01OverviewDefinition, clinical context and the essential points that orientate the chapter.
SJS and TEN form a spectrum of immune-mediated keratinocyte death, usually medicine triggered. A flu-like prodrome may precede painful dusky macules, atypical flat targets and blistering. Epidermis shears with gentle lateral pressure and mucosal epithelium erodes, often at several sites. Classification uses the maximum detached or detachable body surface, not total erythematous rash. The deeper colour change can be subtle in richly pigmented skin, so pain, texture, mucosal examination and serial mapping are essential. Erythema multiforme usually has raised classic acral targets with limited detachment and is often infection associated, but diagnostic uncertainty with mucosal loss still warrants urgent review.
DRESS and AGEP are different severe reactions. DRESS has a longer latency and systemic footprint: facial oedema, fever, diffuse infiltration, nodes, eosinophilia or atypical lymphocytes and hepatitis predominate, but nephritis, pneumonitis, myocarditis, thyroiditis and other injury can emerge or relapse after drug withdrawal. AGEP develops more rapidly, particularly after antimicrobials, with pinhead sterile pustules, flexural accentuation, neutrophilia and relatively rapid resolution. Overlap exists; labels are assigned through drug chronology, clinical criteria, serial organ tests and histopathology rather than a single blood count.
Extensive epidermal loss resembles a superficial burn but has lower fluid requirements than a thermal injury and uniquely threatens every mucosal surface. English specialised-service standards place SJS/TEN in an age-specific Burns Centre or specialised dermatology centre co-located with age-specific intensive care. Dermatology or plastic surgery coordinates with critical care, ophthalmology, nursing, pharmacy, microbiology, pain, nutrition and oral, respiratory and urogenital specialists. The immediate determinants of outcome are rapid culprit withdrawal, specialist transfer and consistently executed supportive care; active systemic therapy remains a specialist MDT decision.
Key points
- SJS/TEN typically causes prodrome, disproportionate skin pain, dusky macules or atypical targets, flaccid blisters, epidermal detachment and prominent ocular, oral or genital erosions.
- Classify by detached or detachable surface: SJS below 10%, overlap 10% to 30%, and TEN above 30%; extent can evolve after presentation and must be remapped.
- DRESS usually emerges two to eight weeks after starting a culprit with fever, widespread eruption, facial oedema, nodes, eosinophilia or atypical lymphocytes and liver, kidney, lung or cardiac injury.
- Build a calendar of every medicine started, increased, intermittently taken or stopped in the previous two months, including antimicrobials, anticonvulsants, allopurinol, analgesics and non-prescription products.
- Withdraw likely culprit treatment immediately but do not create avoidable harm by indiscriminately stopping physiological corticosteroid, antiseizure cover or another essential medicine without a safe substitute.
- SJS/TEN care prioritises culprit withdrawal and meticulous multidisciplinary support; no single systemic immunomodulator has conclusive superiority over high-quality conservative care in the UK guideline.
- Early ophthalmology, daily eye, mouth and urogenital review, respiratory surveillance, individualised fluids, enteral nutrition, pain control and non-traumatic wound care prevent lifelong disability as well as death.
- Do not give routine prophylactic systemic antibiotics; culture strategically and treat clinical infection, because indiscriminate exposure selects Candida and resistant colonisation.
- Document the exact culprit and drugs to avoid, notify every care setting and report through MHRA Yellow Card; specialist allergy input is needed when causality remains uncertain or broad avoidance compromises care.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
High-risk medicines
Anticonvulsants, allopurinol, sulfonamide antimicrobials, some NSAIDs, antiretrovirals and other agents can trigger delayed T-cell reactions, with risk shaped by exposure timing and host genetics.
Infection-associated mimic or trigger
Mycoplasma or viral mucositis and erythema multiforme may resemble SJS, while acute infection can also complicate drug-induced epidermal loss and alter treatment.
Uncertain or multiple exposure
Polypharmacy, intermittent dosing and medicines stopped before eruption obscure attribution; a structured latency calendar prevents the newest or most familiar drug being blamed reflexively.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Drug-specific T cells activate
A drug, metabolite or pharmacological interaction with immune receptors activates cytotoxic T cells in susceptible individuals after a characteristic sensitisation period.
