Presence Of Rheumatoid Nodules Research Articles

Prevalence of Autoantibodies (ACPA) and Rheumatoid Factor among Rheumatoid Arthritis Patients in Sulaymaniyah

Background and objectives: Rheumatoid factor and anticitrullinated protein antibodies are the most characteristic autoantibodies for rheumatoid arthritis. Our aims were to evaluate the prevalence of Rheumatoid factor and anticitrullinated protein antibodies and their association with demographic and clinical characteristics of patients with RA. Methods: This is a cross-sectional study which was conducted at Rheumatology and Rehabilitation Center/Sulaymaniyah from February 2022 to November 2022. The study included patients with rheumatoid arthritis from both sexes. Socio-demographic and clinical data were collected. Enzyme linked immunosorbent assay was used to estimate serum levels of rheumatoid factor and anticitrullinated protein antibodies antibody titer. Results: The prevalence of rheumatoid factor was 72.61%. Each of high disease activity, mean DAS28 scores, rheumatoid nodules and deformities were significantly associated with rheumatoid factor positivity (P= 0.015, P= 0.025, P= 0.007 and P<0.001, respectively). The prevalence of anticitrullinated protein antibodies was 68.87%. High disease activity, rheumatoid nodules and deformities were significantly associated with anticitrullinated protein antibodies (P= 0.014, P<0.001 and P<0.001, respectively). Conclusions: The prevalence of rheumatoid factor and anticitrullinated protein antibodies among patients with rheumatoid arthritis was within the global context. High disease activity and the presence of rheumatoid nodules are positively associated with rheumatoid factor-positivity. Number of tender joints and the presence of rheumatoid nodules were positively associated with anticitrullinated protein antibodies-positivity.

Predictors of biologic disease modifying antirheumatic drugs withdrawal due to the development of adverse events in patients with rheumatoid arthritis

Currently, a large number of highly effective biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are used for the treatment of rheumatoid arthritis (RA). However, in addition to effectiveness, it is necessary to evaluate the risk of adverse events (AEs) when using them.Objective: to determine the predictors of bDMARDs and tsDMARDs discontinuation due to AEs in patients with RA.Patients and methods. The study included 661 patients with RA who took bDMARDs and tsDMARDs. The search for predictors of targeted therapy discontinuation due to AEs was carried out in two stages. At the first stage, using the Kaplan-Meier method, we selected indicators that showed the greatest significant single-factor relationship with the duration of retention on therapy. At the second stage, significant independent indicators were obtained by iterative selection of variables within the multivariate proportional risk model according to Cox.Results and discussion. The presence of rheumatoid nodules (p<0.001), high doses of glucocorticoids (GC; p<0.001), low doses of methotrexate (MT; p=0.009) are significant independent factors for increasing the risk of drugs discontinuation due to the development of AEs. The type of bDMARDs/tsDMARD used also significantly correlated with the risk of discontinuation of therapy due to AEs. A relatively high risk of treatment discontinuation was observed with infliximab (IFN) and certolizumab pegol (CZP). Cancellation of IFN was associated with the occurrence of infusion reactions and infectious complications, and CZP was associated with infectious complications.Conclusion. An increase in the dose of MT and decrease in the use of GCs can help prevent the development of AEs leading to the abolition of biologics and tsDMARDs. Significant differences were found between bDMARDs in terms of the risk of their cancellation due to AEs.

Comparison between Young and Elderly Onsetof Rheumatoid Arthritis in a Romanian Cohort

