Long-term outcomes of childhood-onset systemic lupus erythematosus.

OBJECTIVE: Data on the long-term outcome of patients with childhood-onset Systemic Lupus Erythematosus (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity. METHODS: We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up. RESULTS: A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6-22.4] years, 51% of patients had a SLICC-Damage Index score ≥ 1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological, and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥ 1 increased significantly with the duration of the follow-up (p< 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, p= 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥ 6. On multivariate analysis, Sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, p= 0.0002). CONCLUSION: The prevalence of damage remains high in patients with cSLE even when the diagnosis of c-SLE has been made in the recent decades.

An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases clinical management.

Anti-Ro52 (or anti-TRIM21) antibodies are part of the family of anti-Ro/SSA antibodies, historically markers of Sjögren syndrome and systemic lupus erythematosus. Anti-Ro52 antibodies represent one the most frequently encountered autoantibodies in patients with connective tissue disease (primary Sjögren syndrome, systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies). Because of their lack of specificity and detection in patients with non-autoimmune disorders, the usefulness of anti-Ro52 testing in connective tissue diseases is still matter of debate among clinicians and immunologists. Autoantibodies are mainly diagnostic markers for autoimmune diseases but some of them can also be directly involved in the generation of tissue damage. Over the past decade several authors reported associations of anti-Ro52 antibodies with some clinical features - especially interstitial lung disease - and survival in patients with connective tissue diseases. There is also a growing evidence of the role of anti-Ro52 antibodies in the pathogenesis of connective tissue diseases. In this review, we comprehensively discuss the clinical associations of anti-Ro52 antibodies in the different connective tissue diseases and the recent advances on their potential role in the inflammatory response.

An Unexpected Effect of Maraviroc Could Make It a Future Treatment for Sarcoidosis

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Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients.

BACKGROUND: East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease. In Europe, only few studies have described the clinical features and treatment of this disease, especially in France. METHODS: This retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers. RESULTS: Forty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women. CONCLUSION: We report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients' ethnicity.

[Diagnostic journey of type 1 Gaucher Disease patients: A survey including internists and hematologists]. / Parcours diagnostique des patients atteints de maladie de Gaucher de type 1 : enquête auprès de médecins internistes et hématologues.

INTRODUCTION: Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist. METHODS: A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011. RESULTS: Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician. CONCLUSION: GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.

Epidemiological Data on Anaphylaxis in French Emergency Departments.

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxisrelated codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions.

Epidemiological data on anaphylaxis in French emergency departments

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxis-related codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions

ANTECEDENTES: La anafilaxia es un problema prioritario de salud pública en la comunidad mundial alergológica. Sin embargo, los datos epidemiológicos disponibles de morbilidad y mortalidad son mejorables. Presentamos el primer estudio epidemiológico multicéntrico, realizado en siete departamentos de urgencias franceses durante un año, que tuvo como objetivo identificar las cuestiones relevantes para lograr cambios en futuras estrategias, nacionales e internacionales, que deriven en un mejor diagnóstico, tratamiento y prevención de la anafilaxia. MÉTODOS: Se trata de un estudio descriptivo que utilizó la información proveniente de las bases de datos de siete instituciones francesas de salud pública, de la región de Lorena, desde enero hasta diciembre de 2015. Se buscaron nomenclatura y códigos relacionados con la anafilaxia, de la Clasificación Internacional de Enfermedades (CIE-10), y los pacientes fueron validados clínicamente como casos de anafilaxia. RESULTADOS: De los 202.079 ingresos en urgencias, 4.817 tenían códigos relacionados con la anafilaxia CIE-10, 323 de los cuales se validaron clínicamente con el diagnóstico de anafilaxia. Aunque el 45,8% presentó criterios de gravedad, la adrenalina se prescribió solo en el 32,4% de estos casos. En total, 323 casos, el 57,9%, se remitieron posteriormente para un estudio o evaluación alergológica (después o durante la hospitalización) y el 17,3% recibió una receta de adrenalina autoinyectable . CONCLUSIÓN: Según los resultados de este estudio, existe una necesidad urgente e imperiosa de mejorar los planes de salud pública respecto al reconocimiento y tratamiento de la anafilaxia. Los problemas clave detectados en este trabajo, señalan el camino de la toma de decisiones e implementación de acciones de mejora, nacionales e internacionales, para una mejor atención de los pacientes con anafilaxia

