Nadine Magy-Bertrand

A case-control study to assess the risk of immune thrombocytopenia associated with vaccines

The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hematology centers across France recruited 198 incident (ie, newly diagnosed) cases of ITP between April 2008 and June 2011. These cases were compared with 878 age- and sex-matched controls without ITP recruited in general practice. Information on vaccination was obtained from patients standardized telephone interviews. Sixty-six of 198 cases (33.3%) and 303 of 878 controls (34.5%) received at least 1 vaccine within the 12 months before the index date. We found no evidence of an increase in ITP after vaccination in the previous 6 or 12 months (adjusted odds ratio [OR] for the previous 12 months = 1.0; 95% confidence interval, 0.7-1.4). When the 2-month time window was used, higher ORs were observed for all vaccines (OR = 1.3). This increase was mainly attributable to the vaccination against diphtheria-tetanus-pertussis-poliomyelitis (OR = 1.5) and was not statistically significant. The results of the present study show that in an adult population, the exposure to common vaccines is on average not associated with an observable risk of developing ITP.

Validity of the global anti-phospholipid syndrome score to predict thrombosis: a prospective multicentre cohort study

OBJECTIVEnTo investigate the validity of the global APS score (GAPSS) to predict thrombosis in patients with autoimmune diseases.nnnMETHODSnThis prospective cohort study included consecutive patients with aPL or SLE. aPL, aPS-PT and GAPSS were determined. A Cox proportional hazards model assessed the validity of GAPSS and identified other potential independent predictors of thrombosis.nnnRESULTSnOne hundred and thirty-seven patients [43.5 (s.d. 15.4) years old; 107 women] were followed up for a mean duration of 43.1 (s.d. 20.7) months. Mean GAPSS was significantly higher in patients who experienced a thrombotic event compared with those without [10.88 (s.d. 5.06) vs 8.15 (s.d. 5.31), respectively, P = 0.038]. In univariate analysis, age [hazard ratio (HR) = 1.04 (95% CI 1.01, 1.08)] and GAPSS above 16 [HR = 6.86 (95% CI 1.90, 24.77)] were each significantly associated with thrombosis during follow-up, while history of arterial thrombosis [HR = 2.61 (95% CI 0.87, 7.82)] failed to reach significance. Among aPL assays, IgG aPS/PT--a component of the GAPSS--was significantly associated with thrombosis [HR = 2.95 (95% CI 1.02, 8.51)]. In multivariate analysis, GAPSS above 16 remained the only significant predictor of thrombosis [HR = 6.17 (95% CI 1.70, 22.40)].nnnCONCLUSIONnThis first external validation study confirmed that GAPSS can predict thrombosis in patients with aPL and associated autoimmune diseases.

Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection

Objective. The clinical spectrum, etiologies, and best therapeutic approaches of type II mixed cryoglobulinemia (MC) not associated with hepatitis C virus (HCV) infection have been poorly described to date. We studied the clinical presentation and outcome of patients with type II MC with no evidence of HCV. Methods. This was a multicenter retrospective study on the clinical presentation and outcome of patients with type II MC without evidence of HCV infection. Only patients with symptomatic MC were included. Results. Thirty-three patients were included (median followup 67.2 mo). Extensive investigations for associated diseases were performed at presentation. MC was related to an autoimmune disease in 14 patients, to a lymphoid malignancy in 4 patients, and to an infectious disease in 2 patients, while MC was classified as essential (primary) in 13. Essential MC tended to be more severe than secondary disease with, in particular, more frequent renal and peripheral nerve involvement. Most patients were treated with steroid with or without immunosuppressive agents, mainly cyclophosphamide. These treatments were unable to induce sustained remission. One patient was successfully treated with lenalidomide. Seven patients with nonmalignant MC were treated with rituximab; 2 had a sustained complete remission, 3 improved greatly but relapsed within 5 months, and 2 experienced a disease flare. Conclusion. An important proportion of non HCV-related type II MC remains essential. Efforts should be made to find other etiologies than HCV, because treatments with steroid and immunosuppressants are not satisfactory, especially in severe forms. In these situations anti-CD20 therapy may present the best option but should be used with caution. New agents such as lenalidomide remain to be evaluated.

Responsiveness of the 36-item Short Form Health Survey and the Lupus Quality of Life questionnaire in SLE

OBJECTIVESnThis study aimed to estimate the responsiveness to change of a generic [the 36-item Short Form Health Survey (SF-36)] and a specific health-related quality of life questionnaire [the Lupus Quality if Life questionnaire (LupusQoL)] according to SLE patients self-reported changes in health status.nnnMETHODSnIn a cohort of 185 SLE patients, quality of life (QoL) was measured three times at 3 month intervals by the LupusQoL and SF-36 questionnaires. Anchors for responsiveness were defined by patients global assessment of disease impact according to changes in a visual analogue scale (VAS), a 7-point Likert scale and a 0-3 scale of five patient-reported symptoms. Mean change and s.d. in worsening and improving patients according to anchors were estimated using mixed models for repeated measures. Standardized response means (SRMs) were calculated in each group.nnnRESULTSnPatients [mean age 39.6 years (s.d. 10.5), mean Safety of Estrogen in Lupus Erythematosus National Assessment-SLEDAI score 2.6 (s.d. 3.5)] answered a total of 515 questionnaires. For the VAS and Likert global anchors, worsening patients showed a significant decrease in all LupusQoL domains except for burden to others, body image and fatigue and all SF-36 domains with low to moderate responsiveness. Improving patients had a significant increase in all LupusQoL domains except for intimate relationship and all SF-36 domains except for physical functioning and global health with low to moderate responsiveness. Regarding similar domains in the SF-36 and LupusQoL, SRMs were higher in LupusQoL domains in improving patients, while SF-36 domains had larger SRMs in worsening patients.nnnCONCLUSIONnBoth the SF-36 and LupusQoL were responsive to changes in QoL in SLE patients over a 3 month interval. LupusQoL seems to be more appropriate to measure improvements in QoL.

Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands.

The Risk of Systemic Lupus Erythematosus Associated With Vaccines: An International Case-Control Study

Studies have suggested that systemic lupus erythematosus (SLE) may be triggered by vaccinations. We undertook this study to investigate the relationship between vaccination and onset of SLE.

Detection of Interstitial Lung Disease in Systemic Sclerosis through Partitioning of Lung Transfer for Carbon Monoxide

Background: Interstitial lung disease (ILD) is a leading cause of death in systemic sclerosis (SSc). Sensitivities and specificities of the current pulmonary function tests (PFTs) for the detection of ILD in SSc are poor. Objective: To determine whether diffusion capacity of the lungs for carbon monoxide (DLCO) partitioned into membrane conductance for CO (DmCO) and alveolar capillary blood volume (Vcap) could provide more sensitive clues to ILD than current PFTs. Methods: DmCO and Vcap were determined in 35 consecutive SSc patients in whom a cardiac and/or pulmonary vascular abnormality had been rejected according to the recommended screening algorithm. ILD was diagnosed with high-resolution computed tomography. Results: Among 35 patients [6 men; median age (first–third quartile) 61.9 years (49.5–67.7)], 22 had no ILD and 13 did. Total lung capacity (TLC), vital capacity and DLCO [percentage of predicted value (%pred)] were lower in patients with ILD [86 (82–103) vs. 106 (98–112), p = 0.01, 96 (88–112) vs. 114 (104–121), p = 0.04, and 67 (59–81) vs. 80 (71–94), p = 0.02, respectively]. DmCO (%pred) and the ratio of DmCO to Vcap were much lower in patients with ILD [54 (48–72) vs. 83 (66–92), p < 0.001, and 0.22 (0.21–0.27) vs. 0.40 (0.35–0.53), p < 0.0001, respectively]. According to receiver operating characteristic analysis, the DmCO:Vcap ratio displayed higher sensitivity and specificity than TLC, vital capacity and DLCO in identifying ILD in our study group (p < 0.01). Conclusions: These results suggest that the partitioning of DLCO might be of interest for identifying ILD in SSc patients.

Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome

This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×109/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome.

Genital human Papillomavirus infection in patients with autoimmune inflammatory diseases

Treatment advances achieved over the last few years have radically changed the management of patients with autoimmune inflammatory diseases requiring conventional or biological immunosuppressive therapy. These diseases and the drugs used to treat them increase the rate of infections, including genital infections due to the human Papillomavirus (HPV). Genital HPV infections have been extensively studied in organ transplant recipients, HIV-infected patients, and patients with congenital immune deficiencies. Although genital HPV infections usually manifest as benign lesions of the external genital organs (condylomata), they are associated with an increased risk of cancer. Very few data are available on genital HPV infections associated with autoimmune inflammatory diseases or their treatments. Here, we review the published information on this topic.

Anal incontinence and vesico-sphincter events in systemic sclerosis: An epidemiologic bicentric cohort study

OBJECTIVEnTo estimate the frequency and severity of anal incontinence and vesico-sphincter events, associated factors, and impact on the quality of life of patients with systemic sclerosis.nnnMETHODSnQuestionnaires assessing anal incontinence (Miller score), vesico-sphincter events (Urogenital Distress Inventory) and quality of life [Short Form Health Survey 36v2 (SF-36), and Hospital Anxiety and Depression Scale] were mailed to 139 patients with systemic sclerosis at the university hospitals of Besançon and Poitiers, France. Clinical data were collected from the medical records to identify risk factors.nnnRESULTSnAmong the 121 (87%) responders, severe vesico-sphincter events or severe anal incontinence occurred in 3.4% and 12.4% of cases, respectively. Frequent urination (66.3%) and anal incontinence to gas (50.4%) were the most frequent symptoms. Anal incontinence was associated positively with vesico-sphincter events, unrelated to obstetrical factors. No correlations were seen with age, sex, or systemic sclerosis characteristics. In multivariate analysis, moderate or severe vesico-sphincter events was associated with higher anxiety and depression scores and lower SF-36 scores; the same results were observed for anal incontinence, but did not reach significance.nnnCONCLUSIONnVesico-sphincter events and anal incontinence are common in systemic sclerosis, and sometimes severe, with a potential negative impact in quality of life. These results will be confirmed by a case-control study with dynamic and manometric assessment, and could legitimate a systematic screening to ensure early therapy and multidisciplinary individual management.