Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature.
To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc ...patients.
A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed.
Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46-1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p=0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012), and the fact of being male (HR=3.25; p=0.0004).
Long-term data confirmed high mortality of SSc. Male sex, DLCO <70%, cardiac involvement, and CRP> 5mg/l were identified as independent predictors of mortality.
To assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).
We conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors ...associated with response to tocilizumab (assessed using NIH score).
Forty-six patients with TA were included, with a median age of 43 years 29–54, and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 2–3 at baseline to 0 0–1 and 0 at 3 and 6 months, respectively; p < 0.0001). The daily prednisone dose also decreased from 15 mg 8–19 at baseline to 4 mg 5–21 and 5 mg 4.5–9 at 3 and 6 months, respectively (p < 0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% CI 95%; 0.7–0.95, 72% CI 95%; 0.55–0.95 and 48% CI 95%; 0.2–0.1 at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 CI 95%; 1.08–29, p = 0.041), and C-reactive protein level (HR 1.16 CI 95%; 1.01–1.31, P = 0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (p = 0.02).
This large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.
•Tocilizumab can lead patients TA to remission in 80%, have steroid sparing effect and a good safety profile.•Tocilizumab can be used in monotherapy and as first line therapy.•Tocilizumab can be used in monotherapy and is effective as first line therapy.
Fabry disease is a frequent lysosomal storage disorder secondary to the deficiency of alpha-galactosidase A enzyme. This X-linked genetic disease realizes progressive and systemic manifestations that ...affect both male and female. Fabry disease may present as "classical", as "late-onset" or "non-classical" forms. Symptoms and organ involvements of classical Fabry disease are acral pain crisis, cornea verticillata, hypertrophic cardiomyopathy, stroke and chronic kidney disease with proteinuria. Other common symptoms are often poorly recognized, such as gastrointestinal or ear involvements. In classical Fabry disease, symptoms first appear during childhood or during teenage years in males, but later in females. Patients with non-classical or late-onset Fabry disease have delayed manifestations or a single-organ involvement. Diagnosis is therefore difficult when classical organ involvements are missing, in paucisymptomatic patients or in late-onset forms. Recognition of Fabry disease is important because effective treatments are available. They have to be prescribed early. In male, diagnosis is made with alpha-galactosidase A enzyme activity dosage in leukocyte, that is very low or null in classical forms and under 30 percent in late-onset forms. Diagnosis is more challenging in females who may express normal residual enzyme activity. Other plasmatic biomarkers, such as lyso-globotriaosylceramide are interesting, especially in females. In this review, we aimed to summarize main clinical manifestations of Fabry disease to know when to evoke Fabry disease and propose a practical diagnosis algorithm to know how to diagnose.
Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. ...We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI 2.40-9.27;
< 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.
Abstract Background Cryofibrinogenemia is frequently associated with cryoglobulinemia. The aim of this study was to determine the characteristics associated with the presence of cryofibrinogenemia in ...patients with cryoglobulinemic vasculitis. Methods This was a single-center retrospective study that included patients with cryoglobulinemic vasculitis who were tested for cryofibrinogen at a tertiary referral center between January 1, 2011 and December 31, 2012. Twenty-nine patients fulfilled the CryoVas (cryoglobulinemic vasculitis) Survey criteria for cryoglobulinemic vasculitis. Eighteen patients had a detectable cryofibrinogen (CF-positive) and 11 had no detectable cryofibrinogen (CF-negative). Median cryoglobulin levels were 89 ± 129 mg/L in the CF-positive group and 68 ± 82 mg/L in the CF-negative group ( P = .32). Median cryofibrinogen level was 70 ± 174 mg/L. Clinical manifestations were similar in both groups. Cancers and hematological disorders were more frequent among CF-positive patients (39% vs 0%, P = .026). Levels of alpha-1 and alpha-2 globulinemia were higher in the CF-positive group. Cryofibrinogenemia ≥ 100 mg/L was associated with cryoglobulinemic vasculitis (odds ratio OR 2.86; 95% confidence interval CI, 1.06-7.73) in cryoglobulinemic patients. Presence of cryofibrinogenemia was associated with use of corticosteroids, immunosuppressants, or plasmapheresis in cryoglobulinemic vasculitis patients (OR 22.7; 95% CI, 2.02-256.44). Conclusions Our results strongly suggest that presence of cryofibrinogenemia is associated with a more severe phenotype among patients with cryoglobulinemic vasculitis.
