Analysis of two autoimmunity genes, IRAK1 and MECP2, in giant cell arteritis.

OBJECTIVES: The Xq28 region, containing IRAK and MECP2, represent a common susceptibility locus for a high number of autoimmune diseases. Our aim in the present study was to evaluate the influence of the IRAK1 and MECP2 autoimmunity-associated genetic variants in the giant cell arteritis (GCA) susceptibility and its clinical subphenotypes. METHODS: We analysed a total of 627 female biopsy-proven GCA patients and 1,520 female healthy controls of Spanish Caucasian origin. Two polymorphisms, rs1059702 and rs17345, located at IRAK1 and MECP2, respectively, were genotyped using TaqMan® allelic discrimination assays. RESULTS: No association with any of the analysed polymorphisms was evident when genotype and allele frequencies were compared between GCA patients and controls (rs1059702: allelic p-value=0.699, OR=0.96, CI 95% 0.80-1.17; rs17435: allelic p-value=0.994, OR=1.00, CI 95% 0.84-1.19). Likewise, the subphenotype analysis yield similar negative results. CONCLUSIONS: We have assessed for the first time the possible role of IRAK1 and MECP2 autoimmune disease-associated polymorphisms in GCA. Our data suggest that IRAK1 rs1059702 and MECP2 rs17435 genetic variants do not play a significant role in GCA susceptibility or severity.

Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Autoimmune disease-associated CD226 gene variants are not involved in giant cell arteritis susceptibility in the Spanish population.

OBJECTIVES: CD226 genetic variants have been associated with a number of autoimmune diseases. The aim of this study was to investigate the potential implication of the CD226 loci in the susceptibility to and main clinical manifestations of giant cell arteritis (GCA). METHODS: A Spanish Caucasian cohort of 455 patients diagnosed with biopsy-proven GCA and 1414 healthy controls were included in the study. Three CD226 polymorphisms, rs727088, rs34794968 and rs763361, were genotyped using the TaqMan® allelic discrimination technology. PLINK software was used for the statistical analyses. RESULTS: No significant association between the CD226 polymorphisms and susceptibility to GCA was found (rs727088: p=0.92, OR=1.01, CI 95% 0.86-1.18; rs34794968: p=0.61, OR=1.04, CI 95% 0.89-1.22; rs763361: p=0.88, OR=0.99, CI 95% 0.84-1.16). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no association was observed either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. Furthermore, the haplotype analysis revealed no significant association with the clinical manifestations of the disease. CONCLUSIONS: Our results show that the three CD226 polymorphisms analysed do not play a relevant role in the susceptibility to GCA and clinical manifestations of this vasculitis.

Efficacy and Safety of Rituximab in Autoimmune Disease-Associated Interstitial Lung Disease: A Prospective Cohort Study.

OBJECTIVES: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). METHODS: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC) > 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) > 15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening ILD. RESULTS: We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7-69.0) months. At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in seven (18.9%); seven patients (18.9%) died. No significant decline was observed in median FVC (72.2 vs. 70.8; p = 0.530) or DLCO (55.9 vs. 52.2; p = 0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR (95% CI), 0.904 (0.8-0.9); p = 0.015), time to initiation of RTX (1.01 (1.001-1.02); p = 0.029), and mycophenolate (0.202 (0.04-0.8); p = 0.034). Only 28 of the 37 patients (75.6%) were still undergoing treatment with RTX: two patients (5.4%) stopped treatment due to adverse events and seven patients (18.9%) died owing to progression of ILD and superinfection. CONCLUSION: Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD.

Importance of Vaccination against SARS-CoV-2 in Patients with Interstitial Lung Disease Associated with Systemic Autoimmune Disease.

Objectives: To describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19. Methods: We performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with "COVID-19" and "severe COVID-19". Results: We included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946−0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030−0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129−6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004−0.170); p < 0.001) and diabetes mellitus (OR (95% CI), 4.923 (1.508−19.097); p = 0.018). Conclusions: Around 13% of patients with ILD-SAD had SARS-CoV-2 infection, which was severe in approximately one-third. Most patients with severe infection were not fully vaccinated.

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. RESULTS: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2-42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03-3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70-0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72-0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. CONCLUSION: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study.

