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1.
Rheumatol Int ; 44(11): 2445-2455, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39180523

RESUMEN

INTRODUCTION:  Diffuse alveolar hemorrhage (DAH) is a rare complication with high mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and treatment are essential to improve patient prognosis. To determine the characteristics of patients with DAH and their mortality in a Spanish cohort of patients with SLE. METHODS:  Patients from the RELESSER (Spanish Society of Rheumatology Lupus Register) who had had at least one confirmed episode of DAH were included. Epidemiological, clinical, and laboratory characteristics were analyzed. RESULTS:  4024 patients were included in the RELESSER register, 37 (0.9%), had at least one recorded episode of DAH. Only further data for 14 patients could be analyzed. In total, 92.9% were women, and for 4 (28.6%) DAH coincided with the debut of SLE. More than 80% of patients had renal involvement and thrombocytopenia. The most frequent manifestations were dyspnea (85.7%) and hypoxemia (100%), with the classic triad of hemoptysis, anemia and pulmonary infiltrates, appearing in 6 (46.2%) patients. The most frequently used treatments were glucocorticoids (85.7%) and cyclophosphamide (69.2%); plasmapheresis was utilized in 5 patients (35.7%) and 8, (57.1%) received intravenous immunoglobulins; 12 (85.7%) patients required admission to the ICU and 5 (35.7%) died. Tobacco use, history of lupus nephritis (LN), concomitant infection, and treatment with cyclophosphamide were more frequent in patients who died. CONCLUSIONS:  DAH is rare in patients with SLE; in up to one-third of patients, it may appear at the onset of the disease. Some factors, such as smoking, a history of LN, treatment with cyclophosphamide, or concomitant infection, are more prevalent in patients with an unfavorable outcome.


Asunto(s)
Hemorragia , Enfermedades Pulmonares , Lupus Eritematoso Sistémico , Sistema de Registros , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Femenino , Adulto , España/epidemiología , Masculino , Hemorragia/epidemiología , Hemorragia/etiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/terapia , Persona de Mediana Edad , Alveolos Pulmonares/patología , Glucocorticoides/uso terapéutico , Ciclofosfamida/uso terapéutico , Adulto Joven , Inmunosupresores/uso terapéutico , Plasmaféresis
2.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39201334

RESUMEN

Recent studies point to intestinal permeability as an important factor in the establishment and development of rheumatoid arthritis (RA). Tight junctions (TJs) play a major role in intestinal homeostasis. The alteration of this homeostasis is related to RA. Furthermore, RA patients present dysbiosis and a lower microbiota diversity compared to healthy individuals. A cross-sectional study including RA patients and sex- and age-matched healthy controls was performed. The quantification of TJ proteins was carried out by ELISA. Gut microbiota was evaluated by NGS platform Ion Torrent S. The inflammatory variables included were DAS28, CRP, inflammatory cytokines (IL-6, IL-1, TNF-α) and oxidised LDL. Claudin-1 levels showed significant differences between groups. Results evidenced a correlation between claudin-1 values and age (r: -0.293; p < 0.05), IL6 (r: -0.290; p < 0.05) and CRP (r: -0.327; p < 0.05), and between zonulin values and both age (r: 0.267; p < 0.05) and TNFα (r: 0.266; p < 0.05). Moreover, claudin-1 and CRP levels are related in RA patients (ß: -0.619; p: 0.045), and in patients with high inflammatory activity, the abundance of the genus Veillonella is positively associated with claudin-1 levels (ß: 39.000; p: 0.004).


Asunto(s)
Artritis Reumatoide , Disbiosis , Microbioma Gastrointestinal , Inflamación , Humanos , Artritis Reumatoide/microbiología , Artritis Reumatoide/metabolismo , Disbiosis/microbiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Inflamación/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Adulto , Anciano , Claudina-1/metabolismo , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Citocinas/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Uniones Estrechas/metabolismo , Haptoglobinas , Precursores de Proteínas
3.
Int J Mol Sci ; 24(7)2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37047772

RESUMEN

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case-control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17-5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24-6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00-1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00-1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00-1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07-1.46]; p = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.


Asunto(s)
Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Interleucina-18 , Estudios de Casos y Controles , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Biomarcadores
4.
Rheumatology (Oxford) ; 61(6): 2596-2602, 2022 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-34508594

RESUMEN

OBJECTIVE: Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24. METHODS: The endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Least square (LS) mean change from baseline (95% CI) at week 24 for all endpoints was compared between the treatment arms for adjusted comparisons. RESULTS: This analysis included 184 patients on sarilumab monotherapy and 399 patients on sarilumab plus MTX. Differences (P < 0.05) were observed in ethnicity, region, body mass index group, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, swollen joint count, CRP, CDAI and oral glucocorticoid use between these treatment groups. After adjusting for these differences in a mixed-effect model repeated measure, LS mean change from baseline for all assessments was similar between the treatment groups with overlapping CIs: CDAI, -28.79 vs -26.21; DAS28-CRP, -2.95 vs -2.81; CRP, -18.31 vs -16.46; Hb, 6.59 vs 8.09; Pain VAS, -33.62 vs -31.66; FACIT-Fatigue, 9.90 vs 10.24. CONCLUSION: This analysis demonstrated that the efficacy of sarilumab monotherapy was similar to that of sarilumab and MTX combination therapy.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Anticuerpos Monoclonales Humanizados , Antirreumáticos/efectos adversos , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Quimioterapia Combinada , Fatiga/tratamiento farmacológico , Humanos , Metotrexato/efectos adversos , Dolor/tratamiento farmacológico , Resultado del Tratamiento
5.
Rheumatology (Oxford) ; 62(1): 217-224, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-35482477

RESUMEN

OBJECTIVES: To assess the characteristics and risk of lymphoma in a large cohort of patients with SLE. METHODS: A case-cohort analysis was performed within a dynamic cohort of SLE patients from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Clinical and analytical features were compared between the lymphoma SLE group and the control SLE group using an independent-sample Student's t-test or Mann-Whitney test for continuous variables and the χ2 test for categorical variables with Fisher's exact test if necessary. The multivariate analysis was based on a generalized linear model. RESULTS: Twenty-one patients with SLE and lymphoma and 3965 non-lymphoma controls with SLE were studied. Most lymphomas were of B cell origin (n = 15/21), with diffuse large B cell lymphoma being the most frequent histological type (8/21, 38.1%). As in the general population, the risk of lymphoma in SLE was higher in male than in female patients and increased with age. In the lymphoma SLE group, bivariate analysis showed a significantly higher percentage of pericarditis, organic brain syndrome, seizures, vasculitis, haemolytic anaemia, splenomegaly, venous thrombosis and mean modified (excluding lymphoma) SLICC/ACR damage index. In contrast, renal involvement, positive anti-dsDNA, and antimalarials ever were less frequent. CONCLUSIONS: In this large multicentre Spanish cohort, we identified characteristics of SLE that are associated with a higher risk of lymphoma. Antimalarials were significantly negatively associated with risk of lymphoma in SLE patients. Nevertheless, further prospective studies are needed to clarify these findings.


Asunto(s)
Antimaláricos , Lupus Eritematoso Sistémico , Linfoma de Células B Grandes Difuso , Humanos , Masculino , Femenino , Estudios de Cohortes , Antimaláricos/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Factores de Riesgo , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico
6.
Int J Mol Sci ; 23(21)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36361779

RESUMEN

This study aimed to evaluate the role of microRNAs (miRNA) as biomarkers of treatment response in rheumatoid arthritis (RA) patients through a systematic review of the literature. The MEDLINE and Embase databases were searched for studies including RA-diagnosed patients treated with disease-modifying antirheumatic drugs (DMARDs) that identify miRNAs as response predictors. Review inclusion criteria were met by 10 studies. The main outcome of the study was the response to treatment, defined according to EULAR criteria. A total of 839 RA patients and 67 healthy donors were included in the selected studies. RA patients presented seropositivity for the rheumatoid factor of 74.7% and anti-citrullinated C-peptide antibodies of 63.6%. After revision, 15 miRNAs were described as treatment response biomarkers for methotrexate, anti-tumour necrosis factor (TNF), and rituximab. Among treatments, methotrexate presented the highest number of predictor miRNAs: miR-16, miR-22, miR-132, miR-146a and miR-155. The most polyvalent miRNAs were miR-146a, predicting response to methotrexate and anti-TNF, and miR-125b, which predicts response to infliximab and rituximab. Our data support the role of miRNAs as biomarkers of treatment response in RA and point to DMARDs modifying the miRNAs expression. Nevertheless, further studies are needed since a meta-analysis that allows definitive conclusions is not possible due to the lack of studies in this field.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , MicroARNs , Humanos , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Biomarcadores , Epigénesis Genética , Metotrexato/uso terapéutico , MicroARNs/genética , MicroARNs/uso terapéutico , Rituximab/uso terapéutico , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/genética
7.
J Clin Rheumatol ; 28(1): e38-e43, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32956154

RESUMEN

OBJECTIVE: To describe the frequency of polyautoimmunity and multiple autoimmune syndrome in patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This was a cross-sectional observational study of patients with RA, SLE, and controls without autoimmune rheumatic disease. Cases were those with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism criteria, consecutively recruited in a rheumatology clinic. Controls were subjects with no rheumatic autoimmune disease (AIDs) recruited in the same area. Patients filled out a questionnaire on polyautoimmunity. Variables of interest were polyautoimmunity (RA or SLE with other AIDs), whereas secondary variables were rheumatic, skin, endocrine, digestive, and neurological AIDs. Multiple autoimmune syndrome is defined as the presence of 3 or more AIDs and a family history of AIDs. Statistical analyses performed were descriptive, bivariate, and multivariate (dependent variable: polyautoimmunity). RESULTS: The study population comprised 109 patients with RA, 105 patients with SLE, and 88 controls. Polyautoimmunity was recorded in 15 patients with RA (13.8%), 43 with SLE (41%), and 2 controls (2.2%). The most frequent AID in RA was Sjögren syndrome (53.3%), followed by Hashimoto thyroiditis and psoriasis; the most frequent AIDs in SLE were Sjögren syndrome (55.8%) and antiphospholipid syndrome (30.2%), followed by Hashimoto thyroiditis. Obesity was associated with polyautoimmunity in RA (odds ratio [OR], 3.362; p = 0.034). In SLE, joint damage (OR, 2.282; p = 0.038) and anti-RNP antibodies (OR, 5.095; p = 0.028) were risk factors for polyautoimmunity, and hydroxychloroquine was a protective factor (OR, 0.190; p = 0.004). CONCLUSIONS: Polyautoimmunity is frequent in RA and even more frequent in SLE. It was associated with obesity in RA and with joint damage and anti-RNP in SLE. Hydroxychloroquine was a protector.


Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Estudios Transversales , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología
8.
Rheumatology (Oxford) ; 60(4): 1793-1803, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33106841

RESUMEN

OBJECTIVE: The aim of the present study was to describe the demographic, clinical and immunological characteristics of patients with late-onset (≥50 years) SLE vs patients with early-onset SLE (<50 years). METHODS: We performed a cross-sectional retrospective study of 3619 patients from the RELESSER database (National Register of Patients with Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). RESULTS: A total of 565 patients (15.6%) were classified as late-onset SLE and 3054 (84.4%) as early-onset SLE. The male-to-female ratio was 5:1. Mean (s.d.) age at diagnosis in the late-onset group was 57.4 (10.4) years. At diagnosis, patients with late-onset SLE had more comorbid conditions than patients with early-onset SLE; the most frequent was cardiovascular disease (P <0.005). Furthermore, diagnostic delay was longer in patients with late-onset SLE [45.3 (3.1) vs 28.1 (1.0); P <0.001]. Almost all patients with late-onset SLE (98.7%) were Caucasian. Compared with early-onset SLE and after adjustment for time since diagnosis, patients with late-onset SLE more frequently had serositis, major depression, thrombotic events, cardiac involvement and positive lupus anticoagulant values. They were also less frequently prescribed immunosuppressive agents. Mortality was greater in late-onset SLE (14.3% vs 4.7%; P <0.001). CONCLUSION: Late-onset SLE is insidious, with unusual clinical manifestations that can lead to diagnostic errors. Clinical course is generally indolent. Compared with early-onset disease, activity is generally reduced and immunosuppressants are less commonly used. Long-term prospective studies are necessary to determine whether the causes of death are associated with clinical course or with age-associated comorbidities in this population.


Asunto(s)
Edad de Inicio , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Adulto , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Estudios Transversales , Diagnóstico Tardío , Depresión/epidemiología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Grupos Raciales , Sistema de Registros , Estudios Retrospectivos , Serositis/epidemiología , Distribución por Sexo , España/epidemiología , Trombosis/epidemiología
9.
Rheumatology (Oxford) ; 60(11): 5329-5336, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33950249

RESUMEN

OBJECTIVE: SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.


Asunto(s)
Enfermedades del Sistema Digestivo/etiología , Lupus Eritematoso Sistémico/complicaciones , Sistema de Registros , Adulto , Comorbilidad , Enfermedades del Sistema Digestivo/epidemiología , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España/epidemiología , Adulto Joven
10.
Int J Clin Pract ; 75(4): e13707, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32931643

RESUMEN

OBJECTIVE: To describe the incidence and fatality of coronavirus disease 2019 (COVID-19) and identify risk factors to fatality in patients with inflammatory articular diseases (IAD). METHODS: This is a cross-sectional observational study of IAD patients and COVID-19 with controls matched for age, sex, and RT-PCR. A control group was used to compare the cumulative incidence (CI) and case fatality rate (CFR). The main outcomes of the study were CI and CFR. Other variables included comorbidities, treatments, and characteristics of the COVID-19. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with IAD. RESULTS: Of the 1537 patients who fulfilled the inclusion criteria, 23/1537 (1.49%) had IAD 13 (0.8%) had rheumatoid arthritis (RA), 5 psoriatic arthritis (PsA) (0.3%) and 5 axial spondyloarthritis (0.3%). There were no significant differences in CI of COVID-19 and CFR in patients with IAD compared with COVID-19 patients without IAD. In RT-PCR positive patients, the CI of COVID-19 in PsA and AS was higher. Of the 23 IAD patients, 2 RA patients (8.6%) died. The patients did no show characteristics of the COVID-19 disease different from the population. In multivariate analysis, the factor associated with fatality in patients with IAD was older age (OR [95% CI], 1.1 [1.0-1.2]). CONCLUSION: COVID-19 CI, fatality rate and other features do not seem to be increased in IAD patients. Older age was associated with fatality in patients with IAD.


Asunto(s)
COVID-19 , Artropatías , Anciano , COVID-19/epidemiología , Estudios Transversales , Humanos , Incidencia , Artropatías/epidemiología , Factores de Riesgo , SARS-CoV-2
11.
BMC Musculoskelet Disord ; 22(1): 372, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33882889

RESUMEN

BACKGROUND: Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50-60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. METHODS: For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. RESULTS: The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). CONCLUSIONS: The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.


Asunto(s)
Artritis Reumatoide , Autoanticuerpos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Humanos , Péptidos Cíclicos , Estudios Prospectivos , Estudios Retrospectivos , Factor Reumatoide
12.
J Clin Nurs ; 30(1-2): 266-275, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33113279

RESUMEN

BACKGROUND: Studies in axial spondyloarthritis (AxSp) have shown that intensity of pain, anxiety, depression and inflammatory activity are associated with poor sleep quality. AIM: To describe mood and sleep disorders and positive psychological factors in patients with AxSp and psoriatic arthritis (PsA) and to evaluate the psychological factors that are potentially involved in sleep disorders. DESIGN: Multicenter cross-sectional observational study based on a series of patients with AxSp and PsA. PARTICIPANTS: Participants were selected consecutively from patients aged ≥18 years with AxSp or PsA followed at the rheumatology department of 4 Spanish hospitals. INCLUSION CRITERIA: age ≥18 years, AxSp (ASAS criteria) or PsA (CASPAR criteria), ability to understand the study and prepared to complete the questionnaires. METHODS: Main outcomes: Oviedo Sleep Quality questionnaire result. SECONDARY OUTCOMES: psychological status evaluated using the Hospital Anxiety and Depression Scale (HADS) questionnaire, health-related quality of life evaluated using SF-36, perception of pain evaluated using the short questionnaire for assessment of pain (BDU) and fatigue evaluated using the Fatigue Scale (FACIT) questionnaire. We performed a descriptive multivariate linear regression analysis to study factors that were independently associated with sleep disorders. The STROBE guidelines were adopted. RESULTS: We included 301 patients (152 [50.5%] with AxSp and 149 [49.5%] with PsA). The multivariate linear regression analysis for the whole sample showed that insomnia was inversely associated with emotional recovery and biologic disease-modifying antirheumatic drugs and directly associated with depression in both groups. The analysis by disease (AxSp and PsA) showed that insomnia was independently associated with depression and emotional recovery. CONCLUSIONS: Insomnia may be associated with other mood disorders, quality of life and inflammatory activity in the patients studied here. RELEVANCE TO CLINICAL PRACTICE: A nurse intervention can be carried out to prevent sleep disorders knowing the consequences and triggers of the problem.


Asunto(s)
Artritis Psoriásica , Trastornos del Sueño-Vigilia , Espondiloartritis , Adolescente , Adulto , Artritis Psoriásica/complicaciones , Artritis Psoriásica/epidemiología , Estudios Transversales , Humanos , Calidad de Vida , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/psicología , Espondiloartritis/complicaciones , Espondiloartritis/epidemiología
13.
Ann Rheum Dis ; 79(12): 1544-1549, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32796045

RESUMEN

OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Espondiloartropatías/tratamiento farmacológico , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Factores de Edad , Anciano , Alanina/análogos & derivados , Alanina/uso terapéutico , Artritis Psoriásica/complicaciones , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Betacoronavirus , COVID-19 , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Comorbilidad , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/epidemiología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Combinación de Medicamentos , Femenino , Glucocorticoides/uso terapéutico , Hospitalización , Humanos , Hidroxicloroquina/uso terapéutico , Modelos Logísticos , Lopinavir/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Polimialgia Reumática/complicaciones , Polimialgia Reumática/tratamiento farmacológico , Polimialgia Reumática/epidemiología , Pronóstico , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Factores de Riesgo , Ritonavir/uso terapéutico , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales
14.
Rheumatology (Oxford) ; 59(8): 2043-2051, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31808534

RESUMEN

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.


Asunto(s)
Antirreumáticos/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Autoinmunidad/efectos de los fármacos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Antirreumáticos/administración & dosificación , Enfermedades Autoinmunes/inmunología , Estudios Transversales , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Sistema de Registros , Adulto Joven
15.
Lupus ; 29(12): 1556-1565, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32807021

RESUMEN

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.


Asunto(s)
Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Adulto , Anticuerpos Antifosfolípidos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Análisis de Regresión , Estudios Retrospectivos , España/epidemiología
16.
Ann Rheum Dis ; 78(3)2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30552173

RESUMEN

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.


Asunto(s)
Artritis Psoriásica/genética , Glicosaminoglicanos/genética , N-Acetilglucosaminiltransferasas/genética , Psoriasis/genética , Transducción de Señal/genética , Adulto , Artritis Psoriásica/epidemiología , Artritis Reumatoide/epidemiología , Artritis Reumatoide/genética , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , América del Norte/epidemiología , Polimorfismo de Nucleótido Simple , Psoriasis/epidemiología , España/epidemiología
17.
Rheumatol Int ; 38(12): 2167-2182, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29808295

RESUMEN

OBJECTIVE: To establish feasible and practical recommendations for the management of the psychological needs of patients with rheumatoid arthritis (RA) from the moment of diagnosis through the course of the disease. METHODS: A nominal group meeting was held with an RA expert team including rheumatologists and psychologists, at which a guided discussion addressed the most important psychological and emotional needs in RA. Based on the comments collected, and a literature review, a matrix document of recommendations for telematics discussion was prepared, as well as a Delphi survey to test agreement with these recommendations. Agreement was defined if at least 80% of participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grading of recommendations was established following the Oxford criteria, and the degree of agreement through the Delphi. RESULTS: Thirteen recommendations were established, addressing several key processes: (1) identification of psychological problems and needs in patients with RA, and a guideline for their management in daily practice; (2) communication with patients; (3) referral criteria to mental health professionals. CONCLUSIONS: These recommendations are intended to help health care professionals openly address the psychological aspects of patients in daily practice to follow and treat them properly.


Asunto(s)
Adaptación Psicológica , Artritis Reumatoide/terapia , Costo de Enfermedad , Emociones , Servicios de Salud Mental/normas , Psiquiatría/normas , Psicología/normas , Reumatología/normas , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/fisiopatología , Artritis Reumatoide/psicología , Consenso , Técnica Delphi , Humanos , Comunicación Interdisciplinaria , Salud Mental , Grupo de Atención al Paciente , Reumatólogos/normas
18.
Rheumatol Int ; 37(10): 1709-1718, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28631046

RESUMEN

The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the discriminative ability of the Morisky-Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity [odds ratio (OR) 1.45; 95% CI, 1.03-2.03; p = 0.032] and subcutaneous route (OR 3.70; 95% CI 1.02-13.48; p = 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Cumplimiento de la Medicación , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
19.
BMC Med ; 14(1): 133, 2016 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-27609333

RESUMEN

BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. METHODS: Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls. RESULTS: In the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (P FDR < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (P FDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an over-representation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways. CONCLUSIONS: This study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs.


Asunto(s)
Enfermedades Autoinmunes/orina , Biomarcadores/orina , Inflamación/orina , Metaboloma , Artritis Reumatoide/metabolismo , Artritis Reumatoide/orina , Enfermedades Autoinmunes/complicaciones , Biomarcadores/metabolismo , Estudios de Casos y Controles , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/orina , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/orina , Humanos , Inflamación/etiología , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/orina , Espectroscopía de Resonancia Magnética , Metabolómica/métodos , Psoriasis/metabolismo , Psoriasis/orina
20.
Rheumatology (Oxford) ; 55(6): 1106-11, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26983453

RESUMEN

OBJECTIVE: RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. METHODS: A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. RESULTS: In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]. CONCLUSIONS: SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants.


Asunto(s)
Artritis Reumatoide/genética , Autoanticuerpos/sangre , Sitios Genéticos , Predisposición Genética a la Enfermedad , Intercambiador de Sodio-Calcio/genética , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Intercambiador de Sodio-Calcio/sangre , Población Blanca/genética
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