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Stevens-Johnson syndrome Dr A Galetto 1 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. 2 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 3 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 ? 4 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 5 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 6 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 7 Generalized eruption of lesions that initially had a target-like appearance but then became confluent, brightly erythematous, and bullous. 8 Multiple bulles overlying diffuse erythema are present. 9 Diffuse erythema and large areas of denuded epidermis are present. 10 Multiple bullae and areas of denuded epidermis 11 widespread erythema and confluent vesiculation, leading to detachment of the skin. 12 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 13 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 14 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 15 Multiple erosions and crusts are present on the lips of this patient with Stevens-Johnson syndrome. 16 17 Stevens-johnson and toxic epidermal necrolysis Clinical features • Ocular • Pain and photophobia • Severe conjonctivitis with purulent discharge and bullae • Corneal ulceration is frequent 18 Marked conjunctival injection and discharge 19 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. 20 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. 21 22 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 23 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 24 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 25 Stevens-johnson and toxic epidermal necrolysis Complications: Long term sequelae • Dermatologic: scarring • Ophtalmologic: corneal scarring • Oral and genital: synechiae and stenosis 26 Stevens-johnson and toxic epidermal necrolysis Prognosis: • Mortality rate is near 25 % • Disease severity is the main risk factor of death 27 Stevens-johnson and toxic epidermal necrolysis Laboratory abnormalities: 28 Stevens-johnson and toxic epidermal necrolysis Case definition: 29 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. 32 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 33 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 • 34 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 35 Stevens-johnson and toxic epidermal necrolysis management: • Systemic corticosteroids and intravenous gammaglobulin are used at some centers but are not recommanded 36 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. 37 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 38 Resolution of the case: This boy has recovered without any complication 39 Diagnosis: 40 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 41 Thank you Dr. A Galetto 42