StevensГўВЂВ“Johnson Syndrome, Emergency Medicine

Basics

Description

- The most common causes include medications and infections: - Damage to the skin is thought to be mediated by cytotoxic T lymphocytes and mononuclear cells aimed at keratinocytes expressing (drug-related) antigens - Cytokines from activated mononuclear cells probably contribute to cell destruction and systemic manifestations

- Prodrome: - Usually 1 " пїЅ3 days prior to development of skin lesions - Fever - Headache - General malaise - Upper respiratory infection (URI) symptoms - Arthritis, arthralgias, and myalgias prior to mucocutaneous lesions

Stevens " пїЅJohnson syndrome (SJS) is an idiosyncratic, severe mucocutaneous disease:Blistering of <10% of the body surface area (BSA)95% of patients have mucous membrane lesions:Usually at 2 or more sites85% have conjunctival lesionsLesions often involving face, neck, and central trunk regions become confluent over hours to days
On a continuum with toxic epidermal necrolysis (TEN); but thought to be a distinct disease entity from erythema multiforme (EM):SJS: <10% of BSASJS " пїЅTEN overlap syndrome: 10 " пїЅ30% of BSATEN: >30% of BSA, can affect up to 100% BSA

Etiology

The most common causes include medications and infections:Damage to the skin is thought to be mediated by cytotoxic T lymphocytes and mononuclear cells aimed at keratinocytes expressing (drug-related) antigensCytokines from activated mononuclear cells probably contribute to cell destruction and systemic manifestations
Causative medications:Antibiotics (e.g., penicillin, sulfonamide)AnticonvulsantsOxicamsNSAIDsAllopurinol
Infections:Mycoplasma pneumoniaeHerpes simplex

Diagnosis

Signs and Symptoms

History

Prodrome:Usually 1 " пїЅ3 days prior to development of skin lesionsFeverHeadacheGeneral malaiseUpper respiratory infection (URI) symptomsArthritis, arthralgias, and myalgias prior to mucocutaneous lesions
Skin: Mild to moderate skin tenderness followed by skin pain, burning sensation, and paresthesias
Eye: Conjunctival burning or itching
Mucous membranes: Painful micturition, painful swallowing
Drug exposure precedes symptoms usually by 2 wk:Re-exposure may result in onset of symptoms within 48 hr
Risk factors include HIV, genetic factors, viral infections, and underlying immunologic diseases

Physical Exam

Rash: Target lesions, erythematous or purpuric macules with or without confluence, and raised flaccid blisters or bullae with skin detachment that spread with lateral pressure (Nikolsky sign) on erythematous areas
Mucous membrane: Erythematous tender erosions of the mouth, pharynx, trachea, genitalia, or anus; possibly pseudomembrane formation
Eye: Mild to severe conjunctivitis with possible formation of pseudomembranes and corneal ulcers

Essential Workup

A complete history and physical exam with careful attention to mucous membranes, percentage of blistering, and identification of likely etiology пїЅ пїЅ

Diagnosis Tests & Interpretation

Lab

Electrolytes
Liver enzymes may be mildly elevated
CBC:Anemia and lymphopenia are common
UA

Imaging

Chest radiography if pneumonia is a consideration пїЅ пїЅ

Diagnostic Procedures/Surgery

Skin biopsy of lesions and mucous membranes demonstrates necrosis of the entire epidermal layer with formation of subepidermal split above basement membrane пїЅ пїЅ

Differential Diagnosis

SJS if <10% of BSA
Overlapping SJS and TEN (skin detachment between 10% and 30% of BSA plus widespread macules or flat atypical target lesions)
TEN (skin detachment >30% of the BSA plus widespread macules or flat atypical targets)
EM
Thermal burns
Phototoxic reactions
Exfoliative dermatitis
Pustular drug eruptions
Bullous fixed drug eruptions
Paraneoplastic pemphigus
Graft-versus-host disease in bone marrow transplant patients
Toxic shock syndrome
Staphylococcal scalded skin syndrome

Staphylococcal scalded skin syndrome is in the pediatric differential diagnosis of severe blistering mucocutaneous diseases пїЅ пїЅ

Treatment

Pre-Hospital

ABCs
Observe universal precautions
IV access if indicated
Transport to burn center if >30% of body surface involved

Initial Stabilization/Therapy

Endotracheal intubation and ventilatory support may be required for impending respiratory failure (more commonly associated with TEN)
IV fluids

