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Drugs as immunogens
Complete
of administration:
- parenteral route more likely than oral
route to
cause sensitization and anaphylaxis
- inhalational route: respiratory or
conjunctival
manifestations only
- topical: high incidence of sensitization
Scheduling of administration:
- intermittent courses: predispose to
sensitization
of the drug:
80% of allergic drug reactions
due to:
- penicillin cephalosporins
sulphonamides (sulpha drugs)
- ASA/NSAIDs
1 : Immediate Hypersensitivity
- IgEmediated
- occurs within minutes to 4-6 hours of drug
exposure
Type 2 : Cytotoxic reactions
- antibody-drug interaction on the cell surface
results in destruction of the cell eg.
hemolytic
anemia due to penicillin, quinidine, quinine,
cephalosporins
3 : Serum sickness
- fever, rash (urticaria, angioedema, palpable
Classification of hypersensitivity
The
Hypersensitivity Reactions
I (immediate)
II (cytotoxic)
III (immune
complex)
IV (delayed)
V
(stimulating/blocki
ng)#
Antigens
Pollens, moulds,
mites, drugs,
food and
parasites
Cell surface or
tissue bound
Exogenous
(viruses,
bacteria,
fungi,
parasites)
Autoantigen
s
Cell/tissue
bound
Cell surface
receptors
Mediators
IgG, IgM,
IgA and
complement
TD, Tc
activated
macrophages
and
lymphokines
IgG
Diagnostic
tests
Skin-prick tests:
wheal and flare
Specific IgE in
serum
Coombs test
Indirect
immunofluorescen
ce (antibodies)
Red cell
agglutination
Precipitating
antibodies
ELISA
Immune
complexes
Skin test:
erythema
induration
(e.g.
tuberculin
test)
Indirect
Immunofluorescenc
e
Time taken
for reaction
to develop
5-10min
6-36 hours
4-12 hours
48-72 hours
Variable
10
I (immediate)
II (cytotoxic)
III (immune
complex)
IV (delayed)
V
(stimulating/blocki
ng)
Immunopathology
Oedema,
vasodilation, mast
cell degranulation,
eosiniophils
Antibody-mediated
damage to target
cells
Acute
inflammatory
reaction,
neutrophils,
vasculitis
Perivascular
inflammation,
mononuclear cells,
fibrin
Granulomas
Caseation and
necrosis in TB
Hypertrophy or
normal
Diseases and
conditions
produced
Asthma (extrinsic)
Urticaria/oedema
Allergic rhinitis
Anaphylaxis
Autoimmune
Haemolytic
anaemia
Transfusion
reactions
Haemolytic
disease of
newborn
Goodpastures
syndrome
Addisonian
pernicious
anaemia
Myasthenia gravis
Autoimmune (e.g.
SLE,
glomerulonephritis
, rheumatoid
arthritis)
Low-grade
persistent
infections (e.g.
viral hepa
hepatitis)
Disease caused by
environmental
antigens (e.g.
far
farmers lung)
Pulmonary TB
Contact dermatitis
Graft-versus-host
disease
Insect
Insect bites
Leprosy
Neonatal
hyperthyroidism
Graves disease
Myasthenia gravis
Exchange
transfusion
Plasmapheresis
Immunosuppressiv
es/cytotoxics
Corticosteroids
Immunosuppressiv
es
Plasmapheresis
Immunosuppressiv
es
Corticosteroids
Removal of
antigen
Treatment of
individual disease
Treatment
Antigen avoidance
Antihistamines
Corticosteroids
(usually topical)
Sodium
cromoglicate
Epinephrine for
life-threatening
RAST, radioallergosorbent
test; SLE,
conditions
11
12
Analgesics,
such as codeine,
morphine, nonsteroidal antiinflammatory drugs (NSAIDs, such
as ibuprofen or indomethacin), and
aspirin
Antibiotics such as penicillin, sulfa
drugs, and tetracycline
13
Frequent
14
15
Rash
Fever
Muscle
Penicillin
Urticaria
Penicillin, aspirin
Vasculitis
Gold, hydralazine
Phenolphthalein in
laxatives, tetracyclines,
paracetamol
Pigmentation
Minocycline (black),
amiodarone (slate grey)
Lupus erythematosus
Penicillamine, isoniazid
Photosensitivity
Thiazides, chlorpromazine,
sulphonamide, amiodarone
Pustular
Carbamazepine
Erythema nodosum
Sulphonamides, oral
contraceptive
17
Anticonvulsants
