Association between dementia and systemic rheumatic disease: A nationwide population-based study.

OBJECTIVES: Systemic rheumatic disease is characterized by autoimmunity and systemic inflammation and affects multiple organs. Few studies have investigated whether autoimmune diseases increase the risk of dementia. Herein, we evaluate the relationship between systemic rheumatic disease and dementia through a population-based study using the Korean National Health Insurance Service (NHIS) claims database. METHODS: We conducted a nationwide population-based study using the Korean NHIS database, consisting of individuals who submitted medical claims from 2002-2013. Dementia was defined as having an acetylcholinesterase inhibitors (AChEIs) prescription along with symptoms satisfying the Alzhemier's disease (AD) International Classification of Diseases (ICD)-10 codes (F00 or G30), or vascular dementia (VaD; ICD-10 or F01) criteria. Control subjects were matched to the dementia patients by age and sex. The study group was limited to those diagnosed with rheumatic disease at least 6 months prior to diagnosis of dementia. Rheumatic disease was defined by the following ICD-10 codes: Rheumatoid arthritis (RA: M05), Sjögren's syndrome (SS: M35), systemic lupus erythematosus (SLE: M32), and Behcet's disease (BD: M35.2). RESULTS: Of the 6,028 dementia patients, 261 (4.3%) had RA, 108 (1.6%) had SS, 12 (0.2%) had SLE, and 6 (0.1%) had BD. SLE history was significantly higher in dementia patients (0.2%) than in controls (0.1%) and was associated with dementia (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.19-5.15). In subgroup analysis, SLE significantly increased dementia risk, regardless of dementia type (AD: OR, 2.29; 95% CI, 1.06-4.91; VaD: OR, 4.54; 95% CI, 1.36-15.14). However, these associations were not sustained in the mild CCI or elderly group. CONCLUSION: SLE was independently associated with a higher risk of dementia, including AD and VaD when compared to the control group, even after adjustment. SLE patients (<65 years old) are a high-risk group for early vascular dementia and require screening for early detection and active prevention.

La voz pasiva de la fibromialgia / Passive voice of fibromyalgia

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Correlation between TM joint disease and rheumatic diseases detected on bone scintigraphy and clinical factors.

The aim of this study was to evaluate the effect of rheumatic disease as a risk factor for temporomandibular disease (TMD). A total of 143 outpatients reporting symptoms indicating rheumatic disease at their first visit to the rheumatology clinic were included. We evaluated the temporomandibular joint (TMJ) with scintigraphic images, and standard questionnaires were administered for the symptomatic assessment for all patients. The patients were classified into 'healthy controls' or as per their diagnosis into 'osteoarthritis', 'axial spondyloarthritis', 'peripheral spondyloarthritis', 'rheumatoid arthritis', or 'other rheumatic diseases' groups. The patients were also differentiated depending on the presence or absence of axial involvement. The relation between the rheumatic disease type and findings at the TMJ were evaluated using statistical analyses. Axial spondyloarthritis, peripheral spondyloarthritis, and rheumatic arthritis patients showed significantly higher scintigraphic uptake at the TMJ compared with those in the control and osteoarthritis groups (axial spondyloarthritis: 4.5, peripheral spondyloarthritis: 4.5, rheumatoid arthritis: 4.09, control: 3.5, osteoarthritis: 3.4, p < 0.0001). Compared with patients without axial involvement, patients with axial involvement also showed significantly higher TMJ scintigraphic uptake (axial involvement: 4.24, without axial involvement: 3.50, p < 0.0001) with elevated symptomatic rates in TMD (axial involvement: 17.82, without axial involvement: 9.97, p < 0.005).

Nomenclátor jerarquizado en reumatología / Hierarchical nomenclature in rheumatology

INTRODUCCIÓN: Una misión de la Sociedad Española de Reumatología es aportar las herramientas necesarias para alcanzar la excelencia asistencial. En la actualidad no existe una referencia que cuantifique la complejidad de los actos médicos de esta especialidad. MATERIAL Y MÉTODO: Se elaboró una relación de los actos propios del reumatólogo y se estableció un sistema de clasificación jerárquica a partir de la construcción de un índice de complejidad, calculado mediante el tiempo de realización y el grado de dificultad de cada acto. RESULTADOS: Los resultados del método Delphi tendieron a una opinión grupal consensuada (media σ2 - σ1=0,75-1,43=-0,68, media IQR2 - IQR1=0,8-1,9=-1,1). El rango de valores del índice de complejidad osciló de 48 a 465 puntos. Entre las consultas, las que alcanzaron mayor gradación fueron la primera visita al paciente hospitalizado (366) y la visita a domicilio (369). Entre las técnicas diagnósticas, destacaron las biopsias. Las que puntuaron más alto fueron: biopsia ósea (465), de nervio sural (416) y sinovial (380). La ecografía tuvo una puntuación de 204, la capilaroscopia de 113 y la densitometría de 112. Entre las técnicas terapéuticas, la máxima dificultad (388), la alcanzó la infiltración/artrocentesis/ inyección articular infantil. La puntuación de la inyección articular con control ecográfico fue de 163. El informe clínico de minusvalía, 323 y el informe pericial, 370. CONCLUSIONES: Este trabajo ha permitido elaborar un nomenclátor de 54 actos en reumatología donde se identifican como actos más complejos la realización de biopsias (ósea, nervio sural, sinovial), la visita a paciente hospitalizado, la visita a domicilio, la infiltración infantil bajo sedación y la elaboración de un informe pericial. La ecografía osteomuscular es considerada el doble de compleja de una visita sucesiva, la capilaroscopia o la densitometría ósea

INTRODUCTION: One of the missions of the Spanish Society of Rheumatology is to provide the necessary tools for excellence in health care. Currently, there is no reference point to quantify medical actions in this specialty, and this is imperative. MATERIAL AND METHOD: A list of actions was drawn up and a hierarchical classification system was established by developing a complexity index, calculated based on the completion time and difficulty level of each action. RESULTS: The results of the Delphi method tended to the consensus opinion within a group (mean σ2 - σ1=0.75-1.43=-0.68, mean IQR2 - IQR1=0.8-1.9=-1.1). The values of the complexity index ranged between 48 and 465 points. Among consultation actions, those reaching the highest scores were the first inpatient visit (366) and visits to the patient's home (369). Among diagnostic techniques, biopsies were prominent, those with the highest score were: bone biopsy (465), sural nerve biopsy (416) and synovial biopsy (380). Ultrasound scan scored 204, capillaroscopy 113 and densitometry 112. Among therapeutic techniques, infiltration/ arthrocentesis/articular injection in children reached the highest difficulty (388). The score for ultrasound-guided articular injection was 163. The score for clinical report on disability was 323 and expert report 370. CONCLUSIONS: A nomenclature of 54 actions in Rheumatology was compiled. Biopsies (bone, sural nerve, synovial), inpatient visits, visits to the patient's home, infiltrations in children, and the preparation of the expert report were identified as the most complex actions. Musculoskeletal ultrasound is twice as complex as subsequent visits, capillaroscopy or bone densitometry

Juvenile polyautoimmunity in a rheumatology setting.

Overt polyautoimmunity (PolyA) corresponds to the presence of more than one well-defined autoimmune disease (AD) manifested clinically in a single patient. The current study aimed to describe the main characteristics of juvenile PolyA in a pediatric rheumatology setting and analyze the chronological aspects, index cases, familial autoimmunity, and clustering pattern. This was a cross-sectional and multicenter study in which 313 children with overt PolyA were included. Patients were systematically interviewed and their medical records reviewed using a questionnaire that sought information about demographic, clinical, immunological, and familial characteristics. A hierarchical cluster analysis was done to determine similarities between autoimmune diseases based on PolyA. PolyA occurred simultaneously in 138 (44%) patients. Multiple autoimmune syndrome was observed in 62 (19.8%) patients. There were 25 index diseases of which, systemic lupus erythematosus (SLE, n = 134, 42.8%), juvenile idiopathic arthritis (JIA, n = 40, 12.7%), Hashimoto's thyroiditis (HT, n = 24, 7.66%), immune thrombocytopenic purpura (ITP n = 20, 6.39%), antiphospholipid syndrome (APS, n = 15, 4.79%), and vitiligo (VIT, n = 15, 4.79%) were the most frequent and represented 79.23% of the total number of patients. Familial autoimmunity influenced PolyA. A high aggregation of autoimmunity was observed (λr = 3.5). Three main clusters were identified, of which SLE and APS were the most similar pair of diseases (based on the Jaccard index) followed by HT and JIA, which were related to ITP and Sjögren's syndrome. The third cluster was composed of localized scleroderma and VIT. Our findings may assist physicians to make an early diagnosis of this frequent condition. Pediatric patients with ADs should be systematically assessed for PolyA.

