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      Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose

      , , , ,   ,
      Clinical Toxicology
      Informa UK Limited

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          Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study.

          Emergency department visits for acute allergic reactions are common. Although the diagnosis and classification of these allergic reactions is primarily empiric, it is not always clear whether certain signs and symptoms constitute systemic mediator release syndromes, such as anaphylaxis, and thus may warrant more aggressive therapy or follow-up. We sought to determine associations between various clinical signs and symptoms with both plasma histamine levels and serum tryptase levels in adult patients presenting to an emergency department with acute allergic syndromes. The clinical correlates of raised beta-tryptase levels were also investigated. Ninety-seven adult emergency department patients were prospectively studied by using a questionnaire, physical examination, and serum-plasma sampling. Plasma histamine and serum total and beta-tryptase levels were determined. Clinical groupings were compared for mediator levels by using simple and multivariate analysis. Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15 ng/mL) were observed in 42 and 20 patients, respectively. Detectable beta-tryptase (>/=1 ng/mL) was observed in 23 patients, including 15 of the patients with elevated total tryptase levels. Suspected food allergy incidences and the duration of reaction were similar in patients with increased histamine levels and in patients with increased tryptase levels. Increased total tryptase levels, histamine levels, or both were observed in some patients who did not have airway, cardiovascular, or abdominal signs. Histamine levels correlated better with clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were observed more frequently in patients characterized by the following clinical signs in univariate analysis: the presence of urticaria, more extensive erythema, abnormal abdominal findings, and wheezing. Total tryptase increases were observed more frequently only in patients with urticaria. Histamine levels correlated with initial heart rates. In multivariate analysis the extent of urticaria was the best single predictor of plasma histamine levels and of either an elevated histamine or tryptase level. Detectable beta-tryptase levels were observed in some patients who had neither elevated total tryptase nor elevated histamine levels. Unlike patients without detectable beta-tryptase levels, patients who had detectable beta-tryptase levels had a significant correlation between total tryptase and histamine levels (P <.05). Raised histamine and, less commonly, raised tryptase levels are observed in almost 50% of patients presenting to emergency departments with acute allergic reactions. Some cases associated with systemic mediator release do not have classical features of severe anaphylaxis, such as hypotension or tachycardia. The lack of total tryptase elevations in many patients with elevated plasma histamine levels suggests basophil involvement. The clinical utility of beta-tryptase determinations in the evaluation of acute allergic reactions needs further study.
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            Physiologic manifestations of human anaphylaxis.

            In the course of a controlled study to evaluate different forms of immunotherapy for subjects with insect-sting hypersensitivity, we observed 11 subjects who had systemic cutaneous urticarial reactions and 3 subjects who experienced systemic anaphylaxis. With the exception of tachycardia, there were no cardiopulmonary changes in the subjects with urticaria, whereas the major manifestation of anaphylactic shock in the other three subjects was severe hypotension that was probably secondary to peripheral vasodilation. Significant abnormalities in gas exchange developed in two subjects. In one, bronchospasm precipitated a respiratory arrest followed by endotracheal intubation with mechanical ventilation. Although plasma histamine levels were not related to the development of cutaneous reactions, the plasma histamine levels correlated with the severity and duration of the cardiopulmonary changes observed during anaphylactic shock. The two subjects with the most severe shock showed evidence of intravascular coagulation characterized by a diminution of Factor V, Factor VIII, fibrinogen, and high molecular weight kininogen, as well as changes in components of the complement system. Standard therapy with epinephrine and fluids, usually recommended for the treatment of systemic anaphylaxis, did not immediately reverse either the hemodynamic or the respiratory abnormalities in the two subjects with the most severe anaphylactic shock. Hemodynamic recovery was gradual and did not seem directly related to any specific therapeutic intervention.
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              Tryptase genetics and anaphylaxis.

              Tryptases secreted by tissue mast cells and basophils can enter the bloodstream. In human subjects tryptases are encoded by several genes and alleles, including alpha, beta, gamma, and delta. Common variations include complete absence of alpha genes. Until recently, alpha tryptase was considered to be the major tryptase secreted at baseline and in mastocytosis. However, lack of alpha tryptase genes has little effect on circulating tryptase levels, which are now thought mainly to consist of inactive pro-beta tryptase secreted constitutively rather than stored in granules with mature tryptases. Pro-beta tryptase levels thus might reflect total body mast cell content. In contrast, mature beta tryptase can increase transiently in severe systemic anaphylaxis and confirm the diagnosis. However, it might fail to increase in food anaphylaxis or might increase nonspecifically in samples acquired after death. Thus pro- and mature beta tryptase measurements are useful but associated with false-negative and false-positive results, which need to be considered in drawing clinical conclusions in cases of suspected anaphylaxis.

                Author and article information

                Journal
                Clinical Toxicology
                Clinical Toxicology
                Informa UK Limited
                1556-3650
                1556-9519
                October 20 2008
                October 20 2008
                : 46
                : 8
                : 697-702
                Article
                10.1080/15563650802245497
                18803085
                c3ad3dac-3052-4690-b25a-fca4e8bb8edb
                © 2008
                History

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