WBR0074

Author	PageAuthor::Anonymous (Reviewed by Will Gibson and Yazan Daaboul)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 32-year-old homosexual intravenous drug user is admitted with a worsening respiratory distress accompanied by fever and nonproductive cough. Arterial blood gas values on room air are pH 7.52, PaCO2=28 mmHg, HCO3=22 mEq/L, and PaO2=70 mmHg. His CD4+ count is 150 cells/μl. Chest X-ray reveals bilateral perihilar interstitial infiltrates suggesting an infectious etiology. The causative organism is detected in bronchoalveolar lavage (BAL) with silver stain. The next day, he starts to have back pain, dizziness, headache, coldness in hands and feet, pale skin, and chest pain. Peripheral blood smear shows irregularly fragmented erythrocytes. Supravital stain of the smear shows immature red cells with dark blue dots and curved linear structures in the cytoplasm. Which of the following medications is most likely to be the cause of his symptoms?]]
Answer A	AnswerA::Atovaquone
Answer A Explanation	[[AnswerAExp::For mild-to-moderate PCP, alternative therapeutic regimens include: dapsone plus TMP, primaquine plus clindamycin, and atovaquone. However, atovaquone is not classically associated with hemolytic anemia.]]
Answer B	AnswerB::Clindamycin
Answer B Explanation	AnswerBExp::For mild-to-moderate disease, alternative therapeutic regimens include: dapsone plus TMP, primaquine plus clindamycin, and atovaquone. However, clindamycin is not classically associated with hemolytic anemia.
Answer C	AnswerC::Methylprednisolone
Answer C Explanation	[[AnswerCExp::Patients with moderate-to-severe disease should receive adjunctive corticosteroids as early as possible and certainly within 72 hours after starting specific PCP therapy. However, methylprednisolone is not classically associated with hemolytic anemia.]]
Answer D	AnswerD::Pentamidine
Answer D Explanation	AnswerDExp::For moderate-to-severe disease, clindamycin-primaquine or pentamidine can be used. However, pentamidine generally is not classically associated with hemolytic anemia.
Answer E	AnswerE::Primaquine
Answer E Explanation	[[AnswerEExp::For mild-to-moderate disease, alternative therapeutic regimens include: dapsone plus TMP, primaquine plus clindamycin, and atovaquone. Common triggers of hemolytic anemia include sulfonamides and other drugs such as chloroquine, isoniazid, nalidixic acid, nitrofurantoin, and primaquine.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::Pneumocystis pneumonia (PCP) is an opportunistic infectious disease caused by Pneumocystis jirovecii. The risk of PCP increases when CD4+ cell levels are less than 200 cells/μl in HIV-positive patients. Symptoms of PCP include fever, dyspnea, non-productive cough, weight loss, and night sweats. Chest films typically show diffuse, symmetrical, perihilar interstitial infiltration that may progress to a homogenous, ground-glass opacification of lung fields. Pneumocystis jirovecii is usually detected using silver stain in BAL. Hypoxemia, the most characteristic laboratory abnormality, can range from mild (room air arterial oxygen ≥70 mm Hg or alveolar-arterial O2 gradient <35 mmHg) to moderate (A-a gradient ≥35 and <45 mm Hg) to severe (A-a gradient ≥45 mm Hg). Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice for PCP. For mild-to-moderate disease, alternative therapeutic regimens include: dapsone plus TMP, primaquine plus clindamycin, and atovaquone. For moderate-to-severe disease, clindamycin-primaquine or pentamidine can be used. Patients with moderate-to-severe disease should receive adjunctive corticosteroids as early as possible and certainly within 72 hours after starting specific PCP therapy. The patient's hospital course is complicated by hemolytic anemia due to increased oxidative stress, which typically occurs one or two days after TMP-SMX intake in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder that frequently affects African Americans and patients of Middle Eastern descent. G6PD deficiency is characterized by profound hemolytic anemia, high reticulocyte count, and hemoglobinuria. Additionally, Heinz bodies, bite cells, spherocytes, and reticulocytes may be evident on peripheral blood smear. Common causes of hemolysis in patients with G6PD deficiency include: TMP-SMX, antimalarial drugs (such as primaquine and chloroquine), sulfa drugs, isoniazid, nalidixic acid, nitrofurantoin, fava beans, and other non-pharmacologic stressors such as infections. Educational Objective: Hemolytic anemia due to glucose-6-Phosphate Dehydrogenase (G6PD) deficiency may be precipitated by primaquine, a treatment option for Pneumocystis pneumonia (PCP) in HIV-positive patients. References: Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207. First Aid 2014 page 253 (drugs that cause hemolytic anemia in patients with G6PD deficiency) First Aid 2014 page 386 (G6PD deficiency summary)]]
Approved	Approved::Yes
Keyword	WBRKeyword::G6PD, WBRKeyword::X-linked recessive, WBRKeyword::Genetics, WBRKeyword::Hematology, WBRKeyword::Hemolytic anemia, WBRKeyword::Heinz bodies, WBRKeyword::Blood, WBRKeyword::HIV, WBRKeyword::Side effect, WBRKeyword::Anemia, WBRKeyword::AIDS, WBRKeyword::Pneumonia, WBRKeyword::PCP
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