Déterminer si la prévalence de l’athérosclérose infraclinique est plus importante chez les patients atteints de lupus érythémateux systémique (LES) que les témoins sains, en évaluant leur épaisseur intima-média carotidienne (EIMC), leur nombre de plaques carotidiennes (PC) ou leur vasodilation flux-dépendante (VFD).Les données ont été cherchées dans les bases de données Medline, Cochrane et Embase. Deux investigateurs indépendants ont sélectionné les études comparant le niveau d’athérosclérose des patients LES à celui de témoins sains. Les résultats des mesures ont été regroupés par une méta-analyse. Les facteurs influençant le résultat de l’EIMC, de la VFD ou du nombre de PC ont été collectés.Un total de 68 articles, sélectionnés parmi 202 initialement identifiés, a été sélectionné pour la méta-analyse. Les patients LES présentaient une augmentation significative de l’EIMC (différence moyenne 0,08 mm, 95 % IC [0,06–0,09], p < 0,05), du nombre de PC (odds ratio 2,01, 95 % CI [1,63–2,47], p < 0,05), et une diminution significative de la VFD (différence moyenne MD −3,96 %, 95 % CI [−5,37 à −2,54)], p < 0,05). L’hétérogénéité de l’analyse était élevée. Cependant, une analyse en sous-groupe incluant uniquement les études respectant les dernières recommandations internationales a montré une augmentation toujours significative de l’EIMC avec une hétérogénéité négligeable (différence moyenne 0,04 mm, 95 % CI [0,02–0,06], p < 0,05 ; I2 = 23 %).Les patients LES présentent une athérosclérose infraclinique plus marquée que les témoins sains. L’EIMC est une mesure particulièrement prometteuse concernant l’évaluation du risque cardiovasculaire, car non invasive, non irradiante, et reproductible, contrairement à la VFD qui est influencée par de nombreux facteurs comme le tabagisme. Ainsi, l’EIMC pourrait être une alternative de choix à la mesure des PC, jusque là considérée comme le gold standard. Les études futures devront se concentrer sur la réduction de l’hétérogénéité de ces mesures en utilisant des procédures standardisées.

Au sein des lipodystrophies la maladie de Dercum (adiposis dolorosa) tient une place à part en raison de l’existence à côté d’une obésité importante d’une lipomatose douloureuse, de sa prédominance féminine et de l’absence de profil génétique particulier même dans les rares formes familiales. Son traitement local et/ou général est décevant. Le rôle possible des adipokines est évoqué.

Le présent travail résume brièvement depuis la préhistoire jusqu’à nos jours l’histoire de ce qui se nomme maintenant la spondylarthrite.

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 19 juillet 2014

Background The Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is a rare autoinflammatory disorder of skin and bone that can be classified with the inflammatory spondyloarthropathies (1). Genetic predisposing factors for SAPHO syndrome have been long suspected because of (i) reported familial clustering of the syndrome - although most cases are sporadic - (2), and (ii) the existence of two mouse models of the syndrome (the cmo and Lupo strains), each with a different spontaneous recessive mutation in the Pstpip2 gene (3,4). Previous studies excluded a role for the genes PSTPIP2, LPIN,NOD2, IL1RL2, IL1RN, IL36RN and SIGLEC15 in the pathogenesis of the syndrome (5,6). Objectives Identify and validate candidate genes involved in the pathogenesis of familial SAPHO syndrome by performing whole-exome sequencing (WES) of affected subjects and unaffected relatives. Methods We investigated a cohort of 44 SAPHO subjects that includes 5 families segregating the syndrome. After obtaining written informed consent, we extracted DNA from peripheral blood samples by using automated magnetic-bead technology (Chemagen). Exomes captured with Agilent SureSelect V5+UTR kit were subjected to paired-end sequencing on an Illumina HiSeq200 sequencer (Sistemas Genόmicos). Candidate genes and putatively pathogenic variants were identified by using Variant Analysis software (Ingenuity). Validation was undertaken by Sanger sequencing, segregation analysis and functional assays when appropriate. Results We identified several potentially pathogenic variants in our cohort in genes whose products are potentially involved in the pathogenesis of SAPHO syndrome. In affected subjects we also found variants known to predispose to autoinflammatory/autoimmune disease in genes such as NOD2/CARD15. Conclusions WES is a very powerful tool to investigate the genetic factors underlying rare inherited autoinflammatory disorders that cannot be analyzed by classical genetic methods such as positional cloning. References Clin Exp Rheumatol 1988; 6: 109-112. Joint Bone Spine 2007; 74: 123-126. Bone 2006; 38: 41-47. Blood 2006, 107; 3350-3358. J Rheumatol 2010; 37; 401-409. Ann Rheumat Dis 2013; 72 - Suppl 3; 169. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4251

