What is the treatment for DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome?

Treatment of DRESS Syndrome

Immediately discontinue the suspected causative drug and initiate systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day) with prompt dermatology consultation for all suspected cases. 1, 2

Initial Management Steps

Drug Withdrawal:

• Stop the offending medication immediately as the single most critical intervention—this is non-negotiable and takes priority over all other treatments 1, 3
• If multiple drugs are potential culprits, use clinical judgment to discontinue the most likely offender(s), though you may need to stop all non-essential medications 3

Immediate Consultation:

• Obtain dermatology consultation urgently for all suspected cases 1, 2
• Request skin biopsy if diagnosis is uncertain (pathology shows lymphocytic CD4+ infiltrates with eosinophils) 4

Diagnostic Workup

Complete the following tests before initiating treatment:

• Complete blood count with differential (assess for eosinophilia >700/μL) 1, 5
• Comprehensive metabolic panel including liver enzymes (ALT, AST, alkaline phosphatase, bilirubin) and kidney function (BUN, creatinine) 1, 5
• Urinalysis to evaluate for nephritis 1, 5
• Blood cultures to exclude infection 1
• Total body skin examination documenting extent of rash 1

Severity Assessment and Admission Criteria

Severe DRESS requires ICU or burn unit admission when:

• Multi-organ involvement is present (hepatitis, nephritis, myocarditis, pneumonitis) 1, 2
• Extensive skin involvement (>30% body surface area) 2, 5
• Hemodynamic instability or severe constitutional symptoms 1

Systemic Corticosteroid Therapy

Unlike Stevens-Johnson syndrome, corticosteroids are NOT contraindicated in DRESS and are the cornerstone of treatment 1:

• Start IV methylprednisolone 1-2 mg/kg/day for severe cases 1, 2
• Wean over at least 4 weeks minimum—rapid tapering leads to relapse 1, 2
• Prolonged immunosuppression may be necessary due to T-cell immune-directed toxicity 1
• Do NOT use prophylactic corticosteroids when initiating high-risk drugs, as this is ineffective and may increase rash risk 1

Second-Line Therapies for Steroid-Refractory Cases

IVIG (Intravenous Immunoglobulin):

• Consider total dosage of 1-2 g/kg for patients not responding to systemic steroids 1, 6
• Evidence shows fever resolution within median 1 day and liver enzyme improvement within 13 days after IVIG 6
• Add IVIG within approximately 7 days if inadequate response to steroids 6

Cyclosporine:

• May be considered in severe or steroid-unresponsive cases 1

Supportive Care Measures

Provide comprehensive supportive management:

• Fluid and electrolyte balance management 1, 2
• Minimize insensible water losses 1, 2
• Infection prevention measures (critical given immunosuppression) 1, 2
• Topical corticosteroids and oral antihistamines for symptomatic relief 1, 2
• Serial clinical photography to track skin manifestations 1

Specialist Consultations Based on Organ Involvement

Consult appropriate specialists immediately:

• Ophthalmology, otolaryngology, urology, or gynecology for mucous membrane involvement 1
• Cardiology for myocarditis or pericarditis 2
• Pulmonology for pneumonitis 2
• Nephrology for significant kidney dysfunction 2
• Pain or palliative care for symptom management 1

Critical Pitfalls to Avoid

Common errors in DRESS management:

• Delayed recognition due to 2-6 week latency period after drug initiation—maintain high index of suspicion 2, 5
• Premature steroid tapering (must taper over minimum 4 weeks to prevent relapse, which occurs in 12% of cases) 1, 2
• Failing to distinguish DRESS from Stevens-Johnson syndrome or toxic epidermal necrolysis—DRESS has eosinophilia, longer latency, and organ involvement 4, 2, 5
• Continuing the offending drug while awaiting confirmatory testing 3

Monitoring and Follow-up

• Track clinical response with serial laboratory monitoring of liver enzymes, kidney function, and eosinophil counts 1
• Mortality rate is approximately 10%, primarily from visceral organ compromise 3
• Avoid patch testing or intradermal testing until at least 6 months after acute reaction and at least 1 month after stopping systemic corticosteroids 2