What is the recommended treatment for drug reaction with eosinophilia and systemic symptoms (DRESS)?

DRESS Syndrome Treatment

Immediately discontinue the suspected causative drug and start IV methylprednisolone 1-2 mg/kg/day with a minimum 4-week taper, as this is the cornerstone of DRESS management. 1, 2, 3

Immediate Management Steps

Drug Discontinuation and Consultation

• Stop the offending medication immediately—this is the single most critical intervention and takes priority over all other treatments 1, 2, 3
• Obtain urgent dermatology consultation for all suspected cases 1, 2, 3
• Severe cases require admission to burn unit or ICU with dermatology and wound care services 1, 3

Initial Diagnostic Workup

• Complete blood count with differential to assess eosinophilia (>700/μL or >10%) 1
• Comprehensive metabolic panel evaluating liver function (ALT, AST, alkaline phosphatase, bilirubin) and kidney function (BUN, creatinine) 1
• Urinalysis to evaluate for nephritis 1, 3
• Blood cultures if febrile to rule out infectious mimics 1
• Skin biopsy only if diagnosis is uncertain (shows perivascular lymphocytic infiltration with dermal edema and eosinophils) 1

First-Line Systemic Treatment

Corticosteroid Therapy

• Start IV methylprednisolone 1-2 mg/kg/day as first-line therapy 1, 2, 3
• Taper over a minimum of 4 weeks—this extended duration is mandatory due to T-cell immune-directed toxicity with long-lasting memory responses 1, 2
• Premature taper leads to relapse in 12% of cases 1, 2
• Unlike Stevens-Johnson syndrome, corticosteroids are NOT contraindicated in DRESS 1, 3
• Start proton pump inhibitor for gastrointestinal prophylaxis during corticosteroid therapy 1

Supportive Care Measures

Symptomatic Management

• Topical corticosteroids: moderate-to-high potency (mometasone 0.1% or betamethasone 0.1%) for cutaneous symptoms 1
• Oral antihistamines: second-generation agents like loratadine 10 mg daily for daytime pruritus 1
• First-generation antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for nighttime itch due to sedative properties 1
• Fluid and electrolyte balance management 1, 2, 3
• Infection prevention measures 1, 2, 3

Oral Ulcer Management (if present)

• Dexamethasone 0.1 mg/mL mouth rinse for multiple or difficult-to-reach ulcerations 1
• Clobetasol 0.05% gel for limited, accessible ulcers 1
• Viscous lidocaine 2% for immediate topical analgesia 1

Second-Line Therapies for Steroid-Unresponsive Cases

Alternative Immunosuppression

• Intravenous immunoglobulin (IVIG): 1-2 g/kg total dosage for patients not responding to systemic steroids 1, 3
• Cyclosporine: consider in severe or steroid-unresponsive cases 1, 3
• Other options reported in literature include cyclophosphamide, N-acetylcysteine, and plasmapheresis, though evidence is limited 4, 5

Organ-Specific Considerations

Cardiac Involvement (occurs in 4-21% of cases)

• Assess NYHA functional class and left ventricular ejection fraction 1
• Use loop diuretics (furosemide 20-40 mg once or twice daily, titrated to effect) for fluid retention 1
• ACE inhibitors for heart failure with reduced ejection fraction 1
• Avoid NSAIDs as they adversely affect heart failure outcomes and may have been the causative agent 1
• Withdraw calcium channel blockers with negative inotropic effects if ejection fraction <40% 1

Hepatic Involvement (most common organ manifestation)

• Monitor ALT >2 times upper limit of normal 1
• Serial liver function tests during treatment 1

Renal Involvement

• Monitor creatinine >1.5 times baseline 1
• Elevated serum creatinine at presentation predicts fatal outcomes 1

Critical Pitfalls to Avoid

• Never rechallenge with the suspected drug—DRESS involves severe T-cell-mediated delayed reactions with long-lasting memory responses 1, 2
• Do not perform patch testing or delayed intradermal testing until ≥6 months after complete resolution AND ≥4 weeks after discontinuing systemic steroids (>10 mg prednisone-equivalent)—early testing risks systemic relapse 1
• Do not use prophylactic corticosteroids when initiating medications known to cause DRESS—this has not proven effective and may increase risk of skin rash 3
• Do not taper steroids prematurely—minimum 4 weeks required to prevent relapse 1, 2

Common Causative Drugs to Identify

• Antibiotics (74% of cases): vancomycin, sulfonamides, beta-lactams 1
• Anticonvulsants (21% of cases): phenytoin, carbamazepine, phenobarbital 1, 6
• Antiretrovirals: nevirapine (17-32% incidence), abacavir (2.3-9% incidence) 1
• Allopurinol: associated with 23% of fatal cases 7
• NSAIDs: account for <5% of DRESS cases but include oxicam derivatives and diclofenac 1

Prognosis and Monitoring

• Overall mortality rate is approximately 9% 7
• Relapse occurs in 12% of cases, particularly with viral reactivation 1, 2
• Use serial clinical photography to track skin manifestations 3
• Elevated serum ferritin at presentation predicts fatal outcomes 1
• Higher lymphocyte counts indicate need for systemic corticosteroids 1