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ImportanceCatastrophic antiphospholipid syndrome (CAPS) is a severe, rare complication of antiphospholipid syndrome (APS), but cutaneous involvement has not yet been adequately described.ObjectiveTo describe cutaneous involvement during CAPS, its clinical and pathological features, and outcomes.Design, Setting, and ParticipantsThis cohort study was a retrospective analysis of patients included in the French multicenter APS/systemic lupus erythematosus register (ClinicalTrials.gov: NCT02782039) by December 2020. All patients meeting the revised international classification criteria for CAPS were included, and patients with cutaneous manifestations were analyzed more specifically.Main Outcomes and MeasuresClinical and pathological data as well as course and outcome in patients with cutaneous involvement during CAPS were collected and compared with those in the register without cutaneous involvement.ResultsAmong 120 patients with at least 1 CAPS episode, the 65 (54%) with skin involvement (43 [66%] women; median [range] age, 31 [12-69] years) were analyzed. Catastrophic antiphospholipid syndrome was the first APS manifestation for 21 of 60 (35%) patients with available data. The main lesions were recent-onset or newly worsened livedo racemosa (n = 29, 45%), necrotic and/or ulcerated lesions (n = 27, 42%), subungual splinter hemorrhages (n = 19, 29%), apparent distal inflammatory edema (reddened and warm hands, feet, or face) (n = 15, 23%), and/or vascular purpura (n = 9, 14%). Sixteen biopsies performed during CAPS episodes were reviewed and showed microthrombi of dermal capillaries in 15 patients (94%). These lesions healed without sequelae in slightly more than 90% (58 of 64) of patients. Patients with cutaneous involvement showed a trend toward more frequent histologically proven CAPS (37% vs 24%, P = .16) than those without such involvement, while mortality did not differ significantly between the groups (respectively, 5% vs 9%, P = .47).Conclusions and RelevanceIn this cohort study, half the patients with CAPS showed cutaneous involvement, with a wide spectrum of clinical presentations, including distal inflammatory edema. Skin biopsies confirmed the diagnosis in all but 1 biopsied patient.

Objective APS is a heterogeneous disease with different phenotypes. Using an unsupervised hierarchical cluster analysis, we aimed to determine distinct homogeneous phenotypes among APS patients. Methods We performed an observational, retrospective study of APS patients enrolled in the French multicentre ‘APS and SLE’ registry who met the Sydney classification criteria. The clustering process involved an unsupervised multiple correspondence analysis followed by a hierarchical ascendant clustering analysis; it used 27 variables selected to cover a broad range of APS clinical and laboratory manifestations. Results These analyses included 509 patients, mainly women (77.8%). Mean (s.d.) age at APS diagnosis was 36.2 (14.6) years, and mean follow-up since diagnosis 10.3 (8.5) years. This hierarchical classification cluster analysis yielded four homogeneous groups of patients: cluster 1, mostly with venous thromboembolism without any associated autoimmune disease; cluster 2, older, lowest proportion of women, history of arterial events, and/or with migraines, arterial hypertension, diabetes mellitus, or dyslipidaemia; cluster 3, younger, highest proportion of women, associated SLE or other autoimmune diseases, and a history of venous thromboembolism or pregnancy morbidity; and cluster 4, mainly with a history of catastrophic antiphospholipid syndrome, aPL-associated nephropathy, and pregnancy morbidity, with frequent triple positivity and more deaths (16.7%). Conclusions Our study applied an unsupervised clustering method to distinguish four homogeneous APS patient subgroups that were predominantly venous; arterial; associated with SLE or another autoimmune disease; and arterial microthrombotic. Heterogeneous pathophysiological mechanisms may explain these findings.

Objective HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels. Methods This case–control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy. Results The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P Conclusion SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.

