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1292 Part X: Malignant Myeloid Diseases Chapter 84: Polycythemia Vera 1293

increased risk of developing an MPN, and chronic inflammation is Budd-Chiari syndrome may be the first clinical manifestation of
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suggested to contribute to mutagenesis and clonal evolution in PV. 66–68 PV; endogenous erythroid colony formation and JAK2 V617F mutation
A recent molecular profiling study found that a number of immune and have been described in many of these patients before any clinical evi-
inflammatory genes were either up- or downregulated in PV patients, dence of polycythemia. 84,85 PV is the most frequent underlying disease
among them interleukin-10, interleukin-4, complement 5, short pen- associated with Budd-Chiari syndrome. The association of Budd-
traxin C-reactive protein, fibrinogen, orosomucoid, and transforming Chiari syndrome and PV is so strong that many experts advocate
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growth factor-β . The dysregulation of immune and inflammatory screening for PV with JAK2 V617F mutation analysis in all patients who
1
genes in PV may represent an additional avenue for future therapeutic present with hepatic vein thrombosis. 86,87 Budd-Chiari syndrome is a
development. serious condition, often requiring a liver transplant for treatment. 85,88,89
Cutaneous Findings
CLINICAL FEATURES Pruritus occurs in approximately 40 percent of PV patients. It is usually
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aggravated by bathing or showering (aquagenic pruritus), and may be
SIGNS AND SYMPTOMS so severe it markedly compromises the quality of life of the patient. 82,91
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PV usually has an insidious onset, most commonly during the sixth It has been attributed to increased numbers of mast cells in the skin
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decade of life, although onset may occur from childhood to old age. and to elevated histamine levels, although these associations were not
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Presenting signs and symptoms may include headache, plethora, pru- found in other studies. 94
ritus, thrombosis, and gastrointestinal bleeding, but many patients are Several PV patients have developed the dermatologic disorder,
diagnosed because elevated hemoglobin, and sometimes other cell acute febrile neutrophilic dermatosis (i.e., Sweet syndrome). 95,96
counts, are found on a periodic medical examination. Others cases may Erythromelalgia
be uncovered during investigation for blood loss, iron-deficiency ane- Erythromelalgia is a syndrome characterized by warmth of the extrem-
mia, or thrombosis. Symptoms are reported by at least 30 percent of ities; painful, reddened digits; a burning sensation; and erythema of the
patients at the time of diagnosis; other patients may admit to symptoms fingers, hands, and feet (Fig. 84–1) that is associated with thrombocy-
on direct questioning. The most common symptoms, in decreasing tosis. It characteristically responds rapidly to low-dose aspirin therapy.
order of frequency, are headache, fatigue, weakness, pruritus, dizzi- In severe cases, it results in ischemic necrosis of the digits and may lead
ness, and night sweats, but these symptoms are more likely in those PV to their amputation. This syndrome occurs in less than 5 percent of PV
patients transforming to MF (Chap. 86). 70 patients. 75,81 It is not specific to PV or other MPNs, and in one series
PV generally occurs in older patients, a population who may of 168 patients with erythromelalgia, less than 10 percent had PV. A
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already have an elevated rate of vascular abnormalities (e.g., coronary causative role for transient microvascular occlusion by platelet aggre-
artery disease). Development of PV represents an additional increase in gates has been proposed (Chap. 112). 98,99
the risk of vascular events.
Abdominal Findings
Thrombosis and Hemorrhage Portal hypertension, varices, and abdominal pain are not uncom-
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Thrombotic episodes are the most common and most important compli- mon, and are often caused by unrecognized splenic or hepatic vein
cation of PV, 71–73 occurring in approximately one-third of PV patients. thromboses. The occurrence of Budd-Chiari syndrome is noted above
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From one-half to three-quarters of these events are arterial ; ischemic (see “Hepatic Vein Thrombosis [Budd-Chiari Syndrome]” above). The
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strokes and transient ischemic attacks account for the majority of arte- incidence of peptic ulcer is four to five times greater than in the gen-
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rial complications. In some studies, 40 to 60 percent of patients develop eral population. Gastrointestinal bleeding may be the first presenting
at least one thrombotic event over a period of 10 years, the annual inci- symptom of PV, with iron deficiency caused by gastrointestinal blood
dence being approximately equal throughout this period. However, loss frequently masking erythrocytosis. 87
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in prospective studies, thrombosis was most common just prior to
and during the first few years after diagnosis. 74,77,78 The most common Cardiovascular Findings
serious complication is a cerebrovascular accident, which accounts for Cardiovascular complications include angina, myocardial infarction,
approximately one-third of thrombotic events, followed in frequency and congestive heart failure, related to a predisposition to thrombosis in
31,75,77
by myocardial infarction, deep vein thrombosis, and pulmonary embo- the coronary circulation.
lism. The allelic burden of the JAK2 V617F mutation has been correlated Pulmonary Hypertension
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with activation of thrombotic pathways in PV patients, 79,80 although this Pulmonary hypertension occurs in a higher than expected frequency
idea is not universally accepted. 39 in patients with PV. The suggested etiologies include smooth muscle
Bleeding and bruising is a common complication of PV, occurring hyperplasia induced by the release of platelet-derived growth factor from
in approximately one-quarter of patients in some series. Although activated platelets, obstruction of pulmonary circulation by megakary-
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such episodes are usually minor (e.g., gingival bleeding, nose bleeding, ocytes, extramedullary hematopoiesis, and unrecognized recurrent
easy bruising), serious gastrointestinal and other hemorrhagic compli- thrombotic events. 102,103 None of these etiologies are clearly established.
cations with a fatal outcome can also occur. 31,75,81,82
Hepatic Vein Thrombosis (Budd-Chiari Syndrome) Budd- Neurologic Findings
Chiari syndrome is a catastrophic and often fatal complication of PV. In Neurologic symptoms such as dizziness and headache are very common
one series, it occurred in 10 percent of 140 PV patients, but was less in PV. 31,75,77,81,104 Spinal cord compression secondary to extramedullary
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common in a European collaborative study. Budd-Chiari syndrome is hematopoiesis has been documented. 105
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caused by a thrombosis in the hepatic venous outflow, leading to ische-
mia from reduced perfusion through hepatic arterioles and necrosis Findings in Other Organ Systems
of hepatocytes. Budd-Chiari syndrome may present as ascites with or The increased nucleic acid turnover that results from the excessive pro-
without right-upper-quadrant abdominal pain, hepatosplenomegaly, liferation of marrow cells often leads to an increase in blood uric acid
and jaundice. concentration; gout can be exacerbated in some patients. 31

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