University of California, San Francisco Logo

University of California, San Francisco | About UCSF | Search UCSF | UCSF Medical Center

Bartonella
HIV and Bartonella: Bacillary Angiomatosis and Peliosis
transparent image
transparent image
transparent image
transparent image
Introduction
transparent image
transparent image
Historical Perspective
transparent image
transparent image
Epidemiology
transparent image
transparent image
Clinical Presentation
transparent image
transparent image
transparent imageCutaneous Bacillary Angiomatosis
transparent image
transparent imageOsseous Bacillary Angiomatosis
transparent image
transparent imageSplenic and Hepatic Bacillary Peliosis
transparent image
transparent imageGastrointestinal and Respiratory Tract Bacillary Angiomatosis
transparent image
transparent imageLymph Node Bacillary Angiomatosis
transparent image
transparent imageCentral Nervous System Bacillary Angiomatosis
transparent image
transparent imageBone Marrow Bacillary Angiomatosis
transparent image
transparent imageBacteremia
transparent image
transparent imageEndocarditis
transparent image
transparent imagePregnancy-Associated Bacillary Angiomatosis
transparent image
transparent imagePediatric Bacillary Angiomatosis
transparent image
Diagnosis
transparent image
transparent image
transparent imageObtaining Tissue Specimens for Diagnosis of Bacillary Angiomatosis
transparent image
transparent imageHistopathology of Bacillary Angiomatosis and Bacillary Peliosis
transparent image
transparent imageHistologic Differential Diagnosis
transparent image
transparent imageSerology
transparent image
transparent imageCulture of Bartonella Species from the Blood of Patients with Bacillary Angiomatosis and Bacillary Peliosis
transparent image
transparent imageCulture of Bartonella Species from Bacillary Angiomatosis Tissue
transparent image
transparent imagePolymerase Chain Reaction Diagnosis of Bacillary Angiomatosis
transparent image
Antibiotics
transparent image
transparent image
Relapse
transparent image
transparent image
Cutaneous Lesions
transparent image
transparent image
Osseous Lesions
transparent image
transparent image
Hepatic and Splenic Bacillary Peliosis
transparent image
transparent image
Bacteremia
transparent image
transparent image
Prevention
transparent image
transparent image
Acknowledgment
transparent image
transparent image
transparent image
References
transparent image
transparent image
Tables
Table 1.Treatment of Bartonella Infections in HIV-Infected Patients
transparent image
Table 2.Clinical Efficacy of Antibiotics in the Treatment of Bacillary Angiomatosis and Bacillary Peliosis
transparent image
transparent image
Figures
Figure 1.Bacillary Angiomatosis Nodule of the Finger and an Evolving Vascular Papule
transparent image
Figure 2.An Unusual-Appearing Plaque of Cutaneous Bacillary Angiomatosis
transparent image
Figure 3.Wrist Mass Due to Bacillary Angiomatosis
transparent image
Figure 4.Subcutaneous Bacillary Angiomatosis Nodules in a Patient with Concomitant Kaposi's Sarcoma
transparent image
Figure 5.MRI of Soft-Tissue Mass of Bacillary Angiomatosis in the Anterior Right Thigh
transparent image
Figure 6.Radiograph of Cortical Bone Erosion of the Radius in Wrist Mass Due to Bacillary Angiomatosis
transparent image
Figure 7.Abdominal CT Scan Showing Hepatosplenomegaly in Peliosis Hepatis
transparent image
Figure 8.Hematoxylin- and Eosin-Stained, Biopsied Cutaneous Bacillary Angiomatosis Lesion
transparent image
Figure 9.Warthin-Starry Stained Cutaneous Bacillary Angiomatosis Tissue
transparent image
Figure 10.Transmission Electron Micrograph of Bacillary Organisms in Cutaneous Tissue
transparent image
transparent image
Related Resources
transparent imageJournal Articles
transparent imageGuidelines and Best Practices
transparent imageOnline Books and Chapters
transparent imageSlide Sets
transparent image
transparent image
transparent image
transparent image
Introduction
transparent image

Bacillary angiomatosis (BA) is a disease characterized by unique vascular lesions caused by infection with small, gram-negative organisms of the genus Bartonella. Virtually all patients with this disease are infected with HIV, although six immunocompetent patients with BA have been described.(1-3)

There are two conceptually distinct Bartonella-associated syndromes: bacteremia (in the absence of focal tissue vascular proliferative response) and the tissue infection (BA or BP) associated with angiogenic response. This review uses the term BA to refer to the localized, vascular proliferative response in skin and extracutaneous organs, and bacillary peliosis (BP) to refer to the blood-filled, peliotic changes of the liver or spleen parenchyma resulting from infection with either B. quintana or B. henselae.

transparent image
Historical Perspective
transparent image

Stoler et al(4) initially reported this disease in 1983, describing a patient with advanced HIV disease who developed disseminated subcutaneous nodules that resolved completely after treatment with erythromycin. Subsequently, they noted that the clinical appearance of cutaneous lesions of three additional patients resembled Kaposi's sarcoma (KS), but as with their first patient, the histologic and electron microscopic examination of the lesions revealed small, gram-negative rods interspersed among proliferating endothelial cells.(5) In 1987, a report described five HIV-seropositive patients with cutaneous vascular neoplasms that were called epithelioid angiomatosis.(6) The lesions were papular, nodular, or polypoid; numbered few or in the hundreds; and were often mistaken for KS. Two of the patients died due to widespread dissemination of these lesions. In 1988, four additional HIV-infected patients with vascular lesions were described.(7) When many of these vascular lesions were later discovered to contain numerous bacilli, the disease became known as bacillary angiomatosis, to reflect both the infectious and vascular proliferative nature of the disease.(8)

An association between the cat scratch disease (CSD) bacillus and the organism seen in BA lesions was proposed in 1988.(9) The Warthin-Starry staining and electron microscopic characteristics of the bacilli in both BA and CSD tissues were identical,(9,10) and tissue from five BA cases demonstrated immunoreactivity with antisera raised against the isolated CSD bacillus.(11) Subsequently, DNA sequencing established that this putative CSD bacillus, Afipia felis,(11,12) is different from the BA bacillus.(12-14) More recently, B. henselae was isolated from lymph nodes of immunocompetent individuals with CSD,(15) and the domestic cat was identified as the major reservoir for this Bartonella species.(16,17) These and subsequent data conclusively identify B. henselae as the principle cause of CSD.

Investigators had noted a close genetic relationship between the BA organism and Rochalimaea quintana, the agent of trench fever.(18) In addition, the organisms causing cutaneous BA also cause both a vascular abnormality of the liver known as peliosis hepatis(19,20) and bacteremia in HIV-infected and non-HIV-infected persons in the absence of skin lesions.(21,22) This new organism was named Rochalimaea henselae in 1992,(23,24) but became Bartonella henselae when the entire genus of Rochalimaea was merged with the genus of Bartonella in 1993.(25) Subsequently, by culturing BA bacilli directly from cutaneous lesions, Koehler et al. found that not only B. henselae, but also B. quintana causes BA.(26) In addition to these two species, there are now seven additional extant species of Bartonella, none of which has been associated with infection in HIV-infected individuals.

transparent image
Epidemiology
transparent image

Numerous anecdotal reports link cat exposure and the development of both BA and BP.(2,9,19,26,27-41) The relationship between cat contact, numerous other environmental exposures, and development of BA or BP was examined systematically for the first time in a large case-control study(42) that demonstrated a significant epidemiologic association between traumatic cat exposure (cat bite or cat scratch) and development of BA or BP; no other environmental exposure was statistically associated.

