Etiology
Exposure to allergen in presensitized individuals is the cause of immune-mediated anaphylaxis. Common allergens include drugs, foods, and insect stings, but exercise with or without presence of an allergen may also be a trigger. Sometimes, a cofactor (such as a nonsteroidal anti-inflammatory drug [NSAID], alcohol, or another food) is required to provoke food-associated and exercise-induced anaphylaxis.[22]
Approximately one third to one half of reactions are triggered by food. Ingestion, food aerosols (e.g., peanut particles produced during processing, airborne proteins associated with preparation of shellfish or egg powder used in bakeries), as well as handling of the culprit food (e.g., peanuts, tree nuts, egg, milk, and fish) may trigger severe reactions.[23] Food-associated, exercise-induced anaphylaxis occurs when a patient exercises within 2 to 4 hours after ingestion of a specific food (e.g., wheat, celery, shellfish, though possibly after ingestion of any food).[17]
While sensitization to food proteins is the most common form of allergy to foods of both plant and animal origin, sensitization to carbohydrate epitopes leading to allergic reaction to mammalian meat has been described. This form of food allergy involves sensitization to the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-gal). Alpha-gal is a carbohydrate moiety that is present on cells and tissues of all mammals except the higher order primates (including humans). Tick bites can lead to sensitization of humans to alpha-gal, and subsequent ingestion of meat (e.g., beef, pork, lamb) leads to a delayed allergic reaction. The reaction typically occurs 3 to 6 hours after ingestion. Cross-reactivity with cetuximab has been reported (alpha-gal is present on the Fab portion of the cetuximab heavy chain).[24]
Insect stings with the ubiquitous Hymenoptera (wasps and bees) are commonplace globally, while ant stings and spider bites are limited to their geographic prevalence.[25]
Drug-induced anaphylactic reactions occur in the hospital setting and in the community. For adults, antibiotics, especially penicillin, and NSAIDs have been found to be common causes of medication-related anaphylaxis.[18][19][20]
The risk of anaphylaxis after vaccine administration is low. A review of the Vaccine Safety Datalink estimated the risk of anaphylaxis after vaccination to be 1.31 per million doses.[21]
Anaphylaxis during anesthesia in adults is most often due to reactions to neuromuscular-blocking agents, but may also be due to reactions to intravenous anesthetics, opioid analgesics, NSAIDs, local anesthetics, colloids, antibiotics, and latex.[26][27] In children anaphylactic reactions during anesthesia are more often due to latex, which makes a latex-free environment crucial.[28]
Cases of anaphylaxis to human seminal fluid are rare; the majority are immunoglobulin E (IgE) mediated allergic reactions to plasma proteins. Skin testing using seminal fluid from the male partner and desensitization have been described.
Pathophysiology
The clinical symptoms derive from proinflammatory and vasoactive mediators and cytokines released by massive degranulation or release from basophils and mast cells. Classically, this cascade is initiated by an IgE-mediated hypersensitivity reaction.
Allergens are introduced into the body by various routes: ingestion, inhalation, parenteral, or skin contact. On first exposure, a susceptible person forms IgE antibodies specific to the antigen presented. IgE antibodies attach to high-affinity Fc receptors on basophils and mast cells.
On subsequent exposure, binding of antigen to the IgE antibodies leads to bridging and triggers the degranulation of mast cells. Histamine, prostaglandin D2, leukotrienes, platelet-activating factor, tryptase, nitric oxide, and eosinophil and neutrophil chemotactic factors have diverse effects on target organs and lead to the clinical manifestations of anaphylaxis. These manifestations include increased vascular permeability, vasodilation, and myocardial dysfunction, leading to hypotension and cardiovascular collapse, as up to 50% of intravascular volume can shift to the extravascular compartment in minutes. Altered smooth muscle tone results in bronchospasm and asthma in the respiratory tract, and may also lead to uterine cramps. Activation of the autonomic nervous system causes tachycardia, anxiety, and mucus hypersecretion. Increased platelet aggregation and subsequent recruitment of more immune cells complete the picture of the systemic inflammatory response.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may also trigger cell activation by altering arachidonic acid metabolism. Activation of complement, the complement peptides (anaphylatoxins) such as C3a and C5a, and their direct action on mast cells and basophils may lead to mediator release, producing symptoms indistinguishable from the classic IgE-mediated reaction.[29]
Classification
Classification of anaphylaxis according to causative mechanism[1]
Immunologic IgE-mediated reactions
food
airborne allergens
latex
venom
medication
alpha-gal
food-dependent, exercise-induced anaphylaxis
hormones
seminal fluid
radiocontrast media
Immunologic non-IgE-mediated reactions
immune aggregate
intravenous immunoglobulin
medication
radiocontrast media
Nonimmunologic reactions
opiates
physical factors (e.g., exercise, cold, heat)
Idiopathic
increased mast cell sensitivity/degranulation
unrecognized allergens
Masqueraders
Munchausen stridor
vocal cord dysfunction
Allergic Diseases Resource Center classification[2]
The Allergic Diseases Resource Center makes a distinction between:
Anaphylaxis: immunologic, particularly IgE-mediated reactions
Nonallergic anaphylaxis: clinically identical to anaphylaxis; however, not immunologically mediated.
Use of this content is subject to our disclaimer