Showing papers in "Clinical Rheumatology in 2016"
TL;DR: As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice.
Abstract: Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases. Prevalence estimates of fatigue within rheumatic diseases vary considerably. Data on the prevalence of severe fatigue across multiple rheumatic diseases using a similar instrument is missing. Our aim was to provide an overview of the prevalence of severe fatigue across a broad range of rheumatic diseases and to examine its association with clinical and demographic variables. Online questionnaires were filled out by an international sample of 6120 patients (88 % female, mean age 47) encompassing 30 different rheumatic diseases. Fatigue was measured with the RAND(SF)-36 Vitality scale. A score of ≤35 was taken as representing severe fatigue (90 % sensitivity and 81 % specificity for chronic fatigue syndrome). Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjogren’s syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %). In logistic regression analysis, severe fatigue was associated with having fibromyalgia, having multiple rheumatic diseases without fibromyalgia, younger age, lower education, and language (French: highest prevalence; Dutch: lowest prevalence). In conclusion, one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice.
136 citations
TL;DR: Generalized joint hypermobility was relatively common in this healthy college student population; GJH was not associated with increased incidence of injury or symptoms commonly attributed to JHS, but JHS was associated with increase incidence of some injuries and symptoms.
Abstract: Generalized joint hypermobility (GJH) and joint hypermobility syndrome (JHS) are gaining increased attention as potential sources of pain and injury. The aims of this study were to evaluate prevalence of GJH and JHS and to determine whether musculoskeletal injuries and symptoms commonly attributed to GJH and JHS were more common within a “healthy” college student population. The study involved a convenience sample of 267 college and graduate students, aged 17–26. GJH was assessed using the Beighton score with a cutoff of 5/9, while JHS was assessed using the Brighton criteria. Injury history and symptoms were assessed by recall. Prevalence of GJH was 26.2 % overall (females 36.7 %, males 13.7 %). Prevalence of JHS was 19.5 % overall (females 24.5 %, males 13.7 %). Injury rates were not significantly different for individuals who had GJH vs. those who did not have GJH. Individuals with JHS were significantly more likely to have had sprains, back pain, and stress fractures. Symptoms were no different between those with GJH and those who did not have GJH. However, individuals with JHS were significantly more likely to report clumsiness, easy bruising, and balance problems than those who did not have JHS. GJH and JHS were relatively common in this healthy college student population; GJH was not associated with increased incidence of injury or symptoms commonly attributed to JHS, but JHS was associated with increased incidence of some injuries and symptoms.
95 citations
TL;DR: The data have confirmed that the use of anti-IL-1β drugs is efficacious and safe with an overall acceptable retention on treatment.
Abstract: Growing data have provided encouraging results on the use of interleukin (IL)-1 inhibitors in Behcet’s disease (BD). This study was aimed at reporting the largest experience with anti-IL-1 agents in BD patients. We evaluated 30 BD patients receiving treatment with anti-IL-1 agents. The primary aims of the study were to evaluate the efficacy of anakinra (ANA) and canakinumab (CAN) in a cohort of BD. The secondary aims were to evaluate the overall safety profile of the treatments, explore the timing of response to therapy and any adjustment of dosage and frequency of drugs studied, and investigate predictive factors of response to therapy. The frequency of first line therapy was 90 % with ANA and 10 % with CAN. The overall number of subjects in complete remission after 12 months of therapy with anti-IL-1 drugs was 13: 6 maintained the initial therapy regimen, 1 maintained the same initial anti-IL-1 drug with further therapeutic adjustments, and the remaining 6 shifted from ANA to CAN. Among them, 3 used CAN for at least 12 months without therapeutic adjustments, 1 had therapeutic adjustments, and 3 had an overall history of a 12-month complete remission. Adverse events (AEs) were reported in 15 % patients who received ANA, represented in all cases by local cutaneous reactions, while no AE were observed in patients who received CAN; we did not observe any serious AEs (SAEs) during the follow-up period. Our data have confirmed that the use of anti-IL-1β drugs is efficacious and safe with an overall acceptable retention on treatment.
94 citations
TL;DR: This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects.
Abstract: Adult-onset Still’s disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi’s criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects.
91 citations
TL;DR: The utilization rate of TAA increased rapidly in the USA from 1998 to 2010, but post-arthroplasty mortality rate was stable and both can impact outcomes after TAA.
