The anaphylaxis hypothesis of sudden infant death syndrome (SIDS): mast cell degranulation in cot death revealed by elevated concentrations of tryptase in serum

Holgate, Stephen T.; Walters, C.; Walls, Andrew F.; Lawrence, Steve; Shell, David J.; Variend, S.; Fleming, PJ; Berry, P J; Gilbert, Ruth; Robinson, Clive

doi:10.1111/j.1365-2222.1994.tb03316.x

Cited by 59 publications

(34 citation statements)

References 23 publications

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“…However, in trauma victims, increased hemolysis showed a positive correlation with increase in tryptase concentrations [9]. Elevated values are often seen in sudden infant death syndrome (SIDS) [10][11][12], but whether this is due to agonal asphyxia or if it is a postmortem artifact, due to sampling of blood from the heart is not clear [12].…”

Section: Introductionmentioning

confidence: 95%

Mast cell tryptase in postmortem serum—reference values and confounders

2006

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We have investigated the effects of some factors suspected of inducing spuriously increased tryptase concentrations, specifically sampling site, conjunctival petechial bleeding and prone position at the time of death as indicators of premortem asphyxia, and resuscitation efforts by external cardiac massage. Tryptase was measured in blood from the femoral vein in 60 deaths: 39 control cases who died rapidly (within minutes) from natural causes (sudden cardiac death and acute aortic dissection), 16 with death caused by prolonged asphyxia (traumatic compression of the chest and suffocation due to body position or smothering), and five anaphylactic deaths. In 44 of these cases, tryptase was measured in both heart and femoral blood. Mast cell tryptase was analyzed with a commercial FEIA method (Pharmacia Diagnostics AB, Uppsala, Sweden) measuring both alpha- and beta-tryptase. Assuming that tryptase values in the control group were gamma distributed, we calculated the upper normal limits for tryptase concentrations in femoral blood. It was found that 95% of the controls had values below 44.3 mug/l (femoral blood), SD 5.27 mug/l. All but one of the anaphylactic deaths had tryptase concentrations exceeding that limit. Tryptase was significantly elevated in femoral blood from anaphylactic deaths (p<0.007), compared with the controls. Also, in the cases where death had occurred due to asphyxia tryptase was elevated in femoral blood (p<0.04). A significant difference in tryptase concentrations was seen between blood from the heart and the femoral vessels (p<0.02) in the whole material (n=44). Tryptase concentrations in femoral blood were not influenced by prone position at death, or resuscitation efforts. It is concluded that asphyxia premortem seems to affect tryptase concentrations, that postmortem tryptase measurements should be done in serum from femoral blood, and that the normal upper limit, covering 95%, is 44.3 microg/l.

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Section: Introductionmentioning

confidence: 95%

Mast cell tryptase in postmortem serum—reference values and confounders

2006

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“…Tryptase has been measured in several body fluids: nasal lavage fluid [15], tears [16, 17], bronchoalveolar lavage [18] and intra-articular fluid [19]. Postmortem measurement of serum tryptase revealed altered levels in sudden infant death syndrome [20] and in a small number of unexpected deaths, possibly cases of clinically unrecognized fatal anaphylaxis [21]. …”

Section: Discussionmentioning

confidence: 99%

Tryptase as Severity Marker in Drug Provocation Tests

Komericki¹,

Arbab²,

Grims³

et al. 2006

Int Arch Allergy Immunol

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Background: In the absence of objective symptoms, it is difficult to assess an adverse reaction during drug provocation testing. We evaluated the value of serum tryptase levels to distinguish between positive, negative and, even more important, so-called ‘hysterical’ reactions (conversion symptoms). The latter are occasionally observed in drug provocation tests when the patient experiences ambiguous subjective symptoms. Methods: In a prospective single-center study, 303 patients underwent 785 drug provocation tests. Blood was taken for tryptase measurement on each test day before and after drug challenge, and the changes in serum tryptase levels in patients with no reactions were compared with those who experienced immediate reactions to a drug. Results: Thirty-four of 785 drug provocations were clinically judged as being positive. Despite objective symptoms, median serum tryptase values in the afternoon were even lower than baseline levels. However, this decrease was not statistically significant. In the 751 patients suffering no objective reactions, the median values of posttesting tryptase values were statistically significantly decreased as compared with pretesting values. Conclusions: The measurement of serum tryptase levels does not appear to be helpful to differentiate mild allergic or nonallergic reactions from ‘hysterical’ ones. The milder decrease in the group with objective drug reactions might indicate slight mast cell activation in some patients. More severe clinical drug reactions led to stronger mast cell degranulation. Mild reactions did not increase the tryptase levels consistently.

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“…Well described in children, this immunopathological component, known as cytokine storm hypothesis, is a combination of inadequate secretion in response to viral infection of pro-inflammatory cytokines (IFNγ, IL-1, IL-6, and TNFα) with a deficit in anti-inflammatory cytokines such as IL-10 [23]. It causes microscopic inflammatory changes of the respiratory tract, frequently observed in sudden deaths, consisting in peribronchial inflammatory infiltrates, increase in IgM-producing cells in trachea, and mast cell degranulation [24,25]. The RSV, in particular, is known to cause a major and inappropriate inflammatory response, which explains its frequent detection in sudden death of the child [26].…”

Section: Respiratory Viruses As a Cause Of Sudden Deathmentioning

confidence: 99%