OBJECTIVES: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. PATIENTS AND METHODS: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. RESULTS: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8-93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3-2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0-2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4-3.9]), and smoking (HR, 2.7 [95%CI, 1.6-4.7]). CONCLUSION: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.

Neurosarcoidosis: Analysis of a series of 20 patients. / Neurosarcoidosis: análisis de una serie de 20 pacientes.

INTRODUCTION: Neurosarcoidosis is a rare complication of sarcoidosis. There are small series on the condition and very few from Spain. We conducted a retrospective study of neurosarcoidosis in Virgen de la Victoria Hospital over the last 10 years. PATIENTS AND METHOD: the medical records of patients diagnosed with sarcoidosis in our setting in the last 10 years were reviewed. RESULTS: One hundred twenty patients with sarcoidosis, 20 patients with probable neurosarcoidosis: 30% at the beginning of the illness, 55% later, 15% had isolated neurosarcoidosis. Forty percent had polyneuropathy, 15% cranial neuropathy, 15% myopathy, 10% hemispheric symptoms. OTHERS: headache, myelitis, seizures, confusional syndrome. They were treated with steroids, some of them with immunosuppressive treatment. Seventy-two percent improved or were stabilized. Therefore, neurosarcoidosis prevalence in our hospital was 11%, similar to other published series, with similar features, but polyneuropathy was more frequent. Early diagnosis is very important as prognosis is favourable with treatment.

Incidence of cancer in a cohort of Spanish patients with systemic lupus erythematosus.

OBJECTIVE: To determine the incidence and prevalence of cancer in a cohort of patients with systemic lupus erythematosus (SLE) and identify associated risk factors. PATIENTS AND METHODS: The study comprised a dynamic cohort of SLE patients (November 1989 to December 2006) at a tertiary referral centre. An adjusted external control from the hospital tumour registry was used. RESULTS: The study included 175 SLE patients (90% women), with a mean time at risk of 1370.5 patient-years. Fourteen women (8%) died, mainly from cardiovascular events. No patient died due to malignancy. We found 35 tumours in 28 patients, 25 of them after the diagnosis of SLE, of which 5 were malignant. The rate of benign tumours was 14.6/1000 patient-years (95% CI, 8.9-22.5) and of malignant tumours 3.6/1000 patient-years (95% CI, 1.5-8.8), with a crude incidence odds ratio for malignant tumours of 3.5 (95% CI, 1.5-7.9). However, this significance was lost after standardizing the rates. Concerning associated risk factors, differences were found in the mean erythrocyte sedimentation rate [HR 1.4 (1.1-1.7)], and the presence of thrombosis [HR 6.9 (1.49-41.2)], especially arterial thrombosis. CONCLUSIONS: We found a crude incidence rate of cancer that was almost four times greater in our SLE patients as compared with the expected rate in the hospital area of western Malaga.

Atypical Vascular Involvement in a Case of Behçet's Disease.

Introduction. Behçet's disease (BD) is a form of vasculitis of unknown etiology which is rare in our environment. It is characterized by a variety of clinical manifestations and usually affects young adults. Recurrent oral and genital ulcers are a characteristic and extremely frequent symptom, but mortality is linked with more significant symptoms such as aortic pseudoaneurysm, pulmonary pseudoaneurysm, and cerebral venous thrombosis. Patient and Method. We present a case of a young male with atypical BD and severe polyvascular involvement (previous cerebral venous thrombosis and current peripheral venous thrombosis, acute ischemia, and peripheral arterial pseudoaneurysm) who required urgent surgical intervention due to a symptomatic external iliac pseudoaneurysm. Result. The pseudoaneurysm was successfully treated, we performed an iliofemoral bypass, and we treated it with steroids and immunosuppressive therapy. Conclusions. These rare clinical manifestations highlight the importance of considering BD in young patients, even in usual cases of vascular intervention, whether arterial or venous in nature.

A nonsynonymous functional variant of the ITGAM gene is not involved in biopsy-proven giant cell arteritis.

OBJECTIVE: To investigate whether a functional integrin alpha M (ITGAM) variant is involved in susceptibility to and clinical manifestations of giant cell arteritis (GCA). METHODS: A Spanish cohort of 437 white patients with biopsy-proven GCA and 1388 healthy controls were genotyped using the TaqMan allele discrimination technology. RESULTS: No association was observed between ITGAM rs1143679 and GCA (p = 0.80, OR 0.97). Similarly, subphenotype analyses did not yield significant differences between the case subgroups and the control set or between GCA patients with or without the main specific features of GCA. CONCLUSION: Our results suggest that the ITGAM rs1143679 variant does not play an important role in the pathophysiology of GCA.

