MD Notes

creation date: 2026-06-21 19:03
tags: Pathologies

Stevens-Johnson Syndrome

Background

Definitions

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterized by skin necrosis and detachment of the epidermis.

SJS and TEN are a part of a continuum based on the percentage of skin body surface area (BSA) detached:

  • SJS: <10% BSA detached
  • SJS/TEN: 10-30%
  • TEN: >30%

Etiology

In most cases, SJS/TEN is due to medications. High risk medications that precipitate SJS/TEN one week to one month after initiation are:

  • Allopurinol
  • Lamotrigine
  • Aromatic antiseizure medications (eg. carbamazepine, phenytoin, phenobarbital)
  • Antibacterial sulfonamides
  • COX-2 inhibitor NSAIDs
  • Anticancer therapies (eg. tyrosine kinase inhibitors, immune checkpoint inhibitors)

Other medications may also cause SJS but are not necessarily considered high risk.

Other causes (15%) of cases do not have clear drug causality:

  • Infection (particularly Mycoplasma)
  • Other exposures to chemical, traditional medications, vaccinations, food (unclear evidence)
  • Idiopathic (occult exposures, or yet-to-be-identified agents)

Pathogenesis

SJS/TEN is a drug-specific T cell-mediated reaction. This is a type IV hypersensitivity reaction.

Briefly, the pathogenesis can be summarized as:

  • Genetic predisposition
  • Drug antigen presentation
  • T cell-mediated response and immune dysregulation
  • Release of cytotoxic mediators and death signals
  • Keratinocyte cell death and detachment of necrotic tissue

Risk Factors

SJS/TEN is rare, occurring 5-6 per million per year. Risk factors include:

  • Genetic predisposition
  • HIV
  • Connective tissue disease
  • Malignancy
  • Age (≥65)

Clinical Presentation

Signs & Symptoms

Prodrome
Prodromal symptoms may appear flu-like:

  • Malaise
  • Fever
  • Myalgia
  • Sore throat
  • Conjunctivitis

These symptoms may precede or occur together with the cutaneous lesions.

Cutaneous lesions
Lesions start on the face and thorax before spreading to other areas in a symmetrical distribution They progress as:

  1. Ill-defined, coalescing, erythematous macules
  2. Dusky erythema, purpuric spots, atypical targets, and flaccid bullae (after 2-3 days)
  3. Extensive sheet-like detachment and erosions of skin

Skin tenderness is common and palms and soles develop edematous erythema. The scalp is typically not affected.

After 7-9 days, the process arrests, and the skin re-epithelializes over 7-21 days.

Extracutaneous manifestations
Mucous membrane

  • Oral erosions, blisters, hemorrhagic cheilitis
  • Nasopharyngeal erosions, blisters, epistaxis, epiglottis
  • Genital erosions and blisters

Ocular

  • Conjunctival hyperemia
  • Pseudomembrane formation
  • Corneal epithelial defect

Kidney and liver

Pulmonary

  • Specific lung injury such as sloughing of bronchial epithelium
  • Pneumonia, pulmonary edema, atelectasis
  • Acute respiratory failure requiring mechanical ventilation

Gastrointestinal

  • Abdominal pain
  • Diarrhea
  • Hematemesis
  • Melena/rectal bleeding
  • Ileus

Hematologic

Bloodstream infections

  • Bacteremia
  • Sepsis and septic shock
  • Candidemia

History & Physical Exam

It is important to assess drug causality based on:

  • Latency – exposure to suspected drug 1-4 weeks prior to onset, although rarely, can be up to 8 weeks
  • Drug notoriety – whether suspected drug is high-risk for SJS/TEN

Scoring
The ALDEN algorithm can be used to gauge the likely cause based on:

  • Time of ingestion to onset of reaction
  • Half-life of the drug
  • Previous history
  • Notoriety of drug
  • Alternative diagnoses

The SCORTEN score is used to gauge mortality risk.

Diagnosis

Criteria

There is no formal diagnostic criteria for SJS/TEN. It generally involves clinical, histological, and laboratory findings, as well as exclusion of alternative diagnoses.

Work-up

Skin biopsy
Routine histopathologic examination and direct immunofluorescence can support the diagnosis. Findings include:

  • Basal keratinocyte apoptosis
  • Full thickness necrolysis
  • Separation of epidermis at the dermo-epidermal junction

Laboratory studies
Routine studies include:

  • CBC with differential
  • Coagulation studies
  • Metabolic panel
  • ESR/CRP

Additionally:

  • Bacterial and fungal cultures for wounds/blood/mucosal lesions due to high risk of infection
  • PCR for Mycoplasma pneumoniae in children without clear drug causality

Imaging
A chest radiograph is obtained routinely due to high risk of pulmonary involvement.

Differential

Differential diagnosis includes:

  • Erythema multiforme
  • Exanthematous drug eruptions
  • Drug reactions with eosinophilia and systemic symptoms (DRESS)
  • Acute generalized exanthematous pustulosis
  • Generalized bullous fixed drug eruption
  • Staphylococcal scalded skin syndrome
  • Acute graft-versus-host disease
  • Reactive infectious mucocutaneous eruption
  • SJS/TEN-like acute cutaneous lupus erythematosus
  • Paraneoplastic pemphigus
  • Linear IgA bullous dermatosis

Red Flags / Complications

SJS/TEN has a 10-30% mortality. With death being caused by a number of complications:

  • Sepsis
  • Acute respiratory distress syndrome
  • Disseminated intravascular coagulation
  • Multiple organ failure

Other complications include:

  • Recurrence of SJS
  • Skin, hair nails sequelae (eg. pigmentation, scarring, chronic pruritus)
  • Ocular sequelae (eg. dry eye, photophobia, neovascularization of cornea)
  • Oral and dental changes
  • Urogenital scarring and symptoms
  • Pulmonary complications (eg. chronic bronchitis)
  • Chronic pain
  • Psychosocial and psychiatric disorders

Management

Management of SJS should take place in specialized centres, especially those with ≥10% BSA detachment.

Supportive Care

The mainstay of care is supportive management to deal with the consequences of failing skin barrier.

  • Wound care (surgical vs. conservative)
  • Fluids and temperature management
  • Nutrition
  • Pain control
  • Prevention and treatment of infections

Management of Complications

Acute respiratory involvement may require ventilation. As intubation is often challenging with oral mucosal involvement, ICU should be involved.

Urogenital involvement may require examination, dressing, localized care, and potent corticosteroids.

Ocular involvement requires ophthalmic evaluation and therapy based on findings.

Adjunctive Pharmacologic Therapy

There are no established pharmacologic treatment. Evidence is limited but studies have suggested benefits from:

  • Cyclosporine
  • Etanercept
  • Systemic corticosteroids
  • Combinations of IVIG and systemic corticosteroids

Due to the self-limited nature of the acute phase, initiation of immunomodulatory agents outside the initial 8 days from onset is unlikely to be disease modifying.

References

Tools / Guidelines

Additional Reading

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