DRESS Syndrome Treatment
Immediately discontinue the suspected causative drug and initiate systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day) with a prolonged taper over at least 4 weeks, as this represents the cornerstone of DRESS syndrome management. 1, 2
Immediate Management Steps
Drug Discontinuation:
- Stop the offending medication immediately—this is the single most critical intervention 1, 2, 3
- If multiple drugs are potential culprits, use clinical judgment to discontinue the most likely causative agent based on the 2-6 week latency period typical for DRESS 1, 2
Prompt Consultation:
- Obtain dermatology consultation urgently for all suspected cases 1, 2, 3
- For severe cases with >30% body surface area involvement or significant organ dysfunction, admit to ICU or burn unit 2, 3
Systemic Corticosteroid Therapy
First-Line Treatment:
- Initiate IV methylprednisolone at 1-2 mg/kg/day 1, 2
- Unlike Stevens-Johnson syndrome, corticosteroids are NOT contraindicated in DRESS and are essential due to the T-cell immune-directed toxicity 2, 3
- Taper over a minimum of 4 weeks to prevent relapse, which occurs in approximately 12% of cases 1, 2
- Rapid tapering is a common pitfall—prolonged immunosuppression is necessary given the underlying pathophysiology 3
Critical Warning:
- Do NOT use prophylactic corticosteroids when initiating medications known to cause DRESS, as this has not proven effective and may increase rash risk 3
Second-Line Therapies for Steroid-Unresponsive Cases
Alternative Immunosuppression:
- Consider intravenous immunoglobulin (IVIG) at 1-2 g/kg total dosage if inadequate response to corticosteroids 2, 3
- Cyclosporine may be employed in severe or steroid-refractory cases 2, 3
Supportive Care Measures
Essential Supportive Management:
- Maintain fluid and electrolyte balance while minimizing insensible water losses 1, 3
- Implement infection prevention protocols given immunosuppression and skin barrier compromise 1, 3
- Apply topical corticosteroids for symptomatic relief of cutaneous manifestations 1, 2
- Prescribe oral antihistamines for pruritus management 1, 2
Monitoring Requirements:
- Serial clinical photography to track skin progression 3
- Complete blood count with differential to monitor eosinophilia 2
- Comprehensive metabolic panel for hepatic (ALT, AST) and renal function (creatinine) 2
- Urinalysis to evaluate for nephritis 2, 3
Specialist Consultation Based on Organ Involvement
Multiorgan Assessment:
- Hepatology for hepatitis (most common organ manifestation with ALT >2× upper limit of normal) 2
- Nephrology for nephritis (creatinine >1.5× baseline) 2, 3
- Cardiology for myocarditis or pericarditis 1, 2
- Ophthalmology, otolaryngology, urology, or gynecology for mucous membrane involvement 3
- Pain/palliative care for symptom management 3
Critical Pitfalls to Avoid
Testing Contraindications:
- Do NOT perform patch testing or delayed intradermal testing until at least 6 months after complete resolution AND at least 1 month (preferably 4 weeks) after discontinuing systemic corticosteroids >10 mg prednisone equivalent 1, 2
- Drug challenge with the suspected culprit is absolutely contraindicated except in extreme circumstances where benefit clearly outweighs risk 2
Diagnostic Considerations:
- Skin biopsy showing lymphocytic CD4+ infiltrates with eosinophils supports the diagnosis if uncertain 3
- Distinguish from Stevens-Johnson syndrome/toxic epidermal necrolysis by the presence of eosinophilia, longer latency (2-6 weeks vs days), and prominent organ involvement 1, 3
Prognosis and Long-Term Management
Expected Outcomes:
- Most patients recover completely with appropriate drug withdrawal and corticosteroid therapy 4
- Mortality rate is approximately 10%, primarily from visceral organ compromise 4
- Relapse risk is 12%, particularly with cases associated with viral reactivation (EBV, HHV-6) 1
Genetic Considerations: