Is dyshidrotic eczema associated with Pembrolizumab (PD-1 inhibitor)?

Dyshidrotic Eczema and Pembrolizumab (PD-1 Inhibitor)

Dyshidrotic eczema is not specifically listed as an associated adverse effect of pembrolizumab (PEMGARDA), but various skin reactions including eczematous eruptions are documented with PD-1 inhibitor therapy. 1

Skin Reactions Associated with Pembrolizumab

Pembrolizumab, like other PD-1 inhibitors, commonly causes dermatologic immune-related adverse events (irAEs). According to clinical guidelines, skin reactions are among the most frequent adverse events observed with these medications:

• Incidence: Skin adverse events occur in approximately 34% of patients receiving PD-1 inhibitors like pembrolizumab 1
• Timing: These typically develop early in treatment, within the first few weeks after initiation 1

Common Skin Manifestations

1. Maculopapular rash (15% of patients on PD-1 inhibitors) 1
2. Pruritus (13-20% of patients) 1
3. Vitiligo (particularly in melanoma patients, up to 25% in some studies) 1

Less Common Skin Reactions

Several less common dermatologic manifestations have been reported with pembrolizumab:

• Lichenoid reactions 1, 2
• Psoriasiform eruptions 1
• Eczematous dermatitis 1
• Bullous dermatitis 1
• Eruptive keratoacanthomas 3
• Lupus-like cutaneous reactions 4

Assessment and Management of Skin Reactions

When a patient on pembrolizumab presents with skin symptoms that could be dyshidrotic eczema:

1. Rule out other etiologies of the skin problem (infection, other drug effects, systemic disease) 1
2. Assess severity using CTCAE classification:
   • Grade 1: <10% BSA affected
   • Grade 2: 10-30% BSA affected
   • Grade 3: >30% BSA affected
   • Grade 4: Life-threatening reactions 1

Treatment Algorithm

For presumed dyshidrotic eczema or similar dermatologic reactions:

Grade 1 (Mild):

• Continue pembrolizumab therapy
• Topical emollients
• Mild-strength topical steroids once daily
• Antihistamines for pruritus 1

Grade 2 (Moderate):

• Consider holding pembrolizumab temporarily
• Moderate to potent topical steroids twice daily
• Oral antihistamines for pruritus
• Consider dermatology consultation 1

Grade 3-4 (Severe):

• Hold pembrolizumab
• Start oral prednisone 0.5-1 mg/kg/day
• If no improvement in 2-3 days, increase to 2 mg/kg/day
• Dermatology consultation
• Consider skin biopsy 1

Refractory Cases

For steroid-refractory dermatologic reactions:

• Cyclosporine has shown effectiveness in resolving pembrolizumab-associated lichenoid dermatitis 2
• Topical roflumilast cream 0.3% once daily has been reported to help with pembrolizumab-induced pruritus 5

Clinical Implications

1. Severity: Most skin reactions are low-grade and manageable without discontinuing therapy 1

2. Potential Prognostic Value: Interestingly, development of skin adverse events may be associated with better treatment response. Patients who develop cutaneous adverse events have shown significantly longer progression-free intervals compared to those who don't 6

3. Monitoring: Regular skin examinations are important, as the incidence of skin reactions may be underreported in clinical trials due to lack of systematic dermatologic evaluations 1

Important Caveats

• Life-threatening dermatologic emergencies like Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome require immediate discontinuation of pembrolizumab, hospitalization, and specialist management 1

• Immunosuppressive treatments for managing skin reactions have not been shown to negatively affect the clinical outcomes of cancer treatment with immune checkpoint inhibitors 1

• Patients with a history of autoimmune skin conditions may be at higher risk for exacerbation while on pembrolizumab therapy 1