Anaphylaxis

Definition

Anaphylaxis arises when mast cells and possibly basophils secrete potent mediators that have effects on vasculature, smooth muscle, mucous glands, and nerves, thereby eliciting a systemic response. Although mast cells in any organ system may be involved, dictated in part by the distribution of the instigating stimulus, the principal targets are the cardiovascular, cutaneous, respiratory, and gastrointestinal systems, where mast cells are most abundant. Anaphylaxis occurs when mast cells are activated by multivalent allergens that bind to and aggregate immunoglobulin E (IgE) and high-affinity IgE receptors (FcɛRI) on their surfaces. These activated mast cells then secrete mediators, such as histamine, tryptase, prostaglandin d4, and leukotriene c4, that cause the systemic symptoms of immediate hypersensitivity.

Epidemiology

Approximately 1500 to 2000 deaths are attributed to anaphylaxis annually in the United States. Anaphylaxis to foods and insect stings each account for about 100 deaths per year.

The lifetime incidence of anaphylaxis in adults is estimated at 2 to 8%. In children, in whom food allergy is more common, the incidence of anaphylaxis is likely higher. More than 80% of physicians practicing allergy/immunology, emergency medicine, general medicine, or pediatrics report having witnessed anaphylaxis. Medications, insect stings, and foods are the most common triggers, followed by environmental allergens and latex ( Table 233-1 ). In some cases, the cause of anaphylaxis is unknown. About 50% of the reactions occur at home, 15% at a medical facility, and 6 to 7% at another person’s home, at work, or at a restaurant. Antibiotics and radiocontrast media are the most commonly identified triggers in hospitals, and COX-1 inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs) are a leading cause of anaphylaxis seen in emergency departments. Chemotherapy agents ( Chapter 234 ) and monoclonal antibodies also are common causes of anaphylaxis. In the perioperative setting, anaphylactic reactions occur with a frequency of about 1 in 2000 to 10,000 cases. Muscle relaxants or antibiotics are the most common triggers, but latex, induction drugs, chlorhexidine, and other agents also can be the culprit. Advanced age, use of a β-blocker or angiotensin pathway inhibitor, hereditary α-tryptasemia, and concomitant mastocytosis ( Chapter 235 ) increase the risk for severe anaphylaxis. Hereditary α-tryptasemia, which is caused by an increased copy number of the gene that encodes α-tryptase, may be present in up to 5% of the population.

Some type of food allergy is self-reported in 19% of adults and likely is present in as many as 11%, but only about half of these allergies are classified as serious. About 20% of children lose peanut sensitivity by school age, but a small portion will regain peanut sensitivity later in life, particularly if they continue to avoid this food. Most children lose their allergic sensitivities to cow’s milk, egg, wheat, or soy by 5 years of age, whereas sensitivities to tree nuts and seafoods are typically persistent.

Latex provokes anaphylaxis in a small but significant group of individuals, particularly patients who have undergone multiple surgical procedures early in life and individuals with frequent exposures later in life, such as medical personnel. Estimates of the prevalence of latex hypersensitivity range from 1 to 6% in the general population and about 10% among regularly exposed health care workers. Each year, latex-induced anaphylaxis occurs in about 200 individuals and causes an average of 3 deaths. The majority of children labeled as penicillin allergic lose their sensitivity as adults.

Pathobiology

The mediators produced by activated mast cells and basophils initiate many of the signs and symptoms of anaphylaxis. These cells constitutively express the high affinity receptor for IgE, FcɛRI, on their surface, thereby enabling these cells to be armed by antigen-specific IgE and triggered by antigens that aggregate IgE:FcɛRI complexes. In addition to mast cells and basophils, other cells that likely participate in anaphylaxis include eosinophils, monocytes, antigen-presenting cells, platelets, and epithelial cells.

Most IgE-dependent mast cell activation events occur at local sites and result in local disease, such as allergic conjunctivitis, rhinitis, or asthma when allergens land on the corresponding mucosal surface of a sensitive individual and diffuse into the tissue where mast cells reside. Anaphylaxis presumably requires the allergen (or nonallergen agonist) to distribute systemically to activate mast cells at remote sites. However, activation of the contact system by mast cell products (e.g., heparin or tryptase) results in the production of bradykinin, which may also enhance the severity of anaphylaxis. Impaired metabolism of the mast cell mediator platelet-activating factor also may enhance severity.