What is DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)?

DRESS Syndrome: Drug Reaction with Eosinophilia and Systemic Symptoms

DRESS syndrome is a severe, potentially life-threatening cutaneous adverse drug reaction characterized by skin rash, facial edema, eosinophilia, and internal organ involvement that typically occurs 2-6 weeks after drug initiation. 1

Key Characteristics

Clinical Presentation

• Cutaneous manifestations:

  • Morbilliform rash with facial edema (most common)
  • Can present in four distinct patterns:
    1. Urticated papular exanthem
    2. Morbilliform erythema
    3. Exfoliative erythroderma
    4. Erythema multiforme-like reaction with atypical targets (associated with more severe hepatic involvement) 2

• Systemic features:

  • Fever (nearly universal)
  • Lymphadenopathy
  • Internal organ involvement (particularly liver, kidneys, lungs, heart)
  • Hematologic abnormalities:
    • Eosinophilia (>700 cells/μL or >10% of total WBC)
    • Atypical lymphocytosis 1

Common Causative Medications

• Anticonvulsants
• Sulfonamides
• Antibiotics
• Nevirapine and other antiretrovirals
• Allopurinol 1, 3

Pathophysiology

DRESS syndrome involves:

• Genetic predisposition
• Abnormal drug metabolism
• Reactivation of herpes family viruses (HHV-6, EBV)
• Aberrant T-cell and eosinophil responses 4

Diagnosis

DRESS can be distinguished from other severe cutaneous adverse reactions like Stevens-Johnson Syndrome (SJS) by:

Feature	DRESS	SJS
Facial edema	Present	Absent
Mucosal involvement	Less common	Prominent
Eosinophilia	Present	Absent
Latency period	2-6 weeks	Shorter (1-3 weeks)
Skin biopsy	Interface dermatitis with eosinophils	Full-thickness epidermal necrosis
Internal organ involvement	Common	Less common

1

Management

1. Immediate discontinuation of the culprit drug (most critical step)
2. Systemic corticosteroids for moderate to severe cases:
   • Methylprednisolone 0.5-1 mg/kg/day for moderate cases
   • Methylprednisolone 1-2 mg/kg/day for severe cases 1
3. Supportive care:
   • Continuous hemodynamic monitoring
   • Strict hydroelectrolytic balance
   • Prevention of secondary infections
   • Appropriate skin care 1
4. Alternative therapies for steroid-resistant cases:
   • Cyclosporine (second-line)
   • IVIG (add-on therapy for steroid-hyporesponsive cases) 5

Indications for ICU Admission

• Extensive skin involvement (≥10% body surface area)
• Significant mucosal involvement
• Severe organ dysfunction:
  • Shock requiring vasopressors
  • Need for mechanical ventilation
  • Acute renal failure
  • Pulmonary edema or ARDS 1

Prognosis and Follow-up

• Mortality rate approximately 10%, primarily from visceral organ compromise
• Most patients recover completely with appropriate therapy
• Potential for chronic complications including autoimmune diseases
• Patients should:
  • Permanently avoid the causative medication
  • Create a medical alert for drug allergy
  • Undergo monitoring for potential sequelae 1
  • Consider patch testing and delayed intradermal testing (≥6 months after healing) to identify culprit drugs 1

Important Clinical Pearls

• The erythema multiforme-like cutaneous presentation may indicate more severe hepatic involvement and worse prognosis 2
• DRESS has a longer latency period (2-6 weeks) than most other drug reactions, which can complicate identification of the culprit medication 3
• Viral reactivation may influence the severity of DRESS presentation and should be considered in treatment planning 4
• Patients should avoid structurally related compounds to prevent cross-reactivity 1