Reactive and undifferentiated arthritis in North Africa: use of PCR for detection of Chlamydia trachomatis.

Little is known about the possible role of Chlamydia in patients with reactive or unclassified arthritis in North Africa. This study used polymerase chain reaction (PCR) to survey this population. In addition, we compared the results in three different laboratories for PCR analyses for Chlamydia trachomatis (Ct) in synovial fluid (SF) and tissue (ST) from these North African patients with reactive arthritis (ReA), undifferentiated arthritis (UA), and in rheumatoid arthritis (RA) and osteoarthritis (OA). Eight ReA (six posturethritic, two postenteritic), 23 UA, 13 OA, and 12 RA patients were studied in Algeria, Morocco, and Tunisia. Serum, SF, and ST were obtained from each patient. Ct-PCR was performed in the three different laboratories and compared to Ct-serology [microimmunofluorescence (MIF) and anti-hsp60 enzyme-linked immunosorbent assay (ELISA)] performed in one laboratory. The rate of Ct-PCR positivity in SF/ST was low: none out of the eight ReA and three out of 23 UA patients. In the controls, Ct DNA was detected in two OA SF and in one RA SF. There was no concordance for Ct-PCR positivity between the three laboratories. MIF suggested previous Ct infection (IgG-positive) in two out of five posturethritic ReA, none out of one postenteritic ReA, one out of 17 UA, and nine out of 21 RA/OA patients tested. No MIF-positive patient was PCR-positive from SF or ST. However, anti-hsp60 IgG was detected in all four out of four patients positive by PCR and in 11 out of 44 PCR-negative patients (p = 0.002). In this multinational comparative study, the rate of Ct-PCR-positive synovial specimens in North African ReA/UA patients was low. Concordance among the three PCR testing laboratories was poor indicating the need for test standardization. All Ct-PCR-positive patients were found positive by anti-hsp60 IgG serology.

Fibromyalgia: a randomised, controlled trial of a treatment programme based on self management.

OBJECTIVE: To evaluate the efficacy of a treatment programme for patients with fibromyalgia (FM) based on self management, using pool exercises and education. METHODS: Randomised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme; 164 patients with FM were allocated to an immediate 6 week programme (n = 84) or to a waiting list control group (n = 80). The main outcomes were changes in quality of life, functional consequences, patient satisfaction and pain, using a combination of patient questionnaires and clinical examinations. The questionnaires included the Fibromyalgia Impact Questionnaire (FIQ), Psychological General Well-Being (PGWB) index, regional pain score diagrams, and patient satisfaction measures. RESULTS: 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations. Six months after programme completion, significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ (total score p = 0.025; fatigue p = 0.003; depression p = 0.031) and PGWB (total score p = 0.032; anxiety p = 0.011; vitality p = 0.013,). All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups; between-group differences were statistically significant for "control of symptoms", "psychosocial factors", and "physical therapy" No change in pain was seen. CONCLUSION: A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment. These improvements are sustained for at least 6 months after programme completion.

Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.

OBJECTIVE: To determine whether abnormalities of peripheral and central nociceptive sensory input processing exist outside areas of spontaneous pain in patients with fibromyalgia (FM) as compared with controls, by using quantitative sensory testing (QST) and a neurophysiologic paradigm independent from subjective reports. METHODS: A total of 164 outpatients with FM who were attending a self-management program were invited to participate in the study. Data for 85 patients were available and were compared with those for 40 non-FM controls matched for age and sex. QST was performed using thermal, mechanical, and electrical stimuli at locations of nonspontaneous pain. Pain assessment was 2-fold and included use of subjective scales and the spinal nociceptive flexion reflex (NFR), a specific physiologic correlate for the objective evaluation of central nociceptive pathways. Questionnaires regarding quality of life and the impact of FM were available. RESULTS: Participants were mainly middle-aged women, with a mean disease duration of 8 years. Between-group differences were significant for neurophysiologic, clinical, and quality of life measures. In patients with FM, peripheral QST showed significantly altered cold and heat pain thresholds, and tolerance to cold pain was radically reduced. The median NFR threshold in patients with FM (22.7 mA [range 17.5-31.7]) was significantly decreased compared with that in controls (33 mA [range 28.1-41]). A cutoff value of <27.6 mA for NFR provided sensitivity of 73% and specificity of 80% for detecting central allodynia in the setting of FM. CONCLUSION: Our results strongly, although indirectly, point to a state of central hyperexcitability of the nociceptive system in patients with FM. The NFR can be used to assess central allodynia in FM. It may also help discriminate patients who may benefit from use of centrally acting analgesics.