Objective: To investigate the prevalence, clinical features and outcomes of coronavirus disease 2019 (COVID-19) among sarcoidosis patients. Methods: We retrospectively collected features of COVID-19 in a cohort of patients with sarcoidosis followed in a single tertiary university hospital. Results: Among 199 sarcoidosis patients [mean age 58.8 (±14) years, 86 (43.2%) men], 26 (13%) were diagnosed with COVID-19 [definite (n=7), probable (n=12) and possible (n=7)]. Twenty-four out of 26 patients (92%) had at least one comorbidity, and 11/26 (42%) had two or more comorbidities. Demographic and clinical features of COVID-19 positive patients were similar to those of COVID-19 negative patients. The administration of hydroxychloroquine or immunosuppressant was not associated with the occurrence or the severity of COVID-19. Four out of 26 (15.4%) COVID-19 positive patients required admission to hospital and two of them died. Hospitalized patients [mean age of 61 (±11.5) years] were receiving higher doses of long term treatment with corticosteroids than non-hospitalized patients; 4/4 had pulmonary and 2/4 cardiac involvement of sarcoidosis, and all one or more comorbidity. Conclusion: The prevalence of COVID-19 in sarcoidosis is slightly higher to that of the general population. Almost half of the COVID-19 positive patients have two or more comorbidities and about 15% present a severe course.

International audience; Objective: To report the efficacy of rituximab plus belimumab in patients with refractory cryoglobulinemia vasculitis (CV).Methods: Belimumab was administered intravenously at a dose of 10 mg/kg on days 0, 14, 28 and then every month in association with rituximab in 4 patients with refractory CV. Demographic, clinical and laboratory characteristics, treatment modalities and outcomes were recorded.Results: All patients had type II IgM Kappa cryoglobulinemia, which was associated with primary Sjögren syndrome (n = 1), hepatitis C virus infection (n = 1), and essential (n = 2). Main manifestations of CV included purpura (n = 4), arthralgia and peripheral neuropathy (n = 3), and glomerulonephritis and skin ulcers (n = 1). In all cases, CV was refractory and/or relapse following rituximab. Intravenous belimumab infusion along with rituximab resulted in rapid clinical response in the four patients. Osteitis and recurrent urinary tract infections occurred in two patients.Conclusion: Belimumab along with rituximab showed promising results in refractory patients with CV.

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.

International audience; The dynamic of the temporal correlations between brain areas, called functional connectivity (FC), undergoes complex transformations through the life span. In this review, we aim to provide an overview of these changes in the nonpathological brain from fetal life to advanced age. After a brief description of the main methods, we propose that FC development can be divided into four main phases: first, before birth, a strong change in FC leads to the emergence of functional proto‐networks, involving mainly within network short‐range connections. Then, during the first years of life, there is a strong widespread organization of networks which starts with segregation processes followed by a continuous increase in integration. Thereafter, from adolescence to early adulthood, a refinement of existing networks in the brain occurs, characterized by an increase in integrative processes until about 40 years. Middle age constitutes a pivotal period associated with an inversion of the functional brain trajectories with a decrease in segregation process in conjunction to a large‐scale reorganization of between network connections. Studies suggest that these processes are in line with the development of cognitive and sensory functions throughout life as well as their deterioration. During aging, results support the notion of dedifferentiation processes, which refer to the decrease in functional selectivity of the brain regions, resulting in more diffuse and less specialized FC, associated with the disruption of cognitive functions with age. The inversion of developmental processes during aging is in accordance with the developmental models of neuroanatomy for which the latest matured regions are the first to deteriorate.

ObjectivesThe predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti–melanoma differentiation-associated gene 5 antibody–positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease.MethodsTo characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5−; n = 190/201) based on selected variables, collected retrospectively, without any missing data.ResultsWithin anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5− patients with myositis.ConclusionAnti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.

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.

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

The catastrophic antiphospholipid syndrome (CAPS) develops in at least 1% of patients with antiphospholipid syndrome, either primary or associated with systemic lupus erythematosus. CAPS reveals the antiphospholipid syndrome in about 50% of cases. The CAPS is characterized by rapidly-progressive widespread thromboses mainly affecting the microvasculature in the presence of antiphospholipid antibodies. In a few days, the patients develop multiorgan failure with renal insufficiency with severe hypertension, pulmonary, cerebral, cardiac, digestive and/or cutaneous involvement. The vital prognosis is frequently engaged. CAPS is often precipitated by infectious diseases, surgical procedures and/or withdrawal or modification of the anticoagulation. CAPS overall mortality rate has decreased and is currently below 30%. The main differential diagnoses are other thrombotic microangiopathies, and heparin-induced thrombocytopenia. The treatment of CAPS consists of the association of anticoagulation and steroids, plus plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is added only in patients with active systemic lupus erythematosus. The potential contribution of some additional therapies (rituximab, eculizumab or sirolimus) needs to be assessed. The prevention of CAPS is essential and is based upon the adequate management of the perioperative period when surgery cannot be avoided, the prompt treatment and the prevention with immunization of infections and the education of patients with antiphospholipid syndrome, especially for the management of oral anticoagulants.