[Lupus erythematosus treatment with belimumab in daily practice: Retrospective study of 15 patients]. / Traitement du lupus érythémateux par le bélimumab en pratique courante : étude rétrospective de 15 malades.

BACKGROUND: Belimumab (an anti-BLyS monoclonal antibody) was recently approved for the treatment of systemic lupus erythematosus (SLE). The aim of the study was to describe efficacy and safety of the drug as well as its impact on serologic parameters and the role of long-term systemic sparing of treatment in clinical practice in LE. PATIENTS AND METHODS: We conducted a retrospective study at Reims University Hospital between 2012 and 2016 including consecutive patients with LE treated with belimumab. Efficacy was evaluated in terms of clinical progression, and normalisation of laboratory factors (anti-DNA antibody and C3 serum levels) and sparing of associated long-term systemic therapies for LE. RESULTS: Among the 15 patients included, a therapeutic response was obtained in 9 patients (60%), with partial remission in 8 of 9 cases. The median titre of anti-DNA antibody was 50IU/mL (range: 4-50) and the median C3 level was 0.82g/L (range: 0.36-1.23) before initiation of belimumab, vs. 25.5IU/mL (range: 2-50) and 0.89g/L (range: 0.34-1.22) at the last evaluation, respectively, without significant modification (P=0.12 and P=0.45). The median dose of prednisone at the time of the first belimumab infusion was reduced from 9.5mg/day (range: 0-18) to 6mg/day (range: 0-20) at the last clinical evaluation. Eight patients (53%) experienced adverse events, and these were very slight or moderate in all cases. CONCLUSION: Belimumab appears to be an effective and well-tolerated treatment for moderately severe systemic LE, allowing sparing of maintenance corticosteroid therapy in order to decrease its frequent adverse events.

Does the route of immunoglobin replacement therapy impact quality of life and satisfaction in patients with primary immunodeficiency? Insights from the French cohort "Visages".

BACKGROUND: IgG replacement therapy (IgRT) in primary immunodeficiencies (PID) is a lifelong treatment which may be administered intravenously (IVIg) or subcutaneously (SCIg), at hospital or at home. The objective of the VISAGE study was to investigate if route and/or place for IgRT impact patients' satisfaction regarding IgRT and quality of life (QoL) in real-life conditions. METHODS: The study enrolled PID patients at least 15 years old receiving IgRT for at least 3 months. Satisfaction and QoL were evaluated at enrollment and over a 12-month follow-up period by Life Quality Index (LQI) which measures 3 dimensions of satisfaction: treatment interference, therapy related problems and therapy settings (factors I, II and III) and SF-36 v2 questionnaire. RESULTS: The study included 116 PID patients (mean age 42 ± 18 years, 44 % males, 58 % with scholar or professional occupation) receiving IgRT for a mean of 8.5 ± 8.4 years. At enrollment they were receiving either home-based SCIg (51 %), hospital-based IVIg (40 %) or home-based IVIg (9 %). Patients exhibited a high degree of satisfaction regarding IgRT whatever the route and place for administration. LQI factor I was higher for home-based SCIg (86 ± 2) than for hospital-based IVIg (81 ± 3) and home-based IVIg (73 ± 5; p = 0.02 versus home-based SCIg); no difference was found for LQI factor II; LQI factor III was higher for home-based SCIg (92 ± 2) than for hospital-based IVIg (87 ± 5) and hospital-based IVIg (82 ± 3; p = 0.005 versus home-based SCIg). By contrast, every dimension of QoL was impaired. Over the follow-up period, 10 patients switched from hospital-based IVIg to home-based SCIg and improved LQI factor I (p = 0.004) and factor III (p = 0.02), while no change was noticed in LQI factors II and QoL. Meanwhile, no change in satisfaction or QoL was found in patients with stable route of IgRT. When asked on their preferred place of treatment all but one patient with home-based treatment would choose to be treated at home and 29 % of patients treated at hospital would prefer home-based IgRT. CONCLUSION: PID patients expressed a high degree of satisfaction regarding IgRT, contrasting with impaired QoL. In real-life conditions awareness of patient's expectations regarding the route or place of IgRT may be associated with further improvement of satisfaction.

