A 41-year-old woman comes to clinic due to severe shortness of breath, cough, and hemoptysis. She recently immigrated to the United States and reports that her father, who stayed behind in her country of origin, has similar respiratory symptoms. A chest radiograph reveals right upper lobe fibrosis and her sputum is positive for acid-fast bacilli. A diagnosis of active pulmonary tuberculosis is made and she is begun on a regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. She presents for a follow-up visit one month later and says that her symptoms have improved and she feels "much better." Her sputum is now negative for acid-fast bacilli. Laboratory results are as follows: What is the next best step in the management of this patient?

Question

A 41-year-old woman comes to clinic due to severe shortness of breath, cough, and hemoptysis.  She recently immigrated to the United States and reports that her father, who stayed behind in her country of origin, has similar respiratory symptoms.  A chest radiograph reveals right upper lobe fibrosis and her sputum is positive for acid-fast bacilli.  A diagnosis of active pulmonary tuberculosis is made and she is begun on a regimen of isoniazid, rifampin, ethambutol, and pyrazinamide.  She presents for a follow-up visit one month later and says that her symptoms have improved and she feels "much better."  Her sputum is now negative for acid-fast bacilli.  Laboratory results are as follows:  What is the next best step in the management of this patient?

Quizplus · Accepted Answer

Explanation: Isoniazid (INH) is a bactericidal antibiotic that is particularly effective against replicating Mycobacterium tuberculosis when used in conjunction with other agents such as rifampin, ethambutol, and pyrazinamide. INH is not without adverse effects, however, and has been associated with hepatotoxicity, which can manifest as a mild INH hepatotoxicity or severe INH hepatitis. Mycobacterium tuberculosis Severe INH hepatitis presents with clinical manifestations similar to those seen with viral hepatitis (eg, fatigue, nausea, flu-like symptoms, jaundice, aminotransferases >10 times upper limit of normal). The risk of developing this more ominous form of severe hepatitis is estimated to be 2.6% for those who drink alcohol daily, already have liver disease, or are age ≥50. If signs and symptoms of severe INH hepatitis are observed, the drug should be discontinued immediately. In contrast, ~10%-20% of patients taking INH will experience mild, subclinical hepatic injury (mild INH hepatotoxicity) demonstrated only by minor elevations in serum aminotransferases (typically <100 IU/L). The prognosis is excellent in these patients and the condition is self-limited, allowing for INH therapy to be maintained with close follow-up. Because the patient in this question is relatively young and otherwise asymptomatic, she can continue taking INH as long as her liver function tests are regularly monitored and remain only mildly elevated. (Choice B) Most of the first-line antituberculosis drugs are hepatotoxic and should be replaced by second-line antituberculosis drugs in patients who develop significant hepatotoxicity with the initial regimen. This patient, however, shows no signs of severe hepatotoxicity. A change in treatment plan is not indicated. (Choice C) Although the patient's sputum is negative for acid-fast bacilli, she is not likely to have fully cleared the dormant bacilli after one month of treatment. (Choice D) A liver biopsy is indicated in patients with asymptomatic elevation of liver enzymes of unknown etiology, as tissue examination will allow for a better understanding of the pathologic process involved. However, the aminotransferase elevations in this patient are most likely due to tuberculosis treatment. Therefore, no biopsy is indicated at this time. (Choice E) There is some evidence that glucocorticoids are of benefit in the treatment of severe miliary tuberculosis. However, this patient does not have miliary tuberculosis. Educational objective: Approximately 10%-20% of patients on isoniazid will develop mild aminotransferase elevation within first few weeks of treatment. This hepatic injury is typically self-limited and will resolve without intervention.

A 41-Year-Old Woman Comes to Clinic Due to Severe Shortness