- 2Keratinocytes undergo death
Cytotoxic mediators including granulysin and death-receptor signalling cause widespread full-thickness epidermal necrosis, separation and mucosal epithelial loss in SJS/TEN.
- 3Barrier loss drives physiology
Denuded dermis loses fluid, heat and protein, permits microbial invasion and produces high metabolic demand, haemodynamic instability and severe nociceptive pain.
- 4DRESS inflammation enters organs
A prolonged drug-specific immune response, sometimes accompanied by herpesvirus reactivation, recruits eosinophils and lymphocytes into liver, kidney, lung, heart and endocrine tissue.
- 5AGEP recruits neutrophils
Drug-driven cytokines attract neutrophils rapidly into superficial epidermis, creating many sterile pustules with fever and leukocytosis but less full-thickness necrosis than TEN.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Severe skin pain, dusky macules or atypical targets, flaccid blisters, sheet-like detachment and acute erosive mucositis after a high-risk medicine define the core syndrome.
Grit, photophobia, red eye, discharge, lid-margin ulceration or reduced vision may progress quickly to conjunctival scarring, dry eye and irreversible corneal damage.
Hoarseness, cough, dyspnoea, hypoxia, increased secretions or haemoptysis can reflect sloughing respiratory epithelium and predict a need for rapid critical-care intervention.
Delayed fever, diffuse infiltrated eruption, prominent facial oedema, lymphadenopathy, eosinophilia or atypical lymphocytes with liver, renal, lung or cardiac injury supports DRESS.
Abrupt sheets of tiny sterile non-follicular pustules beginning in folds, with fever and neutrophilia shortly after a medicine, suggests acute generalised exanthematous pustulosis.
Grey, purple-brown or minimally red tender skin may already be necrotic; examine reflected light, texture, blisters and mucosae and compare with the patient's baseline.
Hypothermia, tachycardia, hypotension, oliguria, confusion, severe pain, expanding detachment or hypoxia indicates barrier and organ failure regardless of the named SCAR.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Medicine chronology and causality assessmentFirst step - Why
- Identify the likely culprit quickly enough to reduce ongoing injury.
- Interpretation and limitations
- Plot exact start, dose change, intermittent exposure and stop dates over at least 8 weeks, compare known latency and notoriety, and include medicines already stopped before the rash.
- 02
Full skin and mucosal surface map - Why
- Classify SJS/TEN and detect evolving eye, oral, genital and airway disease.
- Interpretation and limitations
- Record total rash and detached or detachable surface separately on a body chart, photograph with consent, and repeat daily because SJS can evolve into overlap or TEN.
- 03
Skin biopsies - Why
- Confirm epidermal necrosis and exclude immunobullous or other mimicking disease.
- Interpretation and limitations
- Send lesional skin in formalin for routine histology and a separate perilesional specimen in the correct medium for direct immunofluorescence; treatment and transfer do not await results.
- 04
Full blood count and film - Why
- Detect eosinophilia, atypical lymphocytes, neutrophilia, cytopenia and prognostic abnormalities.
- Interpretation and limitations
- Eosinophilia can appear late in DRESS and also occur in AGEP; neutropenia increases infection risk, while any blood pattern must be integrated with organs, timing and biopsy.
- 05
Serial organ and metabolic profile - Why
- Find DRESS involvement and quantify acute skin-failure physiology.
- Interpretation and limitations
- Repeat urea, creatinine, electrolytes, bicarbonate, glucose, magnesium, phosphate, liver tests, albumin and CRP; add troponin, ECG, echocardiography, gas or imaging to symptoms.
- 06
SCORTEN within 24 hours - Why
- Estimate mortality risk and inform the intensity of SJS/TEN monitoring.
- Interpretation and limitations
- Score age over 40, malignancy, pulse over 120, detachment over 10%, urea over 10 mmol/L, glucose over 14 mmol/L and bicarbonate below 20 mmol/L; never use a low score to delay transfer.
- 07
Microbiology and sepsis assessment - Why
- Detect invasive infection without treating colonisation indiscriminately.
- Interpretation and limitations
- Culture blood for sepsis and sample several sloughy or crusted skin sites serially; a newly predominant organism plus rising pain, hypotension, oliguria or hypoxia increases invasive-infection concern.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Erythema multiforme major
Raised typical three-zone acral targets, an infectious trigger and limited detachment favour erythema multiforme, although severe mucositis still needs specialist assessment.
Generalised bullous fixed drug eruption
Sharply demarcated recurrent dusky plaques at previous sites, shorter re-exposure latency and islands of unaffected skin suggest bullous fixed drug eruption.
Autoimmune blistering disease
Pemphigus, bullous pemphigoid, linear IgA disease and paraneoplastic pemphigus are separated by morphology, histology and perilesional direct immunofluorescence.
Staphylococcal scalded skin
Superficial toxin-mediated cleavage, periorificial fissuring and absent mucosal erosions, particularly in children or renal failure, contrast with full-thickness SJS/TEN necrosis.
GPP or AGEP
Pustules, psoriasis history, drug latency, eosinophilia, flexural distribution, histology and time to resolution distinguish generalised pustular psoriasis from acute drug pustulosis.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01First-line emergency sequenceStop culprit and transfer earlyFirst stepFirst linePainful blistering, epidermal loss or severe mucositis raises SJS/TEN or another SCAR.+
- 1Stop the likely culprit immediately, preserve essential treatment with safe alternatives, assess ABCDE and airway, weigh the patient and map skin and every mucosal site.
- 2Contact dermatology, critical care and the regional specialised service early; arrange care in an age-specific Burns Centre or dermatology centre co-located with intensive care.
- 3Obtain histology and immunofluorescence biopsies, FBC, metabolic and organ profiles, cultures and imaging without delaying transfer or supportive treatment.
- 4Calculate SCORTEN within 24 hours, record causality reasoning and notify ophthalmology immediately so the first formal eye examination occurs within 24 hours.
02Gold-standard supportive careProtect every failing surfaceSJS/TEN is suspected or confirmed in specialist care.+
- 1Nurse in a warm side room with barrier precautions, minimise shear and adhesives, place lines through unaffected skin when possible and deliver background and procedural analgesia.
- 2Clean gently with warmed saline, cover with greasy emollient and non-adherent dressings and let the skin-failure MDT choose conservative or surgical wound management daily.
- 3Guide fluid by perfusion, urine, weight, electrolytes and lactate because SJS/TEN usually needs less than a Parkland thermal-burn calculation; start early enteral nutrition when oral intake fails.
- 4Provide daily eye, mouth and urogenital examinations, respiratory monitoring, thrombosis and pressure protection and systemic antibiotics only for clinical infection with microbiology advice.
03DRESS organ sequenceTrack injury beyond the rashDelayed eruption with fever, facial oedema, eosinophilia, nodes or organ-test abnormality suggests DRESS.+
- 1Withdraw the likely culprit and seek dermatology and the relevant organ-specialist input, admitting systemic disease even when skin detachment is limited.
- 2Trend blood count, liver, kidney and inflammatory tests and screen heart, lung, thyroid and other organs from symptoms and culprit profile; abnormalities may evolve after withdrawal.
- 3Use topical therapy for skin symptoms and reserve systemic corticosteroid or another immunomodulator for specialist assessment of significant organ disease, infection risk and a slow relapse-aware taper.
- 4Continue post-discharge organ and thyroid surveillance, document avoidances precisely and do not perform unsupervised re-exposure or challenge.
04Discharge safetyMake re-exposure difficultAcute skin and organ disease has stabilised enough for transfer or discharge.+
- 1Give a plain-language written diagnosis, exact culprit and related drugs to avoid, reaction date, uncertainties and safe alternatives; update electronic records and the GP.
- 2Submit an MHRA Yellow Card and arrange specialist drug-allergy or dermatology investigation when attribution is uncertain or broad avoidance compromises future care.
- 3Arrange early eye and dermatology or burns follow-up plus oral, genital, respiratory, psychological and organ-specific care, explaining that late scarring and DRESS relapse can occur.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
White soft paraffin and liquid paraffin 50:50 ointment
Apply gently over intact and denuded epidermis after warmed cleansing and whenever the surface dries, generally at least every 4 hours during acute specialist care.Application can shear fragile epidermis, so use experienced nursing or aerosolised delivery when appropriate; paraffin-contaminated linen and dressings are a major fire hazard and require strict flame avoidance.
