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A case of pleurisy associated with antibodies to Rickettsia conorii

2003; Elsevier BV; Volume: 9; Issue: 5 Linguagem: Inglês

10.1046/j.1469-0691.2003.00539.x

1469-0691

S. Alexiou‐Daniel, Afrodite Tea, George Ilonidis, Antonis Ántoniadis,

Vector-Borne Animal Diseases

Rickettsia conorii is endemic in Mediterranean area. We describe an unusual sace of R. Conorii infection, which concerns a farmer with clinical, radiological and cytological findings of pleurisy without evidence of malignancy. An elevated antibody titre for R. Conorii was observed, using an indirect immunofluorescent antibody test. After treatment with Doxycycline, the patient presented a significant improvement of his clinical and radiological image and a four-fold decrease of the antibody titre for R. conorii. Rickettsia conorii is endemic in Mediterranean area. We describe an unusual sace of R. Conorii infection, which concerns a farmer with clinical, radiological and cytological findings of pleurisy without evidence of malignancy. An elevated antibody titre for R. Conorii was observed, using an indirect immunofluorescent antibody test. After treatment with Doxycycline, the patient presented a significant improvement of his clinical and radiological image and a four-fold decrease of the antibody titre for R. conorii. Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii [1Raoult D Roux V Rickettsioses as paradigms of new or emerging infectious diseases.Clin Microbiol Rev. 1997; 10: 694-719PubMed Google Scholar, 2Parola P Raoult D Ticks and tickborne disease: an emerging threat.Clin Infect Dis. 2001; 32: 897-928Crossref PubMed Scopus (743) Google Scholar]. Several classical clinical features have been proposed to facilitate the diagnosis in the typical, and usually mild, forms of the disease [1Raoult D Roux V Rickettsioses as paradigms of new or emerging infectious diseases.Clin Microbiol Rev. 1997; 10: 694-719PubMed Google Scholar, 2Parola P Raoult D Ticks and tickborne disease: an emerging threat.Clin Infect Dis. 2001; 32: 897-928Crossref PubMed Scopus (743) Google Scholar]. However, unusual manifestations, which have been mainly reported in the severe forms, complicate the diagnosis [3Raoult D Zuchelli P Weiller PJ et al.Incidence, clinical observations and risk factors in the severe form of Mediterranean spotted fever among patients admitted to hospital in Marseilles 1983-1984.Infection. 1986; 12: 111-116Abstract Full Text PDF Scopus (96) Google Scholar]. We present an unusual case of pleurisy associated with antibodies to Rickettsia conorii. A 30-year-old immunocompetent man, a farmer from a rural area of northern Greece, presented at the pulmonary clinic of the Kastoria General Hospital with a 10-day history of headache, low-grade fever, chills, myalgia, dry cough and left pleuritic chest pain. The physical examination disclosed fever (38 °C) and diminished breath sounds over the left lung. Liver and spleen were not enlarged, and there were no peripheral lymph nodes palpable. No rash was observed. A chest X-ray showed a pleural effusion without any involvement of the lungs. The patient received cefuroxime intravenously for 2 days and diclofenac orally, but the symptoms persisted. Because his condition worsened despite therapy, he was eventually admitted to the Hippokrates Hospital of Thessaloniki. During his hospitalization, the fever increased (40 °C), while the rest of the initial symptoms persisted. Neither rash nor inoculation eschar was observed. The laboratory studies revealed an elevated C-reactive protein (CRP) level (78 mg/L), accelerated erythrocyte sedimentation rate (ESR) (82 mm/h), a white blood cell count of 24 000/mm3, a platelet count of 114 000/mm3, and slightly elevated serum alanine and aspartate aminotransferases, as well as lactate dehydrogenase (Table 1). Arterial blood gas measurements were normal. D-Dimer testing was negative (<0.5 mg/L). The blood and sputum cultures were negative, and the tuberculin skin test was also negative.Table 1Changes in results of laboratory investigationsVariableOn admissionAfter doxycycline3 months laterBlood samplingC-reactive protein (mg/L)7825<12Erythrocyte sedimentation rate (mm/h)82407Hematocrit (%)434242Platelets (per mm3)114000123 000288 000Leukocyte count (per mm3)24 20010 0008600Neutrophils (%)766256Lymphocytes (%)173137Monocytes (%)656Eosinophils (%)121Creatinine (μmol/L)697168Sodium (mmol/L)142141140Potassium (mmol/L)4.34.24.3Alanine aminotransferase (U/L)584524Aspartate aminotransferase (U/L)474232Lactate dehydrogenase (U/L)248195187Alkaline phosphatase (U/L)606267γ-Glutamyl transpeptidase (U/L)353535ThoracocentesisTotal protein (g/dL)5.6Glucose (mmol/L)3Lactate dehydrogenase (U/L)560Leukocyte count (per mm3)1200Neutrophils (%)73Lymphocytes (%)27pH71 Open table in a new tab A CT scan of the thorax (Figure 