Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN)
Clinical Snapshot
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are not 2 separate diseases. They are one severe, drug-induced mucocutaneous reaction — a form of epidermal necrolysis driven by widespread, cytotoxic T-cell and natural-killer-cell-mediated keratinocyte death — that differs from case to case only in how much body-surface area (BSA) the epidermis sloughs from. Both share the same high-risk culprit drugs, the same prodrome and mucosal findings, and the same management approach, which is why this chapter treats them as one condition classified by severity rather than as 2 unrelated entries.[1]
Classification by body-surface-area detachment
| Classification | Epidermal detachment |
|---|---|
| Stevens-Johnson syndrome (SJS) | Under 10% of body surface area |
| SJS/TEN overlap | 10% to 30% of body surface area |
| Toxic epidermal necrolysis (TEN) | Over 30% of body surface area |
Classify using the maximum detachment reached at any point during the illness, not only the detachment present at the first assessment — SJS can and often does progress to overlap or TEN over the following days. This is exactly why early recognition, immediate causative-drug withdrawal, and early transfer to a unit capable of burn-level care matter so much.[2]
This is rare but genuinely life-threatening. A drug cause is identified in most adult cases; in children, infection — particularly Mycoplasma pneumoniae — accounts for a larger share (see Special Populations). Mortality rises sharply with the amount of skin involved and is estimated using the SCORTEN severity score (see Assessment and Diagnosis). The single most important intervention in this entire chapter is immediate identification and withdrawal of the causative drug — every other intervention is supportive or adjunctive.[3]
Recognize the Condition
Prodrome
A nonspecific prodrome of fever, malaise, sore throat, cough, and conjunctival burning or itching typically precedes skin findings by 1 to 3 days, occasionally longer. This is easy to mistake for a routine viral illness, and the diagnosis is often missed at this stage — which matters, because the causative drug is usually still being taken during it.
Cutaneous findings
- Ill-defined, dusky-red or purpuric macules and atypical (flat, 2-zone) target-like lesions, often starting on the trunk and face and spreading, sometimes rapidly, over hours to days.
- Lesions coalesce and progress to flaccid blisters and sheet-like epidermal detachment, exposing a raw, red, weeping dermis that resembles a partial-thickness burn.
- Positive Nikolsky sign — gentle lateral pressure or rubbing on erythematous (but not yet blistered) skin causes the epidermis to shear off. A positive Nikolsky sign strongly supports the diagnosis, but its absence does not rule it out.
- Skin pain, often described as burning, that is out of proportion to how the skin looks early on — pain disproportionate to visible findings is itself a warning sign, not a reassurance.
Mucosal findings
Mucosal involvement — painful erosions, blistering, and crusting — affects 2 or more mucosal surfaces in most cases, and is one of the features that most reliably distinguishes SJS/TEN from a routine morbilliform drug rash:
- Oral/oropharyngeal — painful erosions of the lips, buccal mucosa, and oropharynx; hemorrhagic crusting of the lips is a classic finding.
- Ocular — conjunctival injection, photophobia, pain, discharge, and erosions. This is the mucosal site with the greatest risk of severe, permanent long-term sequelae if not managed correctly from day 1 (see Non-Pharmacologic Treatment and Monitoring).
- Genital/urogenital — erosions of the genital mucosa are common and frequently under-examined; ask about and examine this site specifically rather than relying on the patient to raise it.
