What is the treatment for psoriasiform reactions secondary to Keytruda (pembrolizumab)?

Treatment of Psoriasiform Reactions Secondary to Keytruda (Pembrolizumab)

The treatment of psoriasiform reactions secondary to pembrolizumab should follow a severity-based approach, with high-potency topical corticosteroids as first-line therapy for mild to moderate cases, and systemic corticosteroids for severe cases.

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) 1
• Rule out other causes of skin reactions including infections or effects from other medications 1
• Check for mucosal involvement and systemic symptoms to exclude dermatological emergencies like DRESS syndrome or Stevens-Johnson syndrome/TEN 1

Treatment Algorithm Based on Severity

Grade 1 (Mild) Psoriasiform Reaction

• Continue pembrolizumab therapy 2, 1
• Apply high-potency topical corticosteroids (e.g., clobetasol 0.05% or fluocinonide 0.05% cream/ointment) twice daily to affected areas 2
• Consider adding topical vitamin D analogs for additional benefit 2, 3
• Use emollients and antihistamines for symptom management 2, 1
• Reassess after 2 weeks; if worsening or no improvement, proceed to next step 2

Grade 2 (Moderate) Psoriasiform Reaction

• Consider temporarily holding pembrolizumab therapy 2, 1
• Continue high-potency topical corticosteroids twice daily 2
• Consider adding narrow-band UVB phototherapy if available 2
• If inadequate response, initiate oral prednisone (0.5-1 mg/kg/day) with a steroid taper over 4-6 weeks 2, 1
• Consider apremilast or acitretin (if no childbearing potential) 2
• Reassess after 2 weeks; if worsening or no improvement, proceed to next step 2

Grade 3-4 (Severe or Life-threatening) Psoriasiform Reaction

• Hold pembrolizumab therapy until severity decreases to grade 0-1 2, 1
• Initiate systemic corticosteroids (prednisone 1-2 mg/kg/day) with a slow taper over 4-6 weeks 2
• Consider dermatology consultation for additional immunosuppressive options 1
• For refractory cases, consider steroid-sparing agents such as methotrexate, cyclosporine, or biologics targeting IL-17 or IL-23 pathways 2
• For life-threatening reactions, permanently discontinue pembrolizumab and hospitalize the patient 1

Special Considerations

• Combination therapy with topical corticosteroids and biologics has shown efficacy in managing severe psoriasiform reactions while continuing immunotherapy 4, 5
• In case reports, IL-17 inhibitors (secukinumab, ixekizumab) have been successfully used to treat immunotherapy-induced psoriasis while allowing continuation of cancer treatment 4, 5
• Clobetasol propionate spray 0.05% has shown effectiveness as add-on therapy to biologic treatments for moderate to very severe plaque psoriasis 6

Monitoring and Follow-up

• Regular skin assessments are essential as reactions can develop within days to weeks of starting treatment but can also appear after several months 1
• Most dermatologic immune-related adverse events are low-grade and manageable, but severe events require prompt intervention 2, 1
• For patients with pre-existing psoriasis, close monitoring is particularly important as exacerbations are more common 5

Pitfalls to Avoid

• Do not delay treatment of severe reactions, as they can rapidly progress to life-threatening conditions 2, 1
• Avoid harsh soaps or cleansers containing alcohol, as they can worsen irritation 1
• Do not permanently discontinue immunotherapy for mild to moderate dermatitis that responds to treatment, as this can impact cancer outcomes 1
• Be aware that some conventional psoriasis treatments (e.g., cyclosporine) may have interactions with cancer therapies or affect immune response 2