Neurosarcoidosis: análisis de una serie de 20 pacientes / Neurosarcoidosis: Analysis of a series of 20 patients

INTRODUCCIÓN: La neurosarcoidosis es una rara complicación de la sarcoidosis. Existen series cortas de pacientes con esta afectación. En España son prácticamente inexistentes. Planteamos realizar un estudio retrospectivo sobre neurosarcoidosis en el Hospital Virgen de la Victoria a lo largo de 10 años. PACIENTES Y MÉTODOS: Búsqueda en la base de datos hospitalaria de los pacientes con este diagnóstico en los últimos 10 años. RESULTADOS: Ciento veinte pacientes con sarcoidosis, de los cuales 20 pacientes compatibles con neurosarcoidosis probable: el 30% fue inicio de la enfermedad, el 55% ya estaban diagnosticados de sarcoidosis y el 15% tuvieron neurosarcoidosis aislada. El 40% presentaron polineuropatía, el 15% neuropatía craneal, el 15% miopatía y el 10% focalidad del sistema nervioso central. Otros: Cefalea, mielitis, crisis epiléptica y cuadro confusional. Se trataron con esteroides, y a veces se asociaron otros inmunosupresores. El 72% de los casos se estabilizaron o hubo mejoría. Por tanto, la prevalencia de neurosarcoidosis en nuestro hospital es del 11%, parecido a otras series publicadas, con características similares, pero con mayor frecuencia de polineuropatía. El pronóstico de la enfermedad es aceptablemente favorable con tratamiento, por lo que es importante el diagnóstico precoz

INTRODUCTION: Neurosarcoidosis is a rare complication of sarcoidosis. There are small series on the condition and very few from Spain. We conducted a retrospective study of neurosarcoidosis in Virgen de la Victoria Hospital over the last 10 years. PATIENTS AND METHOD: the medical records of patients diagnosed with sarcoidosis in our setting in the last 10 years were reviewed. RESULTS: One hundred twenty patients with sarcoidosis, 20 patients with probable neurosarcoidosis: 30% at the beginning of the illness, 55% later, 15% had isolated neurosarcoidosis. Forty percent had polyneuropathy, 15% cranial neuropathy, 15% myopathy, 10% hemispheric symptoms. Others: headache, myelitis, seizures, confusional syndrome. They were treated with steroids, some of them with immunosuppressive treatment. Seventy-two percent improved or were stabilized. Therefore, neurosarcoidosis prevalence in our hospital was 11%, similar to other published series, with similar features, but polyneuropathy was more frequent. Early diagnosis is very important as prognosis is favourable with treatment

Incidencia de cáncer en una cohorte de pacientes con lupus eritematoso sistémico / Rheumatology in the community of Madrid: current availability of rheumatologists and future needs using a predictive model

Objetivo. Determinar la incidencia y prevalencia del cáncer en una cohorte de pacientes con lupus eritematoso sistémico (LES) e identificar los factores de riesgo asociados. Pacientes y métodos. El estudio incluyó una cohorte dinámica de los pacientes con LES (de noviembre de 1989 a diciembre del 2006) en un centro hospitalario de tercer nivel. Se utilizó un control externo ajustado por edad y sexo a través de un registro hospitalario de tumores de la misma área sanitaria. Resultados. El estudio incluyó a 175 pacientes con LES (90% mujeres), con un tiempo en riesgo de 1370,5 pacientes-año. Catorce mujeres (8%) murieron, principalmente por eventos cardiovasculares. Ningún paciente falleció por tumor maligno. Se encontraron 35 tumores en 28 pacientes, 25 de ellos después del diagnóstico de LES, de los cuales 5 fueron malignos. La tasa de tumores benignos fue de 14,6/1000 pacientes-año (IC del 95%, 8,9–22,5) y de los tumores malignos 3,6/1000 pacientes-año (IC del 95%, 1,5 a 8,8), con una razón de momios de incidencia cruda para los tumores malignos de 3,5 (IC del 95%, 01,05 a 07,09). Sin embargo, esta significación se perdió cuando se estandarizaron las tasas. En cuanto a los factores de riesgo asociados, se encontraron diferencias en la velocidad de sedimentación globular media (HR 1,4 [1,1–1,7]), y la presencia de trombosis (HR 6,9 [1,49 a 41,2]), en especial la trombosis arterial. Conclusiones. Encontramos una tasa cruda de incidencia de cáncer casi 4 veces mayor en los pacientes con LES en comparación con la tasa esperada en nuestra área de influencia del hospital (zona oeste de Málaga) (AU)

