Facteurs pronostiques de survie et de survie sans progression au cours de la pneumopathie interstitielle diffuse de la sclérodermie systémique

Contexte: La pneumopathie interstitielle diffuse (PID) est une complication fréquente de la sclérodermie systémique, elle est actuellement la première cause de mortalité au cours de cette pathologie. Son évolution est hétérogène, rendant nécessaire une meilleure connaissance des facteurs pronostiques de cette complication afin de déterminer les patients à risque d aggravation en vue d une surveillance rapprochée ou de l introduction d un traitement.Méthode: Nous avons collecté de manière rétrospective les données cliniques, biologiques, fonctionnelles et scanographiques de 75 patients sclérodermiques d âge moyen 52 +- 16 ans présentant une PID et suivis régulièrement par des EFR. La progression de la PID était définie par une diminution confirmée de la CVF>=10% ou de la DLCO>=15% par rapport à la valeur initiale ou l introduction d un traitement immunosuppresseur à visée pulmonaire. Nous avons recherché parmi les données initiales, au moment du diagnostic de PID, les facteurs prédictifs de survie et de survie sans progression. Pour cela, tous les scanners thoraciques ont été relus en aveugle des données cliniques par deux radiologues différents afin d évaluer l extension et le type d atteinte pulmonaire selon le score de Wells et le score de Goh. Résultats: La survie à 1 an, 2 ans, 3 ans, 5 ans et 10 ans était respectivement de 97%, 96%, 94%, 90% et 85%. Les facteurs initiaux associés à la survie comprenaient l âge au diagnostic (p=0,002), la CVF (p=0,034), la DLCO (p=0,021), la CRP (p=0,003), le taux d hémoglobine (p=0,005) ainsi que la présence d anticorps anti-centromères (p=0,0002). La survie sans progression à 1 an, 2 ans, 3 ans, 5 ans et 10 ans était respectivement de 79%, 66%, 52%, 45% et 28%. Les facteurs associés à la survie sans progression comprenaient le score NYHA lors du diagnostic de PID (p=0,006) et l extension de l atteinte interstitielle sur le scanner thoracique initial (p=0,014). Le type de sclérodermie, le sexe, le test de marche de 6 minutes, l extension de l atteinte réticulaire ou la proportion de verre dépoli, la distinction entre atteinte extensive et limitée de la PID selon le score de Goh n avaient pas de valeur pronostique au sein de notre population d étude. Conclusion: La PID au cours de la sclérodermie est associée, dans notre série de patients non sélectionnés, à une mortalité modérée mais à une progression significative chez la plupart des patients. L extension de l atteinte interstitielle sur le scanner initial et l existence d une dyspnée significative doivent faire redouter une forme agressive de PID et mener à une surveillance rapprochée des patients.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

18F-FDG positron emission tomography scanning in systemic sclerosis-associated interstitial lung disease: a pilot study

International audienceBackground: Interstitial lung disease is a common complication of systemic sclerosis (SSc-ILD), and it remains difficult to accurately predict its course. Progressing ILD could be more metabolically active, suggesting that the 18F-FDG tracer could be a tool in the managing of SSc-ILD.Methods: In our center, SSc patients and controls (non-Hodgkin lymphoma cured after first-line regimen) who had received a PET/CT were screened retrospectively. The FDG uptake (visual intensity, pattern, SUVmax) was systematically recorded in > 30 regions of interest (ROIs) linked to SSc in a blind reviewing by 2 independent nuclear medicine physicians using a standardized form.Results: Among the 545 SSc patients followed up in our center, 36, including 22 SSc-ILDs, had a PET/CT, whose indication was cancer screening in most cases. The mean ± SD age was 57.9 ± 13.0 years with 20/36 females. Fourteen patients had a disease duration of less than 2 years. A third had anti-centromere antibodies and 27.8% had anti-topoisomerase antibodies. Pulmonary FDG uptakes were higher in SSc patients than in controls (n = 89), especially in those with ILD compared with those without ILD. Pulmonary FDG uptakes were positively correlated with the ILD severity (fibrosis extent, %FVC, and %DLCO). No significant difference was found in the FDG uptakes from extrathoracic ROIs. Progressing SSc-ILDs within the 2 years after PET/CT (n = 9) had significant higher pulmonary FDG uptakes at baseline than stable SSc-ILDs (n = 13).Conclusion: PET/CT could be a useful tool in the assessment of the severity and the prediction of pulmonary function outcome of SSc-ILD

Evolution of high-resolution CT-scan in systemic sclerosis-associated interstitial lung disease: Description and prognosis factors

