What is Stevens-Johnson syndrome?

Stevens-Johnson Syndrome: Definition and Overview

Stevens-Johnson syndrome (SJS) is a severe, life-threatening mucocutaneous reaction characterized by widespread epidermal detachment affecting less than 10% of body surface area, accompanied by painful blistering, multisite mucositis, and systemic symptoms, most commonly triggered by medications or infections. 1

Disease Spectrum and Classification

SJS exists on a severity spectrum with toxic epidermal necrolysis (TEN), differentiated by the extent of epidermal detachment 1:

• SJS: Epidermal detachment <10% body surface area (BSA) plus widespread purple/red macules or flat atypical targets 1
• SJS/TEN overlap: Detachment of 10-30% BSA plus widespread purpuric macules or flat atypical targets 1
• TEN: Detachment >30% BSA 1

Pathophysiology

The disease is driven by drug-induced cytotoxic T lymphocytes (CTLs) that trigger widespread keratinocyte apoptosis and necrosis 1:

• CD8+ CTLs undergo clonal expansion through MHC class I-restricted drug presentation and infiltrate the skin 1
• Granulysin is the key mediator of keratinocyte apoptosis, found in high concentrations in TEN blister fluid 1
• Other proapoptotic molecules include TNF-α, IFN-γ, Fas ligand, perforin, and granzyme B 1, 2

Clinical Presentation

Prodromal Phase

A prodrome of fever, malaise, and upper respiratory tract symptoms typically precedes the eruption by several days 1, 3:

• Ocular inflammation may develop before skin signs 1
• Cutaneous pain is a prominent early feature that should alert physicians to incipient epidermal necrolysis 1

Cutaneous Features

The skin manifestations evolve in a characteristic pattern 1:

• Earliest lesions: Atypical targets and/or purpuric macules 1
• Initial distribution: Upper torso, proximal limbs, and face, then spreading to trunk, distal limbs, palms, and soles 1
• Nikolsky sign: Gentle lateral pressure causes detachable epidermis to slide over dermis (positive in areas of epidermal necrolysis) 1
• Lesions reach maximum extent 5-7 days after disease onset 1
• Flaccid bullae form as necrotic epidermis separates from dermis, leaving exposed, weeping dermis 1

Mucosal Involvement

Multisite mucositis affecting the eyes, mouth, nose, and genitalia is typically an early and prominent feature, producing erosive and hemorrhagic lesions 1, 4:

• This distinguishes SJS/TEN from staphylococcal scalded skin syndrome (SSSS), which characteristically lacks mucosal involvement 4

Etiology

In Adults

Medications are the predominant cause 1:

• High-risk drugs: Anti-infective sulfonamides, anticonvulsants, NSAIDs (oxicam type), allopurinol, nevirapine, and chlormezanone 5
• Symptoms typically begin 4-28 days after drug initiation 3

In Children

Both infections and drugs are important triggers 1, 4:

• Infections account for up to 50% of pediatric cases, with Mycoplasma pneumoniae responsible for up to 50% of infection-related cases 4
• Herpes simplex virus is another important infectious trigger 4
• Most commonly implicated medications: Anticonvulsants and antibiotics 1, 4

Histopathology

Skin biopsy may be necessary to support clinical diagnosis and exclude other blistering disorders 1:

• Variable epidermal damage ranging from individual cell apoptosis to confluent epidermal necrosis 1
• Basal cell vacuolar degeneration and subepidermal vesicle/bulla formation 1
• Subepidermal cleavage (versus intraepidermal cleavage in SSSS) 4
• Mild, predominantly perivascular infiltrate of lymphocytes and histiocytes in the dermis 1

Prognosis and Mortality

The disease carries significant mortality and morbidity 1:

• SJS mortality: <10% 1
• TEN mortality: Up to 30% 1
• Overall SJS/TEN mortality: Approximately 22% 1
• Pediatric mortality appears lower than in adults 4
• Survivors often develop significant long-term sequelae including ocular complications, mucosal strictures, and cutaneous scarring 1, 6

Incidence

SJS/TEN is rare, with an incidence of approximately 1-2 cases per million per year 1

Critical Management Principles

Immediate withdrawal of any suspected culprit medication is mandatory and decreases mortality risk 1, 4:

• Transfer to a specialist center with multidisciplinary team experience is essential 1
• Patients with >10% BSA involvement, comorbidities, or requiring ventilation should be admitted to PICU or burns center 1
• Supportive care is crucial and likely more important than specific immunomodulating treatments 6