Article

The Lifetime Risk of Adult-Onset Rheumatoid Arthritis and Other Inflammatory Autoimmune Rheumatic Diseases

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Abstract

Objective Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge with regard to their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown. This study was undertaken to estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjögren's syndrome, and to provide an overall estimate of the risk of developing inflammatory autoimmune rheumatic disease over a lifetime.Methods Using the incidence rates obtained from our population-based studies of rheumatic diseases among residents of Olmsted County, Minnesota, and mortality rates from life tables for the general population, we estimated the sex-specific lifetime risk of rheumatic disease.ResultsThe lifetime risk of RA developing in US adults was 3.6% for women and 1.7% for men, and the lifetime risk of rheumatoid factor–positive RA was 2.4% for women and 1.1% for men. The second most common inflammatory autoimmune rheumatic disease was PMR, with a lifetime risk of 2.4% for women and 1.7% for men. The overall lifetime risk of inflammatory autoimmune rheumatic disease was 8.4% for women and 5.1% for men.Conclusion One in 12 women and 1 in 20 men will develop an inflammatory autoimmune rheumatic disease during their lifetime. These results can serve as useful guides in counseling patients regarding their lifetime risk of these conditions and have important implications regarding disease awareness campaigns.

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... The causes of aortitis can be broadly categorized into infectious and noninfectious. While most cases are noninfectious, it is critical to rule out infectious causes for proper treatment [1][2][3][4][5][6][7][8][9]. Causative organisms include Salmonella, Streptococcus, Staphylococcus, syphilis and tuberculosis bacteria, and viruses [1]. ...
... His consistently normal WBC count and lack of evidence of masses on imaging made lymphoma or other malignancy unlikely. Because our patient already had hypothyroidism, he was at an increased risk of other autoimmune disorders, which made us investigate large vessel vasculitides, such as giant cell arteritis (GCA) or Takayasu's disease [3,7,10]. Of the two vasculitides mentioned, GCA would be the most likely condition in this patient [11]. ...
... However, he did not report headache, claudication of the jaw or tongue upon swallowing, visual changes, tenderness in the temporal area, or anemia, some of which are required by the diagnostic criteria set by the American College of Rheumatology (ACR) [9,10]. Given the demographics of our patient, Takayasu's disease would be unlikely since the average age of the patients at diagnosis is 25-30 years and 75-97% of the cases are females [7,8,13]. He had no signs of limb claudication, decreased peripheral pulses, or differences in blood pressures across the limbs [8,13]. ...
Article
Aortitis is an inflammatory phenomenon involving one or more layers of the aorta and can have infectious or noninfectious etiologies. Complications of aortitis include aneurysm, dissection, and rupture, which can lead to ischemic organs and ultimately death. Noninfectious aortitis is often secondary to trauma or results from a systemic inflammatory process. It is further categorized based on clinical characteristics, laboratory findings, and imaging. There are some cases in which the etiology cannot be determined and is, therefore, idiopathic in nature. We present a case of a 67-year-old male who presented with malaise, abdominal pain, anorexia, and significant weight loss for several months. Imaging revealed retroperitoneal fibrosis and aortitis. After an extensive workup, we diagnosed idiopathic aortitis and treated the patient with high-dose corticosteroids that led to symptom improvement.
... This phenomenon is commonly referred to as senescence-associated secretory phenotype (SASP). SASP-induced IL-1β and TNFα drive stromal cells into senescent conditions resulting in reduced regenerative processes such as wound healing [12]. Increased basal levels of C-reactive protein (CRP) or pro-inflammatory cytokines like IL-6 or chemokines like IL-8 are generally associated with a shortened lifetime [9]. ...
... In stark contrast, giant cell arteritis occurs at very old age [16]. In comparison to these conditions, the documented relationship of rheumatoid arthritis (RA) incidence with age appears to be enigmatic because the incidence rate peaks between the age of 55 and 85 years, but strongly declines thereafter [12,[17][18][19]. In contrast to the incidence, the severity of RA symptoms correlates with age and increases significantly beyond the age of 65 [20]. ...
... score < 5), intermediate severity (max. score of [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] or strong severity (max. score > 20). ...
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Background The incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains. Methods Young and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c . The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function. Results While the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4 ⁺ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo. Conclusion While old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.
... Rheumatoid Arthritis (RA) is a systemic autoimmune disease that affects 0.24% of the general population worldwide, according to the Global Burden of Disease 2017study (Disease, 2018Safiri et al., 2019), with a higher prevalence in females than males. The risk to develop RA is age-dependent, with an incidence peak between 65 and 80 years of age and a lifetime risk of 1.7% in men compared to 3.6% in women (Crowson et al., 2011;Eriksson et al., 2013;World Health Organization, 2018). RA main clinical manifestations include pain and swelling of hands, wrists, and foot and knee (polyarthritis) joints. ...
... histones (citH3), DNA fiber and antimicrobial proteins (MPO, elastase, others) released by neutrophils to entrap and facilitate the killing of pathogens in a process named NETosis (Disease, 2018). In RA pathogenesis, the role of NETosis has been investigated (Crowson et al., 2011;Eriksson et al., 2013), demonstrating that when NETosis occurs, citrullinated proteins are released and, when recognized by anticitrullinated protein antibodies (ACPAs), initiate and propagate the aberrant immune responses and inflammation that is characteristic of RA (World Health Organization, 2018; Safiri et al., 2019). NETs have also been shown to provide a scaffold for the alternative complement pathway, leading to C5a generation. ...
Article
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Bone remodeling is a physiological, dynamic process that mainly depends on the functions of 2 cell types: osteoblasts and osteoclasts. Emerging evidence suggests that complement system is crucially involved in the regulation of functions of these cells, especially during inflammatory states. In this context, complement component 5a (C5a), a powerful pro-inflammatory anaphylatoxin that binds the receptor C5aR1, is known to regulate osteoclast formation and osteoblast inflammatory responses, and has thus been proposed as potential therapeutic target for the treatment of inflammatory bone diseases. In this review, we will analyze the role of C5a-C5aR1 axis in bone physiology and pathophysiology, describing its involvement in the pathogenesis of some of the most frequent inflammatory bone diseases such as rheumatoid arthritis, and also in osteoporosis and bone cancer and metastasis. Moreover, we will examine C5aR1-based pharmacological approaches that are available and have been tested so far for the treatment of these conditions. Given the growing interest of the scientific community on osteoimmunology, and the scarcity of data regarding the role of C5a-C5aR1 axis in bone pathophysiology, we will highlight the importance of this axis in mediating the interactions between skeletal and immune systems and its potential use as a therapeutic target.
... According to the latest data, the overall prevalence of rheumatoid arthritis (RA) varies from 0.24-0.5% to up to 1% in the global population [3], [4], [5], [6], making it one of the most common autoimmune rheumatic diseases [7], [8], [9], [10], [11]. Women are 3-5 times more likely to be affected by this disease than men, and the initial symptoms of the disease can occur anywhere between 25 and 60 years of age [12], [13], [14]. ...
... PADI4 is located on chromosome 1p36 and encodes the enzymes responsible for the arginine to citrulline conversion [10], which, in turn, promotes the synthesis of ACPA. ACPA is known to be a culprit in RA emergence, as these autoantibodies have been found in the synovial fluid of RA patients [63], [64]. ...
Article
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BACKGROUND: The prevalence of rheumatoid arthritis (RA) is 1% in the global population. The lack of epidemiological studies in developing countries makes it difficult to obtain a complete global epidemiological picture of RA. RA develops due to the interaction of multiple genetic and environmental factors, though the contribution of these factors to the various disease occurrence seen in different populations is unclear. AIM: The aim of our study was to analyze the dynamics of the general prevalence and incidence of RA among the population of Kazakhstan in 2017–2019 as well as to investigate the three most common single-nucleotide polymorphisms (SNP) of RA in the Kazakhstan population. METHODS: The analysis of statistical data on Form 12 “On the health of the people and the health care system” was carried out. Prevalence and incidence rates were calculated according to generally accepted rules. Demographic data for the Republic of Kazakhstan were obtained from the official website stat.gov.kz. Our study included 70 RA patients and 113 control subjects. Blood samples were collected and genotyped for peptidylarginine deiminase 4 (PADI4), protein tyrosine phosphatase 22, and human leukocyte antigen (HLA)-DRB9 SNPs by reverse transcription polymerase chain reaction. RESULTS: The prevalence of RA in Kazakhstan in 2017–2019 was 0.36–0.38%, with an incidence rate of 0.085–0.087%, which can be comparable to data of other countries in Central Asia. The allele and genotypes frequency analyses were carried out between patients and controls. The HLA-DRB9 showed significant association of the G allele odds ratio (OR) 1.96 (95% confidence interval [CI]: 1.252–3.081), p= 0.0025 and G/G genotype OR = 3.67 (95% CI: 1.58–8.54), p = 0.00162 with RA in our sample. Strong association between anti-citrullinated protein antibody (ACPA) profile and PADI4 (OR 12.19 [95% CI: 2.19–67.94], p = 0.00115) was found. CONCLUSION: There was an increase in RA prevalence with age among females and a higher crude prevalence and incidence of RA in the southern regions of Kazakhstan. HLA-DRB9 prevailed in Kazakhstani patients with RA, PADI4 showed association with ACPA-positive RA. Further studies on larger samples are required to confirm our obtained results.
... The prevalence of RA in the US has increased; it has been estimated that about 1.28-1.36 million adults were diagnosed in 2014 [2]. The risk of developing RA is 3.6 percent in women and 1.7 percent in men [3]. In other words, one in every 12 women and one in every 20 men are predicted to develop an autoimmune rheumatic disease [3]. ...
... The risk of developing RA is 3.6 percent in women and 1.7 percent in men [3]. In other words, one in every 12 women and one in every 20 men are predicted to develop an autoimmune rheumatic disease [3]. ...
Article
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Rheumatoid arthritis (RA) is a chronic destructive type of arthritis. It has a high prevalence in females as compared to the male population globally. It mainly affects the synovium of peripheral joints and leads to the destruction of joints with time. Patients with RA usually have a high burden of inflammation which may lead to certain physical disabilities and debilitating effects on mental health and cognitive ability. The question we investigated here in this systematic review is how changing lifestyles and increasing exercise or physical activities affects one's cognitive abilities. This article adheres to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. We used different databases such as PubMed, MEDLINE, and ScienceDirect to find relevant articles. To ensure the quality of the finally selected 12 studies, we followed different quality appraisal tools. Based on our review, we found out that increasing physical activities and aerobic exercises positively increase overall well-being and decrease the inflammatory load, which will ultimately positively impact cognitive function in this subgroup of patients. We also discover certain key players affecting motivation, perception, and adherence to physical activities. We encourage future studies to be done on this topic to help in increasing quality of life and increasing independence in this group of patients. Counseling and addressing patient concerns are very important and keep disease activity well controlled so that physical activities become feasible.
