What is the updated protocol for diagnosis and management of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome?

Updated Protocol for Diagnosis and Management of DRESS Syndrome

Immediately discontinue the suspected causative drug and initiate systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day) with a minimum 4-week taper for all suspected DRESS cases, as this represents the cornerstone of management. 1, 2

Diagnostic Approach

Clinical Recognition

• DRESS presents 2-6 weeks after drug exposure with a characteristic triad: morbilliform rash involving >30% body surface area, fever >38°C, and systemic organ involvement 1, 3
• The latency period distinguishes DRESS from immediate drug reactions and is critical for identifying the culprit drug 4, 1
• Constitutional symptoms include rigors, myalgias, and arthralgias accompanying the rash 1, 3

Diagnostic Workup

Clinical diagnosis remains the gold standard, using the RegiSCAR scoring system to classify cases as "no," "possible," "probable," or "definite" 4, 1

Required laboratory evaluation includes:

• Complete blood count with differential to document eosinophilia (>700/μL or >10% of WBCs) 1, 3
• Comprehensive metabolic panel assessing hepatic involvement (ALT >2× upper limit normal is most common organ manifestation) and renal function (creatinine >1.5× baseline) 1, 3
• Urinalysis to evaluate for nephritis 1, 3
• Skin biopsy if diagnosis uncertain, showing lymphocytic CD4+ infiltrates with eosinophils 3

Distinguishing Features

• DRESS differs from Stevens-Johnson syndrome/TEN by the presence of eosinophilia, longer latency period, and prominent organ involvement rather than mucosal involvement 3
• Unlike SJS/TEN, corticosteroids are NOT contraindicated in DRESS 1, 3

Management Protocol

Immediate Actions

1. Discontinue all suspected drugs immediately - this is the single most crucial intervention 1, 2, 3
2. Obtain urgent dermatology consultation for all suspected cases 1, 2, 3
3. Initiate systemic corticosteroids - IV methylprednisolone 1-2 mg/kg/day 1, 2, 3

Severity-Based Treatment Algorithm

For severe cases (extensive skin involvement, significant organ dysfunction, or hemodynamic instability):

• Admit to burn unit or ICU with dermatology and wound care consultation 1, 3
• Continue IV methylprednisolone 1-2 mg/kg/day 1, 3
• Provide aggressive supportive care: fluid/electrolyte management, minimize insensible losses, infection prevention 1, 3

For steroid-unresponsive cases (no improvement after 7 days of adequate steroid therapy):

• Add IVIG at total dosage of 1-2 g/kg, which hastens fever resolution (median 1 day) and liver enzyme improvement (median 13 days) 1, 5
• Consider cyclosporine as alternative immunosuppression 1

Steroid Tapering Protocol

Wean corticosteroids over a minimum of 4 weeks - this extended taper is essential due to T-cell immune-directed toxicity and prevents relapse (occurs in ~12% of cases) 1, 2, 3

Rapid tapering risks disease flare, as DRESS involves prolonged T-cell activation requiring sustained immunosuppression 1, 3

Supportive Care

• Topical corticosteroids and oral antihistamines for symptomatic relief 1, 2
• Serial clinical photography to track progression 3
• Consult appropriate specialists based on organ involvement (ophthalmology, cardiology for myocarditis/pericarditis, nephrology) 3
• Consider pain/palliative care consultation for symptom management 3

Critical Pitfalls to Avoid

Testing Timing Errors

Do NOT perform patch testing or delayed intradermal testing until at least 6 months after complete resolution AND at least 4 weeks after discontinuing systemic steroids (>10 mg prednisone equivalent) 4, 1, 2

Testing too early yields false negatives and risks reactivating the reaction 4

Drug Challenge Contraindication

Drug challenge with the suspected culprit is contraindicated except in extreme circumstances where benefit clearly outweighs risk 1

DRESS represents a severe T-cell-mediated delayed reaction with long-lasting memory responses, making rechallenge dangerous 4

Premature Steroid Discontinuation

Tapering faster than 4 weeks significantly increases relapse risk, particularly with viral reactivation-associated DRESS 1, 2

Prophylactic Steroid Misuse

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

Adjunctive Diagnostic Testing (When Culprit Drug Uncertain)

If the offending agent remains unclear after clinical assessment, delayed intradermal testing (dIDT) and/or patch testing may support drug causality, but only after the appropriate waiting period 4

Testing parameters:

• Delayed intradermal: 0.02-0.05 mL volume, read at 24 hours for induration 4
• Patch testing: 10-30% trade product or 1-10% pure substance, remove at 48 hours with readings at 24-72 hours, 96 hours, and 7 days 4
• Evidence quality is very low for these modalities; clinical diagnosis remains superior 4

Monitoring and Follow-up

Blood eosinophilia serves as a useful marker of disease progression and treatment response 6

Close monitoring of organ function (hepatic, renal, cardiac) throughout treatment course is essential given the multi-organ nature of DRESS 1, 3