Is it possible to identify early predictors of the future cost of chronic arthritis? The VErA project.

This study was conducted to identify early predictors of the total cost of inflammatory arthritis (IA). One hundred and eighty patients affected by undifferentiated arthritis (UA) or rheumatoid arthritis (RA) were included in the French Very Early rheumatoid Arthritis (VErA) cohort between 1998 and 2001. Health economic data for 2003 were collected using a patient self-questionnaire. Results were analysed in terms of direct, indirect and total costs in 2003 euros (2003euro) for the population as a whole and in diagnostic subgroups. A payor perspective (the French National Health Insurance, in this case) was adopted. Multiple linear regression models were used to identify predictors of total cost from among the criteria assessed on recruitment. Results of the study showed that for the study population as a whole, the mean total cost was euro4700 per patient. The costs attributable to the RA and UA sub-groups were euro5928 and euro2424 per patient, respectively. In a univariate analysis, certain parameters were significantly correlated with a higher cost of illness. In the multivariate analysis, some of these parameters were further identified as being predictive of higher cost. Two strong significant, early predictors of total cost were identified: higher pain (P = 0.002) and the presence of rheumatoid factor (P = 0.004). In the RA sub-group, lower grip strength of the dominant hand (P = 0.039) was another predictor of the illness's subsequent economic impact. In conclusion, our data show that simple clinical and laboratory parameters can be used early in the course of IA to predict the condition's impact on healthcare budgets.

Diagnostic and prognostic values of anti glucose-6-phosphate isomerase antibodies in community-recruited patients with very early arthritis.

The objective of this study was to determine the diagnostic and prognostic values of antiglucose-6-phosphate isomerase (GPI) antibodies in patients with very early arthritis. Anti-GPI antibodies were measured by ELISA using purified GPI from rabbit muscle in: (i) 383 sera from healthy blood donors (n = 120), well-established rheumatoid arthritis (RA) (n = 99) and non-RA differentiated arthritis (NRADA) (n = 164) patients; (ii) 195 sera obtained from community-recruited patients with very early inflammatory arthritis (VErA cohort) that were studied for 1 year and classified as having RA (n = 116), NRADA (n = 41), and undifferentiated arthritis (UA) (n = 38) after the follow-up period. The criterion for severity was the progression of radiographic damage. Prevalence of anti-GPI antibodies was significantly higher in well-established RA patients (45.4%) compared to healthy subjects (2.5%). Anti-GPI antibodies were also present in sera from NRADA: systemic lupus erythematosus 53%, polymyositis 45.4%, adult-onset Still's disease 44%, systemic sclerosis 42.8%, spondylarthropathies 25% and primary Sjögren's syndrome 5.8%. No significant association was found between the presence of anti-GPI antibodies and the 3 diagnostic groups from the VErA cohort. No correlation was observed between anti-GPI and autoantibodies usually associated with RA. Anti-GPI antibodies were not predictive of radiological progression in patients with very early arthritis. Thus, anti-GPI antibodies are not useful for discriminating RA from non-RA rheumatic diseases and do not constitute a predictive factor of structural damage.

Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis.

The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP (95.2%). dACRF positive predictive value was high (98.2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.

Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign.

It is thought that the risk of atypical hyperplasia (AH) increases with age, particularly among postmenopausal women. Three hypotheses were investigated to try to explain this phenomena: use of hormone replacement therapy (HRT), increased breast cancer screening and improvements in radiological quality. Data were collected from the Bouches du Rhône breast cancer screening programme database and from the pathological registry of all women operated on for breast diseases in the district. The AH incidence rate was studied using a Poisson regression analysis. The change in the profile of breast diseases was explored through studying changes in the proportion of AH among benign lesions and malignant diseases. The AH incidence rate significantly increased over time (13.6% per year). The proportion of AH among the benign diseases increased with time and was significantly higher for HRT users (Odds Ratio (OR)=2.05; 95% Confidence Interval (CI): 1.43-2.93). While AH decreased with age among HRT non-users, it increased among users as a proportion of both benign and malignant lesions. The AH incidence rate significantly increased among pre- and postmenopausal women. Our study suggests that this increase is partly explained by the incidental discovery of these lesions by mammography and partly by a real increase of the disease among HRT users.

Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients.

