DRESS Syndrome: Management and Treatment Overview
Immediate Management
Immediately discontinue the suspected causative drug and initiate systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day) for all suspected DRESS cases, followed by prompt dermatology consultation. 1, 2
First-Line Actions
- Stop the offending medication immediately - this is the single most critical intervention that directly impacts mortality 1, 2, 3
- Obtain dermatology consultation urgently for all suspected cases 1, 2
- Admit severe cases (significant organ involvement or >30% body surface area) to ICU or burn unit 2, 3
Clinical Recognition
DRESS presents with a characteristic constellation after a 2-6 week latency period following drug exposure, distinguishing it from immediate drug reactions: 1, 2
- Morbilliform (maculopapular) confluent rash involving >30% body surface area 1, 2
- Fever >38°C with constitutional symptoms (rigors, myalgias, arthralgias) 2, 3
- Eosinophilia >700/μL or >10% of WBCs 2
- Lymphadenopathy 1, 2
- Multi-organ involvement: hepatitis (ALT >2x upper limit normal - most common), nephritis (creatinine >1.5x baseline), myocarditis, pericarditis, or pneumonitis 1, 2
Most Common Culprit Drugs
- Anticonvulsants (phenytoin, carbamazepine) 4, 5
- Allopurinol (associated with HLA-B*58:01) 2
- Sulfonamides 4
- Dapsone and vancomycin 5
Diagnostic Workup
Obtain the following immediately upon suspicion: 2, 3
- Complete blood count with differential (assess eosinophilia, atypical lymphocytes)
- Comprehensive metabolic panel (ALT, AST, alkaline phosphatase, bilirubin, BUN, creatinine)
- Urinalysis (evaluate for nephritis)
- Blood cultures (rule out infection)
- Skin biopsy if diagnosis uncertain (shows lymphocytic CD4+ infiltrates with eosinophils) 3
Use the RegiSCAR scoring system to classify cases as "no," "possible," "probable," or "definite" based on clinical and laboratory findings 2
Pharmacologic Treatment
Systemic Corticosteroids (First-Line)
- IV methylprednisolone 1-2 mg/kg/day 1, 2, 3
- Wean over minimum 4 weeks - this extended taper is critical due to T-cell immune-directed toxicity and prevents relapse (occurs in ~12% of cases) 1, 2, 3
- Unlike Stevens-Johnson syndrome, corticosteroids are not contraindicated in DRESS and are necessary for adequate immunosuppression 2, 3
Second-Line Therapies (Steroid-Unresponsive Cases)
- Intravenous immunoglobulin (IVIG) 1-2 g/kg total dosage - add within 7 days if inadequate response to steroids, with fever resolution typically within 1 day and liver enzyme improvement within 13 days 1, 2, 5
- Cyclosporine - consider for severe or steroid-refractory cases 1, 2
Supportive Care
Provide comprehensive supportive measures: 1, 3
- Fluid and electrolyte balance management
- Minimize insensible water losses
- Infection prevention measures (critical given immunosuppression)
- Topical corticosteroids for symptomatic relief
- Oral antihistamines for pruritus
- Serial clinical photography to track progression
Specialist Consultation
Consult appropriate specialists based on organ involvement: 3
- Ophthalmology, otolaryngology, urology, or gynecology for mucous membrane involvement
- Cardiology for myocarditis/pericarditis
- Nephrology for significant renal involvement
- Pain/palliative care for symptom management
Critical Pitfalls to Avoid
- Do NOT perform patch testing or intradermal testing until at least 6 months after complete resolution AND at least 1 month (preferably 4 weeks) after discontinuing systemic steroids 1, 2
- Drug challenge with the suspected culprit is contraindicated except in extreme circumstances due to severe T-cell-mediated memory responses 2
- Do NOT use prophylactic corticosteroids when initiating medications known to cause DRESS - this has not proven effective and may increase rash risk 3
- Do NOT taper steroids too quickly - minimum 4-week taper is essential to prevent relapse 1, 2
Pathophysiology Context
The syndrome involves reactivation of herpes family viruses (EBV, HHV-6) and T-cell immune-directed toxicity, explaining the delayed presentation and need for prolonged immunosuppression 1, 2. Genetic predispositions through MHC/HLA associations (e.g., HLA-B5701 for abacavir, HLA-B58:01 for allopurinol) play a significant role 1, 2.