Rheumatoid arthritis (RA) is a chronic inflammatory disease that predominantly affects middle-aged adults in the third to fifth decades of life, but can also occur at any age. Significant differences were observed between patients with the diagnose of the disease under the age of 65 years – young- onset of RA (YORA) and those with the onset over the age of 65 years -elderly-onset of RA (EORA). The literature has shown that patients in the EORA group, in comparison to the young, have more severe onset, shorter duration of morning stiffness, lower frequency of sero- positivity and a more important biological inflammatory syndrome. Objective: Describe and compare the clinical characteristics, laboratory features, functional status, therapeutic approach and disease progression in elderly-onset and young-onset rheumatoid arthritis (RA) patients. Materials and methods: This retrospective, transversal study included 102 patients diagnosed with rheumatoid arthritis according to the ACR / EULAR criteria and who had at least 3 visits to our clinic, the last one during 2019-2020. Depending on the age at disease onset, we divided them into 2 groups- EORA and YORA and analyzed them comparing the clinical, laboratory and treatment data obtained at diagnosis. Subsequently we studied the evolution of the disease activity and the therapy efficiency at 6 months of follow-up and at the last hospitalization for each group. Results: The percentage of women is similar and predominant in both groups, YORA and EORA (68.3% and 71.8%). YORA was associated with a longer disease length and a prolonged symptom duration prior to the diagnosis in comparison to EORA (p<0.001 and P=0.002). Extra-articular manifestations were more frequent in elderly onset RA patients at diagnosis, especially the presence of rheumatoid nodules (46.2% vs 22.2%. p=0.011) and weight loss (82.1% vs 34.9%, p<0.001). Anemia was statistically associated with the EORA group (p=0.037). Analyzing the radiological findings, there was a greater number of patients who showed erosions (48.7%) and geodes (28.2%) in EORA, than in YORA group (33.3% and 19.0%). The prevalence of specific auto-antibodies positivity as anti-CCP was higher in YORA (76.2% vs 53.8%, p=0.019), as well as the positivity of Rheumatoid factor (RF) (84.1% vs 61.5%, p=0.010). The majority of patients began treatment with synthetic DMARD monotherapy, 54.0% of YORA and 64.1% of EORA. Methotrexate was the main drug administrated in both groups (61.5% in EORA and 54.0% in YORA, p-value= 0.602). Other medications, such as Sulfasalazine and Leflunomide, were less preferred in the two groups. Biologic therapy was preferred in younger patients than in those with RA at 65 years of age or over (69.8% vs 35.9%, p=0.001). Disease activity measured with DAS28(CRP) score was similar between the two groups at baseline, but significantly lower for YORA patients measured at the last hospitalization (p=0.020), treat to target (low disease activity and remission) being achieved in 53% of cases in the YORA group versus 23% of EORA patients (p=0.002). Conclusions: The definite diagnosis of RA was delayed in YORA patients in comparison to EORA patients and the extra-articular manifestations of the disease were more frequently found in the EORA group. Seropositivity was statistically significantly associated with the YORA group. Anemia was predominant in patients with disease onset over 65 years old. Both groups underwent DMARDs therapy in the early stages of the disease, but biologic therapy was more often administered in younger patients. Disease activity at diagnosis was similar in both groups, but in dynamic, the treat to target endpoint was achieved more frequent in YORA population.

INVESTIGATION OF THE FREQUENCY OF FC GAMMA RECEPTOR IIIA V/158/F GENE POLYMORPHISM AND COMPARISON OF CLINICAL AND LABORATORY FINDINGS IN RHEUMATOID ARTHRITIS (RA)

<div><!--block-->Objective: Rheumatoid Arthritis (RA) is a chronic multisystem disease with unknown etiology that progressively affects peripheral joints. Receptors, which serve as links between humoral and cellular immune responses, recognize the Fc region of immunoglobulin G (FcR) and have become the focus of many research studies concerning the etiology and pathogenesis of autoimmune diseases. This region displays extensive genetic variation, which has been associated with susceptibility to various chronic inflammatory disorders including RA. This study aimed to investigate the frequency of the FcγRIIIA V158F genetic polymorphism and compare clinical and laboratory findings in RA.&nbsp;<br><br>Materials and Methods: Between April 2010 and June 2011, 105 patients, who had been diagnosed with RA according to the American Rheumatology Association (ARA) diagnostic criteria, were admitted to the Cukurova University Department of Rheumatology outpatient clinic and 110 healthy controls were included in this study. Patient groups were divided into stages using the ARA functional classification. The FcγRIIIA V158F gene polymorphism of patients was investigated from blood samples using the real-time Polymerase Chain Reaction (PCR) method.&nbsp;<br><br>Results: There was no significant difference in the distribution of the FcγRIIIA polymorphism between patients and controls (p=.106). There were no significant differences between the distribution of age at diagnosis of patients with the gene polymorphism (p=.919) or in the gene polymorphism (p=.552). No association was found between the gene polymorphism and clinical signs of disease such as eye involvement and the presence of rheumatoid nodules. There was also no significant association between the gene polymorphism with rheumatoid factor, anticyclic citrullinated peptide, and antinuclear antibodies (p=.625, p=.136, p=.716, respectively).&nbsp;<br><br>Conclusion: In our study, no significant relationship was found between the FcγRIIIA V158F gene polymorphism and the pathogenesis of RA.&nbsp;</div>

Rhupus syndrome. A rare combination

Abstract Rhupus syndrome is a rare combination of rheumatoid arthritis and systemic lupus erythematosus, and is characterized by the presence of erosive arthritis together with symptoms and signs of systemic lupus erythematosus. Among its complications, is the presence of rheumatoid nodules, and neurological and renal involvement that further complicates its prognosis, thus significantly reducing the perception of health-related quality of life in patients who suffer from it. The case is presented of a female patient diagnosed with lupus erythematosus, who during the course of the disease, developed clinical and humoral signs that led to the diagnosis of syndrome Rhupus syndrome. This is believed to of relevance to the knowledge of the medical community.

Disease Activity, Oxidized-LDL Fraction and Anti-Oxidized LDL Antibodies Influence Cardiovascular Risk in Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have a shortened lifespan compared to the general population. The high rate of premature mortality in the RA population can be attributed to cardiovascular disease (CVD). The aim of the study was to look for non-classic risk factors that can at least partially explain the enhanced cardiovascular (CV) risk in patients with RA. This was an observational study with 37 RA patients and 24 healthy volunteers as controls. The participants' medical history was taken, and systematic coronary risk evaluation (SCORE) and carotid ultrasonography examinations were performed on all the participants. Laboratory tests included antibodies anti-cyclic citrullinated peptide (anti-CCP), inflammatory markers, lipid level, oxidized low-density lipoprotein (oxLDL) level and the level of anti-oxLDL antibodies. Both SCORE and oxLDL fraction were elevated in RA patients as compared to the healthy controls (3.1 ± 3.7 vs. 0.8 ± 1.2, p = 0.005; and 0.029 ± 0.033% vs. 0.014 ± 0.006%, p = 0.04, respectively). In the RA group, the presence of anti-CCP was associated with thickening of the carotid intima-media complex and SCORE elevation. In the RA group, significant correlations were found between SCORE and mean carotid intima-media thickness (IMT; RP = 0.34, p = 0.040), disease activity score (RP = 0.42, p = 0.011), erythrocyte sedimentation rate (ESR; RP = 0.35, p = 0.036), and disease duration (RP = 0.52, p = 0.002). In RA patients with carotid plaques, the oxLDL fraction was significantly elevated in comparison to those without plaques (0.055 ± 0.070% vs. 0.022 ± 0.018%, p = 0.033). In the RA group, there was a significant negative correlation between mean carotid IMT and the serum concentration of anti-oxLDL antibodies (RP = -0.38, p = 0.02). No association was noted between the presence of rheumatoid nodules and SCORE or carotid IMT. Among RA patients, disease activity, ESR, disease duration, the presence of anti-CCP antibodies, the oxLDL fraction and the level of anti-oxLDL antibodies influence CV risk.

