Rheumatoid Arthritis: Launay D

Launay D, Hachulla E, Hatron PY, Jais X, Simonneau G, Humbert M. · Centre National de Référence de l'Hypertension Artérielle Pulmonaire, UPRES EA2705, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Assistance Publique Hôpitaux de Paris, Université Paris-Sud 11, Clamart, France. · Medicine (Baltimore). · Pubmed #17873760 No free full text.

Abstract: Primary Sjögren syndrome (pSS) is a fairly common autoimmune disease with glandular and extraglandular manifestations. Pulmonary involvement mainly corresponds to small airways and interstitial lung disease. Pulmonary arterial hypertension (PAH) is rare: to our knowledge, only 32 cases have been reported in pSS patients to date. PAH is a disease of the small pulmonary arteries characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary vascular resistance, and, ultimately, right ventricular failure and death. We report 9 new cases of pSS-associated PAH with a complete assessment including clinical characteristics (of both PAH and pSS), hemodynamic parameters, medical management, and outcome. We also review the 19 fully documented PAH patients with pSS reported in the English-language literature, therefore analyzing a total of 28 cases (27 women; mean age at PAH diagnosis, 50 +/- 11 yr; range, 23-68 yr). Functional impairment at diagnosis was severe, with a New York Heart Association (NYHA) functional class of III or IV in most cases. Seven of 15 (47%) patients for whom data were available had history or evidence of right heart failure at PAH diagnosis. Hemodynamic parameters were moderate to severe with a mean pulmonary artery pressure of 44 +/- 11 mm Hg (range, 24-60 mm Hg) and a cardiac index of 2.91 +/- 0.72 Lmin(-1)m(-2) (range, 1.36-3.88 Lmin(-1)m(-2)). Standard PAH therapy (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, or prostanoids) was initially effective in some patients but had short-term and long-term failures. Some patients were treated with first-line immunosuppressants alone leading to improvement in some, but second-line standard PAH therapy was added in all cases thereafter. The best treatment strategy remains to be defined. Estimated survival rates were low (73% and 66% at 1 and 3 years, respectively). Compared with pSS patients without PAH, patients with pSS-associated PAH had Raynaud phenomenon, cutaneous vasculitis, and interstitial lung disease significantly more frequently. They also more frequently had antinuclear, anti-Ro/SSA, and anti-RNP autoantibodies, as well as positive rheumatoid factor and hypergammaglobulinemia. These data suggest that systemic vasculopathy, B-cell activation, and autoimmunity could play a role in the pathophysiology of pSS-associated PAH. In conclusion, this report underlines the rarity and severity of PAH in pSS patients. The best therapeutic regimen remains to be defined but should include standard PAH therapy and/or immunosuppressants.

Launay D, Hachulla E. · Service de médecine interne, Hôpital Claude-Huriez, CHRU, Lille (59). · Presse Med. · Pubmed #15615241 No free full text.

Abstract: PRINCIPLE AND OTHER CAUSES: Takayasu's arteritis, giant cell arteritis and Behçet's disease are the three main causes of inflammatory aortitis. More rarely, aortitis can be observed in Cogan's syndrome, atrophic polychondritis, sarcoidosis, ankylosing spondylitis and in rheumatoid arthritis. RISKS OF PROGRESSION: Takayasu's arteritis is distinct with the development of stenotic lesions of the aorta. With the other causes, aortitis can be complicated by ectasia or even aneurysm, with the risk of rupture. Indeed, during giant cell arteritis, patients are 17 times more likely to develop thoracic aortic aneurysm. Aortic regurgitation is a frequent complication of inflammatory aortitis. Sometimes, aortitis is only manifested by general signs such as fever or an inflammatory syndrome. SUPPLEMENTARY EXPLORATIONS: Recent advances in diagnosis and follow-up of patients with inflammatory aortitis concern the use of non-invasive imaging techniques: Doppler ultrasonography, computed tomography with injection of a contrast product and magnetic resonance imaging, which currently replace the aortography. DIAGNOSTIC PROBLEMS: Infectious aortitis, inflammatory atheromatous aneurysm and retroperitoneal fibrosis are sometimes misleading differential diagnoses.

Gondran G, Fauchais A, Lambert M, Ly K, Launay D, Queyrel V, Benazahari H, Liozon E, Loustaud-Ratti V, Hachulla E, Jauberteau M, Hatron P, Vidal E. · Internal Medicine Department, Limoges University Hospital, France. · Scand J Rheumatol. · Pubmed #18612931 No free full text.

Abstract: OBJECTIVE: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient. METHODS: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study. RESULTS: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04). CONCLUSION: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.

Mekinian A, Lambert M, Queyrel V, Launay D, Morell-Dubois S, Hachulla E, Mathurin P, Hatron PY. · Service de médecine interne, hôpital Huriez, CHRU de Lille, place de Verdun, rue Polonovski, 59037 Lille, France. · Rev Med Interne. · Pubmed #18572281 No free full text.

Abstract: Adult-onset Still's disease is a systemic disorder without specific histological feature. Diagnosis requires to rule out any other disorder including neoplasia. Nevertheless, patients with paraneoplastic adult-onset Still's disease have been reported. We report a patient with an adult-onset Still's disease who presented with a liver involvement at onset. Two years later, a liver angiosarcoma was diagnosed. This report underlines the difficulty of the diagnosis of the adult-onset Still's disease even in the presence of Yamaguchi et al.'s [J Rheumatol 19 (1992) 424-30] and Fautrel et al.'s [Medicine 81 (2002) 194-200] classification criteria and may suggest a link between the initial clinical picture and the discovery nearly two years later, of a liver angiosarcoma.

Crinquette C, De Seze J, Maurage CA, Launay D, Ferriby D, Delalande S, Hachulla E, Stojkovic T, Vermersch P. · Service de Neurologie, Groupe Hospitalier de l'Institut Catholique de Lille. · Rev Neurol (Paris). · Pubmed #18033046 No free full text.

Abstract: BACKGROUND: Polymyositis with cranial neuropathy has been rarely reported. CASE REPORTS: We describe here three cases of polymyositis with trigeminal or facial neuropathy. Patients had muscular weakness, myalgia, rhabdomyolysis, endomysial infiltration with necrosis and regeneration at biopsy of muscle and, for two of them, a myopathic pattern at electromyogram. Two patients had also a Sjögren's syndrome and anti-nuclear antibodies. Anti-JO1 antibodies were presents in only one case. The outcome for one patient was good with corticosteroids alone. One other improved with the adjunction of immunoglobulin. The third one had a macrocheilia, a facial diplegia, antibodies against voltage-gated potassium channels and a neuromyotonia secondary to a paraneoplastic syndrome. He died after one year despite a treatment by corticosteroids and immunoglobulin. Patients fulfilled the diagnosis of polymyositis according to clinical, electromyographic, biological and histopathologic criteria. For the two patients with Sjögren's syndrome, the question of a primitive or a secondary Sjögren's syndrome remains unknown. CONCLUSION: The occurrence of a cranial neuropathy in polymyositis should make us looking for an association with paraneoplastic syndrome or connective tissue disease.

Lefranc D, Launay D, Dubucquoi S, de Seze J, Dussart P, Vermersch M, Hachulla E, Hatron PY, Vermersch P, Mouthon L, Prin L. · Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Université Lille 2, Lille, France. · Arthritis Rheum. · Pubmed #17907141 links to  free full text

Abstract: OBJECTIVE: To characterize discriminant human brain antigenic targets in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), using a standardized immunoproteomic approach. METHODS: Self-IgG reactivity against normal and injured human brain tissues was studied by Western blotting of sera from 169 subjects, 16 patients with NPSLE, 12 patients with SLE without neuropsychiatric manifestations (non-NPSLE), 32 patients with Sjögren's syndrome with or without central nervous involvement, 82 patients with multiple sclerosis, and 27 healthy subjects. A proteomic approach was then applied to characterize discriminant antigens identified after comparisons of all patterns. RESULTS: The serum self-IgG reactivity patterns against human brain tissue differed significantly between patients with NPSLE and the control groups. Four normal brain antigenic bands were specifically or preferentially recognized by sera from NPSLE patients (p240, p90, p77, and p24). Protein band p240 was characterized as microtubule-associated protein 2B (MAP-2B), p77 as Hsp70-71, and p24 as triosephosphate isomerase. Protein band p90 was not characterized. In contrast, 1 other protein band (p56, characterized as septin 7) was never recognized by sera from NPSLE patients but was recognized by a majority of sera from non-NPSLE patients. CONCLUSION: Our findings show that the immunoproteomic approach is a reliable method for assessing serum self-IgG reactivities against human brain tissue in NPSLE. Our characterization of some of the identified discriminant antigens, such as MAP-2B, triosephosphate isomerase, and septin 7, suggests that the stability of neuronal microtubules might be involved in the pathophysiology of NPSLE.

Foguem C, Launay D, Lambert M, Quemeneur T, Hachulla E, Wallaert B, Hatron PY. · Service de médecine interne, hôpital Claude-Huriez, CHRU de Lille, 59037 Lille, France. · Rev Med Interne. · Pubmed #16876917 No free full text.

Abstract: INTRODUCTION: Cystic lung disease is characterised on chest iconography by foci of decreased lung density with definable and thinned walls (wall thickness<4 mm) and with length's diameter superior at 1 cm. Cystic lung disease is exceptionally associated with the Sjögren's syndrome; very few cases have been described. EXEGESIS: We report two cases of cystic lung disease associated with Sjögren's syndrome, one occurring in a Lupus-Sjögren's overlapping syndrome, and another revealing primary Sjögren's syndrome. CONCLUSION: The Sjögren's syndrome should be recognised as could be associated with Cystic lung disease; and latent Sjögren's syndrome should be researched in presence of cystic lung lesions.

