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2025 PACUPrep BCCCP Preparatory Course Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Diagnostic & Classification Strategies in SJS/TEN

Lesson 38, Topic 2

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Diagnostic & Classification Strategies in SJS/TEN

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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.

Figure 1: Classification by Body Surface Area (BSA). The percentage of detached or detachable epidermis determines the diagnosis and has significant prognostic implications.

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:

SCORTEN Criteria and Associated Mortality Risk
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.

Key Distinguishing Features of SJS/TEN and Its Mimickers
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.

Dermatology: Biopsy, skin care plan • Critical Care/Burn: Hemodynamics • Ophthalmology: Urgent consult • Pharmacy: Med reconciliation

Figure 2: Integrated Care Pathway for SJS/TEN. A structured approach from initial assessment to specialized multidisciplinary care is essential for improving survival.

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.

2025 PACUPrep BCCCP Preparatory Course

Pulmonary

Participants 432

Diagnostic & Classification Strategies in SJS/TEN

Diagnostic & Classification Strategies in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN)

Lesson Objective

1. Clinical Presentation & Prodrome

A. Prodrome (1–3 days before rash)

B. Cutaneous Evolution

C. Mucosal Involvement (>90% of cases)

2. Laboratory & Imaging Evaluation

3. Histopathology & Diagnostic Biopsy

A. Technique

B. Key Histopathologic Findings

C. Direct Immunofluorescence (DIF)

4. Body Surface Area (BSA)-Based Classification

BSA Estimation Tools

5. Prognostic Scoring Systems

The SCORTEN Score

6. Differential Diagnosis

7. Integration into a Clinical Pathway

Editor’s Note: Future Directions

References