WBR0684

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 33 year old man presents to the emergency department (ED) complaining of severe abdominal pain and vomiting. He has no significant past medical history except for bouts of red urine and yellow skin color, especially in the early morning following late night exercise. Physical examination is remarkable for skin jaundice, hepatomegaly, abdominal distention with shifting dullness, and lower extremity edema. Following appropriate imaging, the patient is diagnosed with Budd-Chiari syndrome and adequate management is initiated. Further investigation including flow cytometry shows decreased expression of CD59 and CD55 on red blood cells. Which of the following is an appropriate pharmacologic therapy for this patient's condition?]]
Answer A	AnswerA::Eculizumab
Answer A Explanation	AnswerAExp::Eculizumab is a monoclonal antibody against complement protein C5 that is currently used to treat PNH.
Answer B	AnswerB::Infliximab
Answer B Explanation	AnswerBExp::Infliximab is an anti-TNF alpha used in autoimmune diseases, such as Crohn's diseases of rheumatoid arthritis.
Answer C	AnswerC::Rituximab
Answer C Explanation	AnswerCExp::Rituximab is an anti-CD20 antibody used to treat B cell neoplasms including multiple myeloma, acute lymphocytic leukemia and certain B-cell non-Hodgkin's lymphomas.
Answer D	AnswerD::Gamma-interferon
Answer D Explanation	AnswerDExp::Gamma-interferon is used in conditions such as chronic granulomatous disease (CGD).
Answer E	AnswerE::Tacrolimus
Answer E Explanation	AnswerEExp::Tacrolimus is a calcineurin inhibitor that prevents the secretion of IL-2.
Right Answer	RightAnswer::A
Explanation	[[Explanation::The patient is presenting with paroxysmal nocturnal hemoglobinuria (PNH). PNH is a disease of the red blood cells (RBC), where deficiency of cell-membrane glycophosphatidylinositol (GPI) causes a subsequent deficiency of GPI-anchored proteins on the RBC surface. The normal physiologic function of the missing GPI-linked proteins is to inhibit complement activation. RBCs without sufficient complement-inhibiting factors are lysed in a complement-dependent fashion. PNH is the only disorder of RBC membrane integrity that is typically acquired (compare to hereditary spherocytosis for example). Patients typically experience any of the following: Hemolytic anemia, thrombosis, and abnormal hematopoiesis, including pancytopenia. The patient in the vignette describes his nocturnal hemoglobinuria, that is clinically frequently mistaken for hematuria. In PNH, hemoglobin breakdown most commonly occurs in episodes, especially after times of stress, such as exercise or infections. Because thrombosis is a feature of PNH, patients usually have thrombotic events in unusual locations, such as in the hepatic veins or the portal system. In this vignette, the patient was diagnosed with Budd-Chiari syndrome, or hepatic vein thrombosis. Finally, flow cytometry showing decreased or absent CD55 and CD59 on RBC is diagnostic of PNH. Treatment is usually by eculizumab, a humanized monoclonal antibody that binds to complement protein C5 and inhibits its cleavage into C5a and C5b. Educational Objective: Eculizumab is a humanized monoclonal antibody used to treat PNH. References: Parker C, Bessler M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709. ]]
Approved	Approved::Yes
Keyword	WBRKeyword::PNH, WBRKeyword::Paroxysmal nocturnal hemoglobinuria, WBRKeyword::Haemoglobinuria, WBRKeyword::Jaundice, WBRKeyword::Abdominal pain, WBRKeyword::Budd-chiari sydrome, WBRKeyword::Chiari, WBRKeyword::Flow cytometry, WBRKeyword::Thrombosis, WBRKeyword::Hemolytic anemia, WBRKeyword::Pancytopenia, WBRKeyword::CD55, WBRKeyword::CD59, WBRKeyword::Hemolysis, WBRKeyword::Complement
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