DRESS Syndrome Management
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
First Steps in Sequence
- Stop the offending drug as the single most critical intervention—this is non-negotiable and must occur before any other treatment 1, 2, 3
- Obtain dermatology consultation urgently 1, 2, 3
- Start IV methylprednisolone 1-2 mg/kg/day immediately for all suspected cases 1, 2, 3
- Unlike Stevens-Johnson syndrome, corticosteroids are NOT contraindicated in DRESS and are first-line therapy 1, 3
Diagnostic Workup
Required Laboratory Studies
- Complete blood count with differential to assess for eosinophilia (>700/μL or >10% of WBCs) 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 exclude infectious mimics 1
Additional Diagnostic Considerations
- Skin biopsy if diagnosis is uncertain—expect perivascular lymphocytic infiltration with dermal edema and CD4+ lymphocytes with eosinophils 1, 3
- Use the RegiSCAR scoring system to classify cases as "no," "possible," "probable," or "definite" 1
- Recognize the characteristic 2-6 week latency period after drug exposure, which distinguishes DRESS from immediate drug reactions 1, 2, 4
Clinical Features to Confirm Diagnosis
Cardinal Features
- Morbilliform (maculopapular) confluent rash involving >30% of body surface area 1
- Fever >38°C with constitutional symptoms (rigors, myalgias, arthralgias) 1, 3
- Eosinophilia as a hallmark feature 1
- Lymphadenopathy 1
Organ Involvement Patterns
- Hepatitis is the most common organ manifestation (ALT >2× upper limit of normal) 1
- Nephritis with creatinine >1.5× baseline 1
- Cardiac involvement including myocarditis and pericarditis (occurs in 4-21% of cases) 1
- Facial edema is present in approximately 44% of cases 5
Systemic Corticosteroid Protocol
Dosing and Duration
- Start IV methylprednisolone 1-2 mg/kg/day 1, 2, 3
- Taper over a MINIMUM of 4 weeks—this is critical because DRESS involves T-cell immune-directed toxicity with long-lasting memory responses 1, 2, 3
- Premature steroid taper leads to relapse in approximately 12% of cases 1, 2
- Start proton pump inhibitor for gastrointestinal prophylaxis during corticosteroid therapy 1
Common Pitfall to Avoid
- 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
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 antihistamines like loratadine 10 mg daily for daytime pruritus 1
- For nighttime itch, use first-generation antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for sedative properties 1
Oral Ulcer Management (if present)
- High-potency topical corticosteroids: dexamethasone 0.1 mg/mL mouth rinse for multiple sites or clobetasol 0.05% gel for limited ulcers 1
- Viscous lidocaine 2% for immediate topical analgesia 1
- Bland, non-alcoholic sodium bicarbonate mouthwash up to hourly as needed 1
General Supportive Care
- Fluid and electrolyte balance management 1, 2, 3
- Minimize insensible water losses 1, 3
- Infection prevention measures 1, 3
Severe Cases and Refractory Disease
Admission Criteria
- Severe symptoms or significant organ involvement require hospital admission 3
- Consider ICU or burn unit admission with dermatology and wound care services for severe cases 1, 3
Second-Line Therapies for Steroid-Unresponsive Cases
- Intravenous immunoglobulin (IVIG) at 1-2 g/kg total dosage 1, 3
- Cyclosporine may be considered in severe or steroid-unresponsive cases 1, 3
Specialist Consultations Based on Organ Involvement
- Ophthalmology, otolaryngology, urology, or gynecology for mucous membrane involvement 3
- Pain or palliative care consultation for symptom management 3
- Cardiology if cardiac involvement is suspected 1
Long-Term Monitoring and Follow-Up
Serial Monitoring
- Use serial clinical photography to track skin manifestations 3
- Monitor for emergent autoimmunity during long-term follow-up 6
- Watch for relapse, particularly with DRESS associated with viral reactivation 2
Drug Testing Contraindications
- NEVER perform drug challenge with the suspected culprit except in extreme circumstances—DRESS involves severe T-cell-mediated delayed reactions with long-lasting memory 1, 2
- Patch testing or delayed intradermal testing should NOT be performed until ≥6 months after complete resolution AND ≥4 weeks after discontinuing systemic steroids (>10 mg prednisone-equivalent) 1, 2
- The sensitivity of patch testing in DRESS is approximately 64%, but early testing risks systemic relapse 1
Common Causative Drugs
Most Frequently Implicated Classes
- Antibiotics (74% of cases): vancomycin, sulfonamides, beta-lactams 1
- Anticonvulsants (21% of cases): phenytoin, carbamazepine, phenobarbital 1
- Allopurinol is associated with 23% of fatal cases and has strong HLA-B*58:01 association 1, 5
- Antiretrovirals: nevirapine (17-32% incidence), abacavir (2.3-9% incidence) 1
- NSAIDs account for <5% of DRESS cases, with oxicam derivatives and acetic-acid NSAIDs showing higher association 1
Genetic Predispositions
- HLA-B*58:01 is linked to allopurinol-induced DRESS 1
- HLA-B*3505 is associated with nevirapine-induced DRESS in Thai populations 1
- Consider genetic testing (e.g., HLA-B*5701 for abacavir) before prescribing certain medications to prevent hypersensitivity reactions 2