Multidimensional analysis of clinical symptoms in patients with Fabry's disease.

AIM: Fabry's disease is an X-linked inherited lysosomal storage disorder caused by the deficient activity of alpha-galactosidase A. The interrelationships between clinical symptoms in Fabry patients have not yet been fully established. Using cluster and multivariate analysis, the aim of the study was to determine the relationships among clinical symptoms and organ involvement, and predictive clinical symptoms for disease severity. METHODS: Clinical data obtained from 108 French Fabry patients were retrospectively collected and analysed using multiple correspondence analysis and hierachical ascendant classification. Multivariate analysis was also performed to determine among clinical symptoms predictors for cardiac disease (HRT), renal involvement (KDN) and brain complication (STR). RESULTS: The cohort comprised 41 male patients (aged 28.9 ± 11.6 years) and 67 female patients (aged 40.4 ± 15.5 years). Three main clusters of clinical symptoms could be delineated, characterising disease progression: the first cluster grouped digestive disorders (found in 30% of the patients) and exercise intolerance (32%), the second, cluster dyshidrosis (47%), acroparesthesia (67%), angiokeratoma (44%) and cornea verticillata (54%), the third, cluster grouped KDN (30%), HRT (39%) and STR (25%) and hearing loss (44%). In univariate analysis, the patient age predicted HRT and KDN, dyshidrosis predicted HRT and STR, angiokeratoma predicted KDN and cornea verticilla and hearing loss predicted KDN, HRT and STR. In multivariate analysis, hearing loss and age were independent predictors of organ complication. CONCLUSION: Among the various interrelated clinical symptoms occurring in Fabry disease, patients with dyshidrosis and particularly hearing disorders appear to be at higher risk of organ complications.

[Epstein-Barr virus and cytomegalovirus primary infections: a comparative study in 52 immunocompetent adults]. / Étude comparative des primo-infections à Epstein-Barr virus et à cytomégalovirus chez 52 patients immunocompétents.

OBJECTIVE: The objective of this study was to compare epidemiological, clinical, and biological data of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) primary infections in immunocompetent adults, admitted in the infectious disease department of the Reims Teaching Hospital between 2000 and 2005. PATIENTS AND METHODS: Inclusion criteria were the presence of anti-VCA IgM antibodies or the presence of CMV specific IgM antibodies and the absence of any other positive serology. Differences in reported percentage were compared with a Khi(2) test or Fischer's exact test, when appropriate. Continuous variables were compared with the Mann-Whitney Test. RESULTS: There were no significant changes over the years in the numbers of EBV (n=32) and CMV (n=20) primary infections. The patient's mean age was 22.7 years (14-48 years) in EBV primary infections and 38.6 years (13-66 years) in CMV primary infections (P<0.01). The clinical variables significantly associated with primary EBV infection were sore throat and cervical lymphadenopathy (P<0.01). Arthromyalgia and respiratory manifestations were less frequent in EBV primary infection (P<0.01). The biological variables significantly associated with EBV primary infection were a marked alanine aminotransferase elevation and a marked lymphocytosis with atypical lymphocytes (P<0.001). Thrombopenia was less frequently associated with EBV primary infection (P<0.001). CONCLUSION: Clinical and biological presentations of EBV and CMV primary infections were similar. The simultaneous serologic diagnosis of these two infections remains necessary to provide a specific diagnosis, for the most efficient patient care.

