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

What is DRESS Syndrome?

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome is a rare, potentially life-threatening drug-induced hypersensitivity reaction characterized by a morbilliform rash involving >30% of body surface area, fever >38°C, eosinophilia, lymphadenopathy, and multi-organ involvement that typically occurs 2-6 weeks after exposure to the offending medication. 1

Defining Clinical Features

The hallmark presentation includes:

• Cutaneous manifestations: A morbilliform (maculopapular) confluent rash that typically involves more than 30% of body surface area, distinguishing it from milder drug reactions 1, 2
• Fever: Temperature >38°C with constitutional symptoms including rigors, myalgias, and arthralgias 1, 3
• Characteristic latency period: The reaction occurs 2-6 weeks after drug exposure, which is critical for identifying the culprit drug and distinguishes it from immediate drug reactions 1, 2
• Facial edema: Present in approximately 58% of cases 4

Hematologic and Laboratory Abnormalities

Key laboratory findings include:

• Eosinophilia: Defined as >700/μL or >10% of white blood cells, present in 95% of patients and typically peaks around 10 days after skin manifestations appear 1, 4
• Atypical lymphocytosis: Reactive lymphocytes reported in 26% of patients 4
• Leukocytosis: Present in 84% of cases 4

Multi-Organ Involvement

Systemic manifestations determine the severity and mortality risk:

• Hepatitis: The most common organ manifestation, with ALT >2 times the upper limit of normal, occurring in 74% of patients 1, 4
• Nephritis: Presents with creatinine >1.5 times baseline, with abnormal kidney function tests in 32% of cases 1, 3, 4
• Cardiac involvement: Can include myocarditis and pericarditis, with troponin elevation in 42% of patients 1, 4
• Pulmonary involvement: Pneumonitis may occur 2
• Lymphadenopathy: Commonly present as a systemic feature 1, 2

Pathophysiology

The underlying mechanisms involve:

• Viral reactivation: Reactivation of herpes family viruses, particularly EBV and HHV-6, plays a central role 1, 2
• T-cell immune-directed toxicity: Activation of lymphocytes leads to delayed hypersensitivity with long-lasting memory responses 1, 2
• Genetic predisposition: Specific HLA associations linked to particular drug reactions (e.g., HLA-B58:01 with allopurinol-induced DRESS, HLA-B5701 with abacavir) 1, 2

Common Causative Medications

The most frequently implicated drugs include:

• Antibiotics: Account for 74% of cases, including vancomycin, sulfonamides, and beta-lactams 5, 4, 6
• Anticonvulsants: Account for 21% of cases, including phenytoin, carbamazepine, and phenobarbital 5, 4, 7
• Allopurinol: A xanthine oxidase inhibitor with strong HLA-B*58:01 association 8
• Antiretrovirals: Particularly nevirapine (17-32% incidence) and abacavir (2.3-9% incidence) 5

Diagnostic Approach

Diagnosis is clinical, based on the RegiSCAR scoring system:

• Required workup includes: Complete blood count with differential to assess eosinophilia, comprehensive metabolic panel evaluating liver function (ALT, AST, alkaline phosphatase, bilirubin) and kidney function (BUN, creatinine), urinalysis to evaluate for nephritis, and skin biopsy if diagnosis is uncertain 1, 3
• RegiSCAR scoring: Classifies cases as "no," "possible," "probable," or "definite" based on clinical and laboratory findings (≥6 points confirms diagnosis) 1, 4
• Histopathology: Skin biopsy shows lymphocytic CD4+ infiltrates with eosinophils 3, 8

Distinguishing DRESS from Other Severe Cutaneous Reactions

Critical differentiating features:

• Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN): Characterized by blistering and epidermal detachment affecting <10% (SJS) to >30% (TEN) of body surface area, with mucosal membrane involvement, but typically lacks eosinophilia and has shorter latency 5, 3
• DRESS distinguishing features: Presence of eosinophilia, longer latency period (2-6 weeks vs. days), and prominent organ involvement 3

Prognosis and Complications

Mortality and morbidity considerations:

• Mortality rate: Approximately 5% in reported case series 4
• Recovery time: Mean recovery time is 2 weeks with appropriate treatment 4
• Relapse risk: Occurs in approximately 12% of cases, particularly with DRESS associated with viral reactivation 2
• Multi-organ failure: The severity is directly related to systemic involvement, which can result in multi-organ failure 7

Critical Pitfalls to Avoid

Important clinical caveats:

• Do not perform drug challenge: Drug challenge with the suspected culprit is contraindicated except in extreme circumstances, due to the severe T-cell-mediated delayed reaction with long-lasting memory responses 1
• Delayed allergy testing: Patch testing or delayed intradermal testing should not be performed until at least 6 months after complete resolution and at least 4 weeks after discontinuing systemic steroids (>10 mg prednisone equivalent) 1, 2
• Avoid prophylactic corticosteroids: Do not use prophylactic corticosteroids when initiating medications known to cause DRESS, as this has not proven effective and may increase the risk of skin rash 3