Risk Factors
Drugs — the dominant cause in adults
High-risk drug classes — covered with full cross-reactivity and avoidance guidance in Drug Tables — include the aromatic anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, phenobarbital), lamotrigine, allopurinol, sulfonamide antibiotics (particularly sulfamethoxazole-trimethoprim), oxicam-class NSAIDs (piroxicam, meloxicam), nevirapine, and sulfasalazine.[4]
Timing
For a first exposure to a new drug, onset is classically 4 to 28 days after starting it, most often within the first several weeks. On re-exposure to a drug that previously caused a reaction, onset can be far more rapid — sometimes within 48 hours. This timing window is central to identifying which of several recently started drugs is the likely culprit (see Assessment and Diagnosis, and the ALDEN causality method).[5]
Genetic risk (HLA) — real, actionable pharmacogenomics
- HLA-B*15:02 and carbamazepine or oxcarbazepine — strongly associated with SJS/TEN specifically (not milder rashes) in patients of Han Chinese and broader Southeast Asian ancestry, where the allele is comparatively common. Current pharmacogenomic guidance recommends genotyping before starting either drug in a patient from a population where this allele is common, and avoiding both drugs if the patient tests positive and a suitable alternative exists.[6]
- HLA-B*58:01 and allopurinol — associated with allopurinol-induced SJS/TEN, again with a markedly higher allele frequency in Han Chinese, Thai, and Korean populations; risk is compounded by higher allopurinol starting doses and renal impairment.[1]
Other risk factors
- HIV infection increases the risk of SJS/TEN markedly, with the sharpest increase seen for sulfonamide antibiotics and nevirapine.
- Active malignancy, and radiotherapy given around the same time as an anticonvulsant.
- Active or recent infection — in children specifically, Mycoplasma pneumoniae can trigger a related but distinct entity, MIRM (Mycoplasma-induced rash and mucositis), with different management emphasis and a better prognosis than drug-induced disease (see Special Populations).
- A personal history of SJS/TEN — re-exposure to the same or a cross-reactive drug carries a high risk of a faster, often more severe recurrence.
- Connective tissue disease (e.g., systemic lupus erythematosus) has been proposed as a contributing factor in some patients.
Red Flags & Refer
Any patient with suspected SJS/TEN needs emergency-level escalation. There is no outpatient management pathway for this condition.
- Skin pain out of proportion to findings, a positive Nikolsky sign, blistering, or sheet-like skin detachment in a patient on a new or recently changed drug — treat as suspected SJS/TEN until proven otherwise and escalate immediately. Do not wait for dermatology or biopsy confirmation before stopping the suspected drug.
- Involvement of 2 or more mucosal sites (oral, ocular, genital), even with limited skin findings — this pattern alone should trigger urgent same-day assessment.
- Any BSA involvement approaching or reaching 10% — transfer to a burn unit or a specialized dermatology/ICU unit with burn-level wound-care capability. Delay in transfer is associated with worse outcomes.[2]
- Systemic instability — fever, tachycardia, hypotension, or signs of evolving sepsis — needs immediate resuscitation in parallel with dermatologic management.
- Any eye involvement needs same-day ophthalmology consultation, regardless of how mild it looks. Early, aggressive ocular care changes long-term outcomes and cannot be safely deferred.
Assessment & Diagnosis
A clinical diagnosis, supported by biopsy
Diagnosis is made on the clinical picture described above — prodrome, characteristic skin lesions, a positive Nikolsky sign, and mucosal involvement. Skin biopsy (with a portion sent for urgent frozen section where available) supports the diagnosis, typically showing full-thickness epidermal necrosis with minimal dermal inflammation, and helps exclude mimics — but do not wait for biopsy results before stopping the suspected causative drug.
Estimating body-surface-area detachment
Use the rule-of-nines, as in burn assessment, or the palm method — the patient's own palm and fingers, not the examiner's, represents approximately 1% BSA — to estimate the percentage of detached and detachable (Nikolsky-positive) skin. Reassess BSA at least daily during the acute phase, since detachment typically continues to progress for several days even after the causative drug is stopped.