... Giant cell arteritis (GCA) is a rare, large-vessel vasculitis that affects the aorta and its branches [1]. It has variable presentations, including fever, myalgias, headache, jaw claudication, and transient vision loss. ...
... His symptoms persisted for another week, and he presented to our institution, where he was admitted for further evaluation. Lab workup was remarkable for leukocytosis 1 2 1 3 to 16.9 K/uL (3.5-10.5K/uL), mild transaminitis, and elevated inflammatory markers, with CRP 272 mg/L (<8.1 mg/L) and ESR 97 mm/hr (0-20 mm). ...
Article
Giant cell arteritis (GCA) is a large vessel vasculitis with variable presentations, including fevers, myalgias, headache, and jaw claudication. A particularly concerning symptom is transient vision loss, which may become irreversible without prompt recognition and treatment. The pathogenesis of GCA is incompletely understood, but it seems that the innate and adaptive immune systems play a key role in vessel inflammation, remodeling, and occlusion. We present a case of a 79-year-old male who developed GCA two days after he received his second dose of a COVID-19 mRNA vaccine. He presented with headaches, fever, and myalgias. Lab workup revealed elevated inflammatory markers, with C-reactive protein (CRP) 272 mg/L (<8.1 mg/L) and erythrocyte sedimentation rate (ESR) 97 mm/hr (0-20mm/hr). Imaging of the head, with CT and MRI, was unremarkable. His headache persisted despite supportive treatment, and he developed new, transient blurred vision, which increased suspicion for GCA. He underwent bilateral temporal artery biopsies, which were consistent with GCA. His symptoms resolved quickly with oral prednisone 60mg daily, and his inflammatory markers returned to normal within a month. A review of the literature revealed several case reports of giant cell arteritis following influenza vaccination. However, no large-scale studies have demonstrated a causal relationship between GCA and immunization. Our case demonstrates the first instance of GCA following a COVID-19 mRNA vaccine. We propose that the upregulated immune response to the vaccine acted as a trigger for GCA in this patient with predisposing factors. While causation cannot be determined based on one case alone, our case demonstrates an opportunity for further research into the relationship between vasculitis and immunizations. Despite this isolated case, the proven benefits of COVID-19 mRNA vaccines significantly outweigh any theoretical risk of immune dysregulation following administration.
... The incidence of rheumatoid arthritis increases with age and it affects predominantly middle-aged people and elderly. 23 Likewise, the aging process itself is already associated with increased systemic oxidative stress and diminished immune cell functions (immunosenescence), which contribute to the development of rheumatoid arthritis. 24e27 Therefore, the present study investigated the effects of orally administered a-tocopherol-loaded polycaprolactone nanoparticles on articular inflammation and oxidative stress in the plasma, liver and brain of middle-aged rats with adjuvant-induced arthritis. ...
Article
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Background and aim The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged Holtzman rats with Freund's adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison. Experimental procedure Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/Kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/Kg p.o.). Animals were treated during 18 days after arthritis induction. Results Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs. Conclusion Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy.
... Rheumatoid arthritis impacts approximately 2% of the U.S. adult population [29]. It is approximately twice as common in women as men and affects some groups disproportionately, such as Pima Native Americans, in which rates are as much as 10 times higher than for other groups [30,31]. Plaque psoriasis and ankylosing spondylitis are less prevalent but can be treated with the same medications, and thus were included in the study. ...
Article
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Objective To determine how additional explanatory text (context) about drug side effects in a patient medication information handout affected comprehension and perceptions of risk and efficacy. Methods We conducted an online experiment with a national sample of 1,119 U.S. adults with rheumatoid arthritis and related conditions, sampled through random-digit dialing, address-based sampling, and online ads. We randomized participants to receive one of several versions of a patient information handout for a fictitious drug, either with or without additional context, then measured comprehension and other outcomes. Results Additional qualitative context about warnings and side effects resulted in lower comprehension of side effect information, but not information about uses of the drug or warnings. The effect of additional context on risk perceptions depended on whether the medication handout was delivered online or through the mail. Those who received a hardcopy of the handout with additional context had higher perceived risk of side effects than those who saw the version without additional context. Conclusion More clarifying information is not always better and may lead to cognitive overload, inhibiting comprehension. Practice implications Additional research should further explore effects of context in online vs. hard-copy formats before practice implications can be determined.
... In general, women are 2-3 times more likely to develop RA than men. Indeed, the cumulative lifetime risk of developing adult-onset RA has been roughly estimated at 3.6% for women and 1.7% for men [5,6]. ...
Article
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Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.
... RA occurs at any age, there are more than 20 million prevalent cases of RA, given the general increase in life expectancy worldwide, and the number of elderly patients with RA is increasing annually. Globally, the agestandardized point annual incidence of RA has increased by 8.2% compared to 1990 (4,5). The ratio of male patients to female patients with RA is approximately 1:3, which is possibly associated with the stimulation of the immune system by estrogen (6,7). ...
Article
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Inflammasome is a cytoplasmic multiprotein complex that facilitates the clearance of exogenous microorganisms or the recognition of endogenous danger signals, which is critically involved in innate inflammatory response. Excessive or abnormal activation of inflammasomes has been shown to contribute to the development of various diseases including autoimmune diseases, neurodegenerative changes, and cancers. Rheumatoid arthritis (RA) is a chronic and complex autoimmune disease, in which inflammasome activation plays a pivotal role in immune dysregulation and joint inflammation. This review summarizes recent findings on inflammasome activation and its effector mechanisms in the pathogenesis of RA and potential development of therapeutic targeting of inflammasome for the immunotherapy of RA.
... HFLS-RA cells present a series of invasive features, including enhanced proliferation, increased aggressiveness, and production of inflammatory mediators [4]. Previous studies reported that the lifetime risk of RA is 3.6% for women and 1.7% for men [5]. The current main clinical treatment strategy of RA is drug therapy, including immunosuppressive drugs and biologics. ...
Article
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Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. Methods The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. Results RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3′-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. Conclusion In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway.
... 21,22,64 Therefore, comparing dissimilar, but overlapping time periods should not substantially influence the domain-specific estimates. 61,68 Supporting the validity of our findings, the relative risk for rheumatoid arthritis was not significantly different between the GRC and REP cohorts (RR = 0.91, 95% CI = 0.60, 1.38) and was similar to the FDNY-to-REP rheumatoid arthritis relative risk (RR = 0.91, 95% CI = 0.65, 1.24). Although not statistically significant, the GRC-to-REP systemic lupus erythematosus comparison was in the same direction as that observed by the FDNY. ...
Article
Background The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. Objectives Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. Methods Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists’ review of consenting responders’ medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. Results Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. Conclusions The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.
... This is why the prevalence of RA can reach up to 1% of the general population in some countries. The lifetime risk of developing RA is 3.6% in women and 1.7% in men [3]. The prevalence of RA has remained stable from 1990 to 2010. ...
Article
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Rheumatoid arthritis (RA) is a systemic autoimmune disease that preferably affects small joints. As the well-timed diagnosis of the disease is essential for the treatment of the patient, several works have been conducted in the field of deep learning to develop fast and accurate automatic methods for RA diagnosis. These works mainly focus on medical images as they use X-ray and ultrasound images as input for their models. In this study, we review the conducted works and compare the methods that use deep learning with the procedure that is commonly followed by a medical doctor for the RA diagnosis. The results show that 93% of the works use only image modalities as input for the models as distinct from the medical procedure where more patient medical data are taken into account. Moreover, only 15% of the works use direct explainability methods, meaning that the efforts for solving the trustworthiness issue of deep learning models were limited. In this context, this work reveals the gap between the deep learning approaches and the medical doctors’ practices traditionally applied and brings to light the weaknesses of the current deep learning technology to be integrated into a trustworthy context inside the existed medical infrastructures.
... La tasa mundial es más alta en mujeres que en hombres siendo la de mortalidad en adultos, del 3.6% para mujeres y 1.7% en varones. 4,5 Durante su evolución, la AR puede ser monoarticular (monoartritis) llegando a afectar grandes articulaciones; o puede comportarse de forma poliarticular (poliartritis) cuando la afectación es ≥5 articulaciones. 2 Por lo general suelen haber antecedentes de traumas como mecanismo gatillo o desencadenante de la AR. ...
Article
Introducción: la artritis reumatoide es una patología inmunitaria que cursa con inflamación poliarticular simétrica de predominio periférico la misma que conduce a la deformidad de la articulación y sus componentes, inclusive facetas articulares y hueso. Puede existir compromiso extraarticular y sintomatología sistémica. Presentación del caso: paciente masculino de 58 años con antecedente de Artritis Reumatoide hace 10 años. Ingresa al Servicio de Traumatología con diagnóstico de artritis séptica en rodilla derecha fue tratado con antibióticos, drenaje y limpieza quirúrgica, con buena respuesta clínica y disminución de los signos locales de flogosis articular. Su cuadro febril persistió durante semanas el mismo que cedió de manera dramática con la administración de glucorticoides. Discusión: en la artritis reumatoide, la fiebre puede asociarse con exacerbaciones de la sinovitis, vasculitis y serositis. Al persistir el cuadro febril acompañado de una buena evolución clínica, biometría hemática normal y pancultivos limpios, se sospechó en fiebre de causa no infecciosa y se procedió a la administración de dexametasona. Conclusión: la fiebre puede ser una expresión clínica extraarticular común o atípica de un grupo importante de enfermedades reumáticas inflamatorias. Existen pruebas complementarias junto a una historia clínica minuciosa la cuál nos llevaría al diagnóstico presuntivo o definitivo.
... Lupus can present with hemolytic anemia, leucopenia and thrombocytopenia, thrombotic thrombocytopenic purpura, and multiple organ involvement (3). Rheumatoid arthritis (RA) is also an autoimmune disease with autoantibody formation, symmetrical arthritis of small and large joints with non-specific hematologic manifestations (4). Several studies evaluated the role of blood groups in different diseases. ...
