Bartonella henselae has been identified as an aetiological pathogen. Bacillary splenitis occurred during immune restoration induced by highly active antiretroviral therapy (HAART). The initiation of HAART in HIV-infected patients may be associated with the onset of acute inflammatory reactions to previously silent infections. These so-called paradoxical reactions were first reported against cytomegalovirus , mycobacteria , and hepatitis B , and were subsequently attributed to the immune restoration, even partial, conferred by HAART . We report a case of B. henselae infection contracted during the phase of immune restoration by HAART in a young HIV-positive woman, with an unusual evolution.
A 35-year-old woman living in Corsica, France, who acquired HIV-1 in 1986 and was co-infected by hepatitis C virus, was hospitalized in March 1999 because of mental deterioration. She had developed oesophageal candidiasis in 1995, and had complied poorly with several antiretroviral regimens, the first initiated in 1993. On admission her CD4 cell count was 23 cells/mm3 and her plasma viral load was 3.36 log10. Neurological and brain computed tomography findings were consistent with HIV encephalitis, and an antiretroviral regimen consisting of zidovudine (600 mg/day), lamivudine (300 mg/day) and indinavir (2400 mg/day) was started during the hospital stay. At week 6 of HAART her clinical status improved markedly, with a 5 kg weight gain and an increase in the mini-mental score from 20 to 26/30. After discharge, she returned home where she adopted a kitten. She was readmitted on 12 May 1999 because of intense abdominal pain and fever (38.5°C). The only noteworthy finding on physical examination was splenomegaly. Abdominal ultrasonography and computed tomography scan showed marked heterogenic splenomegaly. Routine laboratory test results were normal and her CD4 cell count was 109 cells/mm3. Because of the radiological aspect of the spleen, splenectomy was performed on 9 June 1999.
The excised spleen weighed 339 g and bore multiple nodules and abscesses (Fig. 1a). Histological examination showed a necrotizing suppurative granulomatous inflammation with numerous granulomas surrounding stellate or round microabscesses (Fig. 1b). The granulomatous reaction consisted of a rim of epithelioid cells, sometimes with giant cells in the outer zone. We observed neither pseudoneoplasic vascular proliferation nor cystic vascular spaces, in keeping respectively with bacillary angiomatosis and bacillary peliosis. Ziehl–Neelsen acid fast and periodic acid Schiff staining disclosed no micro-organism. In contrast, Warthin–Starry staining revealed multitudes of characteristic granular organisms organized in clusters in extracellular sites, mainly in the centres of stellate microabscesses (Fig. 1c). Polymerase chain reaction testing for B. henselae  on spleen tissue was positive. An immunofluorescent antibody assay showed IgG (1/1024) and IgM (1/40) antibodies to B. henselae. A stored serum sample taken in March 1999 did not contain antibodies to B. henselae. The patient was treated with oral doxycycline. One month later she was well, with a CD4 cell count of 146 cells/mm3 and a plasma HIV-RNA load of 645 copies/ml.
B. henselae, an emerging human pathogen, is the aetiological agent of cat scratch disease, a benign and generally self-limited disease of young immunocompetent adults, but which can cause severe infections in immunocompromised patients. Several clinical forms have been reported in patients with AIDS, including bacillary angiomatosis (mainly involving the skin), bacillary peliosis with hepatosplenic involvement, and fever with bacteraemia; the most characteristic histological feature of these infections is endothelial cell proliferation. In contrast, Bartonella species can be associated in the spleen or liver with necrotizing granulomatous lesions, similar to those found in the lymph nodes of patients with cat scratch disease [6,7]. In immunosuppressed patients these granulomatous lesions are rare, histologically unfinished and are more often associated with vascular abnormalities. Differences in host immune function may also play a role in disease progression [8,9]. In our patient the spleen lesions were inflammatory and necrotizing, with no vascular abnormalities, rare features previously described in immunocompetent patients with bacillary splenitis. This may be explained both by the recent nature of B. henselae infection (borne out by exposure to a kitten, seroconversion, and anti-B. henselae IgM), and by the immune restoration on HAART in concomitance with contamination. The histological features and timing of symptom onset (several weeks after HAART initiation, with a fivefold increase in the circulating CD4 cell count) suggest a disease related to immune restoration.
1. Jacobson MA, Zegans M, Pavan PR. et al
. Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy. Lancet 1997, 349: 1443–1445.
2. Race EM, Adelson-Mitty J, Kriegel GR. et al
. Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet 1998, 351: 252–255.
3. Proia LA, Siew Lin Ngui, Kaur S. et al
. Reactivation of hepatitis B in patients with human immunideficiency virus infection treated with combination antiretroviral therapy. Am J Med 2000, 108: 249–251.
4. Foudraine NA, Hovenkamp E, Notermans DW. et al
. Immunopathology as a result of highly active antiretroviral therapy in HIV-1 infected patients. AIDS 1999, 13: 177–184.
5. Roux V, Raoult D. The 16S-23S rRNA intergenic space of Bartonella
) species is longer than usually described in other bacteria. Gene 1995, 156: 107–111.
6. Ventura A, Massei F, Not T. et al
. Systemic Bartonella henselae
infection with hepatosplenic involvement. J Pediatr Gastroenterol Nutr 1999, 29: 52–56.
7. Liston TE, Koehler JE. Granulomatous hepatitis and necrotizing splenitis due to Bartonella henselae
in a patient with cancer: case report and review of hepatosplenic manifestations of Bartonella
infection. Clin Infect Dis 1996, 22: 951–957.
8. Tappero Jordan W, Koehler Jane E, Berger Timothy G. et al
. Bacillary angiomatosis and bacillary splenitis in immunocompetent adults. Ann Intern Med 1993, 118: 363–365.
9. Koehler Jane E, Tappero Jordan W. Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus. Clin Infect Dis 1993, 17: 612–624.