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Introduction Les valvulopathies associees au lupus erythemateux systemique (LES) et/ou au syndrome des anti-phospholipides (SAPL), dont l’endocardite de Libman-Sachs, sont des complications rares de ces deux pathologies. L’objectif de cette etude etait de decrire les caracteristiques cliniques, biologiques, echo-cardiographiques et evolutives des patients porteurs de valvulopathies severes liees au LES et/ou SAPL ayant necessite un remplacement valvulaire, et d’etudier leurs histologies valvulaires. Materiels et methodes Etude Francaise retrospective observationnelle et multicentrique (n = 5), proposee par le Centre Hospitalier Universitaire de Reims et realisee sous l’egide de la SNFMI. Les patients inclus devaient avoir une valvulopathie severe ayant necessite un recours a la chirurgie valvulaire et etre porteurs d’un LES et/ou SAPL repondant aux criteres internationaux. Le compte-rendu de l’histologie valvulaire devait etre disponible. Resultats Vingt-trois patients (dont 20 femmes) âges en moyenne de 39 ± 15 ans au diagnostic de valvulopathie, ont ete inclus dans l’etude. Tous etaient porteurs d’un SAPL, avec evenements thrombotiques chez 22 (96 %) d’entre eux, de phenotype arteriel chez 15 (65,2 %) patients dont 6 (26 %) avaient au moins un episode de syndrome catastrophiques des anti-phospholipides (CAPS). Onze patients (48 %) avaient un LES associe au SAPL. La maladie systemique (SAPL avec ou sans LES) etait connue avant la mise en evidence de la valvulopathie chez seulement 12 (52 %) patients. Vingt patients (87 %) etaient porteur d’un anticoagulant circulant lupique, 20 (87 %) d’un anti-cardiolipine et 13 (56 %) avaient une triple positivite APL. Vingt patients (87 %) avaient une seule valve pathologique, 18 patients etaient porteurs d’une valvulopathie mitrale (78 %) et 8 (35 %) d’une valvulopathie aortique. Les epaississements (n = 19 ; 83 %) et les insuffisances valvulaires (n = 19 ; 83 %) etaient les anomalies les plus frequemment observees. Quinze patients (62 %) ont eu un remplacement valvulaire par valve mecanique, deux par une bioprothese (8,7 %) et 6 d’une chirurgie valvulaire conservatrice (26 %), dont 5 ont du etre reoperes dans un delais moyen de 1 ± 1,8 ans. Neuf (39 %) patients ont presente des complications postoperatoires precoces dont trois CAPS, une thrombose de prothese et un deces postoperatoire precoce (echec d’extubation apres deux mois de reanimation). Dix-huit patients (78,3 %) avaient un fonctionnement valvulaire juge normal a distance de l’intervention. La moitie des patients avaient des sequelles neurologiques (liees a des evenements ischemiques peri operatoires) a la fin du suivi (47 %). Quatre patientes du groupe chirurgie reparatrice ont eu une grossesse normale apres la chirurgie. Trois types de lesions valvaires histologiques ont ete observees au sein des valves prelevees : 8 (34 %) patients avaient une endocardite de Libman-Sacks typique (avec de larges vegetations delabrantes), 9 (39 %) une valvulopathie fibro-calcifiee degenerative et 6 (26 %) des lesions combinees (fibro-degeneratives et petites exulcerations). Conclusion Les valvulopathies graves (necessitant une chirurgie) au cours du LES et/ou du SAPL sont fortement associees au SAPL thrombotique, surtout de phenotype arteriel. La moitie des patients avaient des sequelles neurologiques en rapport avec des evenements ischemiques au dernier suivi et la chirurgie valvulaire comportait un risque eleve de CAPS.

Background Catastrophic antiphospholipid syndrome (CAPS) is the most severe complication of antiphospholipid syndrome (APS). Vitamin K antagonists (VKAs) are the reference treatment for preventing relapsing thrombotic complications in patients with APS, but direct oral anticoagulants (DOACs), such as rivaroxaban, are nonetheless sometimes used in patients with antiphospholipid antibody profiles or APS. Recent studies showed that DOACs were associated with more arterial thromboses among patients with APS. The potential role of DOACs as a trigger factor of CAPS is not known. Methods We describe two patients who developed a CAPS in the week following the institution of rivaroxaban. Results We report the onset of definite CAPS in the week following introduction of rivaroxaban treatment in two patients, one with APS and the other with antiphospholipid laboratory findings only. Both were triple positive for antiphospholipid antibodies. The affected organs were the heart, kidneys, skin, and liver for Patient 1, and the heart, kidneys, skin, adrenal gland, and central nervous system for Patient 2. The causative role of rivaroxaban is highly probable given that (1) CAPS occurred rapidly after this treatment was started, (2) an alternative trigger factor was found in Patient 1 only (a colonoscopy), and (3) Patient 1 had been clinically stable for 18 years with VKA as anticoagulant treatment, while Patient 2 did not have APS and had had no symptoms for 4 months (rivaroxaban had been introduced because at a scheduled visit, she reported neurological symptoms that occurred four months before and were retrospectively compatible with a brain transient ischemic accident). One similar case was reported in 2017, also following the introduction of rivaroxaban, in a patient with triple positive venous thrombotic APS who was stable for years on warfarin and who developed definite CAPS (involvement of the myocardium and adrenal glands as well as a pulmonary embolism) in the week after rivaroxaban 20 mg daily replaced warfarin to meet the patient‘s desire for a less burdensome treatment.1 Finally, in the randomized study published by Ordi-Ros et al, one of the patients treated with rivaroxaban developed a CAPS.2 Conclusions These two cases, as well as two previous reported cases, underline the importance of avoiding DOACs in patients with APS, especially those triple positive for antiphospholipid antibodies. VKAs must remain the reference anticoagulation treatment in this setting. References Crowley MP, Cuadrado MJ, Hunt BJ. Catastrophic antiphospholipid syndrome on switching from warfarin to rivaroxaban. Thromb Res 2017; 153; 37–9. Ordi-Ros J, Saez-Comet L, Perez-Conesa M, Vidal X, Riera-Mestre A, Castro-Salomo A, et al. Rivaroxaban versus vitamine K antagonist in antiphospholipid syndrome: a randomized noninferiority trial. doi: 10.7326/M19-0291. [Epub ahead of print]; 2019

Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on pathophysiology are scarce and suggest an autoimmune mechanism. Recently, the possibility of dividing patients with RP into three distinct clinical phenotypes has been suggested: the hematological form representing less than 10% of patients, essentially older men with associated myelodysplasia and poor prognosis, the respiratory form representing about 25% of patients with predominant tracheobronchial involvement, and the mild and most frequent form, representing 65% of patients, with a good prognosis. Recent data on survival shows an improvement of overall prognosis compared to historical series. Reported poor prognosis factors are male gender, associated haemopathies and cardiac involvement. Few recent series suggest an interest for positron emission tomography for the diagnosis and the follow-up of treatment. Due to the lack of randomized therapeutic trial, treatment remains empirical and is mainly based on oral corticosteroids sometimes associated with immunosuppressive agents. The use of biologic agents has recently been reported in small retrospective series with different outcome. Finally, some selected patients with mild and occasional peripheral chondritis might justify a treatment with colchicine or a therapeutic abstention with occasional short-term corticosteroids therapy.

Introduction Le syndrome catastrophique des anti-phospholipides (CAPS) est une complication rare et severe du syndrome des anti-phospholipides (SAPL), et est caracterise par de multiples thromboses predominant dans les petits vaisseaux et pouvant mener a une defaillance multi-viscerale. L’objectif de notre etude etait de preciser la semiologie clinique des atteintes cutanees qui sont peu decrites dans la litterature, leur presentation histologique, ainsi que leur pronostic. Patients et methodes Etude retrospective a partir de la base francaise SAPL-Lupus (coordination centres Cochin et Lille). Les criteres d’inclusion etaient d’avoir presente au moins un episode de CAPS (criteres de Sydney) avec atteinte cutanee specifique. Resultats Parmi 120 patients ayant presente un CAPS, nous avons inclus 65 patients (dont 43 femmes, 66 %) avec une atteinte cutanee. L’âge moyen au diagnostic du CAPS etait 43 ans ± 16. Le SAPL etait primaire chez 32 (49 %) patients et le CAPS etait inaugural chez 21 (35 %) patients. Durant l’episode de CAPS, les principales lesions cutanees etaient : un livedo racemosa ou une eruption livedoide d’apparition ou d’aggravation recente (n = 29, 45 %), des ulcerations ± necrotiques (n = 27, 42 %), un aspect d’œdeme inflammatoire distal (des mains, pieds ou du visage) (n = 15, 23 %) et/ou du purpura (n = 9, 14 %). La localisation des lesions etait precisee pour 43 patients et predominait alors aux membres inferieurs (n = 19, 44 %), membres superieurs (n = 18, 42 %), oreilles (n = 13, 30 %) et/ou face (n = 3, 7 %). Dix-neuf patients (29 %) presentaient des hemorragies sous-ungueales en flammeches. L’atteinte de l’oreille etait significativement plus frequente en cas de CAPS survenant au cours de la grossesse (8/16 (50 %) versus 5/49 (10 %) en l’absence de grossesse, p Conclusion L’atteinte de la peau concerne la moitie des patients au cours du CAPS. Les lesions les plus frequentes comportaient l’aggravation ou l’apparition d’un livedo, des ulcerations ± necrotiques, des hemorragies en flammeches, du purpura, mais aussi un aspect d’œdeme inflammatoire distal avec des lesions erythemateuses, chaudes et douloureuses des paumes, plantes et/ou oreilles. L’apparition de telles lesions doit faire penser au diagnostic de CAPS dans un contexte evocateur.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ

Introduction Le syndrome des antiphospholipides (SAPL) est un syndrome heterogene, pouvant comporter de nombreuses manifestations cliniques (thrombotiques, obstetricales, cutanees, neurologiques ou encore cardiaques) qui s’integrent parfois dans un syndrome catastrophique des antiphospholipides (CAPS). Ce syndrome peut s’associer a d’autres maladies auto-immunes, notamment le lupus systemique (LS). L’objectif de cette etude est de determiner de nouveaux phenotypes cliniques parmi les patients atteints de SAPL, en utilisant une methode non supervisee en « cluster hierarchique », afin d’etudier les differents sous-groupes phenotypiques homogenes de SAPL. Patients et methodes Cette etude a porte sur les patients inclus dans le registre multicentrique francais « SAPL et Lupus ». Les patients inclus avaient un SAPL defini par les criteres de classification de Sydney [1] . Une analyse en cluster hierarchique a ete realisee a l’aide d’une analyse des correspondances multiples, puis par une classification hierarchique ascendante, en utilisant 27 variables incluant les criteres de classification, et un large panel de caracteristiques cliniques et biologiques du SAPL. Une comparaison des caracteristiques entre les differents sous-groupes a ete realisee a l’aide de tests du Chi2 et d’analyse de variance. Resultats Au total, 509 patients ont ete inclus dans l’analyse, en majorite de sexe feminin (78 %). L’âge median (intervalle interquartile) au diagnostic de SAPL etait de 32,8 ans [25,2–45,7] et la duree mediane de suivi etait de 8,5 annees [3,3–16,0]. L’analyse en cluster hierarchique a permis d’identifier 4 groupes homogenes de patients, representes par les variables cliniques ou biologiques predominantes suivantes : –cluster 1 : patients plutot de sexe feminin (82 %), presentant des manifestations thrombotiques veineuses (78 %), sans maladie auto-immune associee (2,2 %) ; –cluster 2 : patients plus âges (45,8 ans), avec une predominance feminine moins nette (35 % d’hommes), presentant une atteinte arterielle (89 %), une atteinte valvulaire (21 %), des migraines (21 %), un livedo (35 %), une hypertension arterielle (49 %) et des comorbidites cardiovasculaires (diabete, dyslipidemie) ; –cluster 3 : patients de sexe feminin (92 %), plus jeunes (30,7 ans), atteints d’un LS (77 %), ou d’une autre maladie auto-immune (30 %), avec des thromboses veineuses (74 %), une thrombopenie (48 %) et une anemie hemolytique (14 %) ; –cluster 4 : patients ayant souvent presente un CAPS (77 %), avec une nephropathie associee au SAPL (92 %), une hypertension arterielle d’origine renale (61,4 %), une epilepsie (14,3 %), une thrombopenie (46 %) et une valvulopathie (44 %), ainsi qu’une forte predominance d’anticoagulant circulant (88 %) et d’anticorps anticardiolipine (96 %). Bien qu’associes a des variables discriminantes, certains clusters pouvaient se chevaucher et presenter des variables similaires. Conclusion Notre analyse a permis de degager 4 differents sous-groupes phenotypiques de SAPL, en utilisant une methode non supervisee sans a priori : des femmes avec thromboses veineuses, des patients plus âges avec atteinte arterielle, cutanee, neurologique et cardiovasculaire, des femmes lupiques avec un SAPL, et des patients atteints de CAPS et d’atteinte renale specifique. Nos resultats confirment l’idee d’une heterogeneite au sein des patients atteints de SAPL, sous-tendant de potentiels mecanismes physiopathologiques differents.

Background:One of the 3 features of obstetrical antiphospholipid syndrome (APS) is severe preeclampsia (PE). Its time of occurrence, the associated risk of thromboses and systemic lupus erythematosus (SLE) have not been reported yet.Objectives:We analyzed severe PE in a series of women with APS.Methods:We retrospectively collected data of female patients from 5 French internal medicine and 1 Italian rheumatology units. Inclusion criteria were: a severe PE/eclampsia(1), that occurred before 34 weeks of gestation (WG) in patients who met the APS classification criteria(2).Results:40 patients were enrolled (Table 1). Because of known APS/positive aPL/previous obstetrical complications, 23(57.5%) patients were treated during the index PE: 4 with low dose aspirin (LDA), 4 with low molecular weight heparin (LMWH), and 15 with a combination of both. 7 patients were also treated with hydroxychloroquine, 8 with corticosteroids and 3 with immunosuppressants. 17(42.5%) patients received no treatment. 24(60%) live births were observed. During a follow-up period of 3 years, 26(65%) patients had at least 1 new pregnancy, with a total of 38 pregnancies which resulted in 33(86.8%) live births. 57.5% pregnancies who resulted in live births occurred without any maternal or fetal complications. All 26 patients who had at least 1 pregnancy after index PE were treated with LDA; LMWH was given at prophylactic and therapeutic dosage in 13(50%) patients, respectively. No patient experienced 3 consecutive miscarriages.Table 1.40 APS patients with severe PEOverall features (n, %)Patients40 (100)Age at PE, (median, IQR)30.5 (27-33)PE term, WG (median, IQR)25.5 (23-29) Live births24 (60) Birth term, WG (median, IQR)25.5 (23.7-30.3) Associated SLE12 (30)Maternal complications (n, %)25 (62.5) HELLP18 (45) E6 (15) CAPS3 (7.5) Placental abruptions3 (7.5)Fetal complications (n, %)31 (77.5) IUGR18 (45) IUFD11 (2.5) Preterm delivery22 (55)Obstetrical history (n, %) Primiparous21 (52.5) Index PE before APS12 (30)Thrombosis (n, %) Thrombosis before PE index14 (35.0) Thrombosis after PE index2 (5.0)Abs at APS diagnosis (n, %) aPL triple positivity21 (52.5) IgG/IgM anti-cardiolipin34 (85.0) IgG/IgM anti-β2GPI25 (62.5) LAC33 (82.5)Legend to Table 1:PE: preeclampsia; APS: antiphospholipid syndrome; IQR: interquartile range; WG: weeks of gestation; SLE: systemic lupus erythematosus; HELLP: Hemolysis, elevated liver enzymes, low platelet; E: eclampsia; CAPS: catastrophic APS; IUGR: intrauterine growth restriction; IUFD: intrauterine fetal death; CHB: congenital atrioventricular block; aPL: antiphospholipid antibodies; LAC: lupus anticoagulant.Conclusion:Among the APS criteria, “3 consecutive miscarriages criterion” was not found. The majority of patients also experienced thrombosis and SLE before the index PE.References:[1]Diagnosis and Management of preeclampsia and eclampsia. International Journal of Gynecology &Obestetrics 2002;77:67-75.[2]Miyakis S, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295e 306.Disclosure of Interests:Maddalena Larosa: None declared, Nathalie Morel: None declared, Meriem BELHOCINE: None declared, Amelia Ruffatti: None declared, Nicolas Martin Silva: None declared, Romain Paul: None declared, Luc Mouthon: None declared, Michel DREYFUS: None declared, Jean-Charles PIETTE: None declared, Odile Souchaud-Debouverie: None declared, Catherine Deneux-Tharaux: None declared, Vassilis Tsatsaris: None declared, Emmanuelle Pannier: None declared, Gaêlle Guettrot Imbert: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Nathalie Costedoat-Chalumeau Grant/research support from: UCB to my institution

Background The diagnosis of systemic lupus erythematosus (SLE) is based on the association of clinical and biological manifestations and on clinical experience. In 2012, a major revision by the Systemic Lupus International Collaborating Clinics (SLICC) group sought to improve their sensitivity and specificity. In replications, the SLICC classification produced fewer errors than the previous version; its higher sensitivity but lower specificity meant that some patients could be classified with SLE although they had another disease. In fact, the distinction between PAPS, APS associated with SLE, and isolated SLE may be difficult in some cases because the two diseases share some clinical and biological manifestations. Objectives To assess the limitations of the SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for systemic lupus erythematosus (SLE), in patients with primary antiphospholipid syndrome (PAPS). Methods Retrospective study of a cohort of APS patients (Sydney criteria). We successively excluded patients with1 at least one “SLE-specific” manifestation (biopsy-proven SLE nephropathy, arthritis, cutaneous, or neurologic SLE manifestations, pericarditis, autoimmune haemolytic anaemia, oral and nasal ulcers, non-scarring alopecia, anti-dsDNA, and anti-Sm antibodies),2 any other autoimmune connective tissue disease, and/or3 antinuclear antibodies>1/320. Careful file review confirmed PAPS among the remaining patients. We then assessed the number of SLICC criteria each patient met. Results Among these 214 APS patients, we excluded 85 with at least one SLE-specific manifestation, 8 with another connective tissue disease, and 21 with antinuclear antibodies>1/320, leaving 100 patients with primary APS. Among them, 28% met at least 4 SLICC classification criteria including one clinical and one immunological criterion (antiphospholipid antibodies, aPL, by definition) and could thus theoretically be classified with SLE. Fourteen had an arterial phenotype (50%), 9 a history of catastrophic APS (32%), and 18 a triple-positive profile for aPL (64%). None had developed SLE during a median follow-up of 12 [6.5–17] years. Conclusions Because 28% of our patients with longstanding and strictly defined PAPS could be mistakenly classified as SLE, they were at risk of deleterious therapeutic management. We therefore suggest that any future classification for SLE should specifically require at least one SLE-specific criterion for patients with aPL. References [1] Petri M, Orbai A-M, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum2012;64:2677–86. doi:10.1002/art.34473 [2 ] Piette JC, Wechsler B, Frances C, et al. Exclusion criteria for primary antiphospholipid syndrome. J Rheumatol1993;20:1802–4. [3] Asherson RA, Khamashta MA, Ordi-Ros J, et al. The ‘primary’ antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 1989;68:366–74. [4] Gomez-Puerta JA, Martin H, Amigo M-C, et al. Long-term follow-up in 128 patients with primary antiphospholipid syndrome: do they develop lupus? Medicine (Baltimore) 2005;84:225–30. Disclosure of Interest None declared

Introduction Le syndrome catastrophique des antiphospholipides (CAPS) se caracterise par la survenue simultanee de thromboses multiples, typiques par leur predominance microcirculatoire et pouvant conduire a un tableau de defaillance multiviscerale. L’atteinte du segment posterieur de l’œil a ete exceptionnellement rapportee dans la litterature. Patients et methodes Etude retrospective multicentrique des patients ayant presente une atteinte du segment posterieur de l’œil dans un contexte de CAPS (selon les criteres de classification du CAPS revises en 2010) [1] inclus dans la base de donnees francaise « syndrome des antiphospholipides (SAPL)/lupus » au 30/10/2018 (Clinicaltrials NCT 02782039 ). Nous avons egalement inclus les patients de la litterature repondant a ces criteres. Resultats Parmi 61 patients ayant presente un CAPS, nous avons identifie 8 patients avec atteinte du segment posterieur (13 %, cette atteinte n’etant neanmoins pas recherchee systematiquement). Nous avons analyse au total 20 patients (8 cas personnels et 12 cas de la litterature) d’âge median 29,5 ans [extremes 16–79]. Dix-huit etaient des femmes. L’atteinte ophtalmologique etait generalement bilaterale (n = 16). Elle consistait en une retinopathie vasculaire occlusive (n = 15), une vascularite retinienne (n = 1, dans un contexte de lupus associe) et/ou une choroidopathie (n = 9). Tous les patients rapportaient une symptomatologie ophtalmologique (1 donnee manquante) : baisse de l’acuite visuelle (n = 16), scotome (n = 4) et/ou amaurose (n = 1). Un deces etait observe. Parmi les 19 patients suivis pendant une mediane de 13 mois [2 mois–11 ans], 10 patients avaient des sequelles visuelles (53 %, 2 donnees manquantes). Les sequelles faisaient suite a une atteinte vasculaire occlusive retinienne (n = 6), a une atteinte vasculaire occlusive retinienne et choroidienne (n = 3) ou a une atteinte choroidienne seule (n = 1). A la fin du suivi, un patient etait aveugle et trois etaient monophtalmes. Conclusion L’atteinte du segment posterieur de l’œil au cours du CAPS etait volontiers bilaterale. L’atteinte vasculaire occlusive retinienne etait predominante, le plus souvent severe. Les sequelles visuelles etaient frequentes. Nous proposons de faire un fond d’œil chez tous les patients atteints de CAPS afin de ne pas meconnaitre cette atteinte susceptible de passer au second plan du fait de la severite clinique des patients.

Introduction Le syndrome catastrophique des antiphospholipides (CAPS) se caracterise par la survenue simultanee de thromboses micro et macro-circulatoires multiples pouvant conduire a une defaillance multiviscerale. Les connaissances concernant les caracteristiques cliniques et biologiques de ces patients restent limitees. Patients et methodes Etude retrospective multicentrique des patients ayant presente un CAPS (criteres de classification revises en 2010) [1] inclus dans la base de donnees francaise « syndrome des antiphospholipides (SAPL)/lupus » au 01/02/2019 (Clinicaltrials NCT 02782039 ). Resultats Nous avons inclus 88 patients (59 femmes, 67 %) ayant presente un CAPS a un âge median de 39 ans [16–78] (1 donnee manquante (DM)). Le CAPS etait inaugural chez 30 patients (34 %). Trente-deux patients avaient un lupus erythemateux systemique associe (36 %). La biologie antiphospholipides comportait un anticoagulant circulant lupique (n = 78, 90 %, 1 DM), des anticorps anticardiolipine (n = 79, 91 %, 1 DM) et des anticorps anti-B2GP1 (n = 58, 67 %, 1 DM), 51 patients etant triples positifs (59 %, 1 DM). Les atteintes d’organe du CAPS etaient renales (n = 68, 77 %), cardiaques (n = 56, 64 %), cutanees (n = 52, 59 %), neurologiques (n = 41, 47 %), hepatiques (n = 38, 43 %), surrenaliennes (n = 31, 35 %), pulmonaires (n = 31, 35 %), ophtalmologiques (n = 11, 12 %) voire spleniques (n = 7, 8 %), intestinales (n = 6, 7 %), pancreatiques (n = 4, 5 %) ou encore osteo-medullaire (necrose, n = 1, 1 %). Cela s’associait parfois a une thrombose arterielle (n = 20, 23 %) ou veineuse (n = 17, 19 %) peripheriques. Une thrombopenie etait presente chez 69 patients (85 %, 7 DM ; taux median de plaquettes de 50 000/mm3 [9 000–148000]) et une anemie hemolytique chez 38 (47 %, 7 DM). Un facteur declenchant etait retrouve chez 59 patients (80 %, 14 DM) notamment grossesse (n = 21, 28 %), infections (n = 18, 24 %), chirurgie (n = 10, 14 %), et/ou poussee de lupus (n = 4, 5 %). Le CAPS survenait frequemment suite a une modification des anticoagulants (arret ou relais n = 22) ou a un sous-dosage des AVK (n = 10). La prise en charge comportait une anticoagulation curative (n = 82, 94 %, 1 DM), de l’aspirine (n = 32, 37 %, 1 DM), une corticotherapie [orale (n = 72, 83 %, 1 DM), et/ou sous la forme de bolus de methylprednisolone (n = 42, 48 %, 1 DM)], des immunoglobulines polyvalentes intraveineuses (n = 48, 55 %, 1 DM), des echanges plasmatiques (n = 36, 41 %, 1 DM), du rituximab (n = 15, 17 %, 1 DM), un autre immunosuppresseur (n = 11, 13 %, 1 DM), de l’eculizumab (n = 3, 3 %, 1 DM). Dix-huit patients necessitaient une epuration extra renale (n = 18, 21 %, 1 DM). Six patients decedaient des suites de ce premier episode de CAPS (7 %). Durant le suivi, 15 patients (18 %) avaient au moins une recidive de CAPS. Cinquante patients presentaient au moins une sequelle (65 %, 5 DM) ; 20 avaient une insuffisance renale chronique, 20 une insuffisance surrenalienne, 14 des sequelles neurologiques, 10 une insuffisance cardiaque, 4 une sequelle ophtalmologique, 2 une autre sequelle. Huit patients sont decedes au cours du suivi dont un deces attribuable a un nouvel episode de CAPS. Conclusion Cette serie de 88 patients apporte une meilleure connaissance du CAPS, de ses atteintes d’organes et de son pronostic. La frequence elevee d’un facteur declenchant rapporte (80 %), notamment lie aux modifications du traitement par AVK doit inciter le clinicien a davantage de vigilance concernant les patients aux antecedents de SAPL.

Objective To assess the relationship between Takayasu arteritis (TAK) and pregnancy outcome. Methods This study included 240 pregnancies in 96 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK and/or the 1994 Chapel Hill Consensus Conference nomenclature/criteria for vasculitis. We analyzed obstetric and maternal outcomes in women who were pregnant before and/or at the same time as or after TAK diagnosis. We assessed factors associated with complicated pregnancy. Results One hundred forty-two pregnancies occurred in 52 patients before TAK diagnosis (median age at pregnancy 26 years [interquartile range 23–30 years]), and 98 pregnancies occurred in 52 patients concomitant with or after TAK diagnosis (median age at pregnancy 28 years [interquartile range 26–31 years]). Pregnancies concomitant with or after TAK diagnosis had a 13-fold higher rate of obstetric complications compared to pregnancies before TAK diagnosis (odds ratio 13 [95% confidence interval 5–33], P 1) (odds ratio 28.7 [95% confidence interval 7.89–104.7]) were independently associated with obstetric and maternal complications. Conclusion TAK negatively affects pregnancy outcomes. Disease activity increases the risk of obstetric and maternal complications, mainly due to arterial hypertension.

