New insights into the epidemiology of immune thrombocytopenia in adult patients: Impact for clinical practice / [Actualités de l'épidémiologie du purpura thrombopénique immunologique de l'adulte : Impact pour la pratique clinique].

New insights into immune thrombocytopenia (ITP) epidemiology in adult patients highlight three main outcomes of morbidity and mortality: bleeding, infection and thrombosis. This review depicts current evidence about incidence and risk factors of bleeding, infection and thrombosis as well as predictors of chronicity, and shows how this assessment impacts the choice of ITP second-line treatment at the individual-level basis.

Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. RESULTS: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ±â€¯78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.

Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults.

Essentials Risk factors of bleeding in adult immune thrombocytopenia are not known. This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset. Platelet count thresholds associated with bleeding were < 20 × 109 L-1 and < 10 × 109 L-1 . Exposure to anticoagulants was a major risk factor of severe bleeding. SUMMARY: Background The aim of this cross-sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds. Methods We selected all newly diagnosed ITP adults included in the Cytopénies Auto-immunes Registre Midi-PyrénéEN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models. Results Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 109 L-1 . In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 109 L-1 versus ≥ 20 × 109 L-1 , odds ratio [OR] 48.2, 95% confidence interval [CI] 20.0-116.3; between 10 × 109 L-1 and 19 × 109 L-1 versus ≥ 20 × 109 L-1 , OR 5.2, 95% CI 2.3-11.6), female sex (OR 2.6, 95% CI 1.3-5.0), and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1-20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3-14.1). Conclusions Platelet counts of < 20 × 109 L-1 and < 10 × 109 L-1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding.

[Epidemiology and pharmacoepidemiology of immune thrombocytopenia]. / Épidémiologie et pharmacoépidémiologie du purpura thrombopénique immunologique.

During the last decade, the development of large clinical and population-based cohorts led to new findings in the epidemiology and the pharmacoepidemiology of immune thrombocytopenia (ITP). The incidence is estimated to 3-4 for 105 inhabitants/year, with a slight female predominance and peaks in children and patients after 60 years. The incidence rate is 9 for 105 inhabitants/year in males after 75 years. Variations across ethnic groups are discussed. In France, there is a North-South gradient and a peak of incidence during winter suggesting the role of viruses in ITP pathophysiology. Myelodysplastic syndromes are an emergent cause of secondary ITP. The incidence of intracranial bleeding is about 1% by year and the risk increases with aging. Exposure to splenectomy decreases while rituximab and thrombopoietin receptor agonists (TPO-RA) are the most used second-line drugs for persistent ITP. Mortality is slightly increased in primary ITP as compared with the general population. ITP patients have an increased risk of infection, thrombosis and hemorrhage. Aging, lung diseases, splenectomy, corticosteroids and rituximab are risk factors for infection while influenza and pneumococcal vaccines are associated with a 50% decrease of infection risk. Aging, cardiovascular risk factors, lupus anticoagulant and splenectomy are risk factors for thrombosis. The risk of thrombosis associated with corticosteroids and TPO-RAs must be further investigated.

[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.

[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.

[Antiphospholipid antibodies and the risk of thrombosis: a comparative survey between chronic immune thrombocytopenia and primary antiphospholipid syndrome]. / Profil des anticorps antiphospholipides et risque de thrombose : étude comparative entre thrombopénie immunologique chronique et syndrome des antiphospholipides primaire.

PURPOSE: The prevalence of antiphospholipid antibodies (APA) in patients with immune thrombocytopenic purpura (ITP) varies from 25 to 75% in the literature. The risk of thrombosis in this subgroup of patients is debated. In parallel, thrombocytopenia is present in 22 to 42% of patients with antiphospholipid syndrome (APS). PATIENTS AND METHODS: The main study objective was to compare the profile at diagnosis of lupus anticoagulant (LA), anticardiolipin antibody (ACL) and anti-ß(2)GP-I antibody between a cohort of 93 chronic ITP patients and a cohort of 27 primary APS patients. The secondary objectives were: to evaluate the risk of thrombosis in ITP patients depending on the presence of APA; to compare the profile of APA and to assess the occurrence of lupus in APS patients depending on the presence of thrombocytopenia. RESULTS: In ITP patients, the prevalence of APA was 25%; association of several different APA was less frequent than in APS patients; mean titles of ACL and anti-ß(2)GP-I antibodies were comparable between the two cohorts; two spontaneous venous thromboses occurred in ITP patients, with no particular profile of APA (median follow-up: 36 months). Thrombocytopenia was present in 26% of APS patients; it was always moderate and asymptomatic, and sometimes intermittent; no particular profile of APA was associated to thrombocytopenia; only one thrombocytopenic patient developed a systemic lupus and no particular profile of APA could be found associated (median follow-up: 48 months). CONCLUSION: ITP patients with APA have less frequently an association of different APA than APS patients do; their risk of thrombosis appears low.

