[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.

[Rheumatoid arthritis and cardiovascular risk factor : literature review]. / Polyarthrite rhumatoïde et facteur de risque cardiovasculaire. Revue de littérature.

The rheumatoid arthritis remains a common condition and constitutes a diagnostic and therapeutic challenge, especially in the elderly. Rheumatoid arthritis is known to be associated with increased mortality, including coronary and cerebrovascular atherosclerosis. A literature review is conducted on the role of rheumatoid arthritis as a cardiovascular risk factor.

La polyarthrite rhumatoïde demeure une affection courante et constitue un défi diagnostique et thérapeutique, notamment chez le sujet âgé. Il est établi que la polyarthrite rhumatoïde est associée à une augmentation de la mortalité, notamment par athérosclérose coronaire et cérébrovasculaire. Une revue de littérature est réalisée sur le rôle de la polyarthrite rhumatoïde comme facteur de risque cardiovasculaire.

Achilles tendinitis in systemic lupus erythematosus: search for an associated inflammatory disease.

OBJECTIVES: Except for traumatic and iatrogenic causes, Achilles tendinitis (AT) is mostly encountered in the context of inflammatory rheumatic diseases. This study aimed to describe AT in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Among 158 SLE patients who fulfilled the SLE criteria of the ACR classification followed between 1980 and 2013, we selected those who experienced at least one episode of AT not caused by traumatic or toxicity factors. RESULTS: Eight patients (one male, seven females), median age 52 years (range: 35-68), presented with 11 episodes of AT within an average of 10.5 (0-21) years after SLE diagnosis. Clinical presentation of SLE was mainly cutaneous (eight of eight), and articular (seven of eight). Axial symptoms were reported in six patients, two of whom had HLA-B27-positive status, and fulfilled the Amor and European Spondylarthropathy Study Group criteria. Resolution of AT was good with nonsteroidal anti-inflammatory topical or systemic drug therapies, which kept SLE quiescent and avoided any increase of specific treatment. CONCLUSION: Although the association is rare, when AT occurs in SLE patients, physicians should look for associated spondylarthritis.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[In vitro fertilization and systemic lupus erythematosus or antiphospholipid syndrome: An update]. / Fécondation in vitro au cours du lupus érythémateux systémique ou du syndrome des antiphospholipides : mise au point.

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.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Monthly intravenous pulse cyclophosphamide therapy in Wegener's granulomatosis.

OBJECTIVE: To study the long term effects of monthly intravenous cyclophosphamide therapy in Wegener's granulomatosis. METHODS: Fourteen consecutive patients with active Wegener's granulomatos treated with a first-line combination of high-dose prednisone and monthly intravenous pulse cyclophosphamide were retrospectively studied. RESULTS: One patient died from septicemia complicating severe leukopenia after the first pulse. At 8 months after instituting intravenous pulse cyclophosphamide therapy, failure was observed in 6 other patients. Between month 16 and 18, 2 other patients relapsed when the time between 2 pulses was lengthened. Five patients developed cyclophosphamide-related side-effects: infection (n = 2), amenorrhea (n = 1), alopecia (n = 2) and vomiting (n = 2). Except for one fatal infection, no major side-effect of intravenous cyclophosphamide therapy was observed. At the end of the study, all patients were off intravenous cyclophosphamide therapy with more than 6 months of followup. The 6 responders were in remission on low-dose prednisone or without treatment. CONCLUSION: A combination of high-dose prednisone and intravenous cyclophosphamide may achieve long-term remission in 42% of patients with Wegener's granulomatosis. Responders to intravenous cyclophosphamide therapy had less extensive disease than non-responders.

[Influence of seasons on risk of flare-up of systemic lupus: retrospective study of 66 patients]. / Influence de la saison sur le risque de poussée systémique du lupus: étude rétrospective de 66 patients.

PURPOSE: To establish the possible connection between visceral, arthro-cutaneous and biological spreading of systemic lupus (SL) and hours of sunlight. MATERIAL AND METHODS: Retrospective study of 66 SL patients, consisting of 52 visceral and 14 arthro-cutaneous cases taking into account the chronological pattern of each new aggravation, based on 480 clinical records. RESULTS: Increased frequency in visceral aggravation was observed in the post-summer period (August-January) (n = 57), as compared with the pre-summer period (February-July) (n = 25) (RR = 1.75, P = 0.006). This post-summer visceral aggravation was correlated with cutaneous affection (RR = 4.18) and absence of previous corticotherapy (RR = 3.97). Visceral and arthro-cutaneous aggravations taken together revealed a more disturbed immune balance pattern in the post-summer period (anti-dsDNA: 30 versus 25.1 IU/L [P = 0.07]; C3: 0.83 vs 0.921 IU/L [P = 0.05]; C4: 0.146 vs 0.183 [P = 0.05]), providing evidence of greater severity. Moderate thrombopenia (50-120 10(9)/L) accompanying visceral SL with antiphospholipids (n = 33) was more frequent during the post-summer period, even in the absence of aggravation (P = 0.03). The quarterly distribution of visceral aggravations was correlated with average hours of sunlight in the preceding quarter (P = 0.01). CONCLUSION: There is a post-summer increase in the frequency and severity of visceral SL spreading correlated to cutaneous exacerbation and sunlight.

[Pulmonary manifestations of primary Gougerot-Sjögren syndrome. Apropos of 8 cases in a series of 35 patients]. / Manifestations pulmonaires du syndrome de Gougerot-Sjögren primitif. A propos de huit observations dans une série de 35 patients.

Clinical, roentgenologic, functional and broncho-alveolar lavage features of lung involvement in primary Sjögren's syndrome were assessed in a retrospective study of 35 cases. Diffuse interstitial patterns on chest radiography were present in six patients and alveolar patterns were suggestive of lymphoid interstitial pneumonitis or pseudolymphoma in two. Acute and febrile onset mimicked infectious pneumonitis in three patients when dyspnea was the most common clinical feature in others. Patients with primary Sjögren's syndrome and pulmonary disease were older (65 vs 56 years) (P = 0.025), have more frequently extra-glandular manifestations (P = 0.03), keratoconjunctivis sicca (P = 0.018) and biological perturbations (hypergammaglobulinemia (P = 0.03), antinuclear antibodies (P = 0.01) than those without lung involvement. Low diffusion capacity was present in seven patients associated twice to small airways obstruction. Bronchoalveolar lavage revealed in all cases an increased total cells count (mean: 6.96 10(5)/mm3) and a lymphocytic alveolitis (range: 11 to 66%; mean: 38%) associated with an elevated percentage of alveolar neutrophils in four patients. A low CD4/CD8 ratio was related to a pejorative issue. Treatment consisted in corticotherapy combined with oral cyclophosphamide in case of pseudolymphoma.

[Cardiac anomalies in disseminated lupus erythematosus diagnosed by Doppler ultrasonography. Prevalence and association with antiphospholipid syndrome]. / Anomalies cardiaques dans le lupus érythémateux disséminé diagnostiquées par échographie Doppler. Prévalence et association au syndrome des antiphospholipids.

