Rheumatoid Arthritis: Fauchais AL

Hatron PY, Fauchais AL. · Service de médecine interne Hôpital Claude-Huriez CHRU 59037, Lille. · Rev Prat. · Pubmed #11252941 No free full text.

Abstract: Sjogren's syndrome is characterized by the association of a Sicca syndrome prevailing at the ocular and oral level and of extra-glandular involvement of immuno-inflammatory mechanism: nonerosive polyarthritis, Raynaud's phenomenon, cutaneous and (or) neurological vasculitis, pulmonary involvement and interstitial nephropathy. In the typical forms, the biological signs associate a polyclonal hypergammaglobulinemia, sometimes a cryoblogulinemia, rheumatoid factor and anti SSA and anti SSB ANA. The diagnosis is confirmed by minor salivary gland biopsy showing a lymphoid infiltrate in clusters. These biological anomalies, the presence of major salivary gland enlargements and extra-glandular manifestations, characterize the progressive forms of the disease with a high risk of evolution towards malignant lymphoma. Antimalarial drugs are used in the treatment of polyarthritis, corticosteroids and immunosuppressive agents in serious extra-glandular involvement.

Fauchais AL, Boumediene A, Lalloue F, Gondran G, Loustaud-Ratti V, Vidal E, Jauberteau MO. · EA 3842 (IFR 145), University of Limoges, France. · Scand J Rheumatol. · Pubmed #18830907 No free full text.

Abstract: OBJECTIVES: Identification of factors associated with disease activity and B and T cell activation is a challenge in primary Sjogren's syndrome (pSS). Neurotrophins (NTs), recently reported as B cell antiapoptotic, and T-cell activation factors seem to be implicated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Samples from 18 pSS patients and 12 control subjects were studied to determine serum levels of nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and their relationships with T- and B-cell activation and disease activity. Peripheral blood mononuclear cells (PBMCs) from patients with pSS and controls were examined by flow cytometry for HLA-DR expression by activated T cells. B cell activation was evaluated by B cell activating factor (BAFF) serum levels measured by enzyme-linked immunosorbent assay (ELISA) and immunoglobulin (Ig) and free light chain (FLC) levels. RESULTS: Mean serum levels of BDNF in pSS patients were significantly higher than in healthy controls and correlated directly with disease activity. NGF levels were associated with the subgroup of patients with hypergammaglobulinaemia. The pSS group was characterized by peripheral CD4+ and CD8+ T cell activation that correlated positively with BDNF and NGF levels, respectively. CONCLUSION: NT levels are potential biomarkers for lymphocyte activation in pSS patients.

de Seze J, Delalande S, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D, Hatron PY, Vermersch P. · Department of Neurology, Hôpital R. Salengro, CHRU de Lille, Lille, France. · J Rheumatol. · Pubmed #16583474 No free full text.

Abstract: OBJECTIVE: Central nervous system manifestations in Sjögren's syndrome (SS) include focal deficits, optic neuritis, and myelopathies. Acute and chronic myelopathies are frequently severe and sometimes respond poorly to corticosteroids. The efficacy of intravenous (IV) cyclophosphamide (CYC) has been suggested in single case reports. METHODS: We describe the potential usefulness of IV CYC in SS patients with severe myelopathies. Fourteen patients [with acute (n = 6) and chronic (n = 8) myelopathies] were treated with monthly CYC infusions (700 mg/m2) in addition to 500 mg of corticosteroids for one year. We evaluated the disability before and after CYC treatment using a walking distance calculation and the Expanded Disability Status Scale (EDSS). RESULTS: CYC treatment was well tolerated in all cases without serious adverse events. Nine patients (including the 6 with acute myelopathy) were improved after CYC treatment. Three patients were stabilized and 2 patients with chronic myelopathies had moderate progression of disability. The mean walking distance increased from 48.2 m before to 180.4 m after CYC treatment (p < 0.02). Mean EDSS score decreased from 6.6 to 5.7 (not significant). We found a correlation between the length of time before CYC treatment and clinical improvement for both the walking distance (p < 0.02) and the EDSS score (p < 0.05). CONCLUSION: Although a randomized multicenter controlled study is warranted to confirm our findings, IV CYC infusions seem to be useful for the treatment of myelopathies secondary to SS, particularly in acute but also in progressive cases. This treatment should be strongly considered as soon as possible when disease progression is observed.

Doffoël-Hantz V, Loustaud-Ratti V, Ramos-Casals M, Alain S, Bezanahary H, Liozon E, Fauchais AL, Vidal E. · Service de médecine interne A, CHU de Limoges, 87000 Limoges, France. · Rev Med Interne. · Pubmed #15710254 No free full text.

Abstract: Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study. METHODS: Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C. RESULTS: More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment. CONCLUSION: Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.

Liozon E, Loustaud-Ratti V, Soria P, Bezanahary H, Fauchais AL, Nadalon S, Rhaiem K, Ly K, Vidal E. · Service de médecine interne A, Hôpital universitaire Dupuytren, Limoges (87). · Presse Med. · Pubmed #15615235 No free full text.

Abstract: INTRODUCTION: Miscellaneous disorders have been described in association with temporal (giant cell) arteritis (TA), most often anecdotally, except with arteriosclerosis. METHOD: In a retrospective study, we reported our personal experience of disease associations in a series of 250 patients diagnosed with TA and followed-up in the department between 1976 and 2003. RESULTS: Disease associations were found in 43 patients, i.e. 17% of cases: concurrent malignancy (23 patients: 17 cancers and 6 blood diseases), primary Gougerot-Sjögren's syndrome (6 cases), endocrine disease other than Hashimoto's thyroiditis (7 cases: 3 hyperparathyroidism [HPP], 3 hyperthyroidism, 1 association HPP + hyperthyroidism), polyneuropathy (3 cases), essential thrombocythaemia (2 cases), anti-neutrophilic cytoplasmic (anti-myeloperoxidase) antibodies (2 cases), and miscellaneous associations (1 case of RS3PE syndrome, nephrotic syndrome, myasthenia, sarcoidosis, and macro-creatine kinase type 2). More than one disease associated was present 5 patients. In 77% of the patients, there was a strong temporal association between TA and the alternate illness. No systemic necrotizing vasculitis or rheumatoid arthritis was observed in any patient. CONCLUSION: In our experience, there was a frequent, non-fortuitous, association between TA and malignancy. Auto-immune conditions were rare, but the prevalence of Gougerot-Sjögren's syndrome might have been underestimated. Hyperthyroidism and HPP are not exceptional and must be recognised in order to avoid severe bone loss induced by corticosteroids.

Delalande S, de Seze J, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D, Dubucquoi S, Pruvo JP, Vermersch P, Hatron PY. · Department of Neurology, CHRU Lille, France. · Medicine (Baltimore). · Pubmed #15342972 No free full text.

Abstract: Neurologic involvement occurs in approximately 20% of patients with primary Sjögren syndrome (SS). However, the diagnosis of SS with neurologic involvement is sometimes difficult, and central nervous system (CNS) manifestations have been described rarely. We conducted the current study to describe the clinical and laboratory features of SS patients with neurologic manifestations and to report their clinical outcome. We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria. The mean age at neurologic onset was 53 years. Neurologic involvement frequently preceded the diagnosis of SS (81% of patients). Fifty-six patients had CNS disorders, which were mostly focal or multifocal. Twenty-nine patients had spinal cord involvement (acute myelopathy [n = 12], chronic myelopathy [n = 16], or motor neuron disease [n = 1]). Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients. We also recorded diffuse CNS symptoms: some of the patients presented seizures (n = 7), cognitive dysfunction (n = 9), and encephalopathy (n = 2). Fifty-one patients had peripheral nervous system involvement (PNS). Symmetric axonal sensorimotor polyneuropathy with a predominance of sensory symptoms or pure sensory neuropathy occurred most frequently (n = 28), followed by cranial nerve involvement affecting trigeminal, facial, or cochlear nerves (n = 16). Multiple mononeuropathy (n = 7), myositis (n = 2), and polyradiculoneuropathy (n = 1) were also observed. Thirty percent of patients (all with CNS involvement) had oligoclonal bands. Visual evoked potentials were abnormal in 61% of the patients tested. Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS. Thirty-nine patients had a spinal cord MRI. Abnormalities were observed only in patients with spinal cord involvement. Among the 29 patients with myelopathy, 75% had T2-weighted hyperintensities. Patients with PNS manifestations had frequent extraglandular complications of SS. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 21% of patients at the diagnosis of SS and in 43% of patients during the follow-up (mean follow-up, 10 yr). Biologic abnormalities were more frequently observed in patients with PNS involvement than in those with CNS involvement (p < 0.01). Fifty-two percent of patients had severe disability, and were more likely to have CNS involvement than PNS involvement (p < 0.001). Treatment by cyclophosphamide allowed a partial recovery or stabilization in patients with myelopathy (92%) or multiple mononeuropathy (100%). The current study underlines the diversity of neurologic complications of SS. The frequency of neurologic manifestations revealing SS and of negative biologic features, especially in the event of CNS involvement, could explain why SS is frequently misdiagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement. The outcome is frequently severe, especially in patients with CNS involvement. Our study also underlines the efficacy of cyclophosphamide in myelopathy and multiple neuropathy occurring during SS.

Fauchais AL, Lambert M, Launay D, Michon-Pasturel U, Queyrel V, Nguyen N, Hebbar M, Hachulla E, Devulder B, Hatron PY. · Department of Internal Medicine, Regional University Hospital of Lille, France. · Lupus. · Pubmed #15176660 No free full text.

Abstract: The aim of this study is to determine prevalence, clinical significance of antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), anti-beta2GP1 and lupus anticoagulant (LA) in a cohort of 74 patients with primary Sjögren's syndrome (pSS) according to revised European criteria. aPL were found in 25 (34%) patients; IgG in 23 (12 had low titres, six moderate titres and five high titres) and IgM in five (three and two had respectively moderate and high titres). Eight (11%) patients were found to have LA; anti-beta2GP1 antibodies were detected only in three (4%) patients. Only two patients with LA, aPL and beta2GP1 had recurrent venous thrombosis. One patient with moderate titres of aPL exhibited recurrent spontaneous foetal losses. Peripheral neuropathies without cryoglobulinemia were more frequent in the aPL group. Other systemic involvements of pSS were the same in both groups with or without aPL. Patients with aPL have more concurrent immunological diseases such as thyroiditis and primary biliary cirrhosis and a higher prevalence of hypergammaglobulinemia (P < 0.05). Even if aPL prevalence reached 30% in pSS, titres were usually low, with a close correlation with hypergammaglobulinemia but not with antiphospholipid syndrome, which is related to positivity of both LA and aPL.

Dubucquoi S, Solau-Gervais E, Lefranc D, Marguerie L, Sibilia J, Goetz J, Dutoit V, Fauchais AL, Hachulla E, Flipo RM, Prin L. · Department of Immunology, CHRU de Lille, France. · Ann Rheum Dis. · Pubmed #15020336 links to  free full text

Abstract: BACKGROUND: Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. OBJECTIVE: To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. METHODS: Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. RESULTS: Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to approximately 50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. CONCLUSIONS: Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.

de Seze J, Dubucquoi S, Fauchais AL, Hachulla E, Matthias T, Lefranc D, Hatron PY, Vermersch P, Witte T. · Department of Neurology, University of Lille, Lille, France. · J Rheumatol. · Pubmed #14994394 No free full text.

