A 65 y/o female presents to the ED with sudden onset of severe skin tenderness, sparing her scalp. Her PMH is significant for epilepsy. Her labs and vital signs were WNL except for a fever of 102 F and a slight leukopenia. She was controlled on phenytoin but developed a rash on this and was switched to carbamazepine. On PE, her skin was very tender (i.e. couldn’t tolerate light touch), blistered, and erythematous. Raw surfaces exuded serum and she had flaccid bullae on her torso. The patient shows a positive Nikolsky sign.

What is likely her problem? What can you do?

*** THANKS to MAJ (Dr.) Darryl Hodson for his help with this Pearl. **

This patient has toxic epidermal necrolysis (TEN), also known as Lyell’s syndrome. TEN is the most severe cutaneous drug reaction. TEN is rare (1-2:1,000,000) but carries a 30% mortality rate. FYI – a positive Nikolsky sign is when the outer layer of the epidermis separates from the basal layer with gentle pressure.

TEN is more common in older patients. Females are more commonly diagnosed than males (2:1). Although TEN can be caused by graft-vs-host disease (GVHD), immunizations, and various viral infections, the majority of cases are caused by medications. Anticonvulsant agents and NSAIDs are frequently implicated. Lamotrigine (Lamictal®) actually carries a black box warning for TEN. Sulfonamides (TMP/SMX), and ampicillin are the more common antibiotic causes.  Allopurinol is another common cause.

The risk of TEN from aromatic anticonvulsants is highest during the first 8 weeks of treatment.  A reaction to one aromatic anticonvulsant makes a reaction to another more likely. Valproic acid and gabapentin (non-aromatic agents) may be alternatives but valproic acid should NOT be used if Lamictal® is the suspected culprit since it inhibits the hepatic metabolism of the drug, increases the half-life of Lamictal®, and prolongs the patient’s exposure to this medication.

Treatment - Burn center management is the standard of care in addition to removing the offending agent(s). Burn center management appears to decrease morbidity and mortality. Sepsis is the leading cause of death in these patients. Treatment is supportive with other therapies being controversial. Systemic steroids have NOT been show to improve prognosis and are contraindicated once significant desquamation has occurred since they may increase the risk for sepsis. Plasmapheresis and IV immunoglobulin (IVIG) have shown promise but need well-controlled studies to evaluate their efficacy.

If you have a patient with suspected TEN, please notify/contact the pharmacy.  Inform pharmacy of the suspected medication and all other medications the patient is currently on or that you plan to prescribe. Pharmacy will assist to ensure none of the patient’s other medications will increase the half-life of the offending agent.

REFERENCES:

- Elston DM. Toxic epidermal necrolysis. The Clincial Advisor. 2004:7;102-4.
- Harrisons Textboobk of Internal Medicine. 15th ed. 339-340.
- Razny B, et al. Lancet 1999;353:2190-4.
- Razny B, et al. Acta Derm Venerol 1991;72:171-2.