Occurrence and Effect of Lower Extremity Ulcer in Rheumatoid Arthritis — A Population-based Study

To assess the occurrence, risk factors, morbidity, and mortality associated with lower extremity (LE) ulcers in patients with rheumatoid arthritis (RA). Retrospective review of Olmsted County, Minnesota, USA, residents who first fulfilled the 1987 American College of Rheumatology criteria for RA in 1980-2007 with followup to death, migration, or April 2012. Only LE ulcers that developed after the diagnosis of RA were included. The study included 813 patients with 9771 total person-years of followup. Of them, 125 developed LE ulcers (total of 171 episodes), corresponding to a rate of occurrence of 1.8 episodes per 100 person-years (95% CI: 1.5, 2.0 per 100 person-yrs). The cumulative incidence of first LE ulcers was 4.8% at 5 years after diagnosis of RA and increased to 26.2% by 25 years. Median time for the LE ulcer to heal was 30 days. Ten of 171 episodes (6%) led to amputation. LE ulcers in RA were associated with increased mortality (HR 2.42; 95% CI 1.71, 3.42), adjusted for age, sex, and calendar year. Risk factors for LE ulcers included age (HR 1.73 per 10-yr increase; 95% CI 1.47, 2.04), rheumatoid factor positivity (HR 1.63; 95% CI 1.05, 2.53), presence of rheumatoid nodules (HR 2.14; 95% CI 1.39, 3.31), and venous thromboembolism (HR 2.16; 95% CI 1.07, 4.36). LE ulcers are common among patients with RA. The cumulative incidence increased by 1% per year. A significant number require amputation. Patients with RA who have LE ulcers are at a 2-fold risk for premature mortality.

Carotid atherosclerosis in patients with rheumatoid arthritis and rheumatoid nodules

ObjectiveTo determine whether an association exists between the presence of rheumatoid nodules and thickening of the intima-media and plaque of the carotid artery, which is evidence of atherosclerosis. Materials and methods: Observational, cross-sectional study of 124 patients with rheumatoid arthritis from a University Hospital clinic from 2005 to 2006. We divided the patients into 2 groups, 62 with rheumatoid nodules and 62 without rheumatoid nodules, matched for age and sex. Medical history, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide, rheumatoid factor, and a high resolution doppler ultrasound of the carotid arteries were performed. ResultsWomen comprised 89.5% of the patients. The prevalence of a carotid plaque was 57% in our population. The presence of a plaque was associated with age, arterial hypertension and abdominal circumference. Average intima-media thickness (IMT) in patients with a plaque was 0.085cm (±0.02). There was no correlation between laboratory parameters and thickening of the intima-media of the carotid artery. Subcutaneous nodules were present in 33 (47%) of the 70 patients with a carotid plaque and in 29 (54%) of patients without a carotid plaque (p = .471). ConclusionsWe did not find an association between rheumatoid nodules and the presence of a carotid plaque and thickening of the intima-media of the carotid in patients with rheumatoid arthritis.

Laryngeal involvement in rheumatoid arthritis

AbstractThe prevalence of laryngeal involvement in Rheumatoid Arthritis (RA) ranges from 13 to 75%. The specific RA manifestations include the cricoarytenoid arthritis and the presence of rheumatoid nodules in the vocal folds. ObjectiveThe objective of this study is to evaluate the prevalence of dysphonia and laryngeal alterations on videolaryngoscopy in RA patients and their association with disease activity. MethodThis is a clinical cross-sectional study that evaluated patients with rheumatoid arthritis as to their disease activity score in 28 joints (DAS-28), laryngeal symptoms, application of a Portuguese version of the Voice Handicap Index and videolaryngoscopy findings, comparing them with a control group. ResultsWe evaluated 47 (54%) patients with rheumatoid arthritis and 40 (46%) controls. The prevalence of dysphonia and videolaryngoscopy changes was respectively 12.8% and 72.4% in patients with RA. The mean of DAS-28 was 3.3 ± 1.2; 26 (74.3%) of 35 patients presenting active disease had laryngeal changes (p = 0.713). Posterior laryngitis was the most common diagnosis (44.7%). ConclusionThe prevalence of laryngeal disorders in RA patients was 72.4% and the prevalence of dysphonia was 12.8%. There was no significant relationship between laryngeal disorders and disease activity.

