Diagnostic & Classification Strategies in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN)
Lesson Objective
Enable rapid recognition, classification, and risk stratification of SJS/TEN to guide urgent interventions.
1. Clinical Presentation & Prodrome
SJS/TEN often begins with a non-specific flu-like prodrome followed by rapid evolution of painful, dusky skin lesions and widespread mucosal involvement.
A. Prodrome (1–3 days before rash)
- High fever (≥39 °C), malaise, and headache are common.
- Patients may report sore throat, cough, and conjunctival irritation.
- This prodrome occurs in approximately 80% of cases and should raise high suspicion in the context of recent new drug exposures.
B. Cutaneous Evolution
- Lesions begin as erythematous macules with dark, dusky, or purpuric centers (“atypical targets”).
- They rapidly coalesce into flaccid bullae, leading to sheet-like epidermal detachment.
- A positive Nikolsky’s sign, where gentle lateral pressure on the skin induces epidermal shearing, is a key clinical finding.
C. Mucosal Involvement (>90% of cases)
- Painful erosions with pseudomembranes affect oral, ocular, and genital surfaces.
- Severe involvement poses a high risk of long-term sequelae, including ocular symblepharon (adhesions), visual impairment, and urethral strictures.
Clinical Pearls
A prodrome resembling a viral infection in a patient recently started on a high-risk drug (e.g., sulfonamides, antiepileptics, allopurinol) should trigger an immediate and thorough skin examination.
Nikolsky’s sign is sensitive but not specific for SJS/TEN; it must be interpreted within the overall clinical context.
2. Laboratory & Imaging Evaluation
Laboratory tests are crucial for assessing systemic involvement and complications, while imaging is reserved for specific indications like respiratory distress.
- Complete Blood Count (CBC): May show leukocytosis with a left shift, or alternatively, leukopenia and lymphopenia, which are poor prognostic signs. Eosinophilia suggests a possible overlap with DRESS syndrome.
- Metabolic Panels:
- Electrolytes: Hyponatremia, hypokalemia, and hypocalcemia are common due to massive fluid and protein losses from the denuded skin.
- Renal Function: Rising BUN and creatinine signal early acute kidney injury (AKI).
- Hepatic Function: Transaminase elevations are seen in approximately 60% of cases.
- Blood Glucose & Bicarbonate: These are core components of the SCORTEN prognostic score.
- Inflammatory Markers: Elevated C-Reactive Protein (CRP) can help monitor for secondary infections and sepsis.
- Imaging: A chest X-ray and/or Arterial Blood Gas (ABG) are indicated if respiratory symptoms develop, to evaluate for Acute Respiratory Distress Syndrome (ARDS) or bronchial epithelial sloughing.
Clinical Pearl
Daily laboratory monitoring is essential. It guides fluid and electrolyte resuscitation, informs drug dosing adjustments (especially for renal impairment), and allows for the early detection of life-threatening organ dysfunction.
3. Histopathology & Diagnostic Biopsy
A punch biopsy of an active lesion is the gold standard for confirming full-thickness epidermal necrosis and definitively excluding mimickers.
A. Technique
- A 4–6 mm punch biopsy should be taken from the border of a fresh, erythematous, or dusky lesion, including a small portion of adjacent normal-appearing skin.
- Use minimal local anesthesia with epinephrine and fix the sample in formalin.
B. Key Histopathologic Findings
- Full-thickness keratinocyte necrosis (apoptosis) with the formation of a subepidermal cleft or blister.
- A characteristically sparse perivascular dermal infiltrate, composed predominantly of CD8⁺ cytotoxic T lymphocytes.
C. Direct Immunofluorescence (DIF)
- A second biopsy from perilesional skin should be sent for DIF. It will be negative in SJS/TEN, which is crucial for excluding autoimmune bullous diseases like pemphigus or pemphigoid.
Clinical Pearl
While rapid frozen sections can be performed, they may be misleading due to artifact. Standard formalin-fixed histology is preferred for definitive diagnosis and should be obtained urgently.
4. Body Surface Area (BSA)-Based Classification
The extent of epidermal detachment, measured as a percentage of total body surface area (% BSA), is the primary method for classifying the disease spectrum and guiding the required level of care.
BSA Estimation Tools
- Rule of Nines: Commonly used for adults, provides a rapid but approximate estimation.
- Lund-Browder Chart: More accurate for pediatrics as it adjusts for age-related body proportions.
- Digital Planimetry: Used in specialized centers for the most precise measurement.
Key Point
Consistent and accurate documentation of the % BSA is critical for effective interprofessional communication, tracking disease progression, and making appropriate decisions regarding transfer to a specialized burn unit or ICU.
5. Prognostic Scoring Systems
Validated scoring systems like SCORTEN are used to predict mortality risk upon admission, informing discussions about prognosis and guiding decisions on the appropriate level of care, such as transfer to an ICU or burn unit.
The SCORTEN Score
Assessed within the first 24 hours of admission, with one point awarded for each of the following seven criteria:
| Prognostic Factor | Threshold (1 Point) | SCORTEN Score | Predicted Mortality |
|---|---|---|---|
| Age | ≥ 40 years | 0–1 | ~3% |
| Malignancy (presence of) | Yes | 2 | ~12% |
| Heart Rate | ≥ 120 bpm | 3 | ~35% |
| BSA Detached | > 10% | 4 | ~58% |
| Serum Urea (BUN) | > 28 mg/dL (>10 mmol/L) | ≥ 5 | > 90% |
| Serum Glucose | > 252 mg/dL (>14 mmol/L) | ||
| Serum Bicarbonate | < 20 mmol/L |
The ABCD-10 score is an alternative that includes factors like baseline chronic renal failure and the need for acute dialysis, but SCORTEN remains the most widely used tool.
Clinical Pearl
SCORTEN is a dynamic tool. While calculated on admission, it should be reassessed on day 3 to capture evolving organ dysfunction. A worsening score indicates a poor response to initial therapy and a higher mortality risk.
6. Differential Diagnosis
Distinguishing SJS/TEN from other severe cutaneous adverse reactions and blistering conditions is vital to avoid mismanagement.
| Feature | SJS/TEN | DRESS Syndrome | Staph. Scalded Skin (SSSS) | MIRM |
|---|---|---|---|---|
| Lesions | Dusky macules, flaccid bullae | Morbilliform rash, facial edema | Diffuse erythema, superficial sloughing | Sparse or absent skin lesions |
| Mucositis | Severe, in >90% of cases | Variable, often less severe | Mucosa is typically spared | Severe, predominant feature |
| Key Labs | Lymphopenia, elevated BUN | Eosinophilia, atypical lymphocytes | Normal labs, positive culture | Normal labs, positive serology |
| Biopsy | Full-thickness necrosis | Dense eosinophilic infiltrate | Intraepidermal (granular layer) split | Variable, often non-specific |
| Common Cause | Drugs (allopurinol, antiepileptics) | Drugs (antiepileptics, antibiotics) | Staphylococcus aureus exotoxin | Mycoplasma pneumoniae |
7. Integration into a Clinical Pathway
A standardized, multidisciplinary approach involving rapid drug withdrawal, risk stratification, and early transfer to specialized care is proven to optimize outcomes.
Editor’s Note: Future Directions
Emerging biomarkers (e.g., serum granulysin assays) and standardized digital BSA measurement tools are currently under investigation. These innovations promise to further refine and accelerate future diagnostic and prognostic pathways for SJS/TEN.
References
- Seminario-Vidal L, et al. Society of Dermatology Hospitalists supportive care guidelines for Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020;83(6):1414-1429.
- Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Review of Diagnosis and Management. Medicina. 2021;57(9):895.
- Bastuji-Garin S, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115(2):149-153.
- Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39.
- Heuer R, et al. S3 guideline: Diagnosis and treatment of epidermal necrolysis – Part 1: Diagnosis, initial management, and immunomodulating systemic therapy. J Dtsch Dermatol Ges. 2024;22:1448-1466.
