What are the updated criteria and protocol for diagnosing and managing Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)?

DRESS Syndrome: Updated Diagnostic Criteria and Management Protocol

Diagnostic Criteria

DRESS syndrome should be diagnosed using the RegiSCAR scoring system, which classifies cases as "no," "possible," "probable," or "definite" based on specific clinical and laboratory parameters. 1, 2

Core Clinical Features Required for Diagnosis

• Cutaneous manifestations: Morbilliform (maculopapular) confluent rash involving >30% of body surface area 1, 3, 2
• Fever: Temperature >38°C 1, 2
• Characteristic latency period: 2-6 weeks after drug exposure, distinguishing DRESS from immediate hypersensitivity reactions 1, 3, 2
• Lymphadenopathy: Commonly present 1

Laboratory Criteria

• Hematologic abnormalities:

  • Eosinophilia >700/μL or >10% of white blood cells 1, 2
  • Atypical lymphocytes 4, 5
  • Leukocytosis 6

• Organ involvement (at least one):

  • Hepatitis: ALT >2 times upper limit of normal (most common organ manifestation) 1, 2
  • Nephritis: Creatinine >1.5 times baseline 1, 2
  • Cardiac: Myocarditis or pericarditis 1
  • Pulmonary: Pneumonitis 3

Essential Diagnostic Workup

• Complete blood count with differential to assess eosinophilia and atypical lymphocytes 1, 2
• Comprehensive metabolic panel evaluating liver enzymes (ALT, AST, alkaline phosphatase, bilirubin) and renal function (BUN, creatinine) 1, 2
• Urinalysis to evaluate for nephritis 1, 2
• Skin biopsy if diagnosis is uncertain 1
• Blood cultures to rule out infectious causes 2

Critical Differential Diagnosis

DRESS must be distinguished from Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP), as management differs significantly. 3, 2

Key distinguishing features:

• DRESS has a longer latency period (2-6 weeks vs. days for SJS/TEN) 1
• DRESS presents with eosinophilia and organ involvement, whereas SJS/TEN presents with mucosal involvement and epidermal detachment 3
• Unlike SJS/TEN, systemic corticosteroids are NOT contraindicated in DRESS 1

Management Protocol

Step 1: Immediate Actions

Immediately discontinue the suspected causative drug—this is the first and most crucial step. 1, 3

• Obtain prompt dermatology consultation 1, 3
• Assess severity to determine admission needs 1

Step 2: Severity Stratification and Admission Criteria

• Severe cases: Admit to burn unit or ICU with dermatology and wound care services consultation 1
• All suspected cases: Initiate systemic corticosteroids regardless of severity 3

Step 3: First-Line Pharmacologic Treatment

Initiate IV methylprednisolone 1-2 mg/kg/day as first-line therapy. 1, 3

Critical steroid management principles:

• Wean over at least 4 weeks (not shorter) due to T-cell immune-directed toxicity 1, 3
• Premature tapering can lead to relapse, which occurs in approximately 12% of cases 3
• Unlike SJS/TEN, corticosteroids are the standard of care in DRESS 1

Step 4: Second-Line Therapy for Steroid-Unresponsive Cases

For patients not responding to systemic steroids within 7 days 7:

• Intravenous immunoglobulin (IVIG): 1-2 g/kg total dosage 1, 7

  • Fever typically resolves within 1 day of IVIG administration 7
  • Liver enzymes improve within median 13 days 7

• Alternative: Cyclosporine for refractory cases 1

Step 5: Supportive Care

• Fluid and electrolyte management to minimize insensible water losses 1, 3
• Infection prevention measures 1, 3
• Topical corticosteroids for symptomatic relief 1, 3
• Oral antihistamines for pruritus 1, 3

Pathophysiology and Genetic Considerations

DRESS involves reactivation of herpes family viruses (particularly EBV and HHV-6) and T-cell immune-directed toxicity. 1, 3

HLA Associations and Genetic Testing

• HLA-B*58:01: Strongly associated with allopurinol-induced DRESS 1, 2
• HLA-B*5701: Associated with abacavir hypersensitivity 3
• Consider genetic testing before prescribing high-risk medications in susceptible populations 3, 2

Common Culprit Drugs

Most frequently implicated medications 4, 7, 6:

• Carbamazepine (most commonly reported) 4
• Dapsone 7
• Vancomycin 7
• Antiepileptics (general class) 6
• Allopurinol 1, 2
• Antituberculosis medications 6
• NSAIDs 6

Prognostic Indicators

Poor prognostic factors include: 6

• Eosinophil count >6000 × 10³/μL
• Thrombocytopenia
• Pancytopenia
• Leukocytosis
• Coagulopathy
• Fulminant hepatitis or liver necrosis (main causes of mortality)

Overall mortality: 3.8-10% 5, 6

Testing for Drug Causality

Patch testing or delayed intradermal testing should be avoided until at least 6 months after the acute reaction AND at least 1 month after discontinuation of systemic corticosteroids. 8, 3

• Patch testing is the test of choice for identifying the culprit drug once the patient has recovered 6
• For DRESS, delayed intradermal testing with reading at 24 hours may be useful 8
• Drug challenge with the suspected drug is contraindicated except in extreme circumstances where benefit outweighs risk (e.g., antituberculous therapy) 8

Critical Pitfalls to Avoid

• Do not taper steroids rapidly: Minimum 4-week taper is required to prevent relapse 1, 3
• Do not confuse with SJS/TEN: This leads to inappropriate withholding of corticosteroids 1, 3
• Do not delay diagnosis: The 2-6 week latency period often leads to delayed recognition 2
• Do not perform drug testing too early: Wait at least 6 months post-reaction 3
• Do not rechallenge with the culprit drug: This is contraindicated in DRESS 8