Increasing incidence and shifting profile of idiopathic inflammatory rheumatic diseases in adults during this millennium.

To explore the trends in the incidence of idiopathic inflammatory rheumatic diseases (IIRDs) after the turn of the millennium. From a nationwide register maintained by the Social Insurance Institution of Finland, we collected all adult patients with IIRDs granted a new special reimbursement for anti-rheumatic drugs between 2000 and 2014. Temporal trends in the incidences of various IIRDs were estimated in three 5-year intervals. A total of 58,405 adult patients were identified. Between 2000-2004 and 2010-2014, the age-adjusted incidence rate of IIRDs increased from 114 to 116/100000 [incidence rate ratio (IRR) 1.03 (95% CI 1.01 to 1.06)] in women and from 67 to 69/100,000 [IRR 1.10 (95% CI 1.06-1.14)] in men. The incidence of seropositive rheumatoid arthritis (RA) remained stable while that of seronegative RA decreased. For other diagnoses, the incidences either increased (unspecified arthritis, psoriatic arthritis, spondyloarthritis), remained stable (reactive arthritis), or decreased (SLE and the group of diseases with the ICD-10 code M35). The gender difference in spondyloarthritis leveled as the incidence in women increased at a higher rate than in men. Mean age at IIRD diagnosis decreased among women. The total age-adjusted incidence of IIRDs has gradually increased, due to the increase in unspecified arthritis, psoriatic arthritis, and spondyloarthritis. This, in addition to the ascending number of individuals at risk in the population, translates into a growing burden to the health care system.

Rituximab in systemic autoimmune rheumatic diseases: indications and practical use.

Objectives: To review the therapeutic option of Rituximab, a chimeric anti-CD20 antibody, in systemic autoimmune rheumatic diseases (SARDs) such as systemic lupus erythematosus, systemic sclerosis, primary Sjögren syndrome and idiopathic inflammatory myopathy. Methods: A non-systematic review was conducted. Results: The specific role and indication of rituximab in SARDs has been the subject of multiple trials in recent years. Evidence supports the use of rituximab in moderate-to-severe refractory systemic lupus erythematosus, diffuse skin involvement in systemic sclerosis and systemic involvement in primary Sjögren syndrome. Several guidelines have adopted these indications. In addition, there is a consensus about the use of rituximab in refractory myositis. The role of rituximab in interstitial lung disease associated with these SARDs needs to be further explored. Conclusion: Rituximab is a treatment option in several SARDs. Upcoming trials, use in daily practice and the safety profile are elaborated on.

Thrombotic Microangiopathies with Rheumatologic Involvement.

Thrombotic microangiopathies are heterogeneous disorders characterized by microangiopathic hemolytic anemia with thrombocytopenia and renal injury. There are a variety of causes, including metabolic disorders, infections, medications, complement disorders, pregnancy, malignancy, and autoimmune disorders. This review focuses on renal thrombotic microangiopathy in the setting of rheumatologic diseases. Systemic lupus erythematosus is the most common autoimmune disease associated with thrombotic microangiopathy. Other etiologies include scleroderma renal crisis and antiphospholipid antibody syndrome, which can be primary or secondary to autoimmune diseases including systemic lupus erythematosus. There have also been case reports of thrombotic microangiopathy in the setting of rheumatoid arthritis and dermatomyositis.

Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations.

Antinuclear antibodies (ANA) are key biomarkers in the evaluation of rheumatic diseases. The prevalence and clinical significance of uncommon or rare patterns, particularly those directed at the mitotic spindle apparatus (MSA), are not well understood. We aimed to investigate the prevalence and clinical significance of anti-MSA patterns in a Colombian population.During 2013 and 2014, 113,491 consecutive determinations of ANA were studied for the presence of uncommon patterns. Clinical and laboratory data of anti-MSA positive patients were retrospectively collected and analyzed.Of the 113,491 patients tested, 60,501 (53%) were positive for ANA, of which 834 (1.3%) were positive for uncommon/rare patterns of ANA (anti-MSA in 592 cases). Of these 592 cases, complete data were available in 329 patients, of whom 116 had an established diagnosis. Anti-MSA antibodies were the only ANA positive test in 81% patients. At least one fine reactivity was identified in 19/116 (16.3%) of ANA-positive patients, of which anti-Ro was the most prevalent (18/116, 15.5%).The most frequent patterns were nuclear mitotic apparatus (NuMA) (56%) and MSA-2 (25%). The NuMA pattern had the highest ANA titers: mean 320 (range 80-2560) and behaved as monospecific antibodies. The most frequent systemic autoimmune diseases were Sjögren syndrome (SS) (18.1%), rheumatoid arthritis (RA) (13.8%), and systemic lupus erythematosus (SLE) (11%). Undifferentiated connective tissue disease (UCTD) was associated with the centrosome (P < .001), NuMA (P < .02) and MSA-2 (P < .45) patterns. Chronic idiopathic urticaria (CIU) was associated with the NuMA pattern (P < .02) and sensorineural hearing loss (SNHL) was associated with the MSA-2 (P < .001), centrosome (P < .68) and CENP-F (P < .38) patterns, previously unreported findings. Malignancies were found in 8 patients (50% were papillary thyroid cancer).In a large cohort of ANA determinations, uncommon patterns were found in around 1% of cases. The most frequent anti-MSA patterns found were NuMA and MSA-2. More than 50% of patients with anti-MSA had an associated CTD, mainly SS, RA and SLE, and anti-MSA behaved as monospecific antibodies. Other entities of presumed autoimmune origin, like CIU and SNHL, might be associated with these patterns.

[Implementation of an early rheumatoid athritis unit for the early recognition and treatment of the disease]. / Implementación de una unidad de artritis reumatoide temprana en pacientes chilenos derivados desde centros de atención primaria de salud.

BACKGROUND: Early recognition of rheumatoid arthritis (RA) provides clinical benefits in terms of remission induction, reduced disease progression, and eventually treatment free remission. AIM: To describe the setting of a Unit devoted exclusively to the recognition and treatment of early RA in patients referred from primary healthcare centers (PHC) in Chile. MATERIALS AND METHODS: Patients were referred from nine participating PHC from 2014 through 2016. PHC physicians received a formal training to enhance criteria recognition and program adherence. Mandatory referral criteria were an age above 17 years, and arthralgia of less than 1-year duration, plus at least one of the following: morning stiffness of more than 30 minutes, swelling involving more than 3 joints for more than 1 month, a positive squeeze test or abnormal inflammatory serum markers. RESULTS: One hundred twenty patients aged 45 ± 12 years (90% women) were assessed at the early rheumatoid arthritis unit. Median time to referral from PHC to the Unit was 14.6 days. The median duration of symptoms for the overall sample of patients was 10.8 months. RA was identified in 43 patients (36%), with a delay between onset of symptoms and diagnosis of 8.3 months. Regarding the performance of referral criteria, the most sensitive was morning stiffness (80%, sensitivity 95% confidence intervals (CI) 64-89%) and synovitis was the most specific (specificity 83%, 95% CI 72-90%). The positive predictive value of the three clinical criteria altogether was 68.1% (95% CI 47-83%). CONCLUSIONS: Institution of an early RA unit was feasible within the Chilean healthcare system enabling the identification of early RA in one-third of patients.

Moving towards a molecular taxonomy of autoimmune rheumatic diseases.

Autoimmune rheumatic diseases pose many problems that have, in general, already been solved in the field of cancer. The heterogeneity of each disease, the clinical similarities and differences between different autoimmune rheumatic diseases and the large number of patients that remain without a diagnosis underline the need to reclassify these diseases via new approaches. Knowledge about the molecular basis of systemic autoimmune diseases, along with the availability of bioinformatics tools capable of handling and integrating large volumes of various types of molecular data at once, offer the possibility of reclassifying these diseases. A new taxonomy could lead to the discovery of new biomarkers for patient stratification and prognosis. Most importantly, this taxonomy might enable important changes in clinical trial design to reach the expected outcomes or the design of molecularly targeted therapies. In this Review, we discuss the basis for a new molecular taxonomy for autoimmune rheumatic diseases. We highlight the evidence surrounding the idea that these diseases share molecular features related to their pathogenesis and development and discuss previous attempts to classify these diseases. We evaluate the tools available to analyse and combine different types of molecular data. Finally, we introduce PRECISESADS, a project aimed at reclassifying the systemic autoimmune diseases.

Implementación de una unidad de artritis reumatoide temprana en pacientes chilenos derivados desde centros de atención primaria de salud / Implementation of an early rheumatoid athritis unit for the early recognition and treatment of the disease

Background: Early recognition of rheumatoid arthritis (RA) provides clinical benefits in terms of remission induction, reduced disease progression, and eventually treatment free remission. Aim: To describe the setting of a Unit devoted exclusively to the recognition and treatment of early RA in patients referred from primary healthcare centers (PHC) in Chile. Materials and Methods: Patients were referred from nine participating PHC from 2014 through 2016. PHC physicians received a formal training to enhance criteria recognition and program adherence. Mandatory referral criteria were an age above 17 years, and arthralgia of less than 1-year duration, plus at least one of the following: morning stiffness of more than 30 minutes, swelling involving more than 3 joints for more than 1 month, a positive squeeze test or abnormal inflammatory serum markers. Results: One hundred twenty patients aged 45 ± 12 years (90% women) were assessed at the early rheumatoid arthritis unit. Median time to referral from PHC to the Unit was 14.6 days. The median duration of symptoms for the overall sample of patients was 10.8 months. RA was identified in 43 patients (36%), with a delay between onset of symptoms and diagnosis of 8.3 months. Regarding the performance of referral criteria, the most sensitive was morning stiffness (80%, sensitivity 95% confidence intervals (CI) 64-89%) and synovitis was the most specific (specificity 83%, 95% CI 72-90%). The positive predictive value of the three clinical criteria altogether was 68.1% (95% CI 47-83%). Conclusions: Institution of an early RA unit was feasible within the Chilean healthcare system enabling the identification of early RA in one-third of patients.

[Modern perspective on the development conditions and diagnosis of systemic sclerosis].

Systemic sclerosis (SSc) is a multisystem disorder of the connective tissue characterized by a great deal of heterogeneity. This variability is a result of a combination of vascular damage inflammation and fibrosis leading to internal organ complications. The pathogenesis of disorder is still unknown. A large part is given to genetic, epigenetic and environmental factors. There is ongoing research into the new cells and mediators involved in the complicated development of disease. The overlap of vascular, autoimmune/ inflammatory alternations and fibrosis causes the multidirectional and unpredictable course of disease. Vascular complications may dominate in one group, whereas fibrosis in others. In addition, the disorder is characterized by individual variability; therefore although certain prognostic markers do exist, the course of disorder in largely unpredictable. This complexity of SSc, makes it difficult in terms of diagnosis and activity assessment, especially in early stages. Over a number of years, further classification criteria, which were more sensitive and more specific, were developed. The 2013 European League Against Rheumatism/American College of Rheumatology - EULAR/ACR classification criteria for SSc, were revised to include diagnosis in early stages and particularly in limited SSc. Unfortunately, there still exist certain groups of population which do not fulfil these criteria but develop the disorder; therefore, the search for new diagnostic methods which could elevate SSc diagnosis continues.

Prevalence of Disability in Patients With Musculoskeletal Pain and Rheumatic Diseases in a Population From Cuenca, Ecuador.

OBJECTIVE: The aim of this study was to determine the prevalence of disability in patients with musculoskeletal pain and rheumatic diseases in Cuenca, Ecuador. METHODS: We performed a cross-sectional analytical study with randomized sampling in 4877 subjects, from urban and rural areas. COPCORD (Community Oriented Program for Control of Rheumatic Diseases)-validated questionnaire was administered house-to-house to identify subjects with nontraumatic musculoskeletal pain and rheumatic diseases. The subjects were assessed by rheumatologists for diagnostic accuracy, and the Health Assessment Questionnaire Disability Index was administered to assess functional capacity. A logistic regression analysis was conducted to determine the association of rheumatic diseases with functional disability. RESULTS: Functional disability was found in 221 subjects (73.1% women), with mean age 62 (SD, 18.2) years, residing in rural areas (201 [66.5%]), with education of 6.9 (SD, 5.3) years, and of low income (77 [47.2%]). The value of HAQ-DI was a mean of 0.2 (0-2.9). The real prevalence of physical disability was 9.5%. Moderate and severe disability predominated in activities such as kneeling (4.9% and 3.3%), squatting (4.8% and 2.7%), and leaning to pick up objects (3.7% and 0.9%), respectively. Rheumatic diseases associated with physical disabilities were knee osteoarthritis (95 [31.4%]) and hand osteoarthritis (69 [22.8%]), mechanical low-back pain (43 [14.2%]), fibromyalgia (27 [9.5%]), and rheumatoid arthritis (11 [3.6%]; P < 0.001). CONCLUSIONS: Physical disability was associated with older age, female sex, rural residence, lower education, and lower income. Moderate and severe disability predominated in the dimensions of kneeling, squatting, and picking up objects. Rheumatic diseases associated with disability were hand and knee osteoarthritis, back pain, fibromyalgia, and rheumatoid arthritis.