What causes itching and headaches in patients with polycythemia vera (PV)?

Pathophysiology of Post-Bath Itching and Headaches in Polycythemia Vera

Post-bath itching (aquagenic pruritus) and headaches in polycythemia vera patients result from platelet-mediated microvascular disturbances caused by clonal myeloproliferation, with platelets releasing pruritogenic substances like prostaglandins and serotonin, while headaches arise from transient inflammation-based occlusive phenomena involving abnormal platelet-endothelial interactions in arterioles. 1

Mechanism of Aquagenic Pruritus (Post-Bath Itching)

Platelet-mediated pathogenesis:

• Generalized pruritus exacerbated by hot baths is a characteristic feature of PV, documented in 48% of patients either at diagnosis or during disease progression 1
• Platelets and their contents are implicated in the pathogenesis, with the proposed mechanism being platelet release of pruritogenic amines including prostaglandins and serotonin 1
• The condition is termed "aquagenic pruritus" - intense itching triggered by water contact at any temperature without visible skin lesions 1, 2

Contributing factors:

• Iron deficiency may play a pathogenetic role, with studies showing significant correlation between active pruritus and low mean corpuscular volume 1
• Mast cell involvement has been suggested, though evidence remains conflicting 1
• The pruritus can persist despite normalization of blood counts with venesection or cytoreductive therapy 1

Mechanism of Headaches

Microvascular disturbance pathophysiology:

• Headaches represent transient inflammation-based occlusive phenomena resulting from interaction between clonal platelets and arteriolar endothelium 1, 3
• The pathogenesis involves platelet-mediated endothelial cell injury leading to inflammation and transient thrombotic occlusion by platelet aggregates 1
• Thromboxane-mediated platelet activation plays a pathogenetic role 1

Associated microvascular symptoms:

• Headaches occur alongside other microvascular disturbances including light-headedness, transient neurologic or ocular disturbances, tinnitus, atypical chest discomfort, and paresthesias 1, 3
• These symptoms are common manifestations of the underlying myeloproliferative disorder 3, 4

Clinical Significance

Diagnostic implications:

• Aquagenic pruritus is characteristic of PV and should raise clinical suspicion for this diagnosis 1
• In essential thrombocythemia, presence of aquagenic pruritus identifies patients with higher risk of thrombotic events (30.9% versus 17%) and phenotypic evolution 5

Impact on quality of life:

• Pruritus may be the most agonizing aspect of PV, resulting in sleep deprivation and interference with social and physical activities 1
• These symptoms contribute substantially to the disease burden alongside fatigue and constitutional symptoms 4, 6

Treatment Implications

For aquagenic pruritus:

• Low-dose aspirin (81-300 mg daily) inhibits platelet release of pruritogenic substances and provides relief 1
• Selective serotonin reuptake inhibitors (SSRIs) like paroxetine show response rates higher than 80% 1, 3
• Interferon-α reduces pruritus in up to 81% of affected patients and is recommended for intractable cases 1, 3

For headaches and microvascular symptoms:

• Low-dose aspirin (81 mg daily) produces prompt alleviation within hours through inhibition of thromboxane-mediated platelet activation 1
• Cytoreductive therapy with normalization of platelet counts may be necessary for refractory cases 1