Importance of species-specific antigens in the serodiagnosis of Chlamydia trachomatis reactive arthritis.

OBJECTIVES: To determine the most sensitive and specific method of anti-Chlamydia antibody measurement for the serodiagnosis of Chlamydia trachomatis reactive arthritis. METHODS: Immunoblotting, enzyme-linked immunosorbent assays using six synthetic peptides or recombinant antigens and a microimmunofluorescence test were used to determine the presence of IgG, IgM and IgA in serum samples from 17 patients with C. trachomatis reactive arthritis. Twenty patients with other inflammatory arthropathies without evidence of urogenital C. trachomatis infection were used as controls. RESULTS: The best association of sensitivity (76%) and specificity (85%) was obtained when IgG and/or IgA reactivity to two species-specific antigens was determined. These antigens were synthetic peptides, derived from species-specific epitopes in the variable domain IV of the major outer membrane protein (MOMP) (Labsystems, Finland) and recombinant polypeptide encoded by open reading frame 3 of the plasmid (pgp3). CONCLUSIONS: IgG and/or IgA anti-MOMP-derived peptides and anti-pgp3 could be useful for the diagnosis of probable C. trachomatis reactive arthritis.

A six year prospective study of a cohort of patients with fibromyalgia.

OBJECTIVES: To examine the long term prognosis in patients with fibromyalgia (FM). METHODS: Forty five of 70 patients who had participated in a three week trial six years earlier completed again the same questionnaires used previously. RESULTS: Most symptoms had remained stable. Pain had increased, but some aspects of quality of life had improved over time. CONCLUSION: Symptoms of FM persisted over the six years, but patients appeared better able to cope with them.

Comparative study of different enzyme immunoassays for measurement of IgM and IgA rheumatoid factors.

OBJECTIVE: To compare the value of various IgM and IgA rheumatoid factor (RF) tests for the diagnosis of rheumatoid arthritis (RA). METHODS: Firstly, the latex test, one global assay (for IgM, IgA, and IgG RF), six IgM, and four IgA RF assays were compared in a particularly challenging situation-that is, with 67 patients with RA, many of whom were latex negative, and 91 non-RA controls, many of whom were latex positive. More detailed evaluation followed with three IgM RF tests (two commercially available kits and one assay developed in our laboratory) and two IgA RF tests (one commercially available and one from our laboratory) in two more representative samples of rheumatological patients (146 RA and 75 non-RA controls). RESULTS: Diagnostic performance differed considerably between the assays. For IgM RF detection the highest sensitivity (88%) was obtained with the Diamedix kit (specificity 67%) and for IgA RF with the Inova kit (sensitivity 65%, specificity 88%). Combining one IgM and one IgA RF test improved diagnostic performance when both tests were in agreement, but at the cost of yielding 15-27% of discrepant results which did not help in ruling RA in or out. Mean concentration values differed significantly among IgM RF tests, and in most cases concentrations were not correlated. CONCLUSIONS: Available tests for IgM RF isotype vary in accuracy, and none is uniformly better than all the others. For IgA RF isotype, the Inova kit appears to be the best. Quantitative results cannot be compared across tests. Combination of one IgM and one IgA RF test may improve diagnostic accuracy.

