Mast cell activation syndrome (MCAS) is a condition with signs and symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. It can be classified into primary, secondary, and idiopathic. Earlier proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope or near syncope, tachycardia, wheezing, conjunctival injection, pruritus, and nasal stuffiness. Other criteria included a decrease in the frequency, severity, or resolution of symptoms with anti-mediator therapy including H(1) and H(2)histamine receptor antagonists, anti-leukotrienes, or mast cell stabilizers. Laboratory data that support the diagnosis include an increase of a validated urinary or serum marker of mast cell activation (MCA), namely the documentation of an increase of the marker above the patient’s baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/ml, or documentation of an increase of the tryptase level above baseline value on one occasion. Less specific assays are 24-h urine histamine metabolites, PGD(2) (Prostaglandin D(2)) or its metabolite, 11-β-prostaglandin F(2) alpha. A recent global definition, criteria, and classification include typical clinical symptoms, a substantial transient increase in serum total tryptase level or an increase in other mast cell derived mediators, such as histamine or PGD2 or their urinary metabolites, and a response of clinical symptoms to agents that attenuate the production or activities of mast cell mediators.
There is no standardised method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2x baseline tryptase+2mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS).
IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3 to 6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked. This article is protected by copyright. All rights reserved.
Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges
- The journal of allergy and clinical immunology. In practice
- Published almost 3 years ago
Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown.
In this rostrum we aim to increase awareness of anaphylaxis in infancy in order to improve clinical diagnosis, management, and prevention of recurrences. Anaphylaxis is increasingly reported in this age group. Foods are the most common triggers. Presentation typically involves the skin (generalized urticaria), the respiratory tract (cough, wheeze, stridor, and dyspnea), and/or the gastrointestinal tract (persistent vomiting). Tryptase levels are seldom increased because of infant anaphylaxis, although baseline tryptase levels can be increased in the first few months of life, reflecting mast cell burden in the developing immune system. The differential diagnosis of infant anaphylaxis includes consideration of age-unique entities, such as food protein-induced enterocolitis syndrome with acute presentation. Epinephrine (adrenaline) treatment is underused in health care and community settings. No epinephrine autoinjectors contain an optimal dose for infants weighing 10 kg or less. After treatment of an anaphylactic episode, follow-up with a physician, preferably an allergy/immunology specialist, is important for confirmation of anaphylaxis triggers and prevention of recurrences through avoidance of confirmed specific triggers. Natural desensitization to milk and egg can occur. Future research should include validation of the clinical criteria for anaphylaxis diagnosis in infants, prospective longitudinal monitoring of baseline serum tryptase levels in healthy and atopic infants during the first year of life, studies of infant comorbidities and cofactors that increase the risk of severe anaphylaxis, development of autoinjectors containing a 0.1-mg epinephrine dose suitable for infants, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis recurrences.
Postmortem diagnosis of sudden death due to anaphylaxis can be very difficult due to the non-specific pathological findings in forensic practice. Postmortem serum tryptase has been used as an indicator of possible ante-mortem anaphylaxis. Though many previous studies have been conducted to explore the diagnostic significance of serum tryptase for lethal anaphylaxis, inconsistent results were documented. In this study, we made a retrospective study and presented a systematic review and meta-analysis that aims to summarize the diagnostic significance of postmortem serum tryptase in the deceased with and without anaphylactic shock and to calculate a cutoff value for future reference in the identification of deaths due to anaphylactic shock. A complete literature search in the PubMed, Cochrane Library, CNKI and Embase databases (published prior to March 1st, 2017) was performed. The quality of the eligible literature was evaluated according to the Newcastle-Ottawa Quality Assessment Scale (NOS), and the relevant data was extracted. The procedure of meta-analysis was performed by RevMan 5.3 software. Subgroup analysis was performed according to different causes of death. A total of nine studies with 296 patients were identified. The NOS of each included study was equal to 7. The results indicated that high concentrations of tryptase were significantly associated with anaphylactic shock when compared to the other causes of death. The weighted mean difference (WMD) was 29.53 (95% CI = 7.58-51.47, p = 0.008). Similar results were detected in the subgroup analysis when compared to deaths due to cardiovascular disease (CVD). However, no obvious elevation of tryptase in decedents with CVD compared to the other cause of death was observed (WMD = 4.42, 95% CI = -0.94-9.79). We concluded that high serum tryptase is a promising diagnostic biomarker for deaths due to anaphylactic shock, especially when it is higher than 30.4 μg/L.
We describe 2 patients who developed anaphylactic shock after sugammadex administration during anesthesia. Both had no history of prior sugammadex administration. The serum tryptase concentrations were elevated after the allergic reaction. Basophil activation testing 1 month after the events was positive for sugammadex in 1 patient, and negative in the other. However, it was positive for light-exposed sugammadex solution in both patients, suggesting a possible allergic reaction to a denatured compound of sugammadex generated by light exposure of the sugammadex solution.
Tryptase increase on the first day of hymenoptera venom immunotherapy might be a predictor of future systemic reactions during treatment
- Journal of investigational allergology & clinical immunology
- Published almost 3 years ago
Serum tryptase (ST) decreases in long-term venom immunotherapy (VIT). A circadian tryptase variation with a small decrease has been found after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likehood of future systemic adverse reactions (SAR) during treatment.
Serum mast cell tryptase is used to support the diagnosis of anaphylaxis. The recommended clinical cut-off for total tryptase (<11.4μg/L) appears unsuitable in the post mortem setting due to largely unknown processes which result in significantly elevated levels in these samples. Consequently there is no widely accepted tryptase cut-off level for diagnosing an anaphylactic death. This 5-year retrospective study compared total tryptase levels in post mortem femoral blood in anaphylactic deaths and control. Univariate and multivariate analysis was used to assess the relative contribution of other factors (age, gender, post mortem interval, and presence of resuscitation) on post mortem tryptase levels. Nine anaphylactic deaths and 45 controls were identified. Receiver-operating characteristic (ROC) curve analysis identified an optimal cut-off of 53.8μg/L, with sensitivity of 89%, and specificity of 93%, for total post mortem tryptase in femoral blood to diagnosis anaphylaxis. No other factors showed any statistical significant contribution to post mortem tryptase elevation. Femoral total post mortem tryptase level of 53.8μg/L and above is a useful ancillary test in diagnosing an anaphylactic death.
The measurement of mast cell tryptase is commonly used to support the diagnosis of anaphylaxis. In the post-mortem setting, the literature recommends sampling from peripheral blood sources (femoral blood) but does not specify the exact sampling technique. Sampling techniques vary between pathologists, and it is unclear whether different sampling techniques have any impact on post-mortem tryptase levels.