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OBJECTIVES: Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison to patients with SLE (onlySLE) or myocarditis alone (onlyMyo). METHODS: A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomised by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or magnetic resonance. RESULTS: Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; p= 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; p= 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and to patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-beta-2-glycoprotein I antibodies (aB2GPI, p= 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (p= 0.003). CONCLUSION: myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course.
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Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24 months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30 months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario.
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OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Granulomatosis con Poliangitis , Enfermedades Pulmonares Intersticiales , Poliangitis Microscópica , Reumatología , Humanos , Poliangitis Microscópica/complicaciones , Poliangitis Microscópica/diagnóstico por imagen , Poliangitis Microscópica/epidemiología , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico por imagen , Granulomatosis con Poliangitis/epidemiología , Anticuerpos Anticitoplasma de Neutrófilos , Estudios Transversales , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/etiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Mieloblastina , Demografía , PeroxidasaRESUMEN
INTRODUCTION: Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). OBJECTIVES: The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. MATERIALS AND METHODS: A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. RESULTS: One-hundred and six patients were included (median age at onset of 55 years [IQR 42-67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13-77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4-9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51-13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. CONCLUSIONS: Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Hemorragia/epidemiología , Hemorragia/etiología , Alveolos Pulmonares/patología , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Femenino , Hemorragia/diagnóstico , Hemorragia/mortalidad , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad , Pronóstico , Vigilancia en Salud Pública , Estudios RetrospectivosRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of apremilast in treating oral ulcers (OUs), the cardinal and high-disabling feature of Behçet's disease (BD). METHODS: Twelve consecutive patients affected by BD with recurrent/relapsing OUs resistant and/or intolerant to conventional therapy were enrolled and prospectively followed. The primary endpoint was the number of OUs at week 12. Secondary endpoints were modification from baseline to week 12 in Behçet's Syndrome Activity Score (BSAS), Behçet's Disease Current Activity Form (BDCAF) score, Behçet's Disease Quality of Life (BDQOL) scale and pain of OUs, as measured by a visual analogue scale (VAS). All adverse events (AEs) were recorded during follow-up. Non-parametric tests (Wilcoxon rank test) were used and a P-value <0.05 was considered statistically significant. RESULTS: After 12 weeks of apremilast, there was a significant reduction in the number of OUs [0.58 (s.d. 0.67) vs 3.33 (s.d. 1.45) at baseline, P = 0.02] that was paralleled by improvement in disease activity: BSAS was 16.8 (s.d. 9.1) [from 45.9 (s.d. 19.6) at baseline] (P = 0.02), BDCAF score was 0.72 (s.d. 0.65) [vs 2.45 (s.d. 1.0) at baseline] (P = 0.04) and the VAS score for pain decreased to 23.3 (s.d. 13.7) [vs 67.9 (s.d. 17.2) at baseline] (P = 0.02). Consistently, an improvement of BDQOL was assessed (P = 0.02). Clinical improvement led to complete steroid discontinuation in six patients and a tapering of the prednisone dose in two patients (P = 0.016). Colchicine was discontinued in six of nine patients (P = 0.031). AEs related to apremilast occurred in four patients (mainly due to gastrointestinal AEs), leading to drug discontinuation in all of them. CONCLUSION: Our preliminary real-world data support the use of apremilast as an effective therapeutic strategy against BD-related recurrent OUs resistant or intolerant to first-line therapy.
