Amyloidosis
PKGhatak,MD
Amyloidosis is not a single entity, under amyloidosis five distinct clinical disorders are included; whereas, 36 chemically distinct proteins associated with amyloidosis are detectable.
The underlying pathology is an accumulation of abnormal protein inside the cells. The abnormally folded protein is resistant to protease enzyme which in normal circumstances does "house cleaning" and it removes undesirable molecules from the inside of cells.
Organs involved in amyloid disease and clinical features.
Eyes.
The accumulated protein damages the cells and the cells die. Damage to blood vessels around the eyes produces easy bruising and the eyes resemble Raccoon eyes.
Amyloid in the retinal blood vessels reflects light back as bright spots. The retina appears as Starry Night when examined with an ophthalmoscope. Macular degeneration and various visual problems may develop.
Heart
The cardiac muscles become loaded with amyloid and become stiff. The ventricles fail to dilate fully during diastole in order to accommodate returning blood. Stagnation of venous blood in the periphery and in the lungs produces congestive heart failure. Normal electrical conduction is disrupted and various heart blocks develop, and cardiac arrhythmia may appear.
Liver.
Accumulated protein results in enlarged liver, biliary obstruction and obstructive jaundice, elevated AST, ALT and Alkaline phosphatase in the blood are present
Mouth.
The enlarged tongue becomes out of proportion to the mouth cavity, the epiglottis enlarges. Obstructive sleep apnea follows.
Intestine. Diarrhea is a common presentation, malabsorption and weight loss follow.
Kidneys.
Damaged glomeruli result in high Creatinine and BUN and later renal failure develops. Loss of protein in the urine produces nephritic syndrome.
Peripheral Nervous System.
Neurological manifestations include peripheral nephropathy of both somatic and autonomic nervous systems and produce various clinical pictures including carpal tunnel syndrome, peripheral neuritis, orthostatic hypotension.
The spleen is generally spared, but when it occurs it produces Howell-Jolly bodies in RBCs.
Skin.
Spotty depigmentation of skin with surrounding hyperpigmented areas in the lower legs is seen.
Endocrine organs.
The thyroid gland and adrenal glands may be involved in producing hypothyroidism and adrenal insufficiency respectively. Pancreas gland amyloid may cause diabetes mellitus.
Joints.
Joint amyloidosis is seen in patients undergoing hemodialysis for a long time. Beta 2 macroglobulin is deposited in knees, wrists, elbows and hips joints.
Clinical classification.
The old classification is Primary and Secondary amyloidosis. The cause of primary amyloidosis is unknown. In the secondary category, amyloid accumulation is the result of the chronic inflammatory process.
Current classification.
AL amyloidosis is also called Primary amyloidosis. The immunoglobulin light chain accumulates in the cells of the heart, kidney, liver and peripheral nerves.
AA amyloidosis is also called Secondary amyloidosis. An acute phase protein is deposited in cells with chronic inflammation like Rheumatoid arthritis and other illnesses. Involved organs are the kidneys, liver, and spleen.
Hereditary or Familial amyloidosis. Due to an inherited defect of the liver enzyme. The liver cells make an abnormal protein called Transthyretin (TTR). TTR accumulates in liver cells, Heart, kidney and peripheral nervous system. Various symptoms are seen depending on the organ impacted.
Wild Type amyloidosis. Here the TTR protein accumulates in the heart of people over 70 years of age. Rarely carpal tunnel syndrome is seen.
But in the wild type, the disease is not inherited. The cause is unknown.
Localized amyloidosis. Here the accumulated protein appears in an isolated organ. Urinary bladder, skin, throat and lungs are involved.
Diagnosis of Amyloidosis.
Biopsy
of abdominal subcutaneous fat and staining tissue by Congo red is the final diagnostic method. If fatty tissue Congo red is negative then a biopsy of the involved organ is indicated.
Blood test. Serum protein electrophoresis detects the offending protein-free immunoglobulin light chain.
Evaluation of the cardiovascular system by echocardiogram, conduction study and Troponin I, NT-proBNP and BNP may also be used but not diagnostic, but a cardiac muscle biopsy is diagnostic.
Treatment of Amyloidosis.
The treatment of amyloidosis varies according to clinical types.
For AL amyloidosis - Stem Cell Transplantation is the best option, however, only about 20% of patients become eligible for stem cell transplants. The rest of this group is generally prescribed Melphalan, Cyclophosphamide and Dexamethasone.
In AA amyloidosis Eprodisate (Kiacta) is most effective.
Patients with ATTR (hereditary) amyloidosis have the best outcome following liver transplantation.
Prognosis.
ATTR amyloidosis patients have the best prognosis, 10-year survival is not unusual.
The patients in other groups have a poor prognosis – generally 2 to 3 years.
Symptomatic treatment for congestive failure, heart block, etc. is used in the usual manner.
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