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Introduction: Data on prevalence of fatigue in rheumatoid arthritis (RA) patients in the era of biological treatments remains scarce, with a lack of case-control studies. This study evaluates the prevalence of fatigue in Spanish women over 50 years with RA using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, explores its association with RA-related variables, and seeks to identify the primary factors influencing fatigue. Ultimately, our objective is to underscore the clinical significance of fatigue as a comorbidity and to advocate for its systematic evaluation in routine clinical practice. Methods: In a case-control study at a tertiary university hospital, 191 women over 50 years (mean age: 67.5 ± 8.8 years) meeting ACR 2010 criteria for RA and age-matched controls were assessed using the FACIT-F scale, SF-12 questionnaire, and RA-related clinical measures. Results: Fatigue was significantly more prevalent in the RA group (61%) compared to controls (37%, p < 0.001), with RA patients showing lower mean FACIT-F scores (36.0 ± 10.6 vs. 40.0 ± 0.6, p < 0.001). Correlations were noted between FACIT-F scores and C-reactive protein, DAS28, RAPID3, HAQ, and SF-12 scores. A multivariate analysis was performed and four models generated. The final model, with an R2 of 0.817, indicates that fatigue is significantly influenced by disease activity (RAPID 3) and mental and physical health (SF12) and age, explaining 81.7% of the variance in fatigue. Conclusion: Fatigue remains significantly prevalent and severe in women over 50 years with RA, strongly linked to disease activity, disability, and diminished quality of life. Systematic fatigue assessment and targeted strategies in clinical settings are essential to address this widespread issue. Future research should explore targeted interventions tailored to this demographic to enhance quality of care.
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OBJECTIVE: To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort. METHODS: Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded. RESULTS: During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI. CONCLUSIONS: New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE.
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Sistema Cardiovascular , Lupus Eritematoso Sistémico , Sistema de Registros , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Estudios Longitudinales , Masculino , Femenino , Adulto , España/epidemiología , Persona de Mediana Edad , Sistema Cardiovascular/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Índice de Severidad de la Enfermedad , Progresión de la Enfermedad , ReumatologíaRESUMEN
OBJECTIVE: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD). METHODS: Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants. RESULTS: Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases. CONCLUSION: Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients.
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Enfermedades Pulmonares Intersticiales , Miositis , Rituximab , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Rituximab/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Miositis/tratamiento farmacológico , Miositis/complicaciones , Estudios Longitudinales , Adulto , Anciano , Resultado del Tratamiento , Progresión de la Enfermedad , Pruebas de Función Respiratoria/métodosRESUMEN
BACKGROUND: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature. METHODS: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted. RESULTS: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them. CONCLUSIONS: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).
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Arteritis de Células Gigantes , Inhibidores de las Cinasas Janus , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Azetidinas/uso terapéutico , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/sangre , Compuestos Heterocíclicos con 3 Anillos , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas/uso terapéutico , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Recurrencia , Estudios Retrospectivos , Sulfonamidas/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms. METHODS: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms. RESULTS: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up. CONCLUSION: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission.
