Toxic Epidermal Necrolysis (TEN)

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

Introduction

Toxic Epidermal Necrolysis (TEN) is a rare, life-threatening skin condition that is characterised by widespread necrosis and detachment of the epidermis, similar to severe burns. It is considered the most severe form of a spectrum that includes Stevens-Johnson Syndrome (SJS) and is typically triggered by a reaction to medications. TEN affects more than 30% of the body surface area, and early recognition and treatment are critical to reducing morbidity and mortality.

Aetiology and Risk Factors

TEN is most commonly triggered by medications, but it can also be associated with infections and, rarely, malignancies. The exact mechanism involves an immune-mediated reaction that leads to widespread apoptosis of keratinocytes:

• Medications: The most frequent triggers include:
  • Antibiotics: Particularly sulfonamides, penicillins, and cephalosporins.
  • Anticonvulsants: Such as phenytoin, carbamazepine, and lamotrigine.
  • NSAIDs: Especially oxicam derivatives.
  • Allopurinol: Frequently associated with TEN, especially at higher doses or in patients with renal impairment.
  • Antiretrovirals: Particularly nevirapine in HIV-positive patients.
• Infections: Some cases of TEN are associated with viral infections, such as herpes simplex virus or Mycoplasma pneumoniae.
• Genetic Predisposition: Certain genetic factors, such as the presence of HLA-B*1502 in Asian populations, increase the risk of TEN with specific drugs like carbamazepine.
• Malignancies: Though rare, TEN can occur in association with underlying cancers.

Clinical Presentation

TEN typically begins with non-specific symptoms before progressing rapidly to widespread skin and mucosal involvement:

• Prodromal Symptoms:
  • Flu-like symptoms such as fever, malaise, sore throat, and cough are common in the early stages.
• Skin Lesions:
  • Initial lesions appear as widespread erythematous macules or patches that may develop into blisters.
  • The blisters rapidly coalesce, leading to large areas of epidermal detachment, often described as "sheet-like." The affected skin is extremely painful and resembles a severe burn.
  • Nikolsky's Sign: Positive in TEN, where slight rubbing of the skin results in the detachment of the epidermis.
• Mucosal Involvement:
  • Severe mucosal involvement is a hallmark of TEN, affecting the oral cavity, eyes, and genitalia. This can lead to significant pain, difficulty eating, swallowing, and severe conjunctivitis.
  • Ocular involvement can lead to keratitis, corneal ulceration, and, in severe cases, blindness.
• Systemic Symptoms:
  • Systemic symptoms such as dehydration, electrolyte imbalance, and risk of sepsis are common due to the loss of the skin barrier.

Diagnosis

The diagnosis of TEN is primarily clinical, supported by a detailed history and physical examination:

• History: Obtain a thorough history, focusing on recent medication use, onset of symptoms, and any previous reactions to drugs.
• Physical Examination: Assess the extent of skin detachment and involvement of mucosal surfaces. The involvement of more than 30% of the body surface area (BSA) is characteristic of TEN.
• Skin Biopsy: A biopsy can confirm the diagnosis, revealing full-thickness epidermal necrosis with minimal inflammation.
• Laboratory Tests: Perform blood tests including full blood count (FBC), urea and electrolytes, liver function tests, and inflammatory markers (CRP, ESR). Blood cultures may be indicated if sepsis is suspected.

Management and Treatment

The management of TEN requires immediate discontinuation of the offending drug, intensive supportive care, and, in some cases, immunomodulatory therapy:

1. Immediate Actions

• Discontinue Causative Agents: Immediately stop any suspected drug that could be triggering the reaction.
• Hospital Admission: Patients with TEN should be managed in a specialised unit, such as a burns unit or intensive care unit (ICU), due to the need for comprehensive supportive care.

2. Supportive Care

• Fluid and Electrolyte Management: Fluid replacement is critical, as patients are at high risk of dehydration due to extensive skin loss. Electrolyte imbalances should be corrected.
• Wound Care: The affected skin should be treated similarly to burns, with careful wound care to prevent secondary infection. Use non-adhesive dressings and maintain a moist wound environment.
• Nutritional Support: Adequate nutritional intake is essential, 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: Prophylactic antibiotics are not routinely recommended, but treatment should be guided by cultures if infection develops. Strict infection control measures should be implemented to prevent sepsis.
• Temperature Regulation: Patients are at risk of hypothermia due to extensive skin loss; maintaining a warm environment is important.

3. Medications

• Systemic Corticosteroids: The use of corticosteroids in TEN is controversial. Some clinicians may use them in the early stages to reduce inflammation, but the risks of infection and delayed wound healing must be considered.
• Intravenous Immunoglobulins (IVIG): IVIG may be used to halt disease progression, particularly in patients with extensive skin involvement, though evidence of efficacy is mixed.
• Cyclosporine: An immunosuppressant that has shown some benefit in reducing the severity and duration of TEN.
• 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 TEN involves avoiding known triggers and careful use of medications:

• Drug Avoidance: Patients diagnosed with TEN 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 TEN.

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 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 Toxic Epidermal Necrolysis. Available at: https://www.bad.org.uk (Accessed: 26 August 2024).
2. National Institute for Health and Care Excellence (2024) Toxic Epidermal Necrolysis: 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).