International audience; Objective. We describe myelodysplastic syndrome (MDS)–associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study. Methods. In this study, 123 patients with MDS and SIADs were analysed. Results. Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P \textless 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P \textless 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5). Conclusion. The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent

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.

RésuméLa survenue d’une grossesse au cours du lupus systémique est une situation fréquente qui reste associée à une morbi-mortalité maternelle et fœtale plus importante que dans la population générale. Les complications incluent les poussées lupiques, les complications obstétricales (pertes fœtales, retard de croissance in utero, pré-éclampsie, prématurité) et le lupus néonatal. Une biologie ou un syndrome des antiphospholipides augmente nettement le risque de complications obstétricales. L’amélioration de la prise en charge de ces grossesses est conditionnée par leur planification systématique, idéalement au cours d’une consultation pré-conceptionnelle, et par une prise en charge multidisciplinaire avec une collaboration étroite entre interniste/rhumatologue, obstétricien et anesthésiste. L’absence d’activité du lupus, un traitement compatible avec la grossesse adapté aux antécédents et aux risques ainsi qu’une surveillance régulière sont les principaux éléments permettant une issue favorable à ces grossesses à risque. Cette revue a pour objectif de proposer une mise au point sur la prise en charge actuelle de la grossesse au cours du lupus systémique ou du syndrome des antiphospholipides afin de limiter le risque de complications et d’assurer le meilleur pronostic tant maternel que fœtal.AbstractPregnancy in systemic lupus erythematosus patients is a common situation that remains associated with higher maternal and fetal mortality/morbidity than in the general population. Complications include lupus flares, obstetrical complications (fetal loss, in utero growth retardation, prematurity) and neonatal lupus syndrome. The association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetrical complications. Improving the care of these pregnancies depends upon a systematic pregnancy planning, ideally during a preconception counseling visit and a multidisciplinary approach (internist/rheumatologist, obstetrician and anesthetist). The absence of lupus activity, the use of appropriate medications during pregnancy adjusted to the patient's medical history and risk factors, and a regular monitoring are the best tools for a favorable outcome for these high-risk pregnancies. The aim of this review article is to perform an update on the medical care of pregnancy in systemic lupus erythematosus or antiphospholipid syndrome to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

Fertility is not impaired in systemic lupus erythematosus or antiphospholipid syndrome, but, similarly to the general population, these patients may undergo in vitro fertilization. This type of treatment increases the risk of lupus flare, thrombosis, and ovarian hyperstimulation syndrome. This review will focus on in vitro fertilization in systemic lupus erythematosus or antiphospholipid syndrome. Literature data are relatively scant with only 3 reported studies. The first one included 17 patients and 63 cycles of induction ovulation/in vitro fertilization leading to 25 % of lupus flare, no thrombosis, and 3 % of ovarian hyperstimulation syndrome. The second study included 10 patients and 40 cycles of in vitro fertilization showing 31 % of lupus flare, no thrombosis and no ovarian hyperstimulation syndrome. The last one included 34 patients and 83 procedures of in vitro fertilization leading to 8 % of flares, 5 % of thrombosis and no ovarian hyperstimulation syndrome. Interestingly, in this last study, half of the complications were explained by poor adherence to treatment. These data are reassuring but it is important to remember that in vitro fertilization should be scheduled and carefully supervised in the same way as the high-risk pregnancies occurring in these patients.

Objective.To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS).Methods.Medical records of patients with PAPS followed in 6 centers for ≥ 15 years were retrospectively reviewed.Results.One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (± SD) age at diagnosis of 33 (± 10) years. During a median followup of 18 years (range 15–30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD.Conclusion.Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent.

Objective: To report the long-term outcome of neurological involvement in patients with Behcet's disease (BD). Methods: Retrospective analysis of 115 patients fulfilling the international criteria for BD [57% male with median [Q1-Q3] age of 37 [30-46] years] and with neuro-Behcet's disease (NBD) after exclusion of cerebral venous thrombosis. Factors associated with relapse of NBD, dependence and mortality were assessed. Results: Seventy-eight (68%) patients presented with acute NBD and 37 (32%) with a progressive course. The HLA B51 allele was carried by 49% of patients. Overall, 46/115 (40%) patients had a severe baseline disability status, represented by a Rankin score ≥ 3. The 5 and 7 years event-free survival rates were 65% and 53%, respectively. In multivariate analysis, a positive HLA-B51 status was independently associated with the risk of NBD relapse (OR=3.6 [1.5-9.1]). After a median follow-up of 73 [59-102] months, 21 (25.2%) patients became dependent or died. Factors independently associated with poor outcome were paresis at onset (OR=6.47 [1.73-24.23]) and a brainstem location of inflammatory lesions on MRI (OR=8.41 [1.03-68.43]). All 115 patients were treated with glucocorticosteroids, including 53/115 (46.1%) with cyclophosphamide and 40/115 (34.8%) with azathioprine. A trend towards longer event-free survival was observed in severe NBD patients (i.e. Rankin score ≥ 3 at onset) receiving intravenous cyclophosphamide compared with those treated with azathioprine (p =0.06). Conclusion: NBD is a severe condition in which patients with the HLA-B51 allele appear to experience a worse prognosis. © 2013 American College of Rheumatology.

Les manifestations neurologiques de la maladie de Behcet (MB) sont retrouvees chez 5,3 a plus de 50 % des patients selon les series. Elles sont separees en deux grands types d'atteintes : les formes " parenchymateuses ", regroupant les atteintes intracerebrales (meningo-encephalites), par opposition aux formes " extra-parenchymateuses ", incluant les thromboses veineuses cerebrales et les anevrismes arteriels. Les atteintes medullaires et les atteintes peripheriques sont exceptionnelles. Un syndrome de neuro-Behcet (NB) doit etre evoque devant la survenue de troubles neurologiques, en particulier des cephalees et une atteinte pyramidale, chez un homme jeune suivi pour une MB. Neanmoins, sa reconnaissance est difficile lors des formes inaugurales (un tiers des cas), et necessite une connaissance des lesions morphologiques. Ainsi, les lesions de NB parenchymateux sont classiquement inflammatoires en IRM et situees a la jonction meso-diencephalique, ainsi que dans le tronc cerebral, avec rarement une extension sus-tentorielle. Une meningite associee n'est pas systematique, absente dans environ 30 % des cas. La physiopathologie de ces lesions est imparfaitement connue, mais l'infiltrat inflammatoire est majoritairement constitue de polynucleaires neutrophiles et de lymphocytes T actives (notamment de type Th17). Les principaux diagnostics differentiels concernent les pathologies infectieuses (herpes, listeriose, tuberculose), et inflammatoires (sclerose en plaques, sarcoidose) qui doivent etre systematiquement evoquees. Le traitement du NB doit etre initie des son diagnostic afin d'en limiter le risque de sequelles, de rechute ou de deces.

Vascular involvement is a common complication of Behcet's disease (BD) and affects up to 40% of BD patients. These complications worsen the prognosis of BD. The concept of vasculo-Behcet has been adopted for cases in which vascular complications dominate the clinical features. Vascular manifestations affect particularly young men, during the first years following onset of the disease. Venous complications are the most frequent vascular complications, affecting 14 to 40% of BD patients. Superficial and deep lower limb thrombosis is the most frequent venous complications but one third of venous thrombosis concern large vessels (such as cerebral venous thrombosis, pulmonary embolism, and inferior or superior vena cava, etc.). Budd-Chiari syndrome is the worst prognostic factor increasing mortality by 9 times. Arterial complications (2 to 17% of BD patients) include aneurysms and occlusions/stenosis. Main locations of arterial lesions are aortic (abdominal and thoracic), femoral, pulmonary and iliac arteries. Aneurysms are the most severe arterial complications, particularly pulmonary aneurysms associated with a high risk of massive bleeding. Cardiac complications (up to 6% of BD patients) include pericarditis, endocardial lesions (aortic regurgitation and less often mitral insufficiency), myocardial lesions (myocardial infarction, myocarditis and endomyocardial fibrosis) and intracardiac thrombosis (right ventricle and atrium). Coronary lesions complicated to myocardial infarction are the most severe cardiac complications. Treatment is based on corticosteroids and immunosuppressive drugs. The use of anticoagulation in venous thrombosis is still controversial.