Objective: To determine the incidence and prevalence of cancer in a cohort of patients with systemic lupus erythematosus (SLE) and identify associated risk factors. Patients and methods: The study comprised a dynamic cohort of SLE patients (November 1989 to December 2006) at a tertiary referral centre. An adjusted external control from the hospital tumour registry was used. Results: The study included 175 SLE patients (90% women), with a mean time at risk of 1370.5 patientyears. Fourteen women (8%) died, mainly from cardiovascular events. No patient died due to malignancy. We found 35 tumours in 28 patients, 25 of them after the diagnosis of SLE, of which 5 were malignant. The rate of benign tumours was 14.6/1000 patient-years (95% CI, 8.9–22.5) and of malignant tumours 3.6/1000 patient-years (95% CI, 1.5–8.8), with a crude incidence odds ratio for malignant tumours of 3.5 (95% CI, 1.5–7.9). However, this significance was lost after standardizing the rates. Concerning associated risk factors, differences were found in the mean erythrocyte sedimentation rate [HR 1.4 (1.1–1.7)], and the presence of thrombosis [HR 6.9 (1.49–41.2)], especially arterial thrombosis. Conclusions: We found a crude incidence rate of cancer that was almost four times greater in our SLE patients as compared with the expected rate in the hospital area of western Malaga (AU)

Infecciones de piel y partes blandas / Skin and soft tissue infections

No disponible

No disponible

Eficacia y seguridad de asociar ezetimiba a dosis bajas de atorvastatina en la hipercolesterolemia asociada al tratamiento antirretroviral en pacientes con el virus de la inmunodeficiencia humana / Efficacy and safety of adding ezetimibe to low-doses atorvastatin for highly active antiretroviral therapy-related hypercholesterolaemia

Estudio prospectivo, abierto, de pacientes con el virus de la inmunodeficiencia humana (VIH) con dislipemia asociada al tratamiento antirretroviral (TAR) para analizar la eficacia y la seguridad de la ezetimiba junto a dosis bajas de atorvastatina en pacientes que no alcanzan el objetivo de colesterol unido a lipoproteínas de baja densidad (cLDL) con atorvastatina. Se analizaron las modificaciones en el perfil lipídico, riesgo cardiovascular (RCV) a 10 años (ecuación de Framingham), parámetros inmunovirológicos y concentraciones de creatincinasa y transaminasa glutámico pirúvica a las 24 semanas de añadir ezetimiba al tratamiento. Se incluyeron a 27 pacientes, 13 (48%) alcanzaron el objetivo de cLDL y hubo una reducción del colesterol total, cLDL y del porcentaje de pacientes con un RCV a 10 años > 10%. El recuento de linfocitos CD4 aumentó y todos mantuvieron la carga viral del VIH indetectable. No se observaron efectos adversos. El uso de ezetimiba junto a dosis bajas de atorvastatina es eficaz y seguro para el tratamiento de la hipercolesterolemia asociada al TAR (AU)

Prospective, open-label study of HIV-patients with HAART-related dyslipidaemia to analyse the efficacy and safety of ezetimibe plus low-dose atorvastatin in HIV-patients on HAART who do not reach LDL-C goals with atorvastatin. Changes in plasma levels of lipids, cardiovascular risk (CVR) at 10 years (Frahmingam equation), immunovirological parameters, CK and ALT levels were analysed. Twenty seven patients were included, thirteen (48%) achieved LDL-C goals, and a reduction was observed in total cholesterol, LDL-C, and the percentage of patients with a 10 year CVR > 10%. mean CD4 cells count increased, and all patients maintained undetectable HIV viral load. No adverse events were observed. Adding ezetimibe to low-dose atorvastatin is safe and effective for HAART-related hypercholesterolaemia (AU)