To describe the clinical presentation, diagnosis, classification, grading, evaluation of prognosis, and treatment of amyloidosis against the background of its pathomechanisms.
PubMed and MEDLINE databases (1990 to October 2007) and internet were searched for the key word amyloidosis and evaluated on the basis of the authors' own clinical experience and work on the topic.
A clinical suspicion of amyloidosis arises when a patient with a chronic inflammatory disease, plasma cell dyscrasia, or a family history of hereditary amyloidosis develops "an amyloid syndrome" or more rare but specific signs. Microscopy of Congo red stained tissue specimens under polarized light shows birefringent amyloid, which is typed by identification of the amyloid precursor by immunohistochemistry, amino acid sequencing, or proteomics. The diagnosis can be supported by genetic tests. Amyloidosis now covers biochemically and clinically 27 distinct types in man and 9 in animals. Grading to mild, moderate, and severe disease based on laboratory tests and radiology is introduced. Prognosis is affected by the rate of synthesis and the concentration of the circulating precursor. Accurate diagnosis of the underlying disease is mandatory as the treatment is based on disease control and inhibition of amyloid precursor production. Organ-specific treatment, such as transplantation, hemodialysis, treatment of heart failure, pacemakers, and substitution to prevent nutritional deficiencies, is often needed.
As our knowledge of the pathogenesis of amyloidosis and the structure-function relationship of amyloid proteins increases, new therapies will be developed to prevent protein misfolding and aggregation, inhibit fibrillogenesis, and enhance clearance of amyloid.