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.

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.

[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.

[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.

[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.

A centrofacial B lymphoma in a rheumatoid arthritis patient.

We report on a 65-year-old man who was hospitalized for polyarthritis with deterioration of his general state of health and chronic sinusitis. Clinical and biological signs led to the diagnosis of RA associated with localized Wegener's granulomatosis. Methotrexate and corticosteroids led to a distinct improvement in the patient's articular symptoms and in his general condition. One year after the start of treatment, a tumefaction of the right maxillary sinus appeared. Scans revealed a tumoral lesion in the right maxillary sinus. This proved to be a large B-cell lymphoma. The patient received chemotherapy (CHOP) and radiotherapy. This centrofacial lymphoma may be regarded as a B lymphoma of the MALT (mucosal associated lymphoma tumor) type, mimicking a relapse of Wegener's granulomatosis.

[Juvenile idiopathic arthritis and Lyme disease: a case report]. / Association arthrite idiopathique juvenile et maladie de Lyme: a propos d'une observation.

Lyme disease is a systemic infection due to Borrelia burgdorferi. Joint involvement in children, when primary phase is unknown, can be confounded with juvenile idiopathic arthritis. We report a case of a 16 years old girl, who developed at the age of 14 a bilateral and symetrical polyarthritis of big and small joints with fever and cutaneous eruption of trunk. No clinical improvement was seen under disease modified treatment. More biological investigations were performed, leading to the diagnosis of Lyme disease. Clinical recovery was obtained under adapted antibiotherapy, Hence Lyme serology must be performed when atypical polyarthritis appears in a child especially in an endemic region of borrelia burdogferi.

[Understanding rheumatoid arthritis]. / Comment comprendre la polyarthrite rhumatoïde?

Rheumatoid arthritis is a common and severe inflammatory rheumatic disease, for which the immune mechanisms are being decoded little by little. The pathogenic ncludes significant cellular actors of innate immunity (fibroblastic synoviocytes, macrophages, mastocytes...) and adaptive immunity (T and B lymphocytes). These actors interact through the production of and response to specific (cytokines, chemokines and auto-antibodies) and non-specific (prostaglandins, nitrous oxide [NO], complement, proteases) mediators. The chronology of this rheumatoid synovitis is becoming progressively clearer. Its initiation could be the consequence of a precocious activation of the innate immunity, induced by bacterial agents or debris (PAMP). The activation of the synoviocytes and the macrophages via specific receptors (PPR) unleashes an intense inflammatory reaction that triggers a cascade of events. The ongoing nature of this synovitis leads to the intra-articular recruitment of different cells of immunity. This cellular afflux amplifies the macrophagic and synoviocytic activation and proliferation. All of these interactive phenomena end in the production of large quantities of pro-inflammatory cytokines (TNFa, IL1, IL6, IL15, IL17, IL18) but also other pathogenic mediators (auto-antibodies, complement, prostaglandins, nitrous oxide...). This synovitis persists, as it is no longer regulated by a sufficient production of physiological regulators (soluble receptors and inhibitors of cytokines). The consequence of this intense inflammation and synovial proliferation leads to osteo-articular destruction by the production of proteases and the activation of osteoclasts by the RANK/RANK-ligand pathway under the effect of cytokines (TNFa, IL5, IL1, IL6, IL17) and other mediators (prostaglandins) liberated by synoviocytes, macrophages and lymphocytes. The decryption of this puzzle has already created new therapeutic orientations. The identification of new targets is one of the major consequences of this progress in immuno-rheumatology.

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.

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.

Adamantinoma of the tibia and fibula with pulmonary metastasis: an unusual presentation.

Adamantinoma is a rare tumour of long bones, representing less than 1% of them. Adamantinoma commonly occurs in the tibia. It is locally aggressive and recurrences are uncommon after resection. Metastases have been reported in less than 10% of cases. The most common radiographic appearance is multiple sharply demarcated radiolucent lesions surrounded by areas of dense sclerotic bone. The authors report a patient who developed pulmonary metastasis 1 year after complete resection of primary neoplasm.