A 32-year-old woman comes to the office for a regularly scheduled follow-up visit. She has mild fatigue but no other symptoms. Medical history is significant for generalized seizures controlled with chronic phenytoin therapy. Her last seizure was 6 months ago. She does not use tobacco, alcohol, or illicit drugs. She is afebrile and vital signs are within normal limits. Examination shows mild gingival hyperplasia and pallor. There is no jaundice or lymphadenopathy. Cardiopulmonary examination is normal. The abdomen is soft and nontender with no hepatosplenomegaly. Laboratory results are as follows: Supplementation with which of the following could have prevented this patient's condition?

Question

A 32-year-old woman comes to the office for a regularly scheduled follow-up visit.  She has mild fatigue but no other symptoms.  Medical history is significant for generalized seizures controlled with chronic phenytoin therapy.  Her last seizure was 6 months ago.  She does not use tobacco, alcohol, or illicit drugs.  She is afebrile and vital signs are within normal limits.  Examination shows mild gingival hyperplasia and pallor.  There is no jaundice or lymphadenopathy.  Cardiopulmonary examination is normal.  The abdomen is soft and nontender with no hepatosplenomegaly.  Laboratory results are as follows:  Supplementation with which of the following could have prevented this patient's condition?

Quizplus · Accepted Answer

Explanation: This patient with a history of seizure disorder is being treated with phenytoin, an antiepileptic with several common adverse effects, including: Folic acid deficiency: Phenytoin impairs folic acid absorption in the jejunum, which often results in folic acid deficiency over weeks or months. Because folate (tetrahydrofolate) is required for purine and thymidine synthesis, deficiency impairs DNA synthesis, particularly in cells that undergo rapid turnover (eg, hematologic cells). This often leads to megaloblastic anemia (eg, macrocytosis, hypersegmented neutrophils). Gingival overgrowth/hyperplasia: Phenytoin has several effects on the gingival mucosa but is thought to reduce folic acid use in the extracellular matrix of the gums, leading to impaired collagenase activity and a subsequent buildup of gingival matrix. These adverse effects can usually be prevented with oral folic acid supplementation. Because phenytoin also disrupts bone and mineral metabolism (leading to reduced bone density), calcium and vitamin D supplementation are also generally administered. Other medications that commonly cause megaloblastic anemia include methotrexate, trimethoprim, and pyrimethamine due to disruptions in dihydrofolate reductase (the enzyme that mediates tetrahydrofolate production). (Choice B) Iron deficiency causes microcytic anemia and does not enhance gingival growth. (Choice C) Vitamin B₁ (thiamine) deficiency can occur in those who use excess alcohol; it causes Wernicke encephalopathy, which is characterized by gait dysfunction, confusion, and oculomotor palsy. Macrocytic anemia is atypical. ₁ (Choice D) Vitamin B₆ (pyridoxine) deficiency is associated with peripheral neuropathy, not macrocytic anemia. Pyridoxine deficiency often occurs as a consequence of isoniazid therapy for tuberculosis; high risk patients are given pyridoxine supplementation to prevent this adverse effect. ₆ (Choice E) Vitamin B₁₂ deficiency also causes megaloblastic anemia but is not associated with gingival hyperplasia or phenytoin use. ₁₂ Educational objective: Phenytoin commonly causes megaloblastic anemia and gingival hyperplasia due to impaired folic acid absorption in the jejunum. Supplementation with folic acid prevents these adverse effects. Calcium and vitamin D supplementation are also usually given to counter alterations in bone mineral metabolism that impair bone density.

A 32-Year-Old Woman Comes to the Office for a Regularly