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Caratteristiche cliniche e nuovi orizzonti diagnostico-terapeutici delle vasculiti dei grandi vasi e della interstiziopatia polmonare secondaria ad artrite reumatoide.
No full textLe patologie reumatiche autoimmuni sono malattie croniche con un importante impatto sanitario in tutto il mondo. Il loro impatto economico e sociale deriva da una diminuzione della qualità della vita, dalla perdita di produttività e dall'aumento dei costi dell'assistenza sanitaria. Senza approcci adeguati alla gestione dei pazienti e al controllo di queste malattie, ci si può aspettare che questo impatto aumenti con il progressivo invecchiamento della popolazione. Attualmente, per alcune patologie reumatiche, mancano ancora accurati dati epidemiologici e rimane la necessità di progressi significativi in termini di diagnosi precoce, trattamento e gestione dei pazienti.
Sezione A:
L'arterite a cellule giganti (GCA) è la forma più comune di vasculite nei pazienti di età superiore ai 50 anni. Negli ultimi decenni molta attenzione è stata data al coinvolgimento extracranico dei grandi vasi, in particolare dopo lo sviluppo di nuovi strumenti di imaging come PET-TC, angio-RM (MRA) e angio-TC (CTA). Non è noto, tuttavia, quanto queste metodiche siano efficaci per valutare l'attività della malattia durante la terapia. Il trattamento della GCA si basa principalmente sull'uso a lungo termine di glucocorticosteroidi (GC). Tocilizumab è stato recentemente approvato per il trattamento della GCA, tuttavia viene spesso utilizzato in combinazione con GC, con conseguente alto rischio di effetti collaterali.
Partendo da queste considerazioni, abbiamo realizzato uno studio osservazionale monocentrico per valutare le variazioni cliniche e di imaging in una serie di pazienti con GCA trattati con glucocorticosteroidi (GCs) per breve periodo e tocilizumab (TCZ) s.c. Abbiamo inoltre valutato l'efficacia e la sicurezza della monoterapia con TCZ come trattamento di mantenimento nella GCA.
I nostri risultati preliminari hanno dimostrato che le tecniche di imaging sembrano essere utili nel valutare l'attività della malattia nei pazienti con GCA durante il trattamento. TCZ in monoterapia ha dimostrato un buon profilo di sicurezza nei pazienti con GCA, tuttavia il suo potenziale effetto nello stabilizzare o risolvere l'infiammazione dei grandi vasi senza l'uso concomitante di GC deve ancora essere dimostrato in ampi studi clinici randomizzati.
Sezione B:
L'artrite reumatoide (AR) è una malattia infiammatoria cronica che colpisce lo 0,5%-1% della popolazione mondiale. L’interstiziopatia polmonare (ILD) è la forma di coinvolgimento polmonare più comune dell'AR.
Tutti gli studi disponibili sulla prevalenza di ILD in AR sono retrospettivi, con piccole serie di pazienti e numerosi bias, e quindi non affidabili. La diagnosi precoce rimane un essenziale ma difficile obiettivo clinico, in quanto l'aumento delle opportunità di diagnosticare l'ILD potrebbe migliorare la qualità della vita dei pazienti e diminuire la mortalità e l'elevato utilizzo delle risorse sanitarie. Sebbene il coinvolgimento polmonare rappresenti la seconda causa di morte nei pazienti con AR, non esistono approcci di screening randomizzati o linee guida di gestione di tale complicanza.
Diversi agenti terapeutici sono stati suggeriti per il trattamento della RA-ILD, attualmente però non esistono studi clinici controllati randomizzati che supportino solide linee guida terapeutiche.
In questo contesto, gli obiettivi di questo progetto di studio sono:
-effettuare una revisione della letteratura e dello stato dell’arte sul trattamento dell'ILD nei pazienti con AR e discuterne i problemi irrisolti, anche suggerendo una proposta per la loro gestione clinica e analizzando l'evoluzione dell'RA-ILD nei pazienti trattati con tocilizumab e abatacept;
-indagare l'utilità di uno strumento di screening tramite la rilevazione dei crepitii polonari a velcro e la loro analisi mediante un algoritmo opportunamente sviluppato;
- eseguire uno studio osservazionale multicentrico prospettico internazionale per valutare l'incidenza e la prevalenza di ILD in pazienti con AR.Autoimmune rheumatic diseases are chronic diseases with a major health impact worldwide.
Their economic and social burden results from a decreased quality of life, lost productivity, and increased costs of health care. Without appropriate approaches to patient management and control of these diseases, this impact can be expected to increase as the population ages. Challenges in studying rheumatic diseases lie in achieving accurate epidemiological data and making efforts to obtain significant progress in terms of early diagnosis, treatment, and management of patients.
Section A:
Giant-cell arteritis (GCA) is the most common form of vasculitis in patients over 50 years old. Extra-cranic large vessel involvement (LVI) has emerged in recent decades, especially with the development of new imaging tools such as PET-TC, MR-Angiography (MRA) and CT-Angiography (CTA). It is unknown, however, how effective these methods are for assessing disease activity while patients are under treatment. GCA treatment is mainly based on long term use of corticosteroids (GCs). Tocilizumab has recently been approved for the treatment of GCA. However, it is often use in combination with GCs, with subsequent high risk of side effects.
Starting from these considerations, we underwent a monocentric observational study to evaluate clinical and functional/morphological imaging variations in a series of patients with GCA treated with ultra-short corticosteroids (GCs) and tocilizumab (TCZ) s.c. We also evaluated effectiveness and safety of TCZ monotherapy as a maintenance treatment in GCA.
In our preliminary results, radiologic tools seem to be useful methods for assessing disease activity in GCA patients during treatment. TCZ demonstrated a good safety profile in patients with GCA, however its potential effect in stabilize or resolve large vessels inflammation without the concomitant use of GCs has yet to be demonstrated in large randomized clinical trials.
Section B:
Rheumatoid arthritis (RA) is the most common chronic inflammatory disease, affecting 0.5%-1% of the population worldwide. Interstitial lung disease (ILD) is the most common and serious complication of lung involvement in RA.
All the available studies about the prevalence of ILD in AR are retrospective, with small series of patients and numerous biases, and therefore not reliable. Moreover, this complication is often underrated, particularly in its earliest stages. An early diagnosis is challenging, and the increase of the opportunities to diagnose ILD could improve the quality of life of patients and decrease the mortality and the high utilization of healthcare resources. Although lung involvement represents the second cause of death in RA patients, there are no randomized screening approaches or management guidelines.
Several therapeutic agents have been suggested for the treatment of RA-ILD, but nowadays there are no randomized controlled clinical trials to support therapeutic guidelines and treatment of RA-ILD is still based on empirical approaches.
In this background, aims of this study project were:
-to review the current literature on the treatment of ILD in RA patients and discuss the unsolved problems regarding this challenging patient cohort, even suggesting a framework for their management and analyzing the evolution of RA-ILD in patients treated with tocilizumab and abatacept;
-to investigate the usefulness of detecting velcro crackle in lung sounds by analyze them using a suitably developed algorithm, as an early screening of RA-ILD;
-to perform an international prospective multicenter observational study to evaluate incidence and prevalence of ILD in patients with RA
Granuloma annulare as a possible new adverse effect of topiramate
No full textBackgroundGranuloma annulare (GA) is a relatively common, self-limiting condition that can be associated with disorders such as diabetes mellitus, malignancy, and thyroid disease, and with the use of some drugs. Topiramate is approved for the prevention of migraine. Its adverse effects include somnolence, fatigue, paresthesia, anorexia and weight loss, and other abnormalities.ObjectivesWe report a 50-year-old woman in whom topiramate at 50mg/d was initiated in January 2010.Case reportOne month after starting topiramate, the patient presented with painless nodules on the left ankle, which later spread to the left leg. Histopathology of a punch biopsy revealed lymphohistiocytic infiltrate, collagen degeneration, and mucin deposition, all of which are characteristic of GA. Two weeks after the discontinuation of topiramate, the lesion resolved. Two years later, the patient resumed topiramate. Two weeks later, a new GA appeared in the same area and disappeared within a few weeks of discontinuation of the drug.ConclusionsAssociations between the use of topiramate and a GA-like reaction have been reported in recent years. Based on the present case, it would appear that an actual association between GA and topiramate is possible given that: (i) the GA appeared only after the initiation of topiramate; (ii) the GA resolved after the discontinuation of topiramate; (iii) the GA reappeared with the resumption of topiramate in the same area and with the same characteristics as previously; and (iv) the lesion healed after topiramate was suspended
[18F]fluorodeoxyglucose positron emission tomography imaging in a case of relapsing polychondritis
Full text linkClinical image: [18F]fluorodeoxyglucose positron emission tomography imaging in a case of relapsing polychondriti
Severe alopecia complicating systemic sclerosis
No full textAims: To describe a case of systemic sclerosis (SSc) associated with severe alopecia areata (AA) responsive to topical and systemic treatments, including vasoactive and immunosuppressive drugs (mycophenolate mofetil).
Presentation of the Case: A 56 year old woman, affected by SSc as from 5 years back, developed a rapid hair loss that progressively involved a large area of the scalp. AA was diagnosed, after the exclusion of an overlapping systemic lupus erythematosus or fungal infection. Treatment with topical steroids and minoxidil, plus mycophenolate mofetil that was introduced for interstitial lung disease, led to progressive improvement of alopecia up to a complete resolution
within 4 months.
Discussion: This is an interesting observation of SSc complicated by severe AA, which is often observed in patients affected by various autoimmune disorders. A possible common pathogenesis of AA and SSc is also discussed
Efficacy and safety of rituximab in the treatment of connective tissue disease-related interstitial lung disease
No full textInterstitial lung disease (ILD) represents a severe pulmonary complication of connective tissue diseases, rheumatoid arthritis (RA), and antineutrophil cytoplasmic antibody-associated vasculitis. Treatment of ILD, mainly based on immunosuppression, remains challenging. Rituximab (RTX), a monoclonal antibody binding to CD20, is considered a valuable therapeutic choice in cases of refractory ILD. Here, we review the available efficacy and safety data on the use of RTX in the treatment of rheumatic disease-related ILD. Despite controversial efficacy data, RTX seems to be able to stabilize or improve ILD related to RA and antisynthetase syndrome and in established and severe ILD complicating systemic sclerosis. Fewer data are available regarding ILD related to Sjögren syndrome, systemic lupus erythematosus, and antineutrophil cytoplasmic antibody-associated vasculitis. To date, few prospective studies are available and randomized trials are still ongoing with the purpose of exploring the role of RTX in this condition, including the supposed relationship between efficacy and ILD radiologic patterns and safety data, up to now derived mainly from RA studies. Despite an overall acceptable safety profile, concerns remain regarding an increased infectious disease risk in patients with ILD as well as possible lung toxicity and the increased rate of immune-mediated reactions in patients with connective tissue diseases. In conclusion, RTX is a relevant therapeutic option for rheumatic disease-related ILD despite the existing uncertainties; ongoing trials are expected to clarify its use
Radiomics to predict the mortality of patients with rheumatoid arthritis-associated interstitial lung disease: A proof-of-concept study
Full text linkOBJECTIVES: Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients. METHODS: High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables. RESULTS: We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36–120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56–55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05–0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06–0.82) and the flatness (HR 0.42, 95% CI 0.18–0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82–2.83) was also retained as a confounder. CONCLUSION: Radiomic analysis may predict RA-ILD patients’ mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease
Treatment with Rituximab in Systemic Sclerosis Patients: Our Experience in a Pilot Clinical Trial
No full textBackground Systemic sclerosis (SSc) is an immune-mediated disorder characterized by abnormal fibrosis and diffuse microangiopathy with skin and internal organ involvement due to both T- and B-lymphocyte activation. The present study aimed to assess the efficacy of long-term treatment with rituximab (RTX), a chimeric monoclonal antibody that targets B-cell CD20. The rationale for the use of RTX in SSc is based on experimental data suggesting a key role for B cells in regulating the fibrotic process.
