What is the management approach for drug eruptions?

Management of Drug Eruptions

Immediately discontinue the suspected causative drug(s), as early withdrawal—particularly of drugs with short elimination half-lives—is associated with better patient survival in severe reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). 1, 2

Initial Assessment and Risk Stratification

Critical History and Physical Examination

Document the following specific details:

• Timing of rash onset relative to drug initiation, noting that antibiotics and NSAIDs typically cause eruptions within 3 days, while drugs for chronic diseases often require ≥4 days 3
• Prodromal symptoms including fever, malaise, upper respiratory symptoms, and the exact date these began 1
• Mucosal involvement (eyes, mouth, nose, genitalia), as this indicates potential progression to severe cutaneous adverse reactions (SCARs) 1
• All medications taken in the preceding 2 months, including over-the-counter and complementary therapies, with exact start dates 1
• Percentage of body surface area (BSA) involved using Lund and Browder chart, separately documenting erythema versus actual epidermal detachment (the latter has prognostic value) 1
• Respiratory symptoms (cough, dyspnea, bronchial hypersecretion) and gastrointestinal symptoms (diarrhea, abdominal distension) suggesting systemic involvement 1

Essential Investigations

Obtain the following tests immediately:

• Complete blood count with differential, liver and kidney function tests, electrolytes (including magnesium, phosphate, bicarbonate), coagulation studies, and mycoplasma serology 1
• Chest X-ray 1
• Two skin biopsies: one from lesional skin adjacent to a blister for routine histopathology, and one from periblister lesional skin sent unfixed for direct immunofluorescence to exclude immunobullous disorders 1
• Bacterial cultures from lesional skin 1
• Serial clinical photography to document progression 1

Management by Severity Grade

Mild Reactions (Grade 1-2: <30% BSA, No Mucosal Involvement)

Continue the anticancer agent if applicable and initiate:

• Topical corticosteroids: Low-to-moderate potency steroids applied twice daily for papulopustular rashes from EGFR inhibitors 1, 4; high-potency steroids (e.g., clobetasol propionate 0.05%) for palmar-plantar erythrodysesthesia syndrome 1, 4
• Oral tetracycline antibiotics for at least 6 weeks (doxycycline 100 mg twice daily OR minocycline 50 mg twice daily OR oxytetracycline 500 mg twice daily) for EGFR inhibitor-related rashes 1
• Reassess after 2 weeks; if worsening or no improvement, escalate management 1

Moderate-to-Severe Reactions (Grade 3: ≥30% BSA or Intolerable Grade 2)

Hold the causative drug until symptoms resolve to Grade 0-1:

• Systemic corticosteroids: IV methylprednisolone 0.5-1 mg/kg daily, converting to oral prednisone with tapering over at least 4 weeks 1
• Continue topical steroids and oral antibiotics as above 1
• Obtain bacterial/viral/fungal cultures if superinfection is suspected (painful lesions, pustules on extremities, yellow crusts, discharge) and treat based on sensitivities for ≥14 days 1

Severe Cutaneous Adverse Reactions (SCARs: SJS/TEN, DRESS)

Permanently discontinue the implicated drug and admit immediately to a burn unit or intensive care unit:

• IV methylprednisolone 1-2 mg/kg daily for immune checkpoint inhibitor-related SCARs, as the usual prohibition of corticosteroids for SJS does not apply when the mechanism is T-cell immune-directed toxicity 1
• Supportive care identical to major burn management: environmental warming, correction of electrolyte disturbances, high caloric intake, prevention of sepsis, and attention to fluid balance using insensible water loss calculations 1, 2
• Wound care: Topical emollients, petrolatum-based products, and high-strength topical corticosteroids 1
• Avoid systemic corticosteroids in advanced TEN from non-immunotherapy drugs, as they have been shown to be deleterious 2

Special Considerations

Chemotherapy-Related Reactions

For infusion reactions during chemotherapy administration:

• Mild infusion reactions (flushing, rash, chills) to taxanes: Restart infusion at a much slower rate after symptoms resolve, gradually increasing as tolerated—this differs from formal desensitization 1
• Platinum drug reactions: Exercise great caution with desensitization even after mild reactions, as subsequent reactions may be more severe; consult allergy/immunology 1
• Never rechallenge if a previous life-threatening reaction occurred 1

Drug Desensitization

Consider desensitization protocols when:

• First-line chemotherapy is essential for optimal cancer outcomes and no suitable alternative exists 1
• The reaction was mast cell-mediated (immediate hypersensitivity) rather than T-cell-mediated 1
• Do not attempt desensitization for severe delayed T-cell-mediated reactions (SJS/TEN, DRESS, AGEP), as these involve long-lasting memory T-cell responses 1

Prevention Strategies

Counsel all patients receiving high-risk medications on:

• Avoiding frequent hot water washing, skin irritants, and over-the-counter anti-acne medications 1
• Using alcohol-free moisturizers with 5%-10% urea twice daily 1
• Applying SPF 15 sunscreen to exposed areas every 2 hours when outdoors 1
• Prophylactic oral antibiotics (tetracyclines) at treatment initiation for EGFR inhibitors 1

Critical pitfall: Patients with mild reactions to platinum agents may develop severe reactions on rechallenge even with slow infusion; always have emergency equipment available and consider allergy consultation 1. For photosensitive drug eruptions, prevention through patient education about sun protective measures is more effective than treating established eruptions 5.