Introduction Le syndrome des antiphospholipides (SAPL) peut exister isolement (SAPL primaire) ou etre associe a une autre pathologie, generalement un lupus systemique (LS). De nouveaux criteres de classification du LS ont ete etablis par le groupe Systemic Lupus International Collaborating Clinics (SLICC) en 2012. Certains de ces criteres de LS sont non specifiques, car ils ont ete rencontres, plus ou moins frequemment, en cas de SAPL primaire. Ainsi les patients ayant un SAPL primaire peuvent theoriquement remplir jusqu’a 10 criteres SLICC de LS sans en etre atteints. L’objectif de cette etude est d’evaluer le nombre de criteres de LS remplis par des patients ayant un SAPL primaire. Patients et methodes Etude retrospective d’une cohorte de patients presentant un SAPL (criteres de Sydney). Nous avons exclu successivement les patients ayant (1) au moins une manifestation « specifique » de LS (nephropathie immune documentee histologiquement, arthrite, manifestations cutanees ou neurologiques [hors comitialite] de LS, pericardite, anemie hemolytique auto-immune, ulceres buccaux ou nasaux, alopecie non cicatricielle, anticorps anti-ADN natif et/ou anti-Sm) ; (2) toute autre connectivite associee ; (3) ou enfin des anticorps antinucleaires (ANA) > 1/320. Le caractere primaire du SAPL a alors ete confirme apres une reevaluation des dossiers. Nous avons ensuite collige le nombre de criteres SLICC de LS remplis par ces patients presentant un SAPL primaire indiscutable. Les manifestations cliniques et immunologiques prises en compte, car parfois observees au cours du SAPL primaire etaient : un epanchement pleural ou frottement pleural (satellite d’une embolie pulmonaire), une proteinurie > 500 mg/24 h (nephropathie antiphospholipides), une comitialite, une anemie hemolytique mecanique, une lymphopenie, une thrombopenie, des ANA ≤ 1/320, une diminution du complement, un test de Coombs direct positif et une biologie antiphospholipides positive (toujours presente par definition). Resultats Parmi 214 patients avec SAPL, nous avons exclu 85 patients ayant au moins une manifestation « specifique » de LES, 8 ayant une autre connectivite puis 21 ayant des ANA > 1/320, aboutissant a 100 patients atteints de SAPL primaire indiscutable. Parmi ces 100 patients, 28 (28 %) presentaient au moins 4 criteres SLICC, dont un critere clinique et un critere immunologique (a savoir les anticorps antiphospholipides par definition) permettant leur classification theorique en LS : 50 % (n = 14) avaient un phenotype arteriel, 64 % (n = 18) une triple positivite pour les anticorps antiphospholipides et 32 % (n = 9) un antecedent de syndrome catastrophique des antiphospholipides (CAPS). Aucun d’entre eux n’a developpe de lupus pendant un suivi median de 12 [6,5–17] ans. Conclusion Parmi les patients, 28 % presentaient un SAPL primaire indiscutable, et peuvent etre classes par erreur en LS selon les criteres SLICC. Meme si ces criteres de classification ne sont pas destines a poser un diagnostic individuel, leur manque de specificite peut faciliter des erreurs diagnostiques conduisant a une prise en charge inadaptee. Nous suggerons que toute classification futur pour le LS necessite que les patients ayant une biologie antiphospholipides aient au moins un critere « specifique » du LS avant d’autoriser leur classification en LS.

International audience; Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by single or multiple benign lung nodules mimicking lung neoplasma. Histologic analysis reveals homogenous hyaline lamellae, usually surrounded by collection of plasma cells, lymphocytes and histiocytes in a perivascular distribution. The clinical and radiological findings have been described in small series, but the long-term outcomes have rarely been reported. The objectives were to describe the clinical, radiological and outcomes of PHG in new cases and through a literature review. Patients with PHG were found by a multicenter search among French departments of internal medicine, pulmonology and anatomo-pathology. Review of the literature was made through the National Library of Medicine’s MEDLINE database using keywords “hyalinizing granuloma.” Five news cases and 135 cases of the literature were found. There were 82 men and 57 women, mean age at the diagnosis 44.6 years (15–83). Patients were frequently asymptomatic (n = 39, 27.4 %). The nodule was unique in 37 cases (28.9 %) and multiple in 91 cases (71.1 %). 18FDG PET scan revealed hypermetabolism of the nodule in 9/15 cases (60 %). A systemic disease was associated in 65 cases (mainly mediastinal and retroperitoneal fibrosis, autoimmune, tumoral or infectious disease or thromboembolism). The outcomes were evaluated in 73 patients when follow-up was available: 14 patients had a surgical resection of the nodule. Forty-five patients did not receive any immunosuppressive drug. Among these patients, 2 improved, 29 were stable and 14 worsened. Corticosteroids were used as a monotherapy in 19 patients and led to radiological improvement in 8 cases, stabilization in 8 cases and worsening in 3 cases. Five patients were treated with corticosteroids and at least one immunosuppressive drug and 4 patients improved. PHG is a rare benign disease, mimicking lung neoplasma, frequently associated with systemic diseases.

Background— A recent case-control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro–positive patients with systemic lupus erythematosus. A historical cohort assembled from 3 international databases was used to evaluate whether HCQ reduces the nearly 10-fold increase in risk of recurrence of cardiac-NL independently of maternal health status. Methods and Results— Two hundred fifty-seven pregnancies of anti-SSA/Ro-positive mothers (40 exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac-NL were identified from 3 databases (United States, England, and France). Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the unexposed group ( P =0.050). Although there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 21.7%. In a multivariable analysis that adjusted for database source, maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly associated with a decreased risk of cardiac-NL (odds ratio, 0.23; 95% confidence interval, 0.06–0.92; P =0.037). Similar results were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication. Conclusion— Aggregate data from a multinational effort show that in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.

The effects of vitamin D on calcium homeostasis and bone metabolism are well known. In recent years, suboptimal vitamin D status has been recognized as a pandemic. Meanwhile, extra-skeletal effects of vitamin D are becoming better documented, particularly its effects on immunity. The authors present their actions on myeloid dendritic cells, T cells, B cells, as well as on the synthesis of antimicrobial peptides and autophagy, and the potential beneficial effects in autoimmune and inflammatory diseases.

Vitamin D is often confined to its role in calcium homeostasis and bone metabolism. An exponential literature discusses its non-skeletal effects, especially its central role in the physiology of the immune system, where it acts at several levels to maintain self-tolerance. Here, the authors review the experimental, epidemiological and clinical studies, illustrating the potential role of vitamin D in the development and perpetuation of autoimmune diseases such as systemic lupus erythematosus, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases or rheumatoid arthritis.

Pulmonary hypertension (PH) is a serious complication of connective tissue diseases. The prevalence of PH in systemic lupus erythematosus (SLE) ranges from 0.5 to 17.5%, depending on whether echocardiography or right heart catheterization is used as the gold standard for diagnosis. The recent guidelines for the diagnosis and treatment of pulmonary hypertension include several potential causes of PH in SLE, including: a primary vasculopathy similar to idiopathic pulmonary arterial hypertension (PAH); left heart diseases; post-thromboembolic disease; hypoxia and fibrosis resulting from interstitial lung disease; and the infrequent SLE-associated pulmonary veno-occlusive disease. The pathogenesis of PAH associated with lupus is yet unclear, but likely includes a role for the genetic background, the presence of antiphospholipid antibodies, and some level of endothelial dysfunction. The evolution of SLE-associated PH is highly variable and difficult to elicit because the published series have used heterogeneous inclusion criteria. Optimal therapeutic management of PAH associated with lupus is unclear because no dedicated randomized controlled trial is yet available. Treatment usually includes arterial pulmonary vasodilators and immunosuppressive agents when the patients have NYHA functional class II, III or IV dyspnea.

Objective To assess the factors influencing the efficacy of 2 injections of a pandemic 2009 influenza A (H1N1) vaccine in patients with systemic lupus erythematosus (SLE). Methods We conducted a single-center, observational prospective study of 111 patients who were vaccinated with a monovalent, inactivated, nonadjuvanted, split-virus vaccine during December 2009 and January 2010 and received a second dose of vaccine 3 weeks later. The antibody response was evaluated using the hemagglutination inhibition assay according to the guidelines recommended for the pandemic vaccine, consisting of 3 immunogenicity criteria (i.e., a seroprotection rate of 70%, a seroconversion rate of 40%, and a geometric mean ratio [GMR] of 2.5). Results The 3 immunogenicity criteria were met on day 42 (seroprotection rate 80.0% [95% confidence interval (95% CI) 72.5–87.5%], seroconversion rate 71.8% [95% CI 63.4–80.2%], and GMR 10.3 [95% CI 2.9–14.2]), while only 2 criteria were met on day 21 (seroprotection rate 66.7% [95% CI 57.9–75.4%], seroconversion rate 60.4% [95% CI 51.3–69.5%], and GMR 8.5 [95% CI 3.2–12.0]). The vaccine was well tolerated. Disease activity, assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, the British Isles Lupus Assessment Group score, and the Systemic Lupus Activity Questionnaire, did not increase. In the multivariate analysis, vaccination failure was significantly associated with immunosuppressive treatment or a lymphocyte count of ≤1.0 × 109/liter. The second injection significantly increased the immunogenicity in these subgroups, but not high enough to fulfill the seroprotection criterion in patients receiving immunosuppressive treatment. Conclusion Our findings indicate that the efficacy of the vaccine was impaired in patients who were receiving immunosuppressive drugs or who had lymphopenia. A second injection increased vaccine immunogenicity without reaching all efficacy criteria for a pandemic vaccine in patients receiving an immunosuppressive agent. These results open possibilities for improving anti-influenza vaccination in SLE.

