Drug Induced Hypersensitivity Reaction: Causes, Symptoms and Treatment

This article discusses drug induced hypersensitivity reactions, their causes, symptoms and treatment. It explains the different types of hypersensitivity reactions caused by drugs, including IgE-mediated hypersensitivity reaction, IgG-mediated cytotoxicity and T-cell-mediated drug hypersensitivity. The article also covers the Hapten and Prohapten concept and treatment options for drug induced hypersensitivity reactions.

Running head: DRUG INDUCED HYPERSENSITIVITY REACTION
DRUG INDUCED HYPERSENSITIVITY REACTION
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Author’s note

1DRUG INDUCED HYPERSENSITIVITY REACTION
Discuss how drugs can induce hypersensitivities
Hypersensitive reactions caused by drugs are immune mediated reactions to drugs. The
symptoms can be mild or severe and include rashes, anaphylactic reactions and serum sickness.
Some of the common signs of the drug induced hypersensitivity reactions includes hives, rashes ,
fever, swelling of the skin, shortness of breath, runny nose, wheezing or even severe conditions
such as excessive drop in the blood pressure, seizure and loss of consciousness (Aronson 2015).
Drug related hypersensitive reactions are generally reactions of type B mediated by the acquired
immune reaction. Drug-induced hypersensitivity syndrome (DHS) has many exclusive aspects
that includes a postponed onset, inconsistent degradation of the clinical signs or manifestations
post withdrawal of the responsible drugs and the interactions or pharmacodynamics between
multiple drugs having structural and functional differences (Voie et al. 2012). At times it is
difficult to differentiate reactions that are immune and non-immune mediated, as the clinical
signs of an allergic reaction is only observable on re-exposure or long lasting exposure to the
drug (Alomar 2014). However recent researches have shown that a prior exposure to the active
component is not a precondition for the onset of a bad drug interaction. To comprehend the
pathophysiology of drug mediated hypersensitive reaction, it is vital to identify few phenomena
such as the T-call sensitization, cross reactivity and antibody sensitization. The drug binds to the
haptens to form complexes of hapten-carrier, which are received by the Antigen presenting cells
(APCs) and are then moved to the lymphoid tissues (Schnyder and Pichler, 2009). The naïve T-
cell recognizes the complexes and sensitization of the T-cells occurs. Apart from the

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sensitization of the T- cells, thehapten carrier complex also activates the B-cells to multiply and
differentiate in to plasma cells after which antibodies specific to the drug can be produced
(Aronson 2015).
After the initial sensitization to the drug another set of exposure results in the T- cells and the
antibodies to move into the elicitation phase, related to the type I to IV immune reaction
(Schnyder and Pichler, 2009)..
IgE MEDIATED HYPERSENSITIVITY REACTION (TYPE I)
Drug specific IgE is formed due to the primary drug sensitization and renewed contact
with a small amount of drug might induce drug reactions. This sensitive reaction is reached due
to the presence of the mast cells having high attraction Fc receptors (Schnyder and Pichler 2009).
In order to elucidate a hypersensitive reaction the allergen or the drug should attach to the
antigen binding site within the IgE molecule. Cross linking of two or more allergen binding
region can cause activation of mast cells and the secretion of various inflammatory mediators
like leukotriene, histamine, cytokines and prostaglandins (Hausmann et al. 2012). These
molecules are responsible for increased vascular permeability, bronchoconstriction, increased
production of the mucus contribute the addition of the eosinophil. IgE-mediated reactions can
cause angioedema, urticaria, cardiac complications and severe respiratory symptoms (Hausmann
et al. 2012). The drugs that are responsible for Type I hypersensitivity reaction are mainly the
neuromuscular blocking agents and some drugs like penicillin and cephalosporins.

3DRUG INDUCED HYPERSENSITIVITY REACTION
Source: (Goldsby et al. 2003)
IgG-MEDIATED CYTOTOXICITY (TYPE II)
The drugs that are responsible for the type II hypersensitivity reaction are heparin,
aminopyrine, and methyldopa (Kapur et al. 2013). IgG-mediated cytotoxicity mainly occurs
towards the membrane of the erythrocytes, platelets, leukocytes and the hematopoietic precursor
cell in the bone marrow (Schnyder and Pichler 2009).
In some occasions the immune complex forms and binds to the endothelial cells, leading
to the decomposition of the immune complexes with the activation of complement in the blood
vessels. The signs of a type III reaction includes serum sickness caused by the Beta lactams, drug
induced lupus erthematosus, vasculitis caused due to minocycline (Kapur et al. 2013).
T-CELL-MEDIATED DRUG HYPERSENSITIVITY (TYPE IV)

4DRUG INDUCED HYPERSENSITIVITY REACTION
This type of hypersensitivity reaction is caused by the Beta lactams and the sulfa antibiotics.
Source: (Kuby 1994).
THE HAPTEN AND THE PROHAPTEN CONCEPT
Drug induced hypersensitivity reaction can also be caused without prior drug exposure.
This can be understood through the Hapten and the Prohapten concept (Hausmann et al. 2012).
Drugs and the metabolites binds covalently to the proteins, the processed complex is then
produced as a hapten peptide complex on the MHC of the APCs. These complexes are identified
by the effector T- cells. Repeated stimulation of the effector T- cells causes local T-cell mediated
inflammation. This can be well manifested in case of contact dermatitis and systemic drug
hypersensitivity (Adkinson et al. 2012). . The restimulation of the TCM in the lymph nodes can
cause enlargement of the lymph nodes. Some of the drugs can act as prohaptens and can cause
inflammatory response. For example Penicillin is not antigenic, but its metabolized product;
benzylpenicilloic acid can react with the tissue proteins forming benzylpenicilloyl (BPO), that
has got major antigenic properties (Sukasem et al. 2014).

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TREATMENT
Initially the drug has to be discontinued. Supportive treatments like the administration of
antihistamines, epinephrine, and corticosteroids can be made (Shiohara et al. 2012). Rapid
desensitization may necessitate in case of sensitivity has already been established (Pavlos et al.,
2013). Desensitization involves increasing the doses of the antigen to induce sublingual
anaphylaxis reaction before its exposure to the therapeutic regimen (Hamm 2011). The
development of the tests for the assessing the susceptibility of the patients towards the drug is
still a goal (Pavlos et al. 2013). Genotyping and phenotyping are helpful for those groups of
patients who are on multiple drug therapy (Akdis, 2012; Hamm 2011).
As per the recent findings, regarding the pre-exposure sensitization of the patients with
anaphylaxis reaction induced by the neuromuscular blocking agent, shows that prior interaction
with the drug is not prior requirement for the adverse drug reaction and can be caused due to
cross reactivity. Allergies to drugs, owing to the cross interactions can occur in the reactions
mediated by IgE-, IgG-, and T-cells. Pharmacological treatment involved the administration of
the Corticosteroids.

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