Objectives The present study aimed to assess the efficacy of long-term treatment with rituximab (RTX) in systemic sclerosis patients.
Methods Eleven SSc patients (M/F 3/8, mean age 43.2±10.5SD years, mean disease duration 3.6±6.2SD years) underwent to RTX cycle (weekly infusion of RTX 375 mg/m2 of body surface plus 100 mg methylprednisolone for 4 weeks); in 10/11 RTX was repeated every 6 months for a total of 2-6 cycles. Patients' clinical-serological evaluation, including HAQ assessment and visual analogical scale (VAS), was performed every six months.
Results At the end of the follow-up period (3.7±2.8 SD years) an improvement of the skin sclerosis involvement was constantly observed; in particular, patients with diffuse SSc cutaneous variant showed a significant decrease of modified Rodnan skin score (from 25±4.1 to 17.2±4.1; p<0.004). Similarly, the articular involvement, melanodermia, and calcinosis ameliorated if compared to baseline; these positive clinical variations were mirrored by a subjective recovery of patients' well being in all cases (HAQ, VAS). No significant variations were observed with regards to other SSc clinical manifestations; in particular, lung involvement remained stable or showed a moderate progression at the last patients' evaluation. Finally, in no cases significant side effects were observed.
Conclusions Our results indicate that treatment of SSc patients with RTX may be particularly effective for severe skin sclerosis, as suggested by other preliminary trials. The scarce efficacy of RTX on some disease manifestations may suggest the use of combined treatment, namely RTX with other antifibrotic/vasoactive drugs
Measuring microangiopathy abnormalities in systemic sclerosis patients: the role of capillaroscopy-based scoring models
No full textCapillaroscopy is a noninvasive imaging technique for the in vivo study of microcirculation. The role of a qualitative evaluation of capillaroscopy in the assessment of Raynaud's phenomenon secondary to scleroderma spectrum disorder, particularly systemic sclerosis (SSc), is well defined. The usefulness of capillaroscopy in the follow-up of SSc patients and the possible prognostic role for the appearance of typical SSc vascular and visceral involvement, namely, digital ulcers, pulmonary arterial hypertension, and mortality, is suggested by many authors but still under debate. In this regard, and for a reliable and repeatable longitudinal evaluation of SSc microangiopathy, a quantitative analysis should be required. In this review, we describe the current classifications proposed to define the SSc microvascular involvement and the scoring methods suggested for a semiquantitative and quantitative analysis of microangiopathy and its correlation with clinical manifestations of disease
Rheumatoid arthritis extra-articular lung disease: new insights on pathogenesis and experimental drugs
No full textIntroduction: Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature. Areas covered: The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients. Expert opinion: Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years
Granulomatosis with polyangiitis presenting as a renal mass successfully treated with rituximab
No full textGranulomatosis with polyangiitis (GPA) is a granulomatous disorder usually associated with vasculitis involving the small and medium-sized blood vessels that affects the upper and lower respiratory tracts and the kidneys, but almost any organ can be targeted. The typical renal involvement of GPA consists of a segmental necrotising glomerulonephritis, but, very rarely, renal disease could appear as an isolated or bilateral renal mass, requiring a differential diagnosis from neoplasms or granulomatous infections. We describe a patient who, during tests for a kidney mass, was found
to have pulmonary nodules suspected to be metastasis, successfully treated with rituximab
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