Detection of Shigella spp. nucleic acids in the synovial tissue of Tunisian rheumatoid arthritis patients and other forms of arthritis by quantitative real-time polymerase chain reaction.

Enterobacterial components in the joints of patients are believed to contribute to a perpetuating inflammation leading to a reactive arthritis (ReA), a condition in which microbial agents cannot be recovered from the joint. At present, it is unclear whether nucleic acids from Shigella spp. are playing a pathogenic role in causing not only ReA but also other forms of arthritis. Quantitative real-time polymerase chain reaction assay (qPCR) is the method of choice for the identification of bacteria within the synovium. The aim of our study was to detect the presence of Shigella spp. nucleic acids in the synovial tissue (ST) of Tunisian arthritis patients. We investigated 57 ST samples from rheumatoid arthritis (RA) n = 38, undifferentiated oligoarthritis (UOA) n = 12, and spondyloarthritis (SpA) n = 7 patients; 5 ST samples from healthy individuals were used as controls. Shigella spp. DNA and mRNA transcripts encoding the virulence gene A (VirA) were examined using an optimized qPCR with newly designed primers and probes. Using qPCR, Shigella spp. DNA was found in 37/57 (65%) ST samples (24/38, i.e., 63.2% of RA, 8/12, i.e., 67% of UOA, and 5/7, i.e., 71.4% of SpA patients). Paired DNA and mRNA were extracted from 39 ST samples, whose VirA cDNA was found in 29/39 (74.4%) patients. qPCR did not yield any nucleic acids in the five healthy control ST samples. The qPCR assay was sensitive and showed a good intra- and inter-run reproducibility. These preliminary findings generated by an optimized, highly sensitive PCR assay underline a potential role of past gastrointestinal infections. In Tunisian patients, a bacterial etiology involving Shigella spp. in the manifestation of arthritic disorders including RA might be more common than expected.

Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

[The role of type II collagen fragments and X-ray progression of knee osteoarthritis]. / Rôle des marqueurs de dégradation du collagène de type II au cours de la progression de l'arthrose du genou.

AIMS: To investigate the association between type II collagen fragments and the presence of knee osteoarthritis (OA) in the Tunisian population and to determine whether this biomarker can predict X-ray progression of this disease. METHODS: Type II collagen C-telopeptide (uCTX-II) and helical peptide (sHelix-II) were assessed in 125 female patients with knee osteoarthritis aged 54 ± 8 years over 2 years and 57 female age-matched controls. The markers were measured at baseline, 1 and 2 yrs' follow-up corresponding to x-ray time points. RESULTS: Only urinary CTX-II values were significantly 48% higher in knee OA patients compared with controls (p=0.001). The longitudinal changes over 2 yrs in Helix-II were also significantly associated with Joint Space Narrowing: JSN (p=0.03). Over the 2-yr study period average CTX-II levels were not significantly higher in progressor compared with non-progressor (339.96 vs 256.00; NS). CONCLUSION: The data presented here suggest that CTX-II may be useful to identify patients with knee OA. These results demonstrate significantly association between progression of this disease and alterations levels of Helix-II.

Association of LRP5 genotypes with osteoporosis in Tunisian post-menopausal women.

BACKGROUND: Osteoporosis is a highly heritable trait. Among the genes associated with bone mineral density (BMD), the low-density lipoprotein receptor-related protein 5 gene (LRP5) has been consistently identified in Caucasians. However LRP5 contribution to osteoporosis in populations of other ethnicities remains poorly known. METHODS: To determine whether LRP5 polymorphisms Ala1330Val and Val667Met are associated with BMD in North Africans, these genotypes were analyzed in 566 post-menopausal Tunisian women with mean age of 59.5 ± 7 .7 years, of which 59.1% have low bone mass (T-score<-1 at spine or hip). RESULTS: In post-menopausal Tunisian women, 1330Val was weakly associated with reduced BMD T-score at lumbar spine (p=0.047) but not femur neck. Moreover, the TT/TC genotypes tended to be more frequent in women with osteopenia and osteoporosis than in women with normal BMD (p=0.066). Adjusting for body size and other potential confounders, LRP5 genotypes were no longer significantly associated with aBMD at any site. CONCLUSIONS: The less common Val667Met polymorphism showed no association with osteoporosis. The Ala1330Val polymorphism is weakly associated with lower lumbar spine bone density and osteopenia/osteoporosis in postmenopausal Tunisian women. These observations expand our knowledge about the contribution of LRP5 genetic variation to osteoporosis risk in populations of diverse ethnic origin.

