A 43-year-old man visiting the United States from Thailand comes to the emergency department due to 10 days of hemoptysis. He also has had night sweats but reports no fever or weight loss. Temperature is 37.7 C (99.9 F), blood pressure is 118/68 mm Hg, pulse is 86/min, and respirations are 18/min. Physical examination shows right-sided rhonchi and crackles. Chest x-ray shows an infiltrate in the right upper lobe. Sputum samples from 3 consecutive days are also obtained. After 72 hours of tuberculin skin test (TST) placement, there is no induration at the site; however, 2 of 3 sputum sample smears reveal acid-fast bacilli. Which of the following best explains the negative TST in this patient?

Question

A 43-year-old man visiting the United States from Thailand comes to the emergency department due to 10 days of hemoptysis.  He also has had night sweats but reports no fever or weight loss.  Temperature is 37.7 C (99.9 F), blood pressure is 118/68 mm Hg, pulse is 86/min, and respirations are 18/min.  Physical examination shows right-sided rhonchi and crackles.  Chest x-ray shows an infiltrate in the right upper lobe.  Sputum samples from 3 consecutive days are also obtained.  After 72 hours of tuberculin skin test (TST) placement, there is no induration at the site; however, 2 of 3 sputum sample smears reveal acid-fast bacilli.  Which of the following best explains the negative TST in this patient?

Quizplus · Accepted Answer

This patient from Thailand has hemoptysis, night sweats, right upper lobe infiltrate, and positive sputum acid-fast bacillus stain, raising strong suspicion for active pulmonary TB. Tuberculin skin testing (TST) is generally positive in patients with active TB because differentiated lymphocytes recognize injected tuberculin antigens and trigger a strong type IV (cell-mediated) hypersensitivity response, leading to a large wheal of induration within 48-72 hours. However, approximately 25% of patients with active TB have false negative TST (T cell anergy). In these individuals, an impaired lymphocyte response results in minimal or no induration after exposure to tuberculin antigens. Because a weak cell-mediated response increases the risk of severe disseminated TB, patients with active disease who have TST anergy are at much greater risk for TB-related morbidity and mortality. A false-negative TST can also be seen with recent infection (it takes approximately 8 weeks for the cell mediated response to fully form), immunocompromise (eg, HIV), improper injection technique, and natural waning of immunity to latent infection. Because active TB requires a microbial diagnosis (eg, identifying the organism on sputum sample), neither TST nor interferon-gamma release assay can be used to diagnose or exclude the disease. (Choice A) Bacille Calmette-Guérin vaccination uses Mycobacterium bovis, which shares antigens with tuberculous mycobacteria. This vaccination primes the lymphocyte response against Mycobacterium tuberculosis, therefore protecting against infection, morbidity, and mortality. Patients with previous BCG vaccination can have false-positive (not false negative) TST. (Choice B) TB infection is primarily controlled by macrophages and T lymphocytes. The humoral immune system plays a minimal role and does not contribute to TST induration. Therefore, an autoantibody disorder is unlikely to cause anergy. (Choice D) Induration typically takes 48-72 hours to form following TST. This patient's test was negative at 72 hours, an appropriate time frame for TST interpretation. (Choice E) Acid-fast bacillus stain and TST do not differentiate nontuberculous from tuberculous mycobacteria. Therefore, nontuberculous mycobacterial infection is a common cause of a false-positive (not a false-negative) TST. This patient's history of residence in a TB-endemic country, hemoptysis, night sweats, and upper lobe infiltrate are all highly suspicious for pulmonary TB. Educational objective: Approximately 25% of patients with active TB have false-negative tuberculin skin testing (TST) (anergy) due to an impaired cell-mediated immune response. These individuals are at greater risk for severe, disseminated disease and death. False-negative TST can also be seen with immunocompromise, improper injection technique, and recent infection. __________ References: Tuberculin skin test result and risk of death among persons with active TB. (http://www.ncbi.nlm.nih.gov/pubmed/24244358)

A 43-Year-Old Man Visiting the United States from Thailand Comes