Background The Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is currently considered as an autoinflammatory disorder of bone and skin that can be classified with the inflammatory spondyloarthropathies (1). Genetic predisposing factors for SAPHO syndrome have been long suspected because of reported familial clustering of the syndrome, although most cases are sporadic (2). Additional support for a genetic origin of the syndrome is provided by a murine model (the cmo mouse) that carries a spontaneous recessive mutation in the Pstpip2 gene (3). However, previous studies excluded a role for the genes PSIPT2, LPIN and NOD2 in the pathogenesis of the syndrome (4). Two rare autoinflammatory disorders, DIRA and DITRA syndromes, have been related to a genetic deficiency in interleukin-1 (IL-1) and IL-36 receptor antagonists, respectively (5-7). These two conditions, particularly DIRA syndrome, share some features with SAPHO syndrome. Objectives We investigated the possible role of the genes encoding IL-1 receptor antagonist (IL1RN), IL-36 receptor (IL36R), IL-36 receptor antagonist (IL36RN) and cell-surface lectin Siglec-15 (SIGLEC15) in the pathogenesis of SAPHO syndrome. Methods The study was performed on a cohort of 40 SAPHO syndrome subjects that includes 3 familial cases. After obtaining written informed consent, we extracted DNA from peripheral blood samples by using automated magnetic-bead technology (Chemagen). We PCR-amplified and sequenced all exons and intron-exon boundaries of the four candidate genes. In addition, we carried out a genome-wide copy-number variation (CNV) analysis on SNP arrays (Illumina BeadStudio array of 2.5 million SNPs). Results We did not identify any pathogenic mutations in the IL1RN, IL36R, IL36RN and SIGLEC15 genes, although we did detect known polymorphic variations. Heterozygosity and CNV analyses excluded any deletions of the candidate genes in our cohort. Conclusions We found no involvement of the IL1RN, IL36R, IL36RN and SIGLEC15 genes in the pathogenesis of SAPHO syndrome. References Clin Exp Rheumatol 1988; 6: 109-112. Joint Bone Spine 2007; 74: 123-126. Bone 2006; 38: 41-47. J Rheumatol 2010; 37: 401-409. N Engl J Med 2009; 360: 2426-2437. N Engl J Med 2011; 365:620–628. Am J Hum Genet2011; 89: 432–437. Acknowledgements T.C. was a recipient of an “Ayuda Predoctoral” fellowship from CIBERER. This work was supported by grant FIS PI11/00283 from ISCIII (to F.J.d.C.). Disclosure of Interest None Declared

La découverte d’une hyperferritinémie est le plus souvent fortuite. La démarche diagnostique a pour but de rechercher l’étiologie responsable et de vérifier s’il existe ou non une surcharge hépatique en fer. Trois étapes sont proposées. Les éléments cliniques et quelques examens biologiques simples sont suffisants dans un premier temps pour déceler une des quatre causes les plus fréquentes : alcoolisme, syndrome inflammatoire, cytolyse, syndrome métabolique. Aucune de ces causes ne s’accompagne d’une surcharge hépatique en fer importante. S’il existe un coefficient de saturation élevé (> 50 %), une hémochromatose héréditaire sera évoquée en priorité. Dans un deuxième temps, des pathologies plus rares seront recherchées. Parmi celles-ci, seules les pathologies hématologiques chroniques, acquises ou congénitales, sont à risque de surcharge hépatique en fer. Dans un troisième temps, si un doute persiste dans la recherche étiologique, que la ferritinémie est très élevée ou continue à s’élever, il est indispensable de vérifier qu’il n’existe pas une surcharge hépatique en fer. Pour cela, l’IRM avec étude de la charge en fer est l’examen principal qui guidera l’attitude thérapeutique. La découverte d’une cause ne doit pas faire oublier que plusieurs causes sont associées dans plus de 40 % des cas.The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (> 50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases.

The representation of the body in the brain is constantly updated to allow optimal sensorimotor interactions with the external world. In addition to dynamic features, body representation holds stable features that are still largely unknown. In the present work we explored the hypothesis that body parts have preferential associations with relative spatial locations. Specifically, in three experiments, we found consistent preferential associations between the index finger and the top position, and between the thumb and the bottom position. This association was found in a tactile sensory discrimination task, which was conducted both with and without vision, as well as at the implicit conceptual association level. These findings show that body parts and spatial locations are stably associated. Therefore, not only are body segments dynamically mapped in space for perception and action, but they also hold intrinsic spatial information that contributes to somatosensory spatial processing.