Carotid atherosclerosis in patients with rheumatoid arthritis and rheumatoid nodules

ObjectiveTo determine whether an association exists between the presence of rheumatoid nodules and thickening of the intima-media and plaque of the carotid artery, which is evidence of atherosclerosis. Materials and methodsObservational, cross-sectional study of 124 patients with rheumatoid arthritis from a University Hospital clinic from 2005 to 2006. We divided the patients into 2 groups, 62 with rheumatoid nodules and 62 without rheumatoid nodules, matched for age and sex. Medical history, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide, rheumatoid factor, and a high resolution doppler ultrasound of the carotid arteries were performed. ResultsWomen comprised 89.5% of the patients. The prevalence of a carotid plaque was 57% in our population. The presence of a plaque was associated with age, arterial hypertension and abdominal circumference. Average intima-media thickness (IMT) in patients with a plaque was 0.085cm (±0.02). There was no correlation between laboratory parameters and thickening of the intima-media of the carotid artery. Subcutaneous nodules were present in 33 (47%) of the 70 patients with a carotid plaque and in 29 (54%) of patients without a carotid plaque (p=.471). ConclusionsWe did not find an association between rheumatoid nodules and the presence of a carotid plaque and thickening of the intima-media of the carotid in patients with rheumatoid arthritis.

Alterações de tomografia pulmonar de alta resolução em pacientes com artrite reumatoide e suas associações com variáveis clínicas, demográficas, sorológicas e terapêuticas

Extra-articular manifestations are found in up to 50% of the patients with rheumatoid arthritis (RA). To assess the prevalence of pulmonary changes on high-resolution computed tomography (HRCT) in patients with RA and their association with demographic, clinical, serological and therapeutic variables. Seventy-one patients with RA were assessed regarding their age at RA onset, duration of disease, gender, tobacco use, presence of rheumatoid nodules, secondary Sjögren's syndrome, rheumatoid factor, presence of anti-CCP and antinuclear factor, respiratory complaints, use of medications, and pulmonary changes on HRCT. HRCT changes were identified in 55% of the patients, the most common being the presence of ground glass opacities, parenchymal bands, traction bronchiectasis, and honeycombing. None of the clinical variables studied associated with the HRCT findings, except for duration of the disease, which was longer in patients with pulmonary nodules and reticular lesions (ground-glass opacity). There is a high prevalence of HRCT changes in patients with RA, which do not associate with clinical, serological, therapeutic and demographic variables, except for duration of disease.

Relationship between arterial dysfunction and extra-articular features in patients with rheumatoid arthritis

Systemic inflammation may be a common process that underpins both atherosclerosis and extra-articular features (ExRA) of rheumatoid arthritis (RA). We evaluated the relationship between ExRA and arterial dysfunction in 114 consecutive patients with RA (82% women) without overt arterial disease aged 40-65years. A trained research nurse undertook 'SphygmoCor' pulse wave analysis (PWA) using radial applanation tonometry to measure the extent (augmentation index, AIX%) and timing (reflected wave transit time, RWT, msec) of aortic wave reflection. Assessment included fasting blood sample, patient questionnaire and medical record review. Mean differences were adjusted for age, sex, mean blood pressure, smoking pack-years, fasting cholesterol, Stanford HAQ score and erythrocyte sedimentation rate. Mean age was 54 (SD 7) and median RA duration 10 (IQR 4-17) years. There was a trend for arterial dysfunction (higher AIX%; lower RWT) to increase as the number of ExRA features rose, but no difference in AIX% (-0.5, 95%CI -2.8 to 1.8, P=0.65) or RWT (0.3ms, 95%CI -3.6 to 4.2, P=0.86) between 'any ExRA' and 'no ExRA'. Arterial dysfunction was not associated with the presence of rheumatoid nodules, Sjogren's syndrome or carpal tunnel syndrome. Our study was too small to determine whether severe ('Malmo') ExRA (vasculitis, pericarditis, episcleritis) was truly associated with a higher AIX% (3.8, 95%CI -2.3 to 9.9, P=0.22) and lower RWT (-5.5ms 95%CI -13.1 to 2.1, P=0.16). While arterial dysfunction may be associated with the number of ExRA features and severe ExRA, it does not appear to be associated with other ExRA features.

The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of extra-articular disease and predicts radiographic progression of joint destruction over 5 years

Objective: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome.Methods: In a cohort (n = 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0–448).Results: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression.Conclusion: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage.

Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis

IntroductionChemokines and their receptors control immune cell migration during infections as well as in autoimmune responses. A 32 bp deletion in the gene of the chemokine receptor CCR5 confers protection against HIV infection, but has also been reported to decrease susceptibility to rheumatoid arthritis (RA). The influence of this deletion variant on the clinical course of this autoimmune disease was investigated.MethodsGenotyping for CCR5d32 was performed by PCR and subsequent electrophoretic fragment length determination. For the clinical analysis, the following extra-articular manifestations of RA were documented by the rheumatologist following the patient: presence of rheumatoid nodules, major organ vasculitis, pulmonary fibrosis, serositis or a Raynaud's syndrome. All documented CRP levels were analyzed retrospectively, and the last available hand and feet radiographs were analyzed with regards to the presence or absence of erosive disease.ResultsAnalysis of the CCR5 polymorphism in 503 RA patients and in 459 age-matched healthy controls revealed a significantly decreased disease susceptibility for carriers of the CCR5d32 deletion (Odds ratio 0.67, P = 0.0437). Within the RA patient cohort, CCR5d32 was significantly less frequent in patients with extra-articular manifestations compared with those with limited, articular disease (13.2% versus 22.8%, P = 0.0374). In addition, the deletion was associated with significantly lower average CRP levels over time (median 8.85 vs. median 14.1, P = 0.0041) and had a protective effect against the development of erosive disease (OR = 0.40, P = 0.0047). Intriguingly, homozygosity for the RA associated DNASE2 -1066 G allele had an additive effect on the disease susceptibility conferred by the wt allele of CCR5 (OR = 2.24, P = 0.0051 for carrier of both RA associated alleles)ConclusionsThe presence of CCR5d32 significantly influenced disease susceptibility to and clinical course of RA in a German study population. The protective effect of this deletion, which has been described to lead to a decreased receptor expression in heterozygous patients, underlines the importance of chemokines in the pathogenesis of RA.

Lymphoid follicles in joints: What do they mean?

The existence of lymphoid follicles in the synovium of patients with inflammatory arthritis, including the feature we now recognize as a germinal center of proliferating B cells, has been known since the nineteenth century (1). It has also long been recognized that these structures are present in only a minority of cases and are not specific to rheumatoid disease. Most of the lymphocytes seen in synovium are T cells (2), although this analysis does not include B cell–derived plasma cells, which can be very numerous. Perhaps surprisingly, we are still faced with the question: are these B cell–containing follicles telling us something important about the disease and how to treat it, or are they a secondary curiosity? We have probably learned enough about inflammatory arthritis to know that the answer will lie somewhere in between and that every patient may be slightly different. Nevertheless, careful studies, such as the one by Thurlings and colleagues reported in this issue of Arthritis & Rheumatism (3), may reveal broad truths that may at least guide useful treatment strategies. As is often the case, the study by Thurlings et al is most interesting for what was not found. It confirms the historical belief that organized collections of B cells occur in rather few rheumatoid arthritis (RA) synovia. Moreover, it shows that, at least in terms of measures in the Disease Activity Score 28-joint assessment (4), such as the numbers of swollen and tender joints, amount of bone damage, and presence of rheumatoid nodules, lymphoid neogenesis does not seem to determine disease phenotype. It is difficult to escape the conclusion that B cells in joints may not be that important. Should we be surprised? Probably not, since the role of B cells is not usually at a site of inflammation itself. The findings of van Boxel and Paget (2) (T cell predominance) apply to more or less all inflammation. B cells normally contribute to inflammation either by generating plasma cells, which, in lymphoid tissue or at sites of inflammation, secrete antibodies capable of activating inflammatory mechanisms, or by presenting antigen to T cells in draining lymph nodes so that primed T cells can recirculate to inflamed tissue. Starting with antibody production, arguably the most interesting finding reported by Thurlings and colleagues is that the presence of organized B cell collections in synovium was not correlated with the presence of detectable autoantibodies (rheumatoid factor and antibodies against citrullinated proteins). The implication is that if autoantibodies contribute to inflammation through the interaction of immune complexes with macrophage Fc receptors and complement, then in many cases the B cells responsible are to be found largely or wholly in lymph nodes or spleen. This is consistent with the body of data indicating that autoantibody production frequently precedes any clinical sign of cellular infiltration of synovium by up to several years (5). (Interestingly, preclinical autoantibody production can be associated with a rise in C-reactive protein [CRP] levels, suggesting that immune complexes may drive an acute-phase response, perhaps by Kupffer cell activation, without causing inflammation.) It does not, of course, imply that therapies targeting B cells should not be designed to reach synovial B cell collections as well as those elsewhere. But it does tend to imply that this is not the primary objective. In terms of antigen presentation, the prima facie Jonathan C. W. Edwards, MD, Maria J. Leandro, MD, PhD: University College London, London, UK. Dr. Edwards has received honoraria (less than $10,000) from Roche. Dr. Leandro has received consulting fees, speaking fees, and honoraria (more than $10,000) from Roche. Address correspondence and reprint requests to Maria J. Leandro, MD, PhD, Room 317, Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK. E-mail: maria.leandro@ucl.ac.uk. Submitted for publication January 11, 2008; accepted in revised form February 29, 2008. Arthritis & Rheumatism

