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* Context.--Anticyclic citrullinated peptide antibodies are important serologic markers for the diagnosis of rheumatoid arthritis. Several kinds of test reagents for automated immunoassay systems have been developed and used in recent years.Objective.--To evaluate the analytic and diagnostic performance of the new ADVIA Centaur anticyclic citrullinated peptide assay (Siemens Healthineers, Erlangen, Germany) compared with the Elecsys assay (Roche Diagnostics, Mannheim, Germany).Design.--A total of 576 serum samples were collected from subjects, including 156 patients (27%) with rheumatoid arthritis. Precision performance and analytical measurement range for the ADVIA assay were evaluated. Diagnostic performance of the 2 assays was compared based on sensitivity, specificity, and area under the receiver operating characteristic curves.Results.--The ADVIA assay showed a within-laboratory imprecision of 3.4% coefficient of variation for levels of 3.36 and 24.99 U/mL. This assay was demonstrated to be linear from 0.4 to 180.0 U/mL. With default cutoff values, sensitivity and specificity for diagnosing rheumatoid arthritis were 71.2% and 97.9%, respectively, for the ADVIA assay and 73.1 % and 96.9%, respectively, for the Elecsys assay. With the best cutoff values from the analyses of the receiver operating characteristic curve, the sensitivity of the 2 assays was the same at 75.6%. However, the specificity of the ADVIA assay was 96.4%, whereas that of the Elecsys assay was 94.3%. The area under the receiver operating characteristic curve value for the ADVIA assay was 0.867, which was not significantly different from that of the Elecsys assay (0.865).Conclusions.--The ADVIA Centaur anticyclic citrullinated peptide assay showed good analytic and diagnostic performance in diagnosing rheumatoid arthritis.(Arch Pathol Lab Med. 2018;142:1554-1559; doi: 10.5858/arpa.2017-0454-0A), Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by inflammation of the synovial joints with progressive damage, eventually causing severe disability and reduced life expectancy. (1) [...]

Objectives: Arthritis is a broad term covering disparate diseases with varying prognoses. Epidemiological surveys are important tools for arthritis research, but they either fail to specify arthritis subtypes or they provide self-reported arthritis data that are potentially misclassified. This limits their use for research about arthritis subgroups. This study describes and compares characteristics of subjects self-reporting subtypes of arthritis in a Canadian epidemiological survey. We also consider the feasibility of developing methods for distinguishing subtypes of arthritis in such population surveys. Methods: Using data from 119,904 adult participants in the Canadian Community Health Survey (CCHS) cycle 3.1, we identified those self-reporting one of four subtypes of arthritis and compared the four groups with regard to socio-demographic status, lifestyle and health characteristics, medication use, health care utilization and functional outcomes. Cross-tabulations of weighted prevalence were estimated and tested for statistical significance using the chi-square test. Results: Descriptive results showed very few distinguishing characteristics across self-reported arthritis subtypes on 34 investigated variables. Participants with osteoarthritis were more likely to be older and female than other groups. Statistical testing showed no difference between rheumatoid arthritis, osteoarthritis and "other" type of arthritis for physical activity level, health conditions, medication use, health care utilization and functional limitations. Discussion: Characteristics of subjects who self-report different types of arthritis in a typical population health survey (CCHS) are not sufficiently dissimilar to justify valid data analyses and interpretation by arthritis subgroup. Future studies might focus on identifying and implementing supplemental questionnaire items in epidemiological population surveys. Key words: Arthritis; arthritis, rheumatoid; osteoarthritis; epidemiologic methods; cluster analysis; health surveys La traduction du resume se trouve a la fin de l'article. Can j Public Health 2009;100(6):467-71. Objectifs : L'arthrite est un terme large qui englobe differentes maladies ayant des pronostics varies. Les enquetes epidemiologiques sont des outils importants pour la recherche sur l'arthrite. Toutefois, ces enquetes ne permettent pas distinguer les sous-types d'arthrite. Ce probleme limite l'utilisation des enquetes populationnelles pour la recherche sur des soustypes d'arthrite. Notre etude vise a decrire et a comparer les differentes caracteristiques des sujets ayant declare differents sous-types d'arthrite dans l'Enquete sur la sante dans les collectivites canadiennes (ESCC), dans le but de developper une methode permettant de distinguer les soustypes d'arthrite dans les enquetes populationelles. Methodes : Nous avons analyse les donnees de 119 904 adultes ayant participe a l'ESCC (cycle 3.1). Les sujets ayant auto-rapportes un de quatre sous-types d'arthrite ont ete compares relativement a leur statut sociodemographique, leur style de vie, leur etat de sante, leur utilisation de medicaments, leur utilisation du systeme de sante et leur statut fonctionnel. La construction de tableaux croises des frequences ponderees a permis d'estimer la signification statistique des associations a l'aide du chi-carre. Resultats : Les resultats descriptifs ont demontre que les sous-groupes de l'arthrite se distinguaient tres peu relativement aux 34 variables a l'etude. Les participants ayant auto-declare un diagnostic d'arthrose etaient en moyenne plus ages et plus frequemment des femmes par rapport aux autres sous-groupes d'arthrite. Il n'y avait aucune difference statistiquement significative entre les categories arthrite rhumatoide, arthrose et autre type d'arthrite, en ce qui concerne le niveau d'activite physique, l'etat de sante, l'usage de medicaments, l'utilisation du systeme de sante et les limitations fonctionnelles des individus. Discussion : Les caracteristiques des sujets auto-rapportant differents types d'arthrite lors d'une enquete typique sur la sante populationnelle (ESCC) ne sont pas suffisamment differentes pour justifier l'analyse valide et l'interpretation des donnees selon le sous-groupe d'arthrite. Les etudes a venir devront mettre l'accent sur l'identification et la validation de questions supplementaires afin de distinguer les plus importants sousgroupes d'arthrite dans les enquetes epidemiologiques de la population. Mots cles : arthrite; arthrite rhumatoide; arthrose; methode epidemiologique; analyse en grappe, Arthritis is the blanket term for a range of illnesses with widely varying prognoses, osteoarthritis (OA) and rheumatoid arthritis (RA) being the most common. (1) Arthritis is one of the [...]

The case study of a 54-year-old female admitted to the hospital manifesting respiratory failure, hypotension and a cavitary lesion in the lung is discussed. The condition was diagnosed as an old case of rheumatoid arthritis which could lead to pulmonary complications and the line of treatment adopted is highlighted.

TLRs may contribute to the progression of rheumatoid arthritis through recognition of microbial or hostderived ligands found in arthritic joints. Here, we show that TLR2 and TLR4, but not TLR9, are involved in the pathogenesis of autoimmune arthritis and play distinct roles in the regulation of T cells and cytokines. We investigated the involvement of TLR2, TLR4, and TLR9 in the progression of arthritis using IL-1 receptor antagonist-knockout (IL1rn-/-) mice, which spontaneously develop an autoimmune T cell-mediated arthritis. Spontaneous onset of arthritis was dependent on TLR activation by microbial flora, as germ-free mice did not develop arthritis. Clinical and histopathological evaluation of IL1rn-/-Tlr2-/- mice revealed more severe arthritis, characterized by reduced suppressive function of Tregs and substantially increased IFN-[gamma] production by T cells. IL1rn-/-Tlr4-/- mice were, in contrast, protected against severe arthritis and had markedly lower numbers of Th17 cells and a reduced capacity to produce IL-17. A lack of Tlr9 did not affect the progression of arthritis. While any therapeutic intervention targeting TLR2 still seems complicated, the strict position of TLR4 upstream of a number of pathogenic cytokines including IL-17 provides an interesting potential therapeutic target for rheumatoid arthritis., Introduction RA is an autoimmune disease manifested by chronic inflammation and cartilage and bone destruction in multiple joints. Etiopathology of RA has been subjected to intensive research, resulting in the [...]

The single-necleotide polymorphism was tested within the previously linked chromosome region for association with rheumatoid arthritis. Results showed that the halotype STAT4 was associated with increased risk of both rheumatoid arthritis and systematic lupus erythematosus.

T cells, the central mediators of adaptive immunity are involved in normal and abnormal immune responses and they need both antigen-specific and costimulatory signals for their full activation. The selective costimulation modulator abatacept binds to CD80 and CD86, jamming interaction with CD28 and is an approved treatment for rheumatoid arthritis, thus the relevant immunology is described and new clinical findings on the two molecules are summarized.

Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions. Index Terms--Histology, image analysis, magnetic resonance imaging (MRI), rheumatoid arthritis (RA).

Leukotriene (LT) [B.sub.4] is a powerful chemotactic and immune modulating agent that signals via two receptors denoted [BLT.sub.1] and [BLT.sub.2]. Here we report that [BLT.sub.1] and [BLT.sub.2] are expressed at low levels in an apparently silent state in human umbilical vein endothelial cells (HUVEC). However, treatment with LPS leads to a > 10 fold increase in the levels of [BLT.sub.1] mRNA without any significant effects on [BLT.sub.2] mRNA. In parallel, LPS also increases the amounts of [BLT.sub.1] protein. Tumor necrosis factor-[alpha] (TNF-[alpha]) increases the expression of [BLT.sub.2] mRNA [approximately equal to] 6 times above basal levels with only a modest increase in [BLT.sub.1] mRNA. Interleukin-1 [beta] causes variable and parallel increases of both [BLT.sub.1] and [BLT.sub.2] mRNA. The natural ligand [LTB.sub.4] also increases [BLT.sub.1], but not [BLT.sub.2], mRNA and protein expression. Along with the induction of [BLT.sub.1] and/or [BLT.sub.2], HUVEC acquire the capacity to respond to [LTB.sub.4] with increased levels of intracellular calcium and these signals can be blocked by isotype selective BLT antagonists, CP-105696 and LY-255283. In addition, treatment of HUVEC with [LTB.sub.4] causes increased release of both nitrite, presumably reflecting nitric oxide (NO), and monocyte chemoattractant protein-1. Our data indicate that expression of functional BLT receptors may occur at the surface of endothelial cells in response to LPS, cytokines, and ligand, which in turn may have functional consequences during the early vascular responses to inflammation. Moreover, the results point to BLT receptors as potential targets for pharmacological intervention in LT-dependent inflammatory diseases such as asthma, rheumatoid arthritis, and arteriosclerosis. inflammation | arteriosclerosis | rheumatoid arthritis | asthma | nitric oxide

p38 mitogen-activated protein kinase (MAPK) regulates cytokines in arthritis and is, in turn, regulated by MAPK kinase (MKK) 3 and MKK6. To modulate p38 function but potentially minimize toxicity, we evaluated the utility of targeting MKK3 by using [MKK3.sup.-/-] mice. These studies showed that TNF-[alpha] increased phosphorylation of p38 in WT cultured synoviocytes but that p38 activation, IL-1[beta], and IL-6 expression were markedly lower in [MKK3.sup.-/-] synoviocytes. In contrast, IL-1[beta] or LPS-stimulated p38 phosphorylation and IL-6 production by [MKK3.sup.-/-] synoviocytes were normal. Detailed signaling studies showed that NF-[sub.[kappa]]B also contributes to IL-6 production and that TNF-[alpha]-induced NF-[.sub.[kappa]]B activation is MKK3-dependent. In contrast, LPS-mediated activation of NF-[sub.[kappa]]B does not require MKK3. To determine whether this dichotomy occurs in vivo, two inflammation models were studied. In K/BxN passive arthritis, the severity of arthritis was dramatically lower in [MKK3.sup.-/-] mice. Phospho-p38, phospho-MAPK activator protein kinase 2, IL-1[beta], CXC ligand 1, IL-6, and matrix metalloproteinase (MMP) 3 levels in the joints of [MKK3.sup.-/-] mice were significantly lower than in controls. Exogenous IL-1[beta] administered during the first 4 days of the passive model restored arthritis to the same severity as in WT mice. In the second model, IL-6 production after systemic LPS administration was similar in WT and [MKK3.sup.-/-] mice. Therefore, selective MKK3 deficiency can suppress inflammatory arthritis and cytokine production while Toll-like receptor 4-mediated host defense remains intact. cytokines | inflammation | rheumatoid arthritis | fibroblast | signal transduction

Rheumatoid arthritis (RA) is a common, chronic disease where health-related quality of life (HRQL) is one of the main goals of therapy. As such, instruments used to measure HRQL in RA must be able to discriminate across RA severity. The two basic categories of instruments used to measure HRQL are generic instruments and disease-specific instruments. Generic instruments can be further subdivided into preference-based measures which yield both single and multi-attribute utility values anchored at zero (death) and 1.00 (perfect health) as a measure of HRQL. The scores from these types of instruments can be integrated into cost-utility analyses as the weightings for quality adjusted life years. We assessed the construct validity of utility scores from four generic preference-based measures (the Health Utilities Index 2 and 3 (HUI2, HUI3), the EuroQol 5D (EQ-5D), and the Short Form 6-D (SF- 6D) and disease specific measures (the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and the Health Assessment Questionnaire (HAQ)) in a sample of 313 RA patients in British Columbia, Canada. We also estimated the minimally important differences (MID) for each of the measures. Generally, as anticipated, the disease-specific measures were better able to discriminate across groups with higher RA severity: however, utility scores from each of the scales also appeared to discriminate well across RA severity categories. The MID values agreed with those previously reported in the literature for the HUI2, SF-6D and the HAQ and provided new information for the HUI3, EQ-5D and the RAQoL. We conclude that the all of the preference-based utility measures that were evaluated appear to adequately discriminate across levels of RA severity. Keywords: Utility; Rheumatoid arthritis; Construct validity; Canada

Byline: Masaaki Inaba (1), Mayumi Nagata (1), Hitoshi Goto (1), Yasuro Kumeda (1), Keisuke Kobayashi (1), Kiyoshi Nakatsuka (1), Takami Miki (1), Shinsuke Yamada (1), Eiji Ishimura (1), Yoshiki Nishizawa (1) Keywords: ADL; Calcaneus; Osteoporosis; pQCT; Rheumatoid arthritis Abstract: Rheumatoid arthritis (RA) is a major cause of secondary osteoporosis and is frequently associated with both paraarticular and generalized osteoporosis. The present study was designed to investigate the preferential sites of reduction of bone mineral density (BMD), in the early stage of RA, with special emphasis on the differential effect of RA on BMD in trabecular and cortical components. The participants (30 RA patients and 26 healthy participants) were all female with disease duration of less than 1 year. BMD in the radius was measured at 4% (ultradistal site) and 20% (midshaft) to the ulnar length proximal to the end of radius by peripheral quantitative computed tomography. BMD in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. RA patients showed lower BMD preferentially in the trabecular component, but not in cortical bone component of the ultradistal radius than age-matched normal controls. Calcaneus OSI was also significantly reduced. The radial midshaft and lumbar spine did not differ significantly between RA patients and normal controls. Trabecular BMD in the ultradistal radius exhibited negative correlations with serum CRP, ESR, and RF, and calcaneus OSI with M-HAQ score. In conclusion, it was suggested that disease activity of RA and impairment of daily physical activity might be a significant determinant of deterioration of bone structure in paraartciular distal radius and calcaneus, respectively, in early-stage RA patients. Author Affiliation: (1) Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, 545--8585, Osaka, Japan Article History: Received Date: 28/10/2002 Accepted Date: 24/03/2003 Online Date: 22/07/2003

The challenge of caring for patients with a fever of unknown origin is described based on the case of a 59-year-old man. Fever of unknown origin means the doctors cannot find an obvious cause of the fever. In this case, it was Still's disease, which is characterized by fever, arthritis in only one or two joints, and a salmon-colored rash.

ABSTRACT: Diagnosis of rheumatoid arthritis starts with determining whether a patient's pain originates in the joints. Laboratory testing is useful for identifying the type of arthritis present. Standard testing includes [...]

ABSTRACT: The goals of the examination of the patient with established rheumatoid arthritis (RA) include assessing disease activity, evaluating functional status, examining for extra-articular disease, and detecting drug toxicity. Disease [...]

ABSTRACT: Correct diagnosis of rheumatoid arthritis (RA) early in the disease is believed to be the key to effective treatment. An improved understanding of the clinical features of the disorder [...]