Introduction Les dermatomyosites a anticorps anti-MDA5 (DM MDA5+) ont des atteintes extramusculaires au premier plan (lesions cutanees severes, arthralgies/arthrite, fievre) pouvant engager le pronostic vital (atteinte pulmonaire), alors que l’atteinte musculaire est peu marquee. Leur pronostic est sombre (25 % de mortalite) et il est important de definir des facteurs de risque de mortalite pour mieux definir la strategie therapeutique. L’objectif de cette etude est d’identifier des facteurs pronostiques chez les DM MDA5+. Materiels et methodes Nous avons realise une etude nationale multicentrique retrospective grâce au Reseau francais des myosites pour les DM MDA5+. Les criteres d’inclusion etaient : – un diagnostic de DM (definie selon les criteres de l’ENMC en 2004 : un debut progressif subaigu, une faiblesse musculaire plutot proximale, une atteinte cutanee typique comme un erytheme lilace des paupieres, des papules de Gottron ou un erytheme du decollete et une atrophie perifasciculaire a la biopsie musculaire) ; – la positivite des anticorps anti-MDA5. Les recueils des donnees cliniques, paracliniques et evolutives ont ete realises a partir des dossiers des patients. Resultats Quarante et un patients ont ete identifies. L’âge moyen etait de 44 ans (± 16,5) avec un sex-ratio femme/homme de 1,4. Au diagnostic 92 % patients presentaient une atteinte pulmonaire et 87 % une atteinte cutanee. Un tiers (31 %) des patients ont presente une atteinte pulmonaire rapidement progressive (RPILD definie par une aggravation des lesions au scanner thoracique ou une aggravation des EFR pendant une duree inferieure ou egale a 3 mois). Les atteintes articulaires et musculaires (deficit moteur ou elevation des CK) etaient observees respectivement dans 75 % et 51 % des cas. La duree moyenne de suivi etait de 41,2 mois (± 61,3). La plupart des patients ont beneficie de corticosteroides (98 %) et d’immunosuppresseurs (83 %, dont 24 % du cyclophosphamide et 15 % des inhibiteurs des calcineurines) ou de rituximab (7 %), plus ou moins associes a des echanges plasmatiques (20 %) et/ou des immunoglobulines intraveineuses (15 %) selon leur severite. Le taux de mortalite etait de 22 %, avec des 44 % des deces survenus dans les 3 mois suivants le diagnostic. Les deces etaient dus a l’atteinte respiratoire dans 67 % des cas. Parmi les patients vivants, 52 % ont presente au moins une rechute, avec le plus frequemment une rechute pulmonaire (45 % des patients rechuteurs). L’analyse univariee identifie 3 variables liees au deces. Comme attendu les signes de gravite immediate respiratoire ont ete identifies avec une hypoxie severe (paO2 Conclusion Comme attendu, la severite initiale de l’atteinte pulmonaire (RPILD et hypoxie profonde) est un facteur pronostique pejoratif. Cette etude suggere pour la premiere fois que le sexe feminin et l’existence d’une atteinte articulaire seraient des elements de bon pronostic a prendre en compte dans la strategie therapeutique chez les patients sans signe de gravite pulmonaire immediate.

We read with great interest the article by Petri et al. describing the association between hydroxychloroquine (HCQ) blood level and HCQ retinopathy in systemic lupus erythematosus (SLE) (1). Retinopathy occurred in 4.3% of 537 SLE patients. Both mean (p=0.0124) and maximum (p=0.034) HCQ blood levels predicted HCQ retinopathy. By contrast, in a recent case-control study including 23 SLE patients with HCQ retinopathy and 547 controls, no association was found between HCQ blood levels and HCQ retinopathy (2) with a median HCQ blood level of 944ng/mL in the retinopathy group versus 849ng/mL in the control group (p=0.46).

Objective Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP. Methods We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center. Results Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5- and 10-year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis. Conclusion This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes.