Prevalence and prognostic value of cutaneous manifestations in patients with myelodysplastic syndrome.

BACKGROUND: Skin manifestations associated with myelodysplastic syndrome (MDS) may reveal bone marrow transformation into acute myeloid leukaemia. OBJECTIVE: The objective of this study was to assess the prevalence of skin manifestations associated with MDS. In addition, we evaluated the risk of acute myeloid leukaemia transformation associated with skin manifestations. METHODS: We studied a cohort of 157 patients with primary MDS followed up prospectively for a median of 44 months. Skin lesions were prospectively assessed as part of medical examination every 6 months by a board certified dermatologist. Survival analyses were performed to assess the association between the presence of skin lesions and the risk of acute myeloid leukaemia. RESULTS: Fifteen patients (9.55%) experienced skin lesions previously reported as associated with MDS. These were neutrophilic dermatosis (7, 4.46%), specific lesions (5, 3.18%), cutaneous vasculitis (2, 1.27%) and Behçet disease (1, 0.63%). Survival analysis showed that the risk of transformation into acute myeloid leukaemia was slightly but not significantly increased in patients with skin lesions as compared with patients without skin lesions with a relative risk of 2.08 (95% CI 0.92-4.67). CONCLUSION: The prevalence of skin lesions, mostly neutrophilic dermatosis and specific lesions, is relatively high in patients with MDS. There is a trend for a higher risk of transformation into acute myeloid leukaemia in patients with skin lesions.

Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody.

BACKGROUND: To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. OBJECTIVES: The aims of the present study were: (i) to assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. METHODS: The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed. RESULTS: Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud's phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. CONCLUSIONS: Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit 'mechanic's hands', Raynaud's phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

Increased exposure to statins in patients developing chronic muscle diseases: a 2-year retrospective study.

OBJECTIVE: Case reports have suggested that lipid-lowering drugs (LLDs), especially statins, could induce or reveal chronic muscle diseases. We conducted a study to evaluate the association between chronic muscle diseases and prior exposure to LLDs. METHOD: This was a retrospective study of chronic primary muscle disease cases newly diagnosed at the Toulouse University Hospitals between January 2003 and December 2004 among patients living in the Midi-Pyrénées area, France. All patients remained symptomatic for more than 1 year after drug withdrawal, or required drugs for inflammatory myopathy. Data on the patient's exposure to LLDs and to other drugs were compared with that of matched controls (5/1) selected through the Midi-Pyrénées Health Insurance System database. RESULTS: A total of 37 patients were included in the study. Of those, 21 (56.8%) suffered from dermatomyositis (DM) or polymyositis (PM), 12 (32.4%) from genetic myopathy, and 4 (10.8%) from an unclassified disease. The prevalence of exposure to statins was 40.5% in patients and 20% in controls (odds ratio (OR) 2.73, 95% confidence interval (CI) 1.21-6.14; p<0.01). There was a significant positive interaction between statins and proton pump inhibitors exposure (weighted OR 3.3, 95% CI 1.37-7.54; p = 0.02). Statin exposure rate was 47.6% among patients with DM/PM (OR 3.86, 95% CI 1.30-11.57; p<0.01). There was no difference between patients and controls for exposure to fibrates. CONCLUSION: Patients who developed chronic muscle diseases after the age of 50, including DM/PM, had a higher than expected frequency of prior exposure to statins. Further studies are needed to confirm this association and the role of proton pump inhibitors.

Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients.

The objective of the study was to investigate the influence of the blood concentrations of hydroxychloroquine ([HCQ]) and its derivative desethylhydroxychloroquine ([DHCQ]) on lymphocyte activation or differentiation in HCQ-treated lupus patients. We studied the correlations between [HCQ], [DHCQ], and the frequency of various lymphocyte subsets in 58 HCQ-treated lupus patients (mean HCQ dose: 4.93 +/- 1.58 mg/kg/day; mean duration of the disease: 122 +/- 64 months). [HCQ] and [DHCQ] were determined by high-performance liquid chromatography (HPLC). Lymphocyte markers were studied by flow cytometry using monoclonal anti-CD3, -CD4, -CD8, -CD25, -DR, -CD45RA, -CD45RO, -CD19, -CD38, and -CD86 antibodies. sIL2-R serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). [HCQ] and [DHCQ] were 599.9 ng/mL (median: 529.5; range: 55-1935) and 353.43 (median: 286 ng/mL; range: 118-1090). In a multiple regression analysis, [HCQ] and [DHCQ] were associated with the HCQ prescribed dose in mg/kg/day (P = 0.0002 and P = 0.03) and with compliance to the treatment (P = 0.004 and P = 0.03). We found a negative correlation between [HCQ], [DHCQ], and the CD45RO+ cell frequency among CD3+CD4+ cells (P = 0.03 and P = 0.007, respectively). Other lymphocyte subset markers (LSMs) and sIL2-R concentrations were not significantly associated with [HCQ] or [DHCQ]. In the multiple regression analysis, CD45RO+ expression was negatively influenced by [HCQ] (P = 0.005), and positively influenced by smoking habits (P = 0.005) and age (P = 0.005). Similar results were found in the multivariate model including [DHCQ]. Disease activity and taking more than 10 mg/day of corticosteroids or an immunosuppressive drug did not influence CD45RO+ expression. Lupus patients had less CD3+CD4+CD45RO+ cells than controls (P = 0.03). In lupus patients, HCQ and DHCQ may alter the generation or the blood circulation of CD4+CD45RO+ lymphocytes in a concentration-dependent pattern.

[Anti PM-Scl antibodies. Study of prevalence and of meaning]. / Autoanticorps anti-PM-Scl. Etude de prévalence et de signification.

OBJECTIVE: The purpose of our study is to appreciate the prevalence of antibodies anti PM-Scl within the framework of antinuclear antibodies detection and to clarify clinical biological and evolutive features associated to these antibodies. METHODS: 9,747 consecutive antinuclear testing datas allowed us to evaluate anti PM-Scl antibodies frequency. A retrospective analysis of patients characteristics was performed to identify clinical, biological and evolutive signs associated with this antibody over a five years follow up period. RESULTS: Over the 9,747 samples tested for antinuclear antibodies detection, 3,493 (35.8%) are positive. An anti ENA activity is observed in 727 (7.5%) cases and anti PM-Scl in 6 (0.06%). These antibodies are described in systemic sclerosis, myositis or overlap syndromes. All theses diseases showed a low evolutivity over the five years of follow up. CONCLUSIONS: Low prevalence and possible association with an overlap autoimmune syndrome of quite good prognosis are reported with anti PM-Scl antibodies.

[Anti-Ku antibodies. Study of prévalence and of clinical meaning]. / Auto-immunité anti-Ku. Etude de prévalence et de signification clinique.

PURPOSE: Auto-immunity against Ku nuclear antigens is rare and clinical meaning remains badly estimated. Our study is for purposes: to appreciate the prévalence of antibodies anti-Ku within the framework of the search for antinuclear antibodies and to clarify clinical and biological relations associated to this auto-immunity. METHODS: A retrospective study of a series of 10,000 searches for antinuclear antibodies studies the prévalence of the auto-immunity anti-Ku and a retrospective analysis of the data found at the patients bearers of an anti-Ku identifies clinical and biological signs associated with this antibody. RESULTS: Prévalence anti-Ku is low (1/3493 case of antinuclear antibodies) and association is possible with in a myositic process through variable auto-immune contexts (overlap syndrome) of relative good preview. CONCLUSION: Auto-immunity anti-Ku is so characterized with its weak prévalence, a possible observation during different auto-immune diseases with an obvious frequency of the overlap syndrome often concerning a process myositic. Finally a weak évolutivité seems to characterize the auto-immune diseases of the patients with anti-Ku antibodies.

[RS3PE syndrome: an acute edematous polyarthritis of the elderly with variable prognosis]. / Le syndrome RS3PE: une polyarthrite aiguë oedémateuse du sujet âgé au pronostic variable.

The RS3PE syndrome or subacute edematous polyarthritis of the elderly remains a doubtful entity. We report three cases that exhibited different courses: complete recovery, definite rheumatoid polyarthritis, and chronicity as a sign of myelodysplasic disease. These three different courses raise the question of whether RS3PE is a disease or a syndrome. Actually, the use of the term RS3PE syndrome should be restricted to cases with a favorable outcome. Definitive diagnosis thus cannot be reached before complete recovery.