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BACKGROUND: The close relationship between joints and gut inflammation has long been known and several data suggest that dysbiosis could link spondyloarthritis (SpA) to inflammatory bowel diseases (IBD). The introduction of biological drugs, in particular tumour necrosis factor inhibitors (TNFi), revolutionised the management of both these diseases. While the impact of conventional drugs on gut microbiota is well known, poor data are available about TNFi. AIM: To investigate the impact of TNFi on gut microbiota. METHODS: We evaluated 20 patients affected by enteropathic arthritis, naïve for biological drugs, treated with TNFi at baseline and after 6 months of therapy. All patients followed a Mediterranean diet. Patients performed self-sampling of a faecal sample at baseline and after 6 months of therapy. NGS-based ITS and 16S rRNA gene sequencing was performed, followed by the taxonomic bioinformatics analysis. RESULTS: After 6 months of therapy, we detected a remarkable increase in Lachnospiraceae family (Δ +10.3, p=0.04) and Coprococcus genus (Δ +2.8, p=0.003). We also noted a decreasing trend in Proteobacteria (Δ -8.0, p=0.095) and Gammaproteobacteria (Δ -9, p=0.093) and an increasing trend in Clostridia (Δ +8.2, p=0.083). We did not find differences between TNFi responders (SpA improvement or IBD remission achieved) and non-responders in terms of alpha and beta diversity. CONCLUSIONS: Our findings are consistent with the hypothesis that TNFi therapy tends to restore the intestinal eubiosis.
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Espondilartrite , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , RNA Ribossômico 16S/genética , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVES: Hepatitis B (HBV) is a common comorbidity among rheumatic patients. The prevalence of HBV infection and the rate of reactivation remain unclear. The literature data suggested a higher risk in chronic than in past infection. Currently, the literature data are mostly focused on anti-TNF and rituximab. This retrospective observational study aimed to analyse the prevalence of HBV infection and the risk of viral reactivation in a population of rheumatic patients undergoing anti-TNF and non-anti-TNF agents. METHODS: We analysed 1216 rheumatic patients, treated with both csDMARDs and bDMARDs between 2006 and 2017. Serologic markers for HBV (HBsAg, anti-HBs, anti-HBc) were performed prior and during biologic treatment. Patients with chronic or resolved infection were monitored every 3 months. RESULTS: The prevalence of HBV in our cohort was 15.7% (chronic infection: 0.4%, resolved infection: 12.6%, anti-HBc positivity alone: 2.6%). 12 (6.2%) out of 191 HBV infected patients experienced a reactivation. All of them showed markers of past infection. One patient experienced HBV reactivation despite lamivudine. Only one patient experienced acute hepatitis, probably due to the interruption of immunosuppressors in anticipation of surgery, not preceded by any HBV prophylactic treatment. CONCLUSIONS: HBV reactivation is a rare event in patients treated with a bDMARD and it can also occur while taking lamivudine, not only in chronic carriers (as per the literature data) but also in inactive ones. Regular screening followed by prompt treatment can prevent symptoms or complications. Due to the risk of hepatitis following the immune reconstitution, an antiviral therapy should be considered in the case of sudden discontinuation of csDMARDs or bDMARD.
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Antivirais/uso terapêutico , Artrite Reumatoide/imunologia , Vírus da Hepatite B , Hepatite B , Inibidores do Fator de Necrose Tumoral , Ativação Viral , Artrite Reumatoide/terapia , Terapia Biológica , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/farmacologia , Anticorpos Anti-Hepatite B/uso terapêutico , Antígenos de Superfície da Hepatite B , Humanos , Prevalência , Inibidores do Fator de Necrose Tumoral/imunologia , Inibidores do Fator de Necrose Tumoral/uso terapêuticoAssuntos
Doenças Autoimunes/tratamento farmacológico , Infecções por Coronavirus/complicações , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pneumonia Viral/complicações , Doenças Reumáticas/tratamento farmacológico , Antirreumáticos/uso terapêutico , Doenças Autoimunes/complicações , Betacoronavirus , COVID-19 , Humanos , Doenças Inflamatórias Intestinais/complicações , Pandemias , Fatores de Risco , SARS-CoV-2RESUMO
BACKGROUND: The aim of our study was to evaluate the serum concentration of klotho in a cohort of systemic sclerosis (SSc) patients compared to that of healthy controls and to correlate its levels with the degree and the kind of organ involvement. METHODS: Blood samples obtained from both patients and controls were collected and analysed by an ELISA test for the determination of human soluble klotho. Scleroderma patients were evaluated for disease activity through clinical, laboratory, and instrumental assessment. RESULTS: Our cohort consisted of 81 SSc patients (74 females, mean age 63.9 ± 13.1 years) and 136 healthy controls (78 females, mean age 50.5 ± 10.7 years). When matched for age, serum klotho concentration significantly differed between controls and patients (p < 0.001). However, in SSc patients, we did not find any significant association between serum klotho and clinical, laboratory, and instrumental findings. Lower serum levels of klotho were detected in 4 patients who were anticitrullinated peptide antibody (ACPA) positive (p = 0.005). CONCLUSIONS: Our data show a lower concentration of klotho in the serum of SSc patients compared to that of healthy controls, without any significant association with clinical manifestations and laboratory and instrumental findings. The association between serum klotho and ACPA positivity requires further investigation.
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Glucuronidase/sangue , Escleroderma Sistêmico/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To identify factors indicating exercise-induced oxygen desaturation during the 6-minute walk test (6MWT) in patients with diffuse systemic sclerosis (SSc) and initial interstitial lung disease (ILD). METHODS: The study involved 121 consecutive adult anti-Scl 70 autoantibody-positive SSc patients with initial ILD, 93 of whom were followed up for five years. Before enrolment and then annually, the patients underwent high-resolution computed tomography (HRCT), functional lung tests, with carbon monoxide diffusion capacity of the lung (DLCO) and its components (alveolar-capillary membrane [Dm] and pulmonary blood volume [Vc]), the evaluation of dyspnea before and after the 6MWT using the Borg scale, and transthoracic echocardiography. A decrease in peripheral capillary oxygen saturation (SpO2) of ≥4% during the 6MWT was used to define desaturation, the appearance of which led to the patient being withdrawn from follow-up. RESULTS: There were no significant differences in HRCT score during the follow-up, but 32 patients (35%) desaturated during the 6MWT, including 12 (37%) who experienced a severe decrease SpO2 to ≤88%, indicating a high risk of mortality. At baseline, there was no statistically significant difference in any considered clinical characteristics between the desaturating and non-desaturating patients but, at the time of desaturation, the desaturators had lower minimum SpO2% levels during the 6MWT (p<0.0001), and lower DLCO (p<0.0001) and Dm (p<0.0001). Comparison of the desaturators defined on the basis of a reduction in SpO2 to ≤88% and those defined on the basis of a decrease in SpO2 of ≥4% showed that, at baseline, the former had lower minimum SpO2% levels during 6MWT (p<0.001), lower DLCO (p=0.01), a lower DLCO/VA ratio (p=0.05), lower Dm (p<0.005) and Vc values (p<0.5), and higher RVsystP (p=0.01). At the time of desaturation, the desaturators' minimum SpO2 levels during the 6MWT correlated with their DLCO (r=0.78; p<0.001), Dm (r=0.65; p<0.01), Vc (r=0.52;p<0.05) and RV-systP values (r = -0.53; p<0.05). CONCLUSIONS: Our data seem to confirm the close interdependence between pulmonary diffusion and oxygen desaturation during exercise. In SSc combined 6MWT, DLCO and its components may indicate patients at increased risk of developing pulmonary hypertension.
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Dispneia/diagnóstico , Teste de Esforço/métodos , Tolerância ao Exercício , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/fisiopatologia , Esclerodermia Difusa/complicações , Caminhada , Idoso , Biomarcadores/sangue , Monóxido de Carbono/sangue , Dispneia/sangue , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Valor Preditivo dos Testes , Capacidade de Difusão Pulmonar , Testes de Função Respiratória , Fatores de Risco , Esclerodermia Difusa/diagnóstico , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Interstitial lung disease (ILD) is a frequent extra-articular manifestation of RA associated with increased mortality. High-resolution CT (HRCT) is used for diagnosis and follow-up, but its accuracy is counterbalanced by high costs and radiological risk. In the presence of ILD, lung US (LUS) detects vertical artefacts called B-lines. The aims of the present study were to evaluate the accuracy of LUS in the diagnosis of ILD in RA and to validate the use of a pocket-size US device (PS-USD) as a screening tool. METHODS: LUS was performed with standard equipment by a trained physician through longitudinal scans following anatomical lines: 72 segments were considered (28 anteriorly and 44 posteriorly) and B-lines were counted in each segment. A B-lines score >10 identified a positive examination (presence of ILD). A second LUS session for positive/negative judgment was performed by a short-trained physician using a PS-USD. RESULTS: Thirty-nine patients were studied. The sensitivity and specificity of standard LUS vs HRCT were 92% and 56%, respectively. The B-line score was significantly correlated with HRCT score (r = 0.806). A total of 29 patients were studied with a PS-USD. Sensitivity and specificity for PS-USD vs HRCT were 89% and 50%. CONCLUSION: The sensitivity of LUS in the detection of ILD supports its use as a screening test for ILD in RA patients, even in the ambulatory setting with a PS-USD. The strong correlation between echographic and HRCT scores indicates LUS is a valid tool for grading and follow-up of ILD.
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Artrite Reumatoide/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Idoso , Artrite Reumatoide/complicações , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , UltrassonografiaRESUMO
Musculoskeletal symptoms (articular, periarticular and muscular involvement, osteoporosis and related fractures, and fibromyalgia) are the most common frequent extra-intestinal manifestations of inflammatory bowel disease (IBD) and affect 6-46% of patients. IBD-related arthropathy is one of a group of inflammatory arthritides known as seronegative spondyloarthropathies (SpA), which also includes idiopathic ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, and undifferentiated SpA. The articular involvement in IBD significantly affects the patients' quality of the life. Although magnetic resonance imaging (MRI) is still the gold standard for assessing entheseal involvement, ultrasonography (US) is a non-invasive and easily reproducible means of detecting early pathological changes in SpA patients. It can identify characteristic features of SpA such as enthesitis, bone erosions, synovitis, bursitis, and tenosynovitis and is therefore helpful for diagnostic purposes. Anti-TNF drugs should be used to treat AS patients with axial and peripheral symptoms (arthritis and enthesitis) who have persistently high levels of disease activity despite conventional treatment, and adalimumab and infliximab can also be beneficially used in patients with IBD.
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Artrite Reumatoide/imunologia , Doenças Inflamatórias Intestinais/imunologia , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/etiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espondiloartropatias , Sinovite/imunologiaRESUMO
Advances in our understanding of the key mediators of chronic inflammation and tissue damage in rheumatoid arthritis (RA) have fostered the development of targeted therapies and greatly expanded the available treatment options. Abatacept, a soluble human fusion protein that selectively modulates the co-stimulatory signal required for full T-cell activation, is approved for the treatment of moderate to severe RA in the United States, Canada, and the European Union. This review summarises the data on efficacy (disease activity, quality of life, prevention of structural damage) and safety from randomised clinical trials of abatacept plus methotrexate in patients with: i) active RA and an inadequate response to methotrexate who are naïve to biological disease-modifying anti-rheumatic drugs; and ii) methotrexate-naïve early RA with poor prognostic factors. Novel imaging outcomes and biological changes induced by abatacept treatment are also briefly reviewed. Optimal use of abatacept as a first-line biological therapy is discussed in light of the current recommendations and guidelines.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Ativação Linfocitária , Linfócitos T/imunologia , Animais , Antirreumáticos/imunologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Ensaios Clínicos como Assunto , Humanos , Ativação Linfocitária/imunologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.autrev.2013.06.008. The duplicate article has therefore been withdrawn.
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Capilares/patologia , Angioscopia Microscópica , Unhas/irrigação sanguínea , Escleroderma Sistêmico/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Pé , Mãos , Humanos , Itália , Masculino , Angioscopia Microscópica/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravação em Vídeo , Adulto JovemAssuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Adulto , Idoso , Ciclosporina/uso terapêutico , Quimioterapia Combinada/métodos , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Receptores do Fator de Necrose Tumoral/uso terapêutico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The diagnosis of bacterial endocarditis remains a challenge, as nearly half of cases develop in the absence of preexistent heart disease and known risk factors. Not infrequently, a blunted clinical course at onset can lead to erroneous diagnoses. We present the case of a 47-year-old previously healthy man in which a presumptive diagnosis of antiphospholipid syndrome was made based on the absence of echocardiographically detected heart involvement, a negative blood culture, normal C-reactive protein (CRP) levels, a positive lupus anticoagulant (LAC) test, and evidence of splenic infarcts. The patient eventually developed massive aortic endocarditic involvement, with blood cultures positive for Streptococcus bovis, and was referred for valvular replacement. This case not only reminds us of the diagnostic challenges of bacterial endocarditis, but also underlines the need for a critical application of antiphospholipid syndrome diagnostic criteria.
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OBJECTIVE: To identify the determinants of anti-TNF-naive patients' preferences for the route of administration of anti-TNF agents. METHODS: The study was carried out in 50 Italian rheumatology centres (802 patients). All patients completed a 31-item questionnaire addressing their perceptions of current treatment and the preferences for treatment with anti-TNF agents. Statistical methods included analysis of variance (ANOVA), t-test and chi-square test. RESULTS: The response rate to the questionnaire was 97.6%. At the time of the survey, 310 (39.9%) patients were dissatisfied with current treatments, owing to inefficacy, side effects and inconvenience of administration. The i.v. and s.c. routes of administration were preferred by 50.2 and 49.8%, respectively. No significant difference was found in patients by gender, age, RA duration or number of drugs used. Reasons for the choice of i.v. administration were the safety of treatment at the hospital and the reassuring effect of physician presence. The s.c. administration was chosen for the convenience of treatment and in particular for home treatment. Patients dissatisfied with current therapy due to side effects preferred s.c. administration (P = 0.029), whereas patients choosing the i.v. route had slightly higher scores on 'today pain' (P = 0.047) and 'articular pain' (P = 0.023) of the Rheumatoid Arthritis Disease Activity Index (RADAI). CONCLUSIONS: Both i.v. and s.c. treatments were well accepted by patients. However, treatment choice has to be discussed with patients, as individual preference seems to be determined by personal attitudes towards safety and convenience, by past experience and by the perception of current disease status.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Preferência do Paciente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/psicologia , Comportamento de Escolha , Métodos Epidemiológicos , Feminino , Humanos , Infusões Intravenosas , Infusões Subcutâneas , Itália , Masculino , Pessoa de Meia-Idade , Autoadministração , Adulto JovemRESUMO
Inflammatory bowel diseases (IBDs), particularly Crohn's disease (CD) and ulcerative colitis (UC), are associated with a variety of extra-intestinal manifestations (EIMs). About 36% of IBD patients have at least one EIM, which most frequently affect the joints, skin, eyes and the biliary tract. The EIMs associated with IBD have a negative impact on patients with UC and CD, and the resolution of most of them parallels that of the active IBD in terms of timing and required therapy; however, the clinical course of EIMs such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis is independent of IBD activity. The peripheral and axial arthritis associated with IBD have traditionally been treated with simple analgesics, non-steroidal anti-inflammatory drugs, steroids, sulfasalazine, methotrexate, local steroid injections and physiotherapy, but the introduction of biological response modifiers such as tumor necrosis factor-alpha blockers, has led to further improvements.
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Artrite , Doenças Inflamatórias Intestinais , Artrite/tratamento farmacológico , Artrite/imunologia , Artrite/patologia , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: To identify the clinical factors predicting failure or a good clinical response in the cohort of RA patients entered in the Lombardy Rheumatology Network (LORHEN) registry after 3 years of treatment with anti-TNF agents. METHODS: We studied the patients who had received anti-TNF agents and been followed up for a minimum of 6 months. Disease activity at baseline and after 6 months was assessed using the DAS28, and response was evaluated according to the EULAR improvement criteria. RESULTS: 1005 patients (55.72 years) were included in the analysis. at baseline the DAS-28 was 5.91+/-0.95 and a HAQ score was 1.46+/-0.61. At mean of 14.57 months, 29.9% of the patients achieved a DAS-28 of