Distinguishing SJS/TEN from its mimics
| Feature | SJS/TEN | Erythema multiforme majus | Staphylococcal scalded skin syndrome |
|---|---|---|---|
| Typical trigger | Drug (adults); Mycoplasma or drug (children) | Infection, most often HSV | Staphylococcal exotoxin — no drug or HSV link |
| Lesion type | Dusky macules or atypical flat targets, coalescing | Classic raised, 3-zone target lesions, acral-predominant | Diffuse tender erythema with superficial peeling |
| Mucosal involvement | Usually 2 or more sites, prominent | Absent or limited to 1 site | Absent — a key distinguishing feature |
| Level of skin split on biopsy | Full-thickness, subepidermal | Full-thickness, subepidermal | Superficial, within the epidermis, below the stratum granulosum |
| Typical population | Any age; adults predominate | Younger adults | Infants and young children; rare in adults with normal renal function |
SCORTEN severity and mortality-prediction score
SCORTEN is calculated from 7 variables, each scored 1 point if present, assessed within the first 24 hours of admission and ideally recalculated on day 3, when it becomes more accurate. Use it to guide the level of care and to set realistic expectations with the patient and family — not as a gate for whether supportive care is offered.[3]
| Criterion | 1 point if |
|---|---|
| Age | Over 40 years |
| Heart rate | Over 120 beats per minute |
| Associated malignancy | Active cancer or hematologic malignancy |
| Body surface area detached (day 1) | Over 10% |
| Serum urea (BUN) | Over 10 mmol/L |
| Serum bicarbonate | Under 20 mmol/L |
| Serum glucose | Over 14 mmol/L |
| SCORTEN total | Predicted mortality |
|---|---|
| 0-1 | Approximately 3% |
| 2 | Approximately 12% |
| 3 | Approximately 35% |
| 4 | Approximately 58% |
| 5 or more | Approximately 90% |
Causality assessment — the pharmacist's central role
There is no laboratory test that confirms which drug caused an episode of SJS/TEN. Causality is assessed through structured clinical reasoning, and a pharmacist is often best positioned to do this well: build a complete, dated timeline of every prescription, over-the-counter product, herbal or natural health product, and recently restarted drug in the weeks before onset, including exact start dates. A structured algorithm such as ALDEN (Algorithm of Drug Causality for Epidermal Necrolysis) formalizes this using time-to-onset, whether the drug was still being taken at onset, response to withdrawal, prior reaction history, and how strongly that drug is already known to cause SJS/TEN — and performs meaningfully better than unstructured clinical judgment alone.[5]
Treatment Targets
- Identify and immediately withdraw every drug that cannot be excluded as the cause — the single highest-yield intervention, and the only one with a clear, consistent mortality benefit.
- Prevent progression and further epidermal detachment through burn-level supportive and wound care.
- Prevent and promptly treat secondary infection and sepsis, the leading cause of death in TEN.
- Maintain fluid, electrolyte, thermal, and nutritional balance during the acute hypermetabolic phase.
- Prevent long-term mucosal and ocular sequelae through early, aggressive site-specific care.
- Control pain, which is often severe and persistent.
- Establish a confirmed causality assessment and a durable, documented future-avoidance plan before discharge.
Choose Initial Treatment
Stop every drug that cannot be excluded as the cause, immediately, without waiting for biopsy or specialist confirmation. Do not wait to see whether the reaction settles on the current drug — continued exposure worsens outcomes, and earlier withdrawal of a causative drug with a short half-life is associated with improved survival.[2]
Transfer any patient with, or trending toward, 10% or more BSA involvement to a burn unit or a specialized dermatology/ICU unit capable of burn-level wound care. Involve ophthalmology on day 1 for any ocular involvement, however mild.
There is no single, universally agreed-upon systemic immunomodulating drug for SJS/TEN (see Pharmacologic Treatment Options). Supportive care is the only intervention with consistent evidence behind it and is not optional or secondary to a specific adjunctive-drug choice.[1]
Non-Pharmacologic Treatment
Wound care
Manage detached and denuded skin as a partial-thickness burn: a warm, temperature-controlled environment (thermoregulation is impaired once a large surface area is denuded), minimal unnecessary handling, and nonadherent dressings. Current guidance favours a conservative approach to the necrotic epidermis itself — leaving it in place as a biologic dressing over the wound rather than aggressive surgical debridement, since it appears to protect the underlying dermis and reduce infection risk. This differs from traditional burn-unit teaching for thermal burns and should be discussed explicitly with the unit managing the patient.[2]
Fluid and nutrition
Patients need aggressive fluid resuscitation and nutritional support, but fluid requirements in SJS/TEN are generally lower than for a thermal burn of the same body-surface area, because dermal capillary leak is less severe — applying standard burn-resuscitation formulas unmodified can lead to over-resuscitation. Start enteral nutrition early; the hypermetabolic state and substantial protein loss through denuded skin make adequate caloric and protein intake important for wound healing.[2]
Mucosal and site-specific care
Ocular
Daily ophthalmology assessment from day 1, lubrication, and lysis of early conjunctival adhesions to prevent symblepharon formation. Amniotic membrane transplantation is used at some centres for severe ocular involvement, though the evidence base and criteria for its use continue to evolve.
