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DEFINITION
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Anaphylaxis is a potentially life-threatening systemic allergic reaction involving one or more organ systems that typically occurs within seconds to minutes of exposure to the anaphylactic trigger, most often a drug, food, or hymenoptera sting. Other triggers of anaphylaxis include radiocontrast administration or latex exposure. The term “anaphylaxis” was first described in 1902 by Charles Richet and Paul Portier who attempted to immunize dogs against sea anemone toxin in the same way Pasteur was able to vaccinate individuals against the smallpox virus. To their surprise, repeated administration of small, sub-lethal doses of sea anemone toxin reliably induced acute-onset death when re-administered 2–3 weeks after initial “vaccination” to the toxin. The phenomenon was termed ana (anti) - phylaxis (“protection or guarding”) because vaccination with anemone toxin resulted in the opposite intended immune effect. Charles Richet was awarded the Nobel Prize in Physiology or Medicine in 1913 for this work which led to further insights into hypersensitivity and mast cell biology.

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Clinical Manifestations
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While 80–90% of anaphylactic episodes are uniphasic, about 10–20% of cases are biphasic in which anaphylactic symptoms return about an hour or longer after resolution of initial symptoms. Anaphylactic reactions are particularly dangerous when hypotension or hypoxia occurs, leading potentially to cardiovascular collapse or respiratory failure, respectively. There may be upper or lower airway obstruction or both. Laryngeal edema may be experienced as a “lump” in the throat, hoarseness, or stridor, whereas bronchial obstruction is associated with a feeling of tightness in the chest and/or audible wheezing. Patients with underlying asthma are predisposed to severe involvement of the lower airways and increased mortality associated with anaphylaxis. In fatal cases with clinical bronchial obstruction, the lungs show marked hyperinflation on gross and microscopic examination. The microscopic findings in the bronchi, however, are limited to luminal secretions, peribronchial congestion, submucosal edema, and eosinophilic infiltration, and the acute emphysema is attributed to intractable bronchospasm that subsides with death. Angioedema resulting in death by mechanical obstruction occurs in the epiglottis and larynx; however, the process also is evident in the hypopharynx and to some extent in the trachea. On microscopic examination, there is wide separation of the collagen fibers and the glandular elements; vascular congestion and eosinophilic infiltration also are present. Patients dying of vascular collapse without antecedent hypoxia from respiratory insufficiency have visceral congestion with a presumptive loss of intravascular fluid volume. The associated electrocardiographic abnormalities, with or without infarction, in some patients may reflect a primary cardiac event mediated by mast cells (which are prominent near the coronary vessels) or may be secondary to a critical reduction in blood volume.

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Gastrointestinal manifestations represent another severe presentation of anaphylaxis, and include nausea, vomiting, crampy abdominal pain, and/or fecal incontinence. Angioedema of the bowel wall may also cause sufficient intravascular volume depletion to precipitate cardiovascular collapse.

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Cutaneous manifestations are among the most common presentations of anaphylaxis (>90% of cases). Symptoms include urticarial ...

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