Systemic allergic reactions can occur following repeated treatment with many classes of drugs. A relatively common inducer of IgE-mediated allergic reaction is penicillin and other drugs that share aspects of its structure and immunological reactivity. In people who have developed IgE antibodies against penicillin, injection of the drug can cause anaphylaxis and even death. While administration of oral penicillin to an allergic individual can also cause anaphylaxis, the symptoms after oral ingestion are usually less severe and very rarely result in death. One of the reasons that penicillin is particularly prone to inducing allergic reactions is that it acts as a hapten (see Appendix I, Section A-1); it is a small molecule with a highly reactive β-lactam ring that is crucial for its antibacterial activity. This ring reacts with amino groups on host proteins to form covalent conjugates. When penicillin is ingested or injected, it forms conjugates with self proteins, and the penicillin-modified self peptides are recognized as foreign and elicit a host immune response. A large proportion of individuals who are treated with intravenous penicillin develop IgG antibodies against the drug, but these usually cause no symptoms. In some individuals, self proteins conjugated with penicillin provoke a TH2 response that activates penicillin-binding B cells to produce IgE antibody against the penicillin hapten. Thus, penicillin acts both as the B-cell antigen and, by modifying self peptides, as the T-cell antigen. When penicillin is injected intravenously into an allergic individual, the penicillin-modified proteins can cross-link IgE molecules on tissue mast cells and circulating basophils and thus cause anaphylaxis. Great care should be taken to avoid giving a drug to patients with a past history of allergy to that drug or a close structural relative.
As is true for individuals with sensitivity to inhalant allergens, patients with a past history of anaphylactic-type reactions to penicillin or other β-lactam antibiotics can be evaluated by skin-prick testing. A positive skin test, manifested by the formation of a wheal-and-flare reaction at the site of the test, is associated with a substantial risk of developing an anaphylactic reaction when treated with therapeutic doses of the drug.
14-11 Allergen inhalation is associated with the development of rhinitis and asthma.
The respiratory tract is an important route of allergen entry (see Fig. 14.12, third panels). Many atopic people react to airborne allergens with an IgEmediated allergic reaction known as allergic rhinitis. This results from the activation of mucosal mast cells beneath the nasal epithelium by allergens such as pollens that, when they contact the epithelium, release their soluble protein contents, which then diffuse across the mucous membranes of the nasal passages. Allergic rhinitis is characterized by intense itching and sneezing; local edema leading to blocked nasal passages; a nasal discharge, which is typically rich in eosinophils; and irritation of the nasal mucosa as a result of histamine release. A similar reaction to airborne allergens deposited on the conjunctiva of the eye is called allergic conjunctivitis. Allergic rhinitis and conjunctivitis are commonly caused by environmental allergens that are present only during certain seasons of the year. For example, hay fever (known