Case Presentation: A 69-year-old man with a history of chronic obstructive pulmonary disease was admitted with fevers and altered mental status (AMS). He reported 6 months of fevers, with confusion and shortness of breath. He denied cough and sputum production, but endorsed a 20lb unintentional weight loss. He had no history of immunosuppression, imprisonment, or known exposures to Mycobacterium tuberculosis (Mtb). He was born in the Azores and immigrated to the US at age 24. He was previously admitted 5 times to an outside hospital for these complaints, and extensive workup failed to identify an etiology. Prior chest CT showed pulmonary infiltrates and hilar lymphadenopathy, and bronchoscopy with lymph node and lung biopsies showed “inflammatory changes.” During these events, he was treated with antibiotics and steroids, but his fevers recurred. On admission to our institution, the patient’s temperature was 101.4F. Physical exam was notable for a chronically ill-appearing man, alert and oriented to self, anterior cervical lymphadenopathy, and bibasilar crackles in the lungs. Labs showed a Cr of 3.2, albumin of 2.8, ESR > 140, CRP 279, WBC count of 16, 24% bands, hemoglobin of 7.4 and platelet count of 75. The patient was treated with IV ceftazidime for 5 days and his leukocytosis resolved, however his fevers persisted. Extensive diagnostic workup including blood, urine, and induced sputum cultures (including 3 samples for acid fast bacilli), interferon-γ release assay (IGRA) x2, sputum Mtb nucleic acid amplification tests (NAATs) x2, HIV, Coxiella, Brucella, Bartonella, ANA, ANCA, complements, cryoglobulins, ACE, SPEP, peripheral blood flow cytometry were all within normal limits. PET CT showed bilateral pulmonary nodules, and intensely FDG-avid mediastinal, hilar, right supraclavicular and bilateral axillary lymphadenopathy, “suggestive of sarcoidosis.” Repeat bronchoscopy with biopsy was non-diagnostic. Mediastinoscopy was notable for necrotizing lymphadenitis with rare AFB organisms. The patient continued to have fevers, but felt improved when taking acetaminophen, and was discharged home to await culture data. At 30 days, PCR based DNA probe from the specimen was positive for Mtb. At 35 days, cultures from the patient’s mediastinoscopy grew Mtb. All other cultures from the patient’s workup (sputum, BALs, 2 EBUS-guided lung/LN biopsies) were negative. The patient was initiated on standard 4 drug DOT therapy, his fevers resolved, and he improved dramatically.
Discussion: Tuberculosis is a pauci-bacillary disease and is endemic in Portugal and the Azores. A positive IGRA can suggest active TB disease, but a negative result does not rule out Mtb. Sputum culture for AFB remains the gold standard, with a sensitivity and specificity of 88% and 99%. Sputum rapid NAATs are important but have limitations, with a sensitivity and specificity of 66% and 97% in smear negative patients. In this case, the patient’s active TB infection led to fevers with AMS, possibly leading to aspiration events and aspiration pneumonia. Multiple exposures to antibiotics during prior admissions, including fluoroquinolones, may to have contributed to his prior non-diagnostic workup.
Conclusions: As a pauci-bacillary disease, tuberculosis can represent a diagnostic challenge. AFB smears, IGRAs, and NAATs are clinically useful but a negative test does not rule out Mtb infection in certain clinical contexts. A high index of clinical suspicion and meticulous diagnostic workup is often necessary to diagnose TB disease.