Vermersch P, Dufourd-Delalande S, Defoort-Dhellemmes S, Stojkovic T, Launay D, de Seze J. · Clinique Neurologique, Hôpital Roger Salengro, Lille. · Rev Neurol (Paris). · Pubmed #16365626 No free full text.

Abstract: INTRODUCTION: Adie's syndrome is usually a disease of unknown origin. We report two cases secondary to Sjögren syndrome. CASE REPORTS: A 26-year-old man developed in few months a sensitive neuropathy with a bilateral tonic pupil. A 50-year-old woman complained of sensitive signs probably related to a ganglionopathy and dysautonomic disorders affecting sudomotor and vasomotor functions. Adie syndrome had been diagnosed three years earlier. In both patients, the systemic signs and the results of the complementary tests led to the diagnosis of Sjögren's syndrome. Corticosteroids had limited effects on the sensitive signs and no influence on the tonic pupils. CONCLUSION: Adie syndrome, isolated or accompanied by other dysautonomic disorders, may reveal or precede the diagnosis of Sjögren's syndrome.

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.

Aractingi S, Sibilia J, Meignin V, Launay D, Hachulla E, Le Danff C, Janin A, Mariette X. · Hôpital Tenon, Paris, France. · Arthritis Rheum. · Pubmed #11953982 No free full text.

Abstract: OBJECTIVE: To determine whether microchimerism can be implicated in Sjögren's syndrome (SS) by studying minor salivary glands, one of the targets of the disease. METHODS: Labial salivary gland (LSG) biopsy specimens from 16 female patients with primary SS and 11 with systemic sclerosis (SSc) (a disease in which microchimerism is frequently detected) were analyzed. All 27 women had a history of pregnancy with a male baby. Specimens were microdissected, and polymerase chain reaction (PCR) was performed using the unique sex-determining region Y gene probe. RESULTS: The sensitivity of PCR for detecting male cells in LSG was high; the presence of 3 male cells was consistently detected in DNA extracted from a normal female LSG specimen to which male DNA had been added, and 1 male cell was detected in 50% of specimens analyzed. Male DNA was not found in any of the specimens from the 16 SS patients but was detected in 5 (45%) of 11 SSc specimens (P = 0.006). No differences in the rate of detection were found between patients with diffuse and limited SSc (male DNA detected in 2 of 3 and 3 of 8, respectively; P = 0.55) or between patients with and those without secondary SS (1 of 6 and 4 of 5, respectively; P = 0.08). CONCLUSION: The results of our study strengthen the possibility that microchimerism is implicated in SSc. This is the first study to demonstrate the presence of chimeric cells in LSG from 45% of SSc patients, independent of the presence of secondary SS. However, microchimerism was not detected in LSG from patients with primary SS, suggesting that the pathogenesis of the 2 diseases is different.

Kyndt X, Launay D, Hebbar M, Hatron PY, Fournier C, Michon-Pasturel U, Hachulla E, Devulder B. · Service de médecine interne A, Hôpital Claude-Huriez, CHRU, Lille, France. · Rev Med Interne. · Pubmed #10635070 No free full text.

Abstract: PURPOSE: The present study was aimed at assessing the influence of age on clinical and biological features of systemic sclerosis. METHODS: This retrospective study included 151 consecutive patients with systemic sclerosis. The median age at diagnosis was 50.0 years (range: 10-84 years). Patients were divided into two groups according to their age (lower than 50.0 years of age: 73 patients, equal to or above 50 years of age: 78 patients). The following features were compared between the two groups: gender, disease duration, extent of skin sclerosis, Crest syndrome, lung fibrosis, secondary Sjögren's syndrome, antinuclear, anticentromere, and anti-Scl70 antibodies. RESULTS: The disease duration was significantly higher in patients over 50 years of age (7.1 +/- 6.8 years vs 5.5 +/- 5.0 years, P < 0.05). Crest syndrome, secondary Sjögren's syndrome and anticentromere antibodies were significantly more common in patients over 50 years of age (17/73 vs 30/78, P < 10(-2); 9/73 vs 20/78, P < 10(-2), and 19/73 vs 31/78, P < 0.05; respectively). Anti-Scl70 antibodies were significantly more common in patients under 50 years of age (17/73 vs 10/78, P < 10(-2)). No significant difference was found in regard to the other features. CONCLUSION: The clinical and biological patterns of systemic sclerosis are different according to the age at disease onset. Crest syndrome including anticentromere antibodies and Sjögren's syndrome is more common in elderly patients, while anti- Scl-70 antibodies are more common in younger patients. This suggests the involvement of various mechanisms in the pathogenesis of systemic sclerosis, and that these mechanisms may depend on the age.