In Antisynthetase Syndrome, ACPA Are Associated With Severe and Erosive Arthritis: An Overlapping Rheumatoid Arthritis and Antisynthetase Syndrome

International audienceAbstract: Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case–control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P 7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA–ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Importance: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants: The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions: HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures: The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results: A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance: Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration: isrctn.org Identifier: ISRCTN5437125

Characteristics of autoimmune and systemic diseases in the Antilles-Guyana in their environment

Les maladies auto-immunes et systémiques sont des maladies sur lequel le champ de la recherche pose son œil de façon appuyée depuis 15 ans, du fait de l’émergence de thérapies biologiques ciblées. Ces pathologies sont volontiers hétérogènes, au mieux de fréquence ou caractéristiques particulières dans les populations d’origine Africaine. La connaissance de l’épidémiologie, et des caractéristiques de ces maladies est un préalable essentiel à la mise en place de recherche plus fondamentale pour aider à décomposer leurs physiopathologies souvent extrêmement complexes. En effet, la comparaison de différences marquées entre deux expressions dans des populations différentes d’une même maladie peut permettre d’aider à en dénouer le fil. Nous proposons dans ce travail une estimation des caractéristiques du lupus cutané et du lupus systémique en Guyane Française qui retrouve une faible fréquence de la maladie, la plus faible jamais retrouvée dans une population subsaharienne. Nous décrivons en Martinique sur le plan épidémiologique comme clinique une forme rare de myosite appelée syndrome des anti-synthétases semblant très particulière, l’épidémiologie et la description de la maladie de Kikuchi-Fujimoto pour la première fois dans la littérature, l’épidémiologie et les caractéristiques à base de population de la maladie de Behcet, des principales vascularites (périartérite noueuse, micropolyangéite, granulomatose éosinophile avec polyangéite, granulomatose avec polyangéite), de l’hypertension pulmonaire des connectivites qui semblent plus fréquentes que chez les Européens. Les néphropathies du lupus systémiques sont décrites dans la population Guadeloupéenne montrant une grande fréquence des néphropathies prolifératives. Le protocole EUROLUPUS qui permet le traitement de ces néphropathies prolifératives du lupus systémique avec de faibles doses de cyclophosphamide et de corticoïdes, est évalué en Martinique sur 30 patients alors qu’il ne l’a jamais été dans une population d’origine Africaine. Il semble y être aussi efficace que chez les patients d’origine Européenne, alors que les néphropathies y ont un pronostic meilleur. La maladie de Sjögren primaire est décrite en Martinique très proche de ce qu’on trouve en Europe sur le plan du tableau clinique et évolutif alors que cela n’est l’objet d’aucune étude dans une population d’origine noire Africaine. Nous avons par ailleurs montré en Martinique l’amélioration de la prise en charge du lupus systémique en Martinique au travers de la régression au fil du temps d’une des complications de la corticothérapie les plus pénibles pour les patients, l’ostéonécrose aseptique. La sclérodermie systémique est décrite à base de population avec épidémiologie dans les deux départements de Guadeloupe et Martinique, montrant des caractéristiques proches de celles retrouvées chez les AfroAméricains. Nous avons aussi montré la fréquence et la gravité des atteintes ORL des myopathies inflammatoires sur ces 2 départements avec une fréquence inhabituelle de certaines maladies auto-immunes dont le lupus systémique et les myosites inflammatoires associées aux anticorps anti-SRP, et l’absence de myosite à inclusion. Au total, nous apportons une somme de connaissance descriptive de ces maladies auto-immunes et systémiques permettant la mise en place de recherches plus fondamentales avec des bases solides par rapport aux profils hétérogènes de ces maladies.Auto-immunes and systemic diseases are priorities for researchers since 15 years. This is related to the emergence of biological therapies, associated to great efficacy. Although, these diseases are heterogeneous, depending of different parameters such as ethnicity or geography. In the African descent population, we encounter unusual or particular manifestations of these diseases. Also, the knowledge of epidemiology and population based descriptions are crucial to properly initiate works on these populations, but also to understand a particularly complex physiopathology by using differences between populations. We describe in this work the population based characteristics of pure cutaneous lupus and systemic lupus, including an epidemiology of the incidence of the lowest incidence ever found in a population of African heritage. We also describe a population based series of anti-synthetase syndrome, confirming that the presentation is totally different compared to caucasians, and allows in Martinique the incidence, never explored before. We also provide the first evaluation of Kikuchi-Fujimoto disease in a population of African origin, and the first incidence ever realized. We do the same evaluation of the epidemiology of Behcet’s disease in a black origin population that shows that this disease was at a similar frequency in Martinique and in Europe. Micropolyangeitis, polyarteritis, eosinophilic granulomatosis with polyangeitis and Granulomatosis with polyangeitis were evaluated in an epidemiologic study in Martinique, with addition of some cases from other French American region for a more powerful characteristics description. These diseases seem less frequent than in Europe, associated with less severity except for micropolyangeitis. EUROLUPUS, a protocol with low dose IV cyclophosphamide and low dose steroids, used to treat proliferative nephritis of systemic lupus is shown to have the same efficacy in Martinique than in patients of European origin. Primary Sjögren syndrome, evaluated in Martinique, is very similar in expression than what is found in Europe. The decrease overtime of aseptic osteonecrosis, a steroid side effect, is a witness of better control of systemic lupus activity with less usage permitted by protocols and new immunosuppressive drugs such as mycophenolate. Systemic sclerosis is described as very close to African American in a population based study in Martinique and Guadeloupe. We finally show that the rare ENT involvement of idiopathic inflammatory myositis is frequent in our population, associated with poor outcome, and surprisingly frequently related to systemic lupus and necrotizing myositis associated to SRP antibody but not to inclusion body myositis. To conclude, we allow an amount of description of these diseases in our region, including pioneer studies. This works tends to be the basis for studies to be continued in a more fundamental way in our countries