Subsequently, B. henselae was cultured from lymph nodes of several immunocompetent patients with CSD,(15) another disease associated with traumatic cat exposure.(43) B. henselae antibodies were detected in serum of patients with CSD,(44) B. henselae was isolated from a domestic cat,(45) and Bartonella DNA (but not A. felis DNA) was demonstrated in the CSD skin test antigen.(46) B. henselae also was isolated from the blood of all seven cats belonging to four patients with BA due to B. henselae.(16) Thus, pet cats are a major reservoir for B. henselae and probably also the principle vector of B. henselae to humans, because most patients presenting with CSD still have a visible infected scratch.(43) It has been demonstrated, however, that the cat flea readily transmits B. henselae between cats, and thus the potential exists for flea-borne transmission of B. henselae to humans.(47) Another possible arthropod vector of Bartonella species is the tick. Bites from ticks preceded diagnosis of B. henselae bacteremia in two patients.(22,24)

transparent image
Clinical Presentation
transparent image

The presentation of BA varies markedly; reports described Bartonella species infection of virtually every organ system, singly and involving multiple organs. Although most of the reported BA infections document characteristic histopathology, including the essential demonstration of Warthin-Starry-staining bacilli, the majority of reported cases have not documented Bartonella species by molecular tests or culture.

BA occurs most frequently in the later stages of HIV infection; in one study of 42 patients, the median CD4+ cell count was 21 per cubic millimeter (range: 1-228) at the time of diagnosis of BA.(48) In this case-control study, patients with BA infection presented with fever (9%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Although cutaneous BA is the Bartonella lesion most frequently recognized and described in the literature, only 55% of patients in this study had cutaneous or subcutaneous BA lesions; patients with other forms of Bartonella infection in the absence of cutaneous BA lesions are probably not identified in many cases.

One remarkable characteristic of BA infections is the duration of symptoms, lesions, or both prior to diagnosis. In one study of four patients, the minimum estimated duration of cutaneous BA lesions was 8 months for two patients, and may have been longer than 1 year for another.(26)

transparent image
Cutaneous Bacillary Angiomatosis
transparent image

A major challenge in the diagnosis of cutaneous BA is the diverse presentation of lesions;(26,49) the references cited for each of the following types of cutaneous lesion include photographs that present that type of lesion. Skin lesions may be classified as predominantly cutaneous or subcutaneous.(50) Cutaneous lesions are often papular and red with a smooth or eroded surface,(6,7,9,27-31,49,51-55) and papules may enlarge to form large, pedunculated lesions(6,49,56) (Figure 1). These lesions have an obvious vascular appearance and an erythematous base and bleed profusely when traumatized. Other papular lesions and plaques may be dusky in color, dry, scaly, and hyperkeratotic, with minimal clinical evidence of vascularity(26) (Figure 2). Cutaneous BA also may have the appearance of a cellulitic plaque; these cutaneous lesions often overlie osteolytic lesions(26,27) (Figure 3). Dark-skinned patients may develop an indurated, hyperpigmented plaque that may be nearly black.(57) Cutaneous lesions may occur singly or number in the hundreds.(6,29,49,56)

Subcutaneous lesions (Figure 4) may present as one or more deep nodules with flesh-colored(49) or erythematous overlying skin.(57,58) Subcutaneous nodules may erode through the surface and become friable and superinfected.(26) Reports also describe presentation as a single, deep soft-tissue mass with normal-appearing overlying skin (Figure 5).(26,32,59)

The clinical differential diagnosis of cutaneous lesions includes KS, pyogenic granuloma, a number of subcutaneous tumors, and verruga peruana (the latter being a chronic form of infection with Bartonella bacilliformis, occurring only in the Andes Mountains of South America).(6,8) Among HIV-infected patients, distinguishing clinically between BA and KS (especially the nodular, exophytic form) can be extremely difficult, in some cases necessitating biopsy.(8,33,34)

transparent image
Osseous Bacillary Angiomatosis
transparent image

The largest series of BA cases involving bone was reported by Baron et al,(60) but others also have reported osteolytic lesions.(7,26,27,31-33,52,59-63) Osseous BA was documented by biopsy or culture for several of these lesions, but the majority were believed to be BA because of concomitant presence of cutaneous BA lesions and the dramatic response to antimicrobial therapy. Bone lesions are usually extremely painful and most frequently involve the long bones, especially the tibia, fibula, and radius.(7,26,27,31,33,52,60-63) Other lytic lesions presumed to be due to BA occurred in a rib,(60) vertebrae,(32,59) calcaneum,(64) and skull.(62) A soft-tissue mass(60) with or without an erythematous, cellulitic plaque in the dermis may overlie the osseous lesions (see Figure 3).(26,27,31) Radiographs usually show well-circumscribed osteolysis, sometimes with periostitis(60) (Figure 6). Technetium-99m methylene diphosphonate bone scans are always positive at the site of the lytic lesion.(60) Osseous lesions may occur singly or at multiple sites and may precede development of cutaneous disease. Although lytic bone lesions in several HIV-infected patients have been attributed to KS,(65,66) there are few diseases of HIV-infected patients that cause osteolysis, and thus BA must be a primary consideration in the differential diagnosis of any lytic bone lesion.

transparent image
Splenic and Hepatic Bacillary Peliosis
transparent image

In 1990, Perkocha et al(19) described eight patients with peliosis hepatis, unique vascular lesions in liver tissue that were associated with characteristic BA bacilli. The majority of these patients had abdominal pain and fever of 1 to 8 weeks' duration. On physical examination, all eight patients had hepatomegaly, six also had splenomegaly, and two had concomitant cutaneous BA. Two of the patients with peliosis hepatis who had a splenectomy also were found to have BP of the spleen. Hepatic transaminase levels were normal or mildly to moderately elevated. Alkaline phosphatase levels were more strikingly elevated, however, on average five times normal, with levels up to ten times normal. Computed tomography (CT) or ultrasonography revealed heterogeneity of the liver or spleen parenchyma in two patients. (Figure 7) shows a CT scan of the abdomen of a patient with peliosis hepatis. The association between hepatic BP and B. henselae was documented by culture of this organism from the blood of a patient with biopsy-proven peliosis hepatis.(67)

Splenic BP has been documented by histopathology(19,67); the presence of B. henselae in the spleen was documented by the polymerase chain reaction (PCR) in one patient(18) and by culture in another patient with hepatic BP and pancytopenia.(67) Of note is that three additional patients with splenomegaly had thrombocytopenia at the time of presentation; all had resolution of thrombocytopenia when treated with antibiotics administered for their concomitant cutaneous BA infections.(29,30) Bacillary splenitis without peliosis, and in the absence of hepatic involvement, also has occurred in an HIV-negative, immunocompetent patient.(2) Thus, the clinician should strongly consider BP of the liver and/or spleen in the differential diagnosis of patients presenting with enlargement of the liver, spleen, or both in the presence or absence of pancytopenia or thrombocytopenia.

transparent image
Gastrointestinal and Respiratory Tract Bacillary Angiomatosis
transparent image

Involvement of the gastrointestinal (GI) tract was first described by Cockerell et al.(6) Two of their patients had BA lesions of oral, anal, peritoneal, or multiple regions of the GI tract. Lesions in the GI tract may appear as raised, nodular, ulcerated, or angiomatous mucosal abnormalities of the stomach and large and small intestine during endoscopy.(35,68)

