We read with great interest the valuable comments of Sprung et al. on the diagnostic value of total tryptase in allergic events. This group, which has been a pioneer in tryptase discovery and evaluation, points out that the comparison of acute tryptase concentrations with basal values 24 h afterword is more reliable than a single measurement at the time of the reaction.

Indeed, several factors discussed by Sprung et al., as well as in our article,1  may be responsible for elevated basal tryptase concentrations. Mastocytosis, when severe, can be responsible for immediate hypersensitivity reaction but is rare and usually already diagnosed in patients referred to the operating room. This is also the case for acute myelocytic leukemia, myelodysplastic syndromes, hypereosinophilic syndrome, and therapy with recombinant stem cell factor. Finally, mildly increased tryptase concentrations have been reported in stages 4 and 5 chronic renal failure and in hemodialysis patients but not in stages 1 and 2.2 

Although these clinical conditions are relatively uncommon, the interest of basal tryptase measurements at distance from the clinical reaction has long been recognized.3,4  These limits of tryptase measurements have led our group, among others, to promote the development of systematic assessment of immediate perioperative hypersensitivity reactions based on clinical history, tryptase and histamine measurements, and delayed specific allergy investigation, notably skin tests.5,6 

Although we largely agree with most remarks made by Sprung et al., in most cases, patients will survive, allowing for a delayed allergy work-up. This gives an opportunity to perform basal tryptase measurements, thus increasing the diagnostic value of tryptase measurement performed during the reaction, and also to identify possible sensitization using skin testing, even in case of mild reactions in the absence of tryptase increase.

The situation appears completely different in case of unfavorable outcome, when neither delayed tryptase sample nor skin tests can be obtained. Therefore, we focused our study on fatal or life-threatening per-anesthetic anaphylactic reactions compared with other types of shock. We showed that resuscitation maneuvers and treatment of shock did not induce by themselves a significant increase in tryptase concentrations and determined thresholds allowing for a sensitivity exceeding 90%.1 

In addition, as mentioned in our article, we suggested to look for a preanesthetic sample whenever possible to discard other possible causes of basal tryptase increase.

Finally, we agree with Sprung et al. that clinical history and symptoms are of critical importance for the diagnosis of anaphylaxis. However, the medical history of anesthetized patients is considered by anesthesiologists before anesthesia, allowing them to diagnose underlying pathologies potentially responsible for increased basal tryptase concentrations. Therefore, in cases of immediate hypersensitivity reaction occurring within 5 min following antibiotic or muscle relaxant administration, for example, in the absence of any other evident cause of death (i.e., American Society of Anesthesiologists IV or V status, failure to intubate, malignant hyperthermia, succinylcholine-induced hyperkaliemia), our results indicate that an increased tryptase concentration is a strong support for the diagnosis of an allergic reaction.

Competing Interests

Dr. Laroche had congress fees paid by ThermoFisher for other studies presentation. The other authors declare no competing interests.

References

References
1.
Laroche
D
,
Gomis
P
,
Gallimidi
E
,
Malinovsky
JM
,
Mertes
PM
:
Diagnostic value of histamine and tryptase concentrations in severe anaphylaxis with shock or cardiac arrest during anesthesia.
Anesthesiology
2014
;
121
:
272
9
2.
Sirvent
AE
,
González
C
,
Enríquez
R
,
Fernández
J
,
Millán
I
,
Barber
X
,
Amorós
F
:
Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease.
J Nephrol
2010
;
23
:
282
90
3.
Volcheck
GW
,
Mertes
PM
:
Local and general anesthetics immediate hypersensitivity reactions.
Immunol Allergy Clin North Am
2014
;
34
:
525
46, viii
4.
Mertes
PM
,
Malinovsky
JM
,
Jouffroy
L
,
Aberer
W
,
Terreehorst
I
,
Brockow
K
,
Demoly
P
;
Working Group of the SFAR and SFA; ENDA; EAACI Interest Group on Drug Allergy
:
Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice.
J Investig Allergol Clin Immunol
2011
;
21
:
442
53
5.
Fisher
M
,
Baldo
BA
:
Anaphylaxis during anaesthesia: Current aspects of diagnosis and prevention.
Eur J Anaesthesiol
1994
;
11
:
263
84
6.
Laxenaire
MC
,
Moneret-Vautrin
DA
:
Allergy and anaesthesia.
Cur Opinion Anaesth
1992
;
5
:
436
41