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Background Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. Methods HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ Results The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76–0.94) and specificity of 0.89 (95% CI 0.72–0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level ( Conclusions These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

L'effet des antipaludeens de synthese sur les infections virales est etudie depuis plusieurs annees, y compris l'hypothese d'un effet sur le SARS [1]. L'efficacite in vitro de la chloroquine contre le SARS-CoV-2 a ete decrite [2] , ainsi que la superiorite potentielle de l'hydroxycholoroquine. De nombreuses etudes in vivo ont ete menees. Il existe peu de donnees sur l'impact d'un traitement au long cours par hydroxychloroquine (HCQ) sur l'infection a SARS CoV-2 et les tests diagnostiques. Nous avons pour cela analyse les donnees des patients atteints de COVID-19 et suivis pour un rhumatisme inflammatoire chronique et/ou une maladie auto-immune systemique (iRMD-COVID-19) selon la prise ou non d'hydroxychloroquine comme DMARD. Les patients ont ete inclus a partir de la cohorte francaise iRMD-COVID-19 [3]. Les donnees cliniques, diagnostiques et d'evolution de l'infection a SARS CoV-2 des patients traites au prealable par HCQ ont ete comparees a celle des patients n'ayant pas de traitement par HCQ au moment de l'infection. Les criteres d'appariement etaient l'âge, le sexe, les comorbidites, un traitement immunosuppresseur, et l'utilisation de la PCR nasale. Parmi les 871 patients, 82 patients etaient traites par HCQ. Soixante et onze cas traites par HCQ ont pu etre apparies et compares a 191 temoins. Le taux de PCR nasale positive etait de 85 % dans le groupe HCQ contre 81 % dans le groupe controle (absolute standardized difference = 6,0 %). Il n'y avait pas de difference significative entre les cas et les controles concernant les signes cliniques, le taux d'hospitalisation (33,8 % vs 27,7 % ;OR = 1,75 (0,86-3,56) ;p = 0,12), le taux d'admission en soins intensifs (11,3 % vs 9,4 % ;OR= 1,94 (0,69-5,41) ;p = 0,21) et le taux de deces (5,9 % vs 6,6 % ;OR = 1,10 (0,30-4,04) ;p = 0,89). Chez les patients atteints de COVID-19 et suivis pour un rhumatisme inflammatoire chronique et/ou une maladie auto-immune systemique de la cohorte French RMD Covid 19, la prise d'HCQ comme DMARD n'a pas modifie le taux de positivite de la PCR nasale, n'a pas modifie la presentation clinique et n'a pas prevenu la survenue de forme severe de l'infection a SARS CoV-2 comparativement aux patients sans HCQ. (French) [ABSTRACT FROM AUTHOR] Copyright of Revue de Medecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The objective of this study was to evaluate periarticular FDG uptake scores from 18F-FDG-PET/CT to identify polymyalgia rheumatica (PMR) within a population presenting rheumatic diseases. Methods: A French retrospective study from 2011 to 2015 was conducted. Patients who underwent 18F-FDG-PET/CT for diagnosis or follow-up of a rheumatism or an unexplained biological inflammatory syndrome were included. Clinical data and final diagnosis were reviewed. Seventeen periarticular sites were sorted by a visual reading enabling us to calculate two scores: mean FDG visual uptake score, number of sites with significant uptake same as that or higher than liver uptake intensity and by a semi-quantitative analysis using mean maximum standardized uptake value (SUVmax). Optimal cutoffs of visual score and SUVmax to diagnose PMR were determined using receiver operating characteristics curves. Results: Among 222 18F-FDG PET/CT selected for 215 patients, 161 18F-FDG PET/CT were performed in patients who presented inflammatory rheumatism as a final diagnosis (of whom 57 PMR). The presence of at least three sites with significant uptake identified PMR with a sensitivity of 86% and a specificity of 85.5% (AUC 0.872, 95% CI [0.81-0.93]). The mean FDG visual score cutoff to diagnose a PMR was 0.765 with a sensitivity of 82.5% and a specificity of 75.8% (AUC 0.854; 95% CI [0.80-0.91]). The mean SUVmax cutoff to diagnose PMR was 2.168 with a sensitivity of 77.2% and a specificity of 77.6% (AUC 0.842; 95% CI [0.79-0.89]). Conclusions: This study suggests that 18F-FDG PET/CT had good performances to identify PMR within a population presenting rheumatic diseases.

Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations.

The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management.

Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated.Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody.Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome.Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.

Resume Introduction Les metastases hypophysaires sont une etiologie rare de diabete insipide. Elles compliquent habituellement des cancers tres evolues. Observations Nous rapportons les observations de quatre patients chez lesquels la survenue d’un diabete insipide a fait decouvrir une neoplasie bronchique (deux cas) ou mammaire (deux cas) metastatique. Un patient avait un panhypopituitarisme, un autre un diabete insipide associe a une insuffisance corticotrope et deux patients une atteinte isolee de la posthypophyse. Dans un cas, la ponction lombaire montrait une meningite lymphocytaire. L’imagerie par resonance magnetique cerebrale montrait une disparition de l’hypersignal normal de la posthypophyse dans un cas et une infiltration de la posthypophyse dans les trois autres cas. Conclusion Les cancers du sein et du poumon sont les etiologies les plus frequentes des metastases hypophysaires. Meme s’il existe souvent deja d’autres localisations, le diabete insipide peut reveler la maladie et necessiter la realisation d’une biopsie hypophysaire a visee diagnostique.

Isolated pulmonary involvement in Goodpasture's syndrome is exceptionally described. We report a 36-year-old woman with pulmonary haemorrhage and review 28 additional cases of the literature. In fact, these patients had often mild urine abnormalities and constant glomerular lesions. Antiglomerular basement membrane antibodies testing should be systematically ordered in patients presenting with alveolar haemorrhage. Goodpasture's syndrome without renal abnormality could be an early stage of the disease with a better prognosis.

Resume Introduction Si, au cours d’un syndrome nephrotique, des anomalies des indices fonctionnels thyroidiens ont souvent ete observees, une hypothyroidie n’a ete qu’exceptionnellement decrite. Exegese Nous rapportons trois observations de patients adultes (1, 2, 3) qui ont eu une hypothyroidie associee a un syndrome nephrotique (atteinte glomerulaire minime [1], glomerulonephrite extramembraneuse idiopathique de stade I [2] et de stade II [3]). Le traitement etait celui de la glomerulopathie et une hormonotherapie substitutive thyroidienne. L’euthyroidie etait obtenue avec une faible substitution (1, 2) quand la proteinurie diminuait et avec une hormonotherapie plus forte (3) lorsque le syndrome nephrotique n’etait pas controle. Conclusion La fuite urinaire des hormones thyroidiennes et de leurs proteines porteuses au cours du syndrome nephrotique engendre, si elle est abondante, une diminution de la T4 libre et une augmentation de la TSH. La recherche systematique d’une hypothyroidie associee est necessaire, surtout si la proteinurie est massive et prolongee.

Resume Introduction. – L'atteinte pancreatique est une localisation exceptionnelle de la granulomatose de Wegener et merite d'etre signalee. Exegese. – Nous decrivons une observation d'une forme pseudo-tumorale de granulomatose de Wegener localisee au pancreas. Nous discutons six autres observations d'atteinte pancreatique rapportees dans la litterature medicale (deux pseudo-tumeurs, trois pancreatites aigues et une insuffisance pancreatique chronique). Conclusion. – C'est une localisation a ne pas meconnaitre d'autant plus qu'un traitement rapidement instaure et associant corticoides et cyclophosphamide semble efficace.