The effect of parental consanguinity on the clinical and laboratory findings of rheumatoid arthritis

We aimed to evaluate the frequency of consanguinity among the parents of patients with rheumatoid arthritis (RA) and the influence of parental consanguinity on several clinical and laboratory parameters which reflect the severity of the disease. The study population consisted of 265 patients with RA which were divided into two groups with respect to the presence or absence of consanguinity between their parents. The frequency of parental consanguinity was compared with the general population. The two groups were compared with respect to family history of RA, the age of onset, the age at which RA was diagnosed, duration of the disease, the presence of rheumatoid nodules, vasculitis, serositis and the need for orthopaedic surgery, amyloidosis, the presence and level of rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erosive changes on radiographs, and the need for anti-tumour necrosis factor therapy. Twenty-one patients (8%) had parents who were consanguineous, which was not more frequent compared with the general population (14%). The mean age of disease onset and the mean age at which RA was diagnosed were lower in patients with parental consanguinity, although the difference was not statistically significant. The other clinical and laboratory parameters were also not different between the two groups. The present data suggests that parental consanguinity has no effect on disease severity, and the frequency of consanguinity is not increased among the parents of patients with RA. A possible exception is the earlier disease onset and age at diagnosis which needs to be confirmed by larger studies.

Serum leptin in rheumatoid arthritis

Leptin is a peptide hormone that has an essential role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. The role of leptin in the modulation of the immune response and inflammation has been regarded as important. In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. These features suggest that leptin may also influence the inflammatory mechanisms of arthritis in humans. In this study we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA and 30 OA patients who constituted the control group. Serum leptin level was determined using the DRG Leptin ELISA Kit-a solid phase enzyme-linked immunosorbent assay based on the sandwich principle. The serum level of leptin in RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a positive correlation between body mass index (BMI) of RA patients and serum level of leptin (correlation coefficients Spearman's r = 0.81). According to correlation coefficients, serum leptin level is independent of age of RA patients, stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration as well as value of titre of the Waaler-Rose, disease activity score (DAS 28) value and presence of rheumatoid nodules. There was a negative correlation between serum leptin level and glomerular filtration rate (GFR). No correlation between the serum leptin level and T-score was found. An influence of steroid treatment on the serum leptin level was not shown. The median serum leptin level in OA patients was 9.2 ng/ml. There was a positive correlation between body mass index of OA patients and serum level of leptin (correlation coefficients Spearman's r = 0.57). No correlation was found between serum leptin level and patient's age, duration of disease and value of laboratory data. There were no correlations between serum leptin level and visual analogue pain scale (VAS) for the lower-limb afflicted patients as well as stage of disease according to Kellgren and Lawrence's score in OA patients. There was a negative correlation between serum leptin level and T-score value in OA patients (r = -0.58, P < 0.05). No statistically significant differences were found between serum leptin levels for RA and OA patients.