International audienceObjective: The aims of our study were to describe the evolution of interstitial lung disease (ILD) extent on HRCT scan in systemic sclerosis (SSc), to identify baseline prognostic factors associated with ILD evolution and to assess whether the evolution of pulmonary function tests (PFTs) correlated with this evolution.Methods: 58 SSc with ILD (SSc-ILD) patients were included. All HRCT scans and PFTs available were collected. We modelized PFTs and HRCT scans evolution using linear mixed model with random effect.Results: Patients underwent a median number of 3 HRCT scans (total n = 203) and 5 PFTs (total n = 329), during a mean follow-up of 5.3 ± 4.9 years. Mean SSc duration was 2.5 ± 3.1 years at the diagnosis of ILD. Mean baseline ILD extent was 32.3 ± 28.7%. We found a significant mean progression of ILD extent on serial HRCT scans of 0.92 ± 0.36% per year (p = 0.018). Male sex, diffuse cutaneous SSc (dcSSc), presence of anti-topoisomerase 1 antibodies, a higher DLCO, limited ILD and a low coarseness score at baseline in bivariate analysis, and presence of antitopoisomerase 1 antibodies and a coarseness score of 0 in multivariate analysis, were associated with faster progression of ILD extent over time There was a significant correlation between the progression of ILD extent and the decline of DLCO but only a trend for FVC. ILD extent at baseline and during follow-up was associated with survival.Conclusion: Male sex, dcSSc, anti-topoisomerase 1 antibodies and a less severe ILD at baseline were associated with a faster progression of ILD over time. Evolution of DLCO significantly correlated with change in ILD extent on HRCT scan. Our study helps defining the profile of patients at risk of experiencing a progression of ILD on HRCT scans

Predictors of lung function test severity and outcome in systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis-related interstitial lung disease (SSc-ILD) is the leading cause of death in SSc. In this study, we aimed to describe the baseline severity and evolution of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) in patients with SSc-ILD and to assess the baseline clinical, biological and high-resolution CT scan (HRCT) predictors of this evolution. Baseline and serial FVC and DLCO were collected in 75 SSc-ILD patients followed during 6.4±4.2 years (n = 557 individual data). FVC and DLCO evolution was modelled using a linear mixed model with random effect. During follow-up, FVC was stable while DLCO significantly decreased (-1.5±0.3%/year (p<0.0001). Baseline NYHA functional class III/IV, extensive SSc-ILD on HRCT and DLCO<80% were associated with a lower baseline FVC. Absence of digital ulcers extensive SSc-ILD, and FVC<80% and were associated with a lower baseline DLCO. Presence or history of digital ulcers and presence of pulmonary hypertension at baseline or during follow-up were associated with a faster decline of DLCO overtime. Neither age, gender, subtype of SSc nor specificity of autoantibodies were associated with baseline severity or outcome of lung function tests. In this SSc-ILD population, FVC was therefore stable while DLCO significantly declined over time. ILD extension was associated with baseline FVC and DLCO but not with their evolution. Presence or history of digital ulcers and pulmonary hypertension were predictors of a faster decline of DLCO over time

Glucocorticoids Plus Rituximab versus Glucocorticoids Plus Placebo in Non-infectious Active Mixed Cryoglobulinemia Vasculitis: Results of a Placebo-Controlled Randomized Trial

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Clinical phenotype and cytokine profile of adult IgA vasculitis with joint involvement

International audienceObjective Joint involvement can be observed during the course of adult IgA vasculitis (IgAV). However, clinical picture, prognosis, or pathophysiological data associated with this condition have been overlooked. We aimed to describe the clinical characteristics and outcome of IgAV patients with joint involvement and look to a specific cytokine profile.Methods We analyzed clinical and biological data from a nationwide study that included adult IgAV patients. Presentation and outcomes of patients with or without joint involvement were compared at baseline and during follow-up. Plasma cytokine measurements of IgAV patients included in a prospective study were also analyzed using multiplex assays.Results Among 260 patients, 62% had joint involvement. Among them, rheumatological manifestations included arthralgia (100%) or arthritis (16%), mostly involving the knees and ankles. In multivariate analysis, patients with joint involvement, compared to those without, were younger (p = 0.002; OR 0.87; 95% CI 0.80-0.95) and showed more frequent gastrointestinal tract involvement (p = 0.012; OR= 2.08; 95% CI 1.18-3.67). However, no difference in terms of clinical response, relapse, end-stage renal disease, or death was observed between groups. Among 13 cytokines measured, plasma interleukin (IL)-1 beta level was higher in patients with joint involvement compared to those without (mean +/- SEM IL-1 beta, 3.5 +/- 1.2 vs. 0.47 +/- 0.1 pg/ ml; p = 0.024) or healthy controls (vs. 1.2 +/- 0.5 pg/ml; p = 0.076).Conclusion Joint involvement is frequent in adult IgAV and is associated with more frequent gastrointestinal involvement. Increased plasma IL-1 beta levels raise the question of targeting this cytokine in patients with chronic and/or refractory joint involvement

Glucocorticoids Plus Rituximab versus Glucocorticoids Plus Placebo in Non-infectious Active Mixed Cryoglobulinemia Vasculitis: Results of a Placebo-Controlled Randomized Trial

International audienc

Impact of aging on phenotype and prognosis in IgA vasculitis

International audienceObjectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: &lt;36, 36 ≤ age &lt; 52; 52 ≤ age &lt; 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset. Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P &lt; 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P &lt; 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for &gt;6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis

Intravenous immunoglobulins in systemic sclerosis: Data from a French nationwide cohort of 46 patients and review of the literature

International audienceBACKGROUND:As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature.METHODS:46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed.RESULTS:We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome).CONCLUSION:Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing

Evolution of FVC during the follow up.

<p>Panel A represents the individual data of the 75 patients and the red line is the trajectory of FVC using the linear mixed model with random effect. There was no significant change of FVC over time. Panel B is the progression-free survival of FVC. Progression was defined as a decline of ≥10% of baseline FVC.</p