What is the appropriate workup and treatment for a patient suspected of having DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome, presenting with a diffuse pruritic bleeding rash?

DRESS Syndrome Workup

Immediately discontinue all suspected causative medications, obtain a complete blood count with differential, comprehensive metabolic panel, urinalysis, and perform a total body skin examination with attention to all mucous membranes—then initiate IV methylprednisolone 1-2 mg/kg/day for severe cases. 1, 2

Initial Clinical Assessment

Complete skin examination:

• Examine the entire body surface area to quantify extent of rash involvement (typically >30% BSA in DRESS) 1, 3
• Inspect ALL mucous membranes (oral, ocular, genital, anal) for erosions, blistering, or detachment—this helps distinguish DRESS from Stevens-Johnson syndrome/TEN 4, 2
• Document findings with serial clinical photography for monitoring progression 4, 2
• Look specifically for morbilliform (maculopapular) confluent rash, which is the most common presentation 1, 3

Key distinguishing features to assess:

• Timing: DRESS typically occurs 2-6 weeks after drug exposure (not days), unlike immediate drug reactions 1, 3
• Facial edema and lymphadenopathy are common in DRESS 3
• Pruritus is typically present 4
• Fever >38°C is characteristic 3

Laboratory Workup

Essential blood tests:

• Complete blood count with differential to assess for eosinophilia (>700/μL or >10% of WBCs) and atypical lymphocytes 4, 2, 3
• Comprehensive metabolic panel including liver function tests (ALT, AST, alkaline phosphatase, bilirubin) and kidney function (BUN, creatinine) 4, 2, 3
• Hepatitis is the most common organ manifestation with ALT >2 times upper limit of normal 3

Additional critical tests:

• Urinalysis to evaluate for nephritis (hematuria, proteinuria) 4, 2, 3
• Blood cultures if febrile to rule out infection 4

Skin biopsy (if diagnosis uncertain):

• Perform biopsy to assess for lymphocytic CD4+ infiltrates with eosinophils, which is characteristic of DRESS 2
• Helps exclude full-thickness epidermal necrosis (seen in SJS/TEN), paraneoplastic pemphigus, or other autoimmune blistering disorders 4

Immediate Management Based on Severity

For Grade 3-4 or severe DRESS (>50% BSA, organ involvement, or systemic symptoms):

• Admit immediately to burn unit or ICU with dermatology consultation 4, 2
• Initiate IV methylprednisolone 1-2 mg/kg/day, then convert to oral corticosteroids when appropriate 4, 2
• Critical: Taper steroids over at least 4 weeks (minimum) to prevent relapse—this is longer than other drug reactions due to T-cell immune-directed toxicity 1, 2, 3
• Unlike SJS/TEN, corticosteroids are NOT contraindicated in DRESS and are first-line therapy 2, 3

Supportive care measures:

• Fluid and electrolyte balance management 4, 2
• Minimize insensible water losses 4, 2
• Infection prevention protocols 4, 2
• High-potency topical corticosteroids (clobetasol, betamethasone) for symptomatic relief 4
• Oral antihistamines for pruritus 4, 2
• Topical emollients and petrolatum-based products 4

For steroid-unresponsive cases:

• Consider intravenous immunoglobulin (IVIG) at total dosage of 1-2 g/kg 2
• Cyclosporine may be considered as alternative immunosuppression 2

Specialist Consultations

Mandatory consultations:

• Dermatology for all suspected DRESS cases 1, 2
• Wound care services for severe cases 4, 2

Based on organ involvement:

• Ophthalmology for ocular mucous membrane involvement 2
• Cardiology if myocarditis or pericarditis suspected 3
• Nephrology for significant renal dysfunction 3
• Hepatology for severe hepatitis 3

Critical Pitfalls to Avoid

Do NOT:

• Continue the suspected causative drug—immediate discontinuation is paramount 1, 2, 5
• Use prophylactic corticosteroids when initiating high-risk medications (not effective and may increase rash risk) 2
• Perform patch testing or intradermal testing until at least 6 months after complete resolution AND at least 4 weeks after discontinuing systemic steroids 3
• Attempt drug rechallenge except in extreme circumstances—this is contraindicated due to severe T-cell-mediated memory responses 3
• Taper steroids too quickly—minimum 4 weeks required, as relapse occurs in approximately 12% of cases 1, 3

Common causative medications to consider discontinuing:

• Antibiotics (vancomycin, sulfonamides, beta-lactams) account for 74% of cases 3
• Anticonvulsants (phenytoin, carbamazepine, phenobarbital, levetiracetam) account for 21% of cases 3, 6
• Allopurinol (strongly associated with HLA-B*58:01) 3
• Antiretrovirals (nevirapine, abacavir) 3

Monitoring and Follow-up

• Serial clinical photography to track progression or improvement 4, 2
• Monitor for multi-organ involvement including pneumonitis, myocarditis, and nephritis 1, 3
• Watch for viral reactivation (EBV, HHV-6) which is part of the pathophysiology 1, 3
• Mortality is approximately 10%, primarily from visceral organ compromise 5