Stevens–Johnson syndrome

Overview

Stevens–Johnson syndrome (SJS) is a rare, severe, and potentially life-threatening hypersensitivity reaction that affects the skin and mucous membranes. It is characterized by widespread epidermal necrosis, leading to painful blistering, skin peeling, and mucosal ulcerations. SJS is part of a spectrum of disorders that includes toxic epidermal necrolysis (TEN), with SJS involving less than 10% of body surface area and TEN involving more extensive skin detachment.

The syndrome typically develops as an adverse reaction to medications, infections, or, rarely, vaccinations. SJS requires urgent medical attention and often hospitalization due to the risk of severe complications such as infection, dehydration, and multi-organ failure.

Causes

The most common causes of Stevens–Johnson syndrome include:

• Medications: The majority of cases are drug-induced. High-risk medications include sulfonamide antibiotics, anticonvulsants (e.g., phenytoin, carbamazepine), allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), and certain antivirals.

• Infections: Viral infections such as herpes simplex virus, Mycoplasma pneumoniae, and other bacterial or viral pathogens can trigger SJS, especially in children.

• Other factors: Rare causes include vaccines, graft-versus-host disease, and idiopathic cases with no identifiable trigger.

The pathogenesis involves an immune-mediated cytotoxic reaction against keratinocytes expressing foreign antigens, resulting in massive apoptosis and skin detachment.

Symptoms

Symptoms of SJS typically begin 1 to 3 weeks after exposure to the causative agent and include:

• Prodromal phase: Fever, malaise, sore throat, cough, and burning eyes occurring days before skin lesions.

• Skin manifestations: Painful, erythematous macules that rapidly progress to blistering and epidermal detachment, often starting on the face and upper torso and spreading.

• Mucous membrane involvement: Painful erosions and ulcers affecting the mouth, eyes, genitalia, and respiratory tract.

• Nikolsky sign: Gentle lateral pressure on the skin causes the epidermis to shear off, indicating skin fragility.

• Other symptoms: Conjunctivitis, photophobia, difficulty swallowing, and respiratory distress due to mucosal involvement.

Diagnosis

Diagnosis of Stevens–Johnson syndrome is primarily clinical, supported by history and examination. Diagnostic considerations include:

• History: Recent drug exposure or infection preceding symptom onset.

• Physical examination: Characteristic skin lesions with mucosal involvement and positive Nikolsky sign.

• Skin biopsy: Confirms diagnosis by demonstrating full-thickness epidermal necrosis and subepidermal blister formation.

• Laboratory tests: May show leukopenia, anemia, elevated liver enzymes, and electrolyte imbalances.

• Differential diagnosis: Includes bullous pemphigoid, pemphigus vulgaris, erythema multiforme major, and toxic epidermal necrolysis (TEN).

Treatment

Stevens–Johnson syndrome is a medical emergency requiring prompt hospitalization, often in a burn unit or intensive care setting. Treatment involves:

• Immediate withdrawal of offending agents: Discontinuation of any suspected causative drugs.

• Supportive care: Fluid and electrolyte management, wound care, pain control, and nutritional support.

• Infection prevention: Strict aseptic wound care to prevent secondary infections and sepsis.

• Ophthalmologic care: Regular eye examinations and treatment to prevent long-term ocular complications.

• Pharmacologic therapy: Use of systemic corticosteroids, intravenous immunoglobulin (IVIG), cyclosporine, or other immunomodulatory agents remains controversial but may be considered in select cases.

• Multidisciplinary approach: Coordination between dermatology, ophthalmology, critical care, and other specialties.

Prognosis

The prognosis of Stevens–Johnson syndrome depends on the extent of skin involvement, patient age, and presence of comorbidities. Mortality rates range from 5% to 15%, increasing significantly with greater body surface area affected and in elderly or immunocompromised patients.

Survivors may experience long-term complications such as chronic skin scarring, pigmentary changes, ocular damage including blindness, and respiratory or genitourinary sequelae. Early diagnosis, withdrawal of causative agents, and comprehensive supportive care are critical to improving outcomes and reducing morbidity and mortality.