Article
Full-text available
Background: Systemic lupus erythematous (SLE) and rheumatoid arthritis (RA) are autoimmune diseases in which the antigen-antibody system plays an important role. As blood group and Rh are determined by the presence or absence of antigens on the surface of red blood cells (RBCs), we aimed to determine the distribution of ABO and Rh blood groups in SLE and RA patients and its association with disease manifestations. Methods: This short communication is based on a study that was conducted on 434 SLE and 828 RA patients. We evaluated the distribution of ABO and Rh blood groups in RA and SLE patients. Results: This study projected that in lupus patients, Coombs-positive autoimmune hemolytic anemia and arthritis were more common among the B blood type and Rh-positive group, respectively. Furthermore, there was no relation between ABO and Rh blood group and rheumatoid factor (RF) and anti-Cyclic Citrullinated Peptide (anti-CCP) seropositivity. Moreover, there was no difference in distribution of blood groups in RA and SLE patients. Conclusion: The higher frequency of blood group B in hemolytic anemia, and positive Rh in arthritis in lupus patients, develop the hypothesis of probable role of ABO blood group antigen in some manifestations of lupus.
... GCA is the most common form of systemic vasculitis. It occurs above the age of 50, with the highest incidence among Caucasians (Crowson et al., 2011). TAK is a less common form of systemic vasculitis. ...
Chapter
Positron emission tomography combined with computed tomography using 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG-PET/CT) is an established tool in oncology. During the past decade, this functional imaging modality that is based on increased glucose metabolism in inflammatory target cells, has become the reference standard for non-invasive visualization and monitoring of a variety of inflammatory disorders including large vessel vasculitis. Imaging plays an increasing role to confirm a suspected diagnosis of large vessel vasculitis and given the widespread implementation in daily clinical practice, standardization is of utmost importance to ensure consistency in image quality and interpretation. This article provides first, a general introduction on the clinical presentation and challenges in the diagnostic work-up of large vessel vasculitis with a focus on the two major subtypes, giant cell arteritis and Takayasu's arteritis. Secondly, practice points to perform and interpret the results of [¹⁸F]FDG-PET/CT are described in line with the recently published procedural recommendations. Furthermore, the diagnostic performance and prognostic value as well as its role for treatment monitoring are discussed taking into account the recent international recommendations for the use of imaging in large vessel vasculitis in clinical practice. Lastly, several unresolved issues and topics for future research are highlighted before concluding this article with key messages providing an up to date guidance for the role of [¹⁸F]FDG-PET/CT in patients with suspected large vessel vasculitis.
... The annual incidence in the USA and northern Europe is about 40 per 100,000 people [11,12]. The lifetime risk of developing RA is 1.7% for men and 3.6% for women [13]. However, the incidence and prevalence can be up to 10 times higher for some populations, like the Pima Native Americans [14]. ...
Article
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Purpose Radiosynoviorthesis (RSO) using the intraarticular application of beta-particle emitting radiocolloids has for decades been used for the local treatment of inflammatory joint diseases. The injected radiopharmaceuticals are phagocytized by the superficial macrophages of the synovial membrane, resulting in sclerosis and fibrosis of the formerly inflamed tissue, finally leading to reduced joint effusion and alleviation of joint pain. Methods The European Association of Nuclear Medicine (EANM) has written and approved these guidelines in tight collaboration with an international team of clinical experts, including rheumatologists. Besides clinical and procedural aspects, different national legislative issues, dosimetric considerations, possible complications, and side effects are addressed. Conclusion These guidelines will assist nuclear medicine physicians in performing radiosynoviorthesis. Since there are differences regarding the radiopharmaceuticals approved for RSO and the official indications between several European countries, this guideline can only give a framework that must be adopted individually.
... 3,4 Since inflammation in RA involves not only articular parts but also extra-articular structures in up to 50% of RA patients, numerous complications including pulmonary, cardiovascular, and hematologic events develop. 5 The most notable extra-articular manifestations are vascular inflammation and associated cardiovascular diseases (CVD), representing the leading cause of excess mortality in RA. 6,7 A recent review indicated a 50% higher CVD mortality in RA patients than in the general population, with a 41-68% increase in ischemic heart disease, cerebrovascular accidents, and myocardial infarction (MI). [8][9][10] Premature atherosclerosis and coronary artery diseases are the most significant causes associated with CVD in RA patients. ...
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Objectives: To investigate factors associated with major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA). Methods: We conducted a nationwide, population-based, case-control study using Taiwan's National Health Insurance Research Database for 2003-2013. From 2004 to 2012, we identified 108,319 newly diagnosed RA patients without previous MACEs, of whom 7,580 patients (7.0%) developed MACEs during follow-up. From these incident RA patients, we included 5,994 MACE cases and 1:4 matched 23,976 non-MACE controls for analysis. The associations of MACEs with comorbidities and use of anti-rheumatic medications within 1 year before the index date were examined using conditional logistic regression analyses. Results: Using multivariable conditional logistic regression analysis, the risk of MACE in RA patients was associated with use of golimumab [odd's ratio (OR), 0.09; 95% confidence interval (CI), 0.01-0.67], abatacept (OR, 0.13; 95% CI, 0.02-0.93), hydroxychloroquine (OR, 0.90; 95% CI, 0.82-0.99), methotrexate (OR, 0.72; 95% CI, 0.64-0.81), cyclosporin (OR, 1.43; 95% CI, 1.07-1.91), nonsteroidal anti-inflammation drugs (NSAIDs) (OR, 1.36; 95% CI, 1.27-1.46), antiplatelet agent (OR, 2.47; 95% CI, 2.31-2.63), hypertension (without anti-hypertensive agents: OR, 1.04; 95% CI, 0.96-1.12; with anti-hypertensive agents: OR, 1.47; 95% CI, 1.36-1.59), diabetes (OR, 1.27; 95% CI, 1.18-1.37), hyperlipidemia without lipid-lowering agents (OR, 1.09; 95% CI, 1.01-1.17), ischemic heart disease (OR, 1.20; 95% CI, 1.10-1.31), and chronic obstructive pulmonary disease (COPD) (OR, 1.12; 95% CI, 1.03-1.23) in the parsimonious model. The risk of MACE in RA patients also increased markedly in participants younger than 65 years with some comorbidities. Conclusions: This population-based case-control study revealed that the use of golimumab, abatacept, hydroxychloroquine, and methotrexate were associated with a decreased risk of MACE development in newly diagnosed RA patients, while the use of cyclosporin, NSAIDs, and antiplatelet agents, and comorbidities, including hypertension, diabetes, hyperlipidemia without lipid-lowering agent therapy, ischemic heart disease, and COPD, were associated with an increased risk of MACE development in RA patients.
... In the above equation, R represents the response, and b 0 is the arithmetic mean response of the nine runs. The responses in the above equation comprise the quantitative influence of the independent variables A and B; b 1 , b 2 , b 3 , b 4 , and b 5 are the estimated coefficients for the factors A and B. Table 1 illustrates the details of the factorial design applied for the optimization. Fourier transform infrared (FTIR) spectroscopy (4700, Jasco, Tokyo, Japan) was used to detect any interaction between Lfd and nanoparticle excipients. ...
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) nanoparticles (Lfd-NPs) were prepared and assessed as a local drug delivery system capable of alleviating RA-associated inflammation. Lfd-NPs were optimized using the Quality by Design (QbD) approach, applying a 32 full factorial design. In vitro drug release from NPs was examined in simulated synovial fluid. In addition, the in vivo efficacy of Lfd-NPs was evaluated in the Adjuvant Induced Arthritis (AIA) rodent model. Sustained drug release in simulated synovial fluid was observed for up to 168 h. A gradual reduction in paw volume and knee diameter was observed over the course of treatment, indicating the regression of the disease. In addition, significant reductions in serum proinflammatory markers and cytokines, including the C-reactive protein (CRP), rheumatoid factor (RF), TNF-α, IL1-β, and IL-6, were verified upon treatment with Lfd-NPs, suggesting the modulation of immune responses at the pathological site. Most importantly, no remarkable signs of toxicity were observed in Lfd-NP-treated animals. Collectively, intra-articularly administered Lfd-NPs might represent a potential therapeutic alternative to systemically administered drugs for the treatment of rheumatoid arthritis, without eliciting systemic adverse effects.
... Furthermore, in another study, it was found that the NBS supplement was able to stimulate the immune system upon changing the balance of neutrophils to lymphocytes (8). Since 2010, the European League Against Rheumatism and the American College of Rheumatology have elected rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) for serological diagnosis of RA (9). By making some modifications to the treatment, the treatment of this diseases begins shortly after its detection; to this end, immunosuppressive agents like non-steroidal antiinflammatory drugs and glucocorticoids are used (10). ...
... Thus, disease-specific diagnostic biomarkers are lacking for GCA, a disease in which early recognition is key. Despite their obvious value in the diagnostic workup for GCA, imaging techniques are costly and often unavailable in daily clinical practice, and during the pandemic, the access to imaging modalities became even more difficult [3,4,14]. With this study, we aim to answer two research questions. ...
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Background Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts. Methods Treatment-naïve GCA patients participated in the Aarhus AGP cohort ( N = 52) and the Groningen GPS cohort ( N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex. Results In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections. Conclusion This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients.
... Autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, are more predominant in women than men (8.4% vs. 5.1%, p < 0.001), and share inflammatory pathways with atherosclerosis [5,76,77]. Rheumatoid arthritis is a risk factor for PAD (HR 2.29, 95% CI 1.20-4.34) and is associated with an increased risk of myocardial infarction, aneurysmal disease and CVD mortality [5,76,[78][79][80]. ...
Article
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Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide but has been primarily recognised as a man’s disease. The major components of CVD are ischaemic heart disease (IHD), stroke and peripheral arterial disease (PAD). Compared with IHD or stroke, individuals with PAD are at significantly greater risk of major cardiovascular events. Despite this, they are less likely to receive preventative treatment than those with IHD. Women are at least as affected by PAD as men, but major sex-specific knowledge gaps exist in the understanding of relevant CVD risk factors and efficacy of treatment. This prompted the American Heart Association to issue a “call to action” for PAD in women, in 2012. Despite this, PAD and CVD risk in women continues to be under-recognised, leading to a loss of opportunity to moderate and prevent CVD morbidity. This review outlines current evidence regarding cardiovascular risk in women and men with PAD, the relative significance of traditional and non-traditional risk factors and sex differences in cardiovascular risk management.
... Autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, are more predominant in women than men (8.4% vs. 5.1%, p < 0.001), and share inflammatory pathways with atherosclerosis [5,76,77]. Rheumatoid arthritis is a risk factor for PAD (HR 2.29, 95% CI 1.20-4.34) and is associated with an increased risk of myocardial infarction, aneurysmal disease and CVD mortality [5,76,[78][79][80]. ...
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Background Acute iliofemoral deep venous thrombosis (DVT) is associated with development of post thrombotic syndrome (PTS). Thrombolysis and deep venous stenting can restore vessel outflow and may reduce PTS. However, for a proportion patients, subsequent stenosis or re-occlusion necessitates further intervention. This study aimed to identify risk factors, to examine outcomes (reintervention success and PTS) and to develop a classification system for reintervention. Method A retrospective single centre cohort study of patients successfully lysed for iliofemoral DVT between 2013-2017. Patient records and imaging were examined for: demographics, risk factors, extent of thrombus & vessel clearance, stenting, flow, reintervention, anticoagulation compliance, villalta score and secondary patency. Based on this review a system of classification for patients in whom procedures failed is described: constituting technical, haematological, flow related or multiple factors. Results Of 133 patient (143 limbs), 48 limbs (33.6%) required reintervention, of which 25 presented with re-occulsion (17.4%). Median time to reintervention was 45 days. Need for reintervention was associated with IVC thrombus (RR 2.16, p<0.01), stenting across the inguinal ligament (RR 2.08, p<0.01) and anticoagulation non-compliance (RR 7.09, p<0.01).Successful reintervention was achieved in 31 (64.6%) cases: 23/23 (100%) cases managed pre-occlusion vs. 8/25 (36.4%) post-occlusion (RR 32.31, p<0.01).A greater incidence of any PTS was observed for reintervention patients (median villalta score 3 (IQR:1-5) vs. 1 (IQR:1-4), RR 2.28, p=0.029). Cases without complete vessel occlusion (reintervention and control) had lower rate of any PTS (14.0% vs. 42.9%, RR 3.06, p<0.01), and of moderate to severe PTS (3.0% vs. 14.3%, RR 4.76, p= 0.046) Technical issues were observed in 54.2% of reintervention cases and 6.3% of cases not requiring reintervention (p<0.01). Haematological issues were identified in 33.3% of reintervention cases and 1.1% of cases not requiring reintervention (p<0.01). Flow-related issues were observed in 43.8% of reintervention cases and no cases not requiring reintervention(p<0.01). 27.1% of reintervention cases were multifactorial and were associated with a lower rate of vessel salvage, but this did not translate into a significant difference in secondary patency on survival analysis. (RR 1.70, p=0.429.) Conclusion A large proportion of patients required reintervention due to potentially preventable factors. Anticoagulation compliance, thrombus burden and poor flow are important risk factors to consider in patient selection. Reintervention increased the risk of PTS and was more often successful when achieved prior to vessel occlusion.
... As a result, epidemiologic estimates of RA and risk factor identification are largely based on these populations. The incidence and prevalence of RA are much higher in some populations, such as Pima Native Americans, where rates are up to ten times higher than in the majority of population groups (Crowson et al. 2011). Rheumatoid Arthritis (RA) is an auto-immune disease in which the body misidentifies and attacks certain parts of its system as pathogens. ...
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When the immune system attacks the synovium, rheumatoid arthritis develops (the lining of the membrane that surrounds the joints). The resulting inflammation thickens the synovium, which can eventually destroy the joint's cartilage and bone. The purpose of this study is to identify the significant risk factors for Rheumatoid Arthritis in 240 patients at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. Obesity, Gender, Smoking, Age, Alcoholism, and Family History were the selected risk factors for this study, and they were analyzed using logistic regression analysis and descriptive statistics. Alcoholism and age have a significant association with Rheumatoid Arthritis and Age has a positive effect on developing the disease while Alcoholism has a negative effect on developing the disease, according to the statistical analysis. However, there is no link between Rheumatoid Arthritis and gender, obesity, smoking, or family history. Based on the study's findings, it is critical for future clinical research to critically evaluate the lifestyle of patients developing Rheumatoid Arthritis.
... The number of elderly patients with rheumatoid arthritis (RA) has recently increased due to improved vital prognosis of patients with RA [1], increased incidence of elderly onset RA [2,3], and higher cumulative risk of RA in elderly women [4]. In Japan, one of the countries with the highest aged society in the world, the proportion of patients with RA who are aged ≥ 65 years was 60.8%, and the largest proportion was 28.6% of patients with RA aged 70-79 years old [5]. ...
Article
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Background Infection is one of the primary concerns during treatment for rheumatoid arthritis (RA) in elderly patients. However, infection risk of patients with RA receiving targeted therapy (TT) including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKIs) in elderly patients are scarce. The aim of this study was to compare the risk of hospitalized infection (HI) with TT versus methotrexate (MTX) therapy among young, elderly, and older elderly patients with RA. Methods Using Japanese claims data, patients satisfying the following criteria were enrolled: (1) ≥ one ICD10 code for RA; (2) ≥ one prescription of MTX or TT (bDMARDs and JAKIs) between April 2008 and September 2018; and (3) ≥16 years old. We calculated the incidence rate (IR) of HI per 100 patient-years in the young, elderly, and older elderly groups (those aged 16–64, 65–74, and ≥75 years, respectively) and the IR ratio (TT vs. MTX) of HI. A logistic regression model was used to estimate the associations between HI and TT versus MTX in each group. Results The overall IR of HI per 100 patient-years (95% confidence interval) was 3.2 [2.9–3.5], 5.0 [4.6–5.4], and 10.1 [9.5–10.9] in the young, elderly, and older elderly groups, respectively. Concomitant use of MTX or immunosuppressive DMARDs with TT was less frequent in the elderly and older elderly groups. The adjusted odds ratio of TT vs. MTX for HI was 1.3 (1.0–1.7; p = 0.021), 0.79 (0.61–1.0; p = 0.084), and 0.73 (0.56–0.94; p = 0.015) in the young, elderly, and older elderly groups, respectively. Conclusion The overall IR of HI was increased with age. The risk of HI under TT compared to MTX was not elevated in elderly and older elderly patients after adjusting for patients’ characteristics and concomitant treatments.
... patients of Northern European ancestry ≥ 50 years of age [2][3][4]. Clinical manifestations include vision loss, headache, scalp tenderness, and jaw claudication. Noncranial symptoms, such as polymyalgia rheumatica (PMR) and limb claudication, may also occur [5]. ...
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Background Subcutaneous tocilizumab (TCZ SC) is approved globally for giant cell arteritis (GCA). This phase Ib study investigated the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of intravenous (IV) TCZ 6 and 7 mg/kg in patients with GCA. This study explored an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA). Methods Patients with GCA who had received ≥ 5 doses of TCZ IV 8 mg/kg Q4W and achieved remission were enrolled. Patients received 5 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, 5 doses of 6 mg/kg Q4W in period 2. Pharmacokinetic endpoints were maximum concentration ( C max ), minimum concentration ( C trough ), area under the curve over a dosing interval (AUC τ ), and mean concentration ( C mean ) of TCZ after the last dose of each period. Other endpoints included pharmacodynamic markers, safety, and exploratory efficacy. Results In 24 patients, the median (range) age was 65.5 (57–90) years, and 62.5% were female. TCZ exposures ( C max and AUC τ ) were 11.2% and 20.0% lower at the 6- than 7-mg/kg dose. The mean interleukin 6 (IL-6) serum concentrations were elevated at baseline and remained elevated, with slightly higher concentrations in period 1 than in period 2. The mean serum soluble IL-6 receptor concentrations were elevated at baseline and comparable between the 2 doses at steady state. C-reactive protein levels and most erythrocyte sedimentation rates were within normal ranges throughout the study. Overall, 22 patients (91.7%) had ≥ 1 adverse event, and 4 (16.7%) had a serious adverse event. No patients experienced a GCA flare, and all remained in remission throughout the study. Conclusions Both doses of TCZ IV Q4W were generally well tolerated in patients with GCA. The C max and C mean achieved with 6 mg/kg IV Q4W in patients with GCA were similar to those in patients with RA treated with 8 mg/kg IV Q4W, and C trough was within the range observed in patients with GCA treated with SC dosing every week or every 2 weeks. Trial registration ClinicalTrials.gov , NCT03923738
... Worldwide, it is most common in northern latitudes and populations of Scandinavian and Northern European descent [1]. In the UK, PMR is the most common inflammatory musculoskeletal condition presenting in older adults [2], with an overall incidence of 95.9 per 100 000 person years in those aged over 40 years, rising to 314.9 per 100 000 in the over 80s [3]. PMR can be challenging to diagnose and manage because of its heterogeneous presentation, Rheumatology Key messages . ...
Article
Objectives Polymyalgia rheumatica (PMR) causes pain, stiffness and disability in older adults. Measuring the impact of the condition from the patient’s perspective is vital to high-quality research and patient-centred care, yet there are no validated patient-reported outcome measures (PROMs) for PMR. We set out to develop and psychometrically evaluate a PMR-specific PROM. Methods Two cross-sectional postal surveys of people with a confirmed diagnosis of PMR were used to provide data for field testing and psychometric evaluation. 256 participants completed the draft PROM. Distribution of item responses was examined and exploratory factor analysis and Rasch analysis were used to inform item reduction, formation of dimension structure and scoring system development. 179 participants completed the PROM at two-time points, along with comparator questionnaires and anchor questions. Test-retest reliability, construct validity and responsiveness were evaluated. Results Results from the field-testing study led to the formation of the PMR-Impact Scale (PMR-IS), comprising four domains (symptoms, function, psychological and emotional well-being, and steroid side effects). Construct validity and test-retest reliability met accepted quality-criteria for each domain. There was insufficient evidence from this study to determine its ability to detect flares/deterioration, but the PMR-IS was responsive to improvements in the condition. Conclusion The PMR-IS offers researchers a new way to assess patient-reported outcomes in clinical studies of PMR. It has been developed robustly, with patient input at every stage. It has good construct validity and test re-test reliability. Further work is needed to fully establish its responsiveness and interpretability parameters and assess its real-world clinical utility.