Chlamydia trachomatis serology: diagnostic value of outer membrane protein 2 compared with that of other antigens.

Different immunoassays using recombinant antigens or synthetic peptides were evaluated for the serodiagnosis of Chlamydia trachomatis infections. Antigens used included cysteine-rich outer membrane protein 2 (OMP2), heat shock protein 60, the polypeptide encoded by open reading frame 3 of the plasmid (pgp3), synthetic peptides derived from species-specific epitopes in variable domain IV of the major OMP (MOMP) (Labsystems, Helsinki, Finland), and a fragment of the total lipopolysaccharide (Medac, Hamburg, Germany). Because cross-reactions between chlamydial species have been reported, Chlamydia pneumoniae-specific antibodies were also determined by immunoassays (Labsystems). Responses obtained with serum samples from patients with well-defined diseases (i.e., urethral or endocervical samples from which C. trachomatis DNA was amplified) were compared to those obtained with samples from healthy blood donors. The best sensitivity (79%) associated with the best specificity (82%) was obtained when immunoglobulin G (IgG) responses to both MOMP and pgp3 were considered. The highest sensitivity (89%) was obtained with anti-OMP2 IgG, but the lowest specificity (57%) was obtained with this antibody, due to probable cross-reactivity with C. pneumoniae OMP2.

Indirect evidence of intra-articular immunoglobulin G synthesis in patients with Chlamydia trachomatis reactive arthritis.

OBJECTIVES: To investigate whether B-cell stimulation occurs in joints of Chlamydia trachomatis reactive arthritis patients by comparing the immunoglobulin G (IgG) anti-C. trachomatis antibody responses in serum and synovial fluid (SF). METHODS: The number and spectrum of C. trachomatis antigens recognized by paired serum and SF samples from 16 patients with C. trachomatis reactive arthritis and 20 patients with other inflammatory arthropathies independent of this bacteria, were studied by immunoblotting. The responses to five different Chlamydia antigens were also determined in enzyme-linked immunosorbent assays. RESULTS: In C. trachomatis reactive arthritis patients, a higher number of C. trachomatis antigens was recognized by SF (17.6+/-5.1) than by serum (11.1+/-6.3) IgG and a higher intensity of SF IgG binding to the outer membrane protein 2 (OMP2) was observed. CONCLUSIONS: These results suggest an intra-articular IgG production and a possible role of some Chlamydia antigens like OMP2 in the pathogenesis of C. trachomatis reactive arthritis.

Male sex predominance in Chlamydia trachomatis sexually acquired reactive arthritis: are women more protected by anti-chlamydia antibodies?

OBJECTIVE: To determine whether the humoral anti-chlamydia antibody response might be related to the ineffective bacterial elimination seen in patients with Chlamydia trachomatis reactive arthritis, particularly in men, who have a higher prevalence of the disease than women. METHODS: The number and specificity of the antibody responses to 27 different C trachomatis antigens were determined by western blots in serum samples from patients with C trachomatis urogenital infection, with and without reactive arthritis, with a special regard to the sex of the patients. RESULTS: Patients with reactive arthritis had antibodies to significantly fewer chlamydia antigens than those with urethritis only. Antibodies from men recognised significantly fewer antigens than antibodies from women. The IgA class antibodies were slightly more relevant than those of the IgG class for differentiation of patients with reactive arthritis from those with uncomplicated genitourinary infection. CONCLUSIONS: In patients with acute C trachomatis infection the development of reactive arthritis may be related, particularly in men, to a deficient humoral response, to antigens which perhaps play a part in the clearance of the bacteria. Men who cannot generate antibodies to a large number of antigens may be less able to contain the local infection, allowing a wide systemic dissemination of the organisms to the joints.

Chlamydial serology: comparative diagnostic value of immunoblotting, microimmunofluorescence test, and immunoassays using different recombinant proteins as antigens.

