Metabolic abnormalities in patients with inflammatory rheumatic diseases

Patients with rheumatoid arthritis (RA) experience an increased cardiometabolic risk factor burden that is substantially driven by systemic inflammation. This occurs less consistently in patients with ankylosing spondylitis (AS). Psoriatic arthritis most strongly associates with excess adiposity and metabolic risk. RA patients also often have systemic inflammation-induced proinflammatory high-density lipoprotein (HDL) cholesterol particles and lean/muscle mass loss in association with increased adiposity, a condition termed rheumatoid cachexia, which further enhances cardiovascular risk. The presence of proinflammatory HDL and lean mass loss was also reported in patients with AS. Individualized aerobic and resistance exercise programs can improve body composition and metabolic risk factor profiles in RA and AS. Future studies should assess how long-term lifestyle changes can be effectuated and if these can influence cardiovascular events in inflammatory rheumatic diseases. Herein, we review the current evidence on metabolic abnormalities in inflammatory arthritis. We propose management strategies and a research agenda.     

The prevalence and impact of comorbid fibromyalgia in inflammatory arthritis

Fibromyalgia (FM) is one of the most common conditions that rheumatologists encounter. It is characterised by chronic widespread pain, fatigue, sleep disturbances and impaired cognition. The prevalence of comorbid FM among populations with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are considerably higher than among the general population, with pooled prevalence estimates of 18–24% in RA, 14–16% in axSpA and 18% in PsA. Prevalence estimates should be interpreted with care as the criteria for FM have not been validated for use in patients with inflammatory arthritis. Comorbid FM appears to affect assessment of disease severity in these conditions, particularly patient-reported outcome measures, and may influence response to treatment. There is a need for better identification, classification and management of FM in the context of inflammatory rheumatic diseases.     

Association of inflammatory bowel disease with ankylosing spondylitis and rheumatoid arthritis: A nationwide population-based study

Objectives: Tantalizing connections between autoimmune rheumatic diseases (ARDs) and inflammatory bowel disease (IBD) have become evident with regard to their genetic and immunologic background. However, the association between these two disease entities remains unclear. The aim of this study is to investigate the association between each ARD and IBD.

Methods: A nationwide population-based cross-sectional study was performed using the Korean National Health Insurance Claims database. The data of patients with IBD and age- and sex-matched controls between 2009 and 2013 were collected from the database. The prevalence of ARDs, including systemic lupus erythematosus (SLE), inflammatory myositis (polymyositis and dermatomyositis), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), was determined. The associations between each ARD and IBD were analyzed using multivariate logistic regression models.

Results: A total of 40,843 IBD patients (28,197 patients with ulcerative colitis and 12,646 with Crohn’s disease) and 122,529 controls were enrolled. The nonstratified analysis revealed that patients with IBD had significant risk of being concomitantly affected by AS (odds ratio [OR] 5.140, 95% confidence interval [95% CI] 4.069–6.492) and RA (OR: 3.474, 95% CI: 2.671–4.519) after adjusting for age and sex. No significant association was observed between IBD and other ARDs including SLE, inflammatory myositis, SSc, and SjS.

Conclusion: IBD is significantly associated with AS and RA in the large-scaled population-based study. This result suggests that etiopathogenesis of IBD might be shared with AS and RA.     

Cardiovascular morbidity and associated risk factors in Spanish patients with chronic inflammatory rheumatic diseases attending rheumatology clinics: Baseline data of the CARMA Project

ObjectiveTo establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and unexposed individuals attending rheumatology clinics.MethodsAnalysis of data from the baseline visit of a 10-year prospective study [CARdiovascular in rheuMAtology (CARMA) project] that includes a cohort of patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from 67 hospitals in Spain. Prevalence of CV morbidity, CV risk factors, and systematic coronary risk evaluation (SCORE) assessment were analyzed.ResultsA total of 2234 patients (775 RA, 738 AS, and 721 PsA) and 677 unexposed subjects were included. Patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. The prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%), and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR = 1.58; 95% CI: 0.90–2.76; p = 0.10) and AS (OR = 1.77; 95% CI: 0.96–3.27; p = 0.07). Disease duration in all CIRD groups and functional capacity (HAQ) in RA were associated with an increased risk of CVD (OR = 2.15; 95% CI: 1.29–3.56; p = 0.003). Most patients had a moderate CV risk according to the SCORE charts.ConclusionsDespite recent advances in the management of CIRD, incidence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics.     

