Secondary amyloidosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Overview
Historical Perspective
In 1639, Nicolaus Fontanus autopsied a young man who had ascites, jaundice, liver abscess, and splenomegaly and his report has been the first description of amyloidosis. There is no significant data regarding the historical perspective of amyloidosis throughout the 18th century. Rudolph Virchow and Weber are the prominent figures with substantial work on amyloidosis during the 19th century. In 1922, Bennhold introduced Congo Red staining of amyloid that remains the gold standard for diagnosis
Classification
Amyloidosis can also be classified based on the extent of organ system involvement
Pathophysiology
AA amyloid is an abnormal insoluble extracellular protein derived from the spontaneous aggregation of fibrils composed of misfolded proteins, called amyloid precursors. In secondary amyloidosis, the amyloid precursor is SAA, an acute phase reactant, encoded by SAA 1&2 genes. In secondary amyloidosis, intermediate products of SAA metabolism tend to aggregate and form protofilaments that accumulate within extracellular space and form the insoluble amyloid deposits. Secondary amyloidosis is associated with chronic inflammation (such as tuberculosis or rheumatoid arthritis).
Causes
Causes of secondary amyloidosis can include any persistent inflammatory process such as rheumatologic, autoinflammatory, chronic infectious, and other disorders.
Differentiating Amyloidosis from other Diseases
Secondary amyloidosis needs to be differentiated from other conditions causing nephrotic syndrome, hepatosplenomegaly, and peripheral neuropathy.
Epidemiology and Demographics
The incidence of AA amyloidosis is approximately 0.16 per 100,000 individuals in 2008 in the United kingdom. The mortality rate of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries. Secondary amyloidosis more commonly affects children. Men are more commonly affected by amyloidosis than women.
Risk Factors
The most potent risk factor in the development of secondary amyloidosis is a persistent inflammatory disorders. Chronic infections and inflammatory arthritis are among the most common risk factors.
Screening
There is insufficient evidence to recommend routine screening for amyloidosis.
Natural History, Complications and Prognosis
In amyloidosis, insoluble fibrils of amyloid are deposited in organs, causing organ dysfunction and eventually death. Patients with amyloidosis may eventually suffer from heart failure, nephrotic syndrome, hepatomegaly and peripheral neuropathy. In primary amyloidosis, the survival rate depends upon the type of organ involvement and the hematological response to treatment.
Diagnosis
Diagnostic Study of Choice
The diagnostic study of choice in amyloidosis is tissue biopsy of the affected organ. Congo Red staining will show apple green birefringence of the tissue sample under polarized light, and subtyping of light chains(for light chain amyloidosis) can be done via mass spectrometry. Bone marrow biopsy and organ-specific laboratory measurements are also important ancillary tests.
History and Symptoms
In amyloidosis, the range of symptoms depends on specific tissues and organs involved. Symptoms can be quite diverse.
Physical Examination
Common findings in amyloidosis include petechiae, ecchymosis, parotid gland enlargement, increased intraocular pressure, enlarged tongue, hepatomegaly, carpal tunnel syndrome, and Raynaud's phenomenon.
Laboratory Findings
Laboratory findings in amyloidosis include elevated erythrocyte sedimentation rate, increased BUN level, serum creatinine, protein, casts, or fat bodies in urine. Serum troponin, B-type natriuretic peptide, and beta-2-microglobulin are prognostic markers for heart failure. Amyloid deposits can be identified histologically by Congo red staining and viewing under polarized light where amyloid deposits produce a distinctive 'apple green birefringence'. Alternatively, thioflavin T stain may be used. An abdominal fat pad aspiration, rectal mucosa biopsy, or bone marrow biopsy can help confirm the diagnosis. They reveal positive findings in 80% patients.
Electrocardiogram
Electrocardiogram is particularly useful for cardiac amyloidosis. Findings on electrocardiogram include low voltage QRS complexes, left and right ventricular hypertrophy, left atrial abnormalities, pathological Q waves, and AV block.
Chest X-Ray
Chest x-ray findings in a case of amyloidosis include a coin lesion.
CT Scan
CT scan can be done to assess for amyloid deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. However, MRI is more sensitive than CT in the diagnosis of amyloidosis.
MRI
MRI is commonly done to assess for amyloid deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. A cardiac MRI is used when an echocardiogram fails to differentiate amyloidosis from hypertrophic cardiomyopathy.
Echocardiography
Echocardiography is critical in the diagnosis of cardiac amyloidosis. Echocardiogram should be done at diagnosis and routinely thereafter to monitor response to therapy.
Other Imaging Findings
Tissue doppler echocardiography and myocardial strain rate imaging has been shown to be very sensitive for the assessment of myocardial dysfunction in restrictive cardiomyopathy. The developmend of serum amyloid P component (SAP) scans has given physicians the ability to specifically locate amyloid deposits.
Other Diagnostic Studies
A tissue biopsy or fat aspirate should be done to confirm the presence or type of amyloid protein which is involved in the pathogenesis of the disease.
Treatment
There is no treatment for primary amyloidosis. The initial target in the treatment of this disorder is to correct the organ failure, as the disease is discovered at an advanced stage.
Medical Therapy
There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further organ damage and correcting the effects of organ failure. The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.
Surgery
Organ-specific transplant may need to be done, depending on the organ involved. However, surgery is not commonly done in patients with amyloidosis, since it is usually a systemic disease that requires treatment of the underlying cause.
Prevention
Primary Prevention
There is no role for primary prevention in amyloidosis.
Secondary Prevention
There is no role for secondary prevention in amyloidosis.