Bacillary Angiomatosis Workup

Bacillary angiomatosis in patients with who are also 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 may also occur with peliosis.

Indirect immunofluorescent antibody test to detect antibodies to B henselae has been used to diagnose bacillary angiomatosis. Immunoglobulin (IgG) titers of higher than 1:64 against B henselae suggest bacillary angiomatosis. An enzyme immunoassay for the detection of IgG antibodies to B henselae is now available and is reported to be 5-10 times more sensitive than the indirect fluorescent antibody test.

Blood cultures may yield organisms if 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 grown in culture.

Culture of Bartonella from solid tissue is more difficult but possible.

The diagnosis of cutaneous bacillary angiomatosis and extracutaneous disease is most often based on clinical features coupled with biopsies of lesions and appropriate tissue staining (see Histologic Findings). Detection of Bartonella DNA in tissue specimens by polymerase chain reaction (PCR) or Bartonella antigens by immunohistochemical methods is diagnostic.

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.

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. Bone scan findings are always positive at the site of osseus lesions and may help identify the additional areas of involvement not revealed by conventional radiography.

In peliosis hepatis, a CT scan of the liver may demonstrate hypodense ringlike lesions that may enhance with contrast.^[14] The absence of mass effect on adjacent vasculature is characteristic. On MRI, the lesions appear bright on T2-weighted images and dark on T1-weighted images. Enhancement patterns of one published MRI case study suggests centripetal enhancement similar to hemangioma, but another MRI case study suggests centrifugal enhancement.^[15]

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.^[16]

CT scan of the chest and abdomen may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.

In intracerebral bacillary angiomatosis, CT scan of the brain reveals a contrast-enhancing mass lesion.

Biopsy specimens of skin, subcutaneous or mucosal lesions, or, in cases of peliosis hepatis, the liver, are diagnostic.

With gastrointestinal involvement, endoscopic studies may reveal ulcerated nodules of the mucosa of the stomach, small intestine, or large intestine.

With lung involvement, bronchoscopy may reveal polypoid lesions.

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 cytological atypia may lead to a misdiagnosis of angiosarcoma. Solid areas of spindle cells may also be present, which, in some cases, mimic Kaposi sarcoma or other sarcomas.

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.

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.

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.

Bacillary angiomatosis lesions of the lymph nodes, bone, and brain may demonstrate a less lobular pattern than cutaneous lesions and have a less prominent neutrophilic infiltrate.

The granular purple material in tissue sections stained with hematoxylin and eosin are masses of bacteria, which can be demonstrated by modified silver staining (Warthin-Starry silver stain) or electron microscopy. However, the major drawback of Warthin-Starry silver stain is lack of specificity.

Other organisms that stain positive with Warthin-Starry silver stain include Legionellae species (Legionnaires pneumonia), Nocardia species (nocardiosis), Trophermyma whippleii (Whipple disease), Afipia felis (catscratch disease), Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme disease), and Helicobacter pylori (chronic active gastritis). However, bacillary angiomatosis is clinically distinguishable from infections caused by these organisms, except for Nocardia brasiliensis.

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.

Pseudoepitheliomatous hyperplasia has been described in an immunocompromised patient with AIDS and bacillary angiomatosis.^[17] Pseudoepitheliomatous hyperplasia is a histologic reaction pattern characterized by epithelial proliferation in response to various stimuli, including mycobacterial, fungal, and bacterial infections. 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 using cervical lymph node tissue also revealed Bartonella organisms.