A 51-year-old man comes to the office due to frequent itching, especially after bathing. He otherwise feels well except for occasional headaches and dizziness. He has no fever or weight loss. The patient has not visited a doctor in 10 years and does not take medications. He does not use tobacco, alcohol, or illicit drugs. The patient's sister has bipolar disorder, and both parents died in a car accident many years ago. Temperature is 36.7 C (98 F), blood pressure is 140/80 mm Hg, pulse is 76/min, and respirations are 14/min. BMI is 30 kg/m². His face has a ruddy cyanotic appearance. Oropharynx is clear. There is no lymphadenopathy in his cervical, supraclavicular, or axillary chains. Jugular venous pressure is normal. Cardiopulmonary examination shows no abnormalities. Abdomen is soft and nontender; the spleen is palpable 4 cm below the left lower ribs. Laboratory results are as follows: Which of the following is most likely to be seen on further workup?

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11ec25c8_d427_60b0_bc81_bb4700bcab4f_MD0003_00 This patient with aquagenic pruritus (itching after bathing), facial plethora (ruddy cyanosis), splenomegaly, and elevations in all 3 cell lines on complete blood count likely has polycythemia vera (PV). PV is a clonal myeloproliferative disorder characterized by erythrocytosis (increase in red blood cell mass). It is a primary form of polycythemia, almost always caused by a JAK2 mutation. Normally, red blood cell production is dependent on erythropoietin (EPO), a cytokine released by the kidneys (and liver) in response to tissue hypoxia; EPO activates the JAK2 tyrosine kinase, which differentiates late myeloid cells into erythrocytes. In PV, red blood cell production is driven by a constitutively active JAK2 gene rather than by tissue hypoxia; therefore, EPO levels tend to be low. Secondary forms of polycythemia (eg, due to chronic hypoxia or EPO-secreting tumors) are caused by circulating factors (usually EPO) that stimulate the bone marrow to produce more red blood cells. These forms of polycythemia are often characterized by high EPO levels. (Choice A) Erythrocyte sedimentation rate (ESR) is increased in inflammatory or infectious states due to elevated circulating plasma proteins (usually fibrinogen). In PV, there is a higher relative concentration of erythrocytes to fibrinogen, which causes a low (not high) ESR. (Choice B) Serum iron levels are low in most patients with PV due to increased hematopoiesis with subsequent increased iron utilization. (Choice C) Patients with hypoxia-driven forms of secondary erythrocytosis may have low resting arterial oxygen saturations. Patients with PV usually have normal oxygen saturations; the erythrocytosis in PV is EPO (hypoxemic) independent. (Choice E) The BCR-ABL fusion protein is usually seen in chronic myeloid leukemia (CML). CML is typically associated with severe leukocytosis (with leukocytes often >100,000/mm³) and anemia. This patient has mild leukocytosis and severe erythrocytosis, making PV far more likely. Educational objective: Polycythemia vera is a myeloproliferative disorder marked by erythrocytosis. It is a form of primary polycythemia, almost always caused by a mutation of JAK2 in a myeloid precursor cell. Erythropoietin levels tend to be low (unlike most causes of secondary polycythemia). References: Apoptosis and polycythemia vera. (http://www.ncbi.nlm.nih.gov/pubmed/10088639) Current diagnostic criteria for the chronic myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF). (http://www.ncbi.nlm.nih.gov/pubmed/16919893)

A 51-Year-Old Man Comes to the Office Due to Frequent