Objective. To determine the prevalence of the most often tested autoantibodies in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Methods. We identified 90 patients seen in our unit between June 2002 and June 2009, and diagnosed according to the proposed criteria for SAPHO syndrome. Demographic and clinical data were collected as well as immunological results, including antinuclear, antithyroid peroxydase (TPO), antithyroid globulin (Tg), antigastric parietal cell, antismooth muscle, antimitochondria, and anti-liver-kidney microsome (LKM) antibodies. Anticyclic citrullinated peptide (CCP) antibodies were analyzed in 69 patients, antibodies to soluble extractable nuclear antigens in 43, anti-double-stranded DNA (dsDNA) antibodies in 22 [depending on the type of fluorescence of antinuclear antibody (ANA)], and antiendomysium antibodies in 55. Results Autoantibodies were found in 20 patients (22.2%): 14 patients (15.5%) had positive ANA (titer ≥ 1/160); among them, 10 (11%) patients never took a lupus-inducing drug. Antithyroid antibodies (anti-TPO and/or anti-Tg antibodies) were found in only 3 patients (3.3%). Three patients (3.3%) were positive for antigastric parietal cell antibodies and 4 (4.4%) were weakly positive for antismooth muscle antibodies. Antimitochondria and LKM antibodies were negative in all 90 patients. Anti-CCP and anti-dsDNA antibodies were negative in the 69 and 22 patients tested, respectively. One out of 43 patients (2.3%) had anti-SSA antibodies. Antiendomysium antibodies were negative in the 55 patients tested. Conclusion. Our study indicates an increased prevalence of autoantibodies in SAPHO syndrome, with no specific profile. We failed to confirm the reports of an increased prevalence of antithyroid antibodies. These results tend to support a link between autoimmunity and SAPHO syndrome.

La fibromialgia, o meglio la sindrome fibromialgica, è uno stato dolente spontaneo e provocato che colpisce principalmente le donne di età media, associato spesso a un affaticamento generale e locale, a uno stato ansioso-depressivo e a disturbi del sonno. Non è stata identificata alcuna lesione anatomica o biochimica univoca, il che ha portato a un riconoscimento alquanto tardivo, ma attualmente assicurato. I sintomi evolvono nel lungo corso senza alcuna invalidità grave. La diagnosi utilizza, in mancanza di meglio, i criteri dell’American College of Rheumatology (ACR) che, al di fuori dei sintomi, utilizza l’evidenziazione di punti anormalmente dolenti alla pressione. Questi criteri sono criteri di classificazione, in assenza di criteri diagnostici più precisi. Quadri simili sono osservati in diversi stati patologici precisi di varia natura e che, per molti, sono diagnosi differenziali. Lo stesso vale per quadri funzionali quali la sindrome di stanchezza cronica. La fisiopatologia più ammessa esclude la responsabilità iniziale del muscolo e quella di un disordine mentale primitivo. Sembra, grazie ai progressi della ricerca, che si sia in presenza di un disturbo neurologico centrale dove sono alterate la trasmissione, la modulazione e la percezione delle afferenze dolorose a livello del midollo e delle strutture della base del cervello. La gestione, che richiede un minimo di empatia, associa gli analgesici semplici (paracetamolo, tramadolo) ed eventualmente, senza aspettarsi risultati spettacolari, diverse classi di neuromodulatori, compresi antidepressivi e antiepilettici. Tuttavia, una gestione fisica con tecniche varie deve essere associata a una gestione psicologica e medicosociale.

This report is devoted to Philippe Gaucher's life and career. His MD thesis, presented while he was just an intern, is a quite unfrequent example of the description of a new disease, based on the anatomoclinical study of a single case. Since more than 100 years, its eponym is still used in the international literature.

OBJECTIVETo describe characteristics and outcomes of vasculitides associated with malignancies.METHODSThe requirement for inclusion in this retrospective, 10-year study was development of vasculitis in patients with a progressing malignancy. Malignancies secondary to immunosuppressants used to treat vasculitis were excluded. The main characteristics of vasculitides were analyzed and compared according to the type of malignancy.RESULTSSixty patients were included (male/female sex ratio 2.53, mean age 62.4 years). Mean followup duration was 45.2 months. Vasculitides were cutaneous leukocytoclastic (45%), polyarteritis nodosa (36.7%), Wegener's granulomatosis (6.7%), microscopic polyangiitis (5%), and Henoch-Schönlein purpura (5%). Malignancies were distributed as follows: hematologic in 63.1%, myelodysplastic syndrome (MDS) in 32.3%, lymphoid in 29.2%, and solid tumor in 36.9%. Vasculitides were diagnosed concurrently with malignancy in 38% of the cases. Manifestations of vasculitides were fever (41.7%), cutaneous involvement (78.3%), arthralgias (46.7%), peripheral neuropathy (31.7%), renal involvement (23.3%; 11.7% glomerulonephritis, 11.7% microaneurysms, 6.7% renal insufficiency), and antineutrophil cytoplasmic antibody (20.4%). Vasculitis treatments were corticosteroids (78.3%) and immunosuppressant(s) (41.7%). Vasculitis was cured in 65% of patients, but 58.3% died, with 1 death secondary to vasculitis. Independent of subtype, patients with vasculitides associated with MDS more frequently had renal manifestations (P = 0.02) and steroid dependence (P = 0.04) and achieved complete remission less often (P = 0.04) than patients with vasculitides associated with other malignancies. Patients with vasculitides associated with a solid tumor more frequently had peripheral neurologic involvement (P = 0.05). Patients with vasculitides associated with lymphoid malignancy had less frequent arthralgias (P = 0.01) and renal involvement (P = 0.02).CONCLUSIONVasculitides occurring during malignancies present distinctive features according to the vasculitis subtype and nature of the malignancy.