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Introduction: The European Working Group on Sarcopenia in Older People (EWGSOP) has put forward two key proposals for diagnosing sarcopenia: the EWGSOP1 in 2010 and the EWGSOP2 in 2019. These proposals are currently the most widely used guidelines for diagnosing sarcopenia. However, data on the prevalence of sarcopenia in patients with rheumatoid arthritis (RA) based on EWGSOP criteria are limited. This study aimed to: (a) establish the prevalence of sarcopenia in an elderly Spanish cohort of women with RA using both EWGSOP1 and EWGSOP2 criteria; and (b) evaluate the effectiveness of the SARC-F questionnaire in detecting sarcopenia. Methods: In this observational, cross-sectional study, 67 women aged over 65 years who met the ACR 2010 criteria for RA were consecutively recruited from a tertiary university hospital. Assessments included: (a) demographic and anthropometric data; (b) RA-related variables (disease history, analytical evaluation, activity, disability, quality of life); and (c) sarcopenia-related variables (muscle strength, gait speed, skeletal muscle mass, and SARC-F questionnaire). The prevalence of sarcopenia was determined using both EWGSOP1 and EWGSOP2 criteria. Furthermore, the effectiveness of the SARC-F questionnaire for detecting sarcopenia were calculated. Results: The prevalence of sarcopenia was 43% according to the EWGSOP1 criteria and 16% according to the EWGSOP2 criteria. Patients diagnosed with sarcopenia based on the latter criteria also met the EWGSOP1's criteria for sarcopenia. Agreement between the two sets of EWGSOP criteria was poor. The SARC-F questionnaire demonstrated an inherently high sensitivity (100%) as well as good specificity (75%) and diagnostic accuracy (79%) in detecting sarcopenia according to EWGSOP2 criteria. Conclusions: The prevalence rate of sarcopenia among elderly Spanish women with RA varies significantly depending on whether EWGSOP1 or EWGSOP2 criteria are applied. The SARC-F questionnaire is effective for predicting sarcopenia when used in conjunction with the EWGSOP2 criteria, which is currently the most accepted standard in clinical practice.
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OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.
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Lupus Eritematoso Sistémico , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Lupus Eritematoso Sistémico/complicaciones , Estudios Prospectivos , Inmunosupresores , Modelos LogísticosRESUMEN
BACKGROUND: In 2017, belimumab (BEL) was approved in subcutaneous (SQ) administration. The effectiveness after switching from intravenous (IV) to SQ and patient satisfaction in daily clinical practice has not been studied. During the pandemic, patient follow-up and treatment were significantly affected, and some patients need a change from IV to SQ. Our aim was to evaluate daily clinical practice satisfaction to SQ BEL therapy in patients previously treated IV BEL. We hypothesized that SQ BEL in SLE patients previously treated with IV BEL was similar in effectiveness and conferred higher satisfaction. METHODS: Observational, multicenter study, conducted in 7 reference centers in Catalonia. We included stable SLE patients (EULAR/ACR 2019) on treatment with SQ BEL and previous use of IV BEL (at least 3 months on IV BEL before switching). Since there are no well-validated tools for SQ BEL treatment satisfaction, we used RASQ-SQ, validated in patients with lymphoma who switched from IV Rituximab to SQ treatment, and modified for BEL treatment. RESULTS: Twenty-seven patients were included. The more prevalent clinical manifestations observed were related to the skin and joints and the patients had a mean baseline SLEDAI of 2.96 (SD 2.4) and SLICC score of 0.67 (SD 0.88). The median time from treatment with IV BEL before switching to SQ was 21 months (range). 84% of patients reported confidence in SQ BEL. 85.2% felt that treatment with SQ BEL was convenient or very convenient. 85% felt they had gained time with the change. 89% would recommend the SQ injection to other patients. Disease activity (mean SLEDAI) and remission rates remain stable after switching. No major new adverse effects were reported. CONCLUSIONS: Overall satisfaction, satisfaction with via of administration, and satisfaction with the time taken to receive BEL were higher for SQ BEL treatment. A switching SQ strategy is a reasonable alternative for BEL patients.
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Anticuerpos Monoclonales Humanizados , Inmunosupresores , Lupus Eritematoso Sistémico , Humanos , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Lupus Eritematoso Sistémico/tratamiento farmacológico , Satisfacción PersonalRESUMEN
OBJECTIVE: This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season. METHODS: We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season. RESULTS: We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80-84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients. CONCLUSIONS: This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.
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Arteritis de Células Gigantes , Masculino , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Arteritis de Células Gigantes/diagnóstico , Incidencia , España/epidemiología , Biopsia , Estaciones del AñoRESUMEN
OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.
