Imaging plays an important role in the diagnosis as well as in the assessment of disease progression. Joints in the hands, wrists and feet have smaller bones and thinner cartilage than the larger joints. Therefore, early radiographic changes are better seen in them and are recommended radiographs at the baseline and for the periodic assessment of joint disease in the follow-up. The earliest abnormality is periarticular osteopoenia, which is nonspecific and variable. With uncontrolled disease more characteristic changes of cartilage loss (joint space narrowing) and bony erosions appear by 6 to 12 months and keep accumulating over time. Magnetic resonance imaging (MRI) and ultrasonic joint examination are more sensitive for detecting joint changes including synovial hypertrophy, joint effusion, tendon and ligament disease, erosions and rupture of joint cysts (e.g. Baker’s cyst) than routine radiographs. They could be useful in early arthritis when clinical examination and standard radiographs may be unhelpful. (2)
129 Read more
Our results also confirm previous data showing that the distal airway compartment is not sterile and provide de- tailed characterization of the local bacterial taxa using high-throughput sequencing. Although the material stud- ied here is a unique one (consisting of BAL of early- untreated RA patients with short symptom duration and no clinical signs of lung involvement), the relatively low number of participants is a limitation. Bronchoscopic sampling was restricted to only one site in the lower air- ways, thus regional variation could not be investigated. Additionally, no oral samples were concomitantly ob- tained, so the question of cross-contamination with oral secretions could not be evaluated. However, contamin- ation with oropharyngeal microbiota, once a matter of great debate, has not been shown to be a major and fre- quent event that would preclude utilization of bronchos- copy to sample the lower airways [14, 15, 23, 35]. Further, although technical controls were included in our se- quence, BAL samples were obtained prior to adapting our now standardized protocol that uses broncho- scopic environmental controls. This controls may also be of relevance for microbiome studies with low bio- mass samples [36, 37]. Although healthy subjects were significantly younger, age has not been found to be a major factor in other lung microbiome studies [14, 22, 26]. However, it is conceivable that an age-related decrease in bacterial clearance and/or a relatively less robust immune response to the antigenic load could
10 Read more
gender, and CCP positivity) should lower the threshold for evaluation. Though patients with limited mobility from their joint disease are at risk of presenting with more severe pulmonary involvement, screening for pulmonary involve- ment in the asymptomatic patient should occur with a clear plan in mind for dealing with the findings. There is no data to guide the treatment of preclinical disease and is therefore of uncertain benefit. In patients with suggestive signs or symptoms, pulmonary physiology can be useful; however, patients with early and mild disease may have normal PFTs and more sensitive testing for ILD requires an HRCT. Defining the underlying subtype of ILD by histopathologic pattern (NSIP, UIP) is helpful to stratify patients’ risk for disease progression and early mortality; however, HRCT pat- terns are highly predictive of the underlying histopathology and lung biopsy is reserved for cases with atypical clinical or chest imaging features.
11 Read more
patients had systemic or autoimmune disease.  Indeed, ILD under RTX is very rare and does not exceed 0.03% (540,000 cases treated).  Recently, a randomized controlled trial evaluating efficacy and tolerance of RTX in 465 RA patients did not record any correlation with the occurrence of ILD.  Otherwise, some observational studies suggest an effect benefit of RTX on ILD associated with others connectivites especially systemic scleroderma and systemic lupus.  Two recent retrospective studies assessing RTX tolerance in patients PR with an associated ILD (n = 19 and n = 49 respectively) report a stabilization of the pulmonary involvement.  Waiting for other prospective clinical trials and multicenter studies evaluating the efficacy and tolerance of RTX in ILD associated with RA. Finally and according to the data of literature, RTX remains relatively well tolerated in associated ILD with RA.
Rheumatoid arthritis is a systemic inflammatory disorder that most commonly affects the joints, causing progressive, symmetric, erosive destruction of cartilage and bone, which is usually associated with autoantibody production. Rheumatoid arthritis affects ∼ 1% of the population in developed countries. The incidence and prevalence of rheumatoid arthritis in developing countries is thought to be lower, but is difficult to quantify. Although joint disease is the main presentation, there are a number of extra-articular manifestations including subcutaneous nodule formation, vasculitis, inflammatory eye disease and lung disease. Of these manifestations, lung disease is a major contributor to morbidity and mortality. In some cases, respiratory symptoms may precede articular symptoms. It is critical for the pulmonologist to assess for systemic and articular signs and symptoms of connective tissue disease when evaluating a patient with pulmonary disease of unknown aetiology as patients may initially present with pulmonary symptoms. There are a variety of pulmonary manifestations of rheumatoid arthritis, including pulmonary parenchymal disease (interstitial lung disease (ILD)) and inflammation of the pleura ( pleural thickening and effusions), airways and pulmonary vasculature (vasculitis and pulmonary hypertension). These changes may reflect chronic immune activation, increased susceptibility to infection (often related to immunomodulatory medications) or direct toxicity from disease modifying or biological therapy. Prognosis varies depending on the type and severity of involvement. Herein, we review the various manifestations of rheumatoid arthritis-associated lung disease, as well as the recent advances in treatment.
16 Read more
Fig. 4 Estrogen increases immunoglobulin G (IgG) glycosylation in postmenopausal patients with rheumatoid arthritis (RA). Forty-nine postmenopausal women with active RA in a randomized controlled trial were receiving either hormone replacement therapy (HRT) or no HRT. Serum samples were taken at baseline and after 1 year and 2 years of treatment. a Anticitrullinated protein antibody concentrations ( n = 20 – 29; 7 anti-cyclic citrullinated peptide [anti-CCP]-negative patients were excluded from further studies). Mass spectrometry-based analysis of (b) sialic acids, (c) galactose, and (d) fucose on the Fc portion of IgG. Statistical analysis was performed with t tests at selected time points, as well as an investigation over time in HRT-treated individuals. * p < 0.05, ** p < 0.01 ( n = 17 – 25). Groups are presented with a bar indicating mean with SEM. e Messenger RNA (mRNA) expression of St6gal1 and B4galt1 from B cells isolated from peripheral blood collected from healthy donors and stimulated with CpG, interleukin-2, and goat antihuman IgA/IgG/IgM F(ab ′ ) 2 fragments for 5 days to induce plasmablast differentiation. For the last 48 hours, the
11 Read more
Objectives Biologic disease-modifying antirheumatic drugs (bdMArds) have revolutionised treatment and outcomes for rheumatoid arthritis (rA). the expanding repertoire allows the option of switching bdMArd if current treatment is not effective. For some patients, even after switching, disease control remains elusive. this analysis aims to quantify the frequency of, and identify factors associated with, bdMArd refractory disease. Methods patients with rA starting first-line tumour necrosis factor inhibitor in the British Society for rheumatology Biologics register for rA from 2001 to 2014 were included. We defined patients as bdMArd refractory on the date they started their third class of bdMArd. Follow-up was censored at last follow-up date, 30 november 2016, or death, whichever came first. Switching patterns and stop reasons of bdMArds were investigated. Cox regression identified baseline clinical factors associated with refractory disease. Multiple imputation of missing baseline data was used. results 867 of 13 502 (6%) patients were bdMArd refractory; median time to third bdMArd class of 8 years. In the multivariable analysis, baseline factors associated with bdMArd refractory disease included patients registered more recently, women, younger age, shorter disease duration, higher patient global assessment, higher Health Assessment Questionnaire score, current smokers, obesity and greater social deprivation. Conclusions this first national study has identified the frequency of bdMArd refractory disease to be at least 6% of patients who have ever received bdMArds. As the choice of bdMArds increases, patients are cycling through bdMArds quicker. the aetiopathogenesis of bdMArd refractory disease requires further investigation. Focusing resources, such as nursing support, on these patients may help them achieve more stable, controlled disease.
and Her-2/neu , and to inhibit cell death induced by deregulated c-myc , H-Ras , and TNFα . Pre- cisely how Akt activates NF- κ B-dependent transcription is a matter of debate. Several groups, including that of the present author, demonstrated an involvement of IKK, thus implicating I κ B-dependent mechanisms [32,37,39,41,42], while results by other workers demonstrate IκB-indepen- dent mechanisms, in which Akt potentiates the transcrip- tional function of NF- κ B [38,40]. It is possible that the mechanisms connecting Akt with NF-κB, as well as the contribution of NF- κ B pathway in the anti-apoptotic func- tion of Akt, are cell type and stimulus specific. A role for Akt in the pathogenesis of RA and the contribution of Akt to NF- κ B activation in RA synovium are not known, but there is circumstantial evidence that this link may exist. The activity of the PI(3)K/Akt pathway is negatively regu- lated by the phosphatase PTEN, a tumor suppressor fre- quently inactivated in human malignancies  and in some autoimmune diseases, such as Cowden disease and Sjögren’s syndrome . The importance of the PTEN-PI(3)K/Akt connection in autoimmune disease was demonstrated by observations in PTEN +/– heterozygous
The progress of the clinical manifestations of the Amavata (Rheumatoid arthritis) patients of this clinical study was assessed on the basis of important common clinical features of the Amavata which are mentioned in Ayurvedic classics as well as closely resembles with Rheumatoid arthritis and also with the help of criteria fixed by the American Rheumatology Association in 1988 and implemented it after some modification. Sandhishula (Joint pain), Sandhishotha (Joint swelling), Sandhi- sthabdhata (Joint stiffness), Sandhi-sparsha- asahyatva (Joint tenderness), Angamarda (Body ache), Gaurava (Heaviness of the Body), Agni- dourblya (Impaired digestive capacity) were selected as important common clinical features of Amavata for this study and the scoring pattern was adopted separately for assessment of those clinical features.