An overview of biologic disease-modifying antirheumatic drugs in axial spondyloarthritis and psoriatic arthritis

Biologic disease-modifying antirheumatic drugs (bDMARDs) are engineered proteins with high affinity for various proinflammatory immune mediators to reduce inflammation and its sequelae in various rheumatic diseases. These medications, introduced at the advent of the 21st century, have revolutionized the treatment of axial spondyloarthritis (including ankylosing spondylitis) and psoriatic arthritis. Currently approved bDMARDs for axial spondyloarthritis are etanercept, infliximab, adalimumab, golimumab, certolizumab pegol, and secukinumab. For psoriatic arthritis, all of these drugs are approved in addition to ixekizumab, ustekinumab, abatacept, and tofacitinib. Selection of the optimal bDMARD should consider patient comorbidity including uveitis, psoriasis, and inflammatory bowel disease.     

Lymphedema and rheumatological disorders

In the literature, although the prevalence of lymphedema is low in inflammatory rheumatological diseases, rigorous approaches to diagnosis and treatment have led to significant improvement in patients’ quality of life. Lymphedema is observed more frequently in patients with rheumatoid arthritis with respect to case presentations, but it is also observed in psoriatic arthritis, ankylosing spondylitis, systemic sclerosis, and childhood inflammatory rheumatological diseases. Other rheumatological diseases and tumor-related secondary causes should also be kept in mind in the diagnosis of lymphedema. Complex decongestive therapy-skin care, manual lymph drainage, compression and exercise are the primary treatment approaches. Both basic drugs and tumor necrosis factor-α inhibitors have been tried in addition to complex decongestive physiotherapy programs. However, the success of alternative medical treatments is controversial in the literature. It may be useful to include the disease in post-diagnosis complex decongestive physiotherapy program and to use the drugs mentioned in the literature. However, more data are needed to reach conclusive results.     

Characteristics and medical management of patients with rheumatoid arthritis and ankylosing spondylitis

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, progressive, systemic inflammatory rheumatic diseases that lead to serious disability. The objective of this study was to investigate the demographic and clinical characteristics of the patients with RA and AS who were treated in tertiary hospitals in Turkey and to analyze their current medical management. A total of 562 RA and 216 AS patients were evaluated. The mean age of RA patients was 52.1 ± 12.6 years. The female to male ratio was 3.7:1. Of the RA patients, 72.2% had positive rheumatoid factor (RF), 62.9% had high C-reactive protein, and 75.2% had radiological erosion. The ratio of patients with Disease Activity Score (DAS) 28 >3.2 was 73.9% and of those with Health Assessment Questionnaire (HAQ) ≥1.5 was 20.9%. There was a statistically significant increase in RF positivity and HAQ scores in the group with higher DAS 28 score. Frequency of extraarticular manifestations was 22.4%. The ratio of the patients receiving disease modifying antirheumatic drugs (DMARD) was 93.1%, and 6.9% of the patients were using anti-tumor necrosis factor (TNF) blocking agents. In AS, the mean age of the patients was 38.1 ± 10.6, and the female to male ratio was 1:2.5. The time elapsed between the first symptom and diagnosis was 4.3 years. The ratio of peripheral joint involvement was 29.4%. Major histocompatibility complex, class I, B 27 was investigated in 31.1% of patients and the rate of positivity was 91%. In 52.4% of the patients, Bath AS Disease Activity Index (BASDAI) was ≥4. The erythrocyte sedimentation rate, Bath AS Functional Index, and peripheral involvement were significantly higher in the group with BASDAI ≥4. Frequency of extraarticular involvement was 21.2% in AS patients. In the treatment schedule, 77.5% of AS patients were receiving sulphasalazine, 15% methotrexate, and 9.9% anti-TNF agents. Despite widespread use of DMARD, we observed high disease activity in more than half of the RA and AS patients. These results may be due to relatively insufficient usage of anti-TNF agents in our patients and therefore these results mostly reflect the traditional treatments. In conclusion, analysis of disease characteristics will inform us about the disease severity and activity in RA and AS patients and could help in selecting candidate patients for biological treatments.     

Comparative analysis between ankylosing spondylitis and axial psoriatic arthritis patients

Aim of the workTo compare clinical aspects, disease activity, spinal mobility, and radiographic findings between ankylosing spondylitis (AS) and axial psoriatic arthritis (axPsA) patientsPatients and methodsFifty-eight AS and 42 axPsA patients were enrolled. Patients were assessed by clinical examination, spinal mobility measurements, and conventional radiographs of the sacroiliac joints, lumbosacral and cervical spines. Bath.AS Metrology Index (BASMI) and modified Stoke AS Spinal Score (mSASSS) were measured. Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index score and AS Disease Activity Score (ASDAS) were assessed. Results: The mean age of AS and AxPsA patients were comparable (37.2 ± 11.2 years vs 39.6 ± 13.3 years;p = 0.33) and male:female was 2.63 vs 0.24:1 (p < 0.0001). Inflammatory back pain (IBP) was higher in AS (93.1%) than axPsA (76.2%). Peripheral arthritis was higher in axPsA (85.7%) than in AS (39.7%). Dactylitis and nail dystrophy were present only in axPsA (33.3% and 28.6% respectively) while uveitis was more common in AS (60.3%vs 28.6%;p = 0.12). SPARCC score was higher in axPsA (p = 0.12).The median BASMI was higher in AS (2.1) than axPsA (1.2)(p = 0.07). The mSASSS was similar (AS:19.6 ± 4.7;6–40 and axPsA:14.4 ± 2.1;0–32)(p = 0.23). 63.8% of AS patients had grade 3 sacroiliitis while 61.9% of axPsA had grade 2. 75.9% of AS had high ASDAS while 33.3% of axPsA patients had very high activity (p = 0.039).ConclusionsAS patients were more likely to be males, smoked, higher IBP, lower peripheral arthritis, more uveitis, higher limitation in spinal mobility measurements, more spinal deformities, and severe radiographic involvement with nearly equal disease activity as in axPsA patients.     

Patrones de tratamiento biológico en pacientes con enfermedades articulares inflamatorias. Estudio retrospectivo de 4 años de seguimiento

ObjectivesTo describe the therapeutic management of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) in patients initiating treatment with biological agents.Materials and methodsObservational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analyzed.ResultsFour hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS.ConclusionsOur results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments.     

Cardiovascular disease in inflammatory rheumatic diseases

Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.     

Functional assessment measures in rheumatologic disorders

Rheumatologic disorders cause functional impairment and significantly affect health-related quality of life. Functional assessment and health-related quality of life scales are increasingly being used as outcome measures to assess the influence of the diseases and health outcome in clinical studies of patients with rheumatologic diseases. In this article, we review the functional assessment and health-related quality of life measures which have been commonly used as outcome measures in rheumatologic disorders. These measures are Short form-36(SF-36), SF-12, Nottingham Health Profile, Sickness Impact Profile, Euro Qol, SF-6D, Health Utilities Index mark 2 and 3, Stanford Health Assessment Questionnaire, Rheumatoid Arthritis Quality of Life Questionnaire, Arthritis Impact Measurement Scales, Mc Master Toronto Arthritis Patient Preference Disability Questionnaire, Western Ontario and Mc Master Universities Osteoarthritis Index, Lequesne Index, Knee Disability and Osteoarthritis Outcome Score, Knee Disability and Osteoarthritis Outcome Score-Physical Function Shortform, Hip Disability and Osteoarthritis Outcome Score, Hip Disability and Osteoarthritis Outcome Score-Physical Function SF, Fibromyalgia Impact Questionnaire, Psoriatic Arthritis Quality of Life Scale, Gout Assessment Questionnaires, Dougados Functional Index, Bath Ankylosing Spondylitis Functional Index, and Ankylosing Spondylitis Quality of Life Scale.     

