Download Stevens-Johnson Syndrome Allen Repp, M.D. December 4, 2002

STEVENS-JOHNSON SYNDROME
Allen Repp, M.D.
December 4, 2002
Introduction
 In 1922, Stevens and Johnson first described a syndrome of fever, stomatitis, ocular involvement,
and a diffuse macular rash in children
 SJS now refers to a vesiculobullous disease of mucosal surfaces and skin in children and adults
 Due to overlap of clinical features including lesions of skin and mucous membranes and
associations with drug exposure or infections, Stevens-Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN) have traditionally been considered severe manifestations of erythema
multiforme (EM) – and the term erythema multiforme major has been used as a synonym to SJS
by some
 However, more recent literature has suggested that SJS and TEN are distinct from EM based on
some clinical and histopathologic characteristics
 The spectrum of erythema multiforme is characterized by typical target lesions in a postinfectious period with relatively low morbidity (although the condition may be recurrent)
 The spectrum of SJS/TEN is characterized by more diffuse blisters and purpuric macules, is
more commonly associated with exposure to drugs, and has a high morbidity
 In this concept, SJS and TEN represent gradations of severity of the same type of response
Classification
 Stevens-Johnson Syndrome
 Mucosal erosions and epidermal detachment <10% body surface area
 Overlap SJS/TEN
 Epidermal detachment 10-30% body surface area
 Toxic Epidermal Necrolysis
 Epidermal detachment > 30% body surface area
 Toxic Epidermal Necrolysis without Spots
 Epidermal detachment > 10% body surface area with large epidermal sheets but without
macules or target lesions
Clinical Presentation of SJS/TEN
 Children and young adults most commonly affected
 In SJS attributed to drugs, offending agent usually initiated approximately 1-3 weeks prior to
onset of mucocutaneous eruption
 Prodromal illness with symptoms of fever and upper respiratory infection often precedes
mucocutaneous eruption by 1-14 days
 Mucosal lesions:
 Involvement of at least 2 mucosal membranes is a major clinical feature of SJS and TEN
 Patients often present with dysphagia, odynophagia, photophobia, and/or dysuria
 Bullous lesions on conjunctivae, mucous membranes of mouth, nares, anorectal junction,
vulvovaginal region, urethral meatus, and esophagus
 Ulcerative stomatitis with hemorrhagic crusting is classic feature
 Cutaneous lesions:
 Description: Initially, flat atypical targets or purpuric maculae that may be described as painful
or burning. Lesions coalesce to form blisters that may then progress to epidermal
detachment.
 Location: Symmetric, on upper trunk, or widespread. Reportedly, the lesions never involve
the hairy portion of the scalp.
 Other findings: Confluent erythema, facial edema, central face involvement, tongue swelling,
palpable purpura, skin necrosis, epidermal detachment with lateral pressure (Nikolsky’s sign),
mucous membrane erosions may all be seen, and all portend more serious condition
 Ophthalmologic manifestations:
 Conjunctival lesions occur in 85% of patients
 Ophthalmologic involvement may range from mild conjunctival hyperemia to
pseudomembrane formation to keratitis to corneal ulcerations. Synechiae may develop
between conjunctiva and eyelids.
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Long-term complications can include photophobia, corneal scarring, disruption of tear film,
visual impairment, trichiasis (in-turned eyelashes), and ocular cicatricial pemphigoid (chronic,
scarring inflammation of ocular mucosa).
Pulmonary manifestations:
 Patients may present with dyspnea, harsh cough, bronchial hypersecretion, hypoxemia,
and/or patchy interstitial infiltrates on radiography, representing involvement of bronchial
epithelium.
Laboratory findings:
 Anemia and lymphopenia are common, with neutropenia present in up to 1/3 of patients
 Elevated transaminases (2-3x normal) found in up to ½ of patients
Complications: infection, hypovolemia and hypotension, electrolyte abnormalities, malnutrition
Etiologies
 Drugs
 Most cases of SJS are attributed to drugs, with a strong association to a specific medication
identified in approximately 80% of cases.
 Patients undergoing treatment for seizure disorders are most frequently affected
 Most commonly implicated drugs: sulfonamides (RR 172), carbamazepine (RR 90), oxicam
NSAIDs (RR 72), corticosteroids (RR 54), phenytoin (RR 53), allopurinol (RR 52),
phenobarbitol (RR 45), valproic acid (RR 25), cephalosporins (RR 14), quinolones (RR 10),
aminopenicillins (RR 7)
 Infections
 Mycoplasma pneumoniae infection, herpes simplex virus infection, and upper respiratory tract
infections have all been implicated in SJS (although more clearly associated with erythema
multiforme)
 Predisposing Illness
 HLA B12, HIV, and SLE have been associated with higher incidences of SJS
Pathophysiology
 Pathophysiologic mechanisms not well elaborated. Current popular theory proffers that reactive
drug metabolites may bind to carrier proteins on the membranes of epidermal cells and act as
haptens, inducing primarily lymphocytic reaction, inflammatory cytokine release, cell death, and
tissue necrosis.
Diagnosis
 Primarily clinical diagnosis
 Biopsy of denuded epidermis may be helpful if classic lesions not present  demonstrates
perivascular mononuclear infiltrate in papillary dermis, subepidermal blister formation, and full
thickness epidermal necrosis
 Differential diagnosis includes dermal-epidermal vesiculobullous diseases (erythema multiforme,
bullous pemphigoid, dermatitis herpetiformis, porphyrea cutanea tarda, and paraneoplastic
pemphigus), exfoliative erythroderma, staph scalded skin syndrome, acute exanthematous
pustulosis
Treatment
 Early recognition and withdrawal of potential causative agents
 Supportive care (similar to burn patients): aggressive fluid repletion, strict hygiene precautions,
surgical debridement and/or whirlpool therapy to remove necrotic epidermis, artificial tears,
regular ophthalmologic exams
 Treatment of secondary infections
 Directed therapy: Corticosteroids controversial (mixed data). IVIG somewhat effective in small
retrospective trial. Cyclophosphamide, cyclosporine, plasmapheresis, and GCSF have all been
tried, but lack supporting data. Some authors advocate empiric use of acyclovir regardless of
demonstration of HSV.
 Prophylactic therapy: for cases of recurrent erythema multiforme associated with HSV, there is
some evidence supporting chronic oral acyclovir use.
Prognosis
 SJS associated with < 5% mortality, whereas TEN associated with up to 44% mortality.
 Sepsis is major cause of death.
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