Background/Purpose: Familial Mediterranean Fever (FMF) is a prototype of autoinflammatory diseases. Inflammation is expressed by attacks of fever and serositis and elevation of acute phase reactants (AFR). The most dreaded complication of FMF is amyloidosis, being the treatment target to prevent it. There is controversy as to what AFR should be monitored in these patients. The objective was to analyze the performance of the various AFR for the prediction of amyloidosis in FMF.

Methods: We performed a systematic review based on a sensitive search in Medline, Embase, and Cochrane Library, with terms related to FMF, to performance and diagnostic studies, and to longitudinal studies. Selection criteria included: 1) FMF any age; 2) measure of Serum amyloid A (SAA), C-RP, proteinuria, or ESR; 3) amyloidosis should be the outcome measure; 4) sensitivity, specificity, predictive value and other performance parameters could be calculated; and 5) designs should be longitudinal preferably. Two fellows screened the registers captured by the search strategy and collected the data in pre-specified tables. Evidence tables and qualitative synthesis were produced.

Results: The search captured 1516 items of which 26 were selected for detailed review, and 12 were finally included in the review. No study actually analyzed the performance by means of sensitivity and specificity to predict, or even detect, proteinuria or amyloidosis. The studies reviewed combine and stratify variables in a descriptive manner and it is very difficult to interpret the true performance of the tests. Each study was designed ad hoc, thus, yielding a high heterogeneity in designs, parameters measured, and results, despite being set from research questions similar to ours. Many are described as longitudinal; however, the measures are actually performed cross-sectionally. We were able to calculate the performance from three studies (See Table), although the performance was not tested in the appropriate population (ill versus healthy controls instead of amyloidosis yes/no). The correlation between measures is low.

Table. Calculated performance of tests

Conclusion: The evidence supporting the monitoring of FMF with any AFR over the others is limited and of poor quality in general. Well designed longitudinal studies with a mixture of outcomes should be undertaken. Until them, recommending an AFR over other would be based on expert opinion and indirect evidence.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/what-acute-phase-reactants-accurately-identify-patients-who-will-develop-amyloidosis-in-familial-mediterranean-fever-a-systematic-review/