Pregnancy and childbirth after treatment with autologous hematopoietic stem cell transplantation for severe systemic sclerosis requiring parenteral nutrition. Ethical issues

We report a pregnancy in a patient who had undergone autologous hematopoietic stem cell transplantation (AHSCT) for diffuse cutaneous systemic sclerosis (SSc). SSc onset was at age 25, with Raynaud phenomenon and evolved to include diffuse cutaneous, arthritis, pulmonary fibrosis and extensive gastrointestinal involvement. AHSCT (cyclophosphamide/ATG for conditioning) was performed four years later with improvement of all features apart from the gastrointestinal symptoms requiring parenteral nutrition (PN). Forty months after AHSCT, she had a spontaneous miscarriage necessitating curettage. Despite advice to avoid pregnancy because of poor nutritional status and recurring catheter infections from her PN, she fell pregnant one year later. The pregnancy proceeded normally and she delivered at 34 weeks, under cesarean section. The baby girl, (1990g and 4 APGAR score) after initial respiratory distress, is now 4 years old with normal growth and development. Unfortunately, the patient died early in 2008 due to severe disease progression terminating with gastrointestinal obstruction and pericarditis. This first report of a successful pregnancy in a patient with diffuse SSc treated by AHSCT illustrates that despite the possibility for a normal pregnancy, the decision to do so includes aspects of maternal prognosis

Epidemiology and Characteristics of Spondyloarthritis in the Predominantly Afro-Descendant Population of Martinique, a French Caribbean Island

(1) Background: The prevalence of Spondyloarthritis (SpA) varies significantly in different regions and ethnic groups due several factors such as heterogeneity in study populations, the diversity of classification criteria used in epidemiological studies, the prevalence variability of HLA-B27 or disparity in healthcare access. To our knowledge, there is no data on SpA in Martinique, a French region in the Caribbean with a predominantly Afro-descendant population and a high level of healthcare. (2) Methods: This was a retrospective study of all SpA patients treated at the Fort de France University Hospital between 1 January 1997 and 1 January 2008. (3) Results: In our cohort of 86 SpA patients, age at diagnosis was late (41 years old), ankylosing spondylitis (AS) was the most frequent sub-type (60.5%), inflammatory bowel disease was the most frequent extra articular feature (23.3%) and no one had personal familial history of the disease. Inflammatory syndrome concerned 55.6% of patients, no one was positive for HIV and HLA-B27 positivity was low (42.2%). However, HLA-B27 was statistically associated with AS. Out of 64 patients, 41 had sacroiliitis. (4) Conclusion: To our knowledge, this is the first comprehensive descriptive study of SpA subtypes in Martinique, a French region in the Caribbean. We report clinical and biological similarities in our SpA cohort with those of sub-Saharan Africa and with SpA subtypes reported in Afro-descendant populations

Retroperitoneal fibrosis as extramedullary hematopoiesis of a chronic myelomonocytic leukemia

International audienc

Reproducibility and utility of the 6-minute walk test in systemic sclerosis

Objective: To assess the reproducibility and the utility of the 6-minute walk test (6MWT) in systemic sclerosis (SSc). Methods: All patients with SSc who underwent at least two 6MWT within a minimum 3-month interval plus simultaneous routine clinical, biological, and functional evaluations were consecutively enrolled in this observational study over 6 years. Following American Thoracic Society guidelines, each 6MWT was repeated twice to assess the 6-minute walk distance (6MWD) reproducibility, with the highest value being reported for subsequent analysis. Results: Among 56 (38 female) included patients aged 46 +/- SD 12.7 years, with 17 +/- 10 modified Rodnan skin score (mRSS) and 1 +/- 0.8 Scleroderma Health Assessment Questionnaire (SHAQ) at first referral, 277 6MWT evaluations (5 +/- 3.9 6MWT per patient) were performed over 23 +/- 225 months followup. Meanwhile, 8 deaths (87.5% SSc-related) occurred. The mean 6MWD absolute value was 457 +/- 117 m with a 4 +/- 2.2 mean Borg dyspnea score. The 6MWD intraclass correlation coefficient was 0.996 (95% CI 0.995-0.999, p < 0.0001). In multivariate linear regression analysis, these factors were independently associated with a lower 6MWD: sex (R-2 = 0.47, p < 0.0001), mRSS (R-2 = 0.47, p = 0.008), tendon friction rub (R-2 = 0.47, p = 0.003), SHAQ (R-2 = 0.47, p = 0.02), muscle disability score (R-2 = 0.47, p = 0.03), DLCO% (R-2 = 0.47, p = 0.0008), and left ventricular ejection fraction (R-2 = 0.47, p = 0.006). The 6MWD at first referral was an independent predictor for the overall mortality (IIR 0.99, 95% CI 0.988-0.999) and the SSc-related mortality (HR 0.99, 95% CI 0.988-0.999). Conclusion: We show strong reproducibility for the 6MWD and confirm the 6MWT utility to assess the overall prognosis of patients with SSc