Approach Considerations
Bacillary angiomatosis in patients who also are infected with HIV most commonly causes anemia, leukopenia, and CD4+ cell counts of less than 0.2 X 109/L. In a series of 42 patients with bacillary angiomatosis, the average CD4+ cell count was 0.021 X 109/L. A rapid drop in hemoglobin level in the absence of bleeding or hemolysis has been reported in a patient with peliosis and was thought to be secondary to the sequestration of blood into pools in a liver or spleen that was massively enlarged. Thrombocytopenia with coagulopathy also may occur with peliosis.
Elevation of alkaline phosphatase, gamma-glutamyltransferase, and transaminase levels may indicate hepatic involvement. Alkaline phosphatase levels are more markedly elevated (5 times normal on average) than transaminase levels, which are usually mildly to moderately elevated or normal.
Well-circumscribed cortical or periosteal osteolytic lesions, mainly affecting the long bones, can be seen in radiographs in patients with bone involvement. [34, 37]
Procedures
Biopsy
Biopsy specimens of skin, subcutaneous or mucosal lesions, or, in cases of peliosis hepatis, the liver are diagnostic.
Endoscopy
With gastrointestinal involvement, endoscopic studies may reveal ulcerated nodules of the mucosa of the stomach, small intestine, or large intestine.
Bronchoscopy
With lung involvement, bronchoscopy may reveal polypoid lesions.
Laboratory Studies
The diagnosis of cutaneous bacillary angiomatosis and extracutaneous disease most often is based on clinical features coupled with biopsies of lesions and appropriate tissue staining. Detection of Bartonella DNA in tissue specimens via polymerase chain reaction (PCR) assay or of Bartonella antigens targeting the 16S-23S ribosomal RNA gene intergenic transcribed spacer via immunohistochemical methods is diagnostic. [4] Note that a negative result suggests the absence of detectable DNA but does not rule out Bartonella infection. The PCR assay does not differentiate between Bartonella henselae and Bartonella quintana.
Indirect immunofluorescent antibody studies
When indirect immunofluorescent antibody testing is used to detect immunoglobulin (Ig) antibodies to B henselae, IgG titers of higher than 1:64 against B henselae suggest the presence of bacillary angiomatosis.
Enzyme immunoassays
An enzyme immunoassay for the detection of IgG antibodies to B henselae now is available, and is reported to be 5-10 times more sensitive than the indirect fluorescent antibody test.
In addition, an immunoglobulin M–specific enzyme-linked immunosorbent assay for the detection of an early antibody response to B henselae has been developed that discriminates between B henselae–positive and B henselae–negative patient samples with impressive sensitivity (100%) and specificity (97.1%) values. [43]
Blood cultures
Blood cultures may yield organisms in bacillary angiomatosis if they are grown at 35°C in 5% carbon dioxide for 3 weeks using a lysis centrifugation technique. B henselae colonies are rough, cauliflowerlike, and usually deeply embedded in the agar. B quintana colonies are smooth, flat, and shiny and do not pit the agar. Whole-cell fatty acid gas chromatography has been used to identify the organisms once they have been grown in culture. Culture of Bartonella from solid tissue is more difficult but possible.
Radiography
Radiographs of the bones overlying the skin lesions in patients with bacillary angiomatosis may demonstrate simple cortical erosions, osteolytic lesions, extensive cortical destruction, or a periosteal reaction. Typical lytic bone lesions, which usually manifest as focal bone pain, are sometimes localized only to the area where a subcutaneous lesion is present, and can be asymptomatic.
Chest radiography may reveal pulmonary parenchymal nodules, which may have either well-defined or poorly defined borders, with no region of the lung consistently favored.
Bone scan findings always are positive at the site of osseus lesions and may help to identify the additional areas of involvement not revealed by conventional radiography.
CT Scanning and MRI
In peliosis hepatis, a computed tomography (CT) scan of the liver may demonstrate hypodense, ringlike lesions that enhance with contrast. [44] The absence of mass effect on adjacent vasculature is characteristic. On magnetic resonance imaging (MRI), the lesions appear bright on T2-weighted images and dark on T1-weighted images. Enhancement patterns of one published MRI case study suggested centripetal enhancement similar to hemangioma, but another MRI case study suggested centrifugal enhancement. [45]
Although authors disagree on the characteristic radiologic appearance of peliosis hepatis associated with bacillary angiomatosis, the most common presentation on CT scans consists of low-density lesions, some with peripheral enhancement. Homogeneous hypervascularity and nodular peripheral enhancement are not characteristic and would suggest an alternative pathology. [44]
CT scanning of the chest and abdomen may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.
In intracerebral bacillary angiomatosis, CT scanning of the brain reveals a contrast-enhancing mass lesion.
Histologic Findings
Some bacillary angiomatosis lesions have 2 distinct regions of vascular proliferation, a superficial one resembling a pyogenic granuloma or a papular angiokeratoma and a deeper one resembling a histiocytoid hemangioma, with a proliferation of small blood vessels lined by protuberant endothelial cells closely adherent to one another in an epithelioid pattern. The presence of neutrophils adjacent to the blood vessels is noteworthy and may be an important diagnostic clue.
