Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven to be useful for lymph node staging in lung cancer patients1 and in diagnosing intrapulmonary and mediastinal tumors, hilar and/or mediastinal lymphadenopathy, and sarcoidosis.1–3 Recently, EBUS-TBNA has been used in the rapid diagnosis of tuberculosis (TB), increasing the diagnostic yield.4 To date, however, EBUS-TBNA has not been used for the diagnosis of multidrug-resistant TB (MDR-TB). We here use EBUS-TBNA, together with restriction fragment length polymorphism (RFLP) analysis of Mycobacterium tuberculosis isolates, to diagnose MDR-TB, including transmission between family members.
Patient 1 (Index Case)
A 20-year-old bacille Calmette-Guérin--vaccinated male patient was hospitalized in April 2008 because of a 3-week history of cough and a 1-week history of blood-tinged sputum and fever. The patient had lost 4 kg of weight during the previous 4 months. There was no history of TB or other underlying disease. At admission, his body temperature was 38.2°C and his pulse rate was 125 beats/min; other parameters were normal. A chest radiograph showed multiple irregular centrilobular nodules in both the upper lobes. Microscopic examination of the sputum showed acid-fast bacilli (AFB). A tuberculin skin test and a human immunodeficiency virus test were negative. He was preliminarily diagnosed with pulmonary TB and in May 2008 he commenced treatment with isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Two months later, a sputum culture was confirmed as positive for M. tuberculosis, and drug susceptibility testing (DST) showed that the isolate was resistant to INH, RMP, EMB, PZA, kanamycin, and prothionamide but susceptible to streptomycin (SM), p-aminosalicylic acid (PAS), cycloserine (CLOS), amikacin, and ofloxacin. In August 2008, the patient was switched to SM, levofloxacin, PAS, CLOS, and amoxicillin/clavulanate. In November 2008, his sputum culture was negative and he is still undergoing treatment as of January 2010.
Patient 2 (Contact)
A 54-year-old bacille Calmette-Guérin--vaccinated female patient, mother of the index patient (patient 1) and living in the same house for a long period of time, visited our hospital for contact investigation in June 2008. Many years earlier, she had undergone a total thyroidectomy because of thyroid cancer, but she had no history of TB. As she had no symptoms suggestive of TB and her chest radiograph was normal, she was followed up without treatment. One year later, a routine computed tomography scan of her chest showed a newly developed, right-sided paratracheal lymphadenopathy, compared with an earlier computed tomography scan in 2005 (Fig. 1). She was negative for human immunodeficiency virus and routine bronchoscopy was unremarkable. EBUS-TBNA was performed using a bronchoscope (BF-UC260F-OL8; Olympus, Tokyo, Japan) (Fig. 2). The specimen was negative for AFB staining, but a culture was later positive for M. tuberculosis. On the basis of the DST pattern of the index patient, this patient was prescribed treatment with SM, moxifloxacin, PAS, CLOS, and amoxicillin/clavulanate in October 2009. DST of her isolate showed resistance to INH, RMP, EMB, PZA, and prothionamide. RFLP analysis showed that the isolates from both the patients had identical band patterns, confirming the transmission of MDR-TB between family members (ie, from the son to his mother) (Fig. 3).
To the best of our knowledge, this is the first instance in which EBUS-TBNA was used to confirm MDR-TB, indicating the use of this technique in diagnosing both TB and malignancies, in a TB-endemic area.
Of our 2 patients, the son was first diagnosed with pulmonary MDR-TB and his mother was later diagnosed with TB lymphadenopathy. The DST results of the 2 isolates were almost identical, and both the isolates showed the same RFLP profile of the IS6110 segment, confirming the transmission of MDR-TB between family members. Although TB is often transmitted from parents to children within a family,5 our finding was the reverse, in that TB had been transmitted from the son to the mother. Neither the mother nor other family members had a history of TB, and the mother's TB was not infectious, indicating that the son was the index patient.
EBUS-TBNA has proven useful for sampling mediastinal masses and nodes and for staging of lung cancer, as well as in the diagnosis of sarcoidosis, lymphoma, and, more recently, TB.1–4 Given the higher diagnostic yield of EBUS-TBNA over conventional blind TBNA in patients with mediastinal lymph nodes except subcarinal nodes6 and relatively small lymph node size in this case, EBUS-TBNA was preferred to conventional TBNA in this case.
On account of the relative safety of the technique and the high diagnostic yield, EBUS-TBNA should be used to sample accessible lymph nodes and masses, and the specimens obtained should be cultured and stained for AFB, especially in TB-endemic areas.
In conclusion, we used EBUS-TBNA to confirm MDR-TB mediastinal lymphadenopathy transmitted from the son to the mother. EBUS-TBNA may play a significant role in diagnosing TB in TB-endemic areas.
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