DRUG ALLERGY

DEFINITION
 Drug allergy is an unpredictable
immunologically mediated response to a
pharmaceutical and/or formulation (excipient)
agent in a sensitized person with heterogeneous
mechanisms and clinical presentations

Egypt J Pediatr Allergy

Immunol 2013
 EPIDEMIOLOGY
Allergic reactions are thought to account for less than
10% of all adverse drug reactions

The overall incidence of adverse drug reactions in the

general as well as pediatric populations is estimated to
be 6.7%

The most common culprit drugs among new drug

hypersensitivity reactions were antibiotics (32%), radio
contrast media (26%) and anti-neoplastic drugs (17%).
The estimated incidence of drug hypersensitivity
reactions was 0.18 % among hospital admissions

Egypt J Pediatr Allergy

Immunol 2013
MECHANISMS OF DRUG ALLERGY
 All allergic mechanisms depend on interaction
between a foreign antigen and host antibodies or
sensitised lymphocytes

Type of hypersensitivity :
1) Type I : Anaphylactic Reaction ( immediate)

2) Type II : Cell Damage (cytotoxic)

3) Type III : Immune complex- mediated reaction

4) Type IV : Cell- mediated Allergy (delayed)

Avery’s Drug Treatment

4th Edition
IMMUNOLOGICAL CLASSIFICATION OF
DRUG ALLERGY

Avery’s Drug Treatment

4th Edition
IMMUNOLOGICAL CLASSIFICATION OF DRUG
ALLERGY

Avery’s Drug Treatment

4th Edition
IMMUNOLOGICAL CLASSIFICATION OF DRUG
ALLERGY

Avery’s Drug Treatment

4th Edition
IMMUNOLOGICAL CLASSIFICATION OF DRUG
ALLERGY

Avery’s Drug Treatment

4th Edition
FOCTORS INFLUENCING THE OCCURRENCE
OF ALLERGIC DRUG REACTIONS
 1. duration and number of courses of treatment
A reactions increases with the number of courses of
treatment
 2. route of administration
Anaphylaxis,much less common with oral than with
parenteral administration

 3. atopy
Anaphylaxis following administration by oral,
inhalation occurs considerably more often in atopic than in
non atopic individuals

 4. previous history of allergic reactions

 The likelihood of another reaction is greater in
those who have suffered a previous allergic
reaction
Avery’s Drug Treatment
4th Edition
FACTORS INFLUENCING THE OCCURRENCE
OF ALLERGIC DRUG REACTIONS

 5. age
Allergic reaction to drugs seem less common
in children
 6. coexisting disease states

patients with infetious mononucleosis,

lymphoid leukaemia, or hyperuricaemia have a
very much greater likelihood of maculopapular
rash with ampicillin
impaired renal function increases the risk of
haemolitic anaemia occuring with high-dose
penicillin therapy
Avery’s Drug Treatment
4th Edition
CLINICAL MANIFESTATIONS OF DRUG
ALLERGY

 Drug-induced allergic reactions can affect

numerous organ systems and manifest in a
variety of reactions, including various drug-
induced allergic syndromes

 Most of the cases present with cutaneous

manifestations (about 70%) rather than systemic
manifestations or anaphylaxis

Egypt J Pediatr Allergy

Immunol 2013
CLINICAL MANIFESTATIONS OF DRUG
ALLERGY

 1. Anaphylactic Reactions
 2. immunologically mediated reactions

 Againts spesific tissues

 3. Serum Sickness (type III hypersensitivity)

 4. Skin reactions

 5. Fever

Avery’s Drug Treatment

4th Edition
1. ANAPHYLACTIC REACTIONS
 Reactions of the immediate type are largely IgE-
mediated
 Localised reactions
 The skin ( urticaria or angio-oedema)
 The respiratory tract ( bronchial asthma)
 The gastrointestinal tract ( vomiting, abdominal pain
and diarrhoea)
 Generalised systemic anaphylaxis
 acute and life threatening ( hypotension,
bronchospasm,urticaria,laryngeal oedema)

Penicillins , dextrans , iodinated radiocontrast

media, Intravenous anaesthetics and relaxant
Avery’s Drug Treatment
4th Edition
 2. IMMUNOLOGICALLY MEDIATED REACTIONS
AGAINTS SPESIFIC TISSUES

 Many drugs cause autoimmune haemolysis

 Immunologically –mediated disturbances of hepatic
function may also accur

Avery’s Drug Treatment 4th Edition

3.SERUM SICKNESS(TYPE III
HIPERSENSITIVITY)

 In the presence of a realative excess of antigen,

immune complexes are small and not readily
removed,they lodge in small blood vessels,
leading to inflammasion.

 In the initial exposure to a drug, symtoms of the

serum sickness syndrome generally develop after a
latent period of 6 days or more, reflecting the time
taken to synthesise appreciable amounts of antibody.

 Generally, symptoms last a few days to a week,

but may persist for as long as 6 weeks
Avery’s Drug Treatment
4th Edition
CLINICAL MANIFESTATIONS OF DRUG
ALLERGY

Avery’s Drug Treatment 4th Edition

4. SKIN REACTIONS

 Skin reactions include Coombs-Gel type I

reactions, immune complex (type III) reactions,
and cell-mediated (type IV) allergy.
 Drug- induced cutaneous eruptions can occur as
isolated manifestations involving the viscera
 Urticaria and angio-oedema exemplify type I
reactions
 Type III reaction involving blood blood vessels in
the skin and subcutaneous tissues, (oral
anticoagulants)