... Rheumatoid Arthritis (RA), classified as an autoimmune disease, is a long-term progressive disorder that causes inflammation and painful swelling in and around the joints and other body organs 1,2 . The prevalence of RA varies between 0.5 and 1% and begins at any age, but its incidence increases with age 3,4 . RA, similar to most of the other autoimmune diseases, displays a striking imbalance between the two sexes, with two or three times higher prevalence in women than men 5,6 . ...
Article
Background: The high heritability of Rheumatoid Arthritis (RA) has been estimated from different studies. Recently, Genome-Wide Association Studies (GWAS) show a large number of Single Nucleotide Polymorphisms (SNPs) loci affecting susceptibility to RA. The rs934734 polymorphism in the SPRED2 gene is one of these loci. Studies have shown that the SPRED2 gene is involved in the regulation of inflammatory response, leukocyte infiltration, and local chemokine production. In the current study, the possible association between SNP rs934734 (intronic variant) in the SPRED2 gene with RA risk in the Iranian population was evaluated. Methods: One hundred fourteen RA patients and 120 healthy counterparts were recruited in this case-control study to evaluate rs934734 genotypes using the real-time PCR High Resolution Melting method (HRM). Results: Logistic regression analysis demonstrated that GG and AG genotypes compared with AA genotype increase the risk of RA (GG vs. AA; OR=4.61; 95%CI [2.21-9.35]; p<0.001 and AG vs. AA; OR=2.54; 95%CI [1.36-4.76]; p=0.004). Furthermore, subjects with allele G were more frequently affected with RA than subjects with A allele (OR=2.33; 95%CI [1.61-3.38]; p<0.001). Besides, in the patient group, there was a significant correlation between Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) concentration with rs934734 polymorphism (p<0.05). Conclusion: Our findings suggest that rs934734 in SPRED2 strongly underlies RA development and is associated with clinicopathological characteristics of this disease.
Chapter
The vasculitides are a rare group of heterogeneous diseases where the defining feature is inflammation of vessel walls, leading to end-organ damage. These conditions have been usually classified based on the caliber of the blood vessel involved. In recent years, our understanding of these conditions has increased, leading to the development of new therapies and better outcomes in their treatment. In this chapter, we summarize the clinical presentation as well as the diagnostic approach and treatment to the most common forms of primary systemic vasculitis.
Article
Objective: To describe the prevalence of magnetic resonance imaging (MRI) findings in patients with the clinical diagnosis of polymyalgia rheumatica (PMR). Materials and Methods: Sixteen consecutive patients with untreated PMR, meeting the American College of Rheumatology criteria, underwent MRI examinations of the shoulder(s), hip(s), or both, depending on clinical complaints. Six patients also underwent MRI of the spine. Results: We evaluated 24 shoulders, among which we identified subacromial-subdeltoid bursitis in 21 (87.5%), glenohumeral joint effusion in 17 (70.8%), and fluid distention of the long head of the biceps tendon sheath in 15 (62.5%). Peritendinitis and capsular edema were observed in 21 (87.5%) and 17 (70.8%) shoulders, respectively. We also evaluated 17 hips, identifying hip joint effusion in 12 (70.6%), trochanteric bursitis in 11 (64.7%), peritendinitis in 17 (100%), and capsular edema in 14 (82.4%). All six of the patients who underwent MRI of the spine were found to have interspinous bursitis. Conclusion: Subacromial-subdeltoid bursitis, glenohumeral joint effusion, and hip joint effusion are common findings in patients with PMR. In addition, such patients appear to be highly susceptible to peritendinitis and capsular edema. There is a need for case-control studies to validate our data and to determine the real impact that these findings have on the diagnosis of PMR by MRI.
Article
Background: Polymyalgia rheumatica (PMR) is among the most common inflammatory rheumatic diseases in older adults. Presumed risk factors include female sex, previous infections, and genetic factors. No epidemiological data on PMR in Germany have been available until now. Methods: This review is based on publications retrieved by a selective literature search in PubMed. Moreover, the administrative incidence and prevalence of PMR in the years 2011- 2019 was determined from data of the AOK Baden-Württemberg statutory health insurance carrier for insurees aged 40 and older. In addition, we quantified the number of consultations with physicians involved in the diagnosis. Results: The annual age- and sex-standardized incidence and prevalence of PMR from 2011 to 2019 were 18.6/100 000 persons and 138.8/100 000 persons, respectively. The incidence was higher in women than in men (21.8/100 000 vs. 12.8/100 000 persons per year). 60% of the cases were diagnosed in primary care practices. The treatment of PMR with orally administered glucocorticoids usually results in a treatment response within a few days to weeks. Approximately 43% of patients experience recurrent symptoms within a year, requiring adjustment of the glucocorticoid dose. For older patients with impaired physical ability, additional non-pharmacological treatment with exercise programs plays an important role. Conclusion: PMR usually takes an uncomplicated course under treatment and can be managed in primary care, but these patients are often multimorbid and require frequent follow-up. Along with research on the etiology of the disease, further studies are needed to identify the risk factors for a chronic course and to evaluate the potential effects of non-pharmacological measures.
Article
Objectives: Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA. Method: A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930–1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed. Results: During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4–9% and 6–10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19–1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA. Conclusions: Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.
Article
Epstein-Barr virus (EBV) -positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. In recent years, EBVMCU has been reported in the field of oral surgery. On the other hand, medication-related osteonecrosis of the jaw (MRONJ) is an osteomyelitis that occurs in patients receiving antiresorptive agents including bisphosphonates (BP) and/or denosumab developing with bacterial infections such as dental diseases and mucositis. MRONJ caused by EBVMCU in the elderly has not been reported. Here, we report a rare case of MRONJ caused by EBVMCU in the elderly. The patient, an 82-year-old woman, had received BP for more than 2 years. An ulcerative lesion was found in the palatal mucosa; biopsy performed from the site confirmed the diagnosis of EBVMCU. At follow-up, the lesion disappeared spontaneously. At the 6-month follow-up, bone formation was observed at the site of the lesion, and the sequestrum was removed. At the 12-month follow-up healing of the EBVMCU region was seen indicating a good prognosis.
Chapter
The evolution of mankind has always aimed at better living conditions with constantly evolving urbanization and civilization. The persistent efforts in improving the life style and health regime have decreased the rate of infectious diseases but have imposed us at risk of autoimmune disorders. Our environment comprising of flora and fauna not only shape up the surroundings geographically but also evolve and mould immune system of human beings by continuous exposure to different allergens and pathogens. Helminths are known strong immune manipulator, with very well devised strategies to evade human immune system they are able to thrive within the host for long period without evoking an immune insult to the host. This immune suppression arises as a result of Th2 bias induced by the residing helminth and the helminth secreted products. Auto-immune disorders are associated with incessant inflammation and organ damage in the long run. There have been reports suggesting that exposure to helminths confers protection against these auto-immune disorders which are Th1 associated. Hence, helminth derived products might be useful in ameliorating the pathology linked to auto-immune disorders as they might help in restoring the homeostasis. Here, we discuss the potential of helminths and helminth derived products in therapy.
Article
Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterized by severe pain and morning stiffness, mainly affecting the shoulder girdle. A 75-year-old woman, previously healthy, received the first dose of ChAdOx1 vaccine and two weeks later started with pain in the shoulder and pelvic girdles and knees of inflammatory characteristics, accompanied by morning stiffness (about one hour), anorexia, asthenia, and activities of daily living (ADL) dependence. She started analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) with no improvement. The symptoms aggravated three days after the second vaccine dose, and she was referred to our center. At observation, she presented shoulder, hip, and knee active range of motion limitation. Blood analysis revealed an Erythrocyte Sedimentation Rate (ESR) of 120mm/h (reference value < 20mm/h) and C-Reactive Protein (CRP) of 80mg/L (reference value < 5mg/L). Ultrasound showed effusion on both shoulders, hips, and knees. The paraneoplastic syndrome was ruled out. She started oral corticosteroids and a rehabilitation program, and a month later, she presented controlled pain, normal analysis, and ADL independence. This case shows symptomatic and analytic features of PRM after the first vaccine dose and aggravation soon after the second. As such, we consider establishing a potential relationship between the inoculation and the development of PRM. A few cases were published reporting a PRM-like syndrome following a COVID-19 vaccine; however, the underlying mechanism and prognosis are still unknown.
Article
Systemic lupus erythematous (SLE) is an autoimmune disease with a wide range of cardiovascular complications. The main manifestations include diseases of the coronary arteries, valves, pericardium, and myocardium. Multimodality cardiovascular imaging techniques are critical for evaluating the extent of cardiac manifestations in SLE patients, which can provide valuable prognostic information. However, their utility has previously not been well-defined. This review provides a state-of-the-art update on the cardiovascular manifestations of lupus, as well as the role of multimodality cardiac imaging in guiding management of patients with SLE.
Article
Pulmonary hypertension (PH), a syndrome characterized by elevated pulmonary pressures, commonly complicates connective tissue disease (CTD) and is associated with increased morbidity and mortality. The incidence of PH varies widely between CTDs; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease and respiratory disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension, a rare form of PH that is associated with high morbidity and mortality. Future therapies targeting pulmonary vascular remodeling may improve outcomes for patients with this devastating disease.
Chapter
Joint and muscle pain is a common presentation to multiple specialties. This chapter addresses common causes of joint pain and how to differentiate and manage inflammatory causes such as rheumatoid arthritis from noninflammatory causes, such as osteoarthritis. Furthermore, the chapter differentiates between the various types of inflammatory arthritides, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease-associated arthritis, reactive arthritis (seronegative spondyloarthritis), and gout, based on the clinical and laboratory presentations. Finally, the chapter addresses fibromyalgia, a common noninflammatory cause of joint pain and muscle pain.
Article
Objective: To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population. Method: In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored. Results: The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1–35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8–35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5–0.6%) in 2018: 0.8% (95% CI 0.7–0.8%) for women and 0.3% (95% CI 0.3–0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018. Conclusion: The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator.