Ed Treatment/Procedures

Fluid replacement:Fluid losses may be significant
Recognize and treat underlying infections:Sepsis is the primary cause of death, frequently from gram-negative pneumoniaSecondarily infected cutaneous lesions can be treated with debridement of blisters, compresses, and systemic antibiotics
Corticosteroids are controversial
Prophylactic antibiotics may be indicated if systemic steroids are given
Intravenous immunoglobulin (IVIG) may be beneficial
Mild systemic symptoms may be treated with acetaminophen or NSAIDs provided they are not the cause of the mucocutaneous reaction
Mucous membrane lesions are extremely painful and may require parenteral analgesics
Large extensive bullae should be debrided, ideally in a burn unit

Medication

Acetaminophen: 500 mg PO/PR q4 " пїЅ6h (peds: 10 " пїЅ15 mg/kg/dose; do not exceed 5 doses/24 h); do not exceed 4 g/24 h
Acyclovir: 5 " пїЅ10 mg/kg IV q8h (for herpes simplex virus infections)
Ibuprofen: 300 " пїЅ800 mg PO (peds: 5 " пїЅ10 mg/kg/dose)
Morphine sulfate: 0.1 mg/kg/dose IV

First Line

Fluid replacement
Treat underlying etiology
Treat secondary infections
Analgesia

Second Line

Follow-Up

Disposition

Admission Criteria

Patients with SJS should be admitted to the hospital
Patients with extensive epidermal detachment should be admitted to a burn center or a specialized intensive care unit

Discharge Criteria

Patients with EM minor may be discharged with appropriate and timely follow-up пїЅ пїЅ

Issues for Referral

Patients must be made aware of the likely offending drug (and its class) and that it must never be administered to them again пїЅ пїЅ

Followup Recommendations

Follow-up with PCP and/or dermatologist пїЅ пїЅ

Pearls and Pitfalls

SJS may begin like an influenza illness. Lesions appear 1 " пїЅ3 days after the prodrome
The diagnosis is clinical and biopsy is supportive
M. pneumoniae and herpes simplex are more common triggers in children than in adults

Additional Reading

Gerull пїЅ пїЅR, Nelle пїЅ пїЅM, Schaible пїЅ пїЅT. Toxic epidermal necrolysis and Stevens-Johnson syndrome: A review. Crit Care Med. 2011;39:1521 " пїЅ1532.
James пїЅ пїЅJD, Berger пїЅ пїЅTG, Elston пїЅ пїЅDM. Andrews Clinical Dermatology. 10th ed. Philadelphia, PA: Saunders; 2006.
Lee пїЅ пїЅHY, Dunant пїЅ пїЅA, Sekula пїЅ пїЅP. The role of prior corticosteroid use on the clinical course of Stevens-Johnson syndrome and toxic epidermal necrolysis: A case-control analysis of patients selected from the multinational EuroSCAR and RegiSCAR studies. Br J Dermatol. 2012;167:555 " пїЅ562.
Levi пїЅ пїЅN, Bastuji-Garin пїЅ пїЅS, Mockenhaupt пїЅ пїЅM, et al. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: A pooled analysis. Pediatrics. 2009;123:e297 " пїЅe304.
Stella пїЅ пїЅM, Clemente пїЅ пїЅA, Bollero пїЅ пїЅD, et al. Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS): Experience with high-dose intravenous immunoglobulins and topical conservative approach. A retrospective analysis. Burns. 2007;33:452 " пїЅ459.
Wolff пїЅ пїЅK, Johnson пїЅ пїЅRA, Suurmond пїЅ пїЅD. Stevens-Johnson syndrome and toxic epidermal necrolysis. In: Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology. 5th ed. New York, NY: McGraw-Hill, 2005:144 " пїЅ147.

Codes

ICD9

695.13 Stevens-Johnson syndrome
695.14 Stevens-Johnson syndrome-toxic epidermal necrolysis overlap syndrome

ICD10

L51.1 Stevens-Johnson syndrome
L51.3 Stevens-Johnson synd-tox epdrml necrolysis overlap syndrome

SNOMED

73442001 Stevens-Johnson syndrome (disorder)
124911000119100 Stevens-Johnson syndrome - toxic epidermal necrolysis overlap (disorder)
403609001 Drug-induced Stevens-Johnson syndrome (disorder)