Symptoms of amyloidosis

Symptoms of amyloidosis are diverse and depend on the location of amyloid deposits, their prevalence. Localized forms of amyloidosis, for example amyloidosis of the skin, are asymptomatic for a long time, like senile amyloidosis, in which deposits of amyloid in the brain, pancreas, heart are often found only at the dissection.

Expanded symptoms of amyloidosis become with kidney damage, the most frequent localization of amyloid. Gradual distribution of amyloid deposits and involvement in the process of the vascular wall cause the development of leading symptoms of renal amyloidosis. These include increasing proteinuria with a typical occurrence of a nephrotic syndrome, a gradual decrease in blood flow, a decrease in glomerular filtration, azotemia, and often nephrogenic arterial hypertension. In cases of secondary amyloidosis, the manifestations of the underlying disease in which amyloidosis has developed may persist. The clinical picture in this case acquires a peculiar character, in which the signs of nephropathy, especially beginning, can be hardly noticeable.

Proteinuria, the most important and most reliable symptom of kidney amyloidosis, develops in all its forms, but is most characteristic and expressed in secondary amyloidosis, when it occurs in 64-72% of cases. Proteinuria can be detected at different times: both in the first 3 years, and after 10 years of the existence of the underlying disease. As a rule, proteinuria persists in the development of chronic renal failure, including its terminal stage. Prolonged loss of protein by the kidneys, as well as a number of other factors (increased protein breakdown in the body, decreased absorption, and sometimes increased excretion of the protein through the gastrointestinal tract) lead to the development of hypoproteinemia with hypoalbuminemia and associated edematous syndrome. The combination of massive proteinuria with pronounced edema is a characteristic clinical sign of kidney amyloidosis. Simultaneously with hypoproteinemia, and sometimes ahead of it, dysproteinemia develops. The nature of it may depend on the characteristics of the disease in which amyloidosis developed, but often amyloidosis itself is accompanied by a noticeable, albeit non-specific, change in the relationship between different fractions of plasma proteins. Simultaneously with expressed disproteinemia, in most patients, altered sediment samples are observed, as well as an increase in ESR, which may be a consequence of dysproteinemia.

A very common sign of expressed amyloidosis is hyperlipidemia. An increase in the cholesterol content with a violation of the ratio of lipoproteins and an increase in β-lipoproteins and triglycerides of blood can be very significant, especially in children, although not as high as in the nephrotic variant of chronic glomerulonephritis. Hypercholesterolemia is usually maintained in depleted patients also in the uremic stage, together with high proteinuria and edema. This combination of massive proteinuria, hypoproteinemia with hypoalbuminemia, hypercholesterolemia and edema, which is a classic nephrotic syndrome, is very typical for kidney amyloidosis. Nephrotic syndrome develops on average in 60% of patients with amyloidosis of the kidneys. Nephrotic syndrome caused by amyloidosis can proceed classically or without edema, as well as in combination with arterial hypertension and signs of damage to the liver, spleen, adrenal glands, gastrointestinal tract, pancreas. The most characteristic is a gradual development of the nephrotic syndrome after a long stage of moderate proteinuria, which can take a very long time. This distinguishes amyloidosis of the kidneys from chronic glomerulonephritis, in which the nephrotic syndrome often occurs already at the onset of the disease and subsequently recurs. It should be noted that in some patients with amyloidosis, the appearance of this syndrome, triggered by intercurrent infection, cooling, trauma, medication, vaccination or exacerbation of the underlying disease, may also seem sudden. If the previous stage of amyloidosis has not been detected in time, swelling and severe proteinuria can be mistakenly regarded as signs of acute glomerulonephritis or exacerbation of chronic. The emergence of nephrotic syndrome, as in other nephropathies, indicates the severity of kidney damage. Its course in amyloidosis is remarkable for its resistance and early appearance of resistance to various diuretics. Spontaneous remissions, although described, are rare. In addition to proteinuria, there are a number of other changes in urine that make up the urinary syndrome. They are less significant and. Compared with other nephropathies, little expressed. Usually, according to the degree of proteinuria, hyaline and less often granular cylinders are found, which give a sharply positive Schick reaction. They do not possess the basic properties of amyloid: metachromasia with crystalline violet and dichroism. Relatively often, they reveal persistent microhematuria, sometimes macrohematuria. Leukocyturia may occur with or without concomitant pyelonephritis. In amyloidosis, lipiduria with birefringent crystals in the urine sediment can be detected.