Article
Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a variety of factors in the immune system. Awareness of the role of cytokines in SLE has led to new clinical perspectives in its pathogenesis; therefore, the aim of this study was to investigate the effect of vitamin 1, 25(OH) 2 D3 (D3) on the expression of IL-2, IL-4, IL-5, IL-10, and IFN-γ cytokines in patients with lupus. Methods A total of 65 new-onset SLE patients were enrolled in the study. After peripheral blood mononuclear cell isolation, the lymphocytes of each patient were divided into two groups, one treated with a concentration of 50 μmol vitamin D3 (test) and the other untreated with vitamin D3 (control), were cultured. After 24 hours, the cultured cells were collected and the expressions of IL-2, IL-4, IL-5, IL-10, and IFN-γ genes were analyzed by RT-qPCR. Results It was observed that vitamin D3 reduced expression of IFN-γ, IL-4, IL-5, and IL-10 genes by 73, 50, 37, and 29%, respectively, and increased IL-2 gene expression by 31% ( p ≤ 0.05). Conclusion With different patterns of cytokine changes in patients with lupus in different studies, it seems that the pattern of cytokine changes is largely dependent on the phase of the disease and with this study it can be concluded that vitamin D3 administration at the time of diagnosis and in the early stages and before starting treatment have different effects from its administration in the acute stage of the disease, which requires further studies to prove. It seems that in patients with systemic lupus erythematosus, vitamin D should be administered taking into account the phase of the disease.
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Humorally associated autoimmune diseases generally show a female predominance whereas ankylosing spondylitis, a disease that overlaps with psoriatic arthritis (PsA), shows a male predominance. The present review ascertains the current knowledge of sex-specific differences related to psoriatic arthritis (PsA), a chronic, inflammatory condition associated with psoriasis. Sex differences may have important implications for clinical research in PsA and in terms of epidemiology (incidence, prevalence, lifetime risk, survival, and mortality), clinical, radiological, and laboratory features, and response to treatment. While nationwide surveys and large-scale databases and registries show no sex-specific differences, varying male/female ratios have been reported, ranging from 0.42 to 2.75 (comparable with those reported for psoriasis vulgaris: ranging from 0.28 to 2.38). This may reflect subtle, complex, nonlinear interactions between the biological make-up of the individual (genetic and epigenetic differences), hormonal components including menopausal status, environmental exposures including skeletal physical stressing, and psychological variables. There exists methodological heterogeneity and paucity of data concerning sex-specific differences, in terms of the specific population studied, study design, and the diagnostic criteria utilized. Harmonizing and reconciling these discrepancies would be of crucial importance in achieving the ambitious goals of personalized/individualized medicine and further standardized meta-data and Big Data could help disentangle and elucidate the precise mechanisms of underlying potential PsA sex-specific differences.
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Introduction: The American College of Rheumatology (ACR) criteria, and more recently the revised ACR criteria (rACR), are a scoring system developed to aid in the diagnosis of giant cell arteritis (GCA). Our aim was to investigate the value of the non-biopsy criteria of the original ACR criteria and rACR criteria to predict GCA, and investigate the utilization of such scores to avoid biopsy when a very high or very low likelihood of a positive temporal artery biopsy TAB was predicted. Method: We conducted a retrospective cohort study of 59 patients undergoing TAB from 2013 to 2017 in Beaumont Hospital, a tertiary referral centre in Dublin, Ireland. Demographic data, biochemical results, presenting features, and histology results were collected and collated. Results: Data were analysed from 53 patients and ACR scores were compiled. Seventeen scored < 3 and thirty-six scored 3-5. All 11 positive biopsies were in the 3-5 score range. Forty-five patients were analysed with rACR scores. Eight were excluded due to not meeting the inclusion criteria. Of the 11 positive biopsies, 2 were in the 3-4 score range, and 9 were in the ≥5 score range. In the ACR method, 36% of all biopsies scored as low-risk pre-biopsy. In the rACR method, 84.4% of all biopsies scored in the low- and intermediate-risk group pre-biopsy and 15.6% of all biopsies scored in the high-risk group pre-biopsy. Conclusions: This study illustrates the potential value of the rACR scoring system as a useful tool to categorize patients according to risk with a view to avoiding unnecessary TAB. The data suggest that a TAB has a helpful role in low- and intermediate-risk groups but is of minimal benefit in the high-risk group.
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Regulatory T (Treg) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of Treg cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. Treg cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of Treg cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in Treg cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of Treg cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced Treg cell trafficking. Another protein which facilitates Treg cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in Treg cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of Treg cell migration and review the current knowledge about impaired Treg cell homeostasis in RA.
Chapter
The last decade has seen an enormous increase in long non-coding RNA (lncRNA) research within rheumatology. LncRNAs are arbitrarily classed as non-protein encoding RNA transcripts that exceed 200 nucleotides in length. These transcripts have tissue and cell specific patterns of expression and are implicated in a variety of biological processes. Unsurprisingly, numerous lncRNAs are dysregulated in rheumatoid conditions, correlating with disease activity and cited as potential biomarkers and targets for therapeutic intervention. In this chapter, following an introduction into each condition, we discuss the lncRNAs involved in rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus. These inflammatory joint conditions share several inflammatory signalling pathways and therefore not surprisingly many commonly dysregulated lncRNAs are shared across these conditions. In the interest of translational research only those lncRNAs which are strongly conserved have been addressed. The lncRNAs discussed here have diverse roles in regulating inflammation, proliferation, migration, invasion and apoptosis. Understanding the molecular basis of lncRNA function in rheumatology will be crucial in fully determining the inflammatory mechanisms that drive these conditions.
Article
Background/purpose Preclinical vascular inflammation models have demonstrated effective suppression of arterial wall lesional T cells through inhibition of Janus kinase 3 and JAK1. However, JAK inhibition in patients with giant cell arteritis (GCA) has not been prospectively investigated. Methods We performed a prospective, open-label, pilot study of baricitinib (4 mg/day) with a tiered glucocorticoid (GC) entry and accelerated taper in patients with relapsing GCA. Results 15 patients were enrolled (11, 73% female) with a mean age at entry of 72.4 (SD 7.2) years, median duration of GCA of 9 (IQR 7–21) months and median of 1 (1–2) prior relapse. Four (27%) patients entered the study on prednisone 30 mg/day, 6 (40%) at 20 mg/day and 5 (33%) at 10 mg/day. Fourteen patients completed 52 weeks of baricitinib. At week 52, 14/15 (93%) patients had ≥1 adverse event (AE) with the most frequent events, including infection not requiring antibiotics (n=8), infection requiring antibiotics (n=5), nausea (n=6), leg swelling (n=2), fatigue (n=2) and diarrhoea (n=1). One subject required baricitinib discontinuation due to AE. One serious adverse event was recorded. Only 1 of 14 (7%) patients relapsed during the study. The remaining 13 patients achieved steroid discontinuation and remained in disease remission during the 52-week study duration. Conclusion In this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. Larger randomised clinical trials are needed to determine the utility of JAK inhibition in GCA. Trial registration number NCT03026504 .
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Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjögren's syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions--a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.
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To determine time trends in incidence, prevalence, and clinical characteristics of psoriatic arthritis (PsA) over a 30-year period. We identified a population-based incidence cohort of subjects aged 18 years or over who fulfilled ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA between January 1, 1970, and December 31, 1999, in Olmsted County, Minnesota, USA. PsA incidence date was defined as the diagnosis date of those who fulfilled CASPAR criteria. Age- and sex-specific incidence rates were estimated and age- and sex-adjusted to the 2000 US White population. The PsA incidence cohort comprised 147 adult subjects with a mean age of 42.7 years, and 61% were men. The overall age- and sex-adjusted annual incidence of PsA per 100,000 was 7.2 [95% confidence interval (CI) 6.0, 8.4] with a higher incidence in men (9.1, 95% CI 7.1, 11.0) than women (5.4, 95% CI 4.0, 6.9). The age- and sex-adjusted incidence of PsA per 100,000 increased from 3.6 (95% CI 2.0, 5.2) between 1970 and 1979 to 9.8 (95% CI 7.7, 11.9) between 1990 and 2000 (p for trend < 0.001). The point prevalence per 100,000 was 158 (95% CI 132, 185) in 2000, with a higher prevalence in men (193, 95% CI 150, 237) than women (127, 95% CI 94, 160). At incidence, most PsA subjects had oligoarticular involvement (49%) with enthesopathy (29%). The incidence of PsA has been rising over 30 years in men and women. Reasons for the increase are unknown, but may be related to a true change in incidence or greater physician awareness of the diagnosis.
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The geographic variation in rheumatoid arthritis (RA) incidence in the United States is unknown. We studied residential region from January 1, 1921, to May 31, 1976, and RA risk in a prospective cohort of women, the Nurses' Health Study. Information on state of residence was collected at baseline in 1976 (when participants were aged 30-55 years) and on state of residence at birth, at age 15 years, and at age 30 years in 1992. Among 83,546 participants reporting residence for all 4 time points, 706 incident RA cases from June 1, 1976, to May 31, 2004, were confirmed by screening questionnaire and record review for American College of Rheumatology criteria. Residential region was classified as West, Midwest, mid-Atlantic, New England, and Southeast. Multivariate Cox proportional hazards regression models were used to assess relationships between region and RA risk, adjusting for age, smoking, body mass index, parity, breastfeeding, postmenopausal status, postmenopausal hormone use, father's occupation, race, and physical activity. Analyses were performed in participants who lived in the same regions, or moved, over time. Compared with those in the West, women in New England had a 37% to 45% elevated risk of RA in multivariate models at each time point (eg, state of residence in 1976: rate ratio [RR], 1.42; 95% confidence interval [CI], 1.10-1.82). In analyses of women who lived in the same region at birth, age 15 years, and age 30 years, living in the Midwest was associated with greater risk (RR, 1.47; 95% CI, 1.05-2.05), as was living in New England (RR, 1.40; 95% CI, 0.98-2.00). Compared with living in the West at birth, age 15 years, and age 30 years, RA risk was higher in the East. In this large cohort of US women, significant geographic variation in incident RA existed after controlling for confounders. Potential explanations include regional variation in behavioral factors, climate, environmental exposures, RA diagnosis, and genetic factors.