To improve the reliability of the serodiagnosis of Chlamydia trachomatis infections, an immunoblot analysis, a microimmunofluorescence titration, and different immunoassays using synthetic peptides derived from species-specific epitopes in variable domain IV of the major outer membrane protein or recombinant antigens (heat shock protein 70 [hsp70], hsp60, hsp10, polypeptide encoded by open reading frame 3 of the plasmid [pgp3], macrophage infectivity potentiator, and a fragment of the total lipopolysaccharide) were evaluated. Because cross-reactions between chlamydial species have been reported, the microimmunofluorescence tests were also performed with Chlamydia pneumoniae and Chlamydia psittaci used as antigens, and C. pneumoniae-specific antibodies were also determined by immunoassays. Since the presence of antimicrobial antibodies must be interpreted in light of their prevalence in the general population, responses obtained with serum samples from patients with well-defined infection (i.e., with positive urethral or endocervical C. trachomatis DNA amplification) were compared to those obtained with samples from healthy blood donors. The best sensitivity (86%) with a specificity of 81% was obtained for immunoblotting results, when the number of individuals with > or =10 immunoglobulin G (IgG) and/or > or =2 IgM responses to the different C. trachomatis antigens was considered. A 13-kDa antigen was recognized by most of the samples (86% for IgG) from patients with acute urogenital infection but rarely (3%) by those from healthy blood donors (P < 0.0001). The sensitivity and specificity results obtained for serum antibodies to peptides or recombinant antigens were slightly lower than those results obtained for the number of responses to whole C. trachomatis antigens, which were 76 and 77%, respectively, when IgG responses to both recombinant hsp60 and pgp3 were considered.

The representation of the back in idiomatic expressions--do idioms value the body?

OBJECTIVE: Whilst investigating the influence of patients' representations on the impact of teaching in the back school, we took an interest in 1) the place of the back in the French idioms referring to the body; and 2) the meaning these idioms convey about the back. METHODS: The idioms including body part terms were sought on the basis of a compilation of French idioms; it has to be noted that such a compilation, however excellent it may be, can only offer a partial view of lay conversation. Occurrence of body parts and of their connotations were assessed. Idioms were classified as positive, negative or neutral, keeping in mind the difficulties of a strict classification in such a field. Drawings were then performed on the basis of the results of the descriptive analysis. RESULTS: Globally, idiomatic expressions offer a rather negative picture of the body or at least suggest that the body is prominently used to express negative ideas and emotions. This is particularly striking for the idioms associated with the back. CONCLUSION: The analysis of idioms referring to the body allows us to 'see with our own eyes' another aspect of the representations of the body and the back, as they are conveyed in the French language.

Different humoral immune response to Chlamydia trachomatis major outer membrane protein variable domains I and IV in Chlamydia-infected patients with or without reactive arthritis.

OBJECTIVE: The possibility that some bacterial-specific factor(s) may play a role in triggering Chlamydia trachomatis reactive arthritis was investigated. METHODS: Since the variable domains of the major outer membrane protein (MOMP) contain the serovar-determining epitopes of C. trachomatis, the ability of serum IgG to recognize peptides mimicking these epitopes was determined in 2 groups of infected patients, one with and the other without reactive arthritis. Because asymptomatic C. trachomatis infections are frequent, and nonspecific reactions due to inflammation could be observed, this study was also performed with samples from healthy blood donors and from patients with inflammatory arthritis unrelated to C. trachomatis infection. RESULTS: A predominant reactivity against peptides duplicating the J serovar-specific epitopes was only observed in the group of patients with reactive arthritis. For positive samples, differences between the two groups of C. trachomatis-infected patients were clearly observed. The mean numbers of positive responses obtained for each of the 7 peptides of the MOMP domain I or each of the 8 peptides of the MOMP domain IV were significantly higher for samples from patients with reactive arthritis (4.7 and 6) than for those from patients with only C. trachomatis urogenital infection (1.3 and 2.9). CONCLUSION: Patients with reactive arthritis had a pattern of reactivities that was compatible with infection by several serotypes of bacteria. Repeated exposures to C. trachomatis might therefore be involved in the development of the disease.

Is chronic non-specific low back pain chronic? Definitions of a problem and problems of a definition.

BACKGROUND: Chronic low back pain (LBP) accounts for the majority of the disability and costs for LBP. However, the definition of chronicity is unclear. AIM: To elicit practitioners' definitions of chronic LBP patients, both in general and in the patients they were treating; to assess the most common characteristics of these practitioners' chronic LBP patients; and to assess the stability of chronicity in a sample of the general population. METHOD: Semi-structured interviews were conducted with 33 practitioners working in private practice, 71 LBP patients and their therapists, and 252 employees of a chain store who were assessed yearly in a prospective study. RESULTS: The therapists' definitions of chronic LBP patients generally included psychosocial aspects. Only physical symptoms and signs were stressed in the patients they were treating. These patients displayed common characteristics with reference to pain, functional problems, and contact with health care services. Duration of symptoms was not sufficient to define chronicity. In the employee population, chronicity defined according to pain duration was unstable. However, the same was true when chronicity was measured according to the criteria defined in the patient population. CONCLUSION: There is a discrepancy between theory and practice regarding the definition of chronic LBP. This discrepancy concerns not only the literature but also clinical practice itself. The term 'chronic' LBP as currently used is therefore equivocal.

An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition.

In the present study, we tested our hypothesis on the role of a DQ-DR haplotype in rheumatoid arthritis (RA) predisposition. Using two groups of patients and controls, one from The Netherlands and one from Switzerland, we found that DQA1*0301-homozygous and DQA1*0301//DQA1*0101/04-heterozygous individuals are highly predisposed to RA in both populations, while DQA1*0101/04-homozygous are not. The DQA1*0301-DRB1*0403/06/07 and DQA1*0301-DRB1*0901 haplotypes are not associated with RA by themselves but strongly increase the risk of developing disease in DQA1*0301- and DQA1*0101/04-heterozygous. DRB1 alleles carrying the motif DERAA in their third hypervariable region, i.e., *0103, *0402, *1102, *1103, *1301, and *1302, provide a long-lasting protection against RA in DQA1*0101/04- but not in DQA1*0301-positive individuals. These data show that considering both DQ and DR gives a better distinction between patients and controls than the shared epitope hypothesis.

Chlamydia trachomatis antibody detection and diagnosis of reactive arthritis.

OBJECTIVE: To investigate whether determining the presence of serum or synovial fluid (SF) IgG and IgA of anti-Chlamydia antibodies with two recent commercially available enzyme-linked immunosorbent assays (ELISA) using synthetic peptides or recombinant antigen could be helpful to detect possible Chlamydia trachomatis (CT)-involved disease in rheumatological patients without evidence of urogenital CT infection. METHODS: The prevalence of such antibodies was determined in samples from patients with well-defined disease, i.e. CT sexually acquired arthritis and from patients with other inflammatory arthropathies unrelated to CT. RESULTS: When considering IgG and/or IgA anti-MOMP or anti-LPS antibodies, a sensitivity of 100% was obtained for serum and SF samples, but with a low specificity. A sensitivity and a specificity equal or close to 80% were observed for the SF IgG anti-MOMP antibodies. CONCLUSION: Clinically, the most appropriate determination was the SF IgG anti-MOMP antibodies. This commercially available ELISA test could be useful for the diagnosis of probable CT reactive arthritis.

Health care providers should use a common language in relation to low back pain patients.

Uncertainty is the rule rather than the exception when it comes to the underlying causes of 'common' or 'non-specific' low back pain. It may be called many names, depending on whether the diagnostic term is descriptive, anatomopathological or physiopathological. Classifications have been devised, including various criteria: symptoms and signs, duration, treatment, consequences of low back pain on the patients' daily life, etc. Because back pain frequently runs a recurrent course, functional and pain outcomes need to be considered separately: chronic disability and chronic pain may not be parallel. Thus, pain duration (e.g. acute, transient, recurrent, chronic) is only one element in the definition of chronicity. These difficulties in defining and classifying non-specific low back pain may lead to communication problems among health professionals as well as between patients and health professionals. These difficulties raise questions such as: what kind of diagnostic term should we use to avoid dramatization of non-specific low back pain? how can we improve the definition of long-term low back pain? and how can we assure and reassure the patient that this condition is benign in the majority of the population?

Conservative inhospital management of low back pain patients. Factors predicting two-year outcomes.

OBJECTIVE: To evaluate the course of symptoms and occupational outcomes in low back pain patients two years after conservative inhospital therapy. METHODS: Retrospective medical chart study of all patients admitted to a rheumatology department in Geneva in 1993, and telephone interview two years after the admission. RESULTS: Eighty of the 99 patients (81%) identified by the chart review were interviewed by telephone. The course of symptoms (evaluated based on subjective assessments and on the number of subsequent admissions) was similar in the patients who had acute (n = 33) and chronic (n = 47) low back pain at the index admission. Patients who had not returned to work were significantly more likely to report persistent pain (P < 0.001). As many as 61% of patients had not resumed work. Sick leave duration and symptom duration at admission were the factors that had the largest effects on prognosis. Over 90% of patients who were put on sick leave for more than four weeks did not return to work. Permanent cessation of work was recorded in 82% of manual laborers versus 27% of patients in sedentary jobs (P < 0.001). CONCLUSION: Our results are ascribable, at least in part, to the fact that our population included large numbers of patients with persistent pain and of blue collar workers with physically-challenging jobs. Sick leave duration and occupation were the best predictors of the course of symptoms and work status.

Molecular analysis of HLA-DR polymorphism in polymyalgia rheumatica. Swiss Group for Research on HLA in Polymyalgia Rheumatica.

OBJECTIVE: To analyze by molecular typing possible associations of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) compared to controls and patients with rheumatoid arthritis (RA) in Switzerland. METHODS: In a multicenter survey, we recruited 100 patients with PMR with and without signs of giant cell arteritis (GCA), 198 with RA, and 200 controls (volunteer bone marrow donors). HLA-DR generic typing was performed by microtiter plate oligotyping and DR4 subtypes analyzed by dot blot hybridization with sequence specific oligonucleotides or by polymerase chain reaction sequence specific primers. RESULTS: DR4 and DR1 tended to be increased in PMR, compared to controls (36 vs 30%, p = 0.30; and 19 vs 12%, p = 0.16, respectively). Frequencies of all RA associated DR4 and DR1 subtypes tended to be increased in PMR as well. Frequency of the HLA-DR beta 1 70-74 shared motif (QK/RRAA) was significantly higher in PMR than in controls [50 vs 36%, odds ratio (OR) = 1.8, p = 0.018], although lower than in RA (77 vs 36%, OR = 6.0, p < 0.0001), and slightly out of the range of significance if a Bonferroni correction was applied (p = 0.1). At double dose, this epitope was also increased in PMR, but not significantly (5 vs 2%, OR = 2.6, p = 0.17), while it was markedly augmented in RA (22 vs 2%, OR = 14, p = < 0.0001). In patients with the shared epitope, the frequency of clinical signs of GCA tended to be increased (19 vs 10%, p = 0.25). Frequency of the HLA-DR beta 1 DRYF 28-31 motif was identical in PMR (95%) and controls (93%). CONCLUSION: PMR may be associated with the HLA-DR beta 1 70-74 shared epitope. This association, however, would be much weaker for PMR than for RA, particularly with the shared epitope at double dose. PMR is clearly not associated with the HLA-DR beta 1 DRYF 28-31 motif.