WBR0161
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pharmacology |
| Sub Category | SubCategory::Hematology, SubCategory::Oncology |
| Prompt | [[Prompt::A 75-year-old man presents to his physician for excessive pruritus that is exacerbated by taking showers. On physical exam, the spleen is palpable 9 cm below the costal margin. Laboratory testing is notable for a hematocrit of 70%. Further testing confirms the diagnosis with the presence of a JAK2 mutation. Therapy consisting of regular phlebotomy and an agent that inhibits ribonucleotide reductase is initiated. For which of the following conditions may this drug also be used?]] |
| Answer A | AnswerA::Acute Gout |
| Answer A Explanation | AnswerAExp::Acute gout should be treated with NSAIDs and colchicine. However, many patients with polycythemia vera develop gout. |
| Answer B | AnswerB::Basal Cell Carcinoma |
| Answer B Explanation | AnswerBExp::Basal cell carcinoma may be a rare consequence of hydroxyurea therapy. Conversely, hydroxyurea is not indicated for basal cell carcinoma. |
| Answer C | AnswerC::Small Cell Lung Cancer |
| Answer C Explanation | AnswerCExp::Hydroxyurea is not indicated for Small Cell Lung Cancer. |
| Answer D | AnswerD::Rheumatoid Arthritis |
| Answer D Explanation | AnswerDExp::Methotrexate inhibits dihydrofolate reductase and is a first-line agent for rheumatoid arthritis. Hydroxyurea is not indicated for RA. |
| Answer E | AnswerE::Sickle Cell Anemia |
| Answer E Explanation | AnswerEExp::Hydroxyurea can be used in sickle cell disease because it increases the synthesis of fetal hemoglobin. |
| Right Answer | RightAnswer::E |
| Explanation | [[Explanation::The patient in this vignette is suffering from polycythemia vera and is being treated with hydroxyurea. Polycythemia vera (PV) is a myeloproliferative blood disorder in which the bone marrow makes too many red blood cells. PV is caused by mutations in the JAK2 gene, which render erythroid precursors hypersensitive to erythropoietin (EPO). It is more common in the elderly and may be symptomatic or asymptomatic. Common signs and symptoms include itching (pruritus), and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish coloration of the skin. Pruritis is often exacerbated by exposure to warm water, such as when taking a shower or bath. Many patients will exhibit splenomegaly due to erythrocyte trapping. The rapid turnover of erythrocytes in PV can lead to release of uric acid and gout in 20% of patients.
Treatment for PV includes regular phlebotomy to decrease blood count and the number of RBCs. Phlebotomy may be supplemented with hydroxyurea, a compound which inhibits ribonucleotide reductase to starve erythrocyte precursors of necessary deoxynucleotides for DNA synthesis. Hydorxyurea may also be used in sickle cell disease. Through unknown mechanisms, hydroxyurea administration increases the synthesis of fetal hemoglobin which can replace the mutant beta-globin in sickle cell patients and thereby decrease sickling of RBCs. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Cancer, WBRKeyword::Hydroxyurea, WBRKeyword::Chemotherapy, WBRKeyword::Polycythemia, WBRKeyword::Polycythemia vera, WBRKeyword::Itching. Pruritis |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |