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1.
PLoS One ; 15(12): e0243651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33301540

RESUMO

Systemic sclerosis is a disease where microcirculation damage is critical in their beginning and vascular complications have similar pathogenic findings. Digital ulcers are a frequent complication in systemic sclerosis patients and pulmonary hypertension is one of the leading causes of death. The use of bosentan has been shown to be useful for the treatment of pulmonary arterial hypertension and to prevent new digital ulcers. However, is unknown if bosentan can prevent pulmonary hypertension. Our objective was to determine if bosentan is useful to prevent pulmonary hypertension in SSc patients. A retrospective study in 237 systemic sclerosis patients with digital ulcers history treated or not with bosentan to prevent it was made. We analyzed the occurrence of pulmonary hypertension defined by an echocardiogram pulmonary arterial pressure > 40 mmHg in the entire cohort. Demographic, clinical, and treatment variables were recorded for all patients. Statistical significance was denoted by p values < 0.05. Fifty-nine patients were treated with bosentan a median of 34 months. 13.8% of treated patients had pulmonary hypertension vs 23.7% of untreated patients (p 0.13) during the follow up. In multivariate analysis patients not treated with bosentan had 3.9fold-increased risk of pulmonary hypertension compared with patients under bosentan treatment (p < 0.02). Moreover the percentage carbon monoxide diffusing capacity (DLCO) in bosentan treated patients did not decrease from baseline to the end of follow-up (61.8±14% vs 57±20.1%, p = 0.89). We concluded that Systemic sclerosis patients with digital ulcers treated with bosentan seems to have less risk to develop pulmonary hypertension and to stabilize DLCO.

2.
Clin Exp Rheumatol ; 38 Suppl 127(5): 69-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33331268

RESUMO

OBJECTIVES: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD). METHODS: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. RESULTS: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. CONCLUSIONS: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.


Assuntos
Síndrome de Behçet , Estomatite Aftosa , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Úlcera
3.
Clin Immunol ; : 108631, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189888

RESUMO

Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications.

4.
Arthritis Rheumatol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142016

RESUMO

OBJECTIVE: In the SENSCIS trial in subjects with systemic sclerosis-associated ILD (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% versus placebo. We investigated the effects of nintedanib on categorical changes in FVC and other measures of ILD progression. METHODS: In post-hoc analyses, we assessed the proportions of subjects with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC ≥5% predicted or death and absolute decline in FVC ≥10% predicted or death. RESULTS: A total of 288 subjects received nintedanib and 288 received placebo. At week 52, in subjects treated with nintedanib and placebo, respectively, 55.7% and 66.3% had any decline in FVC % predicted, 13.6% and 20.1% had an FVC decline >5%-≤10% predicted, and 3.5% and 5.2% had an FVC decline >10%-≤15% predicted; 34.5% and 43.8% had a decrease in FVC ≥3.3% predicted (proposed minimal clinically important difference [MCID] for worsening of FVC), while 23.0% and 14.9% had an increase in FVC ≥3.0% predicted (proposed MCID for improvement in FVC). Over 52 weeks, the hazard ratio for an absolute decline in FVC ≥5% predicted or death with nintedanib versus placebo was 0.83 (95% CI: 0.66, 1.06) (P=0.14) and the hazard ratio for an absolute decline in FVC ≥10% predicted was 0.64 (95% CI: 0.43, 0.95); P=0.029. CONCLUSION: These results suggest that nintedanib has a clinically relevant benefit on the progression of SSc-ILD.

5.
Reumatol Clin ; 2020 Oct 08.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33041228

RESUMO

OBJECTIVE: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). METHODS: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted 'yes' (yes/no). RESULTS: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients' risk management. CONCLUSIONS: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.

6.
Clin Exp Rheumatol ; 38 Suppl 126(4): 110-115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33025900

RESUMO

OBJECTIVES: Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations. METHODS: All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression. RESULTS: From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia. CONCLUSIONS: DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.


Assuntos
Hepatite Autoimune , Síndrome de Sjogren , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia
7.
Front Med (Lausanne) ; 7: 557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984388

RESUMO

Objective: We set out to analyze the incidence and predictive factors of pulmonary embolism (PE) in hospitalized patients with Covid-19. Methods: We prospectively collected data from all consecutive patients with laboratory-confirmed Covid-19 admitted to the Hospital de la Santa Creu i Sant Pau, a university hospital in Barcelona, between March 9 and April 15, 2020. Patients with suspected PE, according to standardized guidelines, underwent CT pulmonary angiography (CTPA). Results: A total of 1,275 patients with Covid-19 were admitted to hospital. CTPA was performed on 76 inpatients, and a diagnosis of PE was made in 32 (2.6% [95%CI 1.7-3.5%]). Patients with PE were older, and they exhibited lower PaO2:FiO2 ratios and higher levels of D-dimer and C-reactive protein (CRP). They more often required admission to ICU and mechanical ventilation, and they often had longer hospital stays, although in-hospital mortality was no greater than in patients without PE. High CRP and D-dimer levels at admission (≥150 mg/L and ≥1,000 ng/ml, respectively) and a peak D-dimer ≥6,000 ng/ml during hospital stay were independent factors associated with PE. Prophylactic low molecular weight heparin did not appear to prevent PE. Increased CRP levels correlated with increased D-dimer levels and both correlated with a lower PaO2:FiO2. Conclusions: The 2.6% incidence of PE in Covid-19 hospitalized patients is clearly high. Higher doses of thromboprophylaxis may be required to prevent PE, particularly in patients at increased risk, such as those with high levels of CRP and D-dimer at admission. These findings should be validated in future studies.

8.
Lupus ; 29(12): 1556-1565, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32807021

RESUMO

INTRODUCTION: Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). MATERIALS AND METHODS: Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry. RESULTS: We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE (p < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups (p < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p < 0.001). SLE-APS patients showed higher mortality rates (p < 0.001). CONCLUSIONS: SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.

9.
Clin Exp Rheumatol ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32828148

RESUMO

OBJECTIVES: We aimed to investigate the association between the different antiphospholipid antibodies (aPL) and both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) manifestations. METHODS: Patients from the RELESSER registry, a Spanish retrospective, cross-sectional, forty-five hospital registry of adult SLE patients, were included. RESULTS: Out of a total of 3,658 SLE patients, 1372 were aPL positive (555 of them fulfilled criteria for APS). All aPL types showed a negative association with cutaneous SLE manifestations. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) were both associated with haematological, ophthalmological and neuropsychiatric manifestations. IgG isotypes were associated with a higher risk of lupus manifestations compared with IgM. We found that the risk of neuropsychiatric and ophthalmological manifestations significantly increased with a higher number of positive aPL whereas the risk of cutaneous symptoms showed a negative correlation. All types of aPL, and more strongly LA, were associated with non-criteria antiphospholipid syndrome (APS) manifestations such as thrombocytopenia and haemolytic anaemia. Moreover, LA and aCL (particularly IgG isotype) were also associated with Libman-Sacks endocarditis and cognitive impairment. This association was stronger with more than one positive aPL. All types of aPL were also associated with classic APS manifestations, although LA, IgG isotypes, and patients with more than one aPL displayed a higher risk. CONCLUSIONS: There is a hierarchy for aPL and the risk of APS and SLE manifestations. aCL, and especially LA, confer a higher risk for major organ involvement in SLE. IgG isotypes seem to have a more important role. The load of aPL confer a higher risk for APS and certain SLE manifestations.

10.
Lupus ; 29(10): 1216-1226, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32631205

RESUMO

BACKGROUND: The concomitant presence of two autoimmune diseases - systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) - in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus. METHODS: This was a cross-sectional study. We included rhupus patients from 11 different rheumatology departments, and compared them to SLE and RA patients at a ratio of 2:1. All information was recorded following a pre-established protocol. RESULTS: A total of 200 patients were included: 40 rhupus patients and 80 each of SLE and RA patients as controls. Disease duration was similar among SLE and rhupus groups (around 13 years), but the RA group had a significantly lower disease duration. Main clinical manifestations were articular (94.2%), cutaneous (77.5%) and haematological (72.5%). Rhupus patients had articular manifestations similar to those expected in RA. Only 10% of rhupus patients had renal involvement compared with 25% of those with SLE (p < 0.05), while interstitial lung disease was more common in patients affected by RA. The 2019 EULAR/ACR SLE criteria were met in 92.5% of the rhupus patients and in 96.3% of the SLE cohort (p > 0.05). Excluding the joint domain, there were no differences between the numbers of patients who met the classification criteria. CONCLUSION: Rhupus patients follow a particular clinical course, with full expression of both SLE and RA in terms of organ involvement, except for a lower prevalence of kidney affection. The new 2019 EULAR/ACR SLE criteria are not useful for differentiating SLE and rhupus patients. A new way of classifying autoimmune diseases is needed to identify overlapping clusters.

11.
Rheumatol Int ; 40(8): 1259-1265, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533289

RESUMO

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679-90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675-35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003-1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.

13.
Rheumatol Int ; 40(5): 719-726, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32157369

RESUMO

Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjögren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (- 3.8%, p = 0.095) and DLCO (- 8.4%, p = 0.004) was observed. After 2 years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1 year and + 15.3%, p = 0.001 at 2 years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases.

14.
Semin Arthritis Rheum ; 50(6): 1489-1493, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32165035

RESUMO

OBJECTIVE: To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc). METHODS: Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests. RESULTS: Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p<0.03 and p<0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p<0.05) and on morning stiffness at 6 and 12 months (p<0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p<0.05). No changes in lung or gastrointestinal involvement were found. CONCLUSIONS: ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32144182

RESUMO

OBJECTIVE: To describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients. METHODS: We reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo. RESULTS: All patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle. CONCLUSIONS: Patients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle.

17.
Front Immunol ; 11: 625896, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33613568

RESUMO

Objectives: Anti-TIF-1γ autoantibody detection is important for cancer screening in patients with dermatomyositis. The gold standard for anti-TIF-1γ detection, immunoprecipitation, is only available from a few specialized laboratories worldwide, so commercial ELISA/immunoblot tests have emerged in recent years. To analyze their usefulness in diagnosing cancer-associated dermatomyositis, we compared Euroimmun Euroline profile with our previously validated in-house immunoblot assay with human recombinant TIF-1γ. Methods: We included 308 adult patients from Hospital de la Santa Creu I Sant Pau and Vall Hebrón Hospital (Barcelona, Spain) tested for anti-TIF-1γ autoantibodies using the Euroline profile and an in-house immunoblot assay. Results: A total of 27 anti-TIF-1γ were detected by the Euroline and 12 by the in-house assay. Fair agreement was observed between Euroline and the in-house immunoblot Cohen's kappa 0.3163. Expected prevalence of anti-TIF-1γ autoantibodies was observed for the two methods for dermatomyositis and undifferentiated connective tissue diseases, but unexpectedly high prevalence of anti-TIF-1γ autoantibodies was detected by Euroline compared to the in-house immunoblot for other diseases (16.5% Euroline vs 0.8% in-house immunoblot, p<0.01). The in-house IB compared to Euroline more reliably detected cancer in patients with DM with anti-TIF-1γ antibodies (p=0.0014 vs p=0.0502 for in-house immunoblot vs Euroline). Conclusion: We recommend using a second validated method to confirm Euroline-detected anti-TIF-1γ antibodies when the dermatomyositis diagnosis is not definitive. Furthermore, in the context of definite DM diagnosis with negative anti-TIF-1γ antibodies by Euroline and no other myositis specific antibody, is also recommendable to confirm by a second validated method.

18.
Nat Commun ; 10(1): 4955, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672989

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.


Assuntos
Fibrose/genética , Escleroderma Sistêmico/genética , Doenças Vasculares/genética , Teorema de Bayes , Imunoprecipitação da Cromatina , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Conformação de Ácido Nucleico , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
19.
Rheumatol Int ; 39(11): 1875-1882, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522232

RESUMO

The objective of this study was to evaluate the impact of digital ulcers (DUs) in daily life of systemic sclerosis (SSc) Spanish patients. We developed a multicenter observational study to compare functional disability in SSc patients with active DUs vs. those without DUs. An additional correlation between perception of patients and physicians on disability due to DUs was performed. A total of 199 patients were enrolled, 70 (35%) with DUs. Patients with DUs were younger (48 vs. 58 years; p < 0.001) and had more frequently the diffuse subtype of SSc (45 vs. 24%; p = 0.004) than patients without DUs. Patients with DUs showed significantly higher scores in the Cochin Hand Function Scale overall (p < 0.002) and for each of its five dimensions. They also showed higher scores in the Systemic Sclerosis Health Assessment Questionnaire items related to hand function such as, dress and self-care (p < 0.013), eat (p < 0.013) and grip (p < 0.03), and higher Visual Analogic Scale scores for pain (p < 0.013), trouble related with Raynaud's Phenomenon (p < 0.001) and sense of severity (p < 0.004). Impact on daily activities was significantly higher in patients with DUs (p = 0.002), with a non-significant trend to experience higher impact on work productivity (p = 0.07). A high correlation was found between DUs patients and physicians opinion on the impact of DUs (daily life: Pearson R = 0.86; work productivity: Pearson R = 0.87). Study findings show an impaired hand function and increased disability for daily life activities and work productivity in SSc patients with DUs compared with patients without DUs in Spanish population.


Assuntos
Atividades Cotidianas , Eficiência , Doença de Raynaud/etiologia , Escleroderma Sistêmico/complicações , Úlcera Cutânea/etiologia , Local de Trabalho , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Avaliação da Deficiência , Feminino , Dedos/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto Jovem
20.
Ann Rheum Dis ; 78(7): 979-987, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30967395

RESUMO

OBJECTIVE: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. METHODS: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. RESULTS: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). CONCLUSION: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.


Assuntos
Antirreumáticos/uso terapêutico , Rituximab/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Idoso , Feminino , Fibrose , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/etiologia , Sistema de Registros , Testes de Função Respiratória , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Pele/patologia , Resultado do Tratamento , Capacidade Vital
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