Stevens Johnson Syndrome
Definition And Disease Spectrum
- Rare, severe blistering drug hypersensitivity reaction.
- Lies on continuous clinical spectrum alongside Toxic Epidermal Necrolysis.
- Stevens Johnson Syndrome strictly defined by affected body surface area < 10%.
- Overlap syndrome features 10 to 30% affected body surface area.
- Toxic Epidermal Necrolysis defined by > 30% affected body surface area.
Etiology And Risk Factors
- Primarily triggered by systemic medication exposure.
- Genetic predisposition involves specific Human Leukocyte Antigen alleles in certain populations.
- Human Leukocyte Antigen-B*1502 associated with carbamazepine in Han Chinese patients.
- Human Leukocyte Antigen-B*5801 associated with allopurinol in Japanese patients.
| Drug Category | Specific Implicated Agents |
|---|---|
| Antibiotics | Sulfonamides, Beta-lactams, Cephalosporins. |
| Anticonvulsants | Phenytoin, Carbamazepine, Lamotrigine, Barbiturates. |
| Analgesics | Nonsteroidal anti-inflammatory agents, Acetaminophen. |
| Miscellaneous | Allopurinol, Dapsone. |
Pathophysiology
- Drug-specific CD8+ cytotoxic T cells initiate massive immune response.
- Keratinocyte apoptosis triggered directly by perforin/granzyme B and granulysin.
- Secondary apoptosis cascade involves soluble Fas ligand interaction with Fas receptor.
- Macrophages and monocytes contribute heavily via Tumor Necrosis Factor-alpha signaling pathways.
- Additional pathogenesis links to Tumor Necrosis Factor-related apoptosis-inducing ligand and inducer of apoptosis weak pathways.
Clinical Manifestations
Prodrome And Systemic Symptoms
- Prodrome manifests 4 to 28 days post-exposure.
- Features include fever
38°C, influenza-like syndrome, and respiratory tract symptoms.
Cutaneous Lesions
- Eruption begins abruptly on trunk with erythematous or purpuric macules.
- Papules absent, distinguishing from typical Erythema Multiforme.
- Central necrosis develops rapidly, evolving into atypical target lesions, vesicles, and bullae.
- Process results in large areas of epidermal denudation.
- Positive Nikolsky sign characterized by skin denudation with gentle tangential pressure.
- Skin tenderness minimal to absent, distinguishing clinically from Toxic Epidermal Necrolysis.
Mucosal Involvement
- Diagnostic criteria mandate two or more mucosal membranes involved.
- Initial mucosal signs include burning, edema, and erythema of lips and buccal mucosa.
- Progresses rapidly to severe bullae, ulceration, and hemorrhagic crusting.
- Affects ocular, upper airway, esophageal, gastrointestinal, and anogenital mucosae profoundly.
Histopathology And Laboratory Findings
- Skin biopsy reveals full-thickness epidermal necrosis with focal adnexal necrosis.
- Minimal to absent mononuclear cell dermal infiltrate noted.
- Direct immunofluorescence testing remains negative.
- Laboratory abnormalities include lymphopenia, transitory neutropenia, and extreme leukocytosis.
- Elevated erythrocyte sedimentation rate, increased liver transaminases, and mild cytolysis frequently observed.
- Decreased serum albumin and acute renal impairment often present.
Differential Diagnosis
- Toxic Epidermal Necrolysis.
- Erythema Multiforme (distinct due to acral distribution, classic target lesions, and Herpes Simplex Virus etiology).
- Drug Rash with Eosinophilia and Systemic Symptoms.
- Reactive Infectious Mucocutaneous Eruption.
- Staphylococcal Scalded Skin Syndrome (cleavage plane intraepidermal, lacks extensive mucosal necrosis).
- Kawasaki disease.
Management And Complications
Supportive Care
- Immediate discontinuation of offending medication remains most critical intervention.
- Hospitalization in intensive care unit or specialized burn unit urgently required.
| Management Category | Specific Interventions |
|---|---|
| Environment | Intravenous fluids, nutritional support, sheepskin or air-fluid bedding. |
| Wound Care | Daily saline or Burrow solution compresses. Paraffin gauze or colloidal gel dressings for denuded areas. |
| Mucosal Care | Mandatory ophthalmologic consultation. Topical steroids or cryopreserved amniotic membrane prevent vision loss. Glycerin swabs and viscous lidocaine for oral pain. |
| Genitourinary | Monitor closely to prevent strictures or labial/foreskin fusion. Urinary catheterization as needed. |
Systemic Therapy
- Systemic immunosuppressive therapy remains controversial but frequently utilized to arrest progression.
- Intravenous immunoglobulin at 1.5 to 2.0 grams/kilogram/day for 3 days considered in early disease.
- Cyclosporine administered at 3 milligrams/kilogram/day divided twice daily shows rapid efficacy.
- Anti-Tumor Necrosis Factor agents include Infliximab (5 milligrams/kilogram single dose) or Etanercept.
- Prophylactic systemic antibiotics strictly not recommended.
- Systemic antibiotics indicated solely for documented infection or suspected bacteremia (Staphylococcus aureus, Pseudomonas aeruginosa).
Complications
- Severe insensible fluid loss, bacterial superinfection, and massive sepsis lead mortality.
- Internal organ failure encompasses acute tubular necrosis, myocarditis, and hepatitis.
- Long-term sequelae involve severe ocular scarring, corneal opacity, and visual impairment.
- Permanent strictures frequently develop in esophagus, bronchi, vagina, urethra, and anus.