Abstract: The objective of this study was to assess the time trends in utilization, clinical characteristics, and outcomes of patients undergoing total ankle arthroplasty (TAA) in the USA. We used the Nationwide Inpatient Sample (NIS) data from 1998 to 2010 to examine time trends in the utilization rates of TAA. We used the Cochran Armitage test for trend to assess time trends across the years and the analysis of variance (ANOVA), Wilcoxon test, or chi-squared test (as appropriate) to compare the first (1998–2000) and the last time periods (2009–2010). TAA utilization rate increased significant from 1998 to 2010: 0.13 to 0.84 per 100,000 overall, 0.14 to 0.88 per 100,000 in females, and from 0.11 to 0.81 per 100,000 in males (p 0.05). The utilization rate of TAA increased rapidly in the USA from 1998 to 2010, but post-arthroplasty mortality rate was stable. Underlying diagnosis and medical comorbidity changed over time and both can impact outcomes after TAA. Further studies should examine how the outcomes and complications of TAA have evolved over time.
91 citations
TL;DR: A minority of videos are useful for teaching MTX injection, and clinicians need to be familiar with specific resources to help guide and educate their patients to ensure best outcomes.
Abstract: The aim of this study is to identify and evaluate the quality of videos for patients available on YouTube for learning to self-administer subcutaneous methotrexate. Using the search term “Methotrexate injection,” two clinical reviewers analyzed the first 60 videos on YouTube. Source and search rank of video, audience interaction, video duration, and time since video was uploaded on YouTube were recorded. Videos were classified as useful, misleading, or a personal patient view. Videos were rated for reliability, comprehensiveness, and global quality scale (GQS). Reasons for misleading videos were documented, and patient videos were documented as being either positive or negative towards methotrexate (MTX) injection. Fifty-one English videos overlapped between the two geographic locations; 10 videos were classified as useful (19.6 %), 14 misleading (27.5 %), and 27 personal patient view (52.9 %). Total views of videos were 161,028: 19.2 % useful, 72.8 % patient, and 8.0 % misleading. Mean GQS: 4.2 (±1.0) useful, 1.6 (±1.1) misleading, and 2.0 (±0.9) for patient videos (p < 0.0001). Mean reliability: 3.3 (±0.6) useful, 0.9 (±1.2) misleading, and 1.0 (±0.7) for patient videos (p < 0.0001). Comprehensiveness: 2.2 (±1.9) useful, 0.1 (±0.3) misleading, and 1.5 (±1.5) for patient view videos (p = 0.0027). This study demonstrates a minority of videos are useful for teaching MTX injection. Further, video quality does not correlate with video views. While web video may be an additional educational tool available, clinicians need to be familiar with specific resources to help guide and educate their patients to ensure best outcomes.
89 citations
TL;DR: Anti-IL-1 therapies can be successfully used in colchicine-resistant FMF patients and patients with amyloidosis during childhood and adolescent period without major side effects.
Abstract: Colchicine is the standard treatment in familial Mediterranean fever (FMF) patients. New treatment strategies are needed in FMF patients who were unresponsive to colchicine therapy or who had developed amyloidosis. The aim of this study was to present clinical-laboratory features and treatment responses of pediatric FMF patients that were treated with anti-IL-1 therapies. Files of patients who had been followed in our department with diagnosis of FMF were retrospectively evaluated. Patients that have been receiving anti-IL-1 therapies (anakinra or canakinumab) were included to the study. All patients were interpreted with respect to the demographic data, clinical and laboratory features of the disease, genetic analysis of MEFV mutations and treatment responses. Among 330 currently registered FMF patients, 13 patients were included to the study. Seven of them received anti-IL-1 therapy due to colchicine resistance and 6 due to FMF-related amyloidosis (1 of them with nephrotic syndrome, 2 with chronic kidney disease, 3 with renal transplantation). In all treated patients, attacks completely disappeared or decreased in frequency; partial remission occured in nephrotic syndrome patient; and their life quality improved. Anti-IL-1 therapies can be successfully used in colchicine-resistant FMF patients and patients with amyloidosis during childhood and adolescent period without major side effects.
76 citations
TL;DR: Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures, indicating multiple stress fractures.
Abstract: Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995–2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.
71 citations
TL;DR: Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients, and there is a high-risk group that is less protected with rivroxaban, namely those with previous arterial thrombosis or triple positivity.
