What is Amyloidosis?

Amyloidosis is a clinical syndrome caused by the deposition of amyloid in various organ cells in the body, which gradually causes the affected organs to fail. Includes a group of diseases. The presence of amyloidosis in the tissue is called amyloidosis, also known as amyloidosis. Amyloid is a proteinaceous substance. Because it can be dyed tan when it is exposed to iodine, it is blue after adding sulfuric acid. It is similar to the reaction of starch when it is exposed to iodine, so it is called amyloidosis. Amyloidosis is a large amount of various soluble fibrous soluble protein (amyloid) tissues that impair normal tissue function.

Causes of amyloidosis

The cause of the deposition of amyloid products and the tissues in which they are located is unclear. The etiology mechanism may be different in different types of amyloidosis, such as secondary amyloidosis to metabolic disorders of protein precursors (acute phase). Reactant plasma amyloid A), and hereditary amyloidosis will show different proteins. In primary amyloidosis, a monoclonal population of bone marrow cells will produce fragments or entire long chains that can form amyloidosis. Under light microscopy, amyloid is homologous, high-affinity, and has an affinity for Congo red dye in fixed tissues.

Clinical manifestations of amyloidosis

Symptoms and signs are non-specific, determined by the affected organs and systems, and are often masked by the primary disease. The primary disease is fatal before the amyloidosis is suspected, and the renal system is the strongest, only in the early stages. Mild proteinuria can progress to generalized edema, hypoalbuminemia, and large amounts of proteinuria.

Hepatic amyloidosis has hepatomegaly but rarely jaundice, and severe hepatomegaly (liver weight> 7 kg). Despite increased (less persistent) sulfobromophthalate excretion and increased alkaline phosphatase, liver function is usually normal, occasional portal hypertension, and esophageal varices and ascites. Skin lesions cause waxy or translucent changes. Small vessel amyloidosis causes purpura. Heart involvement is common, with enlarged heart, refractory heart failure, and common arrhythmias. Atrial arrest was found in several blood-related families. GI amyloidosis can cause abnormal esophageal motility, flaccid stomach tension, large and small bowel motility, malabsorption, bleeding or pseudo-obstruction. Tongue hypertrophy is common in primary or myeloma-related amyloidosis. Hard texture, symmetrical, non-tenderness such as Hashimoto's disease or Riddle's thyroid disease.

Due to amyloidosis of the thyroid gland, in rare cases of multiple myeloma, amyloid arthropathy is similar to rheumatoid arthropathy, peripheral neuropathy with few clinical manifestations, and mostly in familial amyloidosis and Primary or myeloma-related amyloidosis is common. Lung-related amyloidosis (mostly AL amyloidosis) is characterized by limited pulmonary nodules, tracheobronchial injury, or extensive alveolar deposition.

Amyloidosis test

Laboratory tests for amyloidosis are almost non-specific.

Peripheral blood

Hemoglobin, white blood cell count and classification, and platelets are generally normal. Only 11% of patients have hemoglobin L, which is related to bone marrow involvement, renal insufficiency, or gastrointestinal blood loss in myeloma patients. About 9% of patients had platelet counts> 500 × 10 ⁹ / L. Due to amyloid precipitation caused by spleen dysfunction.

2. Biochemical examination

Some patients have elevated alkaline phosphatase. In addition to considering liver involvement, they are more likely to be due to congestive heart failure. Transaminase bilirubin is within the normal range, and some patients can see an increase. If it is significantly increased, it often indicates that the disease is late. Half of those with nephrotic syndrome had elevated cholesterol and some had triacylglycerol. In addition, 5% of patients have a factor X deficiency but rarely cause bleeding. Some patients had serum creatinine 180 mol / L, while half of them were completely normal.

3. Serum protein

About half of patients with primary amyloidosis can see monoclonal proteins in protein electrophoresis. If further immunoelectrophoresis or immunofixation is used, the positive rate can reach 72%. The median M protein was 14g / L (M protein) and a few were> 30g / L. Gammaglobulinemia occurred in about 1/4 of the patients. K / is 1: 2.3.