The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti–MDA5 + -patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti–MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2–positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti–MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

COVID-19, caused by the SARS-CoV-2, is an unprecedented global pandemic. Advanced age and cardiovascular diseases are recognised as major comorbidities associated with severe forms of COVID-19. Patients with large vessels vasculitis (LVV) could be considered at-risk for severe COVID-19 due to frequent age over 65 years in patients with giant cell arteritis (GCA), severe hypertension in patients with Takayasu arteritis (TAK) and current use of immunomodulating therapies in both LVV. Data on prevalence, clinical presentation and outcome of SARS-CoV-2 infection among patients with LVV are lacking.1–3 Tomelleri et al reported their experience in a single tertiary centre in Lombardy, the Italian region with the highest proportion of infected subjects.2 Their incidence rate of confirmed COVID-19 infection by nasopharyngeal PCR was 2.5% (4/162). Two patients required hospitalisation for COVID-19 interstitial pneumonia and no death was observed. We report our experience on clinical presentation and outcome of COVID-19 among patients with LVV in Paris-Ile de France, another region particularly affected during the same period. A phone survey was conducted between 04 and 20 May 2020, 8 weeks after lockdown started in France, among patients with LVV followed in Pitie-Salpetriere Hospital (Paris, France). Patients with positive nasopharyngeal PCR and/or thoracic CT scan suggestive of …

International audience

Background Studies on bone involvement of sarcoidosis (BS) are scarse. Objectives To analyse in depth main features, treatments and follow up of patients presenting a BS. Methods Among 926 patients with a proved sarcoidosis from four tertiary hospitals in Paris (France) seen between 2000 and 2015, all cases of BS were retrospectively analysed for demography, clinical features, biological tests and imaging results. Inclusion criteria were a) a bone biopsy with epithelioid granuloma and no casein necrosis, or b) radiological evidence of BS, after exclusion of other diagnoses. Results 27 out 926 (2.9%) sarcoidosis patients fullfilled inclusion criteria for BS. Most patients were caucasian (56%), M/F sex ratio 1.5, 30% were active smokers, mean age at sarcoidosis diagnosis was 39±12 years and at BS diagnosis 43±11 years. Extra-osseous involvement of sarcoidosis was found in lymph nodes (93%), lungs (78%), skin (52%), CNS (33%), ENT (33%), and heart (19%). BS was symptomatic in 15/27 (56%) patients i.e. bone pain (15/15), local inflammation (5/15), bone deformation (3/15), arthritis (4/15), and myalgia (5/15). BS was never the revealing symptom of sarcoidosis. BS was more frequently symptomatic when it was a Perthes-Jungling osteitis and an appendicular skeletton involvement. On imaging exams, BS lesions were found at the spine skeletton alone (14/27, 52%), appendicular skeletton alone (10/27, 37%) or both (3/27, 11%). BS lesions had an aspect of pseudo-metastasis (59%), micro-cysts (Perthes-Jungling, 37%) or Paget disease (4%). Bone lesion was unique in 22% and 26% of patients had more than 10 lesions. When a bone biopsy was done it always confirmed the diagnosis (n=9); in all other cases extra-osseous biopsies confirmed the diagnosis of sarcoidosis. Nine patients received a treatment for BS, i.e. prednisone (n=8, 0.25–1 mg/kg/day), hydroxychloroquine (n=8), and methotrexate (n=5). Response to treatment was complete (n=3), partial (n=4) or nul (n=2). Of note, 21 out of 27 patients received an immunosuppressant for a severe form of systemic sarcoidosis (n=11) or for a steroid-sparing effect (n=10). A relapse of BS was noted in 13 patients, with a mean number of relapse of 2.1–24 After a mean follow up of 49 months, BS was in complete remission (8/27, 30%), partial remission (16/27, 59%) or remained active (3/27, 11%). Conclusions Bone involvement remains a rare manifestation of sarcoidosis. It was symptomatic in 56% of patients, mainly when Perthes-Jungling osteitis and appendicular skeletton involvement were present. Extra-osseous involvement of sarcoidosis were always present at the time of BS diagnosis. Treatment remains difficult with frequent relapses. Disclosure of Interest None declared

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 (HCQ200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI80% or MMAS-86). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).

Introduction La dermatomyosite a anticorps anti-MDA5 (Melanoma differentiation-associated gene 5) (DM MDA5 + ) est une maladie systemique touchant la peau, les articulations et le poumon. L’atteinte pulmonaire peut etre rapidement progressive et fatale. L’anticorps anti-MDA5 cible un recepteur reconnaissant les ADN/ARN viraux. La frequence de l’atteinte respiratoire (> 80 % des cas) et la nature de la cible auto-antigenique suggerent un facteur declenchant viral de la maladie. Pour explorer cette question nous avons fait l’hypothese que le debut de la maladie etait rythme par les infections virales saisonnieres a tropisme respiratoire. Ce travail avait pour objectif de determiner si le debut des symptomes etait saisonnier. Materiels et methodes Nous avons realise une etude observationnelle, retrospective et multicentrique (n = 37) sur une cohorte francaise de patients atteinte de DM MDA5 + . Les donnees cliniques, biologiques et radiographiques ont ete etudiees, ainsi que la date d’apparition des premiers symptomes respiratoires (definis par le mois d’apparition des premiers symptomes reportes dans le premier compte rendu). Apres une analyse de la serie temporelle (stationnaire, autocorrelation) la modelisation des resultats (SARIMA) a pu etre appliquee. Les resultats ont ete compares a ceux de la declaration des cas de grippe recueillis par l’institut de veille sanitaire (INVS). Resultats Les patients inclus (n = 121) etaient majoritairement des femmes (diagnostic 2002–2017) d’âge moyen 49 ans. La majorite des patients presentaient des lesions cutanees (87,5 %), une pneumopathie interstitielle (77 %) et des arthralgies (69 %). Un tiers des patients etait febrile au diagnostic. L’atteinte pulmonaire etait rapidement progressive dans un tiers des cas. Un quart des patients sont decedes. La survenue des symptomes a ete classee par trimestre. Dans un premier temps, l’analyse de la repartition des premiers symptomes par trimestre montre qu’ils surviennent plus frequemment en periode hivernale (p = 0,05). Dans un second temps, la modelisation a permis de montrer que la repartition des premiers symptomes etait saisonniere (periodique) (p Conclusion Cette etude a permis de mettre en evidence que le debut des symptomes etait saisonnier avec un pic hivernal comparable a celui des cas declares de grippe. Ensemble, ces donnees suggerent indirectement l’implication d’un virus dans la physiopathologie de la maladie.

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.

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.

Liver disease can be observed in pregnant women whether or not related to pregnancy. Liver disorders can be revealed by pruritus, vomiting, jaundice or abnormal liver blood tests during pregnancy. These liver manifestations can lead to the diagnosis of liver disease specifically associated to pregnancy as intrahepatic pregnancy, intrahepatic cholestasis of pregnancy, Hyperemesis gravidarum, acute fatty liver of pregnancy and preeclampsia-induced liver injury. Pregnancy may also be a risk factor for other liver diseases coincident with pregnancy as viral hepatitis, thrombosis, drug toxicity or gallstone. Finally, pre-existing liver disease must be taken into account given the risk of fœto-maternal transmission risk as well as the risk of decompensation of underlying cirrhosis secondary to the hemodynamic changes caused by pregnancy. The aim of this revue is to perform an update on the various situations that can be observed, the principles of management of these liver diseases, in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27–56) years. The median duration of anticoagulation was 21 (9–118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

International audience; The aim of this study was to characterize, using fMRI, the functional asymmetries of hand laterality task (HLT) in a sample of 295 participants balanced for handedness. During HLT, participants have to decide whether the displayed picture of a hand represent a right or a left hand. Pictures of hands' back view were presented for 150 ms in the right or left hemifield. At the whole hemisphere level, we evidenced that the laterality of the hand and of the hemifield in which the picture was displayed combined their effects on the hemispheric asymmetry in an additive way. We then identified a set of 17 functional homotopic regions of interest (hROIs) including premotor, motor, somatosensory and parietal regions, whose activity and asymmetry varied with the laterality of the presented hands. When the laterality of a right hand had to be evaluated, these areas showed stronger leftward asymmetry, the hROI located in the primary motor area showing a significant larger effect than all other hROIs. In addition a subset of six parietal regions involved in visuo-motor integration together with two postcentral areas showed a variation in asymmetry with hemifield of presentation. Finally, while handedness had no effect at the hemispheric level, two regions located in the parietal operculum and intraparietal sulcus exhibited larger leftward asymmetry with right handedness independently of the hand of presentation. The present results extend those of previous works in showing a shift of asymmetries during HLT according to the hand presented in sensorimotor areas including primary motor cortex. This shift was not affected by manual preference. They also demonstrate that the coordination of visual information and handedness identification of hands relied on the coexistence of contralateral motor and visual representations in the superior parietal lobe and the postcentral gyrus.