Weight-adjusted LMWH thromboprophylaxis
Give the hospital protocol's prophylactic subcutaneous dose once daily, adjusted for body weight and renal function, while mobility is substantially reduced unless contraindicated.Review active bleeding, severe thrombocytopenia, renal impairment and imminent procedures each day; extensive skin loss changes injection-site choice, and therapeutic anticoagulation requires a separate indication.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Sepsis and multiorgan failure
Colonised denuded dermis can seed bloodstream infection, while fluid loss and inflammation contribute to shock, renal injury, respiratory failure and death.
Ocular surface destruction
Acute conjunctival epithelial loss forms adhesions and scars, leading to severe dry eye, trichiasis, corneal opacity, infection and permanent visual impairment.
Mucosal stenosis
Oral, genital, urinary and gastrointestinal erosions can heal with adhesions, painful intercourse, urinary obstruction, swallowing difficulty and chronic mucosal dryness.
Respiratory epithelial loss
Bronchial sloughing can obstruct airways, cause atelectasis and require ventilation; later bronchiolitis obliterans or chronic functional impairment may persist.
Delayed DRESS sequelae
Hepatitis, nephritis or myocarditis can relapse during taper, while thyroid disease and other autoimmune complications may arise months after apparent cutaneous recovery.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Map detached and detachable surface, new lesions, skin pain and re-epithelialisation daily with standardised photographs and consent; record rash area separately from epidermal loss.
- Monitor temperature, pulse, blood pressure, oxygen saturation, mental state, weight, fluid input, urine, pain and nutrition frequently and respond to trends before shock develops.
- Perform and document daily ophthalmic, oral and urogenital review throughout the acute phase; any new respiratory symptom or hypoxia triggers immediate intensivist and airway discussion.
- Trend FBC, renal, liver, bicarbonate, glucose, magnesium, phosphate, albumin and CRP, adding cardiac or lung markers when DRESS or respiratory epithelial disease is possible.
- Sample suspicious skin and blood for infection and look for increased pain, a dominant organism, hypotension, oliguria, confusion or hypoxia; fever alone is not specific in SJS/TEN.
- Reconcile allergy entries across care records and verify the patient can name the culprit, cross-reacting risks and safe alternatives before discharge.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Pain precedes detachment
Disproportionate tenderness on dusky skin can announce keratinocyte necrosis before obvious blistering, making palpation and mucosal examination decisive early tests.
A low score cannot defer care
SCORTEN estimates mortality after the emergency is recognised; it neither excludes evolving disease nor substitutes for early specialist transfer and surveillance.
Burn care is not burn arithmetic
The environment, nursing and wound expertise are valuable, but epidermal necrolysis usually requires less fluid than Parkland calculations predict for thermal injury.
Eosinophilia can arrive late
An initially normal eosinophil count does not exclude DRESS when latency, facial oedema and organ injury fit, so serial blood counts matter.
Active therapy remains unsettled
IVIg, systemic corticosteroids and ciclosporin have advocates, but the UK guideline found no conclusive superior intervention and prioritises specialist-governed supportive care.
Healing skin is not full recovery
Ocular scarring, genital stenosis, respiratory disease, pigment change, chronic pain, fatigue and psychological trauma may emerge after re-epithelialisation.
11Common pitfallsFrequent interpretation and management errors.
- 01
Calling a painful mucosal eruption erythema multiforme without mapping detachable epidermis and reviewing high-risk medicines.
- 02
Waiting for biopsy or a positive Nikolsky sign before stopping the probable culprit and arranging specialist transfer.
- 03
Under-recognising necrosis because early inflammation is grey or violaceous rather than bright red in darker skin.
- 04
Counting the whole erythematous rash as detached surface and misclassifying SJS/TEN severity.
- 05
Using a Parkland formula unchanged and causing pulmonary, intestinal or cutaneous oedema through over-resuscitation.
- 06
Giving prophylactic systemic antibiotics for colonised skin without clinical infection.
- 07
Using one normal eosinophil count to exclude DRESS despite evolving hepatitis and facial oedema.
- 08
Starting unproven systemic immune therapy outside the specialist skin-failure MDT while supportive tasks are incomplete.
- 09
Recording allergy as antibiotics or rash instead of the exact culprit, phenotype, date, severity and safe alternatives.