Vertebral fractures in Gaucher disease type I: data from the French "Observatoire" on Gaucher disease (FROG).

UNLABELLED: Gaucher disease type 1 (GD1), results in a range of skeletal complications including osteopenia, osteoporosis, and osteonecrosis, but there is little published information regarding vertebral fractures. Findings from this observational study indicated that the prevalence of vertebral fractures in a cohort of adult French GD1 patients is approximately 15%. INTRODUCTION: The aim of the study was to assess the prevalence and characteristics of vertebral fractures in a cohort of adult patients with GD1. METHODS: This study was performed in adult patients with GD1 based on a detailed and complete clinical examination. For all patients for whom vertebral fractures were reported, a specific questionnaire was sent to physicians, and imaging data were collected, when available, for centralized analysis. RESULTS: Data were collected from a total of 105 adult GD1 patients. Bone complications were reported in 85% of patients, among whom vertebral fractures were diagnosed in 16 (15%); seven women and nine men (mean age, 45 years). We observed five patients with multiple vertebral fractures and one patient in whom the T3 vertebra was fractured. Most of these patients did not report fracture-related back pain. CONCLUSIONS: The prevalence of vertebral fractures in this cohort of adult patients with GD1 was 15%. Greater awareness of the natural history of vertebral fractures in GD1, and rigorous monitoring of bone fragility and spine involvement in affected patients, should allow earlier detection and initiation of treatment tailored toward improving bone status.

The neurological manifestations of Gaucher disease type 1: the French Observatoire on Gaucher disease (FROG).

BACKGROUND: Gaucher disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. Type 1 GD (GD1), the most common variant, is classically considered non-neuronopathic. METHODS: We performed a national cross-sectional observational survey-the French Observatoire on Gaucher Disease (FROG)-in patients with GD1 between March 2005 and September 2006. The study included all patients over 18 years of age with confirmed GD1 who attended participating centers for regular follow-up. RESULTS: One hundred and five patients were included, in whom we studied the prevalence and characteristics of relevant neurological symptoms associated with the neuraxis. Of these, 51 (49%) GD1 patients presented at least one neurological symptom. Four patients (4%) had Parkinson disease and 22 (21%) presented with at least one parkinsonian sign or at least one sign frequently associated with Parkinson disease. Five patients (5%) had a previous diagnosis of peripheral neuropathy. Other central nervous system symptoms were recorded in 20 (19%) patients and other peripheral nervous system symptoms in 39 (37%) patients. CONCLUSIONS: These data challenge the current classification of GD, and suggest that the three forms of GD each involve a different profile of neurological manifestations.

Immunogenicity and booster efficacy of pre-exposure rabies vaccination.

A multivariate analysis was used to identify factors influencing the immunogenicity of rabies vaccine and to assess the efficacy of booster injections in a cohort of 407 people monitored prospectively for 10 years after primary vaccination. Rabies vaccine (HDCV or PVRV) was injected by intramuscular route either on days 0 and 28 or on days 0, 7 and 28. All the participants received a booster injection on day 365. At the end of follow-up (year 10), 163 subjects had titers >0.5IU/ml (group A) and 59 subjects had titers <0.5IU/ml (group B: poor responders). The number of injections had a significant influence (P<0.001) on the magnitude of the serological response to rabies vaccine, but the type of vaccine and the potency of the batches did not (P=0.07 and P=0.06, respectively). The difference between GMTs on day 365 and day 379 was significantly lower in group B than in group A (13 and 50.70IU/ml, respectively; P<0.001). In conclusion, our study confirms that the rabies pre-exposure vaccination protocol of three intramuscular injections significantly decreases the proportion of poor responders at 10 years. Moreover, our findings indicate that a routine booster injection at 1 year could significantly increase the levels and duration of antibody titers.