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INTRODUCTION: To reach the diagnosis of giant cell arteritis (GCA), signs, symptoms, laboratory tests, imaging findings, and occasionally anatomopathological results from temporal artery biopsy are evaluated. This study describes the results of an algorithm analysis based on clinical and ultrasound evaluation of patients with suspected GCA, highlighting its diagnostic utility by contrasting its use in different clinical suspicion scenarios. METHOD: Prospective multicenter study evaluating patients referred with suspected GCA through a preferential circuit (fast track), grouping them according to low or high clinical suspicion of GCA. Each of these scenarios is evaluated by biopsy and ultrasound for all patients, resulting in positive, indeterminate, or negative outcomes, yielding six possible groups. Potential areas of improvement are explored, emphasizing that, following a negative or indeterminate ultrasound, 18-FDG-PET-CT could be recommended. We analyze the results and application of a diagnostic algorithm, confirming its efficiency and applicability based on whether there is high or low clinical suspicion. RESULTS: Sixty-nine patients (41 in the high suspicion group and 28 in the low suspicion group). There were 41 new diagnoses of GCA: 35 in the high suspicion group and 6 in the low suspicion group. Using ultrasound alone, the initial algorithm has an overall diagnostic efficiency of 72.5%, which improves to 80.5% when including 18F-FDG-PET/CT. The negative predictive value of ultrasound in patients with low clinical suspicion is 84.6%, and the positive predictive value of ultrasound in patients with high suspicion is 100%, improving sensitivity from 57.1% to 80.8% with 18F-FDG-PET/CT in this scenario. Temporal artery biopsy was performed on all patients, with no differences in sensitivity or specificity compared to ultrasound. In cases where all three tests - ultrasound, biopsy, and 18F-FDG-PET/CT - are performed, sensitivity increases to 92.3% in patients with high clinical suspicion. CONCLUSION: In situations of high clinical suspicion, the algorithm provides sufficient information for the diagnosis of GCA if ultrasound is positive. A negative ultrasound is sufficient to rule out the diagnosis in the context of low clinical suspicion. 18-FDG-PET-CT may be useful in patients with high suspicion and negative or indeterminate ultrasound results.
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Algoritmos , Arteritis de Células Gigantes , Tomografía Computarizada por Tomografía de Emisión de Positrones , Ultrasonografía , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/diagnóstico por imagen , Humanos , Estudios Prospectivos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Biopsia , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Arterias Temporales/patología , Arterias Temporales/diagnóstico por imagen , Sensibilidad y Especificidad , RadiofármacosRESUMEN
OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.
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OBJECTIVE: To investigate the usefulness of 18F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB). METHODS: A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months. RESULTS: Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records. Of the 73 patients finally diagnosed with GCA, 18F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis. Overall, the diagnostic performance of 18F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA. CONCLUSION: Our study confirms the utility of 18F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.
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Arteritis de Células Gigantes , Humanos , Arteritis de Células Gigantes/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Arterias Temporales/diagnóstico por imagen , Arterias Temporales/patología , Estudios Retrospectivos , BiopsiaRESUMEN
ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.
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Glomerulonefritis por IGA , Vasculitis por IgA , Inmunidad Mucosa , Nefritis , Humanos , Antígeno CD11c , Frecuencia de los Genes , Genotipo , Glomerulonefritis por IGA/genética , Vasculitis por IgA/genética , Polimorfismo Genético , Inmunidad Mucosa/genéticaRESUMEN
Frogs evolved terrestrial development multiple times, necessitating mechanisms to avoid ammonia toxicity at early stages. Urea synthesis from ammonia is a key adaptation that reduces water dependence after metamorphosis. We tested for early expression and plasticity of enzymatic mechanisms of ammonia detoxification in three terrestrial-breeding frogs: foam-nest-dwelling larvae of Leptodactylus fragilis (Lf) and arboreal embryos of Hyalinobatrachium fleischmanni (Hf) and Agalychnis callidryas (Ac). Activity of two ornithine-urea cycle (OUC) enzymes, arginase and CPSase, and levels of their products urea and CP in tissues were high in Lf regardless of nest hydration, but reduced in experimental low- vs. high-ammonia environments. High OUC activity in wet and dry nests, comparable to that under experimental high ammonia, suggests terrestrial Lf larvae maintain high capacity for urea excretion regardless of their immediate risk of ammonia toxicity. This may aid survival through unpredictably long waiting periods before rain enables their transition to water. Moderate levels of urea and CP were present in Hf and Ac tissues and enzymatic activities were lower than in Lf. In both species, embryos in drying clutches can hatch and enter the water early, behaviorally avoiding ammonia toxicity. Moreover, glutamine synthetase was active in early stages of all three species, condensing ammonia and glutamate to glutamine as another mechanism of detoxification. Enzyme activity appeared highest in Lf, although substrate and product levels were higher in Ac and Lf. Our results reveal that multiple biochemical mechanisms of ammonia detoxification occur in early life stages of anuran lineages that evolved terrestrial development.
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Amoníaco , Glutamato-Amoníaco Ligasa , Animales , Amoníaco/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Larva/metabolismo , Urea/metabolismo , Agua/metabolismo , Anuros/metabolismo , Hígado/metabolismoRESUMEN
BACKGROUND: To examine the performance of the new 2022 American College of Rheumatology (ACR)/EULAR classification criteria for giant cell arteritis (GCA) in routine clinical care, compared with the 1990 ACR GCA classification criteria. METHODS: The fulfilment of 2022 ACR/EULAR and 1990 ACR criteria was tested in our real-life cohort of GCA patients with proven vasculitis by temporal artery biopsy or imaging (a necessary pre-requisite to apply the new criteria is the presence of a confirmed diagnosis of medium- or large-vessel vasculitis). The performance of classification criteria was evaluated in all patients with GCA across different subsets of the disease. Patients with GCA were compared with unselected controls with suspected GCA. RESULTS: A total of 136 patients with proven GCA were identified. The new criteria had a sensitivity of 92.6% and a specificity of 85.2%. According to the clinical phenotypes, the sensitivity was 98.8% in cranial GCA, 92% in extracranial large vessel (LV) GCA and 75% in occult systemic GCA. These data are much better than those observed with the 1990 ACR classification criteria, which showed a sensitivity of 66.1% and a specificity of 85.1% for the total sample, with a sensitivity of 89.1% in cranial GCA, 24% in extracranial LV-GCA and 35.7% in occult systemic GCA. Ten (7.4%) patients in our cohort did not fulfil either of the criteria sets (8 with occult systemic GCA and 2 with extracranial LV-GCA). The sensitivity of the new criteria in patients with occult systemic and extracranial LV-GCA could be greatly improved assigning more weight (3 points) to some imaging findings (axillary involvement and FDG-PET activity throughout the aorta). CONCLUSION: Our study confirms that the new classification criteria are more sensitive in real-life settings than the old ACR criteria across all clinical phenotypes.
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Arteritis de Células Gigantes , Reumatología , Humanos , Estados Unidos , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/patología , Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.
Asunto(s)
Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Complicaciones del Embarazo , Nacimiento Prematuro , Reumatología , Embarazo , Humanos , Recién Nacido , Femenino , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/epidemiología , Síndrome Antifosfolípido/complicaciones , Complicaciones del Embarazo/epidemiología , Estudios Retrospectivos , beta 2 Glicoproteína I , Anticoagulantes , Inmunoglobulina G , Inmunoglobulina MRESUMEN
BACKGROUND: We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States. METHODS: We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs). RESULTS: Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0-1-month-old children was 2.55 per 100,00 pop., whereas for 2-11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0-59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4-21) and 19% (95% CI: 0-33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4-35) for all-cause pneumonia mortality and 22% (95% CI: -19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6-11-month-old infants. CONCLUSIONS: The universal introduction of PCV7, and later PCV13, for children 0-59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia.