- Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions.
- Considered a continuum of the same disease
- Classified based on the percentage of body surface affected by blisters, erosions, and skin detachment:
10% of BSA
10%‒30% of BSA
Toxic epidermal necrolysis
30% of BSA
SJS: Stevens-Johnson syndrome
TEN: toxic epidermal necrolysis
- 1–7 cases per million people per year
- Higher in patients with HIV and active cancer
- SJS is more common.
- Mortality rate:
- SJS: 10%
- TEN: 50%
- More common in women than men, with a ratio of 2:1
- Can occur at any age
- Approximately 70% of cases
- Occurs within 8 weeks of medication onset
- 2nd-most common trigger
- Frequent cause in children
- > 1/3 of cases
- Some HLA types are associated with an increased risk.
- Other risk factors
- Ultraviolet light stimulus
- Radiation therapy
The following table lists the major common medication and infectious causes of SJS/TEN:
Lamotrigine, phenobarbital, carbamazepine, valproate, phenytoin
Aminopenicillins, fluoroquinolones, cephalosporins
|Herpes simplex virus, HIV, coxsackievirus, hepatitis, influenza, mumps, Epstein-Barr virus, enteroviruses|
|Group A beta-hemolytic streptococci, brucellosis, mycobacteria, Mycoplasma pneumoniae, rickettsia, tularemia|
The exact mechanism is unknown, but there are several theories:
- Drug, or infectious, antigen in the skin tissue → stimulates cytotoxic T cells, natural killer T cells (NKT), and natural killer (NK) cells → granulysin release → keratinocyte death
- Apoptosis of keratinocytes → epidermal separation from the dermis → characteristic skin detachment of SJS/TEN
- Dying cells and necrosis → ↑ antigen load → triggers T cells to continue the inflammatory response → development of fluid-filled blisters
This impaired skin integrity can lead to:
- Water loss
- Secondary bacterial infections and sepsis
- Fever (often > 39°C)
- Myalgia and arthralgia
- Keratoconjunctivitis (inflammation of the cornea and conjunctiva)
- Sore throat
- 1‒3 days after the prodrome
- Lasts 8‒12 days
- Cutaneous lesions
- Begin as ill-defined, coalescing macules with purpuric centers or diffuse erythema
- Start on the face and thorax, then spread symmetrically
- Typically spare scalp, palms, and soles
- Tender to touch
- Vesicles and bullae form as the disease progresses
- Skin begins to slough within days
- Nikolsky’s sign: extension of skin sloughing by applying pressure
- Begin as ill-defined, coalescing macules with purpuric centers or diffuse erythema
- Mucosal lesions
- Occur in approximately 90% of cases
- Includes oral, pharyngeal, ocular, and urogenital erosions
- Significant fluid loss
- Severe dehydration
- Hypovolemic shock
- Renal failure
- Bacterial infection
- Sepsis and septic shock are the main cause of death in SJS/TEN patients.
- Most often caused by Staphylococcus aureus and Pseudomonas aeruginosa
- Tracheobronchial epithelial involvement
- Interstitial pneumonitis
- Acute respiratory distress syndrome
- Protein loss: edema
- Electrolyte imbalances
- Epithelial necrosis of the gastrointestinal tract
- Colonic perforation
- Small bowel intussusception
The diagnosis is clinical, based on history and physical exam findings.
- Skin biopsy
- Not required for diagnosis, but can confirm and rule out other conditions
- Keratinocyte necrosis is the hallmark finding.
- Can be partial or full-thickness
- Apoptotic keratinocytes are scattered in the basal layer of the epidermis in early lesions.
- Full-thickness epidermal necrosis and subepidermal bullae later in the disease
- Lymphocytic inflammatory infiltration
- Direct immunofluorescence is negative.
- Supporting workup
- Aids in monitoring treatment and complications
- Basic metabolic panel → evaluate for electrolyte imbalance and renal failure
- Complete blood count → significant leukocytosis may signal an infection
- Bacterial and fungal cultures → bacterial superinfection and sepsis
- Chest radiograph → pneumonia or interstitial pneumonitis
- Immediate hospital admission
- Patients typically require intensive care or a burn unit.
- SCORTEN score (score of toxic epidermal necrolysis) is calculated to determine severity, prognosis, and appropriate setting for management (see table below).
- Withdrawal of causative agent is required.