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Síndrome de Behçet/tratamiento farmacológico , Mucosa Bucal/patología , Calidad de Vida , Talidomida/análogos & derivados , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Síndrome de Behçet/complicaciones , Síndrome de Behçet/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Italia/epidemiología , Masculino , Úlceras Bucales/tratamiento farmacológico , Úlceras Bucales/epidemiología , Úlceras Bucales/etiología , Estudios Prospectivos , Recurrencia , Talidomida/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Recent data have shown a significant efficacy of rituximab (RTX) in SSc. An RTX biosimilar (RTX-B) is a more affordable option. We assessed the safety and efficacy of an RTX-B (CT-P10) in SSc. METHODS: SSc patients treated with RTX-B with at least 6 months of follow-up were retrospectively identified from six Italian referral centres. SSc patients naïve to RTX-B (RTX-Bn) or already treated with RTX originator and switched to an RTX-B (RTX-Bs) were evaluated. A comprehensive assessment of disease characteristics and organ involvement at baseline and after 6 months was obtained. RESULTS: Thirty-three SSc patients were selected: 29 (87.9%) females, mean age 51.6 years (s.d. 14.2), mean disease duration 9.8 years (s.d. 8.1); 21 (64.5%) with dcSSc, 20 (60.1%) anti-topoisomerase I, 7 (21.2%) anti-RNA polymerase III and 6 (18.2%) anti-centromere positive. Seventeen (51.5%) were RTX-Bn and 16 were on RTX-Bs (48.5%). RTX was introduced because of skin progression in 18 patients (54.5%), interstitial lung disease (ILD) worsening in 11 (33.3%) and arthritis in 12 (36.4%). All patients were previously treated with immunosuppressants. At RTX-B introduction, 21 (63.6%) patients were on concomitant immunosuppressants: 15 (71.4%) on MMF and 6 (28.6%) on MTX. Twenty-three (69.7%) were on low-dose steroids. After 6 months, a significant reduction of the modified Rodnan skin score (mRSS), 28-joint DAS and CRP was observed (P = 0.002, 0.005 and 0.008, respectively); the mRSS significantly improved both in RTX-Bn (P < 0.024) and RTX-Bs patients (P < 0.031). No significant changes were observed for lung function tests, either in the entire cohort or in the subgroup of ILD patients. Only one RTX-Bs patient experienced transient neutropenia. CONCLUSION: Our data suggest that RTX-B can represent a cheaper option in SSc patients, as it is effective in improving skin and joint involvement and in stabilizing lung function.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Population aging and multimorbidity challenge health system sustainability, but the role of assistance-related variables rather than individual pathophysiological factors in determining patient outcomes is unclear. To identify assistance-related determinants of sustainable hospital healthcare, all patients hospitalised in an Internal Medicine Unit (n = 1073) were enrolled in a prospective year-long observational study and split 2:1 into a training (n = 726) and a validation subset (n = 347). Demographics, comorbidities, provenance setting, estimates of complexity (cumulative illness rating scale, CIRS: total, comorbidity, CIRS-CI, and severity, CIRS-SI subscores) and intensity of care (nine equivalents of manpower score, NEMS) were analysed at individual and Unit levels along with variations in healthcare personnel as determinants of in-hospital mortality, length of stay and nosocomial infections. Advanced age, higher CIRS-SI, end-stage cancer, and the absence of immune-mediated diseases were correlated with higher mortality. Admission from nursing homes or intensive care units, dependency on activity of daily living, community- or hospital-acquired infections, oxygen support and the number of exits from the Unit along with patient/physician ratios were associated with prolonged hospitalisations. Upper gastrointestinal tract disorders, advanced age and higher CIRS-SI were associated with nosocomial infections. In addition to demographic variables and multimorbidity, physician number and assistance context affect hospitalisation outcomes and healthcare sustainability.
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PURPOSE: Subglottic stenosis (SGS) is a potentially life-threatening manifestation of granulomatosis with polyangiitis (GPA). Endoscopic dilation is effective, but relapses are frequent and the benefit of systemic immunosuppression in this setting is still controversial. We aimed to investigate the role of immunosuppressive treatment on SGS relapse risk. METHODS: This is a retrospective observational study based on review of medical charts among our cohort of patients with GPA. RESULTS: Twenty-one patients with SGS-GPA were identified, with a prevalence of 20% among our entire GPA cohort (n = 105). Compared to patients without SGS, patients with SGS-GPA had an earlier disease onset (mean age 30.2 vs. 47.3 years, p<0.001), and lower BVAS (mean 10.5 vs 13.5; p = 0.018). Five patients didn't receive systemic immunosuppression for SGS and they all (100%) relapsed after the first procedure, while among medical treatment group relapse rate was 44% (p = 0.045). When single treatment regimens are considered, rituximab (RTX) and cyclophosphamide (CYC) yielded a protective role towards the need of subsequent dilation procedure after the first if compared with absence of medical treatment. Patients with SGS and generalized disease, who initially received either a RTX- or a CYC-based induction treatment, and higher cumulative doses of glucocorticoids, showed a delayed median time to SGS relapse (36 vs. 12 months, p = 0.024). CONCLUSIONS: Subglottic stenosis is highly prevalent in patients with GPA and may define a milder systemic disease subset occurring more frequently in younger patients. Systemic immunosuppression provides benefit in preventing recurrence of SGS in GPA patients and regimens based on cyclophosphamide or rituximab might have a non-redundant role in this setting.
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Granulomatosis con Poliangitis , Laringoestenosis , Humanos , Adulto , Rituximab/uso terapéutico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Constricción Patológica/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Estudios Retrospectivos , Terapia de Inmunosupresión , Laringoestenosis/tratamiento farmacológico , Laringoestenosis/etiología , Recurrencia , Resultado del TratamientoRESUMEN
Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a "golden age" of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances.