Granulomatous Hepatitis and Necrotizing Splenitis Due to Bartonella henselae in a Patient with Cancer: Case Report and Review of Hepatosplenic Manifestations of Bartonella Infection

Liston, Thomas E.; Koehler, Jane E.

doi:10.1093/clinids/22.6.951

Cited by 78 publications

(37 citation statements)

References 41 publications

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“…This is the first report of a clinically relevant, nonanticancer drug generating P-gp expression in a cancer cell line. Doxycycline is used for treating a variety of infectious diseases in cancer patients (29,33,44). It has also been used previously for chemical pleurodesis in patients with malignant pleural effusions (15,39) and is currently being investigated as an antiangiogenic agent for the treatment of cancer (19,23).…”

Section: Discussionmentioning

confidence: 99%

Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells

Mealey¹,

Barhoumi

Burghardt

et al. 2002

Antimicrob Agents Chemother

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P-glycoprotein (P-gp) overexpression by tumor cells imparts resistance to multiple antineoplastic chemotherapeutic agents (multiple drug resistance). Treatment of tumor cells with chemotherapeutic agents such as anthracyclines, epipodophyllotoxins, andVinca alkaloids results in induction of P-gp expression. This study was performed to determine if clinically relevant antimicrobial drugs (i.e., drugs that are used to treat bacterial infections in cancer patients) other than antineoplastic agents can induce expression of P-gp in MCF-7 breast carcinoma cells. Expression of P-gp and MDR1 mRNA was determined in samples from MCF-7 cells that were treated in culture with doxorubicin (positive control) and the antimicrobial drugs doxycycline, piperacillin, and cefoperazone. The functional status of P-gp was assessed using laser cytometry to determine intracellular doxorubicin concentrations. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to determine if the cytotoxicity of experimental drugs was related to their ability to induce P-gp expression. MCF-7 cells treated with doxycycline (MCF-7/doxy) were stimulated to overexpress P-gp, whereas cells treated with piperacillin and cefoperazone did not overexpress P-gp. MCF-7/doxy cells were compared to a positive-control subline, MCF-7/Adr, previously selected for doxorubicin resistance, and to MCF-7 cells treated with doxorubicin (MCF-7/doxo). All three sublines overexpressed P-gp and MDR1 mRNA and accumulated less intracellular doxorubicin than did control MCF-7 cells. P-gp expression was induced only by experimental drugs that were cytotoxic (doxorubicin and doxycycline). Doxycycline, a drug that has been used for treatment of bacterial infections in cancer patients, can induce functional P-gp expression in cancer cells, resulting in multidrug resistance.In 1970, Biedler and Riehm (3) described an in vitro model of chemotherapeutic multidrug resistance (MDR) in which cultured cells that were selected for growth in actinomycin D developed resistance to a variety of structurally and functionally diverse cytotoxic compounds. Further studies showed that the emergence of MDR was associated with increased levels of a transmembrane glycoprotein (24), P glycoprotein (P-gp). P-gp, the product of the MDR1 gene, is a 170-kDa protein that functions as an energy-dependent drug efflux pump whose substrates include naturally occurring, lipophilic agents with a complex ring structure such as Vinca alkaloids, anthracyclines, epipodophyllotoxins, and certain rhodamine dyes (18,26,37). Exposure of tumor cells to any of these substrates can generate overexpression of P-gp, resulting in the MDR phenotype.Drug exposure is thought to cause overexpression of P-gp by both selection of resistant cells and induction of P-gp expression at the level of the MDR1 promoter (14, 34). The MDR1 promoter contains a heat-shock consensus element (46) and a putative xenobiotic response element that responds directly to treatment with cytotoxic agents (25,45), supporting th...

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Section: Discussionmentioning

confidence: 99%

Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells

Mealey¹,

Barhoumi

Burghardt

et al. 2002

Antimicrob Agents Chemother

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“…Bartonella henselae is also a frequent cause of prolonged fever in children [33,62]. In immunocompromised patients, bacillary angiomatosis [23] and bacillary peliosis hepatis or splenitis are the most common B. henselae-induced disease manifestations [47]. In people, the major risk factor associated with B. henselae infection is cat exposure, especially cat scratches [14,64].…”

Section: Introductionmentioning

confidence: 99%

Bartonella henselae IgG antibodies are prevalent in dogs from southeastern USA

et al. 2004

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-In contrast to the large body of literature regarding Bartonella henselae in humans and cats, there is little information about B. henselae as an infectious agent in dogs. Due to the paucity of information regarding the B. henselae serology in dogs, we performed a cross-sectional serosurvey using B. henselae antigen in order to compare the seroprevalence between sick and healthy dogs from the south-eastern USA. Ninety-nine sera were collected from clinically healthy dogs. Three hundred and one sera from sick dogs were submitted to North Carolina State University for serologic screening against a panel of arthropod-transmitted organisms. Serological tests were performed using B. henselae (Bh), Rickettsia rickettsii (Rr), Ehrlichia canis (Ec), Bartonella vinsonii subspecies berkhoffii (Bvb), Babesia canis (Bc) and Borrelia burgdorferi (Bb) antigens. Serum B. henselae IgG antibodies were detected in 10.1% of healthy dogs and in 27.2% of sick dogs. The difference in seroprevalence between the two groups was statistically significant. The majority of seroreactive dogs (80%) had low titers of 1:64 or 1:128. In healthy dogs, seroprevalence for Rr was 14.1% and for Bvb was 1%. In sick dogs, Rr seroprevalence was 29.7%, Ec 6.5%, Bvb 4.7%, Bb 1.7% and Bc was 0.85%. Of the sick dogs that were seroreactive to B. henselae antigens, 40.6% were also seroreactive to Rr, 15.0% reactive to Bvb antigens, 14.8% reactive to Ec antigens, 1.8% reactive to Bc antigens and 1.75% reactive to Bb antigens. Sera from dogs experimentally infected with B. vinsonii subsp. berkhoffii, E. canis or R. rickettsii did not cross react with B. henselae antigens, by IFA testing. This study indicates that B. henselae IgG antibodies are prevalent in healthy and sick dogs living in the south-eastern USA. Nevertheless, further studies are needed to evaluate the epidemiological, clinical and zoonotic relevance of B. henselae infection in dogs.Bartonella henselae / dog / serology / vector-borne diseases

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“…Most cases of bacillary peliosis hepatis have been reported in HIV patients, whereas granulomatous hepatitis is more commonly reported in immunocompetent patients. 2 Both types of liver involvement have been described in transplant recipients. [3][4][5] Granulomatous inflammation of the liver was difficult to show in our patient.…”

Section: Discussionmentioning

confidence: 99%

“…Antimicrobial therapy can result in prompt resolution of illness and usually consists of a macrolide or tetracycline derivative. 2 However, the optimal antibiotic and duration of therapy for disseminated disease in immunocompromised patients is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…1 Also, disseminated disease caused by B henselae may result in necrotizing granulomatous involvement of the liver and other organs. 1,2 Infections caused by Bartonella spp are uncommonly reported in transplant recipients. We report a case of a liver transplant recipient who presented with fever of unknown origin and was found to have infection caused by Bartonella spp with granulomatous hepatitis of the transplant allograft.…”

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confidence: 99%

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Disseminated Bartonella infection with granulomatous hepatitis in a liver transplant recipient

Humar

Salit

1999

Liver Transpl

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Disseminated infection with Bartonella spp with granulomatous hepatitis was diagnosed in a liver transplant recipient presenting with fever of unknown origin. Pathological findings on liver biopsy were atypical, with scant granulomas seen only after a second biopsy. The patient responded promptly to antibiotic therapy. Infections caused by Bartonella spp should be considered in transplant recipients with fever of unknown origin. Copyright 1999 by the American Association for the Study of Liver Diseases Bartonella henselae has been recognized as the etiologic agent of cat-scratch disease and the cause of skin lesions known as bacillary angiomatosis, most commonly described in HIV-positive patients. 1 Also, disseminated disease caused by B henselae may result in necrotizing granulomatous involvement of the liver and other organs. 1,2 Infections caused by Bartonella spp are uncommonly reported in transplant recipients. We report a case of a liver transplant recipient who presented with fever of unknown origin and was found to have infection caused by Bartonella spp with granulomatous hepatitis of the transplant allograft. Case ReportA 44-year-old woman who had undergone an orthotopic liver transplantation for hepatitis C and alcoholic cirrhosis 4 years earlier presented with a 3-week history of fever. Past medical history included diabetes mellitus, hypertension, and splenectomy. She complained of daily fever spikes of 39°C to 40°C, headaches, myalgias, arthralgias, fatigue, and drenching night sweats. She had no abdominal pain or gastrointestinal symptoms. Travel history was unremarkable. She had two cats, aged 1 and 3 years, but did not recall any recent scratches. She had no history of tuberculosis exposure, other animal contact, or ingestion of raw milk or cheese. Her current immunosuppression therapy consisted of prednisone, 5 mg/d, and mycophenolate mofetil, 2 g/d. On physical examination, her temperature was 39.5°C. Her liver was palpable 3 cm below the right margin. The remainder of her examination was normal. Laboratory studies showed a normal leukocyte count; aspartate aminotransferase level, 77 U/L; alanine aminotransferase level, 44 U/L; and alkaline phosphatase level, 317 U/L. Routine blood cultures and a cytomegalovirus antigenemia assay were negative. A computed tomographic (CT) scan of her head and a cerebrospinal fluid analysis both showed normal results. Abdominal and thoracic CT scans showed an enlarged liver with no focal lesions and several mildly enlarged mediastinal and intraabdominal lymph nodes. Toxoplasma serological test results and a tuberculin skin test result were negative.A liver biopsy specimen (stained with hematoxylin and eosin) showed moderate to severe portal and parenchymal cellular infiltrates (plasma cells, lymphocytes, and eosinophils). Routine cultures of the liver tissue were negative, as were mycobacterial, fungal, and viral cultures. A second liver biopsy was performed and showed patchy severe portal and periportal cellular infiltrates and a few clusters of cells with foc...

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Granulomatous Hepatitis and Necrotizing Splenitis Due to Bartonella henselae in a Patient with Cancer: Case Report and Review of Hepatosplenic Manifestations of Bartonella Infection

Cited by 78 publications

References 41 publications

Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells

Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells

Bartonella henselae IgG antibodies are prevalent in dogs from southeastern USA

Disseminated Bartonella infection with granulomatous hepatitis in a liver transplant recipient

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