- Supportive care:
- Wound care
- Antibacterial ointments
- Fluid and electrolyte management
- Nutritional support
- Parenteral nutrition for those with dysphagia and odynophagia
- Transition to oral feeds when tolerated
- Ocular care
- Ophthalmology consultation
- Corticosteroid and antibiotic eye drops
- Artificial tears for lubrication
- Temperature management
- Pain control
- Acetaminophen and ibuprofen for mild pain
- Opioids for severe pain
- Monitoring and treatment of superinfections
- Bacterial and fungal cultures of blood, wounds, and mucosal lesions
- Appropriate antibiotics and antifungals, as necessary
- Education on future drug avoidance, including closely related agents
- Wound care
- Controversial treatments:
- Systemic corticosteroids
- Intravenous immunoglobulin (IVIG)
Age ≥ 40 years
Body surface area detached ≥ 10%
Tachycardia ≥ 120/min
Serum urea > 10 mmol/L
Serum glucose > 14 mmol/L
Serum bicarbonate < 20 mmol/L
The SCORTEN score is used to help determine the severity, prognosis, and appropriate setting for management in SJS/TEN patients.
- Score 0‒1: 94% survival, may be treated in non-specialized wards
- Score 2: 87% survival, should be transferred to an intensive care unit, burn unit, or specialized dermatology unit
- Score 3: 53% survival, should be transferred to an intensive care unit, burn unit, or specialized dermatology unit
- Score 4: 25% survival, should be transferred to an intensive care unit, burn unit, or specialized dermatology unit
- Score 5‒7: 17% survival, should be transferred to an intensive care unit, burn unit, or specialized dermatology unit
- Erythema multiforme: an acute, immune-mediated skin eruption with typical targetoid lesions; may be accompanied by systemic symptoms and mucosal involvement. Etiology is usually due to infection from the herpes simplex virus, unlike SJS/TEN, which is usually caused by a medication. Diagnosis is clinical and will differentiate this condition from SJS. Treatment includes supportive care.
- Staphylococcal scalded skin syndrome (SSSS): presents with a painful, desquamative skin rash, especially around the nose, mouth, and anus. The condition results from a staphylococcal toxin, and is usually seen in children. Unlike SJS/TEN, there is no mucosal involvement. Diagnosis is clinical and confirmed with bacterial cultures. A biopsy will show noninflammatory, superficial splitting of the epidermis. Treatment includes antibiotics, wound care, and supportive care.
- Exfoliative dermatitis: a generalized, symmetric, erythematous rash caused by an underlying cutaneous disease (psoriasis, atopic dermatitis), medications, and malignancy (lymphoma). The condition can mimic the early stages of SJS; however, there is no mucosal involvement (which will differentiate the condition from SJS). Diagnosis is made clinically, and treatment focuses on treating the underlying cause, withdrawal of implicated medications, and supportive care.
- Toxic shock syndrome: a systemic syndrome caused by staphylococcus or streptococcus endotoxins. Patients present with fever, shock, and multisystem organ dysfunction. Cutaneous manifestations include a diffuse, erythematous rash and desquamation. Diagnosis is based on blood culture results, clinical history, and exam, which will differentiate this condition from SJS. Treatment includes hemodynamic support, fluid resuscitation, and antibiotics.
- Pemphigus vulgaris: an autoimmune disorder causing intraepidermal blistering and erosions of the skin and mucous membranes. Patients will have cutaneous bullae appearing on normal-appearing skin and painful mucocutaneous erosions. Diagnosis involves a biopsy with immunofluorescence testing showing immunoglobulin G (IgG) antibodies against keratinocytes, differentiating this condition from SJS. Treatment includes corticosteroids, immunosuppressants, and IVIG.
- Bullous pemphigoid: an autoimmune skin disorder causing pruritus, erythematous plaques, and tense, bullous lesions. Mucous membrane involvement is rare. Triggers include medications, trauma, skin conditions, and systemic disease. Biopsy with immunofluorescence shows IgG and complement deposits along the basement membrane, which differentiates the condition from SJS. Treatment includes steroids, immunosuppressants, and anti-inflammatory medications.
- High, W.A. (2019). Stevens-Johsnon syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis. In Corona, R. (Ed.), Uptodate. Retrieved November 7, 2020, from https://www.uptodate.com/contents/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-pathogenesis-clinical-manifestations-and-diagnosis
- High, W.A. (2020). Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae. In Corona, R. (Ed.), Uptodate. Retrieved November 7, 2020, from https://www.uptodate.com/contents/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-management-prognosis-and-long-term-sequelae
- Benedetti, J. (2020). Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). MSD Manual Professional Edition. Retrieved November 7, 2020, from https://www.msdmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-inflammatory-skin-disorders/stevens-johnson-syndrome-sjs-and-toxic-epidermal-necrolysis-ten
- Foster, C.S, Ba-Abbad, R., Letko, E., and Parillo, S.J. (2019). Stevens-Johnson syndrome. In Dahl, A.A. (Ed.), Medscape. Retrieved November 7, 2020, from https://emedicine.medscape.com/article/1197450-overview