Abstract: The current treatment for antiphospholipid syn- drome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of choice. However, VKA limitations, such as un- predictable anticoagulation effects due to interaction with diet and other drugs, require regular monitoring. This may impact on patients' quality of life. Since the approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation and deep vein thrombosis prevention, much has been specu- lated about its use in APS patients. We report here a series of eight APS patients with failure of thrombotic prevention dur- ingrivaroxabanuse.Allpatientshadvenousthrombosisasthe initial manifestation of APS, and two of them also had arterial manifestations. Three patients had triple antibody positivity. Five patients developed arterial events during the treatment with rivaroxaban. Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients. Our preliminary experience as well cases previously reported in the literature suggest that there is a high-risk group that is less protected with rivaroxaban, namely those with previous arterial thrombosis or triple positivity. VKA remains to be the mainstay treatment for thrombotic APS.
69 citations
TL;DR: Serological classification adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival, and histopathological classification predicted response to therapy.
Abstract: Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20–7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75–37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03–2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01–1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01–22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.
65 citations
TL;DR: It was found that skin ulceration, CRP, serum ferritin, anti-MDA5 Ab, and lymphocytopenia were significantly associated with ILD, and Multivariate logistic regression analysis indicated that anti-mda5 Ab+, elevatedCRP, and decreased counts of lymphocyte were independent risk factors for RP-ILD, which can provide a precise predict forRP-ILD in CADM patients.
Abstract: Clinically amyopathic dermatomyositis (CADM) is a unique subset of dermatomyositis, showing a high incidence of lung involvements. The aim of this study is to identify risk factors, other than melanoma differentiation-associated protein (MDA)-5, for developing rapidly progressive-interstitial lung disease (RP-ILD) in patients with CADM. Forty CADM patients, in whom 11 patients developed RP-ILD, were enrolled. Clinical features and laboratory findings were compared between the patients with and without RP-ILD. We found that skin ulceration, CRP, serum ferritin, anti-MDA5 Ab, and lymphocytopenia were significantly associated with ILD. Multivariate logistic regression analysis indicated that anti-MDA5 Ab(+), elevated CRP, and decreased counts of lymphocyte were independent risk factors for RP-ILD, which can provide a precise predict for RP-ILD in CADM patients. When anti-MDA5 Ab(+) was removed from the multivariate regression model, using skin ulcerations, elevated serum ferritin and decreased counts of lymphocyte can also precisely predict RP-ILD. Except for MDA-5, more commonly available clinical characteristics, such as skin ulcerations, serum ferritin, and count of lymphocyte may also help to predict prognosis in CADM.
TL;DR: Patients aged 50–64 with RA use substantially more opioids than their non-RA counterparts, and RA disease characteristics, biologic use at index, treated depression/fibromyalgia, education, and smoking status were not significantly associated with chronic opiate use.
Abstract: Opioid prescriptions have seen an increase across the USA, Canada, Europe, and the UK. In the USA, they have quadrupled from 1999 to 2010. Opioid use among patients with rheumatoid arthritis (RA) over time is not well described. This study examined trends of opioid use in patients with RA. Retrospective prescription data was examined from 2005 to 2014 in a population-based incidence cohort of patients with RA by 1987 ACR criteria and comparable non-RA subjects. Differences in opioid use were examined with Poisson models. A total of 501 patients with RA (71 % female) and 532 non-RA subjects (70 % female) were included in the study. Total and chronic opioid use in 2014 was substantial in both cohorts 40 % RA vs 24 % non-RA and 12 % RA vs. 4 % non-RA, respectively. Opioid use increased by 19 % per year in both cohorts during the study period (95 % confidence interval [CI] 1.15, 1.25). Relative risk (RR) of chronic opiate use for RA patients compared to non-RA subjects was highest in adults aged 50-64 years (RR 2.82; 95 % CI 1.43-6.23). RA disease characteristics, biologic use at index, treated depression/fibromyalgia, education, and smoking status were not significantly associated with chronic opiate use. Over a third of patients with RA use opioids in some form, and in more than a tenth use is chronic. Use has increased in recent years. Patients aged 50-64 with RA use substantially more opioids than their non-RA counterparts.
TL;DR: Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography, and data from this study suggest that eChocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.
