Basics
Description
- Stevens " �Johnson 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 sites
- 85% have conjunctival lesions
- Lesions 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 BSA
- SJS " �TEN overlap syndrome: 10 " �30% of BSA
- TEN: >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) antigens
- Cytokines from activated mononuclear cells probably contribute to cell destruction and systemic manifestations
- Causative medications:
- Antibiotics (e.g., penicillin, sulfonamide)
- Anticonvulsants
- Oxicams
- NSAIDs
- Allopurinol
- Infections:
- Mycoplasma pneumoniae
- Herpes simplex
Diagnosis
Signs and Symptoms
History
- Prodrome:
- Usually 1 " �3 days prior to development of skin lesions
- Fever
- Headache
- General malaise
- Upper respiratory infection (URI) symptoms
- Arthritis, 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 � �
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 � �
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 � �
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 � �
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 pneumonia
- Secondarily 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 " �6h (peds: 10 " �15 mg/kg/dose; do not exceed 5 doses/24 h); do not exceed 4 g/24 h
- Acyclovir: 5 " �10 mg/kg IV q8h (for herpes simplex virus infections)
- Ibuprofen: 300 " �800 mg PO (peds: 5 " �10 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 � �
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 � �
Followup Recommendations
Follow-up with PCP and/or dermatologist � �
Pearls and Pitfalls
- SJS may begin like an influenza illness. Lesions appear 1 " �3 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 � �R, Nelle � �M, Schaible � �T. Toxic epidermal necrolysis and Stevens-Johnson syndrome: A review. Crit Care Med. 2011;39:1521 " �1532.
- James � �JD, Berger � �TG, Elston � �DM. Andrews Clinical Dermatology. 10th ed. Philadelphia, PA: Saunders; 2006.
- Lee � �HY, Dunant � �A, Sekula � �P. 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 " �562.
- Levi � �N, Bastuji-Garin � �S, Mockenhaupt � �M, et al. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: A pooled analysis. Pediatrics. 2009;123:e297 " �e304.
- Stella � �M, Clemente � �A, Bollero � �D, 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 " �459.
- Wolff � �K, Johnson � �RA, Suurmond � �D. 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 " �147.
See Also (Topic, Algorithm, Electronic Media Element)
- Erythema Multiforme
- Toxic Epidermal Necrolysis
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)