Cranial and peripheral neuropathy in rheumatoid arthritis with special emphasis to II, V, VII, VIII and XI cranial nerves

AbstractBackground: Cranial neuropathy in rheumatoid arthritis (RA) is relatively rare compared to the frequently reported peripheral neuropathy.Methods: We investigated the occurrence of subclinical cranial and peripheral nerve involvement in 55 patients with RA.Results: Patients had a mean age of 43.1 years and a mean duration of illness of 6.4 years. All patients presented with electrophysiological findings suggestive of peripheral neuropathy. In addition, 69.1% of them had entrapment neuropathies, in which carpal tunnel syndrome was the most common (54.6%). Sensorimotor neuropathy at sites other than usual entrapment sites was diagnosed in 70.9%, while bilateral distal sensory neuropathy in lower limbs was identified in 29.1%. Among cranial nerves examined, optic and vestibulocochlear neuropathies were common (29.1% of eyes and 40% of ears examined). Spinal accessory neuropathy was reported in 21.8% of records. Neither facial nor trigeminal nerves were affected. Electrophysiological characteristics of neuropathies were indicative of axon loss. Significant association was identified between neuropathy and patients’ ages (P &lt; 0.01), duration of the illness (P &lt; 0.001), presence of rheumatoid nodules (P &lt; 0.001) and disease stages (P &lt; 0.001).Conclusions: Our results indicate that cranial and non‐compressive neuropathies are not uncommon in RA. This extends the pathologic disease spectrum. We do not confirm, but suggest the contribution of chronic immune‐mediated vasculitis and/or neurotoxicity in RA neuropathies. Of clinical importance, subclinical neuropathy may never progress and/or be of clinical significance, which contradicts that of comparable diseases, such as systemic lupus erythematosus. Advances in genetics implicate a complex immune genetics which controls susceptibilities and adaptive molecular mechanisms as a culprit of phenotypical heterogenicity among related diseases.

CHRONIC PANCREATITIS WITH PANCREATIC RHEUMATOID NODULES

Purpose: A 61 year old female nurse anesthetist with a long history of Rheumatoid Arthritis presented with unrelenting upper abdominal pain, intermittent diarrhea and 20 lb. weight loss of three months duration. Computerized tomography of the abdomen showed a very prominent tail of the pancreas. At ERCP, there was a tight stricture at the mid pancreatic duct. Endoscopic ultrasound-guided fine needle aspiration of the tail showed atypical ductal epithelial cells in a background of abundant necrosis and chronic inflammation. She underwent subtotal pancreatectomy, splenectomy and cholecystectomy. The final pathologic diagnosis revealed granulomatous inflammation with central fibrinoid necrosis and necrobiotic debris consistent with rheumatoid nodules. Rheumatoid Arthritis is a rare cause of chronic pancreatitis. This case illustrates the difficulties and challenges involved in the management. The presence of rheumatoid nodules in the pancreas has not been previously described.

Association of autoantibodies to glucose-6-phosphate isomerase with extraarticular complications in rheumatoid arthritis.

In the K/BxN mouse model, autoantibodies against glucose-6-phosphate isomerase (GPI) cause arthritis. The relevance of this model for human disease remains a subject of controversy. We set out to determine whether GPI autoantibodies occur in patients with rheumatoid arthritis (RA) and, if so, at what stage of the RA. Using an enzyme-linked immunosorbent assay, serum from 131 RA patients and 28 healthy controls was tested for autoantibodies against recombinant human GPI. Patients were grouped according to disease duration and presence of rheumatoid nodules, rheumatoid vasculitis, and Felty's syndrome, which are extraarticular complications of RA. Elevated levels of autoantibodies against GPI were present in 5% of patients with uncomplicated RA and 4% of controls. In RA complicated by extraarticular manifestations, anti-GPI antibodies were observed in 18% of patients with rheumatoid nodules, 45% of patients with rheumatoid vasculitis, and 92% of patients with Felty's syndrome. In patients with RA, autoantibodies to GPI are associated with the occurrence of extraarticular complications.