Abstract: Cardiovascular diseases are one of the most important causes of the disability and mortality in patients with systemic lupus erythematosus (SLE). The present study examined the cardiac abnormalities in patients with SLE by echocardiography. Case-control studies were obtained by searching PubMed MEDLINE, Embase, and MD Consult. Systemic review and meta-analysis were performed to assess the cardiac abnormalities based on the changes in the echocardiography in patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy controls were enrolled into this study. We found that patients with SLE developed the pericardial effusion (odds ratio (OR) (95 % confidence interval (CI)) 30.52 (9.70–96.02); p < 0.00001) and the combined valvular alterations (OR (95 %CI) 11.08 (6.98–17.59); p < 0.00001). In addition, SLE patients also exhibited an increase in the left atrial diameter (LAD) (WMD—weighted mean difference (95 %CI) 0.18 (0.06–0.29); p = 0.002), the left ventricular internal diameter in diastole (LVDd) (WMD (95 %CI) 0.07 (0.02–0.12); p = 0.01), and the left ventricular mass index (LVMI) (WMD (95 %CI) 5.69 (2.69–8.69); p = 0.0002). In contrast, the left ventricular systolic function (WMD (95 %CI) −1.22 (−1.69 to −0.75); p < 0.00001) and diastolic function including E/A ratio and E/E’ ratio (WMD (95 % CI) −0.13 (−0.24 to −0.01); p = 0.04; WMD (95 % CI) 1.71 (0.43 to 2.99); p = 0.009) were decreased in SLE patients. Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography. Data from this study suggest that echocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.
TL;DR: The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA.
Abstract: The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA.
TL;DR: The aim of this review is to focus on PsA and psoriasis differential diagnosis and rule out other conditions that can resemble the disease and delay appropriate therapeutic approach.
Abstract: Psoriasis frequency ranges from 1 to 3 % in white population, and arthritis occurs in 10–40 % of psoriasis patients, representing a relevant health issue. Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with psoriasis, in which ocular-, intestinal-, metabolic-, and cardiovascular-related manifestations can variably coexist. In order to favor early PsA and psoriasis diagnosis, it is crucial to rule out other conditions that can resemble the disease and delay appropriate therapeutic approach. Therefore, the aim of this review is to focus on PsA and psoriasis differential diagnosis.
TL;DR: Hyperuricemia was common among residents living in rural Northeast China especially among men and was related to different subtypes of cardiometabolic comorbidities in both gender like abdominal obesity, general obesity, hypertriglyceridemia, hypertension, hypercholesterolemia, and low HDL-C.
Abstract: The increasing trend of hyperuricemia in urban areas of China has been noted in the past decade. However, the prevalence of hyperuricemia in rural China has not been extensively investigated. We aimed to estimate the prevalence and risk factors of hyperuricemia and the associated comorbidities in rural Northeast China. This survey was conducted from July 2012 to August 2013. In this study, a total of 11,576 residents from the rural Northeast China were randomly selected and examined. Hyperuricemia was defined as serum uric acid ≥416 μmol/l in men and ≥357 μmol/l in women. Data regarding the demographic and lifestyle characteristics and the blood biochemical indexes of these participants were collected by well-trained personnel. The prevalence of hyperuricemia was 10.9 % and was more prevalent in men than in women (15.0 vs. 7.3 %, P < 0.001). Multivariate logistic regression models revealed that besides age, hyperuricemia in men was associated with ethnic minority [OR (95 %): 0.683 (0.472,0.989)], physical activity [moderate, OR (95 %): 0.716 (0.596,0.859); high, OR (95 %): 0.527 (0.354,0.786)], current smoking [OR(95 %):1.380 (1.179,1.616)], and current drinking [OR(95 %):0.705 (0.603,0.825)], while in women was only associated with ethnic minority [OR(95 %):0.485 (0.262,0.896)]. After adjusting for possible confounders, hyperuricemia was related to different subtypes of cardiometabolic comorbidities in both gender like abdominal obesity, general obesity, hypertriglyceridemia, hypertension, hypercholesterolemia, and low HDL-C. Besides, in women only, hyperuricemia was related to diabetes and high LDL-C. Hyperuricemia was common among residents living in rural Northeast China especially among men. Ethnic minority, physical activity, current smoking, and drinking contributed to hyperuricemia in this population.
TL;DR: The effect of music has been found to control pain in fibromyalgia patients and music therapy should be suggested in pain management for fibromy arthritis patients as an non-pharmacologic nursing intervention.
