Drug Eruptions

Dr. Andaç Salman

 Benign Cutaneous
Adverse Reactions
to Drugs

Drug-induced Drug-induced
exanthem urticaria- Fixed drug eruption
(morbiliform drug angioedema-
eruption) anaphylaxis
Drug-induced exanthem (morbiliform drug
eruption)
■ Most frequent cutaneous drug reaction
■ Almost any drug
– Ampicillin and penicillin
– Carbamazepine
– Sulphonamides
– Phenytoin
– NSAIDs
– Allopurinol
Drug-induced exanthem (morbiliform drug
eruption)
■ Latency from drug administation to onset of rash: 5-
21 days, typically 7-10 days
■ Trunk and extremity involvement
■ Typical sparing of face
■ Pruritus may be present
Drug-induced exanthem (morbiliform drug
eruption)
■ Differential Dx
– Viral exanthem
Drug-induced exanthem (morbiliform drug
eruption)
■ Spontaneous resolution following the withdrawal of the offending drug

■ Cessation of the culprit drug

■ Resolves with desquamation, sometimes with postinflammatory
pigmentation
■ Symptomatic treatment
■ Emollients
■ Intermediate potency Topical CS for pruritus
Drug-induced urticaria-angioedema-
anaphylaxis
■ Urticaria and angioedema; circumscribed skin edema and erythema
■ Anaphylaxis: bronchoconstriction and hypotension
■ Urticaria is the second most common form of adverse cutaneous drug
eruption

■ Aspirin and NSAIDs mosf frequent causes of urticaria

■ Antibiotics (usually beta-lactams) and NSAIDs most frequent causes of
anaphylaxis
Drug-induced urticaria-angioedema-
anaphylaxis
■ 24-36 hours of latency on the first occasion
■ Within minutes on re-challenges
■ Serum drug specific-IgE, Skin prick testing, intradermal testing,
challenge testing
■ Withdrawal of the offending drug
– After an initial improvement in anaphylaxis, late-phase reactions may
arise in 5-6h
■ Oral/IV antihistamines
■ Oral/IV CS
■ SC adrenaline
ANGIOEDEMA-ACEinh
Fixed Drug Eruption (FDE)

■ Recurrent, well-defined lesions in the same site occuring every time the
drug is taken
■ Short latency, 30min to 8h
■ Top 3 causes; Co-trimoxazole, Tetracyclines, NSAIDs
■ Sharply-defined, round or oval erythematous and oedematous plaque
■ Most commonly involves the lips, genitals, palms and soles
Generalized Bullous FDE

■ Must be differentiated from Toxic Epidermal Necrolysis

– Prior history of similar episodes
– mucosal surfaces are relatively uninvolved;
– the presence of large blisters with intact intervening skin
– the absence of multiple purpuric or target lesions.
Fixed Drug Eruption
■ Post-inflammatory pigmentation may be prominent
■ GBFDE, 20% mortality, same level of treatment as SJS/TEN

■ Oral provocation
■ Patch testing on lesional skin

■ Stopping the offending drug

■ Topical or systemic corticosteroids
■ GBFDE: ICU/Burn unit
 Severe Cutaneous
Adverse Reactions
to Drugs

Drug reaction with Stevens-Johnson

Acute generalized eosinophilia and syndrome/toxic
exanthematous systemic symptoms epidermal necrolysis
pustulosis (AGEP)
(DRESS) (SJS/TEN)
Acute generalized exanthematous
pustulosis (AGEP)
■ 90% of the cases are drug related
■ Infectious etiologies, M.pneumoniae, Coxsackie, CMV

■ Pristinamycin
■ Aminopenicillins
■ Quinolones
■ .
■ .
■ .
Acute generalized exanthematous
pustulosis (AGEP)
■ Short latency: 2-5 days
■ Prodrome of burning or itching in the skin
■ Prescribed drug, OTC products