Resume Introduction La maladie des griffes du chat se manifeste sous la forme d’adenites evoluant dans la majorite des cas spontanement vers la guerison. Nous rapportons deux observations de maladie des griffes du chat avec atteinte pretragienne survenant chez les sujets immunocompetents. Observations Observation 1 : un homme de 28 ans consultait pour une tumefaction cervicale gauche d’apparition recente, avec secondairement une paralysie faciale peripherique et une cytolyse hepatique. Les serologies des hepatites virales, EBV, CMV, VIH, toxoplasmose etaient negatives. La biopsie exerese ganglionnaire retrouvait une lymphadenite granulomateuse et la PCR Bartonella henselae etait positive. Sous doxycycline pendant trois mois, associe a de la rifampicine pendant 15 jours, l’atteinte hepatique disparaissait et la paralysie faciale regressait partiellement. Observation 2 : un homme de 17 ans consultait pour une tumefaction parotidienne droite associee a des adenopathies cervicales posterieures, avec fievre et sueurs profuses. Un volumineux ganglion pretragien droit avec remaniement necrotique etait visible au scanner. La PCR B. henselae sur le liquide de cytoponction ganglionnaire etait positive. L’evolution etait favorable apres un drainage chirurgical et l’echec d’un traitement par macrolides. Conclusion La localisation pretragienne de la maladie des griffes du chat est rare. Cette topographie doit etre connue et necessiter la recherche d’un contact avec un chat apres exclusion d’une localisation tumorale parotidienne, d’un lymphome ou d’une tuberculose. Le diagnostic repose sur la PCR B. henselae . L’evolution est souvent spontanement favorable mais un traitement chirurgical peut etre necessaire.

Objective: To study the levels of procalcitonin (PCT) in various inflammatory states seen in an internal medicine department and to evaluate the possible discriminative role of PCT in differentiating bacterial infection from other inflammatory processes. Methods: PCT, C reactive protein (CRP), and white blood cell count (WBC) were measured in patients admitted to the department for fever or biological inflammatory syndrome, or both. The serum of 173 consecutive patients was analysed according to the aetiological diagnosis. The patients were divided into two groups: group I (n=60) with documented bacterial or fungal infection; group II (n=113) with abacterial inflammatory disease. Results: PCT levels were >0.5 ng/ml in 39/60 (65%) patients in group I. In group II, three patients with a viral infection had slightly increased PCT levels (0.7, 0.8, and 1.1 ng/ml) as did two others, one with crystal arthritis and the other with vasculitis (0.7 ng/ml in both cases). All other patients in group II had PCT levels 0.5 ng/ml was taken as the marker of bacterial infection (sensitivity 65%, specificity 96%). PCT values were more discriminative than WBC and CRP in distinguishing a bacterial infection from another inflammatory process. Conclusion: PCT levels only rose significantly during bacterial infections. In this study PCT levels >1.2 ng/ml were always evidence of bacterial infection and the cue for starting antibiotic treatment.

Background Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. Patients and methods Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade Results Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. Conclusion Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

In France, internal medicine is a speciality obtained after 5 years of theoretical and practical training, often completed by additional years. The last version of the official training program was released in 2004 and was characterised by its polyvalence. After the reform of medical studies was announced, the French young internists group decided to carry out a survey in order to know the vision of the young internist about their initial theoretical and practical training. This survey was done online using a questionnaire from February 10th to April 8th, 2010. One hundred and twenty-three young internists under training completed the questionnaire. The results showed that a high number of trainees chose a subspeciality and took a complementary training afterwards. About 63% of them would rather have more theoretical training through lectures (72%) and oral presentations (58%). Eighty-eight per cent of young internists would rather have a national frame of reference with a common training program. According to 73% of the young internists who completed the survey, the practical training is adapted but 95% of them would like to be given the opportunity to have some consultation during their initial training. Seventy-nine per cent of the young internists seem to be interested in the clinical research but most of them (89%) think to be not well trained enough to do it.

Resume Propos. – En raison de leur rarete et de leurs manifestations cliniques insidieuses, les thromboses veineuses mesenteriques superieures sont de diagnostic difficile. La rapidite avec laquelle ce dernier est fait conditionne l’evolution vers l’infarctus mesenterique et ainsi le pronostic. Methodes. – Nous rapportons les symptomes et les anomalies de la coagulation decouvertes chez six patients ayant fait une thrombose veineuse mesenterique superieure. Resultats. – Cinq des six patients ont ete hospitalises pour une douleur abdominale dont la duree d’evolution etait de neuf jours avant que le diagnostic de thrombose veineuse mesenterique ne soit retenu. Trois d’entre eux avaient de la fievre. Chez deux autres, on retenait un antecedent de thrombose veineuse profonde. Le bilan de thrombophilie a montre, chez tous les patients, une anomalie de la coagulation et deux anomalies etaient associees chez trois des six patients. Dans tous les cas, le scanner abdominal a permis le diagnostic de thrombose veineuse mesenterique superieure. Cinq des six patients ont ete traites avec succes par le seul traitement medical. Conclusions. – Le scanner abdominal doit etre effectue precocement devant tout tableau de douleur abdominale sans cause evidente et ce d’autant plus qu’il existe des antecedents de thrombose profonde. Seul un diagnostic precoce permet une prise en charge medicale des thromboses mesenteriques superieures. La recherche de thrombophilie est necessaire, car elle represente un mecanisme frequent a l’origine de ces thromboses.