Abstract: Fibromyalgia syndrome (FMS) is a chronic syndrome characterized by diffuse musculoskeletal system pain and painful tender points in certain areas of the body. The aim of the investigation was to determine the effects of music on pain in fibromyalgia patients. This randomized clinical trial was carried out with 37 fibromyalgia outpatients as an experimental group (n = 21) and control group (n = 16) at a University Hospital Internal Medicine and Rheumatology Clinic between 1 June and 1 December 2014. The research instruments used were descriptive characteristics questionnaire, Visual Analogue Scale (VAS), music CD which includes water and wave sounds recommended by the Turkish Psychological Association for psychological relaxation, and pain evaluation form. According to the findings, the average age of patients was 43.59 years ± 10.30, 94.6 % were women and 81.1 % were married. The fibromyalgia patients had the disease ranged from 1 month to 20 years, the average of disease duration was 23.6 ± 45.5 months, and the average of pain intensity was 6.89 ± 1.64 on the VAS. Average pain was reported in the experimental group in VAS on day 1 (5.45 ± 2.73), day 7 (4.57 ± 2.71), and day 14 (4.14 ± 2.45), and significant reduction in pain in the listening music group was seen (p = 0.026). A repeated measure analysis of variance controlling for differences between days demonstrated a significant decrease in pain between day 1 and day 14 (p = 0.022). There was no significant decrease in pain among control group participants. The effect of music has been found to control pain in fibromyalgia patients. Music therapy should be suggested in pain management for fibromyalgia patients as an non-pharmacologic nursing intervention.
TL;DR: It is suggested that dysregulation of DNMT1 expression through altered methylation level of other target genes would probably contribute to AS development.
Abstract: Ankylosing spondylitis (AS) is an autoimmune disease with a chronic inflammatory arthritis. The critical role of methylation in the biology of immunocytes has increasingly been surveyed to discover disease etiology. DNA methyltransferase 1 (DNMT1) is an enzyme, which establishes and regulates patterns of methylated cytosine residues. The aim of the current investigation was to unveil if methylation circumstances of CpG sites in DNMT1 promoter could affect the mRNA expression level of this gene in peripheral blood mononuclear cells (PBMCs) from AS patients. PBMCs were isolated from whole blood of 40 AS patients and 40 healthy individuals. Total RNA and DNA contents of leukocytes were extracted. Afterward, quantitative analysis was carried out by real-time PCR using the SYBR Green PCR Master Mix. Finally, to determine the methylation level, PCR products of bisulfite-treated DNA from patients and controls were sequenced. Compared with healthy controls, expression level of DNMT1 in AS patients was significantly downregulated. Methylation of DNMT1 promoter was significantly higher in AS patients in comparison to controls. While a negative correlation between methylation and expression level of DNMT1 was observed in AS patients, both methylation and expression level of DNMT1 did not correlate with clinical manifestations. Considering the observation that decreased expression level of DNMT1 was associated with hypermethylation of DNMT1 promoter in PBMCs from AS patients, this survey suggests that dysregulation of DNMT1 expression through altered methylation level of other target genes would probably contribute to AS development.
TL;DR: The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients’ response to CF101, a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population.
Abstract: The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population.
TL;DR: It is concluded that ultrasound is a reproducible method for assessment of knee osteoarthritis and well correlated with WOMAC.
Abstract: The aim of this work was to assess the reproducibility of ultrasound findings of knee osteoarthritis and to correlate ultrasound findings with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Prospective study was conducted upon 80 patients (56 F, 24 M; mean age 57 years) with primary osteoarthritis of knee joint. All patients underwent clinical assessment with calculation of WOMAC and high-resolution ultrasound of the knee joint. The ultrasound images were analyzed for cartilage thinning, osteophytes, synovial effusion, synovial proliferation, popliteal cyst, and meniscal protrusion. Image analysis was performed by two readers and linear regression analysis was used to determine association of ultrasound findings with WOMAC. There was excellent inter-observer agreement of both readers for cartilage thinning (k = 0.99, P = 0.001), osteophytes (k = 0.94, P = 0.001), synovial effusion (k = 0.98, P = 0.001), synovial thickening (k = 0.96, P = 0.001), popliteal cyst (k = 1.00, P = 0.001), and meniscal protrusion (k = 0.86, P = 0.001). There was significant association of WOMAC with cartilage changes (t = 3.406, 3.302, P = 0.001), osteophytes (t = 3.841, 3.006, P = 0.001), and synovial effusion (t = 4.140 and 2.787, P = 0.05) of both readers. We concluded that ultrasound is a reproducible method for assessment of knee osteoarthritis and well correlated with WOMAC.
TL;DR: Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively.
Abstract: This study aimed to investigate whether knee pain during various activities of daily living (ADLs) is associated with physical activity in patients with early and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs associated with decreased physical activity differ according to disease severity. This cross-sectional study enrolled 270 patients with medial knee OA, assigned to either the early (Kellgren Lawrence [K/L] grade 1-2) or the severe group (K/L grade 3-4). Physical activity was assessed using a pedometer. Knee pain during six ADLs (waking up in the morning, walking on a flat surface, ascending stairs, etc.) was evaluated using a questionnaire. We performed multiple regression and quantile regression analysis to investigate whether knee pain during each ADL was associated with physical activity. In the early group, the more knee pain they experienced while ascending stairs, the lower their physical activity was (75th regression coefficient = -1033.70, P = 0.018). In the severe group, the more knee pain they experienced while walking on a flat surface or bending to the floor or standing up, the lower their physical activity was (unstandardized coefficients = -1850.87, P = 0.026; unstandardized coefficients = -2640.35, P = 0.010). Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively. These findings suggested that a reduction in task-specific knee pain according to disease severity could improve physical activity levels.
TL;DR: This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals.
Abstract: This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals. The Truven Health MarketScan® US Commercial Database was searched for patients aged 18-64 years with back pain diagnosis in a non-rheumatology setting followed by AS diagnosis in any setting during January 2000-December 2012. Patients with a rheumatologist visit on or before AS diagnosis were considered referred. Cox regression was used to determine factors associated with referral time after adjusting for age, sex, comorbidities, physician specialty, drug therapy, and imaging procedures. Of 3336 patients included, 1244 (37 %) were referred to and diagnosed by rheumatologists; the others were diagnosed in primary care (25.7 %), chiropractic/physical therapy (7 %), orthopedic surgery (3.8 %), pain clinic (3.6 %), acute care (3.4 %), and other (19.2 %) settings. Median time from back pain diagnosis to rheumatology referral was 307 days and from first rheumatologist visit to AS diagnosis was 28 days. Referred patients were more likely to be younger (hazard ratio [HR] = 0.986; p < 0.0001), male (HR = 1.15; p = 0.0163), diagnosed with uveitis (HR = 1.49; p = 0.0050), referred by primary care physicians (HR = 1.96; p < 0.0001), prescribed non-steroidal anti-inflammatory drugs (HR = 1.55; p < 0.0001), disease-modifying antirheumatic drugs (HR = 1.33; p < 0.0001), and tumor necrosis factor inhibitors (HR = 1.40; p = 0.0036), and to have had spinal/pelvic X-ray prior to referral (HR = 1.28; p = 0.0003). During 2000-2012, most patients with AS were diagnosed outside of rheumatology practices. The delay before referral to rheumatology was 10 months; AS diagnosis generally followed within a month. Earlier referral of patients with AS signs and symptoms may lead to more timely diagnosis and appropriate treatment.
TL;DR: Low-dose methotrexate 10–15 mg/m2/week orally, as steroid-sparing agent, was administered in 14 patients, and low-dose MTX seems to be effective, steroid sparing, and safe adjunct to treat sarcoidosis with multiorgan involvement.
Abstract: A retrospective chart review was conducted to detect patients with sarcoidosis seen by pediatric rheumatology service from the period of 1992 to 2013 at Children’s hospital of New Orleans. Twenty-seven patients were identified. The average duration of symptoms before diagnosis was 5 (range 1–120) months. Five patients had onset before the age of 5 years and were diagnosed with early-onset sarcoidosis. The most common manifestations at presentation were constitutional symptoms (62 %) followed by ocular (38 %). During the course of illness, 19/27 (70 %) had multiorgan involvement. Common manifestations included uveitis/iritis (77 %), fever (50 %), hilar adenopathy (42 %), arthritis (31 %), peripheral lympadenopathy (31 %), hepatosplenomegaly (31 %), parenchymal lung disease (27 %), and skin rash (19 %). Unusual manifestations included granulomatous bone marrow disease (3 cases), hypertension (2), abdominal aortic aneurysm (large vessel vasculitis; 1), granulomatous hepatitis (1), nephrocalcinosis (1), membranous nephropathy (1), refractory granulomatous interstitial nephritis with recurrence in transplanted kidney (1), CNS involvement (2), parotid gland enlargement (1), and sensorineural hearing loss (1). Biopsy specimen was obtained in 21/27 (77 %) patients, and demonstration of noncaseating granuloma associated with negative stains for mycobacteria and fungi was seen in 18 patients. Elevated angiotensin-converting enzyme level was seen in 74 % of patients. Treatment with oral prednisone was initiated in symptomatic patients with significant clinical improvement. Low-dose methotrexate (MTX) 10–15 mg/m2/week orally, as steroid-sparing agent, was administered in 14 patients. Other immunomodulators included cyclophosphamide (2 patients), etanercept (2), infliximab (2), mycophenolate mofetil (1), and tacrolimus (1). Childhood sarcoidosis is prevalent in Louisiana. Most of the affected children present with a multisystem disease associated with manifestations similar to those of adult patients. Low-dose MTX seems to be effective, steroid sparing, and safe adjunct to treat sarcoidosis with multiorgan involvement. Early-onset disease is less common and associated with increased morbidity, flares, and poor prognosis.
