A 54-year-old man comes to the office due to several months of increased fatigability. He drinks 2-3 cans of beer on the weekends and rarely eats meat. Physical examination reveals pale conjunctivae and hyperdynamic carotid pulses. Hemoglobin level is 7.7 g/dL, leukocytes are 4,500/mm³, and platelets are 170,000/mm³. Folic acid therapy is initiated. Four weeks later the patient's hemoglobin level is 9.1 mg/dL, but he has new tingling in his toes. Which of the following is a likely cause of this patient's current symptoms?

Question

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This patient with anemia was treated empirically for folate deficiency in the setting of heavy alcohol use. He now has worsening neurologic symptoms, consistent with untreated, coexisting cobalamin (vitamin B12) deficiency, possibly due to limited meat intake or to pernicious anemia. Both folate and cobalamin (vitamin B12) deficiency can result in a macrocytic, megaloblastic anemia. Folate supplementation is often given to patients with heavy alcohol use; cobalamin supplementation is not routinely administered because, in these patients, cobalamin deficiency is rare in the absence of chronic pancreatitis. However, cobalamin deficiency can develop with limited animal protein (eg, meat) intake or with advanced age due to decreased intrinsic factor (eg, pernicious anemia) and subsequent malabsorption of vitamin B12. In advanced stages, cobalamin deficiency can result in peripheral neuropathy (eg, tingling) or posterior column defects due to defective myelin synthesis. Because both folate and cobalamin are cofactors in the conversion of homocysteine to methionine, folate supplementation can improve the anemia of cobalamin deficiency. However, because cobalamin is used in other processes as well, neurologic deficits can be precipitated or worsened when folic acid is given without cobalamin supplementation. Therefore, it is important to consider cobalamin deficiency prior to starting folic acid replacement. (Choice A) Several drugs, including many cancer chemotherapy agents, cause peripheral neuropathy. The most commonly implicated agents are vincristine, cisplatin, and the taxanes (docetaxel and paclitaxel). Other drugs that cause peripheral neuropathy include phenytoin, isoniazid, amiodarone, and hydralazine. There is no evidence that this patient is taking any of these drugs. (Choice B) Iron deficiency is not associated with peripheral neuropathy, nor does the associated anemia improve with folate supplementation. (Choice D) Peripheral neuropathy is a common complication of diabetes due to small vessel changes from hyperglycemia. There is nothing in this vignette to suggest that this patient has diabetes mellitus. (Choice E) Extramedullary hematopoiesis refers to red blood cell (RBC) production outside of the bone marrow. It can occur in hematologic malignancies, chronic anemias (eg, thalassemias and sickle cell anemia), or myelofibrosis, or it may be idiopathic. Extramedullary hematopoiesis is not associated with peripheral neuropathy. (Choice F) Autoimmune hemolysis occurs when an IgG autoantibody binds to the RBC membrane and promotes removal of the RBC from circulation in the spleen's reticuloendothelial system. The direct Coombs test will be positive. Autoimmune hemolysis is not associated with peripheral neuropathy nor does it improve with folate supplementation. (Choice G) Factitious disorder is the deliberate production or feigning of symptoms in order to assume a sick role. This vignette does not describe any factors that would raise suspicion for factitious disorder (eg, atypical or dramatic presentation, long medical record, vague historical details, or complex knowledge of medicine). Educational objective: Folate and cobalamin deficiency both result in megaloblastic, macrocytic anemia. Folate supplementation can improve the anemia of either disorder but will not improve the neurologic changes of cobalamin deficiency. It is important to distinguish between the two prior to initiating therapy.

A 54-Year-Old Man Comes to the Office Due to Several