1,721,064 research outputs found
Systemic sclerosis: Recent insight in clinical management
No full textSystemic sclerosis (SSc) is a connective tissue disease characterized by diffuse microangiopathy and immune dysregulation which ultimately result in widespread fibrosis of skin and internal organs. Although the 2013 EULAR/ACR criteria have allowed to improve the sensitivity for SSc diagnosis, it has recently come to light that the traditional subclassification into limited and diffuse cutaneous forms does not appear to fully capture the different phenotypes of the scleroderma spectrum. In this regard, a recent large cluster analysis-based study and other ongoing projects are trying to achieve a better stratification of SSc patients, as the disease course remains largely unpredictable to date. Recent preclinical studies and randomized controlled trials have yielded encouraging results with new drugs targeting inflammatory/immunological and fibrotic pathways. One of the main unmet needs in SSc remains the early identification of patients at high mortality risk, for whom aggressiveness of therapies ought to be determined and weighed against disease prognosis. Furthermore, lung and cardiac transplantation may also be taken into account in some carefully selected patients. Though the prognosis of SSc remains poor, an optimized stratification of patients along with the recent and ongoing advances in therapies could greatly impact the natural course of the disease in the near future. Moreover, it is envisioned that there will be an increasing need in the future to further develop combination therapies to better fight against this complex disease. In this review we discussed new insights into organ involvements and therapeutic options
Scleroderma renal crisis: Case reports and update on critical issues
No full textTo date, scleroderma renal crisis (SRC) remains a life-threatening complication in patients affected by systemic sclerosis (SSc), with high morbidity and mortality. In the last few years, some studies have tried to more precisely identify predictors of SRC and clarify the role of previous drug exposure-in particular, angiotensin-converting enzyme (ACE) inhibitors and corticosteroids-in patients with SSc presenting other well-known risk factors for SRC. Different from the findings of previous reports, more recent findings suggest that the presence of chronic kidney disease, systemic arterial hypertension, and proteinuria might all be predictors of SRC. Moreover, because about 40 to 50% of SRC cases can present signs of microangiopathy, a recent study has proposed SSc thrombotic microangiopathy (SSc-TMA) as a clinically and pathophysiologically different entity from narrowly defined SRC. Even though such clear distinction may not always be applicable/feasible in clinical practice, it highlights that complement pathway dysregulation may play a key pathogenetic role in SRC presenting as TMA. Thus, plasma exchange may be considered in severe refractory cases. Nevertheless, ACE inhibitors and prompt achievement of blood pressure control (to rapidly improve ongoing renal ischemia) remain to date the cornerstone of SRC treatment. Here, we report the cases of three SSc patients with SRC followed at our rheumatology units. While describing these patients' risk factors, clinical presentation, and therapy, we aim to discuss the state of the art in SRC and highlight critical issues
The role of plasma exchange in the management of autoimmune disorders
No full textTherapeutic plasma exchange (TPE) has been mainly used in the treatment of autoimmune diseases. The main mechanisms of action of TPE include the removal of circulating autoantibodies, immune complexes, complement components, cytokines and adhesion molecules, along with sensitization of antibody-producing cells to immunosuppressant agents. TPE is useful in autoimmune haematological, renal, rheumatic and neurological diseases, and is recommended for acute disorders, together with relapsed or worsened chronic diseases that are often unresponsive to conventional treatments. The American Society for Apheresis and the British Society of Haematology have published guidelines on the clinical use of apheresis procedures, indicating the different levels of efficacy of TPE. Based on the evidence from current literature and our personal experience, this review discusses the indications and the suggested regimens for TPE in autoimmune haematological and non-haematological disorders
Skin ulcers in systemic sclerosis: correlation with clinical phenotype in a monocentric cohort from the north-east of Italy
No full textTo evaluate the prevalence of skin ulcers (SUs) and their association with clinical phenotype in a monocentric cohort of patients affected with systemic sclerosis (SSc)
PD-1 gene rs2227981 (PD-1.5) polymorphism analysis in patients with systemic sclerosis