Oral
Frequent gentle mouth care and topical anesthetic/antiseptic rinses to keep the mouth clean enough to allow oral intake and reduce infection risk.
Genital/urogenital
Regular examination and site-specific care to prevent labial or preputial adhesions and urethral stricture. This site is easy to overlook and needs deliberate attention.
Infection prevention
Do not give prophylactic systemic antibiotics in the absence of documented infection — this does not reduce infection risk and contributes to resistance and adverse effects. Instead, monitor closely (see Monitoring and Follow-Up) and treat promptly and specifically once infection is actually identified.[2]
Line and catheter minimization
Minimize invasive lines, catheters, and adhesive tape on compromised skin wherever possible — each is a potential entry point for infection and a source of further mechanical skin trauma.
Special Populations
Genetic counselling for blood relatives
Because HLA-B*15:02 and HLA-B*58:01 are inherited, a confirmed or strongly suspected HLA-linked reaction has implications beyond the patient in front of you: first-degree relatives of the same ancestry share a meaningfully elevated chance of carrying the same allele. Counsel the patient to inform blood relatives of the reaction and the specific drug involved, so this can be discussed with their own prescriber and factored into HLA testing decisions before that relative is ever started on the same drug — a genuine, practical extension of allergy counselling, not routine genetic-counselling overreach.
Monitoring & Follow-Up
Arrange structured multidisciplinary follow-up after discharge — dermatology, ophthalmology, and, where genital or urethral scarring occurred, gynecology or urology — and monitor for longer-term skin, nail, and pigmentary changes. Before discharge, confirm the causality assessment was actually completed and that the resulting allergy documentation was communicated to the patient, their family physician, and their community pharmacy record, not only recorded in the hospital chart.
Common Errors to Avoid
- Waiting for biopsy or specialist confirmation before stopping the suspected causative drug — every day of continued exposure worsens the prognosis.
- Stopping only the "most obvious" recently started drug while continuing others that cannot actually be excluded.
- Substituting one aromatic anticonvulsant for another (for example, carbamazepine to phenytoin) without accounting for real cross-reactivity risk within this drug group.
- Giving prophylactic systemic antibiotics without a documented infection.
- Aggressive surgical debridement of intact-but-detached epidermis rather than managing it as a biologic dressing.
- Underestimating severity because skin findings look mild while significant mucosal, especially ocular, involvement is present.
- Deferring ophthalmology consultation because eye symptoms seem minor at first assessment.
- Vague allergy documentation ("rash with antibiotic") instead of the specific drug, reaction, date, and severity — this actively endangers the patient at the next prescribing decision.
- Failing to counsel the patient, and blood relatives where an HLA-linked drug is involved, on the specific drug and drug-class avoidance needed going forward.
Clinical Decision Algorithm
Drug Tables
How to use this table: doses are adult doses and require patient-specific confirmation. Select any drug name to open its complete Pharmasist Drug Database page.
High-risk culprit drug classes
| Drug | Risk / genetic-ancestry note | Cross-reactivity and avoidance guidance | Comments |
|---|---|---|---|
| Allopurinol | One of the leading culprit drugs overall, and the leading culprit in some regions. HLA-B*58:01 carriage substantially raises risk, particularly in patients of Han Chinese, Thai, or Korean ancestry. | No structurally close alternative is typically needed after a confirmed reaction — febuxostat is a mechanistically different urate-lowering option, though it should still be introduced cautiously and discussed with the prescriber given case reports of hypersensitivity. | Risk is compounded by higher starting doses and renal impairment — starting at a lower, renally adjusted dose is a genuine prevention strategy independent of HLA status. |
| Carbamazepine | A leading culprit drug. HLA-B*15:02 carriage substantially raises risk in patients of Han Chinese and broader Southeast Asian ancestry. | Significant cross-reactivity risk within the aromatic-anticonvulsant group (carbamazepine, oxcarbazepine, phenytoin, phenobarbital) — do not switch to another member of this group after a reaction. | Genotype for HLA-B*15:02 before starting in a patient from a population where the allele is common, where testing is accessible. |
| Oxcarbazepine | Shares the HLA-B*15:02 association with carbamazepine, though the absolute risk is somewhat lower. | Same aromatic-anticonvulsant cross-reactivity group as carbamazepine, phenytoin, and phenobarbital — avoid switching within this group after a reaction. | The same HLA-B*15:02 genotyping guidance applied to carbamazepine applies here. |
| Phenytoin | A leading culprit among the aromatic anticonvulsants, particularly at reaction onset within the first 2 months of therapy. | Same aromatic-anticonvulsant cross-reactivity group as carbamazepine, oxcarbazepine, and phenobarbital — avoid switching within this group after a reaction. | Fosphenytoin, its prodrug, carries the same risk and should be avoided under the same circumstances. |
| Phenobarbital | A well-established culprit among the aromatic anticonvulsants. | Same aromatic-anticonvulsant cross-reactivity group as carbamazepine, oxcarbazepine, and phenytoin — avoid switching within this group after a reaction. | Still used for seizure control in some settings and in neonates — the same avoidance principle applies regardless of indication. |
| Lamotrigine | A leading culprit drug, with risk clearly increased by rapid dose escalation and by combination with valproate (which slows lamotrigine clearance). | Not part of the aromatic-anticonvulsant cross-reactivity group structurally, but avoid re-exposure after a confirmed reaction regardless. | Slow, product-monograph-directed titration is the primary prevention strategy — this is a genuine, modifiable risk factor, not just a dosing formality. |
| Sulfamethoxazole/trimethoprim | One of the leading culprit drugs, with markedly higher risk in HIV-positive patients. | Avoid other sulfonamide antibiotics after a reaction. True cross-reactivity with non-antibacterial sulfonamide-containing drugs (e.g., sulfonylureas, thiazide diuretics, celecoxib) is much lower than historically assumed and remains debated — do not automatically withhold an unrelated sulfonamide-containing drug class without an individualized risk discussion. | Trimethoprim alone is a distinct, much lower-risk exposure and is not equivalent to the combination product for avoidance purposes. |
| Piroxicam | The oxicam NSAID subclass carries higher SJS/TEN risk than other NSAID subclasses. | Avoid the entire oxicam class (piroxicam, meloxicam) after a reaction. Other NSAID subclasses are not established as cross-reactive but should be introduced cautiously and discussed individually. | Risk with NSAIDs overall is concentrated in the first few weeks of use. |
| Meloxicam | Same oxicam-subclass risk as piroxicam. | Avoid the entire oxicam class after a reaction, for the same reason as piroxicam. | One of the most widely prescribed oxicams, which makes deliberate avoidance counselling after a reaction particularly important. |
| Nevirapine | A leading culprit among antiretrovirals, with markedly higher baseline risk in HIV-positive patients generally. | Avoid re-exposure to nevirapine specifically after a reaction; discuss any future antiretroviral regimen change with the treating HIV specialist rather than assuming another agent in the same drug class is equally safe. | Document clearly given how frequently antiretroviral regimens change over the course of treatment. |
| Sulfasalazine | A recognized culprit drug, used in inflammatory bowel disease and rheumatoid arthritis. | Contains a sulfonamide moiety — treat similarly to other sulfonamide-containing drugs for avoidance purposes. | Document clearly for future disease-modifying antirheumatic drug (DMARD) or IBD-therapy selection. |
Evidence note: culprit-drug risk data reflect the RegiSCAR/EuroSCAR case-control medication-risk literature.[4] HLA-genotyping guidance reflects the current Clinical Pharmacogenetics Implementation Consortium recommendation.[6]
Adjunctive immunomodulating therapies — formulation detail
None of these has unambiguous, consensus-level evidence of benefit (see Pharmacologic Treatment Options); use is a specialized-team, case-by-case decision.
