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Difficulty: MediumMonitoring and Treatment Evaluation

A 38-year-old woman presents to the urgent care clinic with a 3-day history of extreme fatigue, sore throat, and new-onset bleeding from her gums while brushing her teeth. She has a history of severe Crohn disease that has been well-controlled on daily azathioprine for the past three years. Three weeks ago, she developed a painful, swollen right great toe and was diagnosed with a gout flare. Her primary care physician started her on allopurinol to prevent future attacks. Her temperature is 38.4°C (101.1°F), blood pressure is 112/72 mm Hg, and pulse is 108/min. Physical examination reveals mucosal pallor, oral petechiae, and pharyngeal erythema without exudate. Which of the following is the most appropriate next step in the evaluation and management of this patient?

  1. Withhold azathioprine and allopurinol, and immediately obtain a complete blood count.Answer
  2. B
    Continue current medications and obtain a comprehensive metabolic panel to evaluate for hepatotoxicity.
  3. C
    Obtain a rapid streptococcal antigen test and initiate empiric oral amoxicillin.
  4. D
    Discontinue allopurinol and initiate oral colchicine for gout management.
  5. E
    Schedule an urgent bone marrow biopsy to evaluate for acute leukemia.

Answer

Withhold azathioprine and allopurinol, and immediately obtain a complete blood count.
The correct answer addresses the critical and potentially fatal drug-drug interaction between azathioprine and allopurinol. Azathioprine is a prodrug that is converted to 6-mercaptopurine (6-MP). 6-MP is subsequently metabolized and inactivated by the enzyme xanthine oxidase. Allopurinol, prescribed for the patient's gout, is a potent xanthine oxidase inhibitor. Coadministration of these two drugs causes a profound decrease in the metabolism of 6-MP, leading to its toxic accumulation. This results in severe bone marrow suppression. The patient's presentation of fever, sore throat, severe fatigue, pallor, and petechiae is the classic triad of pancytopenia: neutropenia, anemia, and thrombocytopenia, respectively. The most appropriate initial step is to immediately withhold both medications and obtain a complete blood count to evaluate the severity of the bone marrow failure.

Step-by-Step Solution

1
Identify the critical drug interaction in the patient's medication history.
The patient is taking both azathioprine and allopurinol.
Azathioprine is converted to 6-mercaptopurine, which is metabolized by xanthine oxidase. Allopurinol inhibits xanthine oxidase, leading to a toxic accumulation of 6-mercaptopurine.
2
Correlate the drug interaction with the patient's physical symptoms.
Fever, sore throat, mucosal pallor, and petechiae are identified as signs of pancytopenia.
The toxic accumulation of 6-mercaptopurine causes severe dose-dependent bone marrow suppression, manifesting as neutropenia (infection/fever), anemia (pallor/fatigue), and thrombocytopenia (petechiae/bleeding).
3
Determine the safest and most appropriate immediate clinical intervention.
The offending medications must be stopped and blood counts must be checked.
Immediate cessation prevents further toxicity, and a complete blood count is the definitive initial diagnostic test to quantify the severity of the myelosuppression.

Key Concept

Patients taking azathioprine or 6-mercaptopurine who are subsequently prescribed allopurinol are at high risk for life-threatening bone marrow suppression due to xanthine oxidase inhibition.
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Topics

Monitoring and Treatment Evaluation

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