Transcript Drug Eruptions

In the name of God
Dr. F. Shariati
In medicine
Most drug-induced cutaneous reactions are mild and
disappear when the offending drug is withdrawn.
 Drugs can also cause hair and nail changes, affect the
mucous membranes, or cause itching without
outward skin changes
Drug Eruptions
 Drug eruptions are diagnosed mainly from the:
 medical history
 clinical examination
 However, they can mimic a wide range of other conditions
Drug Eruptions
A drug-induced reaction should be considered in
any patient who is taking medications and who
suddenly develops a symmetric cutaneous eruption
Drug Eruptions
 to ccurs in approximately 2-5% of inpatients and in
greater than 1%-3% of outpatients
The serious drug eruptions occur in around 1 in
1000 patients
Drug Eruptions
 Drug Reaction mortality : 1.8% percent
 Mortality rates for Stevens-Johnson syndrome (SJS) has a
less than 5%,
whereas the rate for TEN approaches 20- 30%; most
patients die from sepsis
Classification
 By appearance
The most common type of eruption is a morbilliform
resembling measles or erythematous rash, (but the
appearance may also be…….. )
 By mechanism
The underlying mechanism can be immunological in drug or
non-immunological
 By drug
The culprit can be both a prescription drug or an overcounter medication.(antibiotic, analgesic,herbal supplement)
Drug Eruptions
Physiopathology of Cutaneous Drug Reaction
 Allergic Reaction (Immunologic)
less than 6-10%
 Non allergic Reaction (Non Immunologic)
More than . 90%
Non - allergic Drug Reaction
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Over Dose
Side Effects
Cumulative Toxicity
Delayed Toxicity
Facultative Effects
Drug Interaction
Metabolic Changes
Teratogenicity of Fetus
Activation of Effector Pathways
Exacerbation of Diseases
Chromosomal Damage by Drug
Intolerance and Idiosyncrasy
Jarisch — herxheimer reaction
Infectious mono - , ampicillin reaction
Drug Eruptions: clinical appearance
 Drug-induced exanthems
 Urticaria
 Angioedema/anaphylaxis
 DRESS Sydrome
 Hypersensitivity vasculitis
 Exfoliative dermatitis/Erythroderma
 SJS/TEN
 Fixed drug eruption
 Photosensitivity
Drug-induced Exanthems
 Account for close to 75% of all drug eruptions.
 Morbilliform, maculopapular eruptions.
 Most commonly implicated medications are the most commonly
prescribed medications (antibiotics, sulfa).
 Usually begin in generalize areas .
 Often associated with pruritis, low-grade fever, eosinophilia.
 Onset within 2 weeks of starting a new drug, or within days of reexposure.
 Delayed (type IV) hypersensitivity is most likely etiology.
 More common in patients with altered immunity, such as those with
HIV or mononucleosis (“ampicillin rash”).
 Treatment is dicontinuation of the drug. Antihistamines, topical
steroids, and topical antipruritics may also help.
Drug-induced
Exanthems
Urticaria:
Time to onset: immediate, accelerated (hours), or delayed
(days).
immunological(Type I hypersensitivity reactions)
:antibiotics (especially PCN, cephalosporins, and
sulfonamides), local anesthetics, radiocontrast media,
blood products, and gamma globulin.
Non-immune urticaria: Mast cell degranulation by nonIgE mechanisms: opiate analgesics, anesthetic, muscle
relaxants, and Vancomycin (Red Man Syndrome).
Angioedema/Anaphylaxis
 Caused by degranulation of mast cells in the deeper
dermis and subcutaneous tissues.
 May occur along with urticaria (50% of cases)
 Can be life-threatening if it causes laryngeal edema or
tongue swelling.
 Can be non-mast cell mediated, as in the case of ACE-
inhibitors.
Angioedema/An
aphylaxis
DRESs Syndrome
Drug Rash with Eosinophilia and Systemic Symptoms
 Formerly called Hypersensitivity Syndrome (HSS)
 Typically presents with rash and fever (87%), classically
erythematous follicular papules and pustules, but may also include
bullae or purpura.
 Other severe systemic manifestations such as arthralgias,
lymphadenopathy (75%), hepatitis (51%), or hematologic
abnormalities (30%). interstitial nephritis (11%),
 Hematologic abnormalities include eosinophilia, thrombocytopenia,
neutropenia, and atypical lymphocytosis.
 Other symptoms: pruritis, nephritis, oliguria, hepato-renal syndrome,
and asthenia.
 DDx includes SJS/TEN, hypereosinophilic syndrome, and Still’s
disease.
 Skin biopsy is non-specific.
DRESS Syndrome
 Common causes: aromatic anticonvulsants (oxcarbazepine,
carbamazepine, phenytoin, phenobarbital, etc.) and sulfonamides.
 Other drugs implicated:
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lamotrigine
allopurinol
NSAIDs
Captopril
fluoxetine
dapsone
metronidazole
minocycline
antiretrovirals.
Hypersensitivity vasculitis(DHS)
 American College of Rheumatology proposed the following five
criteria. The presence of three or more had a sensitivity of 71% and a
specificity of 84% for the diagnosis
 Age > 16
 Use of possible offending drug in temporal relation to symptoms
 Palpable purpura
 Maculopapular rash
 Biopsy of a skin lesion showing neutrophils around an arteriole or
venule.
 Most likely due to drugs that can act as haptens to stimulate the
immune response: PCN, cephalosporins, sulfonamides, phenytoin, and
allopurinol.
 Additional findings: fever, urticaria, arthralgias, low complement
(CH50) levels, and elevated ESR.
Hypersensitivity
vasculitis
Exfoliative dermatitis/
Erythroderma
 Erythroderma is defined as a cutaneous reactional state with
chronic erythema and scale involving greater than 50% of the
body surface area.
 Usually begins as an eczematous or morbilliform eruption and
progresses.
 Drugs including, gold, arsenic, mercury, PCN, and barbituates, are
implicated in about 10% of cases.
Erythroderma: Marked inflammation and scaling which can
result from a variety of medical conditions.
DICR
SJS/TEN
EMMi
EMMa
TEN
SJS
 Stevens-Johnson Syndrome and toxic epidermal necrolysis are likely
two manifestations on the same spectrum. The disease is best
termed SJS when epidermal detachment involves less than 10% of
the body surface area, whereas TEN involves greater than 30%.
SJS
is distinct from erythema multiforme major, which is
usually caused by infections and runs a benign course. SJS is
usually drug induced and can be fatal.
 SJS and TEN usually occur 1-3 weeks after exposure, but can occur
more rapidly with re-exposure, which suggests an immunologic
mechanism.
 Mucosal involvement is seen in 90% of cases, including painful
crusts and erosions on the oral mucosa, conjuntivae, and genital
mucosa.
Toxic epidermal necrolysis
Fixed Drug Eruptions
 Drug eruption that occurs at the same location every
time a particular medication is used.
 Begins as an erythematous, edematous plaque with a
grayish center or frank bullae, then progresses to
dark, post-inflammatory pigmentation.
 Sites include the mouth, genetalia, face, and acral
areas.
 Causes include phenolphthalein, tetracyclines,
barbituates, sulfonamides, NSAIDs, and salicylates.
fixed_drug_eruption_
Fixed drug eruption
PHTOSENSITIVE DRUG
ERUPTION
Photosensitive drug
eruption:
 thiazides
 phenothiazines
 sulfa drugs
 tetracyclines
 Others
Characteristic Drug Changes
Pigmentation of teeth
due to tetracyclines
LICHENOID DRUG REACTION
 TypeII/III reaction
 lasix, captopril,
chloroquin, gold, beta
blockers, aldomet,
penicillamine, thiazides,
sulfa, many others
 *features diff. From LP:
parakeratosis,hypogranul
osis,EOS spongiosis,
plasmacells,many EOS
LUPUS-LIKE SYNDROM
Skin lesions:
 malar or butterfly rash
 Offending drugs:
procaineamid,hydralazin,
INH,methyldopa,
chlorpromazin,penicillamine,
 PUVA,others
Silver :
lunula discoloration
D-penicillamine: Yellow nail
Cytotoxics: Beau’s lines
Minocycline: blue nails
Investigations
• If history and physical examination are not
sufficient for diagnosis,
Biopsy e.g. by showing eosinophils in
morbilliform eruptions or numerous neutrophils
without vasculitis
CBC count with differential may show
leukopenia, thrombocytopenia, and eosinophilia
in patients with serious drug eruptions
Confluent necrosis of the epidermis in toxic
epidermal necrolysis
Perivascular mixed inflammatory infiltrate with
eosinophils characteristic of drug induced
urticaria
Treatment
• Once the offending drug has been identified, it
should be promptly stopped.
• since traces of the drug may persist for long
periods, and some reactions, continue for many
days without reexposure to the drug
• Patients with morbilliform eruptions can
continue medication even in presence of rash as
the eruption often resolves, especially if the
individual is being treated for a serious disease
stage
• Treatment of a drug eruption depends on the
specific type of reaction
Therapy for exanthematous drug eruptions is
supportive in nature.
First-generation antihistamines are used
mild topical steroids (e.g. hydrocortisone(
moisturizing lotions, especially during the late
desquamative phase
• Topical steroids may provide some relief
• If signs and symptoms are severe, a 2-week
course of systemic corticosteroids
(prednisone, starting at 40- 60 mg) will
usually stop the symptoms and prevent
further progression of the eruption within 48
hours of the onset of therapy
Good Luck