Additional file 2: Table S2. Distributions of potential risk factors for occurrence of cardiovascular events in RA patients at baseline, according to presence of IgM and/or anti-CCP antibodies. (RA: rheumatoid arthritis; CV: cardiovascular; SD: standard deviation; LDL: low density lipoprotein; GlyHb: glycated hemoglobin; ESR: erythrocyte sedimentation rate; Hs CRP: high sensitivity C-reactive protein; anti CCP: anti cyclic citrullinated pro- tein; IgM RF: IgM rheumatoid factor; DAS28: disease activity score in 28 joints; DMARD: disease modifying antirheumatic drug; MTX: methotrexate; TNF inhibitor: tumour necrosis factor α inhibitor; NSAID: non steroidal anti inflammatory drug). *p<0.05 seronegative vs seropositive.
body production are confined to the gut-associated lymphoid tissues (20, 21). Binding studies have demonstrated the capa- bility for antigen-presenting cells to present efficiently shared epitope peptides (this study and references 6, 7). Therefore, failure to confine T cell responses against QKRAA epitope to mucosal tissues could represent an acquired immune abnor- mality in SE positive individuals which associates with the de- velopment of RA. In summary, the elevated peripheral blood T cells’ proliferative responses to QKRAA of SE positive pa- tients are specifically associated with rheumatoid disease, whereas the immune response genes influence magnitude and specificity of the antibody response to the epitope. The exact environmental factors which induce the peripheral spreading of the cellular immune response to the SE are not known (22, 23). The formal testing of this “multistep molecular mimicry” hypothesis may ultimately require the development of a better animal model of RA and analysis of the cytokine patterns of QKRAA-specific T cells. Future studies should also determine if the assessment of immune responses to one or several micro- bial antigens that express QKRAA has prognostic value in pa- tients with early rheumatoid disease.
Trust Case Control Consortium, 2007). The long-established association with the human leukocyte antigen (HLA)–DRB1 locus has been confirmed in patients who are positive for rheumatoid factor or ACPA, alleles that contain a common amino acid motif (QKRAA) in the HLA-DRB1 region, termed the shared epitope, confer particular susceptibility (Gregersen, 1987). These findings suggest that some predisposing T-cell repertoire selection, antigen presentation, or alteration in peptide affinity has a role in promoting autoreactive adaptive immune responses. Other possible explanations for the link between rheumatoid arthritis and the shared epitope include molecular mimicry of the shared epitope by microbial proteins, increased T-cell senescence induced by shared epitope– containing HLA molecules, and a potential proinflammatory signaling function that is unrelated to the role of the shared epitope in antigen recognition (Weyand, 1990; De Almeida, 2010). Many other identified risk alleles in ACPA-positive rheumatoid arthritis consistently aggregate functionally with immune regulation implicating nuclear factor κB (NF-κB)– dependent signaling (e.g., TRAF1–C5 and c-REL) and T-cell stimulation, activation, and functional differentiation (e.g., PTPN22 and CTLA4) (Begovich, 2004; Kurreeman, 2007; Plenge, 2007; Remmers, 2007). Moreover, gene–gene interactions that increase disease risk, as described between HLA-DRB1 and PTPN22, exemplify the complexity of the net risk conferred by any given gene (Kallberg, 2007).
Institutional Ethics Board approval was ob- tained from the Medical Ethics Committee of Zhuzhou Central Hospital. All participating patients were formally informed for the pur- pose of this study and the written informed consents were obtained from all participants. There were totally 75 cases of RA (29 males and 46 females) enrolled in this study. All patients were subjected to the criteria of 2010 ACR/EULAR Classification Criteria for RA. Among 75 patients, there were 37 cases of RA-ILD (subjecting to Interstitial lung diseases diagnosis criteria of American Thoracic Society/ European Respiratory Society). The other 38 cases of RA only patients were served as con- trol group. Exclusion criteria included: 1) RA patients with lung infection, pulmonary tuber- culosis, chronic obstructive pulmonary disease, bronchiectasis or lung tumor; 2) RA patients with pneumoconiosis or interstitial lung dis- ease due to Inhalation of organic dusts; 3) RA
families, histocompatibility testing suggested that susceptibility to arthritis was controlled by a dominant allele with variable penetrance and expressivity at the rheumatoid-like arthritis, first locus (RLA-1). The combined lod scores for the four families (2.70) indicated that the odds in favor of genetic linkage between the major histocompatibility complex and the postulated disease susceptibility gene, RLA-1, were 500:1. In one family, a recombinant event permitted localization of RLA-1 centromeric to HLA-D. Of major interest was the fact that there was significant pleomorphism in the clinical manifestations of arthritis in affected individuals. In some, symptoms first occurred in childhood and in others, in adult life. Even among those with childhood-onset arthritis, different types of juvenile rheumatoid arthritis were observed within the same family.