Granular material resembling fibrin may be beside the neutrophils. This is the bacterium, observed best with either Warthin-Starry silver or Grocott-silver methenamine stain. A similar histologic pattern may be evident in affected oral mucosa, lymph nodes, liver, spleen, bone marrow, larynx, gastrointestinal tract, peritoneum, diaphragm, and bronchial mucosa. [46, 47]
Many blood vessels of varying dimensions lined by swollen endothelial cells that contain bacilli. An infiltrate of acute and chronic inflammatory cells as well as fibrin deposition is noted in places (hematoxylin and eosin, X80).
Lesion showing large masses of blood vessels of markedly varying dimensions lined by swollen endothelial cells. The tissue is friable with evident fragmentation during processing (hematoxylin and eosin, X23).
Some lesions only have a few solitary neutrophils and moderate numbers of bacteria, whereas others have clusters of neutrophils and numerous nearby bacteria, in some cases to the extent of mimicking a frank abscess.
Some bacillary angiomatosis nodules may histologically resemble those of histiocytoid (epithelioid) hemangioma, Kaposi sarcoma, and verruga peruana. A proliferation of both endothelial cells and factor XIIIa–positive dermal dendrocytes is observed in bacillary angiomatosis, verruga peruana, granuloma pyogenicum, and Kaposi sarcoma .
Skin
The overlying epidermis may demonstrate atrophy, ulceration, or, at times, pseudoepitheliomatous hyperplasia. [48] An epithelial collarette may be observed, particularly in those bacillary angiomatosis nodules that clinically resemble pyogenic granuloma. The dermis shows a vascular proliferation with small vessels arranged in clusters around ectatic vessels that may be markedly dilated. A lobular pattern may be observed, with varying amounts of edema and mucinous or fibrotic change between the lobules.
Histologic examination of skin lesions reveals vascular proliferation involving small blood vessels that contain plump cuboidal epithelial cells interspersed with polymorphonuclear inflammatory cell infiltrates and clumps of granular purple material. Coincidental endothelial cell necrosis and cytologic atypia may lead to a misdiagnosis of angiosarcoma. Solid areas of spindle cells may also be present; in some cases, these mimic Kaposi sarcoma or other sarcomas.
Liver
Histologic examination of liver sections in peliosis hepatis reveals dilated, blood-filled spaces in the fibromyxoid stroma that contain inflammatory cells, dilated capillaries, and clumps of granular purple material.
Lymph nodes
Histologic examination of lymph nodes reveals coalescing nodules of proliferated small blood vessels, some with prominent endothelial cells, in the cortical and paracortical areas. The uninvolved parenchyma may show follicular hyperplasia, plasmacytosis, or sinus histiocytosis.
Bacillary angiomatosis lesions of the lymph nodes, bone, and brain may demonstrate a less lobular pattern than cutaneous lesions do, and have a less prominent neutrophilic infiltrate.
Bone
Histologic examination of the bone reveals a lobular proliferation of small blood vessels with prominent endothelial cells. Neutrophils may be sparse, and their lobular nature may not be apparent in some bone biopsy findings.
Pseudoepitheliomatous hyperplasia
Pseudoepitheliomatous hyperplasia, a histologic reaction pattern characterized by epithelial proliferation in response to various stimuli, including mycobacterial, fungal, and bacterial infections, has been described in an immunocompromised patient with AIDS and bacillary angiomatosis. [48] Histologic examination of a finger lesion from this patient demonstrated capillary proliferation with neutrophilic debris and characteristic amorphous granular deposits. Warthin-Starry and Giemsa staining revealed clumps of coccobacilli. PCR assay using cervical lymph node tissue also revealed Bartonella organisms.
Staining techniques
The granular purple material in tissue sections stained with hematoxylin and eosin consists of masses of bacteria, which can be demonstrated by modified silver staining (Warthin-Starry silver stain) or electron microscopy. [46, 47] However, the major drawback of Warthin-Starry silver stain is lack of specificity.
Other organisms that stain positive with Warthin-Starry silver stain include the following:
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Legionella species (Legionnaires pneumonia)
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Nocardia species (nocardiosis)
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Trophermyma whippleii (Whipple disease)
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Afipia felis (catscratch disease)
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Treponema pallidum (syphilis)
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Borrelia burgdorferi (Lyme disease)
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Helicobacter pylori (chronic active gastritis)
However, bacillary angiomatosis is clinically distinguishable from infections caused by these organisms, except for those caused by Nocardia brasiliensis.
Transmission electron microscopy
Transmission electron microscopy reveals clumps of pleomorphic bacilli measuring 0.2-0.5 µm by 1-3 µm that have a trilaminar structure to the cell walls, which is typical of vegetative forms of gram-negative bacilli.
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A 35-year-old retrovirus-negative Mexican immigrant who had undergone recent splenectomy for idiopathic thrombocytopenic purpura, with multiple violaceous nodules on his trunk.
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Many blood vessels of varying dimensions lined by swollen endothelial cells that contain bacilli. An infiltrate of acute and chronic inflammatory cells as well as fibrin deposition is noted in places (hematoxylin and eosin, X80).
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A 40-year-old HIV-positive homosexual man with lichenoid cutaneous plaques on his upper extremities.
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Lesion showing large masses of blood vessels of markedly varying dimensions lined by swollen endothelial cells. The tissue is friable with evident fragmentation during processing (hematoxylin and eosin, X23).
