Treatment of Drug Reaction Rash
Immediately discontinue the suspected causative drug if the reaction is severe, and initiate treatment based on severity: mild rashes require topical corticosteroids and antihistamines, moderate rashes need oral antibiotics if papulopustular features are present, and severe rashes with systemic symptoms demand systemic corticosteroids and hospitalization. 1
Initial Assessment and Immediate Action
Discontinue the offending drug immediately if there is mucosal involvement, blistering, exfoliation, fever >39°C, or intolerable pruritus. 2 The reaction may temporarily worsen after drug cessation, particularly with longer half-life medications. 2
Critical warning signs requiring immediate drug discontinuation include: 2
- Mucosal involvement or blistering
- Elevated liver enzymes (ALT >5x upper limit of normal)
- Fever greater than 39°C
- Progressive constitutional symptoms
- Intolerable pruritus
Treatment Algorithm Based on Severity
Mild Rash (Isolated Cutaneous Involvement)
Apply topical low-to-moderate potency corticosteroids (hydrocortisone butyrate 0.1% or triamcinolone 0.1%) 2-3 times daily to affected areas. 1, 3
For symptomatic relief: 1
- Non-sedating antihistamines (cetirizine, loratadine, fexofenadine) for daytime pruritus
- Sedating antihistamines for nighttime itching
- Aggressive emollient therapy with urea 10% cream three times daily
Important caveat: About 50% of mild-to-moderate antiretroviral-associated rashes resolve spontaneously despite continuation of therapy under close supervision. 2 However, certain experienced clinicians recommend managing mild rashes with antihistamines without drug discontinuation, though this approach has been questioned. 2
Moderate Rash (More Extensive Involvement)
Continue topical corticosteroids and oral antihistamines. 1
Add oral tetracycline antibiotics for 6 weeks if papulopustular features are present (doxycycline 100 mg twice daily or minocycline 50-100 mg twice daily). 1
Apply moisturizers liberally and use alcohol-free formulations with urea 10%. 1
Severe Rash (Systemic Symptoms or Extensive Involvement)
Administer systemic corticosteroids and hospitalize immediately for extensive involvement, systemic symptoms, or suspected Stevens-Johnson syndrome/toxic epidermal necrolysis. 1, 4
Treatment of severe reactions within the first 24 hours with corticosteroids has been shown to be beneficial, particularly for sulfonamide hypersensitivity. 2 Patients with extensive skin detachment should be transferred to an intensive care unit or burn center, as the principles of symptomatic treatment are the same as for burns. 4
Critical distinction: Stevens-Johnson syndrome is fatal in about 5% of cases, while toxic epidermal necrolysis carries a 30% mortality rate. 4
Essential Supportive Care Measures
Regardless of severity, implement these measures: 1
- Avoid hot showers and excessive soap use
- Apply emollients at least once daily to the whole body
- Avoid skin irritants (OTC anti-acne medications, solvents, disinfectants)
- Minimize sun exposure
- Use soap-free shower gel and bath oil
Special Considerations and Common Pitfalls
Do NOT use prophylactic corticosteroids or antihistamines to prevent hypersensitivity reactions to nevirapine or other NNRTIs, as this has not proven effective and may actually increase the risk of developing rash. 2
Rechallenge with the offending drug can lead to serious and possibly fatal reactions, occurring much sooner than on first exposure. 2 Therefore, rechallenge is rarely attempted. 2
Document the reaction thoroughly to prevent future re-exposure to the causative agent. 1
When to Obtain Cultures
Obtain bacterial and fungal cultures when infection is suspected, when there's failure to respond to initial treatment, or when painful lesions, pustules, yellow crusts, or discharge are present. 1
Reassessment Timeline
Reassess after 2 weeks to evaluate response. 1 If no improvement occurs after 2 weeks of appropriate therapy, consider secondary infection or escalate to second-line therapy including topical calcineurin inhibitors (tacrolimus 0.03%-0.1% ointment or pimecrolimus 1% cream). 1
Life-Threatening Presentations Requiring Immediate Action
Severe cutaneous adverse drug reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and drug-induced vasculitis require prompt identification and withdrawal of the suspected offending agent as the crucial first step. 5, 4 Skin biopsy is the gold standard for diagnosis. 5