4. Urine protein

Some patients have urinary protein. In a few patients, concentrated urine electrophoresis showed albumin peaks. In some patients, M protein was detected in the urine by immunoelectrophoresis or immunofixation. The 24-hour urinary light chain discharge is 0.01 to 6.6 g, with an average of 0.4 g, and some patients are> 3 g / 24 h. In summary, the majority of patients diagnosed with primary amyloidosis have M protein found in their serum or urine.

5. ESR

ESR increased faster .

6. Congo Red Test

Congo red test can be done when the disease is suspected: 1% Congo red solution 0.22ml / kg, intravenous injection, 10ml each of venous blood after 4 minutes and 1 hour. Using double serum samples for colorimetric examination, the percentage of stain remaining in the serum can be obtained. In normal humans, this stain is slowly excreted by the liver, with a maximum excretion of 40% in one hour. Because the patient's amyloid quickly absorbed Congo red, serum samples had lost most of the stain after 1 hour or 4 minutes, which was helpful for diagnosis. At the same time, urine should be collected after 1 hour and checked for stains. If there is no stain, the diagnosis can be confirmed. If stained, lipid nephropathy should be considered and identified.

7. Bone marrow smear

Some patients with primary amyloidosis have plasma cells in the bone marrow of 10%, and some patients have plasma cells in the bone marrow of 20% with an average of 7% (1% to 95%).

8. Heart color echocardiogram

Shows myocardial hypertrophy and granular bright spots.

9. tissue biopsy

Under the light microscope, it can be seen that the amorphous substance is precipitated between the cells, and the green refraction under polarized light after Congo red staining is the characteristic of the amyloid substance.

10. Immunohistochemical detection

Enzyme-labeled or fluorescently labeled anti- or anti-K antibodies for immunohistochemical examination can confirm that the amyloid is the chain or K chain.

Diagnosis of amyloidosis

Initial diagnosis of amyloidosis can be made based on the symptoms and signs described above. The diagnosis can only be confirmed by biopsy. Subcutaneous abdominal fat pad aspiration and rectal mucosal biopsy are the most commonly used screening methods. Other useful biopsy sites are gums, skin, and nerves. , Kidney and liver. Green birefringence of amyloidosis can be observed in polarized microscopy with Congo red stained tissue. A scintillation test of isotope-labeled serum AP can confirm the diagnosis of amyloidosis.

Amyloidosis treatment

Symptomatic treatment

To prevent the occurrence of amyloidosis according to the primary disease, amyloidosis itself is a symptomatic treatment. Patients with renal amyloidosis can undergo kidney transplantation. The survival period is longer than other kidney diseases, but the early mortality rate is higher, and amyloidosis will eventually It recurs in the donor kidney, but some transplanters can survive up to 10 years.

2. Drug treatment

Drugs commonly used in treatment plans include prednisone, melphalan or prednisone, melphalan, colchicum, etc. Clinical trials are underway to compare these treatment plans. The stem cell transplantation plan is still controversial. Digitalis can be used in patients with arrhythmia due to amyloid heart disease, but it should be used with caution. Heart transplantation has been successful, and patients must be selected strictly. Colchicum is used to prevent the acute attack of patients with familial Mediterranean fever, and shows that no new amyloid appears after treatment, and amyloidosis is decreasing. The treatment of hereditary amyloidosis by using transthyretin and liver transplantation to remove the synthetic site of the mutant protein has achieved good results.

Prognosis of amyloidosis

The prognosis of secondary amyloidosis depends on the success of the treatment of the primary disease. The prognosis of all types of renal amyloidosis is poor, but if intensive symptomatic treatment (such as treatment of pyelonephritis), patients will remain relatively stable, dialysis and Kidney transplantation will further improve the prognosis. Amyloidosis associated with multiple myeloma has the worst prognosis, often dying within 1 year of age. Localized amyloid masses can be removed without recurrence. Myocardial amyloidosis is the most common cause of death, mainly due to arrhythmia or refractory heart failure. The prognosis of familial amyloidosis varies from family to family.