Tumor-like proliferations of small blood vessels caused by infection with Bartonella henselae.

Epithelioid angiomatosis.

Bacillary angiomatosis (BA) has been described primarily in human immunodeficiency virus (HIV)-positive patients and in a few cases of chronic lymphocytic leukemia patients on immunosuppressive therapy (1). Epidemiologic studies show a significant association between infection with B. henselae and owning or being exposed to cats, particularly young cats infested with fleas (2). Domestic cats are the major reservoir for infection with B. henselae, which is transmitted by fleas from cat to cat (3). B. quintana, the agent responsible for trench fever, may cause central nervous system lesions, lytic bone lesions, and endocarditis and has been occasionally isolated from cases of BA. However, these patients are more likely to be homeless persons exposed to lice (4).

The pathogenic agent of BA and bacillary peliosis, B. henselae, is a small, curved, motile, gram-negative bacillus. Because its culture and speciation are difficult, the identity of this etiologic agent was revealed only after multiple studies and name changes, brought about by the application of molecular techniques. Amplification through polymerase chain reaction (PCR) bacterial 16S ribosomal RNA taken from lesions of BA and analysis of sequences of complementary DNA revealed a new rickettsia-like microorganism closely related to Rochalimaea quintana (5). This agent was named R. henselae (6,7). Subsequently, the two genera—Rochalimaea and Bartonella—were merged under the designation Bartonella, including B. henselae, B. quintana, and B. bacilliformis, which are known to be associated with human diseases, as well as a number of recently described species including some new human pathogens (4,8). B. henselae is now known to cause several clinical syndromes in immunocompetent and immunocompromised patients including cat-scratch disease (CSD), peliosis hepatis, bacteremia with fever, and endocarditis (4). In the studies on immunocompromised patients with BA reported in the literature, Bartonella sp. was detected in blood and biopsy materials by cultures or PCR (9,10).

The natural reservoir host of B. henselae is the domestic cat; cat fleas provide the vector to transmit the agent between cats, causing a chronic intraerythrocytic bacteremia. The bacilli are transmitted to humans, the incidental hosts, through the bite or scratch of an infected cat (4). In BA, infection occurs through the skin by means of traumatic inoculation with flea feces, just as infection with B. quintana, a closely related microorganism causing trench fever, is transmitted through infection with louse feces (11). The question still unanswered is why the same pathogenic agent, B. henselae, is able to cause both BA and CSD, two entirely different clinically pathologic entities. Bacillary angiomatosis is characterized by numerous red to violaceous vascular papules and nodules involving the skin and sometimes extending to lymph nodes and internal organs, whereas CSD consists of a unilateral suppurative lymphadenitis rarely accompanied by other localizations. Bacillary angiomatosis occurs almost exclusively in HIV-infected patients with acquired immune deficiency; CSD affects otherwise normal immune-competent individuals. The basic lesion of the former is angiomatosis; of the latter, necrotizing granulomas. Response to treatment also differs between the two diseases. Antibiotic treatment with erythromycin or doxycycline is curative in BA and totally ineffective in CSD (12,13). Yet, in both lesions, bacilli stainable with the Whartin-Starry silver stain and identified as B. henselae are the only microorganisms consistently present. And, in both diseases, a contact with cats is usually established. A tentative explanation for the differences between the two syndromes induced by the same agent is that the deficient cellular immunity present in patients with BA is unable to mount the granulomatous response seen in CSD patients, and that the vascular proliferation may be caused by unregulated production of angiotropic cytokines in the course of HIV infection (12). Peliosis hepatis is a similar systemic process of vascular proliferation associated with B. henselae and acquired immune deficiency syndrome (AIDS).

The various pathologic lesions produced by Mycobacterium leprae and M. tuberculosis are given as an example in support of the argument that the same agent may produce a broad spectrum of pathologic responses, depending on the degree of cellular immunity of the host (11). However, the mechanisms must be even more complex, because BA of similar appearance has been also reported in an HIV-negative immunocompetent patient (14).

Patients with BA are, with few exceptions HIV seropositive, and may belong to any of the known risk groups: homosexual men, intravenous drug abusers, and recipients of blood transfusions (15). In a series of 13 cases, 12 were men aged 31 to 56 years (12). A few cases of BA and bacillary splenitis have been reported in immunocompetent patients, including one healthy HIV-negative man (14,16).

The cutaneous lesions of BA consist of vascular red to violaceous dome-shaped papules and nodules. They may be superficial in the upper dermis with a collarette, or deep dermal and subcutaneous (12,15). They range in numbers from one to hundreds and show no predilection for specific sites (15).
In addition to the skin, lymph nodes (13,17,18), soft tissues (19), spleen (20), liver (20), and bones (12,13) may be involved. In the liver and spleen, the lesions consist of cystic, blood-filled spaces and are referred to as peliosis hepatis or splenis (20). Some of these patients may present with Bartonella bacteremia, which in immunocompromised patients may occur even in the absence of skin lesions (15). In a study of 37 patients with BA, the presence of lymphadenopathy was significantly associated with B. henselae and not with B. quintana (10). Most skin lesions resolve spontaneously; however, in cases of systemic disease in AIDS patients, severe, occasionally fatal, complications may occur (15,20). Bacillary angiomatosis lesions generally respond to macrolide antibiotics, leading to complete remission (9). Therefore early diagnosis is of utmost importance because it allows curative treatment with antibiotics, whereas unrecognized and untreated BA may end in a fatal outcome.