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Treatment Resistant Lyme Arthritis Caused by Borrelia Garinii

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Treatment Resistant Lyme Arthritis Caused by Borrelia Garinii 284 Ann Rheum Dis 2001;60:284–286 Treatment resistant Lyme arthritis caused by Ann Rheum Dis: first published as 10.1136/ard.60.3.284 on 1 March 2001. Downloaded from Borrelia garinii F-X Limbach, B Jaulhac, X Puechal, H Monteil, J-L Kuntz, Y Piemont, J Sibilia Abstract Recently, four European groups4–7 and our Lyme arthritis is caused in Europe by own8 identified the Borrelia species involved in three main pathogenic species of Borrelia some forms of Lyme arthritis. A variety of burgdorferi sensu lato: Borrelia burgdor- identification techniques were used, including feri sensu stricto, Borrelia garinii, and DNA sequencing of OspA,4 OspA species- Borrelia afzelii. Because few synovial specific primers,5 and reverse line blotting67of samples have yet been analysed by synovial fluid. Discordant results were ob- species-specific DNA amplification meth- tained, particularly concerning the role of B ods, further studies are needed to define garinii, while the clinical presentation and out- the spectra of clinical manifestations come of patients were not described in detail. associated with these diVerent species. Furthermore, because only a few synovial fluid Two cases of treatment resistant Lyme samples were analysed by species-specific arthritis are reported here, in which DNA DNA amplification methods, studies are still amplification of the flagellin gene followed needed to determine which spectrum of by dot-blot hybridisation in the synovial clinical manifestations is associated with B fluid identified B garinii as the causative garinii. In the present work we describe two agent. Clinical and biological data did not patients with treatment resistant Lyme arthri- diVer from the usual descriptions of Lyme tis, in whom DNA amplification and dot-blot arthritis, but as the recently reported hybridisation identified B garinii as the causa- molecular mimicry between OspA and tive species. hLFA1 is not applicable to B garinii, the pathogenesis of the present cases remains Case reports unclear. Future studies should aim at PATIENT 1 assessing the role of B garinii in European Patient 1, a 41 year old woman, presented in Lyme arthritis and its possible pathogenic December 1993 with a history of monarthritis and therapeutic consequences. of the right knee. This had developed in August (Ann Rheum Dis 2001;60:284–286) 1991, a few months after the disappearance of a concentric erythematous eruption on the http://ard.bmj.com/ Lyme borreliosis is a multisystemic disease calf. She could not recall having been bitten by a tick during her frequent forest walks near caused by the spirochaete Borrelia burgdorferi Paris (France). The right knee swelling had (B burgdorferi) sensu lato. On the basis of DNA been treated several times between August similarities, three principal pathogenic species 1991 and January 1993 with corticosteroid Rheumatology of B burgdorferi sensu lato have been identified, infiltrations, but this treatment had never been Department, Hôpitaux B burgdorferi sensu stricto, B afzelii, and B gari- Universitaires de eVective for more than six months. The patient Strasbourg, France nii. Lyme arthritis would seem to be the most had no history of psoriasis, low back pain, or on September 29, 2021 by guest. Protected copyright. F-X Limbach commonly disseminated form of the disease in genital infection. J-L Kuntz the USA, whereas late cutaneous manifesta- J Sibilia On examination at the rheumatology depart- tions of Lyme borreliosis occur almost exclu- ment the right knee was found to be swollen, sively in Europe. This observation, together Bacteriology though with minimal pain. The synovial fluid Department, Hôpitaux with the fact that although all three pathogenic contained 28 × 109 leucocytes/l (64% polymor- Universitaires et species are present in Europe only B burgdorferi phonuclear cells and 36% lymphocytes), while Faculté de Médecine sensu stricto has been isolated in North a synovial biopsy specimen showed a dense de Strasbourg, France America, has led to the hypothesis that the tro- inflammatory infiltrate of lymphocytes and B Jaulhac pism of the diVerent species of B burgdorferi H Monteil plasmocytes. Tests for antinuclear antibodies Y Piemont sensu lato can be either articular, cutaneous, or and rheumatoid factor were negative and the neurological. Because it has been reported that patient’s haplotype was HLA-B18/40 and Rheumatology patient serum samples might react more DRB1*0403/*0404. Radiographs of the right Department, Hôpital strongly with heterologous than with homolo- knee showed demineralisation without any Universitaire Cochin, gous strains,1 serological methods are not suit- erosion. Chlamydia trachomatis serology was Paris, France X Puechal able to assess this correlation, and culture negative. A serological enzyme linked immuno- techniques likewise cannot be applied to syno- sorbent assay (ELISA) test for Lyme disease Correspondence to: vial tissue or fluid. Hence the only reliable was strongly positive with values of 4.2 for IgG Dr J Sibilia, Service de methods for typing Borrelia strains in synovial (>1.1 positive) and negative for IgM, which Rhumatologie, CHU Strasbourg Hautepierre, samples are based on DNA amplification. were confirmed by western blot analyses. 