Stevens-Johnson syndrome and TEN

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe cutaneous reactions on a continuum, with painful blistering and shedding of the skin and mucous membranes. Sulfa antibiotics are among the recognised triggers, alongside antiepileptics, allopurinol, NSAIDs, and others. Mortality is significant, particularly in TEN.

What they are

SJS and TEN are immune-mediated reactions in which T cells direct cytotoxic injury to keratinocytes — the skin and mucosal cells. The cells die in sheets; the upper layer of the skin lifts and shears off. The reaction also affects mucous membranes — mouth, eyes, urogenital — and these are usually involved early, sometimes before the obvious skin signs.

The two are best thought of as one disease at different severities, distinguished by the body surface area of skin detachment. SJS involves less than 10% of body surface area. TEN involves more than 30%. Cases between are called SJS/TEN overlap. Severity guides treatment intensity; the underlying mechanism is the same.

How it presents

The illness usually begins with a flu-like prodrome — fever, malaise, sore throat, sore eyes, sometimes joint pain — for one to three days before skin findings. Then, painful, dusky red or purple spots appear on the trunk and face, sometimes with target-like centres. The areas spread, become darker, and within hours to days the surface skin starts to lift, leaving raw, painful areas. The skin pain is characteristic — far beyond what a typical drug rash produces.

Mucous membranes are involved in the great majority of cases. Painful sores in the mouth make eating and drinking difficult. Eye involvement — conjunctivitis, painful red eyes, sometimes corneal damage — is common and can have lasting consequences. Genital and urinary tract mucosal involvement is also common.

The Nikolsky sign — gentle pressure on apparently intact skin causes the surface layer to slide off — is a clinical bedside finding consistent with SJS/TEN.

Drugs implicated

SJS/TEN can follow many drugs. The most often reported include sulfa antibiotics (notably sulfamethoxazole/trimethoprim), antiepileptics (carbamazepine, lamotrigine, phenytoin, phenobarbital), allopurinol, oxicam NSAIDs, nevirapine, and many others. The reaction is rare for any individual drug; the absolute number of cases mostly reflects how often the drug is used.

Onset is typically within four weeks of starting the offending drug. A previous tolerated course does not always protect — sensitisation can occur over time. A documented past SJS/TEN to a particular drug is a contraindication to re-exposure.

Genetic susceptibility

Specific HLA alleles have been associated with SJS/TEN risk for certain drugs, most notably HLA-B*15:02 with carbamazepine in some Asian populations and HLA-B*57:01 with abacavir hypersensitivity. For sulfa antibiotics, genetic susceptibility patterns have been reported in research settings but are not as clinically established as for the examples above. The general lesson — that severe cutaneous adverse reactions have a meaningful pharmacogenetic component — applies broadly.

Management

Management is hospital-based and multidisciplinary. The first step is stopping the offending drug and any non-essential medications. Patients are managed in burn units or specialised wards because the skin loss is physiologically similar to a severe burn — fluid loss, infection risk, temperature regulation, nutritional support. Eye care is critical to prevent long-term ocular damage. The role of specific therapies (intravenous immunoglobulin, ciclosporin, corticosteroids, TNF inhibitors) has been debated and varies by centre and case.

This site does not describe specific treatment regimens — they are specialist decisions made in tertiary care.

After SJS/TEN

Survivors face a long recovery and the possibility of long-term complications: chronic eye problems (dry eye, scarring, vision loss), skin pigmentation changes, nail loss, and psychological consequences. The risk of recurrence on the offending drug is high; lifelong avoidance of the implicated drug is essential. Avoidance often extends to closely related drugs as a precaution, though the evidence for cross-class avoidance varies.

For sulfa antibiotic-induced SJS/TEN, lifelong avoidance of sulfa antibiotics is the rule. Use of non-antibiotic sulfonamides (furosemide, HCTZ, celecoxib, sulfonylureas, acetazolamide) in such patients is approached cautiously and individually, balancing the structural argument (low cross-reactivity in published cohorts) against the severity of the past event. Specialist input is usual.

If you have had SJS or TEN, this is a permanent flag. Make sure it is recorded clearly in your medical records. Carry the information with you. Medical ID and bracelets covers wearable allergy alerts.

Mortality

Mortality varies by series and supportive care. SJS — the milder end of the spectrum — has reported mortality around 5–10% in published cohorts. TEN — with extensive skin involvement — has substantially higher mortality, often cited around 25–35% in older series, though specialised burn-unit care has improved outcomes in many centres. The SCORTEN clinical scoring system is used to estimate mortality at admission based on age, comorbidities, body surface area involved, and laboratory parameters.

What this means in everyday prescribing

SJS/TEN is rare. The probability that any individual rash on a sulfa antibiotic is the start of SJS/TEN is low. The reason it gets disproportionate attention is the severity. The practical clinical signal is a small set of red-flag features — skin pain, blistering, mucosal involvement, fever — that should prompt rapid drug discontinuation and assessment. Mild vs severe reactions covers these features in more detail.

Stevens-Johnson syndrome and TEN.