Tryptase, anaphylaxis diagnosis

The latest consensus on the definition and management [1] of anaphylaxis agrees on the lack of imiversally accepted diagnostic criteria and reliable laboratory biomarkers to confirm the clinical impression. Sometimes it is not feasible to obtain the samples within the optimum time frame. Moreover, in spite of a correct collection of samples, histamine and/or tryptase are within normal levels. Hence, new markers should be explored and further research into the role of selected mediators is urgently needed. Recently however, studies from animal models have shown promising results. In this chapter we will seek to review our current knowledge on confirmed or putative markers for the in vitro diagnosis of anaphylaxis. 

Two immunoassays have been developed to measure tryptase in human fluids, one that measures mature a/(3-tryptases, i.e. total tryptase, available commercially, and one developed by Schwartz et al. [7] that measures both mature (3-tryptase and immature a/(3-tryptases. This distinction is of clinical relevance since immature tryptases reflect mast cell burden whereas mature tryptases indicate mast cell activation. Thus, for the diagnosis of anaphylaxis it would be extremely important to be able to differentiate between acute anaphylaxis and increases in tryptase due to increase in numbers of mast cells as happens in mastocytosis. Total tryptase would be high in both conditions, whereas mature tryptase will be only high in anaphylaxis but negligible in mastocytosis. 

Histamine concentrations are maximal almost immediately, decrease thereafter with a half-life of about 20 min, and should be assayed within the first hour of a reaction. The sensitivity of this test for the diagnosis of anaphylaxis was estimated at 75%, the specificity at 51%, the positive predictive value at 75% and the negative predictive value at 51%. Tryptase reaches a peak in the patient s serum 30 min after the first clinical manifestations. Its half-life is 90 min, and the levels usually decrease over time. In a recent series, the sensitivity was estimated at 64%, specificity at 89.3%, positive predictive value at 92-95%, and negative predictive value at 54.3% [9]. 

The diagnosis of an allergic reaction to a muscle relaxant is based on clinical features, measurement of histamine and tryptase concentrations in the plasma during the reaction, and subsequent skin testing a few weeks later. However, during general anesthesia isolated sjmptoms can occur, most often hypotension or bronchospasm. Therefore, the clinical features of anaphylaxis may not be recognized as such. 

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