TL;DR: Stabilization in osteolysis and improvement in BMD were observed after single therapy with BPs or combined with radiotherapy, and the complicated chylothorax possibly indicates poor prognosis.
Abstract: Gorham-Stout disease (GSD) is an exceedingly rare disease characterized by progressive osteolysis and angiomatosis. We investigate the features of this disease and evaluate the effects of bisphosphonates (BPs) on it. The clinical, radiological, and pathological characteristics of 12 patients diagnosed with GSD were summarized. Immunohistochemical staining with specific lymphatic endothelial markers (D2-40), vascular markers (CD 31, CD 34), and vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed in specimens of bone biopsy. Patients were treated with either BPs or conjunction therapy of radiation and BPs. The effects of BPs were evaluated by the change of radiological progression, bone mineral density (BMD) and bone turnover biomarkers. To further evaluate the prognosis, a literature review was done. Idiopathic massive osteolysis was found in all patients, including 11 polyostotic and one mono-ostotic osteolysis. Soft tissue lymphangioma was presented in four patents. Four patients were complicated with chylothorax. Endothelial cells lining the proliferative vessels were positive for CD31 and CD34 and D2-40. Mild expression of VEGF and VEGFR-3 was also revealed. Stabilization in osteolysis and improvement in BMD were observed after single therapy with BPs or combined with radiotherapy. High mortality rate was found in patients with chylothorax. Spontaneous, progressive osteolysis is the most typical sign of GSD. BPs and radiotherapy can contribute to the clinical stabilization in bone lesion of GSD. The complicated chylothorax possibly indicates poor prognosis.
TL;DR: Better patient, public and practitioner education about gout being a chronic condition associated with co-morbidities and poor HRQOL may improve understanding and long-term treatment of gout.
Abstract: The objective of the study is to examine the impact of gout and its treatments on health-related quality of life (HRQOL) using focus group interviews. From the baseline phase of a cohort study of HRQOL in gout, 17 participants (15 males, mean age 71 years) with varying attack frequency and treatment with and without allopurinol participated in one of four focus group interviews. All interviews were audio-recorded and transcribed verbatim. Data was analysed thematically. Physical and psychosocial HRQOL in gout was affected by characteristics of acute gout (particularly the unpredictable nature of attacks, location of joint involved in an attack, pain and modifications in lifestyle), lack of understanding of gout by others (association with unhealthy lifestyle, symptoms ridiculed as non-severe and non-serious) as well as participants (not considered a disease) and the lack of information provided by physicians (about causes and pharmacological as well as non-pharmacological treatments of gout). Participants emphasised the impact of acute attacks of gout and prioritised dietary modifications and treatment of acute attacks over long-term urate-lowering therapy. Characteristics of acute gout, lack of understanding and information about gout and its treatments perpetuate poor HRQOL. HRQOL (maintenance of usual diet and reduced frequency of attacks) was associated with urate-lowering treatment. Better patient, public and practitioner education about gout being a chronic condition associated with co-morbidities and poor HRQOL may improve understanding and long-term treatment of gout.
TL;DR: The prevalence of musculoskeletal disorders was 53.7 % and rheumatic diseases 29.6 %.
