Case Presentation: A 68-year-old man presented with dizziness, blurry vision, and leg paresthesias for one week, which started after a bout of gastroenteritis. Past medical was notable for an MCA stroke at age 40 with residual left-sided weakness. He was a never-smoker and had no risk for carbon monoxide exposure. On exam, patient had a ruddy complexion and decreased leg sensation up to his mid-calves bilaterally. Labs were notable for Hb 23 g/dl, Hct 72.8%, WBC 16.4/nL, platelets 182/nL, and low erythropoetin 2.3 IU/L (nl 2.6-18.5). Further workup revealed a JAK2 V617F mutation, consistent with a diagnosis of polycythemia vera.
Discussion: Polycythemia vera (PV) is a trilineage clonal disorder triggered by an inappropriately potent response of the Janus kinase 2 (JAK2) receptor to growth factors, such as erythropoietin (epo). PV is often incidentally diagnosed following routine bloodwork, however early diagnosis and treatment is critical given its subtle presentation and dramatic treatment response. Median survival is less than two years in untreated symptomatic patients compared to over 10 years with treatment. Mortality is driven by complications related to leukemic transformation and increased blood viscosity which can be mitigated by low-dose aspirin, therapeutic phlebotomy, and/or cytotoxic agents.1To that end, the WHO has recently revised their diagnostic criteria for PV to promote earlier diagnoses. Hemoglobin cutoffs were lowered from 18.5 to 16.5 g/dl in men and from 16.5 to 16 g/dl in women in order to increase diagnostic sensitivity. Bone marrow was also upgraded from a minor to major criterion, which will help confirm diagnoses in many patients. JAK mutations are present in up to 98% of patients with PV. Secondary causes of polycythemia, such as hypoxia-mediated etiologies and epo-producing tumors, must be excluded to confirm a diagnosis of PV.2
Lastly, although PV patients often present with non-specific headaches or dizziness, one unique symptom is aquagenic pruritus, which is a water-triggered, histamine-mediated process that preferentially affects patients’ backs, trunks and legs over more distal body parts. Aquagenic pruritus affects roughly half of patients with PV and may precede the diagnosis by an average of three years.3
Conclusions: Hospitalists must have a high index of suspicion for PV particularly given its non-specific presentation and potentially catastrophic consequences. Exclusion of secondary causes of polycythemia and presence of JAK2 mutation will confirm the diagnosis.
1. Tefferi A, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood 2014;124(16):2507-13.
2. Barbui T, et al. The 2016 revision of WHO classification of myeloproliferative neoplasms. Blood Rev 2016;30(6):453-9.
3. Siegel FP, et al. Aquagenic pruritus in polycythemia vera. Am J Hematol 2013;88:665.