Introduction Le syndrome des abces aseptiques (AA) est une entite rare caracterisee par des lesions circonscrites riches en polynucleaires neutrophiles et steriles, qui se manifeste le plus souvent par une fievre associee a un tableau douloureux generalement abdominal, variable en fonction de la localisation. Une reponse spectaculaire a la corticotherapie generale est caracteristique. En 2007, une cohorte de 30 patients a ete decrite, issue de l’enregistrement national (SNFMI-CNIL99-149). Depuis cette publication de nombreux cas ont ete recenses en France. Patients et methodes Nous avons voulu etudier les caracteristiques cliniques, biologiques et radiologiques de ces nouveaux cas, avec leur traitement et les donnees evolutives. Tous les patients francais repondant aux criteres diagnostiques d’AA ont ete inclus. Resultats Vingt-huit nouveaux cas ont ete inclus dans le registre national depuis 2007. Il s’agissait de 57 % de femmes, avec un âge moyen 34,6 ans (extremes 3 ans a 82 ans). Un quart des patients avait une maladie inflammatoire chronique de l’intestin (MICI) qui etait une maladie de Crohn a l’exception d’un cas de rectocolite hemorragique (RCH). Dans la plupart des cas, les AA ont ete diagnostiques apres la MICI sauf dans le cas de la RCH qui ete diagnostiquee 3 ans apres les AA. Les autres maladies associees etaient un lupus systemique, une polyarthrite rhumatoide, une polychondrite atrophiante ou un MAGIC syndrome. Cinquante pour cent des patients etaient fumeurs. Les principaux symptomes etaient des douleurs abdominales (71 %), une fievre (57 %) et un amaigrissement (40 %). Une atteinte cutanee ou muqueuse etait associee dans la moitie des cas (aphtes 20 %, erytheme noueux 7 % ou pyoderma gangrenosum 3 %), ainsi que des manifestations articulaires (arthralgie ou arthrite) dans 28 % des cas et des signes ophtalmologiques dans 7 % des cas (uveite ou episclerite). Le bilan biologique retrouvait une leucocytose a polynucleaires neutrophiles (67 %), une proteine C-reactive augmentee (82 %) et une perturbation du bilan hepatique (39 %). Un TEP-scanner a ete realise dans 42 % et retrouvait un hypermetabolisme au niveau des AA. Les AA etaient spleniques dans 64 % des cas et ne touchaient que la rate dans 14 % des cas. Les autres localisations etaient : adenopathies profondes (40 %), foie (25 %), poumon (25 %), seins (7 %), testicule, prostate, systeme nerveux central (cerveau ou moelle), ORL ou aortique. Trente-cinq pour cent avaient des localisations superficielles. Dans 57 % des cas, au moins deux organes etaient touches. Vingt-huit pour cent des patients ont eu une splenectomie, avec dans deux cas une amelioration transitoire des symptomes, mais une rechute systematique. Une antibiotherapie a ete utilisee dans 68 % des cas sans efficacite. Quatre-vingt-douze pour cent des patients ont recu des corticoides, avec une corticosensibilite constante. La colchicine a ete utilisee dans 71 % des cas, son utilisation en unique traitement a ete un succes dans un cas. Plus de la moitie des patients ont necessite l’ajout d’un immunosuppresseur parmi lesquels : anti-TNF (53 %) avec adalimumab (28 %), infliximab (21 %) ou etanercept (4 %) ; azathioprine (35 %) ; cyclophosphamide (14 %) ; methotrexate (14 %) ; anakinra (10 %) ; thalidomide (7 %). Quarante-six pour cent des patients ont rechute dont 28 % au moins deux fois. Le recul moyen etait de 8 ans. Discussion Les principales caracteristiques cliniques et biologiques de cette serie sont comparables aux donnees connues. Certains elements nouveaux apparaissent toutefois comme le tabagisme qui pourrait etre un facteur de risque. La localisation caracteristique reste l’atteinte splenique mais de nouvelles localisations ont ete decrites telles que des AA mammaires ou un cas d’aortite associee aux AA. Dans la majorite des cas, plusieurs organes sont touches. Le TEP-scanner est devenu un outil diagnostique frequemment utilise. Meme s’il persiste 28 % de splenectomie, celle-ci est tout de meme moins pratiquee que dans la serie precedente (50 %). La prise en charge therapeutique evolue aussi : la corticosensibilite reste la regle mais lorsqu’un immunosuppresseur est necessaire (en cas de rechute ou pour epargne cortisonique), il s’agit majoritairement d’une biotherapie. Celle-ci a ete dans trois cas de l’anakinra dont deux cas avec succes. Conclusion Le syndrome des abces aseptiques est une entite facilement reconnaissable et meme si de nombreux cas ont ete rapportes, il est probablement sous diagnostique. Malgre l’evolution des traitements et l’utilisation frequente des biotherapies, les rechutes restent toujours frequentes et de nombreux organes peuvent etre touches.

Introduction Les donnees concernant l’efficacite et la tolerance des biotherapies (anti-TNFα, tocilizumab, rituximab et anakinra) chez des patients atteints de manifestations auto-immunes (MAI) et systemiques (S) associees aux syndromes myelodysplasiques (SMD) sont limitees. Patients et methodes Etude retrospective multicentrique francaise, ayant inclus 29 patients presentant une MAI et un SMD traites avec au moins une ligne de biotherapie. Les reponses (cliniques, biologiques et globales) ont ete considerees comme completes (amelioration complete des symptomes), partielles (> 50 % d’amelioration) ou absentes. Les donnees ont ete recueillies avant et a la fin de chaque ligne des differents traitements, puis poolees et analysees en lignes de traitement pour comparer les reponses aux corticoides seuls, aux DMARDs et aux biotherapies. Resultats Vingt-neuf patients avec un âge median de 66 ans (19–85) ont ete inclus, 11 % de femmes. Les sous-types de SMD les plus frequents etaient une LMMC (18 %), une AREB-1 (32 %), une CRDM (32 %), un syndrome 5q− (7 %). Le taux de blastes medullaires etait 2 % (0–10), le caryotype etait normal dans 12/24 (50 %) des cas avec un IPSS a 0,5 (0–1). Les MAI ou S associees etaient un rhumatisme inflammatoire (indifferencie et polyarthrite rhumatoide dans 3 cas chacun [10 %]), une maladie de Behcet dans 2 cas (7 %), une vascularite cryoglobulinemique dans 2 cas (7 %), une arterite gigantocellulaire dans 1 cas (4 %), une polychondrite atrophiante dans 8 cas (30 %), un syndrome de Sweet dans 3 cas (10 %) et une vascularite inclassee dans 4 cas (14 %). Au cours du suivi median de 3 ans (1,3–4,5), 116 lignes de traitements ont ete utilisees : corticoides seuls 25 (24 %), DMARDs 30 (25 %), antagonistes du TNF-α 15 (15 %), anakinra 14 (14 %), rituximab 12 (10 %) et tocilizumab 9 (8 %). Le nombre median de lignes etait de 3 (1–9) et plus de 5 lignes ont ete utilisees chez 13 (46 %) patients. Un traitement specifique du SMD (azacytidine) a ete utilise pour des MAI chez 10 patients (9 %). La reponse globale (complete et partielle) etait obtenue dans 54 cas (58 %). En comparant les traitements, la reponse globale a ete notee dans 19/23 cas (78 %) sous corticoides, 8/12 cas (66 %) sous rituximab versus 8/21 (45 %) sous DMARD et 11/31 (33 %) sous anti-TNF-a, tocilizumab et anakinra. L’azacytidine a permis une reponse chez 4/6 patients evaluables. Une corticodependance etait notee chez 25 patients (86 %) avec une moyenne de 27 mg de prednisone/j (10–120). Les anti-TNF-α ont montre une efficacite sur les manifestations articulaires dans 4 cas sur 6. Au cours du suivi, 20 patients (71 %) ont presente au moins une infection grave et 11 une reaction a la perfusion conduisant a l’arret du traitement dans 7 cas. Conclusion Cette etude nationale montre l’efficacite des corticoides dans les MAI associees aux SMD mais avec une corticodependance frequente. La reponse globale aux biotherapies est mauvaise, en dehors du rituximab. L’efficacite de l’azacytidine dans ces manifestations pourrait justifier son utilisation independamment des indications hematologiques.

ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

The aim of this study was to determine the characteristics, treatment, and outcome according to each etiology of pachymeningitis.We conducted a retrospective multicenter French nationwide study between 2000 and 2016 to describe the characteristics, outcome, and treatment of pachymeningitis.We included 60 patients (median age 55.5 years; interquartile range [IQR] 30-80, female/male ratio 0.43). Neurologic signs were present in 59 patients (98%) and consisted of headache in 43 (72%), cranial nerve palsy in 33 (55%), confusion in 10 (17%), seizures in 7 (12%), and focal neurologic signs in 9 (15%). Fever and weight loss were present in 8 (13%) and 13 cases (22%), respectively. Cerebral venous thrombosis was present in 8 cases (13%). Analysis of cerebrospinal fluid showed moderate hyperproteinorachia (median 0.68 g/L; IQR 0.46-3.2) with or without pleiocytosis. Diagnosis included idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each). We found no difference in demographics and neurologic presentation among idiopathic pachymeningitis, Erdheim-Chester disease, and granulomatosis with polyangiitis. In contrast, frequencies were lower with idiopathic pachymeningitis than Erdheim-Chester disease for general signs (6% and 40%, respectively, P = .041) and complete neurologic response (0% vs 39%, P = .045).The detection of extraneurologic signs and routine screening are needed to classify the pachymeningitis origin. Prospective studies are warranted to determine the best treatment in each case.