Extrinsic compression of the common bile duct by enlarged peripancreatic, celiac, and portahepatic nodes caused biliary obstruction in one patient with biopsy-proven BA of the cervical lymph nodes.(69) A retroperitoneal mass associated with BA caused ureteral and duodenal compression in one patient,(62) and another patient developed an intraabdominal mass due to BA that eroded into the jejunum, causing massive gastrointestinal hemorrhage.(70)

Laryngeal obstruction associated with angiomata apparently resulted in the asphyxiative death of one untreated patient.(6) BA was manifest as polypoid endobronchial lesions in one patient: the polypoid lesions were apparent during bronchoscopy in the trachea and bronchi.(71)

transparent image
Lymph Node Bacillary Angiomatosis
transparent image

Lymphadenopathy involving multiple or single lymph nodes occurs frequently in patients with BA. The nodes involved may directly drain either a cutaneous lesion(26,29,36-38,69)or peliotic liver and spleen.(19,72,73) Many reports note biopsy-confirmed BA of the lymph node,(19,39,40,69,73)and the most commonly involved superficial node is inguinal.(26,37,69,73,74) The size ranged from 1 x 3 x 2 cm (splenic hilar)(73) to 6 x 3 x 8 cm (inguinal),(69) and all resolved after appropriate antibiotic treatment. No reports describe suppuration and drainage from BA lymph nodes in the absence of antibiotic treatment.

transparent image
Central Nervous System Bacillary Angiomatosis
transparent image

Spach et al(58) described a man presenting with seizures and a left temporal lobe mass who subsequently developed a cutaneous lesion that was consistent with BA histopathologically. A regimen of oral erythromycin led to complete resolution of the cutaneous lesion and the right facial nerve palsy after 3 months of treatment, and nearly complete resolution of the cerebral lesion by CT after 6 months of treatment.

transparent image
Bone Marrow Bacillary Angiomatosis
transparent image

Angiomatous changes involving bone marrow have occurred in two patients(18,29) with biopsy-proven cutaneous BA. Warthin-Starry staining of bone marrow demonstrated bacilli in one patient,(29) and PCR detected Bartonella DNA in the other patient.(18) Both patients had concomitant hepatosplenomegaly and thrombocytopenia that resolved after appropriate antibiotic treatment.

transparent image
Bacteremia
transparent image

Bacteremia with Bartonella is present in some patients with cutaneous BA and hepatic BP. Additionally, Bartonella bacteremia occurs in the apparent absence of localized tissue infection.(21,23,75) Of two HIV-infected patients,(21) one was later found to have hepatic BP by retrospective analysis of a percutaneous liver biopsy with Warthin-Starry staining.(67) The majority of bacteremic patients had fever, chills, and weight loss that resolved after antibiotic therapy.

transparent image
Endocarditis
transparent image

Spach et al(76) reported an HIV-infected patient with cardiac valvular vegetations documented simultaneously with positive blood cultures for B. quintana. This patient had no cutaneous BA or hepatic BP lesions, and no other organism was isolated. Endocarditis with three Bartonella species has been described, although most frequently in patients without HIV infection and most commonly due to B. quintana.(77,78,79)

transparent image
Pregnancy-Associated Bacillary Angiomatosis
transparent image

A Haitian woman presented in week 26 of gestation with multiple systemic symptoms and several vascular cutaneous nodules.(80) Cutaneous lesions resolved with antibiotic therapy, and the patient subsequently had an uneventful pregnancy and delivery.

transparent image
Pediatric Bacillary Angiomatosis
transparent image

Two reported cases of pediatric BA developed in an immunocompetent child(3) and in a 12-year-old boy with drug-induced immunosuppression.(81) It is thus plausible that BA cases will be identified in HIV-infected pediatric patients. Pediatricians should be aware of the wide spectrum of clinical presentation for BA and BP.

transparent image
Diagnosis
transparent image
transparent image
Obtaining Tissue Specimens for Diagnosis of Bacillary Angiomatosis
transparent image

The best method for diagnosis of cutaneous BA remains biopsy with histopathologic study. Skin specimens are obtained by shave excision (large pedunculated lesions) or punch biopsy (small papular lesions and subcutaneous nodules). Osteolytic lesions are frequently associated with overlying skin lesions accessible to biopsy; however, absence of cutaneous involvement warrants open excisional biopsy of bone.(26) The evaluation of lymph node specimens requires obtaining tissue by incisional or excisional biopsy, because fine-needle aspiration of lymph nodes has proved inadequate for the histologic confirmation of BA (Tappero, unpublished data). Optimal evaluation of parenchymal tissue for splenic and hepatic BP requires splenectomy or wedge excisional biopsy of the liver. Although transvenous liver biopsy(82) and percutaneous liver biopsy(67) have yielded adequate tissue for the diagnosis of bacillary peliosis hepatis, hepatic and splenic aspirates have failed to confirm BP in grossly involved organs of other patients.(36,73) The risk of hemorrhage following percutaneous biopsy in patients with peliotic parenchymal tissue is unknown.

transparent image
Histopathology of Bacillary Angiomatosis and Bacillary Peliosis
transparent image

Tissue specimens reveal a characteristic vascular proliferation on routine hematoxylin & eosin staining, in addition to numerous bacilli demonstrable by modified silver staining (eg, Warthin-Starry, Steiner, Dieterle) or electron microscopy.(8,19,42) These organisms are not visualized following staining for fungi or acid-fast mycobacteria; staining with Brown-Brenn tissue Gram's stain is also negative, which distinguishes the Bartonella bacilli from most other small, gram-negative rods.

Cutaneous and extracutaneous BA lesions typically show a lobular proliferation of small, capillary-sized blood vessels with protuberant, cuboidal, or polygonal endothelial cells containing abundant cytoplasm, with or without cytologic atypia (Figure 8).(8,9,27,58,73,83) A mixed inflammatory infiltrate, including lymphocytes and neutrophils with leukocytoclasis and areas of focal necrosis, is often present. Granular, fibrillary amphophilic material, revealing bacilli on silver staining or electron microscopy (Figure 9), may be scattered throughout myxoid connective tissue, typically in close proximity to vascular lumina surrounded by neutrophilic aggregates. On electron microscopy (Figure 10), these bacilli possess a trilaminar cell wall and contain electron-dense granular material.(9) Lymph node, bone, and brain BA lesions may demonstrate a less lobular pattern than cutaneous BA and have a less prominent neutrophilic infiltrate.

The vascular proliferative pattern exhibited by most cutaneous, lymph node, bone, and brain BA lesions(8,9,26,42,58,73)differs markedly from the peliotic pattern observed in most hepatic and splenic lesions.(19,36,42) On routine staining, involved sections of liver or spleen show a spectrum ranging from dilated capillaries to multiple dilated, thin-walled, blood-filled peliotic spaces with surrounding myxoid stroma and parenchymal cells.(19,42) Stromal areas contain a mixture of inflammatory cells and clumps of granular amphophilic material representing well-visualized bacillary organisms on silver staining and electron microscopy.

transparent image
Histologic Differential Diagnosis
transparent image

BA lesions often have been misdiagnosed histopathologically. Erroneous diagnoses of cutaneous BA lesions have included KS,(9,27,71,84) angiosarcoma,(6,32,59,84) and pyogenic granuloma.(31,37,56) Superficial cutaneous lesions of BA can be easily confused with lobular capillary hemangiomas (pyogenic granulomas) and verruga peruana.(9) Both cutaneous and osseous BA lesions must be distinguished from KS and angiosarcoma.(8,9,33,34,84,85)BA involving either the skin or lymph node also can mimic both epithelioid (histiocytoid) hemangioma and epithelioid hemangioendothelioma histopathologically, and BA of the lymph node may be confused with lymphoma and metastatic carcinoma.(73) Although rare, peliosis of the liver and spleen in the absence of bacillary organisms has occurred in patients with advanced cancer or a variety of infections, and following treatment with anabolic steroids and several other medications.(19)

Any one of the above histopathologic diagnoses in an HIV-infected patient should prompt further evaluation of the tissue for bacilli to determine whether the lesion may actually be due to BA. The diagnostic feature distinguishing cutaneous BA, extracutaneous BA, and parenchymal BP from all other diagnoses is the presence of bacillary organisms (with the exception of the cutaneous lesions of verruga peruana, which are associated with B. bacilliformis bacilli). In addition to silver staining and electron microscopy, immunocytochemical staining using polyclonal rabbit antiserum to B. henselae can demonstrate organisms in lesions of cutaneous BA and BP.(75)

transparent image
Serology
transparent image

An indirect fluorescence antibody (IFA) test developed by Regnery et al at the Centers for Disease Control and Prevention detects antibodies to B. henselae,(44) and appears to be useful for detection of Bartonella antibodies in patients with BA.(86) Sera from seven HIV-infected patients with biopsy-confirmed cutaneous BA were tested and found to have Bartonella antibodies, whereas control sera from seven HIV-infected patients without BA were negative. Examination of banked sera from three of these seven BA patients revealed that Bartonella antibodies were present up to 7 years before the development of BA disease, suggesting infection with this bacterium years before the diagnosis of BA. A fourfold rise in titer preceded the diagnosis of BA in all three patients, raising the possibility of either relapse or reinfection. In another BA patient who had completed 4 months of antibiotic therapy for osseous BA,(26) a rising titer predicted relapse.(86) These studies suggest that this IFA is promising for the diagnosis of BA or other Bartonella-associated infections in HIV-infected patients.

A preliminary report(87) noted that an enzyme immunoassay (EIA) may be of use to detect B. henselae antibodies in the CSF and serum of HIV-infected patients with HIV encephalopathy. Additionally, Slater et al(88) found that in a murine model, an EIA, an IFA test, and an immunoblot assay can enable investigators to distinguish between B. henselae and the trench fever isolate (Fuller strain(89)) of B. quintana. Because BA can be caused by either B. henselae or B. quintana,(26) a serologic assay capable of distinguishing antigenically distinct proteins from these two closely related species will be of great importance in unraveling both the clinical spectrum of disease and the seroepidemiology of populations exposed to these two pathogens.

transparent image
Culture of Bartonella Species from the Blood of Patients with Bacillary Angiomatosis and Bacillary Peliosis
transparent image

Both B. quintana and B. henselae have been isolated from the blood of HIV-infected patients with cutaneous BA(26) and peliosis hepatis,(67) as well as from patients without apparent localized Bartonella infection.(21,23) Bartonella species are optimally isolated from blood using the lysis-centrifugation tubes (Isostat Tubes, Wampole, Cranbury, NJ) and plating onto fresh chocolate or heart infusion agar with 5% rabbit blood, without antibiotics. B. henselae also has been isolated from blood collected in tubes containing ethylenediaminetetraacetic acid (EDTA) and subsequently stored frozen.(23) The degree of bacteremia reported for Bartonella varies from 0.7 to greater than 1,000 colony-forming units per milliliter of blood.(26)

Plates inoculated with blood should be incubated at 35°C for at least 3 weeks in 5% CO2 and high humidity until colonies appear, usually after 5 to 15 days.(21,23,24,26) B. henselae colonies are rough, cauliflower-like, and usually deeply embedded in the agar;(23) in contrast, B. quintana colonies are smooth, flat, and shiny and do not pit the agar.(26) The bacilli are small (2 mm x 0.5 mm) and stain best with Gimenez stain;(23) with gram-staining, Bartonella species are only weakly counterstained with safranin.(20) Although the lysis-centrifugation tubes are relatively expensive, in most microbiology labs blood culture can be performed using these tubes or EDTA-containing blood tubes. Culture from blood represents the most accessible method (compared with biopsy and culture of liver or skin) of isolating Bartonella from patients with either cutaneous BA or peliosis hepatis; however, not all patients with BA or BP are bacteremic.

transparent image
Culture of Bartonella Species from Bacillary Angiomatosis Tissue
transparent image

Recovery of Bartonella from cutaneous tissues of BA has been difficult. Organisms cultivated during initial attempts either were not further characterized(38) or were cultivated in liquid phase but not successfully grown after transfer onto solid agar.(90) Isolation of both B. quintana and B. henselae from cutaneous lesions of patients with advanced HIV disease was first accomplished in a system involving co-cultivation with an endothelial cell monolayer.(26) We have had increasing success isolating Bartonella from BA tissue using direct plating of tissue homogenate onto solid agar, thus making culture a more accessible technique for recovery of Bartonella species from tissues. B. henselae also has been isolated from the spleen of an immunosuppressed renal transplant patient with splenic peliosis(67) and from CSD lymph node tissues of immunocompetent patients(15) by direct plating of tissue homogenate onto agar.

transparent image
Polymerase Chain Reaction Diagnosis of Bacillary Angiomatosis
transparent image

Detection of Bartonella DNA in tissue specimens has been used to diagnose osseous(26) and cutaneous BA(2,18,26,42) and BP of the spleen(2,18) and liver.(42,82) This PCR technique is not commercially available but has important applications in several settings. First, histopathologic diagnosis of osseous BA by hematoxylin & eosin and Warthin-Starry staining may be difficult because of the processing necessary for preparation of bone specimens. For one of our cases of BA osteomyelitis, the initial diagnosis of infection with B. quintana was made by extraction of DNA from the bone specimen followed by amplification using the PCR.(26) Diagnosis of bacillary peliosis hepatis due to B. henselae also has been accomplished using PCR amplification of DNA from a specimen obtained by transvenous liver biopsy.(82) For specimens from nonsterile sites where cultures cannot be performed (eg, gingival and GI endoscopic biopsies), we have used PCR to determine if Bartonella species are present. In addition to diagnosis, the need for speciating Warthin-Starry-positive organisms in biopsy specimens is an important research undertaking. Only by speciation of organisms isolated by culture, or by demonstration of Bartonella DNA in these specimens, can we define the entire spectrum of infection due to Bartonella species.

transparent image
Antibiotics
transparent image

Antibiotic treatment of BA and BP has never been systematically studied, and there is currently no animal model. Based on our clinical experience treating more than 50 patients, reported cases, and, finally, in vivo antibiotic treatment of experimentally-infected cats, we recommend treatment with erythromycin or doxycycline first line (Table 1). If either antibiotic is not tolerated, tetracycline or clarithromycin or azithromycin is used. A recent antibiotic trial treating cats experimentally infected with B. henselae found a statistically significant decrease in levels of bacteremia after treatment with tetracycline and erythromycin but not enrofloxacin (a quinolone derivative) or amoxicillin.(91)

The initial BA patient described by Stoler in 1983(4) was treated empirically with erythromycin and had complete resolution of lesions. Subsequently, erythromycin has been reported to successfully treat many patients with BA and BP.(2,9,18,19,21,24,26-29,31,33,41,42,52,55,58,67,92) Erythromycin is usually administered orally (500 mg four times a day) but should be administered intravenously to patients with severe disease or who are unable to tolerate oral medication. Treatment of BA and BP with oral doxycycline also has been consistently successful.(2,18,23,26,27,36,39,40,56,59) A report also describes resolution of BA lesions caused by B. henselae in an HIV-infected patient treated with tetracycline(26) and in two immunocompetent patients with B. henselae bacteremia.(21) Minocycline was used to successfully treat cutaneous BA in an immunocompetent patient.(2) A number of reports describe resolution of BA lesions following institution of antimycobacterial therapy(7,9,27,41,93); presumably the response is to the rifampin component of this therapy. (Table 2) summarizes antibiotics used to treat Bartonella infections and their apparent clinical efficacy. Note that after the first several doses of an appropriate antibiotic, the patient may experience a Jarisch-Herxheimer-like reaction, with exacerbation of systemic symptoms and fever(26); pretreatment with an antipyretic may attenuate this response.

B. quintana and B. henselae are usually susceptible in vitro to erythromycin, doxycycline, and tetracycline.(21,94) This finding correlates well with the clinical response of patients with BA, but there are discrepancies between the in vitro sensitivities and the clinical response for both B. henselae and B. quintana to other antibiotics, especially those that target steps in cell wall synthesis (eg, penicillin). Penicillin, penicillinase-resistant penicillin, aminopenicillins, first-generation and probably second-generation cephalosporins have no activity against the B. quintana and B. henselae bacilli in BA lesions,(9,26,27,31,33,37,55,64) in contradiction to some in vitro susceptibilities reported for these antibiotics.(21,94) Single reports of improvement with vancomycin(31) or a first-generation cephalosporin(37) most likely represent treatment of superinfection. Indeed, we have cultured B. quintana from the cutaneous BA lesions of a patient intentionally pretreated with cephradine (to reduce the number of superinfecting organisms).(26) The discrepancy between the in vivo and in vitro data may result from the difficulty in performing susceptibility tests with these very fastidious organisms. Alternatively, Bartonella species present in BA lesions may have altered cell wall characteristics,rendering them resistant in vivo to antibiotics that inhibit synthesis of the cell wall.

Other antibiotics have been associated with improvement in lesions or symptoms, but these reports are not sufficiently consistent to warrant their recommendation at present. Complicating these reports of antibiotic response is the frequent coinfection or superinfection with other pathogens in HIV-infected patients. Some third-generation cephalosporins may be effective in treating Bartonella infections: a pregnant patient with cutaneous BA had complete resolution of lesions during 2 weeks of ceftizoxime treatment(80); another patient with B. quintana endocarditis was treated with 5 weeks of ceftriaxone,(76) but a patient with lymph node BA failed to respond to 5 days of ceftriaxone therapy.(69) Response to quinolone antibiotics is equivocal. One patient treated with 5 weeks of erythromycin for B. henselae bacteremia continued to be febrile and achieved permanent remission of fever after receiving an additional 3 weeks of treatment with norfloxacin,(21) and another patient improved dramatically when treatment with ciprofloxacin and gentamicin was instituted.(69) We have, however, progression of BA lesions in patients treated with ciprofloxacin,(40) and this lack of in vivo quinolone efficacy is substantiated by treatment failure in experimental feline bacteremia.(91) Most patients receiving trimethoprim-sulfamethoxazole had no improvement or had progression of lesions,(55,76,80) although one group noted some improvement in one patient treated with this drug.(71) The efficacy of aminoglycosides for treatment of BA also is not definitive, but there is indirect evidence that Bartonella infection may respond to gentamicin: treatment with gentamicin and piperacillin or nafcillin resulted in improvement in several patients.(29,77) However, treatment with mezlocillin and tobramycin was not effective in another patient.(19)

transparent image
Relapse
transparent image

Historically, blood infection with Bartonella species can produce a relapsing illness regardless of the immune status of the patient and often in spite of antibiotic therapy.(21-23,95) Numerous authors have reported relapse of BA lesions of bone and skin.(26,31,33,37,55,69) Although relapse seems likely in patients with recurrence or exacerbation of lesions at a previously affected site, the possibility of reinfection cannot be eliminated, especially in the absence of knowledge of details regarding transmission of Bartonella species. Relapse is most often reported when a shorter course (especially only a few weeks) of antibiotic therapy was administered. Although it is not clear whether treating patients with a prolonged course of antibiotics will eliminate relapse, we have increased the duration of treatment to 2 months or longer depending on the severity of BA disease (see below).

transparent image
Cutaneous Lesions
transparent image

Before institution of antibiotic therapy in patients with cutaneous lesions, the patient should be evaluated for parenchymal and osseous disease. Focal bone pain should be evaluated with a bone scan, and liver function tests should be performed in addition to complete blood count and platelet counts. Involvement of either bone or liver with Bartonella infection requires a longer duration of antibiotic treatment (see below). Oral antibiotic therapy usually is initiated, and response of cutaneous lesions is usually dramatic; although improvement may occur within 1 week, with complete resolution by 1 month,(96) hyperpigmentation at the lesion site may persist indefinitely. We recommend treating patients who have only cutaneous lesions with erythromycin, 500 mg four times a day, or doxycycline, 100 mg twice a day, for 8 to 12 weeks (depending on severity of illness). If relapse occurs, the patient should be retreated for an additional 16 weeks, or possibly indefinitely.

transparent image
Osseous Lesions
transparent image

Optimal dosage and duration of treatment of osseous lesions also is not known. We successfully treated one patient with osseous BA using oral erythromycin for 4 months. This patient self-administered a dose of 500 mg orally six times daily for 2 months, and then a decreased dose of 500 mg four times daily for the remaining 2 months.(27) He had no relapse during the subsequent 24 months until his death. Another patient with B. quintana osteomyelitis, however, received 500 to 1,000 mg erythromycin orally four times daily for 4 months but relapsed with B. quintana bacteremia 1 month after cessation of therapy.(26) The bacteremia and systemic symptoms resolved with reinstitution of erythromycin, and antibiotic therapy was continued until his death 6 months later. Because of the immunocompromised status of most BA patients and the severity of infection, it may be most appropriate to treat patients with osseous BA initially with several weeks of intravenous antibiotics (erythromycin or doxycycline), followed by prolonged, and perhaps indefinite, oral antimicrobial therapy.

We recommend treatment with erythromycin, 500 to 1,000 mg four times a day, or doxycycline, 100 mg twice a day, for a minimum of 4 months. The patient should be monitored closely if antibiotics are discontinued. Treatment efficacy can be assessed after 8 to 12 weeks of therapy by technetium-99m methylene diphosphonate bone scan or radiography, although the improvement and resolution detected by these tests are delayed, as seen with other causes of osteomyelitis.

transparent image
Hepatic and Splenic Bacillary Peliosis
transparent image

Like patients with osseous BA, patients with splenic or hepatic disease should receive prolonged (at least 3 months) and possibly indefinite therapy. The majority of our patients with BP have had severe systemic illness, including nausea and vomiting, which may substantially decrease absorption of oral antibiotics. In addition, oral intake of doxycycline or erythromycin may significantly exacerbate symptoms of BP. These patients should be treated initially with intravenous antibiotics (erythromycin, 500 to 1,000 mg every 6 hours, or doxycycline, 100 mg every 12 hours). Liver function tests usually show improvement, although concurrent infection with other pathogens may preclude normalization. The larger peliotic lesions are frequently visible by CT (see Figure 7), and resolution can be documented by repeat scanning following antibiotic therapy.

transparent image
Bacteremia
transparent image

Ideally, patients with cutaneous or osseous BA lesions and peliosis hepatis should have blood cultures performed. Although no report yet describes endocarditis concomitant with BA or BP, because of the reports of endocarditis with B. quintana and B. elizabethae,(76,77) patients with Bartonella bacteremia should probably be evaluated further with echocardiography. In HIV-infected patients with isolated Bartonella bacteremia, fever usually resolves in less than 1 week after institution of antibiotic therapy, but time to permanent remission of fever was 8 weeks in one patient with B. henselae bacteremia.(21) Optimal duration and route of antimicrobial therapy are again not known, but we recommend a minimum of 2 months with erythromycin, 500 mg four times daily, or doxycycline, 100 mg twice daily, for the HIV-infected person with isolated bacteremia, including an initial period of intravenous therapy for patients with severe systemic symptoms. Endocarditis should prompt prolonged therapy with intravenous erythromycin (500 to 1,000 mg every 6 hours) or doxycycline (100 mg every 12 hours) for a minimum of 2 months.

transparent image
Prevention
transparent image

Because HIV-infected patients may develop severe sequelae from B. henselae infection, and yet usually benefit psychologically from pet companionship, we do not recommend that patients give up their pet cats.(97) Instead, some practical measures are suggested by the foregoing data: HIV-infected patients should avoid rough play that may lead to cat scratches, wash any scratches immediately, control flea infestation, and, if a new cat is brought into the home, a mature cat rather than a kitten is preferred.(97)

BA can be caused by B. quintana as well as B. henselae,(26) and one third of the patients in one epidemiologic study of BA and BP had not been exposed to cats.(42) It is possible that BA in these patients without cat exposure was caused by B. quintana, not B. henselae, and that these patients acquired B. quintana from a different reservoir and vector. In trench fever outbreaks during World War I, B. quintana was transmitted by a louse vector from the human reservoir.(95) In addition, B. quintana bacteremia has been reported in homeless HIV-negative men.(78) Thus, homelessness may be a risk factor for B. quintana infection via body louse exposure, and prevention of infection with this species includes avoidance or eradication of louse infestation. Further study of the reservoirs and vectors of Bartonella species will doubtless improve our ability to recognize and prevent these life-threatening but treatable infections in HIV-infected individuals.

transparent image
Acknowledgment
transparent image

This chapter is modified with permission of JE Koehler and the University of Chicago Press. AIDS commentary: Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus. Clin Infect Dis 1993;17:612-624.