Purpose To propose a manual segmentation method for individual quadriceps femoris (QF) muscles and to test its reliability for muscle volume estimation. Materials and Methods Images were acquired every 5 mm along the thigh using a 3T MRI scanner on 10 young (mean age: 25 years) and 10 older (mean age: 75 years) adults using a three-point 3D Dixon sequence. In each slice, anatomical cross-sectional areas of the individual quadriceps muscles of the dominant leg were outlined by two operators working independently. Differences between operators were assessed by means of Bland–Altman plots and intraclass correlation coefficients (ICC). This study was approved by the local Ethics Committee. Results Precise delimitation of individual muscles along the femur often remains challenging, particularly near their insertion areas where some muscles may be partially or totally fused. There was, however, an excellent interoperator segmentation reliability despite a systematic significant difference between operators (ICC > 0.99), mainly due to delineation divergences. Considering all subjects and muscles, differences between operators were all lower than 4.4%. Conclusion This work has demonstrated the excellent reliability of manual segmentation to assess cross-sectional areas and therefore the volume of individual QF muscles using MRI. It may serve as a basis for a future segmentation consensus of the QF muscles. J. Magn. Reson. Imaging 2014;40:239–247. © 2013 Wiley Periodicals, Inc.

The Emergency Department (ED) is an environment at risk for medical errors.Our aim was to determine the factors associated with the adverse events resulting from medical errors in the ED among patients who were admitted.This was a prospective observational study. For a 1-month period, we included all ED patients who were subsequently admitted to the medical ward. Detection of medical errors was made by the admitting physician and then validated by two experts who reviewed all available data and medical charts pertaining to the patient's hospital stay, including the first review from the ward physician. Related adverse events resulting from medical errors were then classified by type and severity. Adverse events were defined as medical errors that needed an intervention or caused harm to the patient. Univariate analysis examined relationships between characteristics of both patients and physicians and the risk of adverse events.From 197 analyzed patients, 130 errors were detected, of these, 34 were categorized as adverse events among 19 patients (10%). Seventy-six percent of these were categorized as proficiency errors. The only factors associated with a lower risk of adverse events were the transition of care involving a handoff within the ED (0% vs. 19%; p = 0.03) and the involvement of a resident (junior doctor) in addition to the senior physician (37% vs. 67%; p0.01).In our study, the involvement of more than one physician was associated with a lower risk of adverse events.

Introduction: A proportion of patients with clinically amyopathic dermatomyositis (DM) have autoantibody recognizing a 140 kDa protein, identified as melanoma differentiation-associated protein-5 (MDA-5). Most published cases originate from small Asian series. Methods: We report the first French multicentric retrospective series of MDA-5 positive DM. MDA-5 antibodies were detected by Immunodot (D-Tek®). Results: The series included 62 patients (38 women, 30 Afro-Caribbeans, mean age 46.6 years [16-71]). Interstitial lung disease (ILD) was present in 90% of cases with acute or subacute onset in 72%, and fever in 55%. ILD was the revealing condition in one fourth of cases. Chest CT demonstrated a pattern of nonspecific interstitial pneumonitis and/or organized pneumonia. Sixteen patients (25.8%) have been admitted in intensive care unit for an acute respiratory failure and 7 cases developed pneumomediastinum and/or pneumothorax at some point of follow-up. Whereas lung involvement was isolated in 10% of cases, skin manifestations were present in 90% (ulcerations or skin necrosis [47%], hyperkeratosis [55%], facial erythema [47%] and Raynaud9s phenomenon [21%]). Other manifestations included arthritis (71%), myositis (50%), pericarditis (n=3), and severe myocardial impairment (n=2). At the end of follow-up (34.5±39 months), 17 patients died, one received lung transplantation and one heart transplantation. The causes of death were ARDS (n=9) and infection (n=8, including pneumocystis jiroveci: n=3). Conclusion: Our series confirm the severity of dermato-pulmonary syndrome associated with MDA-5 antibodies in a European series. Pneumologists should search for skin lesions and MDA-5 antibodies in patients with acute ILD.

