This article series addresses high risk and low prevalence diseases that are encountered in the emergency department (ED). Much of the primary literature evaluating these conditions is not emergency medicine focused. By their very nature, many of these disease states and clinical presentations have little useful evidence available to guide the emergency physician in diagnosis and management. The format of each article defines the disease or clinical presentation to be reviewed, provides an overview of the extent of what we currently understand, and finally discusses pearls and pitfalls using a question-and-answer format. This article will discuss Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These conditions' low prevalence but high morbidity and mortality, as well as the variable atypical patient presentations and challenging diagnosis, make them a high risk and low prevalence disease.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) comprise a continuum of a delayed hypersensitivity reaction affecting the skin and mucous membranes and is associated with a high risk of morbidity and mortality [[1], [2], [3]]. After an exposure to a causative agent, such as medications or pathogens, a viral-like prodrome progresses into the development of an erythematous, then blistering, and ultimately desquamating rash which can involve the skin; eyes; and mucosa of the mouth, pharynx, gastrointestinal (GI) tract, respiratory tract, and genitals [2,3]. SJS and TEN are distinguished by the total body surface area (TBSA) of skin involved. The former is defined by a TBSA of <10% while the latter is defined by a TBSA of >30%. TBSA involvement between 10 and 30% is designated as SJS/TEN overlap [2,3].

SJS/TEN is rare. A study of inpatient records from 2009 to 2012 in the United States demonstrated an incidence of 9.2 per million adults per year for SJS, 1.6 per million adults per year for SJS/TEN overlap, and 1.9 per million adults per year for TEN; in children, the incidences are 5.3, 0.8, and 0.4 per million, respectively [4,5].

Risk factors for the development of SJS/TEN include certain human leukocyte antigen (HLA) haplotypes; variations in cytochrome p450 metabolism; a history of allergies to medications; and past medical history of human immunodeficiency virus (HIV) infection regardless of treatment status, systemic lupus erythematosus (SLE), connective tissue disorders, psoriasis, epilepsy, malignancy, cerebrovascular accident, and diabetes mellitus [[6], [7], [8]].

SJS/TEN carries a high risk of morbidity and mortality. The mortality rate of SJS is estimated to be 1–5% while the mortality rate of TEN is estimated to be 15–50% [6,[9], [10], [11], [12]]. Another study estimated the mortality of the SJS/TEN continuum at 23% at 6 weeks and 34% at one year [10]. Data suggest the mortality rate for pediatric patients with SJS, SJS/TEN overlap, and TEN is 0%, 4%, and 16%, respectively [5].

SJS/TEN is a delayed hypersensitivity reaction evoked by exposure to certain medications and, less commonly, to pathogens. There are a significant number of medications including allopurinol, anticonvulsants, antimicrobials, phenobarbital, and certain nonsteroidal anti-inflammatory drugs, as well as pathogens such as Mycoplasma pneumoniae and Herpes simplex virus (HSV), that are associated with SJS/TEN [2,8]. Although the microbiological intricacies of the disease process are yet to be fully elucidated, it is suspected that cytotoxic CD8+ T lymphocytes and natural killer cells specific to the causative medication or infection release cytokines and chemokines which recruit other immune cells including neutrophils, monocytes, and eosinophils into the skin and mucosa, resulting in cellular necrosis [3,[13], [14], [15]]. With cessation of exposure to the instigating agent and meticulous supportive care, the affected areas will re-epithelialize [16].