Treatment for Dermatitis from Pembrolizumab
For dermatitis caused by pembrolizumab, topical corticosteroids are the first-line treatment for mild to moderate cases, while oral corticosteroids (starting at 0.5-1 mg/kg/day of prednisone) should be used for severe or extensive dermatitis. 1
Assessment and Grading
- Evaluate the severity using CTCAE criteria: Grade 1 (<10% body surface area), Grade 2 (10-30% BSA), Grade 3 (>30% BSA), or Grade 4 (life-threatening reactions like Stevens-Johnson Syndrome) 1
- Rule out other causes of skin reactions including infections or effects from other medications 1
- Check for mucosal involvement and systemic symptoms (fever, lymphadenopathy) to exclude dermatological emergencies like DRESS syndrome or SJS/TEN 1
Treatment Algorithm Based on Severity
Grade 1 (Mild) Dermatitis
- Continue pembrolizumab therapy 1
- Apply high-potency topical corticosteroids to affected areas 1
- Use emollients to moisturize skin and create a protective barrier 1
- Consider antihistamines for associated pruritus 1
Grade 2 (Moderate) Dermatitis
- Consider temporarily holding pembrolizumab therapy 1
- Apply high-potency topical corticosteroids 1
- For widespread lesions, start oral prednisone 0.5-1 mg/kg/day 1
- If no improvement in 2-3 days, increase corticosteroid dose to 2 mg/kg/day 1
- Once improved to ≤grade 1, initiate a 4-6 week steroid taper 1
- Resume immunotherapy once resolved to ≤grade 1 1
Grade 3 (Severe) Dermatitis
- Hold pembrolizumab therapy 1
- Start oral prednisone 1-2 mg/kg/day or IV methylprednisolone if unable to take oral medication 1
- Consider dermatology consultation 1
- For steroid-refractory cases, consider alternative immunosuppressants such as cyclosporine 2 or methotrexate 3
- Once improved to ≤grade 1, initiate a 4-6 week steroid taper 1
Grade 4 (Life-threatening) Dermatitis
- Permanently discontinue pembrolizumab 1
- Immediate hospitalization and specialist dermatology consultation 1
- High-dose systemic corticosteroids (IV methylprednisolone) 1
- Supportive care as needed 1
Specific Treatment Approaches for Common Presentations
For Lichenoid Dermatitis
- For steroid-refractory lichenoid dermatitis, a single 15mg dose of methotrexate has shown efficacy 3
- Alternatively, cyclosporine has been effective for steroid-refractory lichenoid eruptions 2
For Pruritus
- Topical phosphodiesterase-4 inhibitors like roflumilast cream 0.3% once daily may provide relief for pruritus that is refractory to standard treatments 4
- Topical polidocanol cream or oral antihistamines for significant itching 1
For Eruptive Keratoacanthomas
- Combination of topical clobetasol ointment and intralesional triamcinolone, with or without cryosurgery 5
- This approach allows continuation of pembrolizumab therapy 5
Important Considerations
- Skin toxicities typically develop within days to weeks of starting treatment but can appear after several months 1
- Most dermatologic immune-related adverse events are low-grade and manageable 1
- Vitiligo is frequently seen in melanoma patients on checkpoint inhibitors and may be associated with good clinical response 1
- Severe immune-related adverse events occur more commonly with combination immunotherapy than with monotherapy 1
Pitfalls to Avoid
- Do not use harsh soaps or cleansers containing alcohol as they can worsen irritation 1
- Avoid rubbing irritated skin when drying - pat gently instead 1
- Do not delay treatment of severe reactions, as they can rapidly progress to life-threatening conditions 1
- Do not permanently discontinue immunotherapy for mild to moderate dermatitis that responds to treatment 1