1) confirmed the presence of a pleural effusion with pressure atelectasis of the left lower lung. There were no abnormal findings in the right lung. Abnormal mediastinal lymph nodes were not found. Thoracocentesis and laboratory analysis of the pleural fluid was performed (Table 1). The cytologic examination showed no evidence of malignancy. There was no growth on routine microbiological culture, and Ziehl-Neelsen staining for acid-fast bacilli (AFB) and culture on Lowenstein-Jensen medium were both negative. The patient received amoxicillin-clavulanic acid intravenously for 3 days without clinical improvement. The treatment was subsequently changed to intravenous imipenem and cilastatin sodium and intravenous prednisolone for 5 days, after which the patient's fever declined but the pleural effusion persisted. The use of a thoracic drainage tube was not considered, as the patient did not have severe dyspnea. An indirect immunofluorescent (IFA) antibody test on day 28 after disease onset revealed elevated IgM and IgG titers for R. conorii (1:512 and 1:1024, respectively). The Weil-Felix agglutination test (WFT) using Proteus vulgaris OX-2 antigen was positive at a titer of 1:400 and negative for Proteus vulgaris OX-19 and OX-K antigens. Tests to detect specific antibodies to influenza A and B viruses, parainfluenza viruses, adenoviruses, respiratory syncytial virus, Epstein-Barr virus, Mycoplasma pneumoniae, Chlamydia spp., Legionella pneumophila, Coxiella burnetti, R. typhi, human granulocytic ehrlichiosis (HGE) agent and Leptospira spp. were negative. Widal and Wright agglutination tests, used for the serologic diagnosis of typhoid fever and brucellosis, respectively, were negative. As a result, the patient was treated with doxycycline at a dose of 200 mg orally per day. A significant improvement in his clinical condition was noted on the third day of treatment. Chest X-ray showed a decrease in the amount of pleural fluid. A laboratory follow-up showed reductions in CRP and ESR (Table 1). The administration of doxycycline was discontinued 15 days later, when the patient had already been discharged from the hospital. On day 50 after disease onset, a second serum sample tested by IFA revealed IgG and IgM antibodies to R. conorii at titers of 1:256 and 1:128, respectively, while WFT using P. vulgaris OX-2 had increased in titer to 1:800. Three months later, in a third serum sample, the IgG antibody titer to R. conorii was 1:128, whereas no IgM antibodies were detectable and the WFT was negative. MSF, also known as boutonneuse fever, was described in 1910 in Tunis [4Conor A Bruch A Une fièvre éruptive observée en Tunisie.Bull Soc Pathol Exot Filial. 1910; 8: 492-496Google Scholar]. Tick-borne diseases are geographically localized, and MSF is found from southern Europe to southwestern Asia, India, and Africa [1Raoult D Roux V Rickettsioses as paradigms of new or emerging infectious diseases.Clin Microbiol Rev. 1997; 10: 694-719PubMed Google Scholar, 2Parola P Raoult D Ticks and tickborne disease: an emerging threat.Clin Infect Dis. 2001; 32: 897-928Crossref PubMed Scopus (743) Google Scholar]. The disease is significantly seasonal, with most cases appearing in the spring and summer months [5Font-Creus B Bella-Cueto F Espejo-Arenas E et al.Mediterranean spotted fever: a cooperative study of 227 cases.Rev Infect Dis. 1985; 7: 635-642Crossref PubMed Scopus (98) Google Scholar, 6Raoult D Weiller PJ Chagnon A Chaudet H Gallais H Casanova P Mediterranean spotted fever: clinical, laboratory and epidemiological features of 199 cases.Am J Trop Med Hygiene. 1985; 35: 845-850Google Scholar]. In recent years, there has been an increasing incidence of MSF in several Mediterranean countries [5Font-Creus B Bella-Cueto F Espejo-Arenas E et al.Mediterranean spotted fever: a cooperative study of 227 cases.Rev Infect Dis. 1985; 7: 635-642Crossref PubMed Scopus (98) Google Scholar, 6Raoult D Weiller PJ Chagnon A Chaudet H Gallais H Casanova P Mediterranean spotted fever: clinical, laboratory and epidemiological features of 199 cases.Am J Trop Med Hygiene. 1985; 35: 845-850Google Scholar]. Seroepidemiologic studies in the healthy Greek population have shown a high seroprevalence of R. conorii [7Antoniou M Tselentis Y Babalis T et al.The seroprevalence of ten zoonoses in two villages of Crete.Eur J Epidemiol. 1995; 11: 415-423Crossref PubMed Scopus (24) Google Scholar]. Our patient displayed some of the classical symptoms of MSF and the infection appeared during the spring. However, there was no history of tick bite, and there was no initial black lesion ('tache noir'), which is of high diagnostic value. However, it is reported that this characteristic eschar may be absent in 28% of the patients suffering from MSF [5Font-Creus B Bella-Cueto F Espejo-Arenas E et al.Mediterranean spotted fever: a cooperative study of 227 cases.Rev Infect Dis. 1985; 7: 635-642Crossref PubMed Scopus (98) Google Scholar, 6Raoult D Weiller PJ Chagnon A Chaudet H Gallais H Casanova P Mediterranean spotted fever: clinical, laboratory and epidemiological features of 199 cases.Am J Trop Med Hygiene. 