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

DRESS Syndrome Management

Immediately discontinue the suspected causative drug, initiate IV methylprednisolone at 1-2 mg/kg/day, and consult dermatology urgently—these three interventions form the cornerstone of DRESS management and should be implemented simultaneously for all suspected cases. 1, 2

Initial Emergency Management

Immediate Actions (First 24 Hours)

• Stop the offending drug immediately without waiting for diagnostic confirmation, as this is the single most critical intervention that determines outcomes 1, 2, 3
• Start IV methylprednisolone 1-2 mg/kg/day as first-line systemic therapy for all suspected cases 1, 2, 3
• Obtain urgent dermatology consultation to confirm diagnosis and guide management 1, 2, 3
• Admit severe cases to ICU or burn unit if there is extensive skin involvement (>30% body surface area), significant organ dysfunction, or hemodynamic instability 2, 3

Diagnostic Workup

Perform the following tests immediately to establish baseline organ function and confirm diagnosis:

• Complete blood count with differential to document eosinophilia (>700/μL or >10% of WBCs) 2
• Comprehensive metabolic panel including liver enzymes (ALT, AST, alkaline phosphatase, bilirubin) and renal function (BUN, creatinine) 2
• Urinalysis to assess for nephritis 2, 3
• Blood cultures if febrile to exclude infectious mimics 2
• Skin biopsy only if diagnosis is uncertain—shows perivascular lymphocytic infiltration with eosinophils and dermal edema 2, 3

Systemic Corticosteroid Therapy

Dosing and Duration

• Start with IV methylprednisolone 1-2 mg/kg/day (unlike Stevens-Johnson syndrome, corticosteroids are NOT contraindicated in DRESS) 1, 2, 3
• Taper over a minimum of 4 weeks—this extended duration is critical because DRESS involves T-cell immune-directed toxicity with long-lasting memory responses 1, 2, 3
• Do NOT taper prematurely, as relapse occurs in approximately 12% of cases, particularly with rapid steroid withdrawal 1, 2
• Initiate proton pump inhibitor for gastrointestinal prophylaxis during corticosteroid therapy 2

Common Pitfall

The most frequent error is tapering steroids too quickly (less than 4 weeks), which leads to disease relapse and prolonged morbidity. The minimum 4-week taper is non-negotiable. 1, 2

Supportive Care Measures

Symptomatic Management

• Topical corticosteroids (moderate-to-high potency such as mometasone 0.1% or betamethasone 0.1%) for cutaneous symptoms 2
• Oral antihistamines for pruritus: loratadine 10 mg daily for daytime, or diphenhydramine 25-50 mg or hydroxyzine 25-50 mg at night for sedation 2
• Fluid and electrolyte management to minimize insensible water losses 1, 3
• Infection prevention measures given immunosuppression and skin barrier disruption 1, 3

Oral Ulcer Management (if present)

• Dexamethasone 0.1 mg/mL mouth rinse for widespread oral ulcerations 2
• Clobetasol 0.05% gel for localized, accessible ulcers 2
• Viscous lidocaine 2% for immediate topical analgesia 2

Refractory or Steroid-Unresponsive Cases

If patients fail to improve after 3-5 days of systemic corticosteroids or cannot tolerate steroid side effects:

• Intravenous immunoglobulin (IVIG) 1-2 g/kg total dose as second-line therapy 2, 3
• Cyclosporine may be considered for severe or steroid-unresponsive cases 2, 3
• Alternative immunosuppressants including cyclophosphamide have been reported in case series but lack robust evidence 4, 5

Organ-Specific Monitoring and Consultation

Hepatic Involvement (Most Common)

• Monitor ALT/AST every 2-3 days until trending downward 2
• Hepatitis (ALT >2× upper limit of normal) occurs in the majority of cases 2

Cardiac Involvement (4-21% of Cases)

• Obtain baseline ECG and troponin to screen for myocarditis or pericarditis 2
• Consult cardiology if cardiac biomarkers are elevated or ECG shows abnormalities 2
• Avoid NSAIDs as they worsen heart failure outcomes and may have been the causative agent 2

Renal Involvement

• Monitor creatinine closely—nephritis is defined as creatinine >1.5× baseline 2
• Elevated creatinine at presentation predicts fatal outcomes 2

Pulmonary Involvement

• Obtain chest X-ray if respiratory symptoms develop to assess for pneumonitis 1

Critical Pitfalls to Avoid

Drug Rechallenge

Never rechallenge with the suspected culprit drug—DRESS involves severe T-cell-mediated delayed reactions with long-lasting memory responses, and rechallenge can be fatal 2

Diagnostic Testing Timing

• 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) 2
• Early testing can trigger systemic relapse 2

Prophylactic Corticosteroids

Do NOT use prophylactic corticosteroids when initiating medications known to cause DRESS—this has not proven effective and may increase the risk of skin rash 3

Common Causative Drugs to Identify

The latency period of 2-6 weeks is critical for identifying the culprit drug:

• Antibiotics (74% of cases): vancomycin, sulfonamides, beta-lactams 2
• Anticonvulsants (21% of cases): phenytoin, carbamazepine, phenobarbital 2
• Antiretrovirals: nevirapine (17-32% incidence), abacavir (2.3-9% incidence) 2
• Allopurinol (associated with HLA-B*58:01) 2
• NSAIDs (<5% of cases): oxicam derivatives, diclofenac 2

Genetic Testing Considerations

HLA-B*5701 testing before abacavir and HLA-B*58:01 testing before allopurinol in high-risk populations can prevent hypersensitivity reactions 1, 2

Prognosis and Follow-Up

• Relapse occurs in approximately 12% of cases, particularly with viral reactivation (HHV-6, EBV, CMV) 1, 6
• Autoimmune complications can develop months after resolution, requiring long-term monitoring 6
• Serial clinical photography should document skin manifestations to track response 3
• Avoid all structurally related drugs permanently after recovery 1