Stevens-Johnson syndrome

Dr A Galetto

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 CASE

• A 7 years old boy has fever and pain on swallowing

since five days. Two days ago an eruption began on
his thorax with very painful macules and yesterday
some blister developed on his face and began to be
confluent with area of epidermal detachment.

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His eyes are now red and recovered with purulent
discharge and his lips become swollen with erosions. He
can not drink anymore because of pain on oral lesions.

He is treated for epilepsy since 3 years and his treatment

changed 2 weeks ago for a treatment with
carbamazepine
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 Stevens-johnson and toxic epidermal necrolysis

Question:

You are his doctor and you are wondering:

• How to manage this case ?

• What is the probable cause of his illness ?

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 Stevens-johnson and toxic epidermal necrolysis

Definition

• Stevens-Johnson and toxic epidermal necrolysis

are
• severe mucocutaneous reaction
• triggered by medications
• characterized by extensive necrosis and
detachment of the epidermis
• Are variants of a same disease but are
distinguished only by the severity and the
percentage of the body surface involved by
blisters and erosions
• Are rare disorders: 1 per 1’000’000
• Lyell’s syndrome is equivalent to toxic epidermal
necrolysis
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 Stevens-johnson and toxic epidermal necrolysis

Clinical features

• Acute phase (unspecific):

• Begin in the 3 weeks following introduction

of a medication or immunization
• Fever
• Photophobia and conjonctival itching
• Pain on swallowing
• Malaise and myalgia
• During one to three days before cutaneous
lesions

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 Stevens-johnson and toxic epidermal necrolysis

Clinical features

• Cutaneous lesions:

• Confluent erythematous macules with purpuric

centers
• Skin pain out of proportion to the cutaneous
findings
• Atypical target lesions with darker centers may
be present

• As the disease progresses:

• Vesicules and bullae form
• Areas of epidermal detachment develop
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Generalized eruption of lesions that initially had a target-like
appearance but then became confluent, brightly erythematous,
and bullous.

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Multiple bulles overlying diffuse erythema are
present.

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Diffuse erythema and large areas of denuded
epidermis are present.

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Multiple bullae and areas of denuded epidermis

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widespread erythema and confluent vesiculation, leading
to detachment of the skin.

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Stevens-johnson and toxic epidermal necrolysis
• Nikolsky sign:

• Is the ability to extend the area of superficial

skin detachment by applying gentle lateral
pressure on the surface of the skin at an
apparently uninvolved site.
• The ultimate appearance of the skin is like an
extensive thermal injury

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 Stevens-johnson and toxic epidermal necrolysis

Clinical features

• Mucosal lesions:

• Painful crust and erosions may occur on any

mucosal surface
• Occurs in 90 % of cases

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 Stevens-johnson and toxic epidermal necrolysis

Clinical features
• Oral:
• Oral mucosa and the vermillon border are
almost invariably involved
• Painful hemorragic erosions recovered with
a grayish-white membrane

• Stomatitis and mucositis lead to impared

oral intake malnutrition and dehydratation

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Multiple erosions and crusts are present on the lips of this
patient with Stevens-Johnson syndrome.

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 Stevens-johnson and toxic epidermal necrolysis

Clinical features

• Ocular

• Pain and photophobia

• Severe conjonctivitis with purulent discharge
and bullae
• Corneal ulceration is frequent

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Marked conjunctival injection and discharge

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 Stevens-johnson and toxic epidermal necrolysis

Clinical features

• Urogenital:

• Urethritis and genital erosions

• In women: erosive and ulcerative vaginitis

• Pharyngeal mucosa is affected in nearly all

patients.

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 Stevens-johnson and toxic epidermal necrolysis

Classification

• Extension of skin involvement differenciates between

Stevens-Johnson syndrom, overlap syndrom and toxic
epidermal necrolysis

• Only necrotic skin which is already detached (erosions

or blisters) or detachable skin ( nikolsky positive) should
be included in the surface of skin involvement

• For helping in scoring the skin involvement, remember

that the surface of the patient’s hand corresponds to
one percent of his total body surface area.

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 Stevens-johnson and toxic epidermal necrolysis

Pathogenesis.

• Drug hypersensitivity.

• Genetic factors are linked to drug hypersensitivity

• HIV infection: incidence is1000-fold higher

• Mycoplasma pneumoniae and herpes virus: to

cause Stevens-johnson in children without drug
exposure

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Drugs associated with Stevens-johnson
Strongly associated* Associated•

Allopurinol Amifostine
Carbamazepine Amoxicillin, ampicillin
Lamotrigine Azithromycin, clarithromycine,
Meloxicam erythromycin
Nevirapine Cefadroxil, cefixim,
Phenobarbital, primidone ceftriaxone, cefuroxim
Phenytoin, fosphenytoin Ciprofloxacin, levofloxacin,
Piroxicam, tenoxicam pefloxacin
Sulfadiazine, sulfadoxine, Diclofenac
sulfamethoxazole, Doxycyclin
sulfasalazine Etoricoxib
Metamizole
Oxcarbazepine
Pipemidic acid
Rifampicine

25% of cases cannot be clearly attributed to a drug

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 Stevens-johnson and toxic epidermal necrolysis

Complications:

Acute
• Massive loss of fluids and electrolytes through denude
skin
• Electrolytes imbalance
• Hypovolemic shock with renal failure
• Bacteremia
• Insulin resistance
• Hypercatabolic state
• Hepatic involvment and pancreatitis
• Leukopenia, thrombocytopenia and anemia
• pneumonia
• Multiple organ failure
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 Stevens-johnson and toxic epidermal necrolysis

Complications:

Long term sequelae

• Dermatologic: scarring
• Ophtalmologic: corneal scarring
• Oral and genital: synechiae and stenosis

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 Stevens-johnson and toxic epidermal necrolysis

Prognosis:

• Mortality rate is near 25 %

• Disease severity is the main risk factor of death

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 Stevens-johnson and toxic epidermal necrolysis

Laboratory abnormalities:

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 Stevens-johnson and toxic epidermal necrolysis

Case definition:

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 Differential diagnosis:

• Erythema multiforme:
Target lesions on the extremities
Associated with herpes infections

Target lesions with central bullae are

present on the hand in erythema
multiform 30
 Differential diagnosis:

• auto-immune blistering diseases:

IgA dermatosis
pemphigus
skin biopsy: deposits of immunoglobulins

Linear IgA bullous dermatosis resembling toxic epidermal

necrolysis with extensive bullae and skin detachment 31
 Differential diagnosis

Staphylococcal scalded skin syndrome (SSSS)

• Caused by epidermolytic toxin produced by certain
strains of Staphylococci
• Neonates and young children
• Mucous membranes are not involved
• Skin biopsy: Necrosis of only the upper layers of the
epidermis.

Diffuse erythema and

desquamation are present in
this child with staphylococcal
scalded skin syndrome.

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 Differential diagnosis

• Skin biopsy of Stevens-Johnson syndrome:

full thickness epidermal necrosis

(A) Diffuse confluent erythematous macules and patches with dusky

centers and multiple bullae in a patient recently started on several
new medications.
(B) There is a cell-poor subepidermal blister and full epidermal
necrosis. 33
 Stevens-johnson and toxic epidermal necrolysis

management:

• Immediate withdrawal of any potential causative

agents
• Supportive care
• wound care:
• sterile handling of the wound, use antiseptic
solutions and nonadherent gauze dressings
• Ocular care:
• daily cleaning and lubrication with drops or
ointment

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 Stevens-johnson and toxic epidermal necrolysis

management:

• Fluid and electrolytes management

• Nutritional support
• Pain control
• Treatment of superinfection:
• no prophylactic antibiotics
• Check for signs of superinfection
• Antibiotic choice should be based upon
specifific culture data whenever possible.
• Infections with gram-negative rods
(Pseudomonas) are problematic

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 Stevens-johnson and toxic epidermal necrolysis

management:

• Systemic corticosteroids and intravenous

gammaglobulin are used at some centers but are
not recommanded

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 Resolution of the case:

Questions :

What is the probable cause of his illness ?

This boy is suffering from Stevens-Johnson syndrome

probably triggered by his epilepsy medication.

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 Resolution of the case:

Question : how to manage this case ?

• You must immediately stop his carbamazepine

medication and hospitalize this boy.
• wound care: sterile handling of the wound, use topical
antiseptic solutions and nonadherent gauze dressings
• Ocular care: daily cleaning and lubrication with drops
or ointment
• Give fluids through iv line with compensation of fluid
and electrolytes loss
• Pain control
• No prophylactic systemic antibiotics but look for signs
of superinfection of the skin

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 Resolution of the case:

This boy has recovered without any complication

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Diagnosis:

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 Stevens-johnson and toxic epidermal necrolysis

References:

• Toxic epidermal necrolysis and Stevens-Johnson syndrome

Harr T, French LE.
Orphanet J Rare Dis. 2010 Dec 16;5:39. Review.

• Stevens-Johnson syndrome and toxic epidermal necrolysis:

Pathogenesis, clinical manifestations, and diagnosis
Nirken MH, High WA, Roujeau JC,
Uptodate 2013

• Stevens-Johnson syndrome and toxic epidermal necrolysis:

Management, prognosis, and long-term sequelae
High WA, Nirken MH, Roujeau JC
Uptodate 2013

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Thank you

Dr. A Galetto 42