15 Read more
et al. . To evaluate arthritic pain, the rat was placed in the test box of an incapacitance meter in which a slanted plank is located. The bearing force of each hind limb was quantified by two mechanotransducers, separately placed below the two hind limbs: one is normal and the other is the arthritic limb. The bearing force of each hind limb was estimated as a 5-s aver- age, and the mean bearing force was calculated from four sep- arate estimations. The WDR percentage was calculated as percentage WDR = 100 × (weight borne by ipsilateral limb/ total weight borne by both limbs). The WDR of the hind paws in the normal group was 50:50 (data not shown), indicating that 50% of the weight was carried in each hind paw. As the pain and swelling of the ankle progressed due to induction of arthritis, the balance of weight was disrupted, resulting in a reduction of the WDR in the arthritic leg. All behavioral tests were performed blinded.
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that strongly affects quality of life [1–3]. The core set of outcome measures for RA clinical trials includes three patient-reported outcomes (PROs): pain, physical functioning and patient global assessment of disease activity . In addition, the Outcome Measures in Rheumatology (OMERACT) group, an independent initiative of international health professionals and patient experts interested in outcome measures in rheumatol- ogy, has recommended that fatigue should also be mea- sured in all RA clinical trials; furthermore, sleep quality and ability to work have both been mentioned as im- portant outcomes and targeted for further instrument development [5–7]. Several questionnaires now exist to assess these PROs separately [8–10].
4. Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC: Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum 2003, 48(4):917 – 926. 5. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH, National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part I. Arthritis Rheum 2008, 58(1):15 – 25.
previously identified RNP, Sm, Ro, and La antigens either singly or in combinations. These antigens, which are located on discrete sets of small nuclear or cytoplasmic RNA-protein particles, exhibited a number of antigenic interrelationships. One patient's serum recognized a new particle containing a small RNA which we have called Th; it also precipitated the Ro complexes. Other patients with systemic lupus erythematosus, hepatitis B virus infection, juvenile rheumatoid arthritis, myositis, and rheumatoid arthritis had antibodies that
Rheumatoid Arthritis (RA) is an autoimmune, poten- tially systemic disease characterized by an inflammatory, symmetric, additive and erosive arthritis affecting about 1% of the population of developed countries . The pathogenesis of the disease is currently not fully under- stood, but the lung seems to be a possible source of autoimmunity. Exposure to dust and smoke can lead to the citrullination of peptides, provoking an autoimmune response, with the production of Anti Cyclic Citrulli- nated Antibodies (ACPA) which represent one of the most specific items for the diagnosis [5, 6]. Probably due to autoimmune mechanisms, RA can be directly associ- ated with respiratory system damage not only with ILD, but also with bronchiectasis, pleural effusion, rheuma- toid parenchymal nodules and, rarely, vascular disease. Indirectly RA-associated respiratory damage (generally with ILD or respiratory tract infections) can be caused by the drugs used for treatment .
11 Read more
In this research all informants referred to how they receive support primarily from their partners and immediate families as they prepare food for the family and care for their children. It remained unquestioned that the women performed these activities. Veronika underscored that she does not want to sound egocentric when occasionally taking time to go for manicure; Erika stated that it is a challenge for her to accept tangible support at home as she provides care and support to others as part of her part-time employment. Negotiating support also contained for Julia and Lisa the work of moderating their parents in their efforts to provide them continuously with appointments for and information about complementary treatment. Similarly to the findings by Goodacre and Goodacre (2003) and Nyman and Larsson Lund (2007), the women in this study were negotiating support by and with significant persons. Grant (2001) highlighted that in particular for mothers with rheumatoid arthritis receiving support can become a challenge if the mothers find themselves within a traditional, conservative context. While the participants in the study by Grant (2001) referred in particular to support offered by the women’s partners, this research has also pointed out that social relations informing support are very complex and include the support of the own family and family-in-law, and goes beyond tangible and emotional support. This institutional ethnography disclosed the time, effort, and intent that go into negotiating support and care if support becomes for instance too overwhelming.
233 Read more