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We estimated the remaining lifetime risks of developing Alzheimer's disease (AD) and dementia from all causes, based on data from longitudinal population studies. The risk of developing AD during one's lifetime depends on both disease incidence and life expectancy. Conventional estimates of cumulative incidence overestimate the risk when there is a substantial probability of mortality due to competing causes. A total of 2,611 cognitively intact subjects (1,061 men, 1,550 women; mean age, 66 +/- 7 years) were prospectively evaluated for the development of AD or other dementia. A modified survival analysis was used to estimate both cumulative incidence and the sex-specific remaining lifetime risk estimates for quinquennial age groups above age 65 years. Over a 20-year follow-up period, 198 subjects developed dementia (120 with AD). The remaining lifetime risk of AD or other dementia depended on sex, being higher in women, but varied little with age between 65 and 80 years. In a 65-year-old man, the remaining lifetime risk of AD was 6.3% (95% CI, 3.9 to 8.7) and the remaining lifetime risk of developing any dementing illness was 10.9% (95% CI, 8.0 to 13.8); corresponding risks for a 65-year-old woman were 12% (95% CI, 9.2 to 14.8) and 19% (95% CI, 17.2 to 22.5). The cumulative incidence between age 65 and 100 years was much higher: for AD, 25.5% in men and 28.1% in women; for dementia, 32.8% in men and 45% in women. The actual remaining lifetime risk of AD or dementia varies with age, sex, and life expectancy and is lower than the hypothetical risk estimated by a cumulative incidence in the same population.
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Giant cell arteritis (GCA) (temporal arteritis) and polymyalgia rheumatica (PMR) are common, frequently related conditions in people generally over 50 years of age. Most studies have shown an association of GCA with HLA-DRB1 *04 alleles. As regards isolated PMR, however, the HLA class II genetic susceptibility varies from one population to another. Besides associations with HLA, tumor necrosis factor appears to influence susceptibility to both conditions. Genetic polymorphisms have also been considered to be important candidates as factors of susceptibility to GCA and PMR. In this regard, gene polymorphisms for ICAM-1 (intercellular adhesion molecule 1), RANTES (regulated upon activation, normal T cell expressed, and presumably secreted), and interleukin (IL)-1 receptor antagonist seem to play a role in the pathogenesis of GCA and PMR in some populations. However, additional studies are required to clarify the genetic influence on susceptibility to these conditions.
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To conduct a systematic review of incidence and prevalence studies of rheumatoid arthritis (RA), based on the 1987 revised American College of Rheumatology (ACR) criteria, to compare their methodologies and summarize their results, and to investigate the possible geographic variations and changes over time in the frequency of the disease. We conducted a Medline search between January 1988 and December 2005. Studies reporting the incidence and prevalence of RA in adult populations (16 to 20 years and over), based on 1987 ACR criteria, were eligible for inclusion. From each study included, we extracted the country, year of publication, type of study (retrospective, prospective, or cross-sectional), and incidence or prevalence rates. The study areas were grouped into (a) North American countries; (b) north European countries; (c) south European countries; and (d) developing countries. We examined the geographical differences of prevalence and incidence rates using the Mann-Whitney and the Kruskall-Wallis tests. A total of 28 studies were identified meeting the inclusion criteria. Nine were incidence studies, 17 were prevalence studies, and 2 estimated both prevalence and incidence rates. Incidence studies were not available from developing countries. There is a significant difference of prevalence estimates between northern European and American countries and developing countries. South European countries have lower median incidence rates than North American and north European countries. As concerning the time trends of RA occurrence, only 3 incidence studies provided secular data from the same study area, based on ACR criteria, using the same methods of case ascertainment. Two of these studies indicate a decreasing incidence of RA in Finland and United States of America. The occurrence of RA varies among countries and areas of the world. A decreasing trend has been observed in countries characterized by high rates of RA incidence and prevalence. However, the relatively small number of studies for most areas of the world and the lack of incidence studies for the developing countries limits the understanding of worldwide RA epidemiology.
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Descriptive epidemiological studies of psoriatic arthritis (PsA) in the general population were very limited until the year 2000. Recently, several incidence and prevalence studies of PsA have been reported, suggesting a considerable variation of the disease frequency among different populations. We present a systematic review of incidence and prevalence studies of PsA published after 1987 until December 2006, in order to evaluate and compare their methodology and to summarize their results, and to investigate the possible geographic variations of occurrence of PsA. We conducted a MedLine search including all articles published on PsA incidence and prevalence in the general adult population until December 2006. From each study identified, we extracted the country, year of publication, type of study, criteria of case identification, and incidence or prevalence rates. Methodological criteria for quality included the type of study (prospective or retrospective for incidence studies and retrospective or cross-sectional for prevalence studies), the type of incidence and prevalence rates (crude or adjusted), the criteria of case definition, and the description of the characteristics of the population studied. A total of 13 studies were identified from the literature search meeting our inclusion criteria. There is a wide variation of annual incidence of PsA (median 6.4, range 0.1-23.1 cases per 105 inhabitants). One incidence study used European Spondylarthropathy Study Group (ESSG) criteria for case definition, while the other studies were based on a coexistence of psoriasis and arthritis in several ways. Three prevalence studies used ESSG criteria for case identification, while the other studies were based on a coexistence of psoriasis and arthritis in several ways. The prevalence estimates vary from 1 case per 105 population in a Japanese study to 420 cases per 105 population in an Italian study (median 180). The occurrence and epidemiological profile of PsA are likely to present important variations among countries and areas of the world. However, several methodological issues and mainly the absence of validated or consensual criteria for case identification and classification of the disease put important limitations on the interpretation of epidemiological data. The establishment of standardized criteria for the diagnosis and classification of PsA cases is necessary for further, valid investigation of the disease epidemiology.
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To describe trends in systemic lupus erythematosus (SLE) incidence and mortality over the past 4 decades.
Article
Since the early 1980s, a bewildering array of methods for constructing bootstrap confidence intervals have been proposed. In this article, we address the following questions. First, when should bootstrap confidence intervals be used. Secondly, which method should be chosen, and thirdly, how should it be implemented. In order to do this, we review the common algorithms for resampling and methods for constructing bootstrap confidence intervals, together with some less well known ones, highlighting their strengths and weaknesses. We then present a simulation study, a flow chart for choosing an appropriate method and a survival analysis example. Copyright © 2000 John Wiley & Sons, Ltd.
Article
The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a “classification tree” schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91–94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
Article
Objective To describe trends in systemic lupus erythematosus (SLE) incidence and mortality over the past 4 decades.Methods Using the Rochester Epidemiology Project resources, medical records were screened to identify all Rochester, Minnesota residents with any SLE-associated diagnoses, discoid lupus, positivity for antinuclear antibodies, and/or false-positive syphilis test results determined between January 1, 1980 and December 31, 1992. Medical records were then reviewed using a pretested data collection form in order to identify cases of SLE according to the American College of Rheumatology 1982 revised criteria for SLE. Drug-induced cases were excluded. All identified SLE patients were followed up until death, migration from the county, or October 1, 1997. These data were combined with similar data from the same community obtained between 1950 and 1979, and trends in the SLE incidence and mortality over time were calculated.ResultsOf the 430 medical records reviewed, 48 newly diagnosed cases of SLE (42 women and 6 men) were identified between 1980 and 1992. The average incidence rate (age- and sex-adjusted to the 1970 US white population) was 5.56 per 100,000 (95% confidence interval [95% CI] 3.93–7.19), compared with an incidence of 1.51 (95% CI 0.85–2.17) in the 1950–1979 cohort. The age- and sex-adjusted prevalence rate as of January 1, 1993 was ∼1.22 per 1,000 (95% CI 0.97–1.47). Survival among SLE patients was significantly worse than in the general population (P = 0.017 compared with the 1980–1992 cohort, and P < 0.0001 compared with the 1950–1979 cohort, by log-rank test). Cox proportional hazards modeling demonstrated a statistically significant improvement in the survival rate over time (P = 0.035).Conclusion Over the past 4 decades, the incidence of SLE has nearly tripled, and there has been a statistically significant improvement in survival. These findings are likely due to a combination of improved recognition of mild disease and better approaches to therapy.
Article
Since the early 1980s, a bewildering array of methods for constructing bootstrap confidence intervals have been proposed. In this article, we address the following questions. First, when should bootstrap confidence intervals be used. Secondly, which method should be chosen, and thirdly, how should it be implemented. In order to do this, we review the common algorithms for resampling and methods for constructing bootstrap confidence intervals, together with some less well known ones, highlighting their strengths and weaknesses. We then present a simulation study, a flow chart for choosing an appropriate method and a survival analysis example. Copyright © 2000 John Wiley & Sons, Ltd.
Article
Objective. To determine trends in the incidence and clinical presentation of ankylosing spondylitis first diagnosed between 1935 and 1989 among residents of Rochester, Minnesota, and in the survival of the patients. Methods. Population-based descriptive study. Results. The overall age- and sex-adjusted incidence rate was 7.3 per 100,000 person-years (95% confidence interval 6.1–8.4). The rate tended to decline between 1935 and 1989, but there was little change in the age at symptom onset or diagnosis over the 55-year study period. Overall survival was not decreased up to 28 years following diagnosis. Conclusion. These data indicate that there is a constancy in the epidemiologic characteristics of ankylosing spondylitis and suggest that previously study results indicating changes may have been due to biases in patient selection and study design.
Article
The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
Article
To examine trends in the incidence and prevalence of rheumatoid arthritis (RA) from 1995 to 2007. To augment our preexisting inception cohort of patients with RA (1955-1994), we assembled a population-based incidence cohort of individuals >or=18 years of age who first fulfilled the American College of Rheumatology 1987 criteria for the classification of RA between January 1, 1995 and December 31, 2007 and a cohort of patients with prevalent RA on January 1, 2005. Incidence and prevalence rates were estimated and were age-and sex-adjusted to the white population in the US in 2000. Trends in incidence rates were examined using Poisson regression methods. The 1995-2007 incidence cohort comprised 466 patients (mean age 55.6 years), 69% of whom were female and 66% of whom were rheumatoid factor positive. The overall age- and sex-adjusted annual RA incidence was 40.9/100,000 population. The age-adjusted incidence in women was 53.1/100,000 population (versus 27.7/100,000 population in men). During the period of time from 1995 to 2007, the incidence of RA increased moderately in women (P = 0.02) but not in men (P = 0.74). The increase was similar among all age groups. The overall age- and sex-adjusted prevalence on January 1, 2005 was 0.72% (95% confidence interval [95% CI] 0.66, 0.77), which is an increase when compared with a prevalence of 0.62% (95% CI 0.55, 0.69) in 1995 (P < 0.001). Applying the prevalence on January 1, 2005 to the US population in 2005 showed that an estimated 1.5 million US adults were affected by RA. This is an increase from the previously reported 1.3 million adults with RA in the US. The incidence of RA in women appears to have increased during the period of time from 1995 to 2007. The reasons for this recent increase are unknown, but environmental factors may play a role. A corresponding increase in the prevalence of RA was also observed.
