What is the role of the Regiscar (Registry of Severe Cutaneous Adverse Reactions) scoring system in diagnosing DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome?

RegiSCAR Scoring System for DRESS Syndrome

The RegiSCAR (Registry of Severe Cutaneous Adverse Reactions) scoring system is the validated diagnostic tool that classifies DRESS syndrome cases as "no," "possible," "probable," or "definite" based on clinical and laboratory findings, and should be used to establish the diagnosis when DRESS is suspected. 1, 2

Core Components of the RegiSCAR Score

The scoring system evaluates multiple parameters to generate a classification:

Clinical Features Required

• Fever >38°C - Essential component of the scoring system 1, 3
• Skin eruption - Morbilliform (maculopapular) confluent rash involving >30% of body surface area is the most common presentation 1, 3
• Lymphadenopathy - Presence significantly associated with "probable/definite" DRESS cases 2

Laboratory Abnormalities Scored

• Eosinophilia - Defined as >700/μL or >10% of white blood cells; hypereosinophilia is significantly associated with "probable/definite" DRESS cases 1, 2
• Atypical lymphocytes - Presence of mononucleosis-like atypical lymphocytes 4, 5

Organ Involvement Criteria

• Liver involvement - ALT >2 times upper limit of normal; significantly associated with "probable/definite" DRESS cases 1, 2
• Kidney involvement - Creatinine >1.5 times baseline 1
• Other organs - Lung (pneumonitis), heart (myocarditis, pericarditis) involvement 1, 3

Diagnostic Classification

The RegiSCAR system generates four possible classifications based on the cumulative score:

• "No" DRESS - Does not meet criteria
• "Possible" DRESS - Some features present but incomplete
• "Probable" DRESS - Most criteria met
• "Definite" DRESS - All major criteria fulfilled 1, 2, 4

A RegiSCAR score ≥2 has been validated as effective in diagnosing DRESS syndrome at presentation. 6

Critical Timing Considerations

• Latency period of 2-6 weeks after drug exposure is characteristic and distinguishes DRESS from other drug reactions; this timing is critical for identifying the culprit drug 1, 3, 5
• The scoring system should be applied when this temporal relationship is present along with the clinical syndrome 1

Practical Application at Presentation

While the full RegiSCAR score provides comprehensive validation, a simplified combination model using three parameters can predict DRESS at presentation with 96% sensitivity and 100% specificity: 6

• Total body surface area (TBSA) >35% 6
• Eosinophil count >6% or absolute eosinophil count >450 cells/mm³ 6
• High-sensitivity C-reactive protein (hsCRP) >5 mg/L 6

This combination model at a cutoff of 6.8 performs similarly to the full RegiSCAR validation score for rapid diagnosis. 6

Additional Diagnostic Markers

Beyond the core RegiSCAR criteria, these markers support diagnosis:

• TARC (thymus and activation-regulated chemokine) levels >613.25 pg/mL - Effectiveness statistically similar to RegiSCAR score ≥2 in diagnosing DRESS 6
• Aspartate transaminase (AST) >92 U/L - Supports diagnosis with similar effectiveness to RegiSCAR score 6

Common Pitfalls in Scoring

• Skin rash is described in almost all cases, including "possible cases," so its presence alone is insufficient for diagnosis; the combination with fever, eosinophilia, lymphadenopathy, and organ involvement is what distinguishes "probable/definite" DRESS 2
• Delayed diagnosis is common due to variable presentation and the 2-6 week latency period after drug initiation 1
• The RegiSCAR system requires comprehensive laboratory evaluation including complete blood count with differential, comprehensive metabolic panel, and urinalysis 1

Differential Diagnosis Considerations

The RegiSCAR scoring helps distinguish DRESS from:

• Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) - DRESS has longer latency period, prominent eosinophilia, and more organ involvement 4
• Acute Generalized Exanthematous Pustulosis (AGEP) - Different skin morphology and shorter latency 7
• Viral infections - Temporal relationship to drug exposure and specific laboratory findings differentiate DRESS 1

Prognostic Indicators Within the Scoring Context

While the RegiSCAR score establishes diagnosis, certain findings predict severity:

• Eosinophil count >6000 × 10³/μL - Indicator of poor prognosis 4
• Elevated serum creatinine and ferritin at presentation - Predict fatal outcomes 3
• Thrombocytopenia, pancytopenia, leukocytosis, and coagulopathy - Associated with worse prognosis 4