Hydroxyurea-induced genital ulcers and erosions: Two case reports

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain.     

Unsuccessful surgical treatment of thoracic aortic thrombosis in a patient with essential thrombocythemia

Essential thrombocythemia (ET) is a rare condition with an incidence of several persons per million in Japan, while the incidence of thrombosis ranges from 11% to 25%. We present a woman in her 70 seconds with ET who developed small intestinal necrosis and thrombosis in the proximal descending aorta. The patient underwent partial small bowel resection and replacement of the descending aorta, followed by multiple reoperations for thrombotic and hemorrhagic complications. She eventually died of empyema and sepsis caused by Klebsiella oxytoca. In patients with ET and large vessel thrombosis, we have to carefully judge the indications for surgery.     

Renovascular hypertension and coronary heart disease complicating essential thrombocythemia

A 36-year-old male was evalued for treatment-resistant hypertension.A high platelet count 828. 10⁹ l^–1, led to the diagnosisof essential thrombocythemia (ET). Aorto-renal angiography revealedcritical bilateral renal artery stenosis and coronary angiographyshowed three-vessel disease. Percutaneous transluminal renalangioplasty was only partially successful. The patient receiveda 12-week course of busulphan and subsequently the thrombocytecount decreased to 200. 10⁹ l^–1 Renal angiography 12 monthslater showed bilateral regression of the renal artery stenosiswith lowering of the blood pressure to normal levels.     

骨髓增殖性肿瘤120例JAK2 V617F基因突变的临床分析

目的 探讨JAK2 V617F基因突变在骨髓增殖性肿瘤(MPN)患者中的发生率及临床意义.方法 采用骨髓细胞学和活组织检查方法分析120例患者的骨髓病理状况,监测费城染色体(Ph染色体)和bcr-abl融合基因.从患者骨髓抽提DNA,采用荧光定量PCR技术检测JAK2 V617F基因突变.结果 所有患者均呈现出MPN各自类型的典型特征.Ph染色体和bcr-abl融合基因检测均为阴性.120例MPN患者中JAK2 V617F基因突变的阳性率为66.7％(80/120),其中真性红细胞增多症(PV)为72.7％(16/22),原发性血小板增多症(ET)为66.0％(62/94),4例原发性骨髓纤维化(PMF)患者中2例阳性.JAK2 V617F突变阳性PV患者的外周血白细胞计数(P=0.001)和血小板计数(P=0.010)均高于阴性患者;JAK2 V617F突变阳性ET患者的白细胞计数高于阴性患者(P=0.006);PMF中JAK2V617F突变阳性和阴性患者间各项指标差异均无统计学意义(均P＞0.05).结论 JAK2 V617F基因突变检测有助于bcr-abl阴性MPN的诊断和鉴别诊断,使患者能够在早期被发现和治疗.     

Successful Treatment of Essential Thrombocythemia in a Pregnancy with Recombinant Interferon-α2a

Essential thrombocythemia (ET) in pregnancy is associated with adverse perinatal outcome, which is likely due to thrombosis of the uteroplacental circulation. Obstetrical management is still controversial. Different therapeutic protocols have been adopted, including the use of aspirin, plateletpheresis, and interferon. We herein report a case of ET treated with interferon-2α from 13 weeks gestation until term. Therapy was well tolerated, leading to a linear reduction of platelet and white blood cell count that rapidly returned within normal limits. A healthy, 3,020-g male infant was delivered at 40 weeks gestation. Albeit further experience is required, recombinant interferon-α_2a may play an important role in preventing complications in pregnant patients with ET.     

Pharmacological management of essential thrombocythemia

Introduction: Two factors have deeply influenced the area of essential thrombocythemia (ET). A gain-of-function mutation in the pseudokinase region of the JAK2 gene, which partly explains the pathophysiology of myeloproliferative neoplasms (MPNs), was discovered in 2005 and is present in 50 – 60% of ET patients. Furthermore, the 2008 WHO MPN classification outlined criteria for the separation of ET and early or prefibrotic primary myelofibrosis (PMF). However, these and other new findings have not yet changed the pharmacotherapy of ET, which is based on risk stratification for thrombohemorrhagic risk and aims to reduce thrombosis and bleeding.

Areas covered: Studies on the basis for and the validation of the WHO classification as well as studies on possible new risk factors are covered. The most important drugs for ET treatment and consensus recommendations for management of ET are also presented.

Expert opinion: The new WHO classification should be used for both ET studies and clinical practice, since true ET has a different prognosis than early PMF. The management of patients should be based on risk stratification. Age > 60 years or previous throbosis (high risk) and platelet counts > 1500 × 10⁹/l warrant cytoreductive treatment, and high risk patients and selected low risk patients should be given anti-aggregation therapy.     

Neurological symptoms in essential thrombocythemia: impact of JAK2V617F mutation and response to therapy

Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET‐related NS in the absence of TCE, and the response to therapy. Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported subjective transient and fluctuating NS, without concurrent TCE, which we defined as ET‐related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or hypotension, visual disturbances, and tinnitus. In univariate analysis, ET‐related NS resulted more frequently in young people (P = 0.017) and in females (P = 0.025). We found a higher prevalence of JAK2V617F mutation in ET‐related NS patients (P = 0.021). In multivariate analysis, gender (P = 0.024) and JAK2V617F mutation (P = 0.041) remained significantly associated with the development of ET‐related NS, with a risk of about four times higher for JAK2V617F‐mutated patients (OR = 3.75). Ninety‐seven of 101 patients with ET‐related NS received an antiplatelet (AP) agent at the time of NS, whereas only selected high‐risk ET‐related NS patients were treated with a cytoreductive drug, according to the published guidelines and similarly to patients without NS. We observed that only 32 of 97 (33%) patients with ET‐related NS achieved a complete response after AP treatment. Among the 65 non‐responder patients, 36 (55.4%) improved NS after the introduction of cytoreductive therapy; therefore, the addition of cytoreductive treatment should be considered in this setting.