What is a drug rash?

What is a Drug Rash?

A drug rash is a cutaneous adverse reaction to medication that manifests most commonly as an erythematous, maculopapular (measles-like) eruption, but can range from mild exanthema to life-threatening conditions like Stevens-Johnson syndrome or DRESS syndrome. 1

Clinical Spectrum and Presentations

Drug rashes exist on a spectrum from benign to potentially fatal:

Mild to Moderate Presentations

• Simple exanthema: Isolated skin eruption without systemic symptoms, appearing as red, flat or slightly raised lesions 1
• Maculopapular rash: The most common pattern, presenting as an erythematous, confluent rash that can involve varying amounts of body surface area 1
• Urticarial reactions: Hives or wheals that may be accompanied by angioedema 2

Severe Presentations Requiring Immediate Recognition

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A potentially life-threatening syndrome characterized by morbilliform rash covering >30% body surface area, fever >38°C, eosinophilia (>700/μL or >10% of WBCs), lymphadenopathy, and multi-organ involvement including hepatitis, nephritis, myocarditis, or pneumonitis 3. This occurs 2-6 weeks after drug exposure and involves T-cell mediated toxicity with herpes virus reactivation 3.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): Severe blistering reactions affecting <10% (SJS), 10-30% (overlap), or >30% (TEN) of body surface area, with mucosal involvement of the mouth, eyes, and genitourinary tract 1. These occur in <0.5% of patients but carry mortality rates around 30% for TEN 4.

Timing and Diagnosis

Critical Temporal Patterns

• Typical onset: 1-6 weeks after starting the medication 1
• Key diagnostic principle: Rash or fever occurring >3 months after drug initiation is almost always due to another cause 1
• DRESS-specific latency: 2-6 weeks, which distinguishes it from immediate reactions 3

Diagnostic Approach

Diagnosis relies on clinical criteria including:

• Temporal relationship between drug exposure and rash onset 1
• Effect of drug discontinuation (dechallenge) 1
• Exclusion of other causes like infections or immune restoration disease 1
• Assessment of body surface area affected, presence of systemic symptoms, and organ involvement 5

Critical warning signs requiring immediate drug discontinuation: mucosal involvement, blistering, skin exfoliation, fever >39°C, intolerable pruritus, elevated liver enzymes, or progressive constitutional symptoms 5, 6

Common Causative Medications

The most frequently implicated drug classes include:

• Antibiotics: Account for 74% of DRESS cases, particularly sulfonamides, vancomycin, and beta-lactams 3
• Anticonvulsants: Responsible for 21% of DRESS cases, including phenytoin, carbamazepine, and phenobarbital 3
• Antiretrovirals: Nevirapine (17-32% incidence), abacavir (2.3-9%), and emtricitabine (17%) 1, 3, 6

Management Principles

Immediate Action

Discontinue the suspected drug immediately if severe features are present (mucosal involvement, blistering, systemic symptoms, or organ involvement) 5. The reaction may temporarily worsen after cessation, particularly with longer half-life medications 5.

Treatment Based on Severity

Mild rash: Apply topical low-to-moderate potency corticosteroids and use antihistamines (non-sedating for daytime, sedating for nighttime pruritus) 5. Approximately 50% of mild-to-moderate antiretroviral-associated rashes resolve spontaneously even with continued therapy under close supervision 5.

Moderate rash: Continue topical corticosteroids, add oral antihistamines, and consider oral antibiotics for 6 weeks if papulopustular features are present 5

Severe rash/DRESS syndrome: Initiate systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day) with a minimum 4-week taper to prevent relapse 3. Hospitalization is required for extensive involvement, and severe cases need burn unit or ICU admission 3. For steroid-unresponsive cases, consider IVIG (1-2 g/kg) or cyclosporine 3.

Critical Pitfalls to Avoid

• Never rechallenge with the offending drug, as this can lead to serious and possibly fatal reactions occurring much sooner than initial exposure 1, 6
• Do not use prophylactic corticosteroids or antihistamines to prevent hypersensitivity reactions to drugs like nevirapine, as this has not proven effective and may actually increase rash risk 5
• Avoid premature steroid discontinuation in DRESS syndrome; a minimum 4-week taper is required due to T-cell immune-directed toxicity 3
• 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 3

Resolution Timeline

Most mild-to-moderate rashes begin improving within days of drug discontinuation, but lesions may continue erupting in crops for 2-3 weeks after stopping the medication 6. DRESS syndrome requires prolonged management with gradual steroid taper over at least 4 weeks 3.