Resume La maladie de Takayasu (MT) est une arterite inflammatoire rare des vaisseaux de gros et moyen calibre. Nous presentons ici les modalites de prise en charge proposees par notre equipe. Le diagnostic de MT est habituellement porte devant une arteriopathie des vaisseaux de gros ou moyen calibre, au terme d’un bilan permettant d’eliminer les principaux diagnostics differentiels. Lorsque la maladie parait active, nous proposons en premiere intention une corticotherapie (0,7 a 1 mg/kg par jour de prednisone) avec decroissance progressive. Nous associons generalement un traitement antiagregant plaquettaire, une statine et si besoin un traitement antihypertenseur. En l’absence de criteres valides, la maladie peut etre consideree comme active s’il existe des signes cliniques generaux ou ischemiques, une elevation d’au moins un marqueur inflammatoire, une prise de contraste murale en angio-TDM, des anomalies de signal ou une prise de gadolinium a l’IRM, ou des hyperfixations vasculaires au TEP-scan. Lorsque la MT est evolutive, nous proposons une evaluation morphologique arterielle par echographie doppler des TSA et angio-IRM ou angio-TDM aortique au moins deux fois par an. Lorsque la maladie parait quiescente, la surveillance radiologique est annuelle. Les indications chirurgicales sont rares au cours de la MT. La qualite de vie est fortement alteree au cours de la MT, alors que le pronostic est generalement bon. La prise en charge de la MT est rendue complexe par l’absence de criteres diagnostiques performants, de strategie therapeutique validee et de criteres d’activite fiables. Seuls des travaux cooperatifs permettront d’ameliorer la prise en charge de ces patients.

Introduction Le syndrome des antiphospholipides (SAPL) est defini par une combinaison de thromboses arterielles et/ou veineuses, de complications obstetricales (3 fausses couches spontanees successives, mort fœtale a partir de 10 semaines d’amenorrhee [SA] ou accouchement avant 34 SA du fait d’une insuffisance placentaire) et d’anticorps antiphospholipides persistants. A notre connaissance, il n’y a pas de large etude decrivant les morts fœtales in utero (MFIU) dans ce contexte ou analysant le devenir de ces patientes. Patients et methodes Nous avons analyse retrospectivement l’histoire et les donnees cliniques de patientes suivies dans 4 hopitaux universitaires francais pour un SAPL (criteres de Sydney) et ayant presente une MFIU a 10 SA, ou plus, entre 2000 et 2016. Suivant les criteres de classification, les patientes etaient exclues si la MFIU pouvait etre expliquee par une complication fœtale ou obstetricale sans lien avec le SAPL. Les patientes etaient incluses a condition d’avoir eu un test antiphospholipides positif a 2 reprises a au moins 12 semaines d’intervalle et a moins de 5 ans de l’evenement obstetrical. Resultats Au total, 65 patientes ont ete incluses. Leur âge median a la MFIU etait de 29 ans (Ecart interquartile [EIQ] : 26–33). Avant la MFIU, 11 patientes (17 %) avaient deja eu une naissance vivante et 38 etaient nulligestes (58 %). Le SAPL etait deja documente chez 11 patientes (17 %) et un lupus systemique (LES) diagnostique chez 9 patientes (14 %). Il y avait une prevalence elevee de profils triple positifs (35 %), soit positif pour l’anticoagulant circulant, l’anticardiolipine et l’antiB2-GP1 et 72 % de positivite pour l’anticoagulant circulant. Pendant la grossesse menant a la MFIU index, les traitement recus etaient de l’aspirine a faible dose (n = 7), de l’heparine de bas poids moleculaire (n = 3) ou une combinaison des 2 (n = 6). La MFIU survenait a un terme median de 24 SA (EIQ : 18–27). Elle etait associee dans 16 cas a des complications obstetricales maternelles, a savoir une pre-eclampsie (n = 12), un Hemolysis, Elevated Liver enzymes and Low Platelet count (HELLP) syndrome (n = 6) et/ou un hematome retroplacentaire (n = 5) et dans 25 cas a un retard de croissance intra-uterin (RCIU) (50 % sur 50 donnees disponibles). Il n’y a pas eu de mortalite maternelle. Des infarctus placentaires ont ete retrouves dans 28 des 38 examens anatomopathologiques disponibles (74 %). Pour la grossesse faisant suite a la MFIU, 35 des 45 patientes (78 %) recevant un traitement (aspirine ou heparine de bas poids moleculaire avant 12 SA) ont obtenu une naissance vivante contre seulement 2 des 10 patientes (20 %) n’ayant recu aucun traitement. En incluant un suivi median de 4 ans (EIQ : 2–9), 28 patientes (43 %) avaient presente au moins une thrombose, dont la moitie avant la MFIU index et 29 % avaient un diagnostic de LES. Au total, 54 patientes (83 %) ont eu au moins une naissance vivante. L’âge median au dernier suivi des femmes sans enfant etait de 33 ans (EIQ : 30–45), suggerant potentiellement plus de naissances vivantes a venir. Conclusion La MFIU etait principalement inaugurale, et, est generalement non associee aux complications obstetricales maternelles. Nous avons, en revanche, retrouve un RCIU dans 50 % des cas pour lesquels les donnees etaient disponibles. Il y avait presence d’une biologie antiphospholipides robuste et d’un nombre significatif de LES et de thrombose. Neanmoins, la majorite de ces patientes ont reussi a avoir une naissance vivante sous traitement.

Since the association between antiphospholipid antibodies and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce antiphospholipid antibodies, notably anticardiolipin antibodies. These aPL are usually associated neither with anti-beta2 glycoprotein I antibodies (anti-beta2-GPI) nor with thrombotic events, even if cases of arterial and deep venous thrombosis have been reported in such circumstances. A literature review shows that anticardiolipin antibodies occur frequently in viral infections, particularly in HIV (49.8%), HBV (24%) and HCV (20%). The prevalence of anti-beta2 glycoprotein I antibodies (anti-beta2GPI) is lower (HCV: 1.7%, HIV: 5.6%, HBV: 3.3%) and there is no demonstrated association with a risk of thrombotic events or hematological manifestations defining antiphospholipid syndrome (APS). Regarding other viral infections, including viral hepatitis A, herpes virus (CMV, EBV, VZV), parvovirus B19 and HTLV-1 infections, only a few studies are available but data confirm the high prevalence of antiphospholipid antibodies at the acute phase. Finally, antiphospholipid antibodies, mainly anticardiolipin, are frequently associated with viral infections. Their presence may probably reflect an intense or chronic antigenic stimulation of the immune system. However, their evolution under antiviral therapy and correlation with the quality of the virological control and/or the immune restoration remain to be determined.

In black population, the skin-bleaching with cutaneous topical corticosteroids on a large body area is a widespread practice and is associated with numerous cutaneous complications. We report a 25-year-old Congolese woman who was admitted for weakness, arthralgias and abdominal pain. The association of a relative hyperpigmentation of the small joints of hands and feet with clinical features of hypercorticism led to suspect a chronic use of cutaneous topical steroids for skin-bleaching. On biological tests, plasma cortisol and corticotropin levels were undetectable and the short corticotropin (ACTH) stimulation test was negative, leading to the diagnosis of adrenal insufficiency complicating the chronic use of topical steroids. Clinical symptoms resolved with hydrocortisone therapy. One year later, the patient admitted a five-year continuous use of cutaneous topical steroids (betamethasone, 0.05%). Skin-bleaching through chronic use of cutaneous topical steroids, is a common practice in black women, and should be suspected in the presence of adrenal insufficiency with or without clinical features of hypercorticism, and conversely, skin-bleaching users should be tested for hypothalamo-pituitary-adrenal function.

Resume Le traitement des thromboses du syndrome des anticorps antiphospholipides (SAPL) a longtemps ete empirique, base sur les donnees de cohortes retrospectives. Nous disposons maintenant des resultats d’essais therapeutiques randomises qui permettent d’optimiser les recommandations de prise en charge. Cette revue indique les progres realises mais egalement les incertitudes persistantes. Prevention secondaire des thromboses Alors que la poursuite du traitement par les antivitamines K (AVK) au long cours apres une premiere thrombose est consensuelle, deux essais randomises ont compare des intensites differentes de traitement. De maniere concordante, ces deux etudes ont montre qu’une anticoagulation avec un INR cible compris entre 3 et 4 n’etait pas plus efficace qu’une cible therapeutique entre 2 et 3. Ces etudes concernaient des patients ayant presente de facon preferentielle des thromboses veineuses. Aucun essai therapeutique n’a compare differentes strategies antithrombotiques pour la prophylaxie secondaire des accidents arteriels du syndrome des antiphospholipides. En particulier, l’etude WARSS/APASS ne concerne pas des patients avec syndrome des antiphospholipides defini et n’est donc pas applicable a cette population, comme cela a pu etre propose de facon erronee. Dans l’attente d’autres etudes, le traitement AVK reste le traitement de prophylaxie secondaire chez ces patients. Prevention primaire des thromboses Le risque eleve de thrombose chez des patients asymptomatiques presentant des anticorps antiphospholipides, en particulier dans le lupus systemique, a motive la realisation d’une etude randomisee aspirine versus placebo dans cette situation clinique. Cette etude n’a pas pu demontrer de benefice de l’aspirine en prophylaxie primaire. En conclusion, les resultats des essais therapeutiques recents ont permis d’optimiser la strategie antithrombotique du SAPL, notamment des formes avec maladie thromboembolique veineuse. Des questions non resolues restent posees sur les strategies optimales dans les formes arterielles et en prophylaxie primaire.

Objective:To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE.Methods:The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists.Results:Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken.Conclusion:This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

International audience; PURPOSE OF REVIEW: Hepatitis C virus infection is the main cause of mixed cryoglobulinemia vasculitis. The disease expression of mixed cryoglobulinemia vasculitis is variable, ranging from mild clinical symptoms (purpura, arthralgia) to fulminant life-threatening complications (glomerulonephritis, widespread vasculitis). Treatment of hepatitis C virus-mixed cryoglobulinemia vasculitis may target either the viral trigger (hepatitis C virus) or the downstream B-cell arm of autoimmunity. This review focuses on recent advances in our understanding of the treatment of hepatitis C virus-mixed cryoglobulinemia vasculitis. RECENT FINDINGS: Aggressive antiviral therapy with Peg-IFNalpha and ribavirin should be considered as induction therapy for hepatitis C virus-mixed cryoglobulinemia vasculitis with mild to moderate disease severity and activity. In patients presenting with severe disease, an induction phase of immunosuppression is often necessary while awaiting the generally slow response to antiviral treatments. Combination therapy with rituximab and Peg-IFNalpha plus ribavirin appears logical as it may target both the viral trigger (hepatitis C virus) and cryoglobulin-producing B-cells. SUMMARY: Antiviral therapy and rituximab are the main therapeutic options in hepatitis C virus-mixed cryoglobulinemia vasculitis. Further studies are needed to better define the therapeutic strategy.

Background: Melkersson-Rosenthal syndrome (MRS) is a rare disease whose full-blown form is characterized by orofacial swelling, facial palsy and lingua plicata. Objective: To investigate the complement system as well as its role in patients with MRS. Methods: Seven patients presenting at this hospital between November 2002 and May 2003 and meeting the diagnostic criteria according to Hornstein were evaluated retrospectively. The investigations included clinical signs, an analysis of the complement system including levels of CH50, C3, C4, C1 inhibitor (INH) functions and C1-INH antigen detection. Results: Two female patients showed isolated low levels of functional C1-INH as determined by duplicate tests. Both patients took estrogen-progestin contraceptives. Conclusion: Since deficiency in plasma protease C1-INH is known to lead to recurrent angioedema, we hypothesize that low levels of functional C1-INH may have contributed to the orofacial swelling in the 2 patients.

Antinuclear antibodies (ANA) are widely detected by immunofluorescence on HEp-2 cells in patients with connective tissue diseases and other pathological conditions. We evaluated the first-automated chemiluminescence immunoassay for the detection of ANA (LIAISON ANA screen, DiaSorin). This study was carried out simultaneously in two laboratories by testing 327 patient samples with clinically defined connective diseases, 273 routine samples for ANA screening, and 300 blood donors. A total of 268 out of 337 IIF-positive sera were positive with LIAISON ANA screen (79.5% of agreement) and 240 out of 263 IIF-negative sera were negative with LIAISON ANA screen (91.2% of agreement). After resolution of discrepant results, the concordance reached, respectively, 94.9% and 98.8%. The specificity was 99.3% and the sensitivity was 94%. Unlike results obtained by other ANA screening assays, we observed acceptable sensitivity and specificity. Despite the presence of HEp-2 cell extract, we failed to detect some antibodies as antinucleolar, antinuclear envelope, and antiproliferating cell nuclear antigen. This automated assay allows quick process to results and exhibits satisfactory sensitivity for the detection of the main ANA specificities of connective tissue diseases.

Resume Introduction Depuis la decouverte du virus de l'hepatite C (VHC), de nombreuses manifestations dites extrahepatiques ont ete rapportees avec plus ou moins de preuves solides. Actualites et Points forts Dans cet article, nous proposons une revue des principales manifestations extrahepatiques (MEH) associees au virus de l'hepatite C (VHC) et qui restent un sujet d'actualite plus de quinze ans apres la decouverte de ce virus. La cryoglobulinemie et ses manifestations systemiques, a type de vascularite, restent parmi les plus frequentes et l'avenement des therapeutiques ciblees de type anti-CD20 devrait modifier significativement leur traitement voire leur pronostic. Parmi les autres manifestations extrahepatiques liees au VHC, on n'oubliera pas le syndrome de fatigue chronique, le syndrome sec, le diabete non insulinodependant, les lymphoproliferations B malignes en particulier le lymphome splenique a cellules villeuses et enfin la production d'auto-anticorps. Perspectives et Projets Les mecanismes physiopathologiques sous-tendant ces manifestations extrahepatiques sont encore mal elucides et font l'objet de travaux soutenus. Il en est de meme pour la place des anticorps anti-CD20 dans le traitement des vascularites cryoglobulinemiques.

Resume Propos Les uveites chroniques non infectieuses representent deux tiers des causes des uveites chroniques adressees dans les services d'ophtalmologie de reference. Un cas sur cinq se compliquerait de cecite. Selon la severite de l'uveite et l'orientation diagnostique, le traitement sera decide, traitement local ou traitement par voie generale base sur la corticotherapie et les immunosuppresseurs. Actualites et points forts En dehors de la corticotherapie et de la ciclosporine, l'utilisation des immunosuppresseurs et des biotherapies dans les uveites chroniques non infectieuses n'est pas une indication retenue dans l'autorisation de mise sur le marche (AMM). Cependant, les immunosuppresseurs et les biotherapies ont fait l'objet de plusieurs etudes, bien que les etudes controlees soient rares. Ces etudes controlees ont concerne la ciclosporine, l'azathioprine et le cyclophosphamide IV dans l'uveite de la maladie de Behcet, la ciclosporine et le tacrolimus dans des uveites de cause variee. Le traitement des uveites chroniques non infectieuses s'est recemment enrichi de nouvelles molecules : le mycophenolate mofetil initialement utilise en transplantation d'organes a vu son indication s'etendre au traitement des maladies systemiques ; les anti-TNF utilises initialement dans le traitement de maladies systemiques ; l'interferon dont l'efficacite s'est revelee dans la maladie de Behcet, est actuellement utilise dans des uveites d'autres causes. Perspectives et projets Des etudes controlees sont souhaitables pour preciser notamment la part respective des immunosuppresseurs par rapport aux biotherapies dans le traitement des uveites.

Resume Propos La physiopathologie de la maladie de Behcet (MB) est complexe. De nouvelles donnees experimentales permettent de mieux comprendre les mecanismes qui president a l'apparition des lesions organiques. Actualites et points forts Ces nouvelles donnees mettent en exergue le role effecteur majeur joue par les polynucleaires neutrophiles et les lymphocytes cytotoxiques. Une susceptibilite genetique, des facteurs environnementaux (infections virales et/ou bacteriennes), des anomalies de la reponse inflammatoire (proteines du choc thermique, dysregulation de la production de NO) et un dysfonctionnement du systeme immunitaire interviennent egalement dans la pathogenie de la MB. Perspectives et projets Cette meilleure comprehension de la physiopathologie de la MB devrait permettre a terme de developper de nouveaux traitements plus specifiques.

The rational way to set a diagnosis and estimate a prognosis in rheumatology is to start by setting a tentative diagnosis and then follow a fixed scheme for laboratory testing, eg, by using an agreed algorithm. The use of order algorithms can be extended to post-test algorithms that will assist clinicians in approaching the right diagnosis and prognosis. New methods used in autoimmune serology do not deliver results that can be directly compared to those of older methods, and thus the new methods need to be thoroughly tested with sera from differential diagnostically relevant disease controls to set a clinically meaningful cut-off for positivity. Borderline positive results need to be treated with special care to avoid misuse. Early diagnosis is of great importance, and serological results can be very useful if used the right way. European efforts to secure rational diagnostic work-up in autoimmune rheumatic disease have led to a better dialogue between clinicians and laboratory scientists in several countries.

Resume Introduction La chorioretinopathie sereuse centrale (CRSC) est une pathologie retinienne relativement rare dont les mecanismes physiopathologiques restent mal connus. Elle est caracterisee par l'accumulation de liquide au pole posterieur de la retine, decollant celle-ci sur une zone circonscrite. Elle se manifeste generalement par une baisse d'acuite visuelle ou une anomalie de la vision des couleurs. Souvent idiopathique, elle peut egalement etre associee a de nombreuses situations pathologiques, l'exposition aux corticoides etant souvent au premier plan. Exegese Nous rapportons le cas de deux patients ayant presente une CRSC. Il s'agissait d'une patiente traitee par corticoides depuis 15 ans pour un lupus systemique et d'un patient traite par corticoides depuis quelques mois pour un syndrome hypereosinophilique idiopathique. Une baisse d'acuite visuelle a conduit au diagnostic de CRSC. La diminution des corticoides a permis une amelioration clinique dans les deux cas. Conclusion La CRSC fait partie des effets indesirables oculaires des traitements par corticoides au meme titre que la cataracte et le glaucome chronique et merite donc d'etre connue par les medecins internistes.