HLA risk alleles and gut microbiome in ankylosing spondylitis and rheumatoid arthritis

Human leukocyte antigen (HLA) alleles are associated with a variety of autoimmune diseases. The composition of gut microbiome can be influenced by host immunity, which is partially regulated by HLA. In this review, first we provide evidence from animal and human studies on: if and how HLA-B27, HLA-DRB1 (shared epitope (SE)), and other HLA alleles alter the gut microbiome, then we analyzed the data for several hypotheses to explain the mechanism(s) of HLA alleles influences on gut microbiome, and finally, we discussed several potential clinical implications of HLA alleles and microbial data, such as bacterial biomarkers for diagnosis, treatment, and the screening of high-risk population.     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Corticosteroid usage was assessed in rheumatoid arthritis (RA) and psoriatic arthritis (PA) patients in Italy. A multicentre, observational study was undertaken in 10 Italian rheumatological centres from 1990 to 1992 using a computerised clinical data bank. Nine hundred and seven RA patients and 180 PA patients were studied; 510 (56.2%) RA patients and 44 (24.4%) PA patients were using corticosteroids. The percentage of patients taking corticosteroids ranged from 20.5 to 85.4% for RA patients and from 0 to 55% for PA patients for the different centres. Methylprednisolone was the most prescribed corticosteroid, both in RA patients (63.2%) and in PA patients (65.9%). The average methylprednisolone daily dose was 5.7±3.6 mg in RA patients and 4.5±1.4 mg in PA patients. The data provide evidence that corticosteroids are taken in an unexpectedly high percentage of patients with RA and PA in Italy.     

Lung involvement in inflammatory rheumatic diseases

This chapter describes the involvement of the lung in systemic inflammatory joint disease (IJD) with a particular focus on rheumatoid arthritis, although the topics of pulmonary involvement in ankylosing spondylitis and psoriatic arthritis are also addressed. Interstitial lung disease is the most lethal pulmonary complication of IJD and the chapter describes recent advances in both our understanding of this complication and the therapeutic options that offer real hope for improved outcomes. Although less well recognised, airways disease is just as common and its association with IJD is described in some detail, with a section devoted to the recent surge in interest in bronchiectasis. Acute pulmonary infection is common in IJD and its management is reviewed in some detail. Although pleural disease is less common than it once was, its treatment is explored. We conclude by reviewing the relationship between the drug therapies employed in IJD and their effects on the lung.     

Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis and ankylosing spondylitis without respiratory symptoms

Pulmonary involvement seen in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has been detected increasingly by using highly sensitive diagnostic techniques such as high-resolution computed tomography (HRCT). However, HRCT findings in healthy controls and the effects of smoking and drugs have not been well studied. The aim of this controlled study was to evaluate the relationships between disease-specific clinical, laboratory, HRCT and pulmonary function test (PFT) findings in 20 RA patients using methotrexate (MTX) and 20 AS patients using sulphasalazine who were non-smokers and exhibited asymptomatic respiratory signs. For this purpose, a total of 60 persons (40 patients and 20 healthy controls) were included in this study. A restrictive pattern on PFT was detected in four patients (20%) with AS, one patient with RA and one control (p<0.05). Fourteen patients (70%) with RA and ten patients (50%) with AS had positive HRCT findings. Only one patient (5%) in the control group had abnormal HRCT findings (p<0.05). Interstitial lung disease (ILD) was the most frequently seen HRCT finding in both the RA (35%) and AS (20%) groups. The chest expansion measurement, the score of the visual analogue scale (VAS) for pain and C-reactive protein (CRP) levels were statistically significantly better in patients with AS having normal HRCT than in those with abnormal findings (p<0.05). There was no correlation detected between HRCT and duration of disease, disease activity markers, functional indexes and PFT in patients with RA and AS. HRCT is a sensitive tool in detecting ILD in patients with RA and AS with no signs and symptoms of pulmonary involvement and may be an integral part of such work-up. However, future prospective studies are needed to better determine if HRCT is in fact a predictor of subsequent MTX toxicity.     

Emerging treatment options for spondyloarthritis

The management of spondyloarthritis (SpA) has substantially changed as a consequence of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). However, the treatment options in patients with axial SpA (axSpA) not responding to nonsteroidal anti-inflammatory drugs (NSAIDs) had been restricted to tumor necrosis factor alpha (TNFα) inhibitors for almost 15 years. With the approval of secukinumab, an interleukin (IL)-17A inhibitor, there is a new alternative in the treatment of axial SpA. In patