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• W1569598026 abstract "Q fever is a worldwide zoonosis caused by Coxiella burnetii, a strictly intracellular and highly infectious bacterium that lives in the monocyte/macrophage, its host cell. Q fever is characterized by its clinical polymorphism, and develops as acute infections, some of which will evolve to chronic forms [1Raoult D Tissot-Dupont H Foucault C et al.Q fever 1985–1998. Clinical and epidemiologic features of 1,383 infections.Medicine. 2000; 79: 109-123Crossref PubMed Scopus (431) Google Scholar]. Patients with acute Q fever are more often asymptomatic. The most common syndromes observed in acute Q fever are prolonged fever of unexplained origin, granulomatous hepatitis, and atypical pneumonia. Although infective endocarditis is the main manifestation of chronic Q fever, the other chronic manifestations are vascular infections, chronic infections after pregnancy, and other rare chronic forms such as osteomyelitis, chronic hepatitis, pseudotumour of the lung or infectious arthritis [2Brouqui P Tissot-Dupont H Drancourt M et al.Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis.Arch Intern Med. 1993; 153: 642-648Crossref PubMed Google Scholar]. Liver involvement is common in acute Q fever, and percutaneous liver biopsy can help in the diagnosis. On the other hand, cases of chronic Q fever hepatitis are rarely reported in the literature, and are frequently associated with endocarditis [1Raoult D Tissot-Dupont H Foucault C et al.Q fever 1985–1998. Clinical and epidemiologic features of 1,383 infections.Medicine. 2000; 79: 109-123Crossref PubMed Scopus (431) Google Scholar, 2Brouqui P Tissot-Dupont H Drancourt M et al.Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis.Arch Intern Med. 1993; 153: 642-648Crossref PubMed Google Scholar, 3Stein A Raoult D Q fever endocarditis.Eur Heart J. 1995; 16: 19-23Crossref PubMed Google Scholar, 4Turck WPG Howitt G Turnberg LA et al.Chronic Q fever.Q J Med. 1987; 45: 193-217Google Scholar]. We report in this study the first immunohistochemical detection of C. burnetii in a case of chronic Q fever hepatitis associated with a Q fever endocarditis using a peroxidase-based method and paraffin-embedded tissues. A 30-year-old man suffered from acute Q fever in May 2004 with fatigue, fever, headaches, polyarthralgia, and hepatomegaly. Laboratory findings showed a thrombocytopenia, an increase of liver function indicators (aspartate aminotransferase × 5, alanine aminotransferase × 5, alkaline phosphatase × 2, γ-glutamyltransferase × 2), C-reactive protein × 13, and a prothrombin level of 86%. Q fever was diagnosed by serology. IgG, IgM and IgA titres to phases I and II of C. burnetii were estimated using an indirect microimmunofluorescence assay as previously described [5Tissot-Dupont H Thirion X Raoult D Q fever serology: cutoff determination for microimmunofluorescence.Clin Diagn Lab Immunol. 1994; 1: 189-196PubMed Google Scholar]. To prevent the presence of rheumatoid factors influencing the results, IgM antibodies were removed from the samples before titration of IgG and IgA. Formalin-fixed paraffin-embedded liver specimens were cut to 3-μm thickness and stained with haematoxylin–eosin–saffron, using routine methods. Serial sections were also obtained to perform special stains and immunohistochemical investigations. Special stains, including periodic acid–Schiff, Giemsa, Gram, Grocott–Gomori methenamine silver, Ziehl, and Warthin–Starry stains, were used for detection of bacteria and fungi. Immunohistochemical analysis was performed with a monoclonal anti-C. burnetii mouse antibody as previously described [6Lepidi H Houpikian P Liang Z Raoult D Cardiac valves in patients with Q fever endocarditis: microbiological, molecular, and histologic studies.J Infect Dis. 2003; 187: 1097-1106Crossref PubMed Scopus (101) Google Scholar]. In our laboratory, IgG titres of >1 : 800 are regarded as being diagnostic for chronic Q fever [7Fournier PE Marrie T Raoult D Diagnosis of Q fever.J Clin Microbiol. 1998; 36: 1823-1834PubMed Google Scholar]. The patient exhibited antibody titres to phase I C. burnetii of 1 : 1600, 0 and 0 for IgG, IgM and IgA, respectively, and antibody titres to phase II C. burnetii of 1 : 3200, 0 and 0 for IgG, IgM and IgA, respectively. Isolation of C. burnetii by culture from liver biopsy specimens was not performed. Transoesophageal echocardiography showed a moderate insufficiency of the mitral valve without vegetations. Liver biopsy revealed numerous granulomas disseminated in the liver parenchyma outside the portobiliary spaces. These granulomas were composed mainly of macrophages, without neutrophils, central clear space and fibrin ring. With the immunohistochemical analysis, bacteria were seen as coarse granular immunopositive material in the macrophage cytoplasm (Fig. 1). C. burnetii could only be visualized within liver granulomas, as small, focal collections of infected mononuclear cells with a macrophage morphology. Typical histopathological findings that may be detected in liver specimens during acute Q fever consist of granulomas with a central clear space surrounded by peripheral epithelioid macrophages and lymphocytes. These inflammatory mononuclear cells are often associated in the granulomas with neutrophils and a fibrin ring within or surrounding the granulomas [7Fournier PE Marrie T Raoult D Diagnosis of Q fever.J Clin Microbiol. 1998; 36: 1823-1834PubMed Google Scholar, 8Dupont HL Hornick RB Levin HS Rapoport MI Woodward TE Q fever hepatitis.Ann Intern Med. 1971; 74: 198-206Crossref PubMed Scopus (58) Google Scholar, 9Hofmann CE Heaton Jr, JW Q fever hepatitis. Clinical manifestations and pathological findings.Gastroenterology. 1982; 83: 474-479PubMed Scopus (63) Google Scholar, 10Pellegrin M Delsol G Auvergnat JC et al.Granulomatous hepatitis in Q fever.Hum Pathol. 1980; 11: 51-57Abstract Full Text PDF PubMed Scopus (86) Google Scholar]. On the other hand, immunodection of C. burnetii is negative because patients are able to develop an effective cellular immune response against the bacterium. In contrast, during chronic Q fever, whatever the location, C. burnetii is immunodetected in macrophages. This study represents the first immunodetection of C. burnetii in liver during chronic Q fever. C. burnetii has been also immunodetected in cardiac valves in patients with Q fever endocarditis [6Lepidi H Houpikian P Liang Z Raoult D Cardiac valves in patients with Q fever endocarditis: microbiological, molecular, and histologic studies.J Infect Dis. 2003; 187: 1097-1106Crossref PubMed Scopus (101) Google Scholar]. These observations suggest that patients with chronic Q fever are unable to develop an effective immune response to destroy the bacterium, despite the formation of liver granulomas in the patient studied [11Raoult D Marrie T Mege JL Natural history and pathophysiology of Q fever.Lancet Infect Dis. 2005; 5: 219-226Abstract Full Text Full Text PDF PubMed Scopus (519) Google Scholar]. Few cases of isolated chronic Q fever hepatitis have been described [4Turck WPG Howitt G Turnberg LA et al.Chronic Q fever.Q J Med. 1987; 45: 193-217Google Scholar]. In the series of Raoult et al. [1Raoult D Tissot-Dupont H Foucault C et al.Q fever 1985–1998. Clinical and epidemiologic features of 1,383 infections.Medicine. 2000; 79: 109-123Crossref PubMed Scopus (431) Google Scholar], eight patients presented isolated chronic hepatitis with normal echocardiography. Yebra et al. [12Yebra M Marazuela M Albarran F Moreno A Chronic Q fever hepatitis.Rev Infect Dis. 1988; 10: 1229-1230Crossref PubMed Scopus (21) Google Scholar] described an acute phase of hepatitis in a young man that evolved to chronicity with persistence of pathological liver abnormalities 2 years after intial diagnosis. More often, as in the patient studied in this case, chronic Q fever involvement of the liver is associated with endocarditis [2Brouqui P Tissot-Dupont H Drancourt M et al.Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis.Arch Intern Med. 1993; 153: 642-648Crossref PubMed Google Scholar, 3Stein A Raoult D Q fever endocarditis.Eur Heart J. 1995; 16: 19-23Crossref PubMed Google Scholar]. The exclusion of a diagnosis of Q fever endocarditis based on echocardiographic examination is necessary to confirm the location of chronic Q fever as being only in the liver. In conclusion, the role of the pathologist can be decisive in recognition of the involvement of the liver during Q fever, especially when the microbiologist fails to isolate the causative microorganism. C. burnetii can be detected by immunohistochemical analysis during chronic Q fever hepatitis, one of the causes of granulomatous hepatitis." @default.
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• W1569598026 title "Immunohistochemical detection of Coxiella burnetii in chronic Q fever hepatitis" @default.
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