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
"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.