What Is Systemic Amyloidosis?

Systematic amyloidosis is a disease caused by the deposition of amyloid in the interstitial spaces of extracellular tissues throughout the body, thereby disrupting cell and organ function. The latest definition of the disease proposed by Picken et al. Is that amyloidosis is a set of amyloid deposition syndromes caused by abnormal folding of protein molecules caused by different factors such as heredity, degeneration and infection.

Systemic amyloidosis

Systematic amyloidosis is a disease caused by the deposition of amyloid in the interstitial spaces of extracellular tissues throughout the body, thereby disrupting cell and organ function. The latest definition of the disease proposed by Picken et al. Is that amyloidosis is a set of amyloid deposition syndromes caused by abnormal folding of protein molecules caused by different factors such as heredity, degeneration and infection.

Western Medicine Name

Systemic amyloidosis

Chinese Medicine Name

Systemic amyloidosis

English name

systematic amyloidosis

Other name

Amyloidosis

Affiliated Department

Internal Medicine-Gastroenterology

Disease site

Whole body cells

The main symptoms

Damage cells, organ function

Main cause

Deposition of amyloid

Contagious

Non-contagious

Systemic amyloidosis has heterogeneous clinical manifestations due to differences in deposited amyloid and affected organs. Common organs involved are liver, kidney, nerves, heart, gastrointestinal tract, etc. The affected tissues are more commonly skin, tongue, and lymph nodes. All tissues and organs throughout the body can be affected, but not necessarily clinically. ^[1]

Fibrillin and its precursors: The amyloids that have been clarified are mainly the following.

Amyloid light chain protein (AL) : AL protein consists of part or whole

The exact mechanism of amyloid formation has not been fully understood, but the prerequisite for the deposition of amyloid fibrils is the excessive production of precursor proteins or structural abnormalities. After incomplete degradation of the precursor protein, it becomes easy to fold into anti-parallel -lamellar structure fragments, and in the case of familial amyloidosis polyneuropathy and hemodialysis-related amyloidosis, the complete undegraded TTR and 2-M molecules can also form amyloid fibrils. The primary structure of a protein is very important for its ability to form amyloid fibrils. For example, in the case of hereditary amyloidosis, a single amino acid substitution can make wild-type molecules that could not form amyloids into fibril-producing fibers. Mutant molecules. In addition, there are other factors that have an impact on the deposition process and distribution of fibrils, collectively referred to as amyloid enhancing factor (AEF), which may be related to clinical individual differences. Mechanism of Amyloid Formation. ^[2]

Systemic amyloidosis is the deposition of amyloid in various tissues and organs throughout the body, but some patients only deposit locally, and some of these patients may be in the early stages of systemic amyloidosis and later develop into other Tissue or organ amyloid deposition. This disease mostly occurs in middle-aged and older people over 40 years of age, and the clinical manifestations are extremely uneven, which is related to the type, the location of amyloid deposition, the characteristics of amyloid, and the degree of damage to the affected organs. Common affected organs and tissues are liver, kidney, heart, blood vessels, skin and bone marrow.

General clinical manifestations : General clinical symptoms are non-specific, mainly weight loss and fatigue. Weight loss is most obvious, but the cause is unclear. A more specific sign is purpura around the eyes.

Circulatory system : due to amyloid deposits in the myocardial cell space, coupled with myotrophic vascular basement membrane amyloid deposition, the basement membrane is thickened and the vessel lumen becomes narrow. These factors cause cardiomyocyte insufficiency. Clinical manifestations are arrhythmia, angina pectoris, congestive heart failure and sudden death. Patients with primary, systemic, senile and TTR 122nd isoleucine mutations often have heart involvement. Angina pectoris can occur in some patients despite normal coronary angiography, which may be due to a decrease in coronary blood supply. An image of a pseudo-myocardial infarction can appear on the ECG. The elution rate of nuclide intravenous injection into the body can reach 57% to 61%. This test can understand the survival of active cardiomyocytes. The higher the elution rate, the fewer cardiomyocytes that survive, and the worse the heart function (judge the patient's heart function with echocardiography), often dying within less than one year. AA type amyloidosis can cause

In addition to a detailed medical history, the family history should be focused on the history of rheumatoid arthritis, inflammatory bowel disease, tuberculosis, suppurative osteomyelitis and empyema, and renal dialysis treatment.

