Skin testing using a commercially available benzylpenicilloyl polylysine conjugate may be used to predict the likeli-hood of an immediate-type reactions. Skin testing cannot predict non-IgE-mediated reactions; therefore, a thorough history to determine the necessity for skin testing is important.
Penicilline, the prototypic beta-lactam antibiotic, is the most frequent cause of anaphylaxis in humans. The reaction occurs when the compound is covalently bound to tissue carrier proteins to form drug-protein conjugates known as haptens. Ninety-five percent of tissue- bound penicillin is haptenized as benzylpenicilloyl, termed the major antigenic determinant. IgE antibodies directed at this hapten appear to be implicated in type I hyperensitivity reactions.
REPRESENTATIVE AGENTS CAUSING ANAPHYLAXIS
Multiple substances have been implicated as possible causes of anaphylaxis. The most common substances include drugs, specifically low-molecular-weight compounds. In most cases, the parenteral mode of administration is implicated, although oral, inhaled, and even cutaneous exposure can induce anaphylaxis as well.
Animal models have been use to understand various manifestations of anaphylaxis. Circulatory collapse typically occurs in dogs, rabbits may suffer acute pulmonary hypertension, and guinea pigs may experience acute respiratory obstruction. These reactions are classically mediated by the interaction of IgE, the high-affinity IgE receptor found on mast cells and histamine. However, findings from several rodent studies suggest an alternative pathway involving the Ig receptor, macrophages, platelets and platelet-activating factor may be more important in anaphylaxis than previously realized. Strait and colleagues immunized wild-type, IgE-deficient and mast cell-deficient mice using goat antimouse IgD antibody. This technique induced mastocytosis and a large response to goat antigen (IgG) with increased IgE and IgG production. After fourteen days, they challenged the mice with antigen (goat IgG) or rat antimouse IgE monoclonal antibody (mAb). The severity of anaphylaxis was gauged by changes in body temperature, physical activity, and mortality. Findings in this experimental model included similar anaphylactic responses regardless of anti-IgE, mAb-induced, or goat IgG antigen challenge.
Treatment of anaphylaxis is aimed at restoring blood pressure, decreasing tissue edema, and reversing bronchospasm. Subcutaneous or intravenous epinephrine, oral or intravenous antihistamines, and systemic steroids are the mainstay of treatment. Patients should be monitored for at least six to twelve hours because late-phase reactions are possible.
Late-phase reactions are characterized by induced production of mediators such as leukotrienes, chemokines, and cytokines, which are not performed. Therefore, the effects of these mediators are seen later into the course, usually hours after the onset of an anaphylactic reaction. The late-phase effects include activation and recruitment of TH2 inflammatory cells, including neutrophils and eosinophils, as well as promulgation of the smooth muscle contraction and vasodilatation initiated by the immediate-phase reactants.
Clinically, these reactions lead to:
- Airway and laringeal edema and bronchospasm with potential for complete asphyxiation
- Gastrointestinal tract smooth muscle contraction, causing pain, vomiting, and diarrhea
- Blood vessel dilatation with potential for progression to circulatory collapse
- Cutaneous vascular permeability, resulting in flushing, urticaria, and angioedema