DRUG ERUPTIONS
• Adverse drug reactions are a common
cause of dermatologic consultation.
• drug eruptions are not simply drug
"allergy," but result from variations in
• drug metabolism
• immune status
• coexistent viral disease
• the patient's racial background
• the patient's HLA status
• the inherent chemical structure
• dosage of the medication itself
Non-allergic drug reactions
• Overdosage
• accumulation of drugs
• unwanted pharmacological effects (stretch marks
from systemic steroids) .
• idiosyncratic (odd reaction peculiar to one individual)
• mouth ulcers cytotoxicity of methotrexate.
• Silver based preparations, (argyria).
• vaginal candidiasis: antibiotics remove resident
bacteria
• Dapsone or rifampicin, lepromatous leprosy, may
cause erythema nodosum leprosum
Allergic drug reactions
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appear after the latent period
Chemically related drugs may cross-react.
majority caused by cell-mediated immune reaction
commonly a maculopapular eruption
Helper CD4+ T cells morbilliform eruptions,
cytotoxic CD8+ T cells predominate in blistering
eruptions ( TEN, Stevens–Johnson syndrome) and
fixed drug eruptions.
• urticaria and angioedema, immunoglobulin E (IgE)
mediated type I hypersensitivity reactions
• vasculitis type III immune complex-mediated
reactions.
Evaluation
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1. Previous general experience with the drug
2. Alternative etiologic candidates
3. Timing of events
4. Drug levels and evidence of overdose
5. Response to discontinuation (dechallenge)
6. Rechallenge
Exanthems
Lesions tend to appear
first proximally, in the
groin
and
axilla,
generalizing within 1 or
2 days.
the face may be spared.
Pruritusis
usually
prominent, helping to
distinguish
a
drug
eruption from a viral
exanthem.
Antibiotics,
penicillins
and trimethoprim
Urticaria/angioedema
Medications may induce
urticaria by immunologic
and
nonimmunologic
mechanisms.
In either case, clinically
there are pruritic wheals
or angioedema .
Urticaria may be part of a
more severe anaphylactic
reaction (bronchospasm,
laryngospasm,
or
hypotension).
Aspirin and the NSAIDs common
causes of nonimmunologic
Immunologic urticaria is most
associated with penicillin
Angioedema
is
a
known
complication of angiotensinconverting enzyme inhibitors .
Lisinopril and enalapril more
commonly than captopril
Angioedema typically occurs
within a week of starting
therapy.
Bullous drug reactions
(Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN])
S]S and TEN are considered by some as parts of a
disease spectrum based on the following:
1.commonly induced by the same medications.
2.Patients initially presenting with S]S may progress
to extensive skin loss resembling TEN.
3.The histologic findings are indistinguishable.
More than 100 medications have been reported to
cause S]S and TEN.
S]S has less than 10% body surface area (BSA)
involved, cases with 10-30% are S]S- TEN overlap
cases, and more than 30% BSA erosion is called TEN .
1. trimethoprim-sulfamethoxazole
2.carbamazepine.
3.Antibiotics (long acting sulfa drugs and penicillins),
• Fever and influenza-like symptoms precede eruption
• Skin lesions appear on face and trunk and rapidly
spread. macular, followed by desquamation, or may
form atypical targets that coalesce, form bullae, then
slough.
• In SJS, two or more mucosal surfaces are also eroded, the
oral mucosa and conjunctiva being most frequently affected.
• photophobia, difficulty with swallowing, rectal erosions,
painful urination, and cough
Fixed drug reactions
•Fixed drug reactions (FDE)
are common.
•Fixed drug eruptions are so
named because they recur at
the same site with each
exposure to the medication.
•The time from ingestion of
the offending agent to the
appearance of symptoms is
between 30 minutes and 8
hours, averaging 2 hours.
In most patients, six or
fewer lesions occur, and
frequently only one.
They
may
present
anywhere on the body, but
half occur on the oral and
genital mucosa.
Clinically, an FDE begins as
a red patch that soon
evolves to an iris or target
lesion similar to erythema
multiforme,
and
may
eventually
blister
and
erode.
Lesions of the genital
and oral mucosa usually
present as erosions.
Most lesions are 1 to
several cm in diameter,
but larger plaques may
occur
Characteristically,
prolonged or permanent
postinflammatory
hyperpigmentation
results,
• Erythema multiforme
• Target-like lesions appear
mainly on the extensor
aspects of the limbs, and
bullae may form.
• Sulphonamides
• barbiturates
• lamotrigine
• phenylbutazone
• Acute generalized
exanthematous
pustulosis
• suggests acute pustular
psoriasis, with a dramatic
generalized eruption of red
plaques studded with tiny
non-follicular pustules.
• Patients have fever and
leucocytosis.
• Antibiotics and diltiazem are
the most common drugs to
induce AGEP, which usually
develops after only a few
days.
Drug rash with eosinophilia and
systemic signs syndrome
• triad of fever, rash (from morbilliform to exfoliative
dermatitis) and internal organ involvement
(hepatitis, pneumonitis,nephritis and haematological
abnormalities).
• An eosinophilia and lymphadenopathy
• develops 3–8 weeks after starting the causative drug.
• anticonvulsants
• minocycline
• allopurinol
• sulphonamides
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Hair loss
Predictable
acitretin and cytotoxic agents,
an unpredictable
anticoagulants, antithyroid drugs.
Diffuse hair loss
use of an oral contraceptive.
Hypertrichosis
dose-dependent effect of diazoxide, minoxidil and ciclosporin.
Pigmentation
Melasma may follow an oral contraceptive
phenothiazines
blue–grey colour to exposed areas
heavy metals can cause a generalized browning
clofazimine makes the skin red
mepacrine turns the skin yellow
minocycline turns areas of leg skin a curious greenish grey
colour
Photosensitivity reactions (photosensitive drug reactions)
• most photosensitizing drugs have absorption spectra in
the UVA, UVA penetrates into the dermis where the
photosensitizing drug is present.
• Phototoxic reactions are related to dose of both the
medication and the UV irradiation. appear from hours to
days after exposure.
•Photoallergic reactions are typically eczematous and
pruritic, and may first appear weeks to months after drug
exposure.
.Treatment
may
include
dose
reduction
and
photoprotection, with a sunblock with strong coverage
through the whole UVA spectrum.
Treatment
• withdraw the suspected drug
• In urticaria, antihistamines are helpful.
• topical or systemic corticosteroids can be used, and
applications of calamine lotion may be soothing.
• Plasmapheresis and dialysis
• Anaphylactic reactions require special treatment
• One or more injections of adrenaline (epinephrine)
0.3–0.5 ml should be given subcutaneously
• slow intravenous injection of chlorphenamine
maleate (10–20 mg diluted in syringe with 5–10 mL
blood).
• intravenous hydrocortisone (100 mg), it should be
given in severely affected patients.