What is the step-by-step approach to diagnosing and managing DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome?

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Last updated: August 1, 2025View editorial policy

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Diagnosis and Management of DRESS Syndrome

The management of DRESS syndrome requires immediate discontinuation of the causative medication, hospitalization, and systemic corticosteroid therapy as the mainstay of treatment. 1

Diagnostic Approach

Step 1: Identify Key Diagnostic Features

  • Skin rash (typically morbilliform, confluent, maculopapular eruption)
  • Eosinophilia (>500 cells/μL)
  • Systemic symptoms (fever >38°C)
  • Internal organ involvement (liver, kidney, lung, heart)
  • Temporal relationship to drug exposure (2-6 weeks after initiation) 2
  • Lymphadenopathy

Step 2: Laboratory Evaluation

  • Complete blood count with differential (look for eosinophilia, atypical lymphocytes)
  • Liver function tests (elevated transaminases)
  • Renal function tests (BUN, creatinine)
  • Consider viral studies (HHV-6, HHV-7, EBV, CMV) 1

Step 3: Skin Biopsy (if diagnosis is uncertain)

  • Look for interface dermatitis, perivascular lymphocytic infiltration with eosinophils

Step 4: Apply Diagnostic Criteria

  • Use validated diagnostic criteria (RegiSCAR or Japanese consensus group) to confirm diagnosis 3

Management Protocol

Step 1: Immediate Actions

  • Immediately discontinue the suspected culprit medication 1
  • Hospitalize the patient; severe cases should be admitted to ICU or burn unit 1
  • Consider photographic documentation of skin lesions for monitoring progression

Step 2: Systemic Corticosteroid Therapy

  • For moderate cases: IV methylprednisolone 0.5-1 mg/kg/day 1
  • For severe cases with significant organ involvement: IV methylprednisolone 1-2 mg/kg/day 1
  • Convert to oral steroids once response is noted
  • Taper steroids slowly over at least 4 weeks to prevent rebound 4, 1

Step 3: Supportive Care

  • Topical emollients and high-potency topical corticosteroids for skin symptoms 4
  • Oral antihistamines for pruritus
  • Fluid and electrolyte management
  • Nutritional support
  • Infection prevention measures 1

Step 4: Management of Steroid-Resistant Cases

  • Consider IVIG (1-2 g/kg) for steroid-unresponsive cases 5
  • Alternative immunosuppressants like cyclosporine may be considered in refractory cases 1, 6

Step 5: Specialist Consultation

  • Consult appropriate specialists based on organ involvement:
    • Hepatology for liver involvement
    • Nephrology for kidney involvement
    • Pulmonology for lung involvement
    • Cardiology for cardiac involvement 1

Step 6: Monitoring and Follow-up

  • Daily monitoring of:
    • Vital signs
    • Skin involvement
    • Complete blood count
    • Liver and kidney function tests
    • Other affected organ systems 1
  • Continue treatment until:
    • Resolution of skin manifestations
    • Normalization of laboratory abnormalities
    • Resolution of organ dysfunction 1

Important Considerations

Avoiding Common Pitfalls

  • Delayed recognition: Early diagnosis is critical, especially after the 6th week of treatment with high-risk medications 1
  • Premature steroid tapering: Can lead to rebound symptoms and worsening of condition 1
  • Reintroduction of culprit medication: Must be permanently avoided, including structurally related compounds 1
  • Inadequate monitoring: DRESS can have a prolonged course with flares during steroid tapering

Testing for Drug Causality

  • Patch testing and delayed intradermal testing may help identify culprit drugs 4
  • For DRESS, the sensitivity of patch testing is >50% for many drugs
  • Testing should be delayed until ≥6 months after complete healing of reaction and/or ≥1 month after discontinuation of systemic corticosteroids 4
  • Given the imperfect negative predictive value, patients with a negative test should still avoid the suspected culprit drug 4

Long-term Follow-up

  • Monitor for potential sequelae including autoimmune diseases
  • Provide patient education about avoiding culprit medication and cross-reactive drugs
  • Create a comprehensive medical alert regarding drug allergy

By following this structured approach to diagnosis and management, dermatologists can effectively treat DRESS syndrome and minimize its potentially life-threatening complications.

References

Guideline

Management of DRESS Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

DRESS syndrome: Part II. Management and therapeutics.

Journal of the American Academy of Dermatology, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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