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

Treatment of DRESS Syndrome

Immediate Management

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, 3

The cornerstone of DRESS management is rapid recognition and drug withdrawal, as this severe T-cell mediated hypersensitivity reaction carries significant mortality risk if not treated aggressively. 1, 4

Initial Assessment and Hospitalization Criteria

• Severe cases require admission to burn unit or ICU with dermatology and wound care services consultation, particularly when rash involves >30% body surface area or significant organ involvement is present. 1, 3
• Perform complete workup including: total body skin examination, complete blood count with differential, comprehensive metabolic panel (liver and kidney function), urinalysis, blood cultures if febrile, and skin biopsy if diagnosis uncertain. 1, 3
• Monitor for multi-organ involvement including hepatitis (ALT >2x upper limit normal), nephritis (creatinine >1.5x baseline), and cardiac involvement (myocarditis/pericarditis). 1

Systemic Corticosteroid Therapy

Unlike Stevens-Johnson syndrome, corticosteroids are NOT contraindicated in DRESS and represent first-line therapy. 1, 3

• Start IV methylprednisolone 1-2 mg/kg/day for severe cases with significant organ involvement or extensive skin involvement. 1, 2, 3
• For less severe cases, oral prednisolone 0.5-1 mg/kg/day may be appropriate. 5
• Minimum 4-week taper is mandatory to prevent relapse, as DRESS involves T-cell immune-directed toxicity with long-lasting memory responses. 1, 2, 3
• Initiate proton pump inhibitor for gastrointestinal prophylaxis during corticosteroid therapy. 1

The prolonged taper is critical—premature steroid withdrawal leads to relapse in approximately 12% of cases. 1, 2

Second-Line Therapies for Steroid-Refractory Cases

For patients not responding to systemic steroids within 7 days, add intravenous immunoglobulin (IVIG) at 1-2 g/kg total dosage. 1, 3, 6

• IVIG has demonstrated efficacy in steroid-hyporesponsive DRESS, with fever resolution within median 1 day and liver enzyme improvement within median 13 days after initiation. 6
• Alternative immunosuppressive options include cyclosporine for severe or steroid-unresponsive cases. 1, 3, 7
• Additional agents reported in literature include cyclophosphamide and N-acetylcysteine, though evidence is limited. 7

Supportive Care Measures

• Fluid and electrolyte balance management with attention to minimizing insensible water losses. 2, 3
• Infection prevention measures are critical given immunosuppression and skin barrier disruption. 2, 4
• Topical corticosteroids (moderate to high potency) for symptomatic skin relief. 5, 2, 4
• Oral antihistamines for pruritus management. 5, 2, 3
• Serial clinical photography to track skin manifestations. 3

Specialist Consultation

• Consult appropriate specialists based on organ involvement: ophthalmology, otolaryngology, urology, or gynecology for mucous membrane involvement. 3
• Pain or palliative care consultation for symptom management in severe cases. 3
• Dermatology should be involved from initial presentation through resolution. 1, 2, 3

Critical Pitfalls to Avoid

• Never rechallenge with the suspected drug—DRESS involves severe T-cell-mediated delayed reactions with long-lasting memory responses, making rechallenge potentially fatal. 1
• Do not perform patch testing or delayed intradermal testing until at least 6 months after complete resolution AND at least 4 weeks after discontinuing systemic steroids (>10 mg prednisone equivalent). 1
• Avoid premature steroid taper—minimum 4 weeks required regardless of clinical improvement. 1, 2, 3
• Do not use prophylactic corticosteroids when initiating medications known to cause DRESS, as this has not proven effective and may increase rash risk. 3

Monitoring and Follow-up

• Close monitoring of liver enzymes, kidney function, and complete blood count throughout treatment course. 1
• Watch for viral reactivation (EBV, HHV-6) which contributes to pathophysiology and may predict relapse risk. 1, 2
• Elevated serum creatinine and ferritin at presentation predict fatal outcomes and warrant more aggressive management. 1