Stevens-Johnson syndrome

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Dr A Galetto

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CASECASE

• 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 withcarbamazepine

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Stevens-johnson and toxic epidermal necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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-johnsonDrugs associated with Stevens-johnson

Strongly associated* Associated•

Allopurinol

Carbamazepine

Lamotrigine

Meloxicam

Nevirapine

Phenobarbital, primidone

Phenytoin, fosphenytoin

Piroxicam, tenoxicam

Sulfadiazine, sulfadoxine,

sulfamethoxazole,

sulfasalazine

Amifostine

Amoxicillin, ampicillin

Azithromycin, clarithromycine,

erythromycin

Cefadroxil, cefixim,

ceftriaxone, cefuroxim

Ciprofloxacin, levofloxacin,

pefloxacin

Diclofenac

Doxycyclin

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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-johnson and toxic epidermal necrolysis

Laboratory abnormalities:

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Stevens-johnson and toxic epidermal necrolysisStevens-johnson and toxic epidermal necrolysis

Case definition:

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Differential diagnosis: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

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Differential diagnosis: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

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Differential diagnosisDifferential 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 diagnosisDifferential 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.

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Stevens-johnson and toxic epidermal necrolysisStevens-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 necrolysisStevens-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 necrolysisStevens-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: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: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: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 necrolysisStevens-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 JCUptodate 2013

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Thank you

Dr. A Galetto