Stevens Johnson Syndrome

Definition And Disease Spectrum

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.

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.

Prodrome manifests 4 to 28 days post-exposure.
Features include fever $\geq$ 38°C, influenza-like syndrome, and respiratory tract symptoms.

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.

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.

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.

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.

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 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).

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.