OBJECTIVE: To evaluate the predictive value of clinical, biological and radiological parameters for the prognosis of rheumatoid arthritis (RA) in a community-recruited cohort. METHODS: Ninety-one patients (mean age 49 yr, female/male ratio 2.9) with RA of limited duration (median 2 yr), 80% recruited from the community, were prospectively enrolled in 1996 (T1) and followed until 1999 (T2). Data collected at T1 were demographic characteristics, Ritchie articular index (RAI), extra-articular manifestations, Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP) and autoantibodies (autoAbs) [rheumatoid factors (RF), detected by latex fixation test and ELISA (IgM, IgA and IgG isotypes), anti-filaggrin, detected by immunofluorescence (anti-keratin antibodies, AKA; anti-perinuclear factor antibodies, APF) and ELISA (anti-citrullinated rat filaggrin antibodies, ACRFA), anti-Sa, anti-calpastatin recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI), anti-cardiolipin (ACL), antineutrophil cytoplasmic antibodies (ANCA), anti-annexin V (aANX V) and anti-Ro]. Hands were radiographed at T1 and T2, and read using the Sharp method as modified by van der Heijde. The main assessment criterion was progression of radiologically detected damage between T1 and T2. RESULTS: At T1, RA activity was mild (RAI 11/78; mean CRP 14 mg/ml), with minor functional disability (HAQ 0.8/3) and mild X-ray destruction (mean total Sharp score 9.2/280). At T1, 96% of the patients were on treatment (prednisone 72%, DMARDs 95%). The latex test detected autoAb in 46% of patients, RF-IgM was detected in 51%, RF-IgA in 36%, RF-IgG in 32%, AKA in 33%, APF in 45%, ACRFA in 45%, ACAST-C27 in 14%, ACAST-DI in 5%, anti-Sa in 22%, ACL in 3%, ANCA in 28%, aANX V in 9% and anti-Ro in 2%. At T2, the mean total Sharp score was 22.9. According to univariate analysis, T1 parameters associated with the independent variable were RAI, HAQ, CRP, latex test positivity and T1 Sharp scores. Multivariate analysis retained only latex test positivity and, to a lesser degree, joint-space narrowing score as independent predictors of radiological progression. CONCLUSION: RF is the main factor that can predict radiological progression in community cases of RA of limited duration.

Autoantibodies to the 27 C-terminal amino acids of calpastatin are detected in a restricted set of connective tissue diseases and may be useful for diagnosis of rheumatoid arthritis in community cases of very early arthritis.

BACKGROUND: Calpastatin is the natural inhibitor of calpains, a protease that is overexpressed in rheumatoid synovial tissue and plays a key role in cartilage destruction. Autoantibodies to calpastatin (ACAST) were recently detected in rheumatoid arthritis (RA). Our aim was to determine their prevalence and their clinical significance. METHODS: ACAST were detected in a solid-phase enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27) as the antigen. All sera reacting with this peptide also bound to purified erythrocyte calpastatin in an ELISA and/or an immunoblot assay. The frequencies and clinical significance of ACAST-C27 were assessed in sera from a well-documented population of 102 community-recruited patients (76 females; mean age 50 yr) with RA that had been evolving for <5 yr (median 2 yr) (group 1), 109 healthy blood donors, 289 patients with non-RA rheumatic disease and 88 community cases of very early (median 4 months) arthritis, i.e. 58 RA and 30 non-RA patients (group 2). RESULTS: The sensitivity of ACAST-C27 for RA was 19.5% (20/102) in group 1 and 10.3% (6/58) in group 2. These antibodies were also found in patients with anti-double-stranded DNA-positive systemic lupus erythematosus (SLE) (15.5%) and patients with anti-Ro-positive Sjögren's syndrome (18.5%). However, they were not detected in cases of rheumatism resembling early RA, i.e. peripheral spondylarthropathies. ACAST-C27 were not detected in the 30 non-RA patients of group 2. They were predominantly of immunoglobulin isotype G3 and exclusively expressed lambda chains. Among ACAST-C27-positive sera, eight out of 20 (group 1) and four out of six (group 2) were negative for rheumatoid factor and anti-keratin antibodies/antiperinuclear factor. No relationship was found between ACAST-C27 and clinical, biological or radiological findings. CONCLUSION: ACAST-C27 are detected only in a restricted set of connective tissue diseases and therefore appear to be specific for RA when antibodies that are usually associated with SLE or primary Sjögren's syndrome are negative. Because of their presence in community cases of very early RA, particularly in some seronegative forms, ACAST-C27 may be useful in discriminating recent-onset RA from the more common non-RA rheumatic diseases, such as spondylarthropathies.

[The relationship between Chlamydia pneumoniae and atherosclerosis]. / Les liens entre Chlamydia pneumoniae et athérosclérose.

BACKGROUND: Risk factors for arthrosclerosis have been well identified. More than ten years ago, an infectious process was incriminated, particularly the pathogenic effect of Chlamydia pneumoniae in the development of atheromatous lesions responsible for ischemic cardiovascular diseases. DATA BASES: Several approaches have been used to assess the presence of a relationship between C. pneumoniae and the development of cardiovascular disease. Serological, histopathological (study of the atheromatous plaque), pathophysiological, and finally animal studies using models reproducing the human disease have generally favored an association. Therapeutic trials, especially those testing roxithromycin or azithromycin have demonstrated the action of secondary prevention of ischemic heart disease (unstable angina, myocardial infarction). CONCLUSION: The notion of an association between these two factors is biologically plausible. Several points remain to be clarified, particularly the need to develop a reliable diagnostic method for C. pneumoniae infections. It would also be useful to prove the viability of the pathogen within atheromatous plaques and finally to design studies of immune response to C. pneumoniae infections. Prospective therapeutic trials for primary prevention of cardiovascular disease would be most informative but would be most difficult to conduct.

Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term.

OBJECTIVE: To retrospectively assess, with a sufficiently long followup (mean 11.6 years; median 9 years), the long-term outcome of chronic recurrent multifocal osteitis (CRMO), a multifocal, inflammatory bone disease. METHODS: Patients included were 8 children/adolescents and 7 adults with no family history of rheumatic disease who had been diagnosed as having CRMO between 1979 and 1995. Ten patients had undergone at least 1 bone biopsy of the lesions, with histologic examination and multiple cultures. In 1996, in addition to an in-depth interview, 12 patients underwent an extensive physical examination, laboratory evaluation, HLA-A, B, C, and DR typing, bone radiography and scintigraphy, and computed tomography scan of the sternoclavicular and sacroiliac joints. RESULTS: Remission was observed in 3 patients. The other 12 patients developed various associations of vertebral (n = 10), sacroiliac (n = 6), anterior thoracic (n = 7), peripheral articular (n = 2), enthesopathic (n = 4), or dermatologic (palmoplantar pustulosis in 3 cases and psoriasis in 2) involvements. Spine involvement was the most common and occurred the earliest (median time to appearance after the onset of osteitis 5.63 years). Clinical sacroiliitis was always unilateral. No patients carried the HLA-B27 haplotype. CRMO responded well to nonsteroidal antiinflammatory drugs. Twelve patients met the European Spondylarthropathy Study Group criteria for spondylarthopathy. CONCLUSION: After 10 years, CRMO had usually evolved to spondylarthropathy, but with certain features not usually seen in the latter: predominantly, unilateral sacroiliitis, no familial form, and no link with HLA-B27.

[Pulmonary bilharziasis due to Schistosoma mansoni simulating Carrington's disease]. / Bilharziose pulmonaire à Schistosoma mansoni simulant une maladie de Carrington.

A case of pulmonary Schistosoma mansoni bilharziasis observed in a female patient from Martinique is reported. In view of the unusual clinical and radiological features of the disease and of its rapidly worrying course, an open chest lung biopsy was performed which provided the diagnosis. A search for eggs in the stools was negative, and serological tests were weakly positive, treatment with Praziquantel resulted in rapid and complete cure.

[L4 crural neuralgia and disc hernia of the L4-L5 intervertebral foramen]. / Cruralgies L4 et hernie discale du canal de conjugaison de L4-L5.

Discal L4 crural neuralgia is conventionally considered secondary to a hernia of the L3-L4 disc. Now, another source of discoradicular conflict exists on the path of the L4 root: hernia of the link canal of the L4-L5 canal through which the root leaves the rachidian canal. Of 27 discal neuralgias operated upon, 9 were linked to a hernia of the L3-L4 disc, while 18 were secondary to a hernia of the L4-L5 foramen, that is 2 foramina hernias for 1 "intrarachidian" hernia. The diagnostic difficulties resulting from foramina hernias probably reflect a rarity that is more apparent than real. The etiology of crural neuralgia is conventionally sought at the L3-L4 disc. This search is often unsuccessful: one speaks of "essential crural neuralgia". The scanner provides the only certain way of revealing foramina hernias, and will probably detect increasing numbers and thus reduce the number of "idiopathic crural neuralgias".

[Lumbar disk hernia through the intervertebral foramen. Apropos of 37 surgically treated hernia]. / La hernie discale lombaire du canal de conjugaison. A propos de 37 hernies opérées.

37 lumbar discal herniations situated in the intervertebral foramen were operated on, out of a total of 525 operations for lumbar discal herniations during the same period, that is to say 7%. Perhaps the habitual negativity of the contrast neuroradiologic investigations (saccoradiculography, discography, phlebography) explains its relative rareness. In the futur, the scanner, always positif in our cases, will perhaps enable us to appreciate its exact frequency. The radicular pain may be simple in the territory of a root emerging at the upper discal level, which explains the difficulty of diagnosis. It may also interest two roots, including in that case, the root emerging at the discal herniation level. The great frequency of L4-L5 herniations explains the high number of crural pains by compression of the L4 root. Finally, crural pain, in our series of all the lumbar herniations operated on, seems to be linked to a herniation of the upper discs (L3-L4, L2-L3 : 18 cases) as often as to a herniation of the intervertebral foramen of L4-L5 (17 cases).