OBJECTIVES: Antiphospholipid antibodies in patients with systemic lupus erythematosus (SLE) are widely associated with thrombosis, recurrent abortions and a thrombocytopenia. The purpose of this study was first to evaluate the prevalence of cardiac abnormalities in patients with SLE and secondly to establish the relationship between the findings and the presence of an antiphospholipid syndrome. SUBJECTS AND METHODS: First of all, a total of 52 consecutive patients with SLE and 52 healthy sex-and-age-matched control subjects were evaluated in a cross sectional study. All underwent M mode and two dimensional echocardiography, color flow imaging, pulsed and continuous wave Doppler. Secondly, in the SLE group, subjects exposed to antiphospholipid syndrome (n = 20) were compared to the control subjects. RESULTS: Compared with the control group, patients with SLE had significantly more pericardial abnormalities [(p = 0.0006) RR [3.36-infinity], mitral regurgitation [(p = 0.032) RR 2.48 [1.25-5.6]], tricuspid regurgitation [(p = 0.0016) RR 2.41 [1.58-8.85]. There was no significant difference between both groups for the left ventricular mass (p = 0.07), posterior wall (p = 0.25) and interventricular septum dimension (p = 0.16), and mitral valve thickness (p = 0.66). The antiphospholipid syndrome was significantly associated with increased left ventricular mass (p = 0.0054), posterior wall (p = 0.022) and interventricular septum dimension (p = 0.026). The relative risk increased for tricuspid and pulmonary regurgitation in SLE patients who had the antiphospholipid syndrome. CONCLUSION: The prevalence of left ventricular hypertrophy and right heart valvular regurgitation is significantly raised in SLE patients who have the antiphospholipid syndrome. However, antiphospholipid syndrome does not modify the prevalence of pericardial abnormalities which seems to be due to SLE alone.

[Cost of systemic lupus erythematosus for adult patients with active and treated disease in France (LUCIE study)]. / Coût du lupus systémique en France des patients adultes avec une maladie active et traitée (étude LUCIE).

PURPOSE: To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare. METHODS: A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models. RESULTS: Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P<0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was €4660 versus €3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (€3214 vs €1856; P<0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of €1330 (P<0.05). CONCLUSION: Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.

[Whipple disease revealed by anti-TNFα therapy]. / Maladie de Whipple révélée par les traitements anti-TNFα

INTRODUCTION: Whipple disease is a rare infectious disease with protean clinical manifestations. This infection may mimic chronic inflammatory rheumatisms such as rheumatoid arthritis or spondylarthritis. In this context, introduction of a biotherapy after a diagnostic hesitation does not always lead to early complications. Sometimes, the clinical degradation follows an initial improvement, encouraging continuation of the immunosuppressive treatment and leading consequently to a greater diagnostic delay. CASE REPORTS: We report two cases of Whipple disease diagnosed in the context of an inflammatory disease with anti-TNFα failure. The first patient was a 53-year-old man who presented with an axial and peripheral spondylarthritis who was treated with etanercept and adalimumab. The second was a 42-year-old man who received adalimumab and then etanercept for a peripheral spondylarthritis. CONCLUSION: Whipple disease should be suspected in all patients who present with a chronic inflammatory rheumatism that is partially or not controlled with anti-TNFα therapy and who had persisting elevated acute phase reactants.

[Functional manifestations associated to corticosteroid therapy among the elderly]. / Manifestations fonctionnelles associées à la prise de corticoïdes chez les sujets âgés.

PURPOSE: Corticosteroid therapy is frequently prescribed in the elderly with potentially significant consequences in this frail population. The objective of this study was to describe the functional manifestations associated and the preventive measures prescribed with corticosteroid therapy among patients over 75 years old. PATIENTS AND METHODS: We conducted an exposed/non-exposed, prospective, multi-centre, observational study. Each exposed patient was sex and age (± 2 years) matched to two unexposed subjects. The sample included patients aged over 75 years treated with long-term corticosteroid therapy and hospitalized in an acute geriatric unit between June 2006 and November 2009. Sociodemographic and geriatric characteristics, history of corticosteroid therapy, clinical manifestations and preventive measures prescribed were collected. RESULTS: Fifty exposed and 100 unexposed patients were included. Mean age was 85±6 years. Prevalence of falls, osteoarticular complications, amyotrophy, vertebral fractures, lipodystrophy, purpura, hematomas and cataracts, and the number of medications were higher among patients taking corticosteroid therapy than in controls. Preventive measures were more often prescribed to patients under taking corticosteroid therapy (calcium and vitamin supplementation, potassium supplementation, anti-osteoporosis medication and gastroprotective agents). CONCLUSION: Functional manifestations associated with corticosteroid therapy are frequent among the elderly and may have serious consequences in this frail population. Attention should be paid to the prescription of preventive measures through comprehensive care.