Hepatic Granulomatous Lesions Caused by Systemic Bartonella vinsonii subsp. arupensis Infection in a Child

To the Editors: Cat-scratch disease is usually caused by Bartonella henselae or Bartonella quintana. Systemic infection has been reported in immunocompetent and immunocompromised children with initial symptoms of prolonged fever and hepatic and splenic granulomatous lesions.1 We describe the case of an atypical and rare systemic Bartonella vinsonii subsp. arupensis infection with liver involvement in a child, in whom the diagnosis was difficult because of negative serologic markers. Molecular detection of the pathogen in a liver specimen and in a cat blood sample permitted identification of the etiologic agent and the source of infection. CASE DESCRIPTION An 11-year-old girl was admitted to the Pediatric Department because of 3 weeks of fever and multiple hypoechoic hepatic lesions detected by abdominal ultrasound examination. Contrast-enhanced magnetic resonance imaging confirmed the presence of more than 10 focal liver lesions ranging from 5 to 45 mm in diameter. The child had a kitten. The child had no adenomegaly and presented normal general condition. The liver was moderately enlarged, and liver enzymes were normal. There was leukocytosis (12.000 per mm3) with neutrophilia (80%), a high sedimentation rate (93 mm/h), a high C-reactive protein (12 mg/dL, normal value < 0.5), hypergammaglobulinemia (2.1 g/dL) and hyper-IgG (2150 mg/dL). Two serum samples, collected at admission and 2 weeks later, were negative for anti-B. henselae and anti-B. quintana IgG and IgM by commercial immunofluorescence assay (Focus Diagnostics Inc.). Lymphocyte subpopulations were normal, and the results of Mantoux test and Quantiferon analysis were negative. The patient was treated with azithromycin 500 mg once a day and doxycycline 100 mg twice a day. The girl underwent an ultrasound guided liver biopsy, targeting the periphery of the largest lesion in segment VI revealing a reactive organized lesion. The result of bone marrow examination was negative. After 10 days of persisting fever, a second liver biopsy yielded a peripheral and a central sample from another smaller lesion in segment VII. The first sample had a similar histologic picture as the previous biopsy. The second specimen showed several granulomatous lesions with stellate microabscesses and central necrosis surrounded by an inner layer of palisading histiocytes and an outer rim of lymphocytes; round granulomas with prominent multinucleated giant cells and central caseation were also seen. Tissue Gram, methenamine silver, Ziehl–Neelsen, Grocott and Giemsa stains were negative for bacteria. We suspected systemic cat-scratch disease.2 Samples of the liver and the blood of the cat were sent to the Istituto Superiore di Sanità of Rome for polymerase chain reaction assays for Bartonella. The real-time polymerase chain reaction was performed on purified DNA as previously described.3 The method detects 10 copies and 1 copy per reaction with 100% and 40% reproducibility, respectively. The qualitative analysis based on the species-specific melting temperatures revealed DNA of B. vinsonii subsp. arupensis in all samples. The molecular diagnosis was confirmed by nucleotide sequences on the rpoB gene fragment using previously designed primers.4 The child continued to receive antibiotic treatment with azithromycin 500 mg once a day until resolution of fever, which occurred 4 weeks after the beginning of symptoms, and with doxycycline 100 mg twice a day for 6 weeks. The last follow-up, after 10 months, showed fewer and smaller hepatic lesions. Only the molecular detection of the pathogen supported diagnosis for this case of unusual Bartonella vinsonii subsp. arupensis infection, which is rarely described in humans. Just 1 case in France and 4 in Thailand (3 adults and 1 child) have been reported. The latter, an 11-year-old girl, presented fever, chill, fatigue, myalgia, icterus, headache and elevated liver enzymes.5 Maria Luisa Melzi, MD, PhD Giulia Maria Ferrari, MD Andrea D’Adda, MD Department of Pediatrics University of Milano Bicocca Fondazione MBBM Giorgio Bovo, MD Department of Pathology Sergio Foresti, MD Department of Infectious Diseases Annalisa Cavallero, MD, PhD Microbiology Laboratory Rocco Corso, MD Department of Radiology, San Gerardo Hospital, Monza, Italy Alessandra Ciervo, PhD Fabiola Mancini, PhD Department of Infectious Parasitic and Immune-mediated Diseases Istituto Superiore di Sanità Rome, Italy Andrea Biondi, MD Department of Pediatrics University of Milano Bicocca Fondazione MBBM, Monza, Italy