Background: The clinical epidemiology of immune thrombocytopenia (ITP) is not well known. Some issues (bleeding events at diagnosis, association to other autoimmune diseases, rate of infection prior ...to ITP onset) are not well described in adults. Little is known as regards first-line treatment choice in the real-life practice.
Aim: The aims of this study were to assess i) the clinical epidemiology of incident ITP adults; ii) the use of first-line treatments in this population; and iii) the factors associated with the initial use of intravenous (IV) corticosteroids (CS) and of intravenous immunoglobulin (IVIg) in a real-life setting. This study was carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology.
Methods: Study population was the patients included between June 2013 and December 2014 in the CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) multicenter registry. This multicenter registry is carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology. The originalities of this registry are: the prospective follow-up of newly diagnosed ITPs, aimed at completeness of recording in the French Midi-Pyrénées region, South of France (3 million inhabitants), and the detailed recording of ITP treatment exposures. All the physicians in charge of ITP patients in the region, belonging to the netwotk of the regional center for autoimmune cytopenia, prospectively follow every patient newly diagnosed for ITP during routine visit or hospital stay. ITP is defined in accordance with French guidelines: platelet count <150 x 109/L and exclusion of other causes of thrombocytopenia. In this study, we assessed the clinical epidemiology at ITP onset, as well as ITP treatment use during the week following the diagnosis. Logistic regression models were performed to assess the factors associated with the use of IV CS and of IVIg. The following covariates were included: age, gender, Charlson's comorbidity score, secondary vs. primary ITP, bleeding score and platelet count.
Results: Out of 121 newly diagnosed ITP, 113 patients were followed in the region and gave informed consent. Median age was 65 years (range: 18-95). Half of the patients were female, 24 (21.3%) had a secondary ITP, 57 (50.4%) had a Charlson's score ≥1, median platelet count was 17 x109/L (range: 1-126); 57 (50.9%) had bleeding symptoms, including 2 severe gastro-intestinal tract and 1 intracranial bleeding. Median Khellaf's bleeding score was 5 (range: 0-35). Twenty-five (21.4%) patients had another autoimmune disease (mostly: Hashimoto's thyroiditis, n=6, Sjögren syndrome, n=5, Evans syndrome, n=3) and 23 (20.3%) experienced an infection within the six weeks before ITP onset (including 8 influenza-like and 3 gastro-enteritis like syndromes, the others being various bacterial infections). Sixty-eight (60.2%) patients were treated during the week following the diagnosis. Among them, 66 (98.5%) received CS (median dose: 0.99 mg/kg/d), including 21 (31.3%) IV CS, 29 (43.3%) IVIg, 8 (11,9%) platelet transfusion, 2 romiplostim and 1 rituximab. The factors associated with the use of IV CS were secondary ITP (OR: 5.91; 95% CI: 1.78-19.71) and Khellaf's bleeding score >8 (OR: 4.09; 95% CI 0.96-17.35). Those associated with the use of IVIg were Khellaf's bleeding score >8 (OR: 7.30; 95% CI 1.36-32.27) and platelet count <10 x 109/L (OR: 3.95; 95% CI 1.77-13.29).
Conclusions: This prospective cohort of newly diagnosed ITP adults confirms that severe bleeding is rare at ITP onset. Associated autoimmune diseases and recent infections are frequent. IVIg and IV CS were frequently used, particularly in case of severe bleeding.
Godeau:Roche: Research Funding; Amgen: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Adoue:LFB: Other: Symposium presentations ; OCTAPHARMA: Other: Symposium presentations ; ACTELION: Other: Symposium presentations ; PFIZER: Other: Symposium presentations ; AMGEN: Other: Symposium presentations ; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Other: Symposium presentations.
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