Article
GCA (giant cell arteritis) is a granulomatous vasculitis of large and medium-sized arteries that occurs in individuals 50 years of age or older. [1] A recent study suggested that the age at incidence of GCA may be increasing. [2] To address this issue, we studied the trends in mean age at onset of GCA over a 55-year period.
Article
In the era of genome-wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate-gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses. The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member. Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjögren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1.34), and asthma or polymyalgia rheumatica (SIR 1.32). This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.
Article
Mounting evidence indicates that alterations of autophagy processes are directly involved in the development of many human diseases, including cancers. Autophagy-related gene (ATG) products are main players in the autophagy process. In humans there are 16 known ATG genes, of which four (ATG2B, ATG5, ATG9B and ATG12) have mononucleotide repeats with seven or more nucleotides. Frameshift mutations of genes with mononucleotide repeats are features of cancers with microsatellite instability (MSI). It is not known whether ATG genes with mononucleotide repeats are altered by frameshift mutations in gastric and colorectal carcinomas with MSI. For this, we analysed the mononecleotide repeats in ATG2B, ATG5, ATG9B and ATG12 in 32 gastric carcinomas with high MSI (MSI-H), 13 gastric carcinomas with low MSI (MSI-L), 43 colorectal carcinomas with MSI-H and 15 colorectal carcinomas with MSI-L by a single-strand conformation polymorphism (SSCP) analysis. We found ATG2B, ATG5, ATG9B and ATG12 mutations in 10, 2, 13 and 0 cancers, respectively. The mutations were detected in MSI-H cancers but not in MSI-L cancers. Gastric and colorectal cancers with MSI-H harboured one or more ATG mutations in 28.1% and 27.9%, respectively. Our data indicate that frameshift mutations in ATG genes with mononucleotide repeats are common in gastric and colorectal carcinomas with MSI-H, and suggest that these mutations may contribute to cancer development by deregulating the autophagy process.
Article
To determine trends in the incidence and clinical presentation of ankylosing spondylitis first diagnosed between 1935 and 1989 among residents of Rochester, Minnesota, and in the survival of the patients. Population-based descriptive study. The overall age- and sex-adjusted incidence rate was 7.3 per 100,000 person-years (95% confidence interval 6.1-8.4). The rate tended to decline between 1935 and 1989, but there was little change in the age at symptom onset or diagnosis over the 55-year study period. Overall survival was not decreased up to 28 years following diagnosis. These data indicate that there is a constancy in the epidemiologic characteristics of ankylosing spondylitis and suggest that previously study results indicating changes may have been due to biases in patient selection and study design.
Article
Criteria for the classification of giant cell (temporal) arteritis were developed by comparing 214 patients who had this disease with 593 patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than or equal to 50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated erythrocyte sedimentation rate (Westergren) greater than or equal to 50 mm/hour, and biopsy sample including an artery, showing necrotizing arteritis, characterized by a predominance of mononuclear cell infiltrates or a granulomatous process with multinucleated giant cells. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%. A classification tree was also constructed using 6 criteria. These criteria were the same as for the traditional format, except that elevated erythrocyte sedimentation rate was excluded, and 2 other variables were included: scalp tenderness and claudication of the jaw or tongue or on deglutition. The classification tree was associated with a sensitivity of 95.3% and specificity of 90.7%.
Article
The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
Article
The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
Article
Lifetime and age-conditional risk estimates of developing cancer provide a useful summary to the public of the current cancer risk and how this risk compares with earlier periods and among select subgroups of society. These reported estimates, commonly quoted in the popular press, have the potential to promote early detection efforts, to increase cancer awareness, and to serve as an aid in study planning. However, they can also be easily misunderstood and frightening to the general public. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and the American Cancer Society have recently begun including in annual reports lifetime and age-conditional risk estimates of developing cancer. These risk estimates are based on incidence rates that reflect new cases of the cancer in a population free of the cancer. To compute these estimates involves a cancer prevalence adjustment that is computed cross-sectionally from current incidence and mortality data derived within a multiple decrement life table. This paper presents a detailed description of the methodology for deriving lifetime and age-conditional risk estimates of developing cancer. In addition, an extension is made which, using a triple decrement life table, adjusts for a surgical procedure that removes individuals from the risk of developing a given cancer. Two important results which provide insights into the basic methodology are included in the discussion. First, the lifetime risk estimate does not depend on the cancer prevalence adjustment, although this is not the case for age-conditional risk estimates. Second, the lifetime risk estimate is always smaller when it is corrected for a surgical procedure that takes people out of the risk pool to develop the cancer. The methodology is applied to corpus and uterus NOS cancers, with a correction made for hysterectomy prevalence. The interpretation and limitations of risk estimates are also discussed.
Article
To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia. The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.
Article
To determine time trends in the epidemiology of rheumatoid arthritis (RA) in a population-based cohort. An inception cohort of residents of Rochester, Minnesota > or = 18 years of age who first fulfilled the American College of Rheumatology 1987 criteria between January 1, 1955 and December 31, 1994 (applied retrospectively, as appropriate) was assembled and followed up until January 1, 2000. Incidence rates were estimated and were age- and sex-adjusted to the 1990 white population of the US. A birth cohort analysis was performed, and survival rates over time were examined. The incidence cohort comprised 609 patients, 445 (73.1%) of whom were female and 164 (26.9%) were male, with a mean age at incidence of 58.0 years. The overall age- and sex-adjusted annual incidence of RA among Rochester, Minnesota, residents > or = 18 years of age was 44.6/100,000 population (95% confidence interval 41.0-48.2). While the incidence rate fell progressively over the 4 decades of study, from 61.2/100,000 in 1955-1964, to 32.7/100,000 in 1985-1994, there were indications of cyclical trends over time. Birth cohort analysis showed diminishing incidence rates through successive cohorts following a peak in the 1880-1890 cohorts. Incidence rates increased with age until age 85, but peaked earlier in women than in men. The survival rate in RA patients was significantly lower than the expected rate in the general population (P < 0.001), and no improvement was noted over time. The secular trends demonstrated in this study population, including the progressive decline in the incidence of RA over the last 40 years, suggest that an environmental factor may play a role in the etiology of RA.
Article
It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten-year probabilities of hip fracture were computed in men and women at 10-year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10-year risk at any age between men and women. Ten-year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15-fold range in 10-year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10-year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan [TW]], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong [HK]], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.
Article
To determine time trends in the incidence and survival of polymyalgia rheumatica (PMR) over a 30 year period in Olmsted County, Minnesota, USA. Using the unified medical record linkage system of the Rochester Epidemiology Project, we identified all incident cases of PMR among residents of Olmsted County, MN, between January 1, 1970, and December 31, 1999. Incidence rates were estimated and age- and sex-adjusted to the 1990 US white population. The annual incidence rates were graphically illustrated using a 3 year centered moving average. A Poisson regression model was used to evaluate predictors of PMR incidence. Survival rates were computed and compared with the expected rates in the population. There were 378 incident cases of PMR during the 30 year study period. Of these 66.6% were female and the mean age at incidence was 72.8 years. The overall age and sex adjusted annual incidence of PMR per 100,000 population aged > or = 50 years was 58.7 (95% CI 52.8,64.7). Incidence rates increased with age in both sexes, but in women, unlike in men, incidence fell after age 80. The incidence rates varied over the period of observation, but no significant trends over time were found. In the multivariable analysis, sex (p = 0.023), age (p < 0.001), and age2 (p < 0.001), but not calendar year (p = 0.24) were significant predictors of incidence. Survival among individuals with PMR was not significantly different from that expected in the population (p = 0.06). The incidence of PMR has remained relatively stable over the past 30 years.
Article
To investigate time trends in the incidence and survival of giant cell arteritis (GCA) over a 50-year period in Olmsted County, Minnesota. Using the unified record system at the Mayo Clinic, we identified all incident cases of GCA first diagnosed between 1950 and 1999. Incidence rates were estimated and adjusted to the 1980 United States white population for age and sex. The annual incidence rates were graphically illustrated using a 3-year centered moving average. Survival rates were computed and compared with the expected rates in the population. There were 173 incident cases of GCA during the 50-year study period. Of these, 79% were women and the mean age at diagnosis was 74.8 years. The overall age- and sex-adjusted incidence per 100,000 persons 50 years of age or older was 18.8 (95% confidence interval [95% CI] 15.9-21.6). Incidence was higher in women (24.4; 95% CI 20.3-28.6) than in men (10.3; 95% CI 6.9-13.6). Incidence rates increased significantly over the study period (P = 0.017); in particular, a progressive increase was observed from 1950 to 1979; subsequently, no substantial increases in incidence rates were observed. A cyclic pattern of annual incidence rates was apparent, with evidence of 6 peak periods. Survival among individuals with GCA was not significantly different from that expected in the population (P = 0.80). The incidence of GCA increased over the first 3 decades of the study, then remained stable over the last 20 years. The previously observed cyclic pattern of annual incidence rates was still apparent over a 50-year period. Overall survival in GCA was similar to that in the population.
Article
Olmsted County, Minnesota is one of the few places in the world to conduct comprehensive population-based studies of disease etiology, natural history, and outcomes because of a unique resource, the Rochester Epidemiology Project (REP). This article describes the REP and highlights its research capabilities in the context of the rheumatic diseases.
Article
To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis (PsA) and to construct new criteria from observed data. Data were collected prospectively from consecutive clinic attendees with PsA and other inflammatory arthropathies. Subjects were classified by each of 7 criteria. Sensitivity and specificity were compared using conditional logistic regression analysis. Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold standard definition of "case"-ness. Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria, which were then constructed using a receiver operating characteristic curve. Data were collected on 588 cases and 536 controls with rheumatoid arthritis (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue disorders (n = 14), and other diseases (n = 28). The specificity of each set of criteria was high. The sensitivity of the Vasey and Espinoza method (0.97) was similar to that of the method of McGonagle et al (0.98) and greater than that of the methods of Bennett (0.44), Moll and Wright (0.91), the European Spondylarthropathy Study Group (0.74), and Gladman et al (0.91). The CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria consisted of established inflammatory articular disease with at least 3 points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxtaarticular new bone formation, rheumatoid factor negativity, and nail dystrophy. These criteria were more specific (0.987 versus 0.960) but less sensitive (0.914 versus 0.972) than those of Vasey and Espinoza. The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.