Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An Analysis of Triggers and Implications for Improving Prevention

Am J Med. 2016 Nov;129(11):1221-1225. doi: 10.1016/j.amjmed.2016.03.022. Epub 2016 Apr 15.

Abstract

Background: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe mucocutaneous adverse drug reactions characterized by extensive epidermal detachment. The mortality rates have been reported to vary between 1% and 5% for Stevens-Johnson syndrome and 25% and 35% for patients with toxic epidermal necrolysis. Studies have shown that early recognition and prompt withdrawal of the causative agent leads to increased patient survival.

Methods: A retrospective chart review was conducted on 64 patients admitted to Vancouver General Hospital with a diagnosis of Stevens-Johnson syndrome or toxic epidermal necrolysis from 2001 to 2011. The aim of this study was to identify the medications most often implicated in triggering Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as to delineate the timeline of identification and removal of these triggers.

Results: A trigger was identified in 75% of cases. Allopurinol was the single most common offending agent (20% of cases). Anticonvulsants and antibiotics were common triggers. The offending agent was often removed at time of hospital admission/diagnosis but not at onset of symptoms. A history of prior culprit drug exposure with previous mucocutaneous adverse reaction was noted in 19% of cases with identified triggers. Asians and Native North Americans had a higher mortality than whites, and Asians more frequently had allopurinol as a trigger.

Conclusions: The onset and high mortality rate of Stevens-Johnson syndrome/toxic epidermal necrolysis may be related to unawareness of the early signs and symptoms of Stevens-Johnson syndrome and toxic epidermal necrolysis, the common drug triggers that cause it, and what investigations (human leukocyte antigen typing in Asians) can be done to prevent it.

Keywords: Allopurinol; Drug reactions; HLA testing; Phenytoin; Stevens-Johnson syndrome; Sulfamethoxazole-trimethoprim; Toxic epidermal necrolysis.

MeSH terms

  • Adult
  • Aged
  • Allopurinol / adverse effects*
  • Anti-Bacterial Agents / adverse effects*
  • Anticonvulsants / adverse effects*
  • Asians / statistics & numerical data
  • British Columbia
  • Female
  • Gout Suppressants / adverse effects*
  • HLA Antigens / genetics
  • Humans
  • Indians, North American / statistics & numerical data
  • Male
  • Middle Aged
  • Retrospective Studies
  • Stevens-Johnson Syndrome / etiology*
  • Stevens-Johnson Syndrome / genetics
  • Stevens-Johnson Syndrome / mortality
  • Stevens-Johnson Syndrome / prevention & control
  • Whites / statistics & numerical data

Substances

  • Anti-Bacterial Agents
  • Anticonvulsants
  • Gout Suppressants
  • HLA Antigens
  • Allopurinol