The possibility of the disease should be considered for giant tongue, purpuric skin around the eyes, unexplained cardiac enlargement and heart failure, liver enlargement, proteinuria, systemic lymphadenopathy, refractory pleural effusion and whole blood cell reduction.

Laboratory tests that are helpful for the diagnosis of this disease include urine Bence-Jone protein examination; bone marrow aspiration smear examination, the proportion of immature and mature plasma cells in AL bone marrow of the disease exceeds 15%, and can be seen Myeloma cells; AF-type determination of related variant proteins in plasma.

The diagnosis is to confirm the deposition of amyloid in the interstitial space. The most reliable method is to perform biopsy and pathological examination from the diseased tissue. ^[3]

Urine : 90% of AL amyloidosis has protein in urine, of which coagulated protein can be detected in 1/2 patients, and the daily output is about 1g. This protein is called Bence-Jone protein, which is a monoclonal light chain kappa and / or isoform. It can also detect intact immunoglobulins, which are not found in blood. When the urine is heated to 45 to 60 ° C, coagulated protein appears, and when it is continuously heated to boiling, it disappears. When cooled to 60 ° C, coagulated protein may appear. When doing urine protein electrophoresis, this protein is between beta and alpha globulin. 2 microglobulin can be detected in AH amyloidosis, but it has no diagnostic significance.

Blood : Electrophoresis of plasma protein in patients with type AL amyloidosis can detect M peaks, that is, monoclonal immunoglobulins and their light chains. IgG is the most common, and only light chains can appear. AA type and AS amyloidosis, the former amyloid A is converted from SAP, and its concentration remains unchanged despite a large amount of amyloid A deposition; the latter except for cardiac amyloid to TTR deposition, amyloid source It is multi-channel, so the determination of amyloid in plasma is meaningless. AF type amyloidosis can detect amyloidosis-related variant proteins in blood. Amyloidosis associated with multiple myeloma has hypercalcemia, and its occurrence may be related to the ability of M protein to bind calcium or to parathyroid hormone-related peptide (PTHrP). Liver function tests have elevated alkaline phosphatase and blood urea nitrogen and creatinine during renal failure.

Bone marrow : Myeloma-related amyloidosis and bone marrow aspirate smears can find myeloma cells and increase plasma cells (approximately 15% of nuclear cells).

The main purpose of treatment is to prevent further deposition of amyloid and promote its absorption, and reducing the production of precursor proteins has a significant effect on delaying the progression of the disease. In the case of AA amyloidosis, the treatment of underlying diseases can make the amyloid deposits disappear, such as the treatment of rheumatoid arthritis with alkylating agents, the treatment of familial Mediterranean fever with colchicine, etc., which can protect renal function from damage. Tumor resection can sometimes dissipate amyloid. However, in the amyloidosis of AL, the use of cytotoxic drugs to inhibit the growth of plasma cells is not ideal. After renal transplantation of hemodialysis-related amyloidosis patients, 2-M can return to normal quickly, and the amyloid deposits also disappear. Liver transplantation has been used successfully to treat familial amyloid polyneuropathy caused by mutations in the TTR gene. AL or amyloidosis in the heart can be considered chemotherapy or heart transplantation. In short, there is no effective treatment for this disease, and supportive therapy is still the main method, and organ failure should be actively treated. ^[5]

In recent years, with the emergence of new drugs and clinical detection methods, the treatment of amyloidosis has made great progress. The Renal Department of the Nanjing Military Region General Hospital of the Chinese People's Liberation Army relies on the academician platform, which is the earliest unit in China to carry out autologous stem cell transplantation for the treatment of AL amyloidosis. At present, the number of cases involved has exceeded 50. The treatment effect is satisfactory. The reports of typical cases in our department can be viewed by interested patients.