Acneiform
Corticosteroids
Lichenoid
Chloroquine, thiazides,
gold, allopurinol
Psoriasiform
Penicillin, co-trimoxazole,
carbamazepine, NSAIDs
Pemphigus
Penicillamine, ACE
inhibitors
Erythroderma
Gold, sulphonylureas,
allopurinol
18
rash
Hives - Slightly red and raised swellings
on the skin, irregular in shape, itchy
Photoallergy - Sensitivity to sunlight, an
itchy and scaly rash when you go out in
the sun
Erythema multiforme - Red, raised and
itchy, sometimes look like bull's-eye
targets, sometimes with swelling of the
face or tongue
19
Syndrome (SJS)
and Toxic Epidermal Necrolysis
(TEN)
-A manifestation of acute graft
versus host disease
-Medications with longer half-lives
are more likely than those with
shorter half-lives to pose a risk for
SJS and TEN
20
21
22
23
erosions
Asymmetric skin
involvement with
blisters
Widespread of
skin distribution
<10% total body
surface area
affected
Mucosal
erosions
Flaccid blisters
and denuded skin
Widespread
of
skin distribution
> 30% total body
surface area
affected
24
25
Admit
26
28
Urticaria
What
is urticaria?
It is local wheals and erythema in
the superficial dermis
Urticaria induced by drug is
generally acute and is limited to the
skin and subcutaneous tissues.
29
Urticaria
30
Urticaria
Signs and symptoms
Pruritus (generally the first symptom)
Crops of hives
Lesion (if lesion persists more than 24
hours, the possibility of vasculitis should
be considered)
Diagnostic tests are seldom required
31
Urticaria
Treatment
antihistamine:
diphenhydramine 50-100mg q4h,
hydroxyzine 25-100mg bid or
cyproheptadine 4-8mg q4h
Glucocorticoid for more severe
reactions, especially when
associated with angioedema
(prednisone 30-40 mg/ day po)
33
34
Certain
35
Angioedema
36
40mg/day po)
Adrenaline 1:1000, 0.3ml subcutaneously
should be the 1st line treatment for acute
pharyngeal or laryngeal angioedema
IV antihistamine (e.g. diphenhydramine
50-100mg) to prevent airway obstruction
Intubations or tracheotomy and oxygen
administration may be necessary
37
Penicillin Allergy
Skin
Resolution
of penicillin allergy
- 50% lose penicillin allergy in 5 yr
- 80-90% lose penicillin allergy in 10
yr
Penicillin Allergy
beta
lactam antibiotic
Type 1 reactions : 2% of penicillin courses
Penicillin metabolites:
- 95% : benzylpenicilloyl moiety (the
major
determinant)
- 5% : benzyl penicillin G, penilloates,
penicilloates (the minor
determinants)
Ampicillin rash
non-immunologic
rash
maculopapular, non-pruritic rash
onsets 3 to 8 days into the antibiotic
course
incidence: 5% to 9% of ampicillin or
amoxicillin courses; 69% to 100% in those
with infectious mononucleosis or acute
lymphocytic leukemia
must be distinguished from hives
secondary to ampicillin or amoxicillin
Cephalosporin allergy
beta-lactam
Sulphonamide hypersensitivity
sulpha
reactions urticaria/angioedema
- asthma
- anaphylactoid reaction
prevalence: 0.2% general population
8-19% asthmatics
30-40%
polyps & sinusitis
ASA quatrad: Asthma, Sinusitis, ASA
sensitivity, nasal Polyps (ASAP
syndrome)
history).
Perform allergy skin tests (if
available).
Avoidance of identified drug or
suspected drug(s) is essential.
Avoid potential cross-reacting drugs
(e.g. avoid cephalosporins in
penicillin-allergic individuals).
Medic-Alert bracelet is
recommended.
Use alternative medications, if at
all possible.
Desensitize to implicated drug, if
this drug is deemed essential.
Desensitization to medications
Basic
approach: administer
gradually increasing doses of the
drug over a period of hours to days,
typically beginning with one tenthousandth of a conventional dose
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