Serum mast cell tryptase measurements: sensitivity and specificity for a diagnosis of anaphylaxis in emergency department patients with shock or hypoxaemia

Objective: Clinical diagnosis of ana-phylaxis is principally based onsymptoms and signs. However, par-ticularly for patients with atypicalsymptoms, laboratory confirmationof anaphylaxis would be useful. Thisstudy investigated the utility of mastcell tryptase, an available clinicalbiomarker, for differentiating ana-phylaxis from other causes of criticalillness, which can also involve mastcell activation.Methods: Tryptase was measured(ImmunoCAP) in serum frompatients with anaphylaxis and non-anaphylactic critical illness (controls)at ED arrival, and after 1–2, 3–4and 12–24 h. Differences in bothpeak and delta (difference betweenhighest and lowest) tryptase concen-trations between groups were investi-gated using linear regression models,and diagnostic ability was analysedusing Receiver Operating Character-istic curve analysis.Results: Peak tryptase was fourfold(95% CI: 2.9, 5.5) higher in anaphy-laxis patients (n= 67) than controls(n= 120) (P< 0.001). Delta-tryptasewas 5.1-fold (95% CI: 2.9, 8.9)higher in anaphylaxis than controls(P< 0.001). Optimal test character-istics (sensitivity: 72% [95% CI:59, 82] and specificity: 72% [95%CI: 63, 80]) were observed whenpeak tryptase concentrations were>11.4 ng/mL and/or delta-tryptase≥2.0 ng/mL. For hypotensive patients,peak tryptase >11.4 ng/mL hadimproved test characteristics (sensi-tivity: 85% [95% CI: 65, 96] andspecificity: 92% [95% CI: 85, 97]);the use of delta-tryptase reduced testspecificity.Conclusion: While peak and deltatryptase concentrations were higherin anaphylaxis than other forms ofcritical illness, the test lacks sufficientsensitivity and specificity. Therefore,mast cell tryptase values alone can-not be used to establish the diagnosisof anaphylaxis in the ED. In particu-lar, tryptase has limited utility fordifferentiating anaphylactic fromnon-anaphylactic shock