatory bowel diseases or cancer lead to this form. Discomfort usually occurs in the kidneys, spleen, liver, adrenal glands and gastrointestinal tract.
ATTR amyloidosis follows with a frequency of 8.8 percent. This is about transthyretin as an amyloidosis trigger. This is a protein that is produced during inflammation and is very unstable. The deposits are the cause of senile amyloidosis in the elderly. This form of amyloidosis can be hereditary. Symptoms mainly occur in the eyes, kidneys, heart and rarely in the central nervous system.
Patients suffer from A-beta2-M amyloidosis, also known as AB amyloidosis, much less frequently (1.8 percent). The name refers to the protein beta2 microglobulin. It tends to form fibrils: a problem that occurs particularly in patients on long-term dialysis. Those affected report pain in the joints in particular. In many cases, carpal tunnel syndrome also occurs.
AFib amyloidosis is similarly rare (1.7 percent) . Doctors also speak of 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. The consequences range from the need for dialysis to kidney transplantation.
Can you die from amyloidosis?
The following also applies to questions about the course and prognosis: amyloidosis is not a uniform clinical picture and general statements are not possible. In addition to the subtype, the individual situation plays a role here. The fewer organs that are affected, the better the prognosis.
Scientific studies only give average values; the numbers differ individually. So always talk to your doctor. With standard therapies, patients survive on average three years for AL amyloidosis and four years for AA amyloidosis. Studies have shown that people with AA amyloidosis have a very different course of the disease – depending on the amount of the triggering protein serum amyloid A. With ATTR amyloidosis and after a successful liver transplant, more than half of all patients are still alive 20 years later.
Is amyloidosis hereditary?
There are different types of amyloidosis. The two most common forms are not inheritable. AA amyloidosis is caused by some inflammation, infection, or cancer; hereditary factors play no role here. AL amyloidosis is caused by certain blood disorders and is not directly inherited. Patients requiring long-term dialysis occasionally develop AB amyloidosis. It is due to the treatment.
Hereditary forms include hereditary ATTR amyloidosis, also known as ATTRv amyloidosis. The cause is changes in genes for the protein transthyretin. So far, experts know more than 80 such mutations. AFib amyloidosis is also a familial form. Changes in the gene for fibrinogen are inherited.
Regardless of whether it is inherited or acquired – the same applies to all amyloidoses that those affected form too many difficult-to-dissolve proteins that are deposited and ultimately make them ill. Many of these proteins are dissolved in the blood or organs. Various metabolic diseases, chronic inflammation or chronic infections cause their concentration to increase sharply until they can no longer be dissolved.
In the case of hereditary forms, changes in the genetic code are the cause: modified proteins with different properties are formed and deposited. In many cases, aging is also behind such changes. Proteins find their way into the interstitial spaces between cells. They accumulate and form so-called beta sheets. These are accordion-like folded structures. Finally, microscopic fibers are created that are very resistant. They are deposited and are not removed by the body’s own scavenger cells.
The deposits disrupt the architecture of tissues and are toxic to cells. This leads to restrictions in organ function, for example in the heart, in the kidneys or in the central nervous system.
What are the symptoms of amyloidosis?
The symptoms of amyloidosis vary from person to person. The palette ranges from complete freedom from symptoms, especially at the beginning, to severe, life-threatening symptoms when the disease is well advanced. Depending on which organ is affected, different symptoms develop.
Symptoms of amyloidosis when the kidneys are involved
Poorly soluble proteins form either in the capillary vessels of the renal corpuscles or in the vessels that supply and drain the kidneys. Patients often notice that their urine foams a lot. The kidneys stop working properly and fluid builds up (oedema).
Symptoms of amyloidosis when the cardiac involved
The proteins are also deposited on the heart muscle, which impairs the pumping capacity. Heart failure (cardiac insufficiency). The heart pumps too little blood to supply the body. Sometimes the walls of the heart chambers thicken. Patients are short of breath, have low blood pressure, and suffer from general weakness. Doctors then speak of cardiac amyloidosis.
Symptoms of amyloidosis when the brain and central nervous system are involved
Protein deposits in the brain lead to various symptoms that doctors are familiar with from patients with Alzheimer’s dementia. Those affected have trouble remembering information and learning new things while long-term memory is still functioning. As the disease progresses, fine motor skills and speech deteriorate.
If the deposits form on the nerves outside the brain, many of those affected develop movement disorders or paraesthesia. Depending on where it is deposited, people with amyloidosis may have trouble emptying their stomach, bowels, and/or bladder properly. Erectile dysfunction is also common.
Symptoms of amyloidosis when different soft tissues are involved
Soft tissues have different functions in the body. If proteins are deposited in amyloidosis, this leads to various symptoms. These include swollen, painful joints, nodules under the skin, changes in fingernails or toenails, hair loss and hand discomfort caused by carpal tunnel syndrome.