Resume Propos. – L’urticaire chronique est une pathologie tres frequente pour laquelle une etiologie est rarement objectivee. Les maladies auto-immunes ont recemment ete mises en cause dans sa survenue et tout particulierement les thyroidites auto-immunes. Methodes. – Nous avons collige les observations des patients presentant a la fois une thyroidite de Hashimoto et une urticaire chronique. Resultats. – Six patientes associaient ces deux diagnostics. Quatre patientes dont trois traitees par levothyroxine etaient euthyroidiennes ; les deux autres etaient en hypothyroidie. Pour trois d’entre elles, le diagnostic de thyroidite de Hashimoto a ete effectue dans le cadre du bilan d’une urticaire chronique. Les trois autres ont developpe une urticaire chronique alors que la thyroidite de Hashimoto etait connue. Chez deux patientes hypothyroidiennes, l’urticaire chronique a disparu avec le traitement hormonal substitutif. Une patiente euthyroidienne a ete amelioree par la prescription de L-thyroxine. Une quatrieme patiente euthyroidienne sous levothyroxine n’a eu qu’une amelioration discrete lors de l’augmentation de la posologie de celle-ci. Elle a totalement gueri sous corticotherapie par voie orale. Conclusion. – Les mecanismes liant thyroidite de Hashimoto et urticaire chronique restent mal compris. Les autoanticorps antithyroidiens pourraient etre a l’origine d’une liberation d’histamine en se fixant sur les recepteurs des IgE des mastocytes. Le traitement substitutif hormonal pourrait, en diminuant la stimulation thyroidienne, permettre la disparition les lesions cutanees. Ainsi si un bilan hormonal et immunologique thyroidien doit etre effectue dans l’enquete etiologique des urticaires chroniques, la decouverte d’une thyroidite de Hashimoto doit faire debuter une opotherapie que le malade soit euthyroidien ou hypothyroidien.

Resume Propos. – Le purpura rhumatoide est une vascularite rare chez l’adulte. L’atteinte digestive peut parfois etre a l’origine de complications et justifier un traitement adapte. Les donnees tomodensitometriques de l’atteinte digestive sont peu connues et pourraient etre utiles dans la prise en charge. Patients et methodes. – Six adultes atteints de purpura rhumatoide (criteres de l’American College of Rheumatology) avec des symptomes digestifs ont beneficie d’une tomodensitometrie abdominopelvienne avant tout traitement. Il s’agissait de quatre hommes et deux femmes âges de 19 a 74 ans. Les symptomes abdominaux ont ete concomitants du purpura dans deux cas, ou lui ont fait suite. Resultats. – Des lesions de l’intestin grele etaient constantes avec un epaississement parietal segmentaire prenant l’aspect d’image en double halo chez trois patients. L’atteinte etait duodenale chez deux patients, jejunale chez deux et ileale chez cinq. Deux segments etaient atteints chez un patient et trois segments chez un autre. Un epanchement intraperitoneal etait toujours observe. Il n’existait pas d’atteinte colique radiologique. Une fois les resultats connus, tous les patients ont recu une corticotherapie generale debutee par voie intraveineuse cinq fois a des posologies de 80 a 1 000 mg/j de methylprednisolone. L’evolution clinique a toujours ete favorable et confirmee par echographie ou tomodensitometrie trois fois. Conclusion. – La tomodensitometrie abdominopelvienne a montre des lesions evocatrices de vascularite intestinale par leur aspect, leur topographie et leur caractere segmentaire et focal. Elle a aussi contribue a la recherche d’une eventuelle cause neoplasique sous-jacente, a permis d’ecarter une autre cause de douleur abdominale et surtout une complication abdominale du purpura rhumatoide contre-indiquant la corticotherapie. Ces elements ont conforte l’indication d’une corticotherapie generale et aucun malade n’a eu de complication severe requerant une chirurgie. Ces images ne sont cependant pas specifiques du purpura rhumatoide et doivent etre replacees dans le contexte clinique et biologique.

Resume Objectif Le but de cette etude etait d'evaluer la place de la tomodensitometrie dans le suivi des patients chez lesquels se developpent des lesions pleuropulmonaires au cours d'une granulomatose de Wegener. Materiels et methodes Il s'agissait d'une etude retrospective de dix patients dont le suivi a ete en moyenne de 23 mois, avec des extremes de 4 a 61 mois. Resultats Au stade initial, les lesions qui dominaient etaient les nodules (90% des patients) et les condensations alveolaires (100% des patients). Les nodules ont disparu en 6 mois chez 60% des patients ayant beneficie d'une tomodensitometrie de controle et avaient completement disparu chez tous les patients en 12 mois. Les nodules sous-pleuraux ont regresse en laissant des opacites lineaires de traction cicatricielle. Ces nodules sous-pleuraux pouvaient, lorsqu'ils etaient excaves, se compliquer de pneumothorax. Les condensations alveolaires ont disparu dans 44% des cas le plus souvent dans les 4 mois. Lorsqu'elles persistaient, elles laissaient des infiltrats alveolaires associes a des bronchectasies et des opacites lineaires. Le mode d'expression des rechutes etait similaire a celui des lesions initiales dans 40% des cas. Conclusion Cette etude a montre une disparition sans sequelle de tous les nodules medullaires et corticaux sous traitement. Les nodules sous-pleuraux qui apparaissaient frequents ont ete remplaces par des epaississements cicatriciels. Les condensations alveolaires ont eu une evolution plus variable. Lorsque leur regression etait incomplete, une image de condensation retractile pouvait eventuellement permettre de les differencier d'une complication pulmonaire infectieuse ou d'une rechute de la granulomatose de Wegener dont l'aspect tomodensitometrique le plus evocateur etait nodulaire. La tomodensitometrie a permis de depister des complications souvent meconnues en radiographie standard comme le pneumothorax.

Resume Introduction La nitrofurantoine communement prescrite pour la prevention des infections urinaires peut parfois etre a l’origine d’une complication potentiellement grave : la pneumopathie interstitielle. Observations Deux femmes de 78 et 87 ans traitees par nitrofurantoine depuis respectivement dix mois et six ans ont developpe une toux et une dyspnee resistantes aux antibiotiques faisant decouvrir un syndrome interstitiel. L’arret de la nitrofurantoine a permis une amelioration clinique et radiologique. Conclusion La prescription de nitrofurantoine au long cours doit s’accompagner d’une surveillance et l’apparition d’une symptomatologie respiratoire doit conduire au moindre doute a l’arret du medicament pour garantir la disparition des symptomes.

Resume Introduction De nombreuses localisations extrapulmonaires de la tuberculose ont ete decrites. La localisation linguale est rare et le plus frequemment secondaire a une atteinte pulmonaire ou plus rarement ganglionnaire. Observation Un homme de 64 ans, tabagique chronique souffrait d'une ulceration linguale chronique s'accompagnant d'une anorexie et d'une perte de poids importante. Une biopsie profonde de cette lesion a mis en evidence un granulome epithelioide et gigantocellulaire sans necrose caseeuse, sans bacille acido-alcooloresistant a l'examen direct. Les examens complementaires (radiographie thoracique, scanner thoracoabdominopelvien) montraient des signes de tuberculose disseminee confirmee par la positivite des cultures des prelevements pulmonaires, sanguins et urinaires. L'introduction d'un traitement anti-tuberculeux a permis la disparition rapide de l'ulceration linguale, evitant ainsi une evolution defavorable, voire fatale. Conclusion Une ulceration linguale d'origine tuberculeuse doit etre differenciee d'une lesion cancereuse, traumatique, d'un aphte ou d'un chancre syphilitique. Le diagnostic de l'origine tuberculeuse est difficile mais important a poser du fait de l'amelioration generalement rapide de la lesion apres introduction d'un traitement antituberculeux.