Notch signaling is involved in human articular chondrocytes de-differentiation during osteoarthritis.

CONTEXT: During osteoarthritis (OA), chondrocytes undergo de-differentiation, resulting in the acquisition of a fibroblast-like morphology, decreased expression of collagen type II (colII) and aggrecan, and increased expression of collagen type I (colI), metalloproteinase 13 (MMP13) and nitric oxide synthase (eNOS). Notch signaling plays a crucial role during embryogenesis. Several studies showed that Notch is expressed in adulthood. OBJECTIVE: The aim of our study was to confirm the involvement of Notch signaling in human OA at in vitro and ex vivo levels. MATERIALS AND METHODS: Normal human articular chondrocytes were cultured during four passages either treated or not with a Notch inhibitor: DAPT. Human OA cartilage was cultured with DAPT for five days. Chondrocytes secreted markers and some Notch pathway components were analyzed using Western blotting and qPCR. RESULTS: Passaging chondrocytes induced a decrease in the cartilage markers: colII and aggrecan. DAPT-treated chondrocytes and OA cartilage showed a significant increase in healthy cartilage markers. De-differentiation markers, colI, MMP13 and eNOS, were significantly reduced in DAPT-treated chondrocytes and OA cartilage. Notch1 expression was proportional to colI, MMP13 and eNOS expression and inversely proportional to colII and aggrecan expression in nontreated cultured chondrocytes. Notch ligand: Jagged1 increased in chondrocytes culture. DAPT treatment resulted in reduced Jagged1 expression. Notch target gene HES1 increased during chondrocyte culture and was reduced when treated with DAPT. CONCLUSION: Targeting Notch signaling during OA might lead to the restitution of the typical chondrocyte phenotype and even to chondrocyte redifferentiation during the pathology.

WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology.

CONTEXT: Osteoarthritis (OA) is an articular disorder leading to the degradation of articular cartilage phenotypical chondrocytes modifications, including the acquisition of a fibroblast-like morphology, decreased expression of collagen type II, and increased expression of fetal collagen type I, metalloproteinase 13 and nitric oxide synthase. This promotes matrix degradation and unsuccessful cartilage repair. WNT signaling constitutes one of the most critical biological processes during cell fate assignment and homeostasis. OBJECTIVES: This review aims to give an insight on results from the studies that were interested in the involvement of WNT in OA. METHODS: Studies were selected through a pubmed search. RESULTS: Recent genetic data showed that aberration in WNT signaling may be involved in OA. WNT signals are transduced through at least three cascades: the canonical WNT/ß-catenin pathway, the WNT/Ca(2+) pathway and the WNT/planar cell polarity pathway. Most of the studies used in-vitro models to elucidate the involvement of WNT in the physiopathology of OA. These studies analyzed the expression pattern of WNT pathway components during OA such as WNT5, WNT7, co-receptor LRP, ß-catenin, WNT target genes (c-jun, cyclins) and/or the interaction of these components with the secretion of OA most important markers such as IL-1, collagens, MMPs. Results from these studies are in favor of a deep involvement of the WNT signaling in the physiopathology of OA either by having a protective or a destructive role. CONCLUSION: Deeper researches may eventually allow scientists to target WNT pathway in order to help develop efficient therapeutic approaches to treat OA.

[Study of bone mineral density in adolescent handball players: a study of 20 cases]. / Etude de la densité minérale osseuse chez les adoloescentes handballeuses: a propos d'une étude de 20 cas.

