Download Stevens-Johnson syndrome

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
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 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
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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 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
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necrosis.
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:
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•
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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
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