A dry feeling in the mouth and throat with hoarseness, a swollen tongue, and difficulty swallowing indicate amyloidosis. The eyes are often affected as well: Dry, reddened eyes are just as possible as opacification of the vitreous body or glaucoma. This is a group of eye diseases that damage the optic nerve and eventually limit people’s vision.
Symptoms of amyloidosis when the stomach and intestines involved
In addition, amyloidosis in the digestive tract leads to nausea, flatulence or constipation up to intestinal obstruction. Those affected lose weight unintentionally because components of the food are no longer sufficiently utilized. They are often tired and exhausted quickly. Pain in the abdomen sometimes indicates an abnormal enlargement of the liver.
What does the doctor?
Amyloidosis is a rare disease. Complaints such as tiredness, flatulence, diarrhea, nausea, vomiting, weight loss, joint pain or water retention are quite unspecific – they also occur with many other diseases. Doctors therefore often only make the actual diagnosis after some time.
First examinations at the family doctor
In a conversation with the patient, the doctor records possible previous illnesses and listens to the sounds of breathing, heart, blood vessels and intestines. A full blood count and urine test are also appropriate. Evidence of amyloidosis is provided by high levels of protein in the urine, diseases of the heart muscle (cardiomyopathies), diseases of the nervous system (neuropathy), cancer of the blood-forming system (multiple myeloma) or an enlarged liver.
Diagnosis of amyloidosis by tissue samples and imaging methods
To confirm amyloidosis as a diagnosis, specialists use a special needle to remove some subcutaneous fatty tissue from the affected organ. They send this sample to the laboratory for further analysis. There, specialists examine the tissue by staining it with Congo red, a special chemical, and looking at it under a microscope. Such methods are also suitable for detecting the fibrils. Laboratory physicians provide certain antibodies that only recognize specific proteins as a test.
However, a method from nuclear medicine, SAP scintigraphy, is suitable for finding deposited proteins in the body in AA amyloidosis. Patients receive a low-level radioactive substance (123I-labelled serum amyloid P). It accumulates in regions of the body where amyloid deposits are already found. The doctors record the radiation with a special device called a gamma detector. In this way it can be determined whether and, if so, which tissue has absorbed the marker.
Treatment for amyloidosis
There is no general treatment for amyloidosis. Therapy is based on the one hand on the subtype of amyloidosis and on the other hand – if applicable – on the underlying disease. The doctor tries to reduce the concentration of precursor proteins so that less amyloid is deposited. The aim is to enable patients with amyloidosis to live with the highest possible quality of life. There are also experimental therapies that are currently being investigated in clinical studies.
Supportive treatment
Some therapies from general medicine have proven themselves in amyloidosis. For heart failure, doctors recommend a low-salt diet, draining medication (diuretics) and special heart medication (ACE inhibitors). If the symptoms are more severe, other 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.
If the kidneys are affected, doctors also recommend low-salt diets, diuretics and drugs to lower high levels of blood fat, ACE inhibitors and certain antihypertensive drugs (AT1 antagonists). Severe limitations in kidney function ultimately lead to dialysis or a kidney transplant. If doctors find amyloid tumors, they will surgically remove them.
Therapy of AL amyloidosis
In the case of AL amyloidosis in particular, doctors try to stop the proliferation of plasma cells. These immune system cells produce large amounts of light chain proteins. The treatment of choice is often special chemotherapy (melphalan chemotherapy) followed by autologous stem cell transplantation. The patient receives back his own blood stem cells, which were taken from him before the chemotherapy. If the treatment does not lead to the desired result, special chemotherapy remains as an alternative: the active ingredients thalidomide plus dexamethasone, bortezomib or lenalidomide together with dexamethasone.
Therapy of AA amyloidosis
AA amyloidosis is associated with inflammatory diseases. In order to lower serum amyloid A levels, doctors will always try to find the cause and treat it with appropriate medication. If it is familial Mediterranean fever, an inherited disease with flare-ups of fever and pain, the active ingredient colchicine is the first choice.
In the case of inflammatory rheumatic diseases, so-called biologics are used. These molecules intercept messenger substances in the body and inflammation decreases. There are numerous other treatment options. If the amyloidosis is triggered by tuberculosis, those affected are given a combination of different antibiotics. The drugs usually have to be taken over a long period of time.
Therapy of AATR amyloidosis
If patients suffer from hereditary AATR amyloidosis, an altered form of the protein transthyretin is produced due to mutations in the genome – more than 99 percent in the liver. Liver transplants prevent this and prevent AATR amyloidosis. If possible, this procedure is carried out at the beginning of the disease in order to avoid consequential damage.
Prevention of amyloidosis
There are no preventive measures against hereditary forms of amyloidosis. In order to prevent other forms, it is important to treat chronic infections and chronic inflammatory diseases quickly.
