How to treat drug eruptions?

Treatment of Drug Eruptions

The immediate and most critical step in treating drug eruptions is to discontinue the suspected causative drug(s) as soon as possible, as earlier withdrawal—particularly of drugs with short elimination half-lives—is associated with better patient outcomes and survival. 1

Initial Management: Drug Discontinuation

• Stop all suspected medications immediately upon recognition of a drug eruption, as this is the cornerstone of management and directly impacts prognosis 2, 1
• Obtain a thorough drug history covering the previous 2 months, including over-the-counter medications, complementary therapies, and the exact dates when treatments were started 2
• Document the index date (when first symptoms appeared) and progression of the eruption 2
• Consider that the latency period varies: antibiotics and anti-inflammatory drugs typically cause eruptions within 3 days, while drugs for chronic diseases may take 4 or more days 3

Severity-Based Treatment Approach

Mild to Moderate Drug Eruptions (Grade 1-2)

For localized or mild eruptions:

• Apply topical moderate-to-high potency corticosteroids (such as mometasone furoate 0.1% or betamethasone valerate 0.1% ointment) twice daily to affected areas 2
• Use oral antihistamines for symptomatic relief of pruritus: second-generation agents like loratadine 10 mg daily for daytime, or first-generation agents like diphenhydramine 25-50 mg or hydroxyzine 25-50 mg for nighttime sedation 2
• Reassess after 2 weeks; if no improvement or worsening occurs, escalate treatment 2

Moderate to Severe Drug Eruptions (Grade 2-3)

For widespread or intense eruptions:

• Continue topical high-potency corticosteroids 2
• Add GABA agonists (pregabalin 25-150 mg daily or gabapentin 900-3600 mg daily) as second-line therapy for persistent pruritus unresponsive to antihistamines 2
• Consider systemic corticosteroids (prednisone 0.5-1 mg/kg body weight) for severe cases, though use cautiously as they may be deleterious in advanced toxic epidermal necrolysis 2, 1
• Interrupt the causative drug until severity decreases to grade 0-1 2

Life-Threatening Drug Eruptions (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis)

For severe bullous or exfoliative reactions:

• Discontinue the drug immediately if any signs of bullous or exfoliative skin rash appear 2
• Transfer patient to specialized intensive care or burn units for management of "acute skin failure" 1
• Provide supportive care similar to major burns: environmental warming, electrolyte correction, high caloric intake, and infection prevention 1
• Avoid systemic corticosteroids in advanced TEN as they have been shown to be deleterious and may increase mortality 1
• Consider high-dose intravenous immunoglobulins, though evidence remains limited and requires further confirmation 1

Specific Drug Eruption Types

EGFR Inhibitor-Related Acneiform Eruptions

For papulopustular rashes from targeted cancer therapies:

• Initiate oral antibiotics for 6 weeks (doxycycline 100 mg twice daily, minocycline 50 mg twice daily, or oxytetracycline 500 mg twice daily) combined with topical low-to-moderate potency steroids 2
• For grade ≥3 reactions, add systemic corticosteroids (prednisone 0.5-1 mg/kg for 7 days) or consider low-dose isotretinoin 20-30 mg/day with dermatology consultation 2
• Obtain bacterial/viral/fungal cultures if superinfection is suspected 2

Hand-Foot Skin Reactions

For palmar-plantar eruptions from chemotherapy:

• Apply cooling measures (cold gloves or socks) during infusions for drugs like paclitaxel, docetaxel, and liposomal doxorubicin 2
• Use topical high-potency steroids twice daily 2
• Apply keratolytics (salicylic acid 5-10% or urea 10-40%) for hyperkeratosis 2
• Consider oral dexamethasone (8 mg twice daily for 5 days beginning the day before infusion) for grade 2 reactions 2
• Use lidocaine 5% cream or patches for pain relief 2

Drug-Induced Pemphigus

For blistering eruptions resembling pemphigus:

• Stop the offending drug (particularly thiol drugs, phenol drugs, or other implicated agents) 2
• Recognize that 50% of cases will resolve with drug withdrawal alone (drug-triggered pemphigus), while the other 50% will require treatment as idiopathic pemphigus 2
• For severe cases not responding to drug withdrawal, initiate conventional pemphigus treatment with systemic corticosteroids and adjuvant immunosuppressants 2

Prevention of Recurrence

• Document and communicate the causative drug to the patient, their family, and all healthcare providers 1
• Advise patients to avoid the responsible drug and chemically related compounds permanently 1
• Notify regulatory agencies of severe drug eruption cases 1
• Be aware that 8.9% of drug eruptions relapse, and beta-lactam antibiotics in particular can cause exacerbation upon re-administration 3
• Implement hospital-wide monitoring systems to prevent inadvertent re-exposure 3

Critical Pitfalls to Avoid

• Do not delay drug discontinuation while awaiting diagnostic confirmation, as timing directly impacts survival in severe reactions 1
• Do not use systemic corticosteroids in advanced TEN, as they significantly increase mortality 1
• Do not use thalidomide for TEN, as it significantly increases death rates 1
• Do not assume all drug eruptions are allergic—phototoxic reactions require sun protection counseling and may not recur with rechallenge under different conditions 4
• Do not overlook concurrent infections in patients with pustular eruptions, as bacterial superinfection requires culture-directed antibiotic therapy 2