Confetti on the Lung

Daniel T. Atwood, MD¹, Eleanor D. Muise, MD¹ and Dennis Rosen, MD¹

¹Harvard Medical School, Boston, Massachusetts; Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts

Case:

A 19-year-old male with Crohn’s Disease currently managed with adalimumab and prednisone presented to the Emergency Department with a chief complaint of sore throat. The patient reported two months of unintentional 20lb weight loss, night sweats, and fevers. He was seen by his primary care physician and recently completed a 14-day course of amoxicillin/clavulanate for pharyngitis. The patient also reported new-onset calf pain and chest pain on review of systems. At presentation his vital signs were as follows: temperature 41.2°C, heart rate 131bpm, blood pressure 92/48 mmHg, respiratory rate 16bpm, and SpO₂ 97% in room air. On exam he was ill appearing, but nontoxic, with pertinent findings or oral ulcers, supple neck, tachycardia, and normal vesicular breath sounds. He failed to respond to fluid resuscitation and was admitted to the intensive care unit for vasoactive support. Chest radiograph (Image 1) and, subsequently, CT chest (Image 2) were obtained.

Question:

Based on the presentation and imaging obtained, which element of his clinical history likely contributed most to the diagnosis?

Autoimmune disease
Immunosuppression
Pharyngitis
Calf and chest pain

Answer

B. Immunosuppression

Discussion:

The chest radiograph demonstrated diffuse pulmonary nodules in a miliary pattern. CT chest performed with contrast further confirmed diffusely disseminated micronodules throughout all lung fields. The differential diagnosis of pulmonary micronodules on chest imaging includes mycobacterial infection, fungal infection, and metastatic disease. (1) The CT chest image displayed above is taken from the thin lung series 2mm section to highlight both pulmonary nodules and mediastinal structures. The maximum intensity projection (MIP) series can be used to best highlight pulmonary nodules and to characterize their distribution, though there is loss of differentiation of the soft tissues including mediastinum and chest wall.

The patient’s history of fever and immunosuppression with biologic therapy made infection the most likely diagnosis (Answer B). Pulmonary manifestations of autoimmune disease (Answer A) can include pulmonary nodules, but this does not classically manifest as diffuse micronodules. Lemierre’s syndrome characterized by thrombophlebitis of the internal jugular vein secondary to anaerobic organisms following recent pharyngeal infection (Answer C) was ruled out with a CT neck and would not present with pulmonary micronodules. Deep vein thrombosis and pulmonary embolism, suggested by calf and chest pain (Answer D), was ruled out with CT chest imaging and would not present with pulmonary micronodules. Of note, before the initiation of adalimumab, the patient had a negative T-SPOT.TB (Oxford Immunotec, Abingdon, UK) recorded. The sensitivity and specificity for the T-SPOT.TB test is 95.6% and 97.1%, respectively, which indicates a high likelihood that he was not infected at that time. (2)

Serial sputum samples confirmed the diagnosis of Mycobacterium tuberculosis complex as detected by nucleic acid amplification test (NAAT). Further investigation revealed disseminated disease with peritoneal, central nervous system, renal, and ocular involvement. The patient was prescribed rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy and discharged home to continue directly observed therapy under the direction of the Massachusetts Department of Health. Antibiotic sensitivities demonstrated an isolated resistance pattern to pyrazinamide, which is characteristic of Mycobacterium bovis infection. (3)

M. bovis is a rare but recognized cause of tuberculosis, accounting for fewer than 2% of total tuberculosis cases in the United States annually, and traditionally infects cattle, bison, elk, and deer. Humans can become infected through consumption of unpasteurized milk, direct contact with a wound, or by inhalation of bacteria in the air. (4) M. bovis disease is clinically and radiographically similar to M. tuberculosis, though M. bovis classically results in significant extra-pulmonary disease and typically demonstrates isolated resistance to pyrazinamide. (3,5)

References

Kimmig L, Bueno J. Miliary nodules: not always tuberculosis. Annals of the American Thoracic Society 2017;14(12):1858-1860.
Oxford Immunotec. T-SPOT.TB Package Insert PI-TB-US-0001 V8. Abington, UK. September 2020.
Kurbatova EV, Cavanaugh JS, Dalton T, S. Click E, Cegielski JP. Epidemiology of pyrazinamide-resistant tuberculosis in the United States, 1999–2009. Clinical infectious diseases 2013;57(8):1081-1093.
Centers for Disease Control and Prevention. Tuberculosis (TB) Fact Sheets. Mycobacterium bovis (Bovine Tuberculosis) in Humans. 2012 Available from: https://www.cdc.gov/tb/publications/factsheets/general/mbovis.htm .
Gallivan M, Shah N, Flood J. Epidemiology of human Mycobacterium bovis disease, California, USA, 2003-2011. Emerg Infect Dis 2015;21(3):435-443.

Confetti on the Lung

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