Abstract: This study aimed to estimate the prevalence of musculoskeletal disorders and rheumatic diseases among the indigenous Qom (Toba) population in the city of Rosario, Santa Fe, Argentina. An analytical cross-sectional study using methodology of the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) was performed. Subjects ≥18 years of age were interviewed by advanced students of medicine and nursing, bilingual translator-facilitators, and coordinators. Individuals with musculoskeletal pain (positive cases) were evaluated sequentially for 7 days by internists and rheumatologists for diagnosis and treatment. The study included 1656 individuals (77 % of the census population). Of these, 1020 (61.5 %) were female, with mean age of 35.3 (SD 13.9) years, and 1028 (62.0 %) were bilingual. The public health care system covers 87.1 % of the population. Musculoskeletal pain in the previous 7 days and/or at some time during their life was present in 890 subjects (53.7 %). Of those with pain in the last 7 days, 302 (64.1 %) subjects had an Health Assessment Questionnaire Disability Index (HAQ-DI) score ≥0.8. The most frequent pain sites were lumbar spine (19.3 %), knees (13.0 %), and hands (12.0 %). The prevalence of rheumatic diseases was as follows: mechanical back pain (20.1 %), rheumatic regional pain syndrome (2.9 %), osteoarthritis (4.0 %) rheumatoid arthritis (2.4 %), inflammatory back pain (0.2 %), systemic sclerosis (0.1 %), Sjogren syndrome (0.1 %), fibromyalgia (0.1 %), mixed connective tissue disease (0.06 %), and systemic lupus erythematosus (0.06 %). The prevalence of musculoskeletal disorders was 53.7 % and rheumatic diseases 29.6 %. Rheumatoid arthritis prevalence was 2.4 % using COPCORD methodology, one of the highest reported at present.
TL;DR: Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus.
Abstract: Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.
TL;DR: Patients with RA-ILD are at risk of serious infection and Prednisone use >10 mg per day was associated with higher rates of infection, and immunosuppressive drug use governed by concern for risk of infection in patients with ILD resulting in channeling bias cannot be excluded.
Abstract: The objective of this study is to assess the occurrence of and risk factors for serious infections in rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). All patients with RA-ILD (ACR 1987 criteria for RA) seen at a single center from 1998 to 2014 were identified and manually screened for study inclusion. Follow-up data were abstracted until death or December 31, 2015. Serious infection was defined as requiring antimicrobial therapy and hospitalization. Risk of infection was analyzed by person-year (py) methods using time-dependent covariates started when the medication was first used and stopped 30 days after the medication was discontinued. Of the 181 included patients, 87 (48 %) were female. The mean age at ILD diagnosis was 67.4 (±9.9) years, and median follow-up time was 3.1 (range: 0.01 to 14.8) years. Higher infection rates were observed during the first year after ILD diagnosis (14.1 per 100 py) than subsequently (5.7 per 100 py; p = 0.001). Pneumonia was the most common (3.9 per 100 py). Overall infection risk was higher in organizing pneumonia (OP) (27.1 per 100 py) than usual interstitial pneumonia (7.7 per 100 py) or non-specific interstitial pneumonia (5.5 per 100 py) (p 10 mg per day (15.4 per 100 py). Patients with RA-ILD are at risk of serious infection. Prednisone use >10 mg per day was associated with higher rates of infection. Immunosuppressive drug use governed by concern for risk of infection in patients with ILD resulting in channeling bias cannot be excluded.
TL;DR: The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality and further prospective clinical studies are needed to define whether levels of Kl-6 might have prognostic value or might predict progressive ILD.
Abstract: It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.
TL;DR: IL-37 is an important anti- inflammatory cytokine in AGA by suppressing the production of pro-inflammatory cytokines and may provide a novel research target for the pathogenesis and therapy of GA.
Abstract: Acute gouty arthritis (AGA) is an auto-inflammatory disease characterized by resolving spontaneously, which suggests that negative feedback loops control inflammatory and immunological responses to monosodium urate (MSU) crystals. By now, the molecular mechanism for spontaneous resolution of acute GA remains unclear; this study was undertaken to evaluate whether IL-37 is involved in spontaneous resolution of AGA. A total of 45 acute GA (AGA),29 non-acute GA (NAGA) male patients and 82 male health control (HC) were involved in this study, we measured IL-7 expression in the peripheral blood mononuclear cells (PBMCs), together with levels of IL-1β, IL-6, IL-10, TNF-α and TGF-β1 in the serum. Further, we either inhibited IL-37 expression in human PBMCs with siRNA or over-expressed the cytokine in human macrophages. Pro-inflammatory cytokine IL-1β, IL-6, and TNF-α expressions were significantly higher in the AGA group than in the NAGA or HC group (P < 0.05, respectively). However, anti-inflammatory IL-37, TGF-β1, and IL-10 were greater in the NAGA group than in the AGA and HC groups (P < 0.05, respectively). Expression of IL-37 in MSU crystal-treated macrophages inhibited the expression of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human blood cells. However, anti-inflammatory TGF-β1 and IL-10 expressions in these supernatants were unaffected by over-expression or knockdown of IL-37. Our study indicates that IL-37 is an important anti-inflammatory cytokine in AGA by suppressing the production of pro-inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GA.