International audience; We report on a database, named BIL&GIN, designed for investigating the cognitive, behavioral, genetic, and brain morphological/functional correlates of hemispheric specialization. The database contains records from a sample of 453 adult participants enriched in left-handers (45%, N=205) as compared to the general population. For each subject, socio-demographic data, hand and eye laterality, family handedness, and cognitive abilities in the language, motor, visuo-spatial, and numerical domains have been recorded. T1-MRI and DTI data were also acquired, as well as resting-state functional MRI. Task-evoked functional MRI was performed in a sub-sample of 303 subjects (157 left-handers) using a customized functional battery of 16 cognitive tasks exploring the same three cognitive domains. Performances at the tasks executed in the magnet as well as post-acquisition debriefing were recorded. A saliva sample was obtained from the subjects of this sub-sample from which DNA was extracted. The BIL&GIN contains results of imaging data processing for each subject, namely maps of tissue (GM, WM, CSF) probability, cortical thickness, cortical surface, and diffusion parameters as well as regional values of these phenotypes for regions of both AAL and FreeSurfer parcellations. For the subjects who underwent FMRI, individual SPM contrast maps for each of the 8 runs were also calculated and included in the database, as well as corresponding BOLD variations in ROIs of the AAL and AICHA atlases, and Wilke's hemispheric functional lateralization index. The BIL&GIN data sharing is based on a collaborative model.

The catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition resulting from rapidly progressive widespread thromboses mainly affecting the microvasculature in the presence of antiphospholipid antibodies. Within a few days, the patients develop multiorgan failure with pulmonary distress, renal failure with severe hypertension, cerebral, cardiac, digestive or cutaneous involvement. CAPS develops in less than 1% of patients with antiphospholipid syndrome, either primary or associated with systemic lupus erythematosus. CAPS reveals the antiphospholipid syndrome in about 50% of cases. CAPS may be precipitated by infectious diseases, surgical procedures or discontinuation of anticoagulation. CAPS overall mortality rate has decreased in the past decade and is now around 30%. Within our hospital, it has been reduced to 10%. The main differential diagnoses are other thrombotic microangiopathies, and heparin-induced thrombocytopenia. The treatment of CAPS consists of the empirical association of anticoagulation and corticosteroids, plus plasma exchange or intravenous immunoglobulins. Cyclophosphamide is added in patients with systemic lupus erythematosus. The prevention of CAPS is based upon the adequate management of the perioperative period when surgery cannot be avoided, the prompt treatment of infections and the education of patients with antiphospholipid syndrome.

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.

International audience; Jean Piaget’s theory is a central reference point in the study of logico-mathematical development in children. One of the most famous Piagetian tasks is number conservation. Failures and successes in this task reveal two fundamental stages in children’s thinking and judgment, shifting at approximately 7 years of age from visuospatial intuition to number conservation. In the current study, preschool children (nonconservers, 5–6 years of age) and school-age children (conservers, 9–10 years of age) were presented with Piaget’s conservation-of-number task and monitored by functional magnetic resonance imaging (fMRI). The cognitive change allowing children to access conservation was shown to be related to the neural contribution of a bilateral parietofrontal network involved in numerical and executive functions. These fMRI results highlight how the behavioral and cognitive stages Piaget formu-lated during the 20th century manifest in the brain with age.

OBJECTIVE: The aim of this work was to describe chorea during systemic lupus erythematosus or antiphospholipid antibodies and its long-term outcome. METHODS: We retrospectively analyzed clinical features, laboratory findings, imaging characteristics, and outcome in a series of 32 patients. RESULTS: Most patients were women (28 of 32), and mean age at onset of chorea was 20.6 (9-62) years. Chorea was inaugural for 28 patients. Improvement was observed with various treatments. During follow-up (12.2 ± 11.3 years), severe manifestations of systemic lupus erythematosus were rare. Antiphospholipid antibodies were repeatedly positive for 90% of the patients. Twelve patients developed arterial thrombosis. Prophylactic treatment with antithrombotic therapy might reduce the risk of further thrombosis (8% versus 57%; P = 0.01). Cardiac valvulopathy occurred in 22 patients during follow-up. Chorea relapsed in 8 cases. CONCLUSIONS: Chorea had a good outcome in itself. This long-term follow-up shows, for the first time, that these patients have substantial risk for further arterial thrombosis.

Objectives To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP). Methods We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response. Results This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs. Conclusions This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.