Resume Propos Le syndrome auto-immun multiple realise une condition pathologique rare et particuliere car associant chez un meme malade au moins trois maladies auto-immunes differentes. Le vitiligo occupe une place privilegiee parmi les affections dermatologiques auto-immunes observees au cours des syndromes auto-immuns multiples. Methodes Nous avons realise une etude multicentrique retrospective rassemblant 11 cas de syndromes auto-immuns multiples comportant un vitiligo. Nous avons analyse ses caracteristiques cliniques ainsi que celles des differentes associations auto-immunes. Resultats II s'agissait de 11 syndromes auto-immuns multiples de type III. Le sex-ratio etait de dix femmes pour un homme. Dans sept cas, le vitiligo etait la premiere maladie auto-immune apparue. Il etait bilateral, symetrique et acrofacial huit fois. Parmi les autres maladies auto-immunes, une thyreopathie auto-immune etait associee dans dix cas. Dans le cadre des syndromes auto-immuns multiples, les lesions cutanees du vitiligo prennent donc un caractere acrofacial et elles semblent plus volontiers associees a une thyreopathie auto-immune (10/11) qu'elles precedent sept fois sur 11. Conclusion Ainsi, chez une femme, la decouverte d'un vitiligo acrofacial doit inciter a rechercher des arguments pour une autre maladie auto-immune associee et surtout une thyreopathie auto-immune.

Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D

International audience; INTRODUCTION: Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. PATIENTS AND METHODS: [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. RESULTS: Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). CONCLUSIONS: Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.

Context: Cyclophosphamide is used for renal and major extrarenal involvement in systemic lupus erythematosus (SLE) and is associated with a risk of premature ovarian failure. There are no data available about the relation between anti-Müllerian hormone (AMH) serum levels and the probability of subsequent pregnancy in SLE patients. Objective: We analyzed AMH levels and the probability of pregnancy in SLE women exposed to cyclophosphamide. Design and Setting: We conducted a matched cohort study in referral centers for SLE. Patients: Fifty-six cyclophosphamide-exposed SLE women younger than 40 years of age and 56 control SLE women matched for age within 6 months participated in the study. Main Outcome Measures: AMH was measured in samples from the PLUS study (ClinicalTrials.gov no. NCT00413361). All patients were interviewed in May 2012 regarding their obstetric status. Results: The mean age ± SD of the 112 patients was 31.6 ± 5.8 years. The mean AMH level was low (1.21 ± 1.01 ng/mL) and was significantly lower in patients exposed to cyclophosphamide (P = .03) and in patients older than 30 years (P = .02). During a median follow-up (interval between sampling and the interview) period of 4.2 (range, 2.5–4.8) years, 38 patients sought to become pregnant, and 32 (84.2%) succeeded. In the univariate analysis, the risk of failure was associated with cumulative cyclophosphamide dose (P = .007) and older age (P = .02), but not with AMH. Conclusion: We confirmed that AMH levels are low in SLE patients and decrease significantly with age and cyclophosphamide exposure. Nonetheless, the risk of failure to conceive was low and was predicted by cyclophosphamide exposure and age, but not by AMH levels.

Resume Les auteurs rapportent deux observations de granulomatose de Wegener ou l'insuffisance renale aigue necessitant le recours a l'epuration extrarenale a permis de faire le diagnostic de la maladie jusqu'alors meconnue. L'evolution a ete favorable sous traitement corticoide et immunosuppresseur.

We studied myocardial manifestations of systemic sclerosis in three patients. Two patients were symptomatic. A transthoracic echocardiography, a coronary angiography, a cardiac catheterization, thallium scans with dipyridamol completed by thoracic cold exposure and endomyocardial biopsy with immunohistological study were performed. None of them have coronary stenosis. In the three cases abnormalities of myocardial perfusion were detected, two of them have fibrosis. The immunohistological study always showed an anusual expression of HLA DR on cardiac fibroblasts.

