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Chronic Bartonella species infections (bartonellosis) can lead to inflammation that impacts the heart, nervous system, and more. According to case studies, these stealth pathogens can also target the bones. How can Bartonella affect a structure that is usually impervious to infection?
History: From World War I to HIV/AIDS
During World War I, one million soldiers in Europe suffered from a mild to severe acute illness referred to as “trench fever”. It was characterized by a relapsing fever, headache, and in some cases extreme pain occurring along the lower halves of the legs. This led to the nickname of “shin bone disease/fever”. Patients with leg pain complained of a burning pain they could feel “in their bones,” making it difficult to walk. Whether pain was due to involvement of the bone, the marrow cavity within the bone, or the periosteum surrounding the bone surface is unknown.
Bartonellosis was not known to be the cause of this ailment until J.W. Vinson isolated B. quintana in 1960. The unsanitary conditions that soldiers lived in acted as a breeding ground for the primary vector, human body lice (Pediculus humanus), and made transmission more likely to occur. Infected soldiers most likely developed a persistent B. quintana bacteremia that their immune systems could not effectively clear due to repeated louse exposure (bites and and scratch inoculation of louse feces), as well as their poor overall health during deplorable wartime conditions.
Additional evidence that Bartonella species affect the bones came during extensive research on HIV/AIDS patients in the 1990s. Physicians found that these immunocompromised patients developed serious multi-systemic conditions called bacillary angiomatosis and bacillary peliosis (BA and BP) involving lesions on the skin, liver, and bones. Researchers discovered that the typical culprits for BA and BP were B. henselae, which is now known as the causative agent of cat scratch disease, and B. quintana, an organism historically associated with lice and war. A case report from 2016 describes a 29-year old HIV-positive man with AIDS (uncontrolled HIV infection) who developed nodules on his skin and advanced lesions in the bones of his right hand due to bacillary angiomatosis. Physicians could not confirm the species of Bartonella using PCR, but histopathological evidence and the patient’s clinical history strongly suggested B. quintana exposure.
Children Most at Risk
Among immunocompetent individuals, the literature over the last decade suggests that a large portion of bartonellosis cases involving the bone occur in children with “atypical” cat-scratch disease (acute bartonellosis). Research suggests that about 10% of CSD patients develop atypical manifestations, with only about 0.3% of cases involving a bone. However, suspected bartonellosis cases that describe bone-related complications have been documented in various patient populations over the past century, especially children. There is not enough research to show why the incidence is greater in pediatric cases, but invasion of the bones could be more likely because their immune systems are still developing and/or their bone structures are changing.
Case reports describe children who develop solitary bone tissue infections (osteomyelitis) that affect the limbs, vertebral bodies, or elsewhere. In one case, a 12-year-old girl complained of serious headaches and neck swelling that was found to be caused by a osteolytic lesion in her cranium. A biopsy was not performed to confirm bartonellosis was the cause, but the patient was B. henselae seroreactive and her symptoms resolved following combination antimicrobial therapy.
B. henselae is currently listed as a potential cause of bacterial osteomyelitis in the diagnosis and management guidelines developed by the American Academy of Family Physicians (AAFP). Bone lesions due to bartonellosis are typically discovered via MRI or other imaging techniques such as X-ray. A diagnosis of bartonellosis can be confirmed using blood or lesional biopsy testing. Biopsy of a bone is invasive, but is perhaps the best option for a confirmatory diagnosis through the use of PCR and/or histopathological techniques.
Route of Infection
Little is known about how Bartonella infects bone tissue, either in cases of CSD or in cases of chronic bartonellosis. Research shows that Bartonella genus bacteria have the ability to enter many cell types, so it is possible that osteocytes (bone cells) are among their many host cells. However, the extracellular matrix of bone, composed of collagen and various inorganic compounds, can make infection processes difficult for bacteria. For adults, bacterial osteomyelitis from other bacteria, such as Staphylococcus aureus, occurs most often only after trauma to this protective layer.
Perhaps the more likely route for Bartonella species to infect bone is their ability to infect hematopoietic (blood-creating) stem cells that originate in the bone marrow. Bone marrow is responsible for the production of red blood cells, white blood cells, and platelets. One study shows that B. henselae can infect isolated CD34+ progenitor cells in vitro. Our blog post on Bartonella and blood explains more on how this may lead to persistent intraerythrocytic infection.
On a comparative medicine basis, osteomyelitis was reported in a young cat infected with Bartonella vinsonii subsp. berkhoffii, suggesting that other Bartonella species may cause osteomyelitis in other animal species.
Conclusion
Bone pain has been associated with what we now know to be Bartonella genus infection since World War I. Some other atypical bone infections associated with bartonellosis have been observed in AIDS patients. But it is otherwise healthy children who develop cat scratch disease, an acute Bartonella infection, who seem most likely to have this complication. Even among children, bone lesions have rarely been documented and the pathogenesis has been little researched.
References
Carek, P. J. et al. (2001). Diagnosis and management of osteomyelitis. American Family Physician, 63(12), 2413-2421. https://www.aafp.org/afp/2001/0615/p2413.html
Verdon, R. et al. (2002). Vertebral osteomyelitis due to Bartonella henselae in adults: A report of 2 cases. Clinical Infectious Diseases, 35(12), e141-e144. doi:10.1086/344791 https://academic.oup.com/cid/article/35/12/e141/356641
Doná, D. et al. (2018). Osteomyelitis in cat-scratch disease: A never-ending dilemma – A case report and literature review. Case Reports in Pediatrics, 2018, 1679306. doi:10.1155/2018/1679306 https://www.ncbi.nlm.nih.gov/pubmed/29808150
Diniz, L. M. et al. (2016). Bacillary angiomatosis with bone invasion. Anais Brasileiros de Dermatologia, 91(6), 811-814. doi:10.1590/abd1806-4841.20165436 https://www.ncbi.nlm.nih.gov/pubmed/28099606
Woestyn, S. et al. (2003). Osteomyelitis caused by Bartonella henselae genotype I in an immunocompetent adult woman. Journal of Clinical Microbiology, 41(7), 3430-3432. doi:10.1128/JCM.41.7.3430-3432.2003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC165354/
Roubaud-Baudron, C. et al. (2009). [Cat scratch disease with bone involvement: A case report and literature review] (in French). La Revue de Medecine Interne, 30(7), 602-608. doi:10.1016/j.revmed.2009.01.015 https://www.ncbi.nlm.nih.gov/pubmed/19303175
Varanat, M. et al. (2009). Recurrent osteomyelitis in a cat due to infection with Bartonella vinsonii subsp. berkhoffii genotype II. Journal of Veterinary Internal Medicine, 23, 1273-1277. doi:10.1111/j.1939-1676.2009.0372.x https://onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2009.0372.x
Breitschwerdt, E. B. (2014). Bartonellosis: One Heath perspectives for an emerging infectious disease. ILAR Journal, 55(1), 46-58. doi:10.1093/ilar/ilu015 https://onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2009.0372.x