transparent image
transparent image

References

transparent image
1.   Cockerell CJ, Bergstresser PR, Myrie-Williams C, et al. Bacillary epithelioid angiomatosis occuring in an immunocompetent individual. Arch Dermatol 1990;126:787-790.
transparent image
2.   Tappero JW, Koehler JE, Berger TG, et al. Bacillary angiomatosis and bacillary splenitis in immunocompetent adults. Ann Intern Med 1993;118:363-365.
transparent image
3.   Paul MA, Fleischer JAB, Wieselthier JS, et al. Bacillary angiomatosis in an immunocompetent child: The first reported case. Pediatr Dermatol 1994;11:338-341.
transparent image
4.   Stoler MH, Bonfiglio TA, Steigbigel RT, et al. An atypical subcutaneous infection associated with acquired immune deficiency syndrome. Am J Clin Pathol 1983;80:714-718.
transparent image
5.  Stoler MH, Strauchen JA, Egbert BT, et al. AIDS associated atypical subcutaneous infection (abstract). Am J Clin Pathol 1985;84:560-561.
transparent image
6.   Cockerell CJ, Whitlow MA, Webster GF, et al. Epithelioid angiomatosis: A distinct vascular disorder in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Lancet 1987;2:654-656.
transparent image
7.   Knobler EH, Silvers DN, Fine KC, et al. Unique vascular skin lesions associated with human immunodeficiency virus. J Am Med Assoc 1988;260:524-527.
transparent image
8.   LeBoit PE, Berger TG, Egbert BM, et al. Bacillary angiomatosis: The histopathology and differential diagnosisof a pseudoneoplastic infection in patients with human immunodeficiency virus disease. Am J Surg Pathol 1989;13:909-920.
transparent image
9.   LeBoit PE, Berger TG, Egbert BM, et al. Epithelioid haemangioma-like vascular proliferation in AIDS: Manifestation of cat-scratch disease bacillus infection? Lancet 1988;1:960-963.
transparent image
10.   Wear DJ, Margileth AM, Hadfield TL. Cat scratch disease: A bacterial infection. Science 1983;221:1403-1405.
transparent image
11.   English CK, Wear DJ, Margileth AM, et al. Cat-scratch disease. Isolation and culture of the bacterial agent. J Am Med Assoc 1988;259:1347-1352.
transparent image
12.   Brenner DJ, Hollis DG, Moss CW, et al. Proposal of Afipia gen. nov., with Afipia felis sp. nov. (formerly the cat scratch disease bacillus), Afipia clevelandensis sp. nov. (formerly the Cleveland Clinic Foundation Strain), Afipia broomeae sp. nov., and three unnamed genospecies. J Clin Microbiol 1991;29:2450-2460.
transparent image
13.   O'Connor SP, Dorsch M, Steigerwalt AG, et al. 16S rRNA sequences of Bartonella bacilliformis and cat scratch disease bacillus reveal phylogenetic relationships with the alpha-2 subgroup of the class proteobacteria. J Clin Microbiol 1991;29:2144-2150.
transparent image
14.   Relman DA, Lepp PW, Sadler KN, et al. Phylogenetic relationships among the agent of bacillary angiomatosis,Bartonella bacilliformis, and other alpha-proteobacteria. Mol Microbiol 1992;6:1801-1807.
transparent image
15.   Dolan MJ, Wong MT, Regnery RL, et al. Syndrome of Rochalimaea henselae adenitis suggesting cat scratch disease. Ann Intern Med 1993;118:331-336.
transparent image
16.   Koehler JE, Glaser CA, Tappero JW. Rochalimaea henselae infection. A new zoonosis with the domestic cat as reservoir. JAMA 1994;271:531-535.
transparent image
17.   Chomel BB, Abbott RC, Kasten RW, et al. Bartonella henselae prevalence in domestic cats in California: Risk factors and association between bacteremia and antibody titers. J Clin Microbiol 1995;33:2445-2450.
transparent image
18.   Relman DA, Loutit JS, Schmidt TM, et al. The agent of bacillary angiomatosis: An approach to the identification of uncultured pathogens. N Engl J Med 1990;323:1573-1580.
transparent image
19.   Perkocha LA, Geaghan SM, Yen TSB, et al. Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection. N Engl J Med 1990;323:1581-1586.
transparent image
20.   Relman DA, Falkow S, LeBoit PE. The organism causing bacillary angiomatosis, peliosis hepatis, and fever and bacteremia in immunocompromised patients (letter). N Engl J Med 1991;324:1514.
transparent image
21.   Slater LN, Welch DF, Hensel D, et al. A newly recognized fastidious gram-negative pathogen as a cause of fever andbacteremia. N Engl J Med 1990;323:1587-1593.
transparent image
22.   Lucey D, Dolan MJ, Moss CW, et al. Relapsing illness due to Rochalimaea henselae in immunocompetent hosts: Implication for therapy and new epidemiological associations. Clin Infect Dis 1992;14:683-688.
transparent image
23.   Regnery RL, Anderson BE, Clarridge JE, et al. Characterization of a novel Rochalimaea species, R. henselae, sp. nov., isolated from blood of a febrile, HIV-positive patient. J Clin Microbiol 1992;30:265-274.
transparent image
24.   Welch DF, Pickett DA, Slater LN, et al. Rochalimaea henselae sp. nov., a cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiol 1992;30:275-280.
transparent image
25.   Brenner DJ, O'Connor SP, Winkler HH, et al. Proposals to unify the genera Bartonella and Rochalimaea, with descriptions of Bartonella quintana comb. nov., Bartonella vinsonii comb. nov., Bartonella henselae comb. nov., and Bartonella elizabethae comb. nov., and to remove the family Bartonellaceae from the order Rickettsiales. Int J Syst Bacteriol 1993;43:777-786.
transparent image
26.   Koehler JE, Quinn FD, Berger TG, et al. Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med 1992;327:1625-1631.
transparent image
27.   Koehler JE, LeBoit PE, Egbert BM, et al. Cutaneous vascular lesions and disseminated cat-scratch disease in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Ann Intern Med 1988;109:449-455.
transparent image
28.   Rudikoff D, Phelps RG, Gordon RE, et al. Acquired immunodeficiency syndrome-related bacillary vascular proliferation (epithelioid angiomatosis): Rapid response to erythromycin therapy (letter). Arch Dermatol 1989;125:706-707.
transparent image
29.   Milam M, Balerdi MJ, Toney JF. Epithelioid angiomatosis secondary to disseminated cat scratch disease involving the bone marrow and skin in a patient with acquired immune deficiency syndrome: A case report. Am J Med 1990;88:180-183.
transparent image
30.   Schwartzman WA, Marchevsky A, Meyer RD. Epithelioid angiomatosis or cat scratch disease with splenic and hepatic abnormalities in AIDS: Case report and review of the literature. Scand J Infect Dis 1990;22:121-133.
transparent image
31.   van der Wouw PA, Hadderingh RJ, Reiss P, et al. Disseminated cat-scratch disease in a patient with AIDS. AIDS 1989;3:751-753.
transparent image
32.   Schinella RA, Greco MA. Bacillary angiomatosis presenting as a soft-tissue tumor without skin involvement. Hum Pathol 1990;21:567-569.
transparent image
33.   Berger TG, Tappero JW, Kaymen A, et al. Bacillary (epithelioid) angiomatosis and concurrent Kaposi's sarcoma in acquired immunodeficiency syndrome. Arch Dermatol 1989;125:1543-1547.
transparent image
34.   Steeper TA, Rosenstein H, Weiser J, et al. Bacillary epithelioid angiomatosis involving the liver, spleen, and skin in an AIDS patient with concurrent Kaposi's sarcoma. Am J Clin Pathol 1992;97:713-718.
transparent image
35.   Tuur SM, Macher AM, Angritt P, et al. AIDS case for diagnosis series, 1988. Mil Med 1988;153:M57-M64.
transparent image
36.   Kemper CA, Lombard CM, Deresinski SC, et al. Visceral bacillary epithelioid angiomatosis: Possible manifestations of disseminated cat scratch disease in the immunocompromised host: A report of two cases. Am J Med 1990;89:216-222.
transparent image
37.   Marasco WA, Lester S, Parsonnet J. Unusual presentation of cat scratch disease in a patient positive for antibody to the human immunodeficiency virus. Rev Infect Dis 1989; 11:793-803.
transparent image
38.   Schlossberg D, Morad Y, Krouse TB, et al. Culture-proved disseminated cat-scrach disease in acquired immunodeficiency syndrome. Arch Intern Med 1989;149:1437-1439.
transparent image
39.   Pilon VA, Echols RM. Cat-scratch disease in a patient with AIDS. Am J Clin Pathol 1989;92:236-240.
transparent image
40.  Tappero JW, Koehler JE. Cat scratch disease and bacillary angiomatosis (letter). JAMA 1991;266:1938-1939.
transparent image
41.   Hall AV, Roberts CM, Maurice PD, et al. Cat-scrach disease in patient with AIDS: Atypical skin manifestation (letter). Lancet 1988;2:453-454.
transparent image
42.   Tappero JW, Mohle-Boetani J, Koehler JE, et al. The epidemiology of bacillary angiomatosis and bacillary peliosis. JAMA 1993;269:770-775.
transparent image
43.   Carithers HA. Cat-scratch disease: An overview based on a study of 1,200 patients. Am J Dis Child 1985;139:1124-1133.
transparent image
44.   Regnery RL, Olson JG, Perkins BA, et al. Serological response to Rochalimaea henselae antigen in suspected cat-scratch disease. Lancet 1992;339:1443-1445.
transparent image
45.   Regnery R, Martin M, Olson J. Naturally occurring Rochalimaea henselae infection in domestic cat (letter). Lancet 1992;340:557-558.
transparent image
46.   Anderson B, Kelly C, Threlkel R, et al. Detection of Rochalimaea henselae in cat-scratch disease skin test antigens. J Infect Dis 1993;168:1034-1036.
transparent image