Objective Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen expressed by B cells, is now considered an effective second-line therapy in various systemic diseases. We describe here the effects of rituximab in patients with relapsing polychondritis. Methods This was a retrospective study of 9 patients with relapsing polychondritis who received different regimens of rituximab in addition to their ongoing therapies. Clinical, laboratory, physiologic, and radiologic indicators were used to assess disease activity. We also examined their corticosteroid doses and any change in immunosuppressive agents. We then compared disease activity in the 6 months preceding rituximab administration and at 6 and 12 months after. Results At 6 months, 2 patients showed partial improvement, 4 were stable, and 3 had worsened disease; however, no patient had complete remission. At 12 months (after exclusion of the 3 patients whose disease had worsened at 6 months), 2 patients remained stable and 4 had worsened disease; however, there were no partial or complete remissions. B cells were counted in 8 patients during the first 6 months after treatment, and B cell depletion was observed in all of the patients. Conclusion Although we cannot rule out the possibility that rituximab had a small effect, our patients' clinical courses did not improve significantly with this treatment.

Objective: Poor adherence to treatment is very difficult to diagnose accurately. Hydroxychloroquine (HCQ) has a long elimination half-life and its concentration in whole blood can be measured easily. We evaluated the utility of a very low blood HCQ concentration as a marker of poor compliance in patients with systemic lupus erythematosus (SLE). Methods: We determined HCQ concentrations on a blinded basis in 203 unselected SLE patients. At the end of the study, patients were informed of the results and retrospectively interviewed about their adherence to treatment. Results: 14 patients (7%) said they had stopped taking HCQ (n=8) or had taken it no more than once or twice a week (n=6). Their mean HCQ concentration was 26 ± 46 ng/mL [0-129]. In contrast, the other patients had a mean HCQ concentration of 1079 ng/mL [205-2629]. The principal barriers to adherence were related to HCQ treatment characteristics. Adherence subsequently improved in 10 of the 12 patients whose blood HCQ concentrations were remeasured. Conclusions: Very low whole-blood HCQ concentrations are an objective marker of prolonged poor compliance in SLE patients. Regular drug assays might help physicians to detect noncompliance and serve as a basis for counseling and supporting these patients.

International audience; Background: Visceral leishmaniasis (VL), i.e., infection with Leishmania sp. associated with high fever, weight loss, massive splenomegaly and markedly altered laboratory parameters, is generally fatal if untreated. The possibility of transient spontaneous remission of fully symptomatic visceral leishmaniasis (VL) has been mentioned but, to our knowledge) has never been documented. Case presentation: We report the first documented history of a patient with overt, confirmed VL experiencing a complete remission in the absence of any anti-leishmanial therapy. The diagnosis of VL at the time of the self-resolving episode was strongly suspected based on clinical presentation and presence of antileishmanial antibody, then unequivocally confirmed years later by the presence of an amastigote on a stored smear and the positive quantitative PCR with Leishmania-specific primers from the material scraped from this same slide Conclusion: This report demonstrates that complete spontaneous remission may occur in patients with overt, fully symptomatic VL. VL should therefore be considered in cases of self-resolving or relapsing episodes of fever of unknown origin. Confirmation should be based on both serological tests and specific PCR on a blood sample.

The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5(+)-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

Muscle mass is particularly relevant to follow during aging, owing to its link with physical performance and autonomy. The objectives of this work were to assess muscle volume (MV) and intramuscular fat (IMF) for all the muscles of the thigh in a large population of young and elderly healthy individuals using magnetic resonance imaging (MRI) to test the effect of gender and age on MV and IMF and to determine the best representative slice for the estimation of MV and IMF. The study enrolled 105 healthy young (range 20-30 years) and older (range 70-80 years) subjects. MRI scans were acquired along the femur length using a three-dimension three-point Dixon proton density-weighted gradient echo sequence. MV and IMF were estimated from all the slices. The effects of age and gender on MV and IMF were assessed. Predictive equations for MV and IMF were established using a single slice at various femur levels for each muscle in order to reduce the analysis process. MV was decreased with aging in both genders, particularly in the quadriceps femoris. IMF was largely increased with aging in men and, to a lesser extent, in women. Percentages of MV decrease and IMF increase with aging varied according to the muscle. Predictive equations to predict MV and IMF from single slices are provided and were validated. This study is the first one to provide muscle volume and intramuscular fat infiltration in all the muscles of the thigh in a large population of young and elderly healthy subjects.