BACKGROUND: The physical activity during adolescence seems to correlate with bone mass at the end of the growth period. aim : To determine the effect of handball regularly practiced by teenage girls on the anthropometric parameters and bone mineral density. METHODS: Cross-sectional case-control, made in the rheumatology department of the Rabta hospital, has enrolled adolescent handball players of high level, which were compared to a control group matched by age and sex, but sedentary. We evaluated our two groups for anthropometric parameters and BMD. RESULTS: The lean mass (LM), fat mass (FM), the mean values of BMD at the lumbar spine and femur of our sports were significantly higher than that of sedentary controls. On bone mineral content (BMC), a statistically significant difference was observed between groups of sedentary and athletic teenagers. Positive and significant correlations were found between anthropometric parameters and measurements of BMD, BMC and of bone area. CONCLUSION: The regular practice of handball seems to be an osteogenic factor. It may be advisable in adolescents during the growth period to optimize the bone.

Anomalies of intra-synovial citrullination: is there any interest in the diagnosis of early rheumatoid arthritis?

Autoantibodies to citrullinated proteins (ACPA) are specifically associated with rheumatoid arthritis (RA) and seem to play an important role in its pathogenesis. The specific immunological conflict between ACPA and citrullinated fibrin plays a major role in the self-maintenance of synovial inflammation by forming fibrin deposits in the synovial tissue. These deposits, secondarily citrullinated by a local peptidylarginine deiminase (PADI) enzyme activity, seem to maintain the immunological conflict and the inflammation. Our objective in this work is to study the anomalies of citrullination in a group of patients with early RA, in comparison with a control group of patients suffering from undetermined inflammatory arthritis, osteoarthritis and spondyloarthropathy. For this purpose, we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of ACPA in serum and synovial fluid. By immunohistochemistry, subtype 4 of PADI was also sought in the synovial biopsies taken from all our patients. We found that the ACPA levels in serum and synovial fluid were significantly higher in patients with RA. The enzyme PADI4 was found only in the group with RA and was statistically correlated with ACPA mean levels in sera and synovial fluid. The expression of PADI4 seems to correlate with intra-synovial deposits of fibrin in RA. However, determination of synovial ACPA levels and detection of intra-synovial PADI4 deposits are of no additional benefit compared with assessment of ACPA levels in serum for the diagnosis of early RA.

Endogenous ochronosis with a fatal outcome.

BACKGROUND: Endogenous ochronosis (EO) is an autosomal recessive inherited disorder where there is incomplete oxidation of tyrosine and phenylalanine due to a lack of the enzyme homogentisic acid oxidase. OBJECTIVE: We report a singular observation of EO with a fatal outcome. CASE REPORT: We report the case of a 46-year-old man born to consanguineous parents with a medical history of recurrent renal colic and chronic nonspecific arthropathy. On clinical examination, slate blue pigmentation was seen on the cheeks, forehead, and nose, as well as blue-gray patches on all fingernails and bluish discoloration of the gums. Familial investigation revealed that his sister had similar pigmentation on the ears, hands, and fingernails. Histologic examination of a biopsy specimen from a pigmented lesion showed a dermal deposit of an acellular, eosinophilic material without cell reaction. Based on the clinical and histopathologic data, combined with the family medical history, our patient was considered to have EO with mucocutaneous, articular, and renal involvement. Unfortunately, the diagnosis was late because our patient died a few months later of terminal renal failure. CONCLUSION: Skin signs are the hallmarks of EO and must alert the clinician to look for involvement of vital organs.

[Pathophysiology of complex regional pain syndrome (CRPS) type 1]. / Physiopathologie du syndrome douloureux regional complexe de type 1: Quoi de neuf en 2011.

BACKGROUND: If the pathophysiology of complex regional pain syndrome (CRPS) type 1 remains controversial, most authors agree on a combination in varying proportions, a sensitization of peripheral nerves. AIM: To describe the state of advances in the physiopathology of complex regional pain syndrome type 1. METHODS: Bibliographic research and literature review performed by referring to databases (Medline, Science Direct) RESULTS: The physiopathology of complex regional pain syndrome type 1 remains still poorly understood and controversial. Several arguments demonstrated both peripheral (inflammation, abnormal sympathetic ...) and central (neurological and cognitive) mechanisms. CONCLUSION: A better knowledge of the physiopathology of complex pain syndrome type 1 is necessary in order to adapt efficient curative therapy or to a better prevention of this syndrome.

[Usefulness of magnetic resonance imaging in the diagnosis of early rheumatoid arthritis: a prospective study of 20 cases]. / Intérêt de l'Imagerie par Résonance Magnétique dans le diagnostic des formes débutantes de la Polyarthrite Rhumatoïde : Etude prospective à propos de 20 cas.

