What is the management approach for skin complications in patients with polycythemia vera?

Management of Skin Complications in Polycythemia Vera

Primary Skin Manifestations and Treatment

The two main skin complications in polycythemia vera are pruritus (affecting 33-48% of patients) and erythromelalgia (affecting 3-5.3% of patients), each requiring distinct management approaches. 1, 2

Pruritus Management

For PV-associated pruritus, selective serotonin reuptake inhibitors (SSRIs) such as paroxetine should be first-line therapy, achieving response rates exceeding 80%. 1

Treatment Algorithm for Pruritus:

First-line options:

• SSRIs (particularly paroxetine) - most effective with >80% response rate 1
• Aspirin 300 mg daily - provides relief in many patients through inhibition of platelet release of pruritogenic amines including prostaglandins and serotonin 1

Second-line options when first-line fails:

• Interferon-α - reduces pruritus in up to 81% of affected patients, with the added benefit of cytoreductive therapy 1, 3
• Phototherapy (PUVA or UVB) - provides temporary relief though relapse is common after stopping treatment 1

Additional options with limited evidence:

• Antihistamines (unpredictable and variable responses) 1
• Cimetidine 1
• Atenolol 1
• Sodium bicarbonate baths (case report evidence only) 1

For refractory pruritus:

• Ruxolitinib (JAK1/JAK2 inhibitor) - very effective at producing rapid reductions in pruritus scores, indicated for patients with inadequate response to hydroxyurea 1, 3, 4

Important Considerations for Pruritus:

• Iron deficiency may contribute to pruritus pathogenesis (correlation with low mean corpuscular volume), but iron replacement has not been consistently effective and should not be used indiscriminately 1
• The mechanism of interferon-α benefit may relate partly to decreased phlebotomy need, resulting in lesser iron deficiency 1
• Pruritus can persist despite normalization of blood counts with venesection or cytoreductive therapy 1

Erythromelalgia Management

For PV-associated erythromelalgia, low-dose aspirin (81 mg/day) provides prompt relief within hours in most patients through inhibition of thromboxane-mediated platelet activation. 1

Treatment Algorithm for Erythromelalgia:

First-line:

• Aspirin 81 mg daily - produces prompt alleviation of symptoms within hours 1

Second-line (for aspirin non-responders):

• Cytoreductive therapy to normalize platelet count - necessary in patients who do not respond well to aspirin alone 1

Pathophysiology Context:

• Erythromelalgia occurs in approximately 3% of PV patients and is often associated with thrombocythemia 1
• The syndrome involves platelet-mediated endothelial cell injury resulting in inflammation and transient thrombotic occlusion by platelet aggregates 1

Non-Melanoma Skin Cancer Risk

Patients on ruxolitinib require periodic skin examinations during and after treatment, as basal cell and squamous cell carcinomas have been reported. 4

Integration with Overall PV Management

All skin complication management should occur alongside:

• Phlebotomy to maintain hematocrit <45% 1, 3, 2
• Low-dose aspirin (unless contraindicated) 1, 3, 2
• Cytoreductive therapy for high-risk patients (age ≥60 years or thrombosis history) 1, 3, 2

Critical Pitfalls to Avoid

• Do not rely solely on antihistamines for PV-associated pruritus - they have unpredictable efficacy 1
• Do not indiscriminately use iron replacement for pruritus - it has not been consistently effective 1
• Do not ignore erythromelalgia symptoms - they require prompt aspirin therapy to prevent progression 1
• Do not forget skin cancer surveillance in patients receiving ruxolitinib 4