BA and bacillary peliosis, both characterized by proliferative vascular lesions and first identified in patients with AIDS, were described by Stoler et al (2
) in 1983 and Perkocha et al (3
) in 1990, respectively; however, diseases caused by Bartonella
species have been recognized since the pre-Columbian era in the form of verruga peruana, the chronic, cutaneous stage of infection with Bartonella bacilliformis
. In 1885, a Peruvian medical student by the name of Daniel Carrión demonstrated the link between the chronic stage and the acute hematogenous stage characterized by fever, anemia and transient immunosuppression (Oroya fever). Bartonella infections have been recognized in the form of 'trench fever' since World War One; however, these infections may have been described as early as the middle ages (4
is the only bacterial genus known to cause cutaneous angioproliferation (5
). Of the 14 species identified, five are known to cause disease in humans and only two - B quintana
and B henselae
- have been associated with BA (6
). The spectrum of disease caused by the Bartonella
genus includes endocarditis, trench fever, Oroya fever, Carrión's disease, cat-scratch disease and chronic lymphadenopathy, as well as neurological disorders such as meningoencephalitis and focal central nervous system lesions.
Proliferative lesions of the vasculature are prominent in BA, most commonly involving the skin and presenting as highly polymorphic skin lesions ranging from papules to pedunculated nodules (6
). The major differential diagnosis for cutaneous lesions of BA is Kaposi's sarcoma. Focal lesions may present in many other tissues, including bone, brain, lymph nodes, respiratory tract, cardiac valves, gastrointestinal tract and bone marrow (7
). Bone lesions typically involve the long bones and produce painful lytic lesions, sometimes with overlying skin changes (as in the present patient). Radiological features include well-circumscribed osteolysis with or without associated periostitis (7
). Bacillary peliosis refers to proliferative vascular lesions of the liver and spleen, characterized by blood-filled spaces with bacillary clusters and a fibromyxoid stroma (3
). Hepatomegaly, elevated alkaline phosphatase levels and parenchymal heterogeneity of the liver and spleen (with low-density lesions on ultrasound or CT) are characteristic features (7
A case-control study by Koehler et al (8
) suggested that while both B henselae
and B quintana
typically cause skin lesions, subcutaneous masses and bone lesions are more likely to be due to B quintana
, and bacillary peliosis and lymph node involvement are more likely to be due to B henselae
. The present patient had several bone lesions and subcutaneous masses with a single hypodense, well-circumscribed hepatic lesion on ultrasound without hepatomegaly. This lesion, if due to Bartonella
infection, likely reflects the lesser propensity for B quintana
to cause hepatic lesions. Because the patient was lost to follow-up before a repeat ultrasound could be performed, we were unable to determine if resolution had occurred with doxycycline therapy.
AIDS patients with CD4
cell counts of less than 100x106
cells/L are at increased risk of infection due to Bartonella
). Fever caused by Bartonella
species is likely under-recognized (9
), particularly if skin lesions are absent or few, and the presentation is nonspecific. As a treatable cause of fever, the recognition of risk for Bartonella
infection in immunocompromised hosts is critical to convey appropriate information to the microbiology laboratory. As the present case highlights, standard incubation periods (five days) for blood cultures are inadequate to detect Bartonella
species. Slow carbon dioxide generation may result in inconsistent flagging of culture bottles. Even when cultures flag positive, organisms may not be visualized on Gram stain.
Clinical suspicion of Bartonella
mandates prolonged incubation in a carbon dioxide-rich environment with increased humidity (40%) for up to six weeks (1
). Blind subcultures may improve the detection of bacteremia; in the present case, however, no subcultures performed before day 9 yielded detectable growth on solid media, and subcultures taken after a bottle had flagged positive yielded growth more quickly than blind subcultures. Although extended incubation is not technically demanding, the enriched medium and relatively lengthened culture time may heighten the risk of fungal or bacterial contamination of samples (1
Whereas B henselae
is known to have a reservoir in cats and involves transdermal inoculation of bacteria after close contact, the reservoir for B quintana
remains uncertain (1
). Homelessness, poverty and alcoholism are recognized risk factors for B quintana
infection, and unsanitary living conditions may predispose to ectoparasites that transmit the infection among those at risk (11
The present patient had clinical and epidemiological clues pointing to both B quintana and B henselae. While B quintana is more commonly associated with lytic bone lesions and a history of homelessness, B henselae is suggested by a greater incidence of bacillary peliosis and exposure to cats. 16s ribosomal RNA analysis allowed for the confirmation of B quintana as the cause of BA in the present patient despite the fact that, epidemiologically, his risk for B henselae seemed greater and more recent. While speciation did not affect chemotherapeutic decisions, it encouraged us to defer recommended surgical intervention for the ulnar lesion (en bloc resection of the distal third of the ulna for possible aggressive bone tumour) until we could observe a response to therapy. A prompt response allowed the patient to avoid unnecessary surgery.
The present case also highlights the potential for persistence of bacteremia for prolonged periods, even after the initiation of therapy. Bacteremia persisted for at least five days after therapy began and likely longer, as high-grade fevers continued for several weeks; however, no further blood cultures were obtained. Despite the prolonged bacteremia, the cutaneous and bone lesions showed a prompt improvement, with regression of skin lesions evident within 10 days and sclerosis of the lytic lesion within a month.
Bartonella is an infrequent but important pathogen in immunocompromised patients. While easily treated, infection due to Bartonella may be clinically unrecognized if characteristic skin lesions are absent or overlooked, and microbiologically unrecognized if appropriate protocols are not followed.