■ Sheets of hundreds of non-follicular pustules, most commonly in the

major flexures
■ Background of oedematous erythema
■ Febrile, leukocytosis (neutrophilia)
■ Internal organ involvement 18% (hepatic-renal-pulmonary)
Acute generalized exanthematous
pustulosis (AGEP)
■ Differantial diagnosis
■ Pustular Psoriasis
– Predominance in the folds
– Shorter duration of pustules and fever
– Recent history of drug intake
■ DRESS
– Less pustules
– Invariably have systemic involvement
Acute generalized exanthematous
pustulosis (AGEP)
■ CBC-neutrophilia, eosinophilia
■ Biochemistry, renal and liver dysfunction, hypocalcemia

■ Potent topical CS, Oral CS

■ Emollients
■ If the patient is febrile, exclusion of an infective source
Drug reaction with eosinophilia and
systemic symptoms (DRESS)
■ Atypical lymphocytes, solid organ involvement, lymphadenopathy
■ Prolonged latency-2 to 6 weeks
■ Prodromal phase of asthenia, malaise, fatigue

■ Allopurinol
■ Antiepileptics
■ Antibiotics
■ Sulpha drugs (dapsone, sulphasalazine)
■ ….
Drug reaction with eosinophilia and
systemic symptoms (DRESS)
■ Rash ve typical facial swelling
■ Head and neck oedema
■ Lymphadenopathy in at least two sites
■ Hematological-eosinophilia, lymphocytosis, atypical lymphocytes
on blood film

■ Hepatocellular/obstructive pattern of hepatitis, primary cause of mortality

■ Renal, hematuria, proteinuria
■ Cardiac, pericarditis, myocarditis, chest pain, dyspnea
■ Pulmonary, pleural effusion, plueritis
■ Chronic phase; autoimmune phenomena SLE, AA, Thyroid dysfunction, Type I DM
Drug reaction with eosinophilia and
systemic symptoms (DRESS)
■ Withdrawal of the culprit drug
■ Topical/Oral/IV CS
■ Slow tapering-off period 1-3 months

■ Cyclosporine, IVIg
■ Plasmapharesis
 Stevens-Johnson syndrome/toxic epidermal
necrolysis (SJS/TEN)
■ A spectrum of diseases showing
blistering and epidermal sloughing
■ TEN>SJS/TEN>SJS (depending on the
BSA involvement (>30%, 30-10%,
<10%)

■ Allopurinol
■ Carbamazepine
■ Lamotrigine
■ ….
Stevens-Johnson syndrome/toxic epidermal
necrolysis (SJS/TEN)
■ Latency: typically 7-10 days, ranges from 5 to 28 days
■ Prodrome, malaise, fever, upper respiratory tract symptoms
■ Starts from the face and chest and disseminates widely
■ Pruritus and cutaneous pain
■ Mucosal involvement, before-after-simultaneously
■ Respiratory tract involvement: cough, dyspnea, haemoptysis
■ GI tract involvement, diarrhea
Stevens-Johnson syndrome/toxic epidermal
necrolysis (SJS/TEN)
■ Initial skin lesions are atypical targets or purpuric macules on the
face, upper torso and proximal extremities
■ Spread to involve the rest of the trunk and extremities
■ Lesions increase in size and tend to coalesce
■ Blisters and vesicles, positive Nikolsky sign
■ Erosive and hemorrhagic mucositis (eye, mouth, nose, genitalia)
■ In severe cases involvement of oropharynx, larynx, oesophagus,
respiratory tract
Stevens-Johnson syndrome/toxic epidermal
necrolysis (SJS/TEN)
■ Complications
■ Acute:Hypothermia, Acute Kidney Injury, Anemia, Hypoalbuminemia,
Bronchial erosions and obstruction, Septicemia
■ Long-term: Ocular, eruptive melanocytic nevi, onychomadesis,
bronchiolitis obliterans (poor prognosis, 3*4 months after the acute
episode)
■ Mortality
– SJS <10%
– SJS/TEN 22%
– TEN %30
Stevens-Johnson syndrome/toxic epidermal
necrolysis (SJS/TEN)
■ Skin biopsy to exclude other blistering dermatoses
■ ICU/Burns unit
■ Local skin/mucosa treatment
■ Heated environment
■ Fluid replacement and nutrition
■ Analgesia
■ Monitoring for infection
■ Active therapy IVIg, Cyclosporine, CS