Avery’s Drug Treatment

4th Edition
5. FEVER
 It is mediated by circulating antibodies,
particularly Ig G,but may be a manifestation of
cellular immunity
 The release of endogenous pyrogens from
granulocytes or mononuclear
 Marked and sustained fever may be associated
with inflammatory lesions of smal vissels
 Sulfonamides, penicillins, cefalosporins and their
analogues, quinidine, methyldopa,phenytoin, and
amphotericin B
 Bleomycin (anticancer drugs)

Avery’s Drug Treatment

4th Edition
CLINICALLY SIGNIFICANT ALLERGIES TO
COMMONLY USED DRUGS

1. penicillin Alergy
 Penicillin can cause many types of allergic
reactions
 A proteinaceous fermentation residue may be
present in commercial penicillins, certified as
pure by ordinary standards, with which
penicilloyl groups and minor determinants
conjugate readily.
 The deacylation and replacement of side chains
which are involved in manufacture of the semi-
synthetic penicillins presumably remove the
proteinaceous residue
Avery’s Drug Treatment
4th Edition
1. PENICILLIN ALERGY

 Acute anaphylaxis is less common (given orally)

 penicilin are a frequent cause of acute
imunologically mediated reactions, though they
cause anaphylaxis infrequently
 The risk of anaphylaxis reactions to penicillin is 2
to 3 times greater in atopic patients
 The incidence in patients who are hypersensitive
to penicillin is about 8,2 % ( 1,7 % in patients not
hipersensitive to penicillin )

Avery’s Drug Treatment

4th Edition
1. PENICILLIN ALERGY
 Penicillin induced haemolitic anaemia has also
been described as occuring at low dosages

 Cefalothin-induced haemolysis with a positive

commbs’test occurs at regular dosages in the
absence of renal disease

Avery’s Drug Treatment

4th Edition
2. SENSITIVITY TO ASPIRIN AND OTHER
NSAIDS

 In sensitised individuals, bronchospasm

acompanied by rhinorrhea, conjunctial
congestion,and flushing of the head and neck
may occur within minutes and hours of ingestion
of aspirin

 The inhibition of the cyclo-oxygenase step in the

pathway of prostaglandin may divert arachidonic
acid metabolism towards production of the
bronchiolar constricting leukotrienes LTC4 and
LTD4

Avery’s Drug Treatment

4th Edition
3. ANAESTHETIC AGENTS AND DRUGS
USED IN INTENSIVE CARE
 Most reactions occuring during anaesthesia can be
shown to be of immunologiccal origin
 Cardiovascular collapse, with or without bronchospasm
 Cutaneous and mucosal oedema
 Angio-oedema is dangerous (affects the glottis)

o More common in young adults than in other age

groups

o Females more than males

o Intravenous opioids (heroin , codeine, morphine),

intravenous dextrant is a potent allergen
Avery’s Drug Treatment
4th Edition
4. RADIOGRAPHIC CONTRAST MEDIA
o It is increasingly used by injection
 Adverse effects are due to allergy (5 to 20 %) and
include anaphylaxis
 The incidence of adverse effects is about 33% for
ionic contrast media and 5% for non-ionic agents
 Many of the effects are vascular, particularly
with ionic contrast media, and include vascular
spasm, feelings of heat and hypotension

Avery’s Drug Treatment

4th Edition
5. PHARMACEUTICAL EXCIPIENTS
 This occur in all products and include aerosol
propellants , antimicrobial preservatives,
collouring agents, emulsifying, solubilising and
wetting agents, perfumes, ointment bases,
sweeteners, tablet and capsule binders and
disintegrants and antioxidants.

Avery’s Drug Treatment

4th Edition
6. CYTOTOXIC DRUGS
 These drugs are well known for a variety of toxic
reactions related to their effects on rapidly
dividing cells(mainly haematological and
gastrointestinal toxicity).
 Asparaginase has been implicated as causing
hypersensitivity symptoms in between 6 and 43
% of patients studied.

Avery’s Drug Treatment

4th Edition
ALGORITHM FOR DISEASE MANAGEMENT
OF DRUG ALLERGY.
1. Patient develop a possible
adverse drug reaction

2. Review of medical history,

the patient’s record, physical 3. Consider other
examination, and clinical
NO possibilities
tests support an adverse drug
reaction

yes
5. The adverse reaction is predictable
4. Drug induced allergic (toxicity, side effect, drug interaction)
reaction suspected ? NO or due to idiosincrasy, intolerance or
pseudoallergic effects of the drug
yes
 ALGORITHM FOR DISEASE MANAGEMENT
yes OF DRUG ALLERGY.
6. Future management and prevention of
7. Are appropriate non immune adverse drug reaction
confirmatory tests  Modify dose(for toxicity,side effect, or
available? drug interaction)
 Alternative drug
yes NO  Consider Graded challenges
 Consider prophylactic regimens before
administration (if shown to be effective)
 Patient education
8. Are tests positive?
11. Does test have
NO
high negative
predictive value? NO
yes
yes
13. Patient may be
9. Diagnosis of drug
allergic (despite
allergic reaction 12. Patient not
negative drug specific
confirmed allergic to this drug
or nonspecific
confirmatory tests)
ALGORITHM FOR DISEASE MANAGEMENT
OF DRUG ALLERGY.
13. Patient may be allergic
9. Diagnosis of drug
(despite negative drug
allergic reaction
specific or nonspecific
confirmed
confirmatory tests)

10. Management and prevention of drug allergic reactions

 Anaphylactic reactions require prompt emergency
treatment
 Avoid drug if possible
 Consider induction of tolerance procedure or graded
challenge before administration
 Consider prophylactic regimen before administration ( if
shown to be effective)
 Future prudent use of drugs
 Future use of drug causing non – anaphylactic, life
threatening reaction (stevens-johnson, churg-strauss)
contraindicated
 Patient education
ANNALS OF ALLERGY, ASTHMA &
IMMUNOLOGY, 2010
Thank you