Diagnosis and monitoring of amyloidosis.
The diagnosis of systemic amyloidosis is only occasionally suspected on clinical grounds alone and is more often considered when an associated condition, such as a chronic inflammatory disease or monoclonal gammopathy, is present. No blood test is diagnostic of amyloid although routine haematological and biochemical investigations have important roles in defining the underlying disease process in amyloidosis, and evaluating organ function. A number of non-invasive investigations including echocardiography, electrocardiography and soft tissue scintigraphy with bone-seeking tracers give characteristic results in some patients with amyloidosis, but are non-specific. The diagnosis can only be confirmed by demonstrating the presence of amyloid deposits in the tissues. Histology is the traditional method in routine clinical practice and is sensitive for revealing microscopic deposits and permits immunotyping of fibril proteins. Disadvantages are that biopsies are invasive, open to sampling error and can only give limited information on the distribution and extent of amyloid deposits in an individual. Scintigraphic and turnover studies with radioiodinated SAP are new specific methods for confirming the presence of amyloid in tissues, based on the affinity of SAP for all types of amyloid fibril. Labelled SAP scans survey the whole body macroscopically for the presence and anatomical distribution of amyloid in a quantitative manner, and SAP turnover studies provide information on the whole body amyloid load. Although the availability of SAP scintigraphy presently remains restricted, the technique has been used in over 400 patients with amyloid in prospective studies, and has already provided a number of new insights into the natural history of amyloidosis. These include the observation that there is a consistently poor correlation between the quantity of amyloid in an organ and the resulting degree of functional impairment. Amyloid deposits accumulate at rates which vary substantially between different organs in a single subject and between individuals with similar types of amyloidosis, even when the rates of amyloid fibril precursor protein supply are apparently similar. In some patients amyloid accumulation may plateau without any measurable alteration in the precursor supply. In patients with amyloidosis in whom the supply of fibril precursors is reduced, either as a result of therapy directed towards the underlying process or through a natural remission, substantial regression of amyloid frequently occurs. This has been observed in patients with AA, AL and variant TTR-associated amyloidosis, and is usually associated with clinical benefits. In some such cases, however, the function of affected organs may continue to deteriorate despite halting the accumulation of amyloid, presumably because irreversible structural damage has already occurred.(ABSTRACT TRUNCATED AT 400 WORDS)
Hawkins
P N
PN
Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D000818:Animals; D004285:Dogs; D004452:Echocardiography; D005145:Face / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D000683:Serum Amyloid P-Component / Q000378:metabolism; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon
D000682:Amyloid; D007457:Iodine Radioisotopes; D000683:Serum Amyloid P-Component; D013667:Technetium