Peer Reviewed

Photoclinic

Brucellosis With Pulmonary and Spinal Complications

Volume 60 - Issue 9 - September 2020

AUTHORS:
Eric Kim, MD1 • Alexandra Targan, MD1 • Stephanie Eldred, MD2 • Daniel White, MD1,3

AFFILIATIONS:
1University of Colorado School of Medicine, Aurora, Colorado
2University of Colorado Hospital, Aurora, Colorado
3Denver Health and Hospital, Denver, Colorado

CITATION:
Kim E, Targan A, Eldred S, White D. Brucellosis with pulmonary and spinal complications. Consultant. 2020;60(9):23-25. doi:10.25270/con.2020.06.00007

Received February 15, 2020. Accepted May 11, 2020.

DISCLOSURES:
The authors report no relevant financial relationships.

CORRESPONDENCE:
Daniel White, MD, Lowry Family Health Center, 1001 Yosemite St, Denver, CO 80230 (daniel.white2@dhha.org)

 

A 65-year-old man with no significant medical history presented to the emergency department to which he had been sent from an outside facility to rule out tuberculosis. His primary concern was back pain, but he also reported a history of unintentional weight loss over the past 8 months, slowly worsening fatigue, 1 week of night sweats, and a productive cough without hemoptysis for the last 3 months. His low back pain had started 20 days prior to presentation and had been associated with intermittent numbness and weakness of his legs without fecal or urinary incontinence. The patient had traveled to the United States from Mexico 1 month earlier. He denied sick contacts, including contact with anyone with tuberculosis (TB).

Physical examination. Vital signs at admission were remarkable for a mild fever (temperature, 38.1 °C). On physical examination, he was noted to have poor dentition, with erythema around the base of most anterior maxillary teeth. A grade 2/6 systolic decrescendo murmur was noted loudest at the right upper sternal border. On respiratory examination, the lungs were clear to auscultation bilaterally. There was no abdominal tenderness or frank organomegaly. He was noted to have tenderness to palpation of the right sacroiliac joint, as well as the right paraspinal region at the level of L3-4. He had no spinous process tenderness with palpation. On neurologic examination, cranial nerve function was intact. He did not have any skin lesions on his bilateral extremities or back.

Diagnostic tests. Initial diagnostic evaluation findings were remarkable for a mildly elevated levels of aspartate aminotransferase (43 U/L; reference value, <40 U/L), alanine aminotransferase (76 U/L; reference range, 7-45 U/L), and alkaline phosphatase (269 U/L; reference range, 35-137 U/L). Results of a rapid HIV test were negative. The white blood cell count with differential was normal. Serologic test results for hepatitis B and C were negative.

Magnetic resonance imaging (MRI) of the thoracic spine with and without contrast performed at the outside facility showed likely T7-8 diskitis/osteomyelitis, along with a small epidural phlegmon causing mild spinal canal stenosis without cord compression or cord edema. MRI also revealed a right lung opacity that was concerning for pneumonia. Chest radiographs obtained in our facility showed right perihilar and left lung base opacities. Abdominal ultrasonography showed normal hepatic and splenic echotexture without hepatosplenomegaly.

Given his constellation of findings, chronic infection was considered most likely, with TB high on the differential. Blood cultures were drawn. An interferon-γ release assay (IGRA), a sputum acid-fast bacilli (AFB) culture and smear, and Mycobacterium tuberculosis complex polymerase chain reaction test (MTB PCR) were obtained. Given the significant spinal findings on MRI, a computed tomography (CT)-guided biopsy of the T7 vertebral body was performed.

During his hospitalization, the IGRA results were positive, but AFB smears and cultures and MTB PCR results remained negative for TB. An infectious diseases consultant recommended further workup with Brucella, Histoplasma, and Bartonella serology tests in the setting of the negative smear. New imaging studies, including CT of the chest without contrast, MRI of the lumbar spine with and without contrast, and echocardiography were performed. Chest CT scans demonstrated a dense, focal, wedge-shaped right lower lobe consolidation and also showed multifocal, soft tissue, mildly spiculated pulmonary nodules. MRI newly demonstrated abnormal vertebral body marrow changes at L3-4, possibly consistent with osteomyelitis. Echocardiography showed no valvular vegetations.

Blood cultures and biopsy samples ultimately showed the presence of rare gram-negative coccobacilli (Figure), and Brucella serology test results were positive with high titers.

histology slide
Figure. Microscope image of isolated gram-negative coccobacilli.

On further discussion with the patient, he reported that he had been a butcher in Chihuahua, Mexico, and that he had started drinking unpasteurized goat’s milk a few months ago. All other infectious serology test results returned negative. In light of the clinical scenario and diagnostic findings, the diagnosis of brucellosis was made.

Treatment. Antimicrobial therapy was initially delayed in favor of improving the yield of blood, sputum, and tissue samples. After these were complete, vancomycin and ceftriaxone were initiated for broad coverage. Despite the administration of these antibiotics, the patient continued to have a temperature as high as 39.3 °C during his hospitalization. As cultures and serology test results returned, atypical coverage was added with doxycycline. The patient defervesced on day 3 of doxycycline therapy, and the other antibiotics were discontinued. Gentamicin and rifampin were added to improve the likelihood of resolution of patient’s brucellosis with spondylitis.

Follow-up and outcome. Outpatient parenteral antibiotic therapy with 14 days of intravenous gentamicin was arranged for. The patient was also discharged with oral doxycycline for 3 months and rifampin for 4 months. At follow-up at an infectious disease clinic 14 days after initiation of gentamicin, his cough, fevers, and night sweats had resolved. He still had back pain, although it had been improving. His hepatic enzyme elevations had also resolved.

Of note, final speciation of blood culture confirmed Brucella melitensis after specimens were sent to the Centers for Disease Control and Prevention (CDC) for confirmation.

Discussion. Brucellosis is a zoonotic infectious disease caused by the gram-negative coccobacilli members of the genus Brucella.1 It was first identified in 1886 by the Malta Fever Commission established by the British army and led by microbiologist Major-General Sir David Bruce, after whom the genus was named.1 In a paradigm-shifting moment in 1905 that has been called one of the greatest advances ever made in epidemiology,2 Sir Themistocles Zammit discovered that the disease could be transmitted by healthy-appearing animals.3 Thanks to his discovery, livestock- and disease-monitoring systems have helped to curb the incidence of human brucellosis. Today it is known that Brucella species are typically transmitted by ingestion of infected animal milk, contact with infected animal tissues, or through inhalation of aerosolized particles.4

Brucellosis is a CDC-reportable infection in the United States,5 and the US incidence of brucellosis is very low. According to CDC data, between 1993 and 2002 the annual per capita incidence of brucellosis amounted to approximately 0.39 people per 1 million per year.6 Most cases identified were infections with B melitensis, and patients typically were Hispanic.6 Mexico remains a significant reservoir of human brucellosis.6

Brucella species that can cause human brucellosis include the following: B melitensis, which are principally found in goats and sheep and are the most pathogenic to humans; Brucella suis, which are principally found in swine; Brucella abortus, which is principally found in cattle; Brucella canis, which is principally found in dogs; and Brucella ceti and Brucella pinnipediae, which are principally found in marine mammals.7

Human brucellosis has a range of presenting symptoms, with the most common being fever, constitutional symptoms, and lymphadenopathy.4 The infection can affect various systems and result in focal end-organ damage. Among the hundreds of B melitensis infection case reports published in the literature, we could find no cases featuring both osteomyelitis and pulmonary complications. From most to least common, target systems are osteoarticular, genitourinary, hepatic, neurologic, cardiac, and respiratory systems.8 Complications can include osteoarticular disease, epididymo-orchitis, spontaneous abortion of pregnancy, hepatitis, central nervous system infection, and endocarditis.4 Frank respiratory complications are rare, likely in less than 5% of cases, although complications can include lobar pneumonia and pleural effusions.4,9

Our patient had confirmed brucellosis caused by infection with B melitensis. His presentation had many classic hallmarks, including arthritis progressing to diskitis and vertebral osteomyelitis, hepatitis with transaminase level elevations, and constitutional symptoms. However, his syndrome also had several significantly less-common features that acted as distractors during the initial workup—primarily pulmonary symptoms and imaging findings. His cough and pulmonary imaging findings, along with the positive IGRA results, caused initial concern for TB. Taken with his focal spinal findings, this also raised concern for tuberculous spondylitis (Pott disease). Although this did not result in a clinically significant delay in therapy, earlier elucidation of significant historical features such as his occupation and consumption of goat’s milk would have helped to guide diagnostics.

Ultimately, this case teaches the wisdom of a thorough occupational and exposure history to help raise diagnostic suspicion for uncommon presentations of ultimately more common diseases in particular areas of the world. It also presents an unusual case of brucellosis with pulmonary manifestations combined with spinal diskitis and vertebral osteomyelitis, which appears to not previously have been reported.

REFERENCES:

  1. Hayoun MA, Smith ME, Shorman M. Brucellosis. StatPearls. Updated December 24, 2019. Accessed May 20, 2020. https://www.ncbi.nlm.nih.gov/books/NBK441831/
  2. Tulloch WJ. Sir David Bruce: an appreciation. J R Army Med Corps. 1955;101(2):81‐90. Accessed May 20, 2020. https://militaryhealth.bmj.com/content/jramc/101/2/81.full.pdf
  3. Wyatt HV. How Themistocles Zammit found Malta fever (brucellosis) to be transmitted by the milk of goats. J R Soc Med. 2005;98(10):451‐454. doi:10.1258/jrsm.98.10.451
  4. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med. 2005;352(22):2325‐2336. doi:10.1056/NEJMra050570
  5. Centers for Disease Control and Prevention. Brucellosis case report form. Accessed May 20, 2020. https://www.cdc.gov/brucellosis/pdf/case-report-form.pdf
  6. Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV. The new global map of human brucellosis. Lancet Infect Dis. 2006;6(2):91‐99. doi:10.1016/S1473-3099(06)70382-6
  7. Centers for Disease Control and Prevention. Humans and Brucella species. Reviewed November 12, 2012. Accessed May 20, 2020. https://www.cdc.gov/brucellosis/clinicians/brucella-species.html
  8. Colmenero JD, Reguera JM, Martos F, et al. Complications associated with Brucella melitensis infection: a study of 530 cases [published correction appears in Medicine (Baltimore). 1997;76(2):139]. Medicine (Baltimore). 1996;75(4):195‐211. doi:10.1097/00005792-199607000-00003
  9. Pappas G, Bosilkovski M, Akritidis N, Mastora M, Krteva L, Tsianos E. Brucellosis and the respiratory system. Clin Infect Dis. 2003;37(7):e95‐e99. doi:10.1086/378125