Damage to the tubular kidney apparatus in amyloidosis has not been studied enough, but the deposition of amyloid in the brain substance of the kidneys can lead to polyuria and resistance to vasopressin, difficulty in reabsorbing water in the collecting tubes and tubular acidosis, which can not be corrected with bicarbonate. In amyloidosis, renal dysfunction does not always reflect the degree of histological loading with amyloid. Excretory function of the kidneys can be preserved in nephrotic syndrome, indicating significant deposits of amyloid. Usually clinically renal failure in amyloidosis does not differ from chronic renal failure of another etiology and is characterized by slowly developing azotemia with all its known symptoms. Often it occurs in combination with large proteinuria and the absence of nephrogenic arterial hypertension. The rapid decline of glomerular filtration in amyloidosis can be associated with thrombosis of the renal veins, which can contribute to severe dehydration as a result of uncontrolled use of diuretics. Clinical manifestations of kidney damage in hereditary forms of amyloidosis in many respects resemble nephropathy in secondary amyloidosis, but are usually combined with the defeat of other organs and systems (symptoms of periodic illness, hypertonic syndrome, various allergic manifestations).

Until recently, involvement in the kidney process with primary amyloidosis was not considered characteristic, since the defeat of other organs and systems (heart, nervous system, digestive tract) is usually noted. In primary amyloidosis, with the exception of local amyloidosis, the process is always generalized, often with the prevailing pathology of a particular organ or system.

The defeat of the cardiovascular system is observed in all patients with primary amyloidosis. Arterial and venous vessels of any caliber may be involved in the process. The pathology of the heart is characterized by a large number of nonspecific signs: shortness of breath, palpitations, pains in the chest, changes in borders and tones, arrhythmias, symptoms of one or another heart defect or myocardial infarction, pericarditis. The ECG picture is also diverse and nonspecific. It is important to emphasize that heart damage is typical of primary generalized amyloidosis, and often heart failure is the immediate cause of death. With the unclear etiology of heart failure, especially in elderly patients, and its resistance to treatment, one should always think about amyloidosis of the heart.

Lung infection is noted in half of patients and manifests as shortness of breath, hemoptysis, hemorrhagic infarctions, relapsing pneumonia, pulmonary insufficiency, development of a picture of fibrosing alveolitis and alveolar-capillary block. Combination with heart failure complicates the picture of the disease and complicates the diagnosis of pulmonary pathology, however, progressive dyspnea, relapsing pneumonia along with other clinical signs allow suspected amyloidosis of the lungs.

More than half of the patients have gastrointestinal changes: abdominal pain, constipation, diarrhea, meteorism, vomiting, nausea, intestinal atony and stomach amyloid ulcers with the development of peritonitis, and the like. Especially typical macroglossia with cracks and bedsores, the length of the tongue can reach at this 15 cm or more. An increase in the tongue can lead to dysarthria, salivation, dysphagia and even the total inability to chew and swallow food.

The defeat of the spleen and lymph nodes is also found in half of the patients. Expressed enlarged lymph nodes usually serves as a basis for suspecting lymphogranulomatosis, sarcoidosis, tuberculosis, but it is worth considering the likelihood of amyloid genesis of an increase in the latter. Involvement in the process of the liver and spleen is characterized by an increase and compaction of organs with a slight soreness and relative safety of functions. Casual cases can be the emergence of portal hypertension and hepatic insufficiency. The defeat of the adrenal glands can be suspected with persistent hypotension and adynamia. Arterial hypertension is extremely rare because kidney damage, unlike secondary amyloidosis, is less common (about 40%) and less pronounced.

When the pancreas is affected, development of latent diabetes mellitus and changes in the activity of pancreatic enzymes are possible. Neurological symptoms characteristic of individual forms of hereditary primary amyloidosis, with secondary amyloidosis, may appear in the terminal (uremic) stage of the disease.

In amyloidosis, hyperfibrinogenemia, thrombocytosis, anemia (more often with chronic renal failure or as a manifestation of the disease in which amyloidosis developed), bone marrow plasmocytosis, an increase in the content of hexosamines and a decrease in the serum calcium level.

[1], [2], [3], [4], [5], [6], [7]