Natural history and outcome in systemic AA amyloidosis.

BACKGROUND

Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known about the natural history of AA amyloidosis or its response to treatment.

METHODS

We evaluated clinical features, organ function, and survival among 374 patients with AA amyloidosis who were followed for a median of 86 months. The SAA concentration was measured serially, and the amyloid burden was estimated with the use of whole-body serum amyloid P component scintigraphy. Therapy for inflammatory diseases was administered to suppress the production of SAA.

RESULTS

Median survival after diagnosis was 133 months; renal dysfunction was the predominant disease manifestation. Mortality, amyloid burden, and renal prognosis all significantly correlated with the SAA concentration during follow-up. The risk of death was 17.7 times as high among patients with SAA concentrations in the highest eighth, or octile, (>or=155 mg per liter) as among those with concentrations in the lowest octile (<4 mg per liter); and the risk of death was four times as high in the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration during follow-up was 6 mg per liter in patients in whom renal function improved and 28 mg per liter in those in whom it deteriorated (P<0.001). Amyloid deposits regressed in 60% of patients who had a median SAA concentration of less than 10 mg per liter, and survival among these patients was superior to survival among those in whom amyloid deposits did not regress (P=0.04).

CONCLUSIONS

The effects of renal dysfunction dominate the course of AA amyloidosis, which is associated with a relatively favorable outcome in patients with SAA concentrations that remain in the low-normal range (<4 mg per liter).