Pruritus in Polycythemia Vera Is More Prevalent in Non-Smokers and Is Independently Associated with a Lower Risk of Arterial Thrombosis.

Background: Pruritus in polycythemia vera (PV) has been associated with a high JAK2V617F allele burden (

Methods: The study cohort consisted of a consecutive group of patients with PV who fulfilled the World Health Organization (WHO) diagnostic criteria and in whom information regarding the presence or absence of pruritus at diagnosis was fully documented. Pruritus was graded as being mild, moderate, or severe based on careful review of patient history.

Results:

• Prevalence and severity of pruritus: A total of 418 patients fulfilled the above stipulated criteria for study inclusion (median age of 60 years; 56% males; median follow-up of 73 months). Of these, 131 (31%) experienced pruritus at time of initial diagnosis: mild in 97 patients (74%), moderate in 22 (17%), and severe in 12 (9%). Most patients with mild pruritus (n=92) received no specific therapy for pruritus whereas all 12 patients with severe pruritus required treatment; all 7 patients who received treatment with paroxetine responded.

• Pruritus and JAK2V617F allele burden: Quantitative measurement of JAK2V617F was performed in 64 patients using genomic DNA from archived bone marrow obtained at the time of PV diagnosis. Mutational frequency was 97%; median mutant allele burden was 25.4% (range 0.2 - 93.3%). Among the 62 V617F-positive patients, 24 (39%) had pruritus; the proportion of patients in the upper and lower quartile allele burden ranges were 50% and 0% in the presence of pruritus and 18% and 34% in its absence (p=0.002).

• Clinical correlates of pruritus: Pruritus was more prevalent in non-smokers (35% vs. 19%; p=0.004) and non-diabetics (33% vs. 16%; p=0.04) and was associated with a lower rate of arterial thrombosis at diagnosis (8% vs. 17%; p=0.01) as well as during follow-up (16% vs. 30%; p=0.003).

These significant associations remained intact during multivariable analysis. Pruritus did not have an impact on the rate of leukemic or fibrotic transformation.

Conclusions: Pruritus in PV is independently associated with a lower risk of arterial thrombosis despite high JAK2V617F allele burden and is also more prevalent in non-smokers. These observations suggest that pruritus might be a surrogate for an underlying platelet pathology with functional relevance.