1 Avenue Molière, 67098 When such direct identification methods were Because only small amounts of synovial fluid Strasbourg used, acrodermatitis chronica atrophicans and were available, DNA amplification specific for [email protected] neuroborreliosis were found to be mainly asso- B burgdorferi sensu lato was not interpretable. Accepted 28 June 2000 ciated with B afzelii2 and B garinii,3 respectively. The patient was treated with doxycycline www.annrheumdis.com Lyme arthritis caused by Borrelia garinii 285 (200 mg/day) for one month, with a transient ceftriaxone (2 g/day) and was completely Ann Rheum Dis: first published as 10.1136/ard.60.3.284 on 1 March 2001. Downloaded from recovery. cured, with no recurrence after an 18 months’ In July 1994 the patient had her first relapse follow up. since antibiotic treatment. Puncture of the knee yielded 10 ml of fluid containing 10.4 × Methods 109 leucocytes/l (21% polymorphonuclear cells Synovial fluid samples were obtained from and 68% lymphocytes), while serological each patient by needle puncture. PCR amplifi- ELISA tests gave a value of 2.5 for IgG and cation of a central part of the flagellin gene, were negative for IgM. The patient was treated using as primers two oligonucleotides specific parenterally with ceftriaxone (2 g/day) for three for all B burgdorferi sensu lato species, was per- weeks. Owing to persistent swelling, triamci- formed as previously described9 with both nolone hexacetonide (40 mg) was injected into synovial fluids and gave positive results. To the knee, with successful results. avoid DNA contamination of samples, precau- When painful swelling recurred in January tions previously described9 were taken. A 1995, knee puncture disclosed a synovial fluid species-specific dot-blot hybridisation assay8 containing 7.8 × 109 leucocytes/l (45% poly- was then performed on the PCR products. Oli- morphonuclear cells and 20% lymphocytes). gonucleotide probes specific for the following In this last fluid, DNA amplification using a B burgdorferi sensu lato species were used: B polymerase chain reaction (PCR) specific for B burgdorferi sensu stricto, B garinii, B afzelii, B burgdorferi sensu lato9 was positive. The patient japonica, B andersonii, B valaisiana, and B was successfully treated by an intra-articular bissettii. Synovial samples from the two patients injection of 10 ml of 1% osmic acid. hybridised only with the B garinii probe and In October 1995 symptoms recurred, and there was no evidence of mixed infection. knee puncture yielded 25 ml of inflammatory synovial fluid. A third course of antibiotic Discussion treatment was given, ceftriaxone (2 g/day) This is the first description of Lyme arthritis parenterally for three weeks. There was further caused by B garinii, which was treatment swelling in 1996 requiring the removal of 40 ml resistant in the first case and amoxicillin resist- of synovial fluid (6.2 × 109 leucocytes/l, 90% of ant in the second, albeit after intra-articular which were lymphocytes), and in 1998 still a corticosteroids. Although a diagnosis of Lyme little swelling of the right knee persisted. arthritis is obvious for the second patient, the history of the first patient is more complicated. PATIENT 2 However, this diagnosis was retained based on Patient 2, a 27 year old man living in the East the following data: possible erythema migrans, of France, was referred in February 1998 for recurrent monarthritis with a positive serology arthritis of the left knee. An eVusion of the left for B burgdorferi, positive PCR, the specificity of knee joint, which had developed five months which has previously been shown to be previously, had been treated initially with non- absolute9 for B burgdorferi when precautions are steroidal anti-inflammatory drugs and, because taken to avoid cross contamination between http://ard.bmj.com/ of a lack of eYcacy, with an intra-articular cor- samples. No other diagnosis was made after tivazol injection in November 1997. After a seven years’ follow up. It is noteworthy that the transient improvement, swelling of the left knee clinical manifestations and biological data of had recurred 15 days later. As this patient lives these patients did not diVer from the usual in an endemic area, was frequently bitten by descriptions of Lyme arthritis. Thus both had a ticks, and had a possible previous history of possible history of tick bites and erythema erythema migrans in September 1996, treat- migrans, knee arthritis with marked swelling ment with amoxicillin (4 g/day orally) was but minimal pain, and concordant serological on September 29, 2021 by guest. Protected copyright. given in December 1997 for three weeks but data. This uniform clinical presentation of without eVect. Lyme arthritis, whatever the species involved, Physical examination showed a marked diVers from the recent reports of patients pre- swelling of the left knee, which was moderately senting with erythema migrans, in whom painful.
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