| Drug | Reported dosing | Adverse effects | Comments |
|---|---|---|---|
| Immunoglobulin (human), IV Privigen, generics | Commonly cited total 2 to 4 g/kg IV over 3 to 4 days; not a standardized regimen. | Renal impairment, thrombosis, aseptic meningitis, anaphylactoid reactions especially with IgA deficiency. | Screen for IgA deficiency where feasible before use; evidence for mortality benefit is inconsistent across studies. |
| Cyclosporine Neoral, Sandimmune, generics | Commonly cited approximately 3 to 5 mg/kg/day, oral or IV, for a limited course. | Nephrotoxicity, hypertension, increased infection risk, electrolyte disturbance. | Monitor renal function and blood pressure closely during use; growing observational support for a survival benefit, but randomized-trial evidence is still lacking. |
| Dexamethasone Generics | Regimens vary; short pulse dosing early in the course is discussed more often in recent literature than prolonged tapering. | Infection risk, delayed wound healing, hyperglycemia, GI bleeding, adrenal suppression with prolonged use. | Historically controversial due to concern about prolonged corticosteroid use worsening outcomes — discuss short-course use specifically with the specialized team rather than defaulting to a prolonged taper. |
| Methylprednisolone sodium succinate Solu-Medrol, generics | An alternative IV corticosteroid where used; regimens vary by centre. | Same corticosteroid-class risks as dexamethasone. | Used interchangeably with dexamethasone at some centres for pulse dosing; the controversy and evidence gaps described above apply equally. |
| Etanercept Enbrel, generics | Studied at 25 or 50 mg subcutaneously as a single or repeated dose in small trials — not a standardized regimen. | Infection risk, injection-site reaction. | Based on limited randomized-trial data suggesting improved healing time and possibly survival compared with corticosteroids; not yet widely adopted as standard care. |
References
- Update on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Diagnosis and Management — American Journal of Clinical Dermatology (Shah H, Parisi R, Mukherjee E, Phillips EJ, Dodiuk-Gad RP). Am J Clin Dermatol 2024;25(6):891-908
- Society of Dermatology Hospitalists Supportive Care Guidelines for the Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in Adults — Journal of the American Academy of Dermatology (Seminario-Vidal L, Kroshinsky D, Malachowski SJ, et al.; Society of Dermatology Hospitalists SJS/TEN Guidelines Group). J Am Acad Dermatol 2020;82(6):1553-1567
- SCORTEN: A Severity-of-Illness Score for Toxic Epidermal Necrolysis — Journal of Investigative Dermatology (Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P). J Invest Dermatol 2000;115(2):149-153
- Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Assessment of Medication Risks with Emphasis on Recently Marketed Drugs. The EuroSCAR-Study — Journal of Investigative Dermatology (Mockenhaupt M, Viboud C, Dunant A, et al.). J Invest Dermatol 2008;128(1):35-44
- ALDEN, an Algorithm for Assessment of Drug Causality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Comparison With Case-Control Analysis — Clinical Pharmacology & Therapeutics (Sassolas B, Haddad C, Mockenhaupt M, et al.). Clin Pharmacol Ther 2010;88(1):60-68
- Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update — Clinical Pharmacology & Therapeutics (Phillips EJ, Sukasem C, Whirl-Carrillo M, et al.). Clin Pharmacol Ther 2018;103(4):574-581
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.