The authors report eleven cases of multiple auto-immune syndrome, concerning a total of 15 different auto-immune diseases. This study suggests that auto-immune thyroid disorders (Graves' disease or hypothyroidism resulting from Hashimoto's thyroiditis) are a common feature of multiple auto-immune syndromes, while antithyroid antibodies are constant among our patients. Sjogren's syndrome is also very prevalent, and seems to be non-randomly associated with auto-immune thyroid disorders, a fact which suggests common aetiological factors. Among other auto-immune disorders, the antiphospholipid syndrome has been diagnosed twice. A genetic predisposition to multiple auto-immune syndrome is obvious, as shown by a familial history of auto-immune disorders (found in more than half of the cases), and a predominant HLA phenotype, B8 and/or DR3. The authors plead for a systematic enquiry for multiple auto-immune syndrome in patients with auto-immune thyroid disorders and a family history of auto-immune disorders.

Objective: To study the characteristics of the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in the antiphospholipid syndrome (APS) and its influence on the subsequent pregnancies. Methods: This was a retrospective analysis of 16 episodes of HELLP complicating APS in 15 women. Results: HELLP was complete in 10 cases and partial in six. It occurred during the second trimester in seven cases (the earliest at 18 weeks' gestation), the third trimester in seven cases, and the day following delivery in two cases. Pre-eclampsia was present in six cases and eclampsia in five. Outcome of pregnancies was: live birth (n = 8), stillbirth (n = 2) and fetal death (n = 6). APS was primary in nine women and secondary to systemic lupus erythematosus (SLE) in six. HELLP revealed primary APS in six cases. Seven women were not treated. Low dose aspirin was empirically prescribed in one woman whose APS had been undiagnosed despite a history of two fetal deaths. In the other women, therapy consisted of aspirin (n = 8), low molecular weight heparin with a dose varying between 3000 and 12 000 U daily (n = 5), and high dose immunoglobulin every 4 weeks (n = 2), hydroxychloroquine (n = 4), and prednisone (n = 6). Six women had seven subsequent pregnancies, 3–6 years after the complicated pregnancy. HELLP recurred at 33 weeks' gestation in one woman with SLE treated with prednisone, hydroxychloroquine, aspirin, and enoxaparin, and pregnancy ended in live birth. One woman became pregnant after in vitro fertilisation and embryo transfer, but pregnancy ended in fetal death despite prednisone, hydroxychloroquine, and enoxaparin. Four women had five uneventful pregnancies with 100 mg daily aspirin and heparin. Conclusions: APS may be revealed by HELLP. In APS, HELLP is associated with pre-eclampsia/eclampsia in most cases and seems to occur earlier than in the general population. Heparin plus aspirin may prevent obstetric complications in the subsequent pregnancies.

Background Benefits of use of HCQ on physician reported outcomes (PRO) have been well documented in SLE and Rheumatoid arthritis (RA). HCQ can be measured in blood ([HCQ]) and a target threshold of 1000ng/ml has been proposed. No studies have assessed the predictive role of [HCQ] on PRO in SLE. Objectives Assess the predictive value of [HCQ] with health related quality of life (HRQOL) among patients with SLE. Methods Data from the PLUS study (a prospective randomized, double-blind, placebo-controlled, multicentre study comparing standard and adjusted HCQ dosing schedules and [HCQ]) were utilized. Blood HCQ levels were quantified by HPLC, along with HRQOL PRO assessments (Medical Outcomes Study-Short Form 36 or SF-36) at baseline (J0) and month 7 visits (M7). Paired t test were used to compare HCQ concentrations at the two visits. Spearman correlation coefficients between HCQ concentrations (continuous variable) and HRQOL at J0 and M7 were obtained. Nonparametric t test to compare HRQOL (J0) stratified by HCQ concentrations categories (0-499, 500-1000, >1000 ng/ml) was performed. Linear regression analysis with physical or mental component summary scores as dependent variables, and HCQ (J0) concentration as the predictor variable was performed. P value of ≤0.05 on two tailed tests was considered significant. Results 166 SLE patients9 data were analyzed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty seven percent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at J0 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at M7 (mean difference 366 units, 95% CI -472 to -260, p Conclusions No association of HCQ concentrations with current or future HRQOL (when measured by SF36) were found. This could be a real finding, or reflect inadequacy of sample size or the tool used to capture relevant HRQOL in SLE. Latter is hypothesized as no changes in HRQOL over time were noted irrespective of HCQ concentrations, despite physician-assessed changes in disease activity. Further studies are suggested. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2311

The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or artery thromboses or recurrent miscarriages, or both, associated with the presence of antibodies directed against negatively charged phospholipids—that is, lupus anticoagulant (LA), or anticardiolipin antibodies (aCL), or phospholipid binding proteins, or all three.1 It mainly occurs within systemic lupus erythematosus or as a primary disorder.1 Nearly all organs or tissues may be involved by thrombosis, but to date endocrine manifestations of the APS are mainly restricted to acute or chronic adrenal insufficiency resulting from adrenal haemorrhagic infarctions.2 We describe the case of a patient with primary APS who developed hypopituitarism assumed to result from hypothalamic dysfunction. A 48 year old woman was referred in 1996 for asthenia and a weight gain of 8 kg during the last six months. Her past medical history included two normal pregnancies in 1966 and 1970 and the chance discovery of LA in 1976, which remained present on subsequent determinations. She had experienced four fetal …

Carbamazepine-induced lupus is uncommon; its frequency is less than 0.001% of the cases of lupus treated. Herein we describe a 52-year-old woman who had development of facial erythema, arthralgia, dyspnea, and multiple pulmonary rounded masses and nodules while she was taking carbamazepine for epilepsy. Pulmonary histologic examination showed bronchiolitis obliterans organizing pneumonia. Antinuclear antibodies and antihistone antibodies were present without antibodies to double-stranded DNA. Thirteen months after carbamazepine had been withdrawn, all symptoms had disappeared without the use of anti-inflammatory drugs. Even though pulmonary involvement is possible during carbamazepine treatment, to our knowledge, bronchiolitis obliterans organizing pneumonia on its own or associated with carbamazepine-induced lupus has not been previously described.

Background The prospective, randomized, controlled MAINRITSAN trial compared rituximab (RTX) to azathioprine (AZA) to maintain ANCA-associated vasculitis (AAV) remission. Once remission was obtained with a conventional regimen, patients were randomly assigned to receive a 500-mg RTX infusion on D1, D15, 5.5 months later, then every 6 months for a total of 5 infusions over 18 months, or AZA for 22 months at the initial dose of 2 mg/kg/d. The primary endpoint was the major relapse rate (EULAR/ACR criteria) at 28 months. This study demonstrated that 500 mg of rituximab (RTX) every 6 months was superior to azathioprine (AZA) to maintain ANCA-associated vasculitis (AAV) remission during the 28-month follow-up, with a similar profile of tolerance. Objectives This study describes the extended follow-up of patients included in the MAINRITSAN trial. Methods Extended follow-up was ascertained from the patients included in the trial. Data on relapse and survival were collected from physician records. All patients were analyzed according to the group to which they were randomized. Results Median duration of follow-up was 34.3 months (IQR, 28.7-39.6 months). Six out of 56 (10.7%) RTX patients and 24/53 (45.3%) AZA patients had at least one major relapse. The risk of major relapse remained significantly lower in the RTX-arm compared to the AZA-arm (hazard ratio 0.18, 95% CI 0.09 to 0.42, P Conclusions Despite relapses in the RTX-arm after the end of the study period, RTX remains associated with a lower risk of relapse than AZA. RTX is also associated with a better overall survival compared to AZA. Disclosure of Interest None Declared

A 48 year old woman was referred to hospital for buccal discomfort. Physical examination showed a macroglossia and features of xerostomia. She was diagnosed as having primary Sjögren's syndrome according to the criteria proposed by the European Community study group in 1993. Furthermore, a lower lip salivary gland biopsy showed amyloid deposits that were also seen in the stomach and in the bone marrow. Echocardiography was consistent with cardiac amyloidosis. Serum immunofixation identified a monoclonal IgGlambda. As far as is known, this is the first report of systemic primary amyloidosis associated with Sjögren's syndrome. The relation between these two disorders is discussed.