Abstract: OBJECTIVE: To investigate the diagnostic value of autoantibodies against alpha-fodrin in patients with Sjögren's syndrome (SS) with neurological manifestations compared to SS patients without neurological manifestations, a control group, and patients with other neurological autoimmune diseases including systemic lupus erythematosus (SLE) with neurological manifestations and multiple sclerosis (MS). METHODS: We evaluated alpha-fodrin autoantibodies in 31 patients with SS with neurological manifestations, 53 SS patients without neurological symptoms, 38 patients with SLE, 60 with MS, and 160 controls. RESULTS: Twenty of the 31 SS patients with neurological manifestations (64.5%) had an increased concentration of IgA and/or IgG anti-alpha-fodrin. This was not statistically different from that of SS patients without neurological symptoms (73.6%), but was higher than the number with SSA/SSB antibodies, which were found in 15 (48%) of our SS patients without neurological manifestations. When the results of the 2 tests were combined, 28 of the 31 (90.3%) patients had positive autoantibodies (alpha-fodrin and/or SSA/SSB). Alpha-fodrin antibodies were increased in 8 (13.3%) of the 60 patients with MS, in 6 (15.7%) of 38 patients with SLE, and in 10 (6.3%) of 160 controls. CONCLUSION: Our results confirm that alpha-fodrin antibodies are an additional diagnostic tool for SS. This test is of particular interest for patients with SS with neurological manifestations, in whom anti SSA/SSB antibodies are less frequently found.

de Seze J, Dubucquoi S, Fauchais AL, Matthias T, Devos D, Castelnovo G, Stojkovic T, Ferriby D, Hachulla E, Labauge P, Lefranc D, Hatron PY, Vermersch P, Witte T. · Department of Neurology, University of Lille, France. · Neurology. · Pubmed #12874419 No free full text.

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Legout L, Fauchais AL, Hachulla E, Queyrel V, Michon-Pasturel U, Lambert M, Hatron PY, Devulder B. · Service de médecine interne, hôpital Claude-Huriez, CHRU, 59037 Lille, France. · Rev Med Interne. · Pubmed #11928375 No free full text.

Abstract: PURPOSE: Antisynthetase syndrome (AS) is frequently revealed by interstitial lung disease and arthritis. There are mechanic's hand, Raynaud's phenomenon and anti aminoacyl t-RNA synthetase antibodies. The anti JO-1 antibody is the most frequently identified. We report five cases of antisynthetase syndrome with particular clinical features and good response to corticosteroids. METHODS: There are three women and two men with a median age of 59 years at presentation (range: 44-77). Three patients progressively developed AS: the symptoms are dyspnea (three). Raynaud's phenomenon (one), purpura (one) and hyperkeratosis, scaling and fissuring on the lateral sides of the fingers (two). Patients always had skin signs: hyperkeratosis and scaling (five), purpura (one), Raynaud's phenomenon with normal capillaroscopy (two). Lung disease is present in the five cases with interstitial lesions in CT scans (five), trouble of CO diffusion (three/three) and lymphocytic alveolitis (two/two). Moderate muscular disorders are present in five cases (moderate elevated muscular enzyme: five, positive muscle histology: two). Anti-JO-1 antibodies are present in five cases. AS is associated with connective tissue diseases: rheumatoid polyarthritis in one case and Gougerot-Sjögren in three cases. No malignant tumour is associated. Patients have received oral corticosteroid treatment (five/five) with high doses of intravenous perfusions (three/five) with, initially, a good response. For only one patient, immunosuppressive treatment was necessary because of the articular relapse. The interstitial lung disease had a good response to corticosteroids therapy alone in four cases. Because of the relapse during the tapering off of corticosteroids, corticosteroids were increased in one case and immunosuppressive therapy was required in one case. CONCLUSION: The prognosis of AS depends of the interstitial lung disease. High doses of corticosteroids are required. In our study, the response to corticosteroids is good. Immunosuppressive agents must be added in severe and progressive form of interstitial lung disease in AS.

Fauchais AL, Hatron PY, Michon Pasturel U, Queyrel V, Hachulla E, Biserte J, Devulder B. · No affiliation provided · Rev Med Interne. · Pubmed #11586530 No free full text.

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