Stevens-Johnson Syndrome (SJS)

Introduction | Aetiology and Risk Factors | Clinical Presentation | Diagnosis | Management and Treatment | Prevention | When to Refer | References

Introduction

Stevens-Johnson Syndrome (SJS) is a rare, severe, and potentially life-threatening hypersensitivity reaction that affects the skin and mucous membranes. It is considered part of a spectrum with toxic epidermal necrolysis (TEN), distinguished primarily by the extent of skin detachment. SJS typically involves less than 10% of the body surface area, whereas TEN involves more than 30%. The condition often begins with flu-like symptoms, followed by the rapid onset of painful, blistering, and necrotic skin lesions.

Aetiology and Risk Factors

SJS is most commonly triggered by medications, though infections and, rarely, malignancies can also be contributing factors:

• Medications: The most frequent culprits include:
  • Antibiotics: Particularly sulphonamides, penicillins, and cephalosporins.
  • Anticonvulsants: Such as phenytoin, carbamazepine, and lamotrigine.
  • NSAIDs: Non-steroidal anti-inflammatory drugs, particularly oxicam derivatives.
  • Allopurinol: Commonly associated with SJS, especially at higher doses or in renal impairment.
  • Antiretrovirals: Especially nevirapine in HIV patients.
• Infections: SJS can also be triggered by viral infections such as herpes simplex virus, Mycoplasma pneumoniae, and HIV.
• Genetic Factors: Certain genetic predispositions, such as the presence of the HLA-B*1502 allele in Asian populations, have been linked to an increased risk of SJS with carbamazepine use.
• Malignancies: In rare cases, SJS may be associated with underlying malignancies.

Clinical Presentation

The clinical course of SJS typically begins with non-specific prodromal symptoms, followed by the rapid development of characteristic skin and mucous membrane lesions:

• Prodromal Symptoms:
  • Fever, malaise, and sore throat are common initial symptoms.
  • Patients may also experience headache, cough, and arthralgia.
• Skin Lesions:
  • Red or purpuric macules that progress to blistering and erosions. These lesions often have a targetoid appearance with a central blister surrounded by erythema.
  • The skin becomes painful and tender, and the lesions rapidly spread to involve large areas of the body, leading to extensive epidermal detachment and necrosis.
  • Nikolsky's Sign: Positive in SJS, where slight rubbing of the skin results in exfoliation of the outermost layer.
• Mucous Membrane Involvement:
  • Lesions typically affect the oral, ocular, and genital mucosa, leading to painful erosions and ulceration.
  • Ocular involvement can lead to conjunctivitis, corneal ulceration, and, in severe cases, blindness.
  • Oral lesions can result in difficulty eating and swallowing, while genital lesions may cause dysuria and scarring.

Diagnosis

The diagnosis of SJS is primarily clinical, supported by a thorough patient history and physical examination:

• History: A detailed history of recent medication use (within the last 1-3 weeks), infections, or other potential triggers is crucial.
• Physical Examination: Assess the extent of skin involvement, mucosal involvement, and signs of systemic illness. The skin lesions typically appear on the face, trunk, and limbs.
• Skin Biopsy: A skin biopsy can confirm the diagnosis and differentiate SJS from other blistering conditions. Histopathology shows necrotic keratinocytes and subepidermal blistering.
• Laboratory Tests: Blood tests may show non-specific findings such as elevated inflammatory markers (CRP, ESR), anaemia, and electrolyte imbalances. A full blood count (FBC) may reveal leucocytosis or lymphopenia.
• Severity Assessment: The SCORTEN scale is used to assess the severity and prognosis of SJS/TEN based on factors such as age, heart rate, extent of skin detachment, serum urea, and glucose levels.

Management and Treatment

The management of SJS requires prompt identification of the condition, immediate withdrawal of the offending drug, and supportive care, often in a specialised setting:

1. Immediate Actions

• Discontinue Causative Agents: Immediately stop any suspected drug that could be triggering the reaction.

2. Supportive Care

• Hospital Admission: Patients with SJS should be managed in a hospital, preferably in a burns unit or intensive care unit, due to the need for specialised care.
• Fluid and Electrolyte Management: Fluid replacement is critical, similar to the management of burns, as patients are at high risk of dehydration due to extensive skin loss.
• Wound Care: The affected skin should be treated similarly to burns, with careful wound care to prevent secondary infection. Use of non-adhesive dressings and maintaining a moist wound environment are essential.
• Nutritional Support: Ensure adequate nutritional intake, which may require enteral feeding if oral intake is compromised.
• Pain Management: Pain can be severe and may require systemic analgesics, including opioids.
• Infection Control: Use prophylactic antibiotics judiciously; treatment should be guided by cultures if infection develops.

3. Medications

• Systemic Corticosteroids: The use of corticosteroids in SJS is controversial, but some clinicians may opt for high-dose corticosteroids early in the disease course to reduce inflammation.
• Intravenous Immunoglobulins (IVIG): IVIG may be used in some cases to halt disease progression, particularly in patients with extensive skin involvement.
• Ciclosporin: An immunosuppressant that has shown some benefit in reducing the severity and duration of SJS.
• Other Immunomodulatory Treatments: Emerging therapies, such as TNF-alpha inhibitors (e.g., infliximab), are being explored for their potential benefits in severe cases.

4. Ocular Management

• Ophthalmology Referral: Early involvement of an ophthalmologist is crucial for managing eye involvement to prevent long-term complications such as scarring and blindness.
• Lubricating Eye Drops: Use preservative-free lubricating drops to prevent dryness and further damage.
• Topical Steroids: May be prescribed by an ophthalmologist to reduce inflammation.

Prevention

Preventing recurrences of SJS involves avoiding known triggers and careful use of medications:

• Drug Avoidance: Patients diagnosed with SJS should be advised to avoid the causative medication and related drugs. This information should be clearly documented in the patient’s medical records and shared with all healthcare providers.
• Genetic Testing: In populations at high risk (e.g., HLA-B*1502 carriers), genetic testing before prescribing certain high-risk medications like carbamazepine can help prevent SJS.

When to Refer

Referral to a specialist is necessary in the following situations:

• Severe or Extensive Disease: Patients with significant skin involvement or systemic symptoms should be managed in a specialised unit, such as a burns unit or ICU.
• Ocular Involvement: Early referral to an ophthalmologist is critical for managing eye involvement and preventing long-term complications.
• Complex Cases: Cases requiring advanced immunomodulatory treatments or where there is diagnostic uncertainty should be referred to a dermatologist or an immunologist.
• Psychological Support: Given the potential for long-term physical and psychological impact, referral for psychological support may be beneficial.

References

1. British Association of Dermatologists (2024) Guidelines for the Management of Stevens-Johnson Syndrome. Available at: https://www.bad.org.uk (Accessed: 26 August 2024).
2. National Institute for Health and Care Excellence (2024) Stevens-Johnson Syndrome: Diagnosis and Management. Available at: https://www.nice.org.uk/guidance/ng202 (Accessed: 26 August 2024).
3. British National Formulary (2024) Medications and Management for Severe Cutaneous Reactions. Available at: https://bnf.nice.org.uk/ (Accessed: 26 August 2024).