47.   Chomel BB, Kasten RW, Floyd-Hawkins K, et al. Experimental transmission of Bartonella henselae by the cat flea. J Clin Microbiol 1996;34:1952-1956.
transparent image
48.   Mohle-Boetani JC, Koehler JE, Berger TG, et al. Bacillary angiomatosis and bacillary peliosis in patients infected with human immundeficiency virus: Clinical characteristics in a case-control study. Clin Infect Dis 1996;22:794-800.
transparent image
49.   Cockerell CJ, LeBoit PE. Bacillary angiomatosis: A newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder. J Am Acad Dermatol 1990;22:501-512.
transparent image
50.   LeBoit PE. Bacillary angiomatosis: A systemic opportunisticinfection with prominent cutaneous manifestations. Semin Dermatol 1991;10:194-198.
transparent image
51.   Jimenez-Acosta F, Pardo RJ, Cohen RJ, et al. Bacillary angiomatosis of acquired immunodificiency syndrome: Case report and literature review. J Am Acad Dermatol 1990;22:525-529.
transparent image
52.   Cairo I, Hulsebosch HJ, van der Wouw PA. Bacillary angiomatosis. Br J Dermatol 1991;125:393-394.
transparent image
53.   Spach DH. Review: Bacillary angiomatosis. Int J Dermatol 1992;31:19-24.
transparent image
54.   Schwartzman WA. Infections due to Rochalimaea: The expanding clinical spectrum. Clin Infect Dis 1992;15:893-900.
transparent image
55.   Szaniawski WK, Don PC, Bitterman SR, et al. Epithelioid angiomatosis in patients with AIDS. J Am Acad Dermatol 1990; 23:41-48.
transparent image
56.   Mui BSK, Mulligan ME, George WL. Response of HIV-associated disseminated cat scratch disease to treatment with doxycycline. Am J Med 1990;89:229-231.
transparent image
57.   Webster GF, Cockerell CJ, Friedman-Kien AE. The clinical spectrum of bacillary angiomatosis. Br J Dermatol 1992; 126:535-541.
transparent image
58.   Spach DH, Panther LA, Thorning DR, et al. Intracerebral bacillary angiomatosis in a patient infected with human immunodeficiency virus. Ann Intern Med 1992;116:740-742.
transparent image
59.   Herts BR, Rafii M, Spiegel G. Soft-tissue and osseouslesions caused by bacillary angiomatosis: Unusual manifestations of cat-scratch fever in patients with AIDS. Am J Radiol 1991;157:1249-1251.
transparent image
60.   Baron AL, Steinbach LS, LeBoit PE, et al. Osteolytic lesions and bacillary angiomatosis in HIV infection: Radiologic differentiation from AIDS-related Kaposi sarcoma. Radiology 1990;177:77-81.
transparent image
61.   Conrad SE, Jacobs D, Gee J, et al. Pseudoneoplastic infection of bone in acquired immunodeficiency syndrome. J Bone Joint Surg [A] 1991;73:774-777.
transparent image
62.   Gomez-Jorge JT, Donahue F, Ganz W, et al. Osseous manifestations of bacillary angiomatosis. Skeletal Radiol 1996;25:505-508.
transparent image
63.   Standiford KN, Emery CD, Schiffman RJ. Case report 865. Bacillary angiomatosis. Skeletal Radiol 1994;23:569-571.
transparent image
64.   Omarini LP, Loes SK, Garcia J, et al. Case report 860: Bacillary angiomatosis of the calcaneum. Skeletal Radiol 1994;23:478-481.
transparent image
65.   Meyers SA, Kuhlman JE, Fishman EK. Kaposi sarcoma involving bone: CT demonstration in a patient with AIDS. J Comput Assist Tomogr 1990;14:161-162.
transparent image
66.   Steinbach LS, Tehranzadeh J, Fleckenstein JL, et al. Human immunodeficiency virus infection: Musculoskeletal manifestations. Radiology 1993;186:833-838.
transparent image
67.   Slater LN, Welch DF, Min KW. Rochalimaea henselae causesbacillary angiomatosis and peliosis hepatis. Arch Intern Med 1992;152:602-606.
transparent image
68.   Huh YB, Rose S, Schoen RE, et al. Colonic bacillary angiomatosis. Ann Intern Med 1996;124:735-737.
transparent image
69.   Krekorian TD, Radner AB, Alcorn JM, et al. Biliary obstruction caused by epithelioid angiomatosis in a patient with AIDS. Am J Med 1990;89:820-822.
transparent image
70.   Koehler JE, Cederberg L. Intra-abdominal mass associated with gastrointestinal hemorrhage: A new manifestation of bacillary angiomatosis. Gastroenterology 1995;109:2011-2014.
transparent image
71.   Slater LN, Min KW. Polypoid endobronchial lesions. A manifestation of bacillary angiomatosis. Chest 1992;102:972-974.
transparent image
72.   Leong SS, Cazen RA, Yu GSM, et al. Abdominal visceral peliosis associated with bacillary angiomatosis. Ultrastructural evidence of endothelial destruction by bacilli. Arch Pathol Lab Med 1992;116:866-871.
transparent image
73.   Chan JKC, Lewin KJ, Lombard CM, et al. Histopathology of bacillary angiomatosis of lymph node. Am J Surg Pathol 1991; 15:430-437.
transparent image
74.   Angritt P, Tuur SM, Macher AM, et al. Case for diagnosis. Cat-scratch disease. Mil Med 1988;153:M25-M32.
transparent image
75.   Reed JA, Brigati DJ, Flynn SD, et al. Immunocytochemical identification of Rochalimaea henselae in bacillary (epithelioid) angiomatosis, parenchymal bacillary peliosis,and persistent fever with bacteremia. Am J Surg Pathol 1992; 16:650-657.
transparent image
76.   Spach DH, Callis KP, Paauw DS, et al. Endocarditis caused by Rochalimaea quintana in a patient infected with human immunodeficiency virus. J Clin Microbiol 1993;31:692-694.
transparent image
77.   Daly JS, Worthington MG, Brenner DJ, et al. Rochalimaea elizabethae sp. nov. isolated from a patient with endocarditis. J Clin Microbiol 1993;31:872-881.
transparent image
78.   Spach DH, Kanter AS, Dougherty MJ, et al. Bartonella (Rochalimaea) quintana bacteremia in inner-city patients with chronic alcoholism. N Engl J Med 1995;332:424-428.
transparent image
79.   Drancourt M, Mainardi JL, Brouqui P, et al. Bartonella (Rochalimaea) quintana endocarditis in three homeless men. N Engl J Med 1995;332:419-423.
transparent image
80.   Riley LE, Tuomala RE. Bacillary angiomatosis in a pregnant patient with acquired immunodeficiency syndrome. Obstet Gynecol 1992;79:818-819.
transparent image
81.   Myers SA, Prose NS, Garcia JA, et al. Bacillary angiomatosis in a child undergoing chemotherapy. J Pediatr 1992;121:574-578.
transparent image
82.   Marullo S, Jaccard A, Roulot D, et al. Identification of the Rochalimaea henselae 16S rRNA sequence in the liver of a French patient with bacillary peliosis hepatis (letter). J Infect Dis 1992;166:1462.
transparent image
83.   Walford N, van der Wouw PA, Das PK, et al. Epithelioidangiomatosis in the acquired immunodeficiency syndrome: Morphology and differential diagnosis. Histopathology 1990; 16:83-88.
transparent image
84.   Angritt P, Tuur SM, Macher AM, et al. Epithelioid angiomatosis in HIV infection: Neoplasm or cat-scratch disease? (letter). Lancet 1988;1:996.
transparent image
85.   Tsang WY, Chan JK. Bacillary angiomatosis. A "new" disease with a broadening clinicopathologic spectrum. Histol Histopathol 1992;7:143-152.
transparent image
86.  Tappero J, Regnery R, Koehler J, et al. Detection of serologic response to Rochalimaea henselae in patients with bacillary angiomatosis (BA) by immunofluorescent antibody (IFA) testing. In: Program and abstracts from the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 1992. American Society for Microbiology.
transparent image
87.   Patnaik M, Schwartzman WA, Barka NE, et al. Possible role of Rochalimaea henselae in pathogenesis of AIDS encephalopathy (letter; comment). Lancet 1992;340:971.
transparent image
88.   Slater LN, Coody DW, Woolridge LK, et al. Murine antibody responses distinguish Rochalimaea henselae from Rochalimaea quintana. J Clin Microbiol 1992;30:1722-1727.
transparent image
89.  Vinson JW, Fuller HS. Studies on trench fever. I. Propagation of Rickettsia-like microorganisms from a patient's blood. Path Microbiol 1961;24(Suppl):152-166.
transparent image
90.   Cockerell CJ, Tierno PM, Friedman-Kien AE, et al. Clinical,histologic, microbiologic, and biochemical characterization of the causative agent of bacillary (epithelioid) angiomatosis: A rickettsial illness with features of Bartonellosis. J Invest Dermatol 1991;97:812-817.
transparent image
91.   Regnery RL, Rooney JA, Johnson AM, et al. Experimentally induced Bartonella henselae infections followed by challenge exposure and antimicrobial therapy in cats. Am J Vet Res 1996;57:1714-1719.
transparent image
92.   Goodman P, Balachandran S. Bacillary angiomatosis in a patient with HIV infection. AJR Am J Roentgenol 1993; 160:207-208.
transparent image
93.   Lopez-Elzaurdia C, Fraga J, Sols M, et al. Bacillary angiomatosis associated with cytomegalovirus infection in a patient with AIDS. Br J Dermatol 1991;125:175-177.
transparent image
94.   Myers WF, Grossman DM, Wisseman CLJ. Antibiotic susceptibility patterns in Rochalimaea quintana, the agent of trench fever. Antimicrob Agents Chemother 1984;25:690-693.
transparent image
95.  Strong RP. Trench Fever: Report of Commission, Medical Research Committee, American Red Cross. Oxford: Oxford University Press, 1918.
transparent image
96.   Berger TG, Koehler JE. Bacillary angiomatosis. AIDS Clin Rev 1993:43-60.
transparent image
97.   Regnery RL, Childs JE, Koehler JE. Infections associated with Bartonella species in persons infected with humanimmunodeficiency virus. Clin Infect Dis 1995;21(Suppl 1):S94-S98.
transparent image
transparent image