No full textRecently, some cases of scleroderma-like reactions have been reported in oncological patients treated with immune checkpoint inhibitors (ICIs) and in particular PD-1 inhibitors (nivolumab and pembrolizumab). PD-1 is a checkpoint protein found in T lymphocytes. Its binding with PD-ligand 1 (PD-L1) prevents autoimmunity and promotes self-tolerance by downmodulating T-cell activity. The literature suggests that deficiency in co-inhibitory receptor including PD-1 can be associated with the development of autoimmune diseases. The gene coding for PD-1 (PDCD1) presents several polymorphisms and PD-1 rs2227981 (PD-1.5) polymorphism is one of the most studied as it has been reported in association with other human autoimmune diseases. This study aimed to analyze PD-1 C>T rs2227981 single nuclear polymorphism and its possible association with the development of systemic sclerosis. The study comprehended 144 subjects (69 cases diagnosed with scleroderma with the ACR-EULAR criteria of 2013 and 75 healthy controls). No significant difference emerged between systemic sclerosis patients and healthy controls as regard genotype (p = 0.2775) and allele analysis (p = 0.1568). Our results do not suggest an association between PD-1 C/T rs2227981 polymorphism and a predisposition to develop systemic sclerosis. Despite this, our study does not exclude the association with other PD-1 polymorphisms with systemic sclerosis. Moreover, this study reported a single-center experience, thus the generalization of the findings is limited to similar settings
Determinants of impairment in lung diffusing capacity in patients with systemic sclerosis
No full textOBJECTIVES:
Lung diffusing capacity for carbon monoxide (DLCO) is impaired in interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) associated to systemic sclerosis (SSc), but the mechanism of DLCO reduction remains controversial. We hypothesised that the determinants of DLCO impairment differ in interstitial or vascular involvement of the lung of SSc patients.
METHODS:
DLCO was partitioned into alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) using combined single-breath DLNO and DLCO measurements. Seventeen SSc patients without pulmonary involvement (SSc), 20 SSc patients with ILD (SSc-ILD), with and without PAH, and 21 healthy controls were included.
RESULTS:
DLNO and Dm were reduced in SSc patients as compared with controls, whereas Vc was not significantly different. SSc-ILD patients showed a highly significant decrease in Dm and Vc as compared with SSc patients and controls. Vc tended to be more reduced than Dm in SSc-ILD patients with PAH. Dm and Vc were negatively correlated with PAPs and HCRT scores, but the relationship with the HRCT score was stronger.
CONCLUSIONS:
DLNO is more sensitive than DLCO in detecting functional impairment in SSc without radiologic or haemodynamic alterations. A disproportional reduction of Dm relative to Vc suggests a thickening of the blood-gas diffusion barrier in these patients. In SSc patients with detectable ILD, the gas exchange impairment is due to both components of lung diffusing capacity, and partitioning of DLCO in Dm and Vc is of little use in distinguishing the patients with only ILD from those with ILD complicated by PAH
Improvement with time of vascular outcomes in systemic sclerosis: a systematic review and meta-analysis study
No full textVascular disease in SSc is associated with significant morbidity and mortality. Preliminary data may lead to the suggestion of a modifiable unified-vascular endophenotype. Our aim was to determine whether the prevalence, mortality and severity of SSc-vascular disease have changed over time
Systemic sclerosis sine scleroderma in children
No full textOBJECTIVE: Juvenile systemic sclerosis (JSSc) is a rare condition in childhood and its variety with no skin involvement, sine scleroderma (ssJSSc), is anecdotal. We report the first case series of patients with ssJSSc. METHODS: Demographic, clinical and laboratory data of patients with JSSc followed at our centre were retrospectively collected. Patients with no skin involvement but with all of the features RP, positive ANA, intestinal dysmotility and/or interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH) and/or cardiac or renal involvement typical of scleroderma were defined as having ssJSSc and compared with those with classic JSSc (cJSSc). RESULTS: Among 52 JSSc patients seen in 20 years, five (9.6%) presented with ssJSSc. Their clinical features and those of the only two patients reported in the literature so far were compared with classic JSSc with available complete data. Six patients had cardiac involvement as presenting feature, three primary cardiomyopathy, three secondary to PAH. Two patients died after a brief disease course and one rapidly underwent heart transplantation. In comparison with cJSSc, ssJSSc showed a significantly longer diagnostic delay (20.1 vs 8.3 months, P = 0.017), higher frequency of cardiac involvement (85.7 vs 15.6%, P = 0.001) and worse outcome, intended as mortality or end-stage organ failure rates (42.9% vs 6.2%, P < 0.001). CONCLUSION: Cardiac involvement represents the most important characteristic of ssJSSc and carries a high morbidity and mortality rate. The longer delay in diagnosis underlines the need for a comprehensive rheumatological work-up in patients with isolated cardiomyopathy or PAH/ILD
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