﻿ Allergic Reactions to Drugs a Big Problem and a Model of Delayed Hypersensitivty
Allergy The Allergy Center

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Allergic Drug Reactions

Allergic drug reactions have always been recognized in the medical literature and drug product monographs. The allergy involved is seldom the type 1 reaction, does not involve IgE antibodies and does not show on skin tests. Drug allergy is the prototype of delayed hypersensitivity and can be used as a model of the kind of problems one should also expect from the prodigious array of antigenic molecules that arrive in the air and in the food supply.

For example, the Prozac (fluoxetine) product monograph describes reactions to the drug:

"Allergic reactions: Of 5600 patients given fluoxetine approximately 4% developed a rash and or urticaria... Reported in association with these allergic reactions include rash, fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase reactions... two patients are known to have developed a serious cutaneous, systemic illness. One was considered to have a leukocytoclastic vasculitis, and the other severe desquamation that was considered to be a vasculitis or erythema multiforme. Other patients have had systemic manifestations suggestive of serum sickness... events possibly related to vasculitis, have developed in patients with a rash. Although these events are rare, they made be serious, involving the lung, kidney or liver. Death has been reported to occur in association with systemic events. Anaphylactoid events including bronchospasm, angioedema, and urticaria, alone and in combination have been reported. Pulmonary events, including inflammatory processes of varying histopathology and or fibrosis have been reported rarely. These events have occurred with dyspnea as the only preceding symptom. Whether these events and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known. Furthermore, a specific underlying immunologic basis for these events has not been identified."

Prozac, like many other drugs and like chemicals found in the food supply is capable of causing delayed hypersensitivity reactions with a spectrum of manifestations in many body systems. Although the product monograph declares that mechanism are unknown, it is likely that Prozac acts as a hapten, an incomplete antigen, and when associated with serum proteins, triggers any of the four immune hypersensitivity mechanisms in any combination with mixed results.

The symptom complexes described in the monograph clearly involve more that one mechanism - the anaphylactic responses are probably type 3 with complement activation. Inflammation in target organs is produced by cell-mediated, type IV responses. Intravenous administration of drugs is more often associated with immediate hypersensitivity reactions.

One reason that food antigens are seldom recognized as a source of disease is the complexity and variability of the food supply. Antigens in food are numerous and seldom are discretely presented. Food antigens are variable; they change with variations in agricultural practice, food spoilage, contamination, preparation, cooking, and events in the digestive tract. For most physicians, the food supply of a patient is a given, an act of God, so that food-related hypersensitivity diseases appears to be spontaneous and without cause.

If physicians assumed that all idiopathic hypersensitivity diseases may originate from antigens in the food supply, then they would join us in the search for simple and effective solutions for common and disabling diseases.