What is the treatment for a drug rash?

Treatment of Drug Rash

For mild to moderate drug rashes without systemic symptoms, apply topical low-to-moderate potency corticosteroids (1-2.5% hydrocortisone) and oral antihistamines for symptomatic relief, while for severe reactions with mucosal involvement, blistering, or systemic symptoms, immediately discontinue the offending drug and initiate systemic corticosteroids with consideration for hospitalization. 1

Immediate Assessment and Drug Discontinuation

The first critical step is determining severity to guide management:

• Discontinue the suspected causative drug immediately if there is mucosal involvement, blistering, skin exfoliation, fever >39°C, or intolerable pruritus 2
• Assess body surface area affected, presence of systemic symptoms (fever, malaise, organ involvement), and look for warning signs of severe reactions 1
• Severe cutaneous manifestations including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) require prompt and permanent discontinuation of the offending agent 2
• Obtain bacterial cultures if infection is suspected or if there is failure to respond to initial treatment 1

Treatment Algorithm Based on Severity

Mild Rash (Limited Body Surface Area, No Systemic Symptoms)

• Apply topical low-to-moderate potency corticosteroids (1-2.5% hydrocortisone) to affected areas 3-4 times daily 1, 3
• Use non-sedating antihistamines (cetirizine, loratadine, or fexofenadine) for daytime pruritus 1, 4
• Use sedating antihistamines (clemastine) for nighttime itching 1, 4
• Apply emollients at least once daily to the whole body to prevent xerosis and secondary eczema 1, 4
• Add acetaminophen or ibuprofen for associated fever or discomfort 4
• About 50% of mild to moderate isolated skin rashes resolve spontaneously despite continuation of therapy, though this approach requires close supervision 2

Moderate Rash (Increased Body Surface Area or Papulopustular Features)

• Continue topical corticosteroids and oral antihistamines 1
• Add oral antibiotics for 6 weeks if papulopustular features are present 1
• Apply moisturizers and urea- or polidocanol-containing lotions for pruritus 1

Severe Rash (Extensive Involvement, Systemic Symptoms, or Life-Threatening Features)

• Initiate systemic corticosteroids immediately 1, 4
• Hospitalize for extensive involvement, systemic symptoms, or suspected SJS/TEN/DRESS 1, 5
• For TMP-SMX hypersensitivity specifically, treatment with corticosteroids within the first 24 hours has been shown to be beneficial 2
• Intravenous immunoglobulins have been used in case reports for TEN and DRESS 2
• Oral and intravenous N-acetylcysteine have been used but cannot be recommended until better randomized data are available 2

Critical Warnings About Corticosteroid Use

A crucial caveat exists regarding prophylactic corticosteroid use:

• Prophylactic use of systemic corticosteroids or antihistamines at the time of initiating nevirapine (or other NNRTIs) to prevent development of skin rash has NOT proven effective 2
• In fact, a higher incidence of skin rash has been reported among steroid- or antihistamine-treated patients when used prophylactically 2
• At present, prophylactic use of corticosteroids should be discouraged 2
• This contrasts with therapeutic use of corticosteroids for established severe reactions, which remains appropriate 2, 1

Special Considerations for Specific Drug Rashes

Xerotic and Eczematous Rash

• Avoid hot showers and excessive use of soaps 1
• Apply emollients at least once daily to the whole body 1
• Avoid greasy creams for basic care as they may facilitate folliculitis 4

Antiretroviral-Associated Rashes

• For mild to moderate NNRTI-associated rashes without constitutional symptoms, some experienced clinicians recommend managing with antihistamines for symptomatic relief without drug discontinuation, though continuing treatment during such rashes has been questioned 2
• Reactions may worsen temporarily after cessation of drug therapy, particularly with drugs with longer half-lives such as nevirapine 2
• For abacavir-associated rash, note that rash may be a late or absent feature of hypersensitivity, and discontinuation should be based on progressive constitutional symptoms 2
• Never rechallenge with abacavir if hypersensitivity occurred 2

Preventive Measures and Documentation

• Document the reaction characteristics in detail including timing, morphology, severity, and associated symptoms to prevent future re-exposure 1, 4
• Avoid skin irritants such as OTC anti-acne medications, solvents, or disinfectants 1, 4
• Avoid excessive sun exposure 1
• Do NOT mislabel benign late-appearing maculopapular rashes as true allergies, as this leads to unnecessary use of broader-spectrum, more expensive, and potentially more toxic antibiotics in the future 4

Common Pitfalls to Avoid

• Do not use topical acne medications or retinoids during active drug rash, as they cause irritation and drying 4
• Avoid contact with eyes when using topical corticosteroids 3
• Do not use hydrocortisone in the genital area if vaginal discharge is present 3
• Do not use hydrocortisone for treatment of diaper rash 3
• Stop topical corticosteroids if condition worsens, symptoms persist for more than 7 days, or rectal bleeding occurs 3