Amyloidosis
Amyloidosis—Recent Developments

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Objectives

To describe the clinical presentation, diagnosis, classification, grading, evaluation of prognosis, and treatment of amyloidosis against the background of its pathomechanisms.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Methods

PubMed and MEDLINE databases (1990-2007) and internet were searched for the keyword “amyloidosis” (or occasionally closely related words, such as amyloid or amyloid deposit) in articles published in English. This search strategy revealed 7864 index abstracts. Some of the references were found with special keywords: 13 using “nephrotic syndrome,” 16 using “natriuretic peptide,” 31 using “periodic fever,” and 50 using “Muckle–Wells syndrome.” In particular, more recent articles pertinent to this

Clinical Suspicion of Amyloidosis

Certain symptoms and signs, which can be referred to as “amyloid syndromes,” in the context of chronic infectious/inflammatory diseases, plasma cell dyscrasias, or family history, arouse a clinical suspicion of amyloidosis. In particular, proteinuria, nephrotic syndrome, or renal failure is suspicious in this respect. Enteropathy leading to generalized malabsorption or gastrointestinal bleeding is suggestive of AA amyloidosis, whereas restrictive cardiomyopathy with thromboemboli and

Discussion

The keystone in the diagnosis of amyloidosis is clinical suspicion, which is not easily raised, because despite their shared molecular pathomechanisms the “amyloid syndromes” are heterogenous in their clinical expression. In contrast to many other diseases, the diagnosis of amyloidosis cannot be based on a serum sample but requires histopathologic demonstration of tissue deposition of amyloid using Congo red and type-specific antibodies. As 27 different subtypes have been described, specific

Acknowledgments

This study was supported by Finska Läkaresällskapet and the Else and Wilhelm Stockmann Foundation.

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