Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease–endemic Region

Ricardo G. Maggi, B. Robert Mozayeni, Elizabeth L. Pultorak, Barbara C. Hegarty, Julie M. Bradley, Maria Correa, and Edward B. Breitschwerdt

Author affiliations: North Carolina State University, Raleigh, North Carolina, USA (R.G. Maggi, E.L. Pultorak, B.C. Hegarty, J.M. Bradley, M. Correa, E.B. Breitschwerdt); Translational Medicine Group, PC, North Bethesda, Maryland, USA (B.R. Mozayeni)

Abstract

Bartonella spp. infection has been reported in association with an expanding spectrum of symptoms and lesions. Among 296 patients examined by a rheumatologist, prevalence of antibodies against Bartonella henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii (185 [62%]) and Bartonella spp. bacteremia (122 [41.1%]) was high. Conditions diagnosed before referral included Lyme disease (46.6%), arthralgia/arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%). B. henselae bacteremia was significantly associated with prior referral to a neurologist, most often for blurred vision, subcortical neurologic deficits, or numbness in the extremities, whereas B. koehlerae bacteremia was associated with examination by an infectious disease physician. This cross-sectional study cannot establish a causal link between Bartonella spp. infection and the high frequency of neurologic symptoms, myalgia, joint pain, or progressive arthropathy in this population; however, the contribution of Bartonella spp. infection, if any, to these symptoms should be systematically investigated.

The genus Bartonella comprises at least 26 species or subspecies of vector-transmitted bacteria, each of which has evolved to cause chronic bacteremia in >1 mammalian reservoir hosts (1–4). Among these, bartonellae of 14 species or subspecies have been implicated in zoonotic diseases (5,6), including cat-scratch disease, which is caused by B. henselae transmission during a cat bite or scratch and characterized by acute onset of self-limiting fever and regional lymphadenopathy (7–9). Recent observations, however, are causing a paradigm shift from the assumption that infection with a Bartonella sp. consistently induces an acute, self-limiting illness to the realization that subsets of infected, immunocompetent patients can become chronically bacteremic (10–15).
After B. henselae was confirmed as the primary cause of cat-scratch disease in the early 1990s, several reports described an association between the newly identified bacterium and rheumatic disease manifestations, variously described as rheumatoid, reactive, or chronic progressive polyarthritis (16–20). One study, however, failed to isolate B. henselae from synovial fluid of 20 patients with chronic arthritis (21). Because epidemiologic evidence supports an association between rheumatic symptoms and cat-scratch disease and because arthritis is a primary disease manifestation of Borellia burgdorferi infection (Lyme disease), we explored whether antibodies against and bacteremia with Bartonella spp. can be detected in patients examined for arthropathy or chronic myalgia. Our primary objective was to determine the serologic and molecular prevalence of Bartonella spp. bacteremia in patients referred to a clinical rheumatologist. We also compared self-reported symptoms, health history, and demographic factors with Bartonella spp. bacteremia as determined by an enrichment blood culture platform combined with PCR amplification and DNA sequencing, when possible, to determine the Bartonella species and strain. This study was conducted in conjunction with North Carolina State University Institutional Review Board approval (IRB# 164–08–05).