Question 28

With respect to Toxic Epidermal Necrolysis (TENS): 
a)    List the main causes.                                             (20% marks) 
b)    Outline the management.                                      (80% marks) 

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College answer

a)    Infections:  
Viral e.g. Influenza, Coxsackie, Mumps 
Bacterial e.g. GAS, Diphtheria, Mycoplasma 
b)    General: 
Multi-disciplinary approach with dermatology, plastics, ophthalmology. Best managed in specialised burns unit 
Stop precipitating agents e.g. NSAID / allopurinol General Haemodynamic and respiratory support. 
Reverse-Isolation in single room with room temperature increased to 30-320C. 
Awareness of potentially high fluid loss: may require aggressive replacement 
Wound care: Cover the denuded skin with anti-septic soaked dressings, vigilance for secondary skin infections. No role for prophylactic antibiotics. 
Analgesia for painful skin lesions and for dressing change. 
Eye care: look for conjunctival hyperemia, epithelial defect & pseudomembrane formation. Treat with topical lubricants, topical steroids and topical antibiotic, as guided by ophthalmology. Attempt to place lines through normal skin if possible 
Cyclosporin: Early administration at the dose of 3-5mg/kg is beneficial and is recommended.
Steroids: The use of systemic corticosteroids has not been evaluated in clinical trials & remains controversial. Early observational studies indicated higher frequency of complications & death; but recent meta-analysis found that steroid treatment was associated with reduced risk of death. The dose, route, duration & timing of steroids remain uncertain.  
Plasmapheresis: Reported to be beneficial in small series and case reports, but role still not well defined. 
Anti-TNFα monoclonal antibodies e.g. infliximab has been used successfully in small series of patients, but not recommended. 


It is remarkable that this SAQ on a relatively rare condition had a 58% pass rate. The last time toxic epidermal necrolysis came up (in Question 10 from the first paper of 2005), only 13% of the candidates passed. Presumably, of that 34-candidate cohort from 2005 (of whom 19 were successful), thirteen years later some proportion were senior college fellows and Part II examiners, and now they think this question is a really good idea from an assessment value standpoint.

The best literature for the management of TEN is unfortunately paywalled (Fromowitz et al, 2007). That particular article shines brightest because they incorporate a long (28-point) list of management recommendations from the University of Florida protocol. Fortunately, Schneider & Cohen have an even better article, which is more recent (2017). Additionally, the 2016 UK guidelines are available as a free PDF (Creamer et al, 2016).  These and other resources have been remixed and recut into the summary below.

  • Supportive management:
    • A- Intubation is almost inevitable because of the sedation and analgesic requirements
    • B- Wherever mechanical ventilation can be avoided, humidified oxygen is preferred to regular wall oxygen because of the mucosal injuries
    • C- Expect a hyperdynamic vasodilated circulation with hypovolemia:
      • Replace lost fluid (see F below)
      • Vasopressors to maintain MAP targets
      • Use PICC access (anticipating long term IV access requirements with few normal patches of skin available for PIVCs and CVCs)
      • Beware of line dressings. Where possible, avoid adhesive dressings.
    • D - Expect complex pain needs:
      • The patient will likely require a multimodal approach to analgesia with some combination of IV opiate and opiate-sparing agents like ketamine. For dressing changes, expect to need either general anaesthetic, ketamine sedation or methoxyflurane.
      • Psychological support will be required to the patient and family (disfiguring illness, prolonged ICU stay, extreme pain - all the recipes for PTSD and depression)
    • E - Expect electrolytes to be deranged:
      • Hypernatremia due to water loss
      • Hypophosphataemia due to large-scale tissue regrowth
    • F - Not quite a burns-like fluid management strategy: fluid requirements are usually about 30% lower than for burns of a similar extent (Schenider & Cohen, 2017)
      • Replace large volumes of crystalloid, using a balanced crystalloid
      • Haemoconcentration is a guide to replacement adequacy
      • Albumin replacement will be required due to ongoing protein loss through wounds
    • G - Nutrition needs will be complex:
      • High caloric requirements, like sepsis (probably 125% of predicted) but lower than burns of a similar extent
      • High protein requirements (2.0-2.5g/kg/day) to account for losses and hypercatabolic state
      • Expect oral diet to be impossible owing to mucosal injuries; expect these injuries to frustrate NG placement. Early placement of a feeding NG tube is vitally important.
      • Anticipate constipation due to high dose opiates
      • Ensure vigorous ulcer prophylaxis (high dose steroids will be used)
      • High risk for C.difficile infection (likely, broad spectrum antibiotics will be used)
    • H - Expect the patient to be at high risk of VTE:
      • Chemical thromboprophylaxis needs to be fastidious, as there is usually nowhere to place TEDs and calf compressors
    • I - Infectious diseases specialists need to be included in decisionmaking. Broadly:
      • Antibiotics are not indicated unless there is a clinically evident infection
      • Topical antibiotics for conjunctiva are indicated (chloramphenicol)
      • Antibiotic-coated lines are indicated (especially if placed through affected skin)
      • If somebody started steroids, stop them.
  • Specific management:


Shiga, Sarah, and Rob Cartotto. "What are the fluid requirements in toxic epidermal necrolysis?." Journal of Burn Care & Research 31.1 (2010): 100-104.

Fromowitz, Jeffrey S., Francisco A. Ramos‐Caro, and Franklin P. Flowers. "Practical guidelines for the management of toxic epidermal necrolysis and Stevens–Johnson syndrome." International journal of dermatology 46.10 (2007): 1092-1094.

Arévalo, José M., et al. "Treatment of toxic epidermal necrolysis with cyclosporin A." Journal of Trauma and Acute Care Surgery 48.3 (2000): 473-478.

Schneck, Jürgen, et al. "Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study." Journal of the American Academy of Dermatology 58.1 (2008): 33-40.

Barron, Stacy J., Michael T. Del Vecchio, and Stephen C. Aronoff. "Intravenous immunoglobulin in the treatment of S tevensJ ohnson syndrome and toxic epidermal necrolysis: a meta‐analysis with meta‐regression of observational studies." International journal of dermatology 54.1 (2015): 108-115.

Schneider, Jeremy A., and Philip R. Cohen. "Stevens-Johnson syndrome and toxic epidermal necrolysis: a concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures." Advances in Therapy34.6 (2017): 1235-1244.

Han, Feng, et al. "Successful treatment of toxic epidermal necrolysis using plasmapheresis: A prospective observational study." Journal of critical care 42 (2017): 65-68.

Paquet, Philippe, et al. "Effect of N-acetylcysteine combined with infliximab on toxic epidermal necrolysis. A proof-of-concept study." Burns 40.8 (2014): 1707-1712.

Hunger, Robert E., et al. "Rapid resolution of toxic epidermal necrolysis with anti-TNF-α treatment." Journal of allergy and clinical immunology 116.4 (2005): 923-924.

Wolkenstein, Pierre, et al. "Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis." The Lancet 352.9140 (1998): 1586-1589.

Creamer, D., et al. "UK guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults 2016." British Journal of Dermatology 174.6 (2016): 1194-1227.