Updated Diagnostic Criteria for DRESS Syndrome
The diagnosis of DRESS syndrome is clinical, based on the RegiSCAR scoring system that classifies cases as "no," "possible," "probable," or "definite" based on specific clinical and laboratory findings. 1, 2
Core Diagnostic Features
The diagnosis requires the presence of the following key elements:
Clinical Presentation
- Cutaneous manifestations: Morbilliform (maculopapular) confluent rash involving >30% of body surface area 1, 3
- Fever: Temperature >38°C (100.4°F) 1
- Timing: Characteristic latent period of 2-6 weeks following drug exposure, distinguishing it from immediate drug reactions 1, 3
- Constitutional symptoms: Rigors, myalgias, and arthralgias 1
Hematologic Abnormalities
- Eosinophilia: Defined as >700/μL or >10% of white blood cells 1
- Atypical lymphocytes: Commonly present on peripheral blood smear 4, 5
Systemic Involvement
- Lymphadenopathy: Commonly present 1, 2
- Hepatic involvement: Most common organ manifestation, with ALT >2 times the upper limit of normal or ALT >100 U/L 1, 5
- Renal involvement: Nephritis with creatinine >1.5 times baseline 1
- Cardiac involvement: Myocarditis and pericarditis 1
RegiSCAR Scoring System
The RegiSCAR scoring system is the validated diagnostic tool that grades DRESS cases as "no," "possible," "probable," or "definite" based on the presence and severity of clinical and laboratory findings. 1, 2
Key Discriminating Features
Studies analyzing the RegiSCAR criteria found that hypereosinophilia, liver involvement, fever, and lymphadenopathy were significantly associated with "probable/definite" DRESS cases, whereas skin rash was present in almost all cases including "possible cases." 2
Required Diagnostic Workup
Laboratory Evaluation
- Complete blood count with differential: To assess for eosinophilia and atypical lymphocytes 1
- Comprehensive metabolic panel: Evaluating liver function (ALT, AST, alkaline phosphatase, bilirubin) and kidney function (BUN, creatinine) 1
- Urinalysis: To evaluate for nephritis 1
Additional Testing
- Skin biopsy: If diagnosis is uncertain 1
- Delayed testing for culprit drug identification: Patch testing or delayed intradermal testing should only be performed at least 6 months after the acute reaction and at least 1 month after discontinuation of systemic corticosteroids 1, 3
Critical Diagnostic Pitfalls
Timing Considerations
The 2-6 week latent period is crucial for distinguishing DRESS from other drug reactions—reactions occurring within hours to days are more consistent with immediate hypersensitivity or other severe cutaneous adverse reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis. 1, 3
Differential Diagnosis
DRESS must be distinguished from other severe cutaneous adverse reactions including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Acute Generalized Exanthematous Pustulosis (AGEP), which have different management approaches and prognoses. 3
Pathophysiologic Mechanism
The syndrome involves reactivation of herpes family viruses (particularly EBV and HHV-6) and activation of lymphocytes, leading to T-cell immune-directed toxicity, which explains the prolonged steroid taper requirement. 1, 3
Common Causative Drugs
The most frequently reported causative drugs include carbamazepine, dapsone, vancomycin, allopurinol, and hydroxychloroquine. 6, 4, 2 Genetic predispositions through specific HLA associations are linked to particular drug reactions (e.g., HLA-B*58:01 with allopurinol-induced DRESS). 1, 3
Prognostic Considerations
Mortality ranges from 10-20%, emphasizing the importance of early recognition and prompt treatment. 4, 5 Relapse can occur in approximately 12% of cases, particularly with DRESS associated with viral reactivation. 3