1985; 35: 845-850Google Scholar]. While respiratory involvement is reported in 30% of Rocky Mountain spotted fever cases [8Helmick CG Bernard KW D'Angelo LJ Rocky Mountain Spotted Fever. Clinical, laboratory, and epidemiological features of 262 cases.J Infect Dis. 1984; 150: 480-484Crossref PubMed Scopus (218) Google Scholar], it is quite rare in MSF. Pleurisy caused by R. conorii infection is an extremely unusual clinical manifestation [5Font-Creus B Bella-Cueto F Espejo-Arenas E et al.Mediterranean spotted fever: a cooperative study of 227 cases.Rev Infect Dis. 1985; 7: 635-642Crossref PubMed Scopus (98) Google Scholar, 6Raoult D Weiller PJ Chagnon A Chaudet H Gallais H Casanova P Mediterranean spotted fever: clinical, laboratory and epidemiological features of 199 cases.Am J Trop Med Hygiene. 1985; 35: 845-850Google Scholar, 9Pieron R Lesobre B Mafart Y Meyniel D Coppin M Pulmonary, pleural and pericardial manifestations of rickettsiosis.Poumon Coeur. 1976; 32: 161-167PubMed Google Scholar, 10Lemenager J Morel C Benard Y Freymuth F Rickettsioses pleuro-pulmonaires. A propos de 30 observations.Nouv Presse Med. 1972; 1: 2622PubMed Google Scholar]. According to Light's criteria, the pleural effusion was exudative. There was no evidence of malignancy or pleural tuberculosis [11Light RW Management of pleural effusions.J Formos Med Assoc. 2000; 99: 523-531PubMed Google Scholar]. D-Dimer testing, which is a good screen for pulmonary emboli, was negative [12Light RW Pleural effusion due to pulmonary emboli.Curr Opin Pulm Med. 2001; 7: 198-201Crossref PubMed Scopus (39) Google Scholar]. IFA for the detection of IgM and IgG antibodies to R. conorii is considered to be the test of choice for serologic diagnosis, and is used as a reference technique in most laboratories [13Lascola B Raoult D Laboratory diagnosis of rickettsioses: current approaches to diagnosis of old and new rickettsial diseases.J Clin Microbiol. 1997; 35: 2715-2727PubMed Google Scholar]. The WFT was the only diagnostic method in the past, but it is less specific and sensitive, and therefore is not to be relied on [14Raoult D Rousseau S Toga B et al.Serology diagnosis of Mediterranean boutonneuse fever.Pathol Biol. 1984; 32: 791-794PubMed Google Scholar]. However, authors often observe a good correlation between WFT and the detection of IgM antibodies by IFA [15Amano K Suzuki N Hatakeyama H et al.The reactivity between rickettsiae and Weil-Felix test antigens against sera of rickettsial disease patients.Acta Virol. 1992; 36: 67-72PubMed Google Scholar, 16Amano K Hatakeyama H Okutta M Sutto T Mahara F Serological studies of antigenic similarity between Japanese Spotted Fever Rickettsiae and Weil-Felix test antigens.J Clin Microbiol. 1992; 30: 2441-2446PubMed Google Scholar]. We used this test only to support our findings. The serologic diagnosis of infectious diseases is usually made by the detection of a significant increase in antibody titers between the acute and the convalescent phases of the disease. In our case, the laboratory diagnosis was established by the high titers of IgM and IgG antibodies (titers 1:512 and 1:2048, respectively) to R. conorii on the 28th day of illness, and the fourfold decrease in antibodies on the 50th day (to titers of 1:128 and 1:256, respectively). This form of seroconversion could be explained by the fact that the two serum samples were obtained during the convalescence phase of the disease. The patient was treated with several antibiotics for approximately 30 days, without any improvement of his clinical condition. The impressive clinical and radiologic improvement of the patient following the administration of doxycycline, which is considered to be one of the most effective antibiotics in rickettsial infections, also supports the diagnosis [17Maurin M Raoul D Antimicrobial therapy of rickettsial diseases.in: Raoult D Brouqui P Rickettsiae and rickettsial diseases at the turn of the third millennium. Elsevier, Paris1999: 330-343Google Scholar]. However, as Rickettsia is known to generate cross-reacting antibodies, and no other evidence of R. conorii was found, these symptoms may have been caused by an unidentified cross-reacting microorganism. Although MSF is endemic in Greece, rickettsiosis is not being reported, a fact which may lead physicians to underestimate the incidence of the disease. Despite its rarity, R. conorii infection should be included in the differential diagnosis of pleurisy, especially when other infectious agents are excluded, and treatment with commonly used antibiotics fails to improve the patient's clinical and radiologic condition.