BACKGROUND: Diagnosing early rheumatoid arthritis is difficult and radiographic signs are often late. MRI detects erosions at an early stage and visualizes synovitis, bone edema and tenosynovitis. AIM: To assess the value of MRI for diagnosis of early forms of rheumatoid arthritis. METHODS: Prospective study involving 20 patients who had non erosive rheumatoid arthritis lasting for less than 2 years. MRI of the hand was performed by sequences coronal and axial T1-weighted, T2 with saturated fat signal (FatSat) FatSat and T1 with gadolinium injection. RESULTS: The median age of patients was 52 years and sex ratio M/F of 0.05. The median disease duration was 9 months. Ten patients had antibodies Anti-Cyclic citrullinated protein positive. The MRI was abnormal in 75% of patients. This review found 36 erosions which 50% were in carpal bones, 55 joints with synovitis mainly localized midcarpal and metacarpophalangeal. Bone edema was found mainly in carpal bones. Tenosynovitis affected most frequently the flexor tendons. Seventy percent of patients without anti-Cyclic citrullinated protein had a pathological MRI. CONCLUSION: MRI has an important role in detecting infraradiological lesions in early RA. This contributes to early diagnosis and initiation effective treatment.

[Carpal tunnel syndrome. A Tunisian series]. / Le syndrome du canal carpien : A propos d'une série hospitalière Tunisienne.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most frequent ductal syndrome. Few epidemiological studies in Tunisia exist. AIM: To describe clinical, biological and electromyographic data of Tunisian patients with CTS METHODS: A retrospective study including 80 patients with CTS, during the period going from 2009 to 2010. RESULTS: A female predominance was observed with an average age of 52 years. Acroparesthesia was the main complaint, followed by night awakenings and muscular weakness. Physical examination showed a positive Tinel (91.2%) and Phalen (82.5%) tests, a decrease of tactile sensitivity (26.2%) and a thenar amyotrophy (10%). The Electromyography was abnormal in 85% cases. The most revealing lesions were demyelinating, sensitivo-motor predominance (66%) abnormalities. on Biology, hyperglycemia (12.5%), hyperuricemia (8.7%) and renal failure (7.5%) were the most observed. Medical treatment was drawn on analgesics and anti-inflammatory for 90% of our patients. Local steroid injections were indicated for 35% of patients, leading to a clinical improvement in 90% of cases. Surgery was made in only 13.8% patients. CONCLUSION: Tunisian patients with CTS were female patients, housewifes with obesity or overweight. No other differences were observed in comparison with the literature.

The practical value of biologics registries in Africa and Middle East: challenges and opportunities.

Biologics, including tumor necrosis factor (TNF) inhibitors, are increasingly used for the treatment of inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis. The efficacy of these drugs has been demonstrated in randomized controlled trials (RCTs). However, these studies are conducted in controlled environments, and the results may not necessarily reflect clinical outcomes in daily clinical practice. In Europe and other western countries, numerous biologics registries that enroll and monitor patients receiving biologics have been established. These registries follow patients irrespective of whether they continue with the initial biologic drug. Thus, real-life efficacy data from these registries can be used to assess the long-term safety of biologics through longitudinal studies. In Africa and Middle East (AFME), such registries currently exist only in Morocco and South Africa. In light of the increasing availability of biologics and scarcity of long-term safety data of these agents in the AFME population, there is a need to establish biologics registries in other countries across the region. This review discusses the value of biologics registries versus RCTs as well as safety and efficacy data from observational studies presented as lessons from well-established biologics registries. In addition, the rationale for establishing such registries in the AFME region is also presented.

Systemic lupus erythematosus induced by interferon ß1 therapy in a patient with multiple sclerosis.

Drug-induced lupus erythematosus is defined as a lupus-like syndrome temporally related to a drug exposure. We report a 34-year-old woman with multiple sclerosis who developed, while being treated with interferon ß-1a, myalgia and associated with wrist synovitis. Clinical and immunologic investigations were in favor of systemic lupus erythematosus. Interferon therapy was maintained. Under corticosteroids and antipaludeen treatment, the patient did not develop any other lupic manifestations.

What is the ability of anti-cyclic citrullinated peptide antibodies determination in synovial fluid in discriminating rheumatoid arthritis from non-rheumatoid arthritis patients? A Tunisian cross-sectional study.

Anti-cyclic citrullinated peptide antibodies (ACPA) seem to be produced locally at the site of joints inflammation in the first stage of rheumatoid arthritis (RA). A strong correlation between serum ACPA and ACPA in the synovial fluid (SF-ACPA) is now suggested. A case-control study was conducted to evaluate the usefulness of ACPA determination in SF of patients with RA. A total of 53 patients with a knee-joint effusion (26 RA, 18 peripheral spondyloarthropathies (SPA), and 9 osteoarthritis (OA)) were included in our study. SF samples were obtained by performing therapeutic arthrosynthesis. IgG serum ACPA and SF-ACPA levels were determined by the enzyme-linked immunosorbent assay (ELISA). We have also determined IgG levels in serum and SF by nephelometry. Higher levels of IgG ACPA antibodies in SF (p = 0.045) and serum (p = 0.045) were found in patients with RA with respect to SPA and OA patients. The Spearman correlation analysis showed a significant and positive correlation between ACPA in serum and SF (rho = 0.516; p = 0.007) not only in the RA group but also in patients with SPA. Serum ACPA discriminated RA from non-RA at a cut-off value of 2.7 U/ml (sensitivity, 69%; specificity, 78%; and area under the curve (AUC), 0.72), whereas SF-ACPA discriminated RA from non-RA at a higher cut-off value of 4.95 U/ml (sensitivity, 73%; specificity, 61%; and AUC, 0.71). Our study suggests that the determination of SF-ACPA give complement information to serum ACPA in patients with RA.

[Rheumatic manifestations of genetic hemochromatosis]. / Les manifestations ostéo-articulaires de l'hémochromatose.

BACKGROUND: Rheumatic manifestations of genetic hemochromatosis are frequent with axial or peripheral arthropathies (mono-, oligo- or polyarticular). These manifestations are characterized by articular damage and osteoporosis. AIM: To review the rheumatic manifestations of genetic hemochromatosis. METHODS: A narrative review of literature. RESULTS: The diagnosis should be brought to mind when we discover arthropathy resembling degenerative joint disease with involvement of unusual articular sites, almost identical to the arthropathy in calcium pyrophosphate dihydrate crystals deposition disease (chondrocalcinosis). CONCLUSION: There is a significant bone loss in HC that cannot solely be explained by hypogonadism or cirrhosis and must lead to measure bone mass density to each patient with HC.

[Effect of inhaled corticosteroids on bone mineral density in asthmatic adults: a 20 cases study]. / Effet de la corticothérapie inhalée sur la densité minérale osseuse chez l'adulte jeune asthmatique : a propos de 20 patients.

BACKGROUND: Inhaled corticosteroids are widely used in the treatment of asthma but their safety on bone density is controversial. AIM: To study in a population of adults with asthma receiving inhaled corticosteroids for long term, the effect of this therapy on bone mineral density. METHODS: Prospective study including 20 asthmatics, aged from 20 to 45 years, treated with inhaled corticosteroids for 12 months or more, with no risk factors for osteoporosis. We compared osteodensitometric parameters in our patients, bone mass and T-score at vertebral and femoral witness to a population matched by age and sex. RESULTS: The average age of our patients was 35.45 ± 5.43 years and the average BMI was 30.03 ± 5.77 kg/m2. The average daily dose of corticosteroid was 925 ± 133.27g of equivalent of beclometasone with an average take of 33.5 ± 21.3 months. The vertebral site bone mass average was 1216 ± 0106 g/cm2 in the studied group and 1201 ± 0099 g/cm2 in the control group without significant difference (p = 0380). At femur, the bone mass average was 1037 ± 0143 g/cm2 in the patient group and 1056 ± 0107 g/cm2 in the control group (p = 0380). We did not find a significant link between bone mineral density and cumulative dose or the duration of taking inhaled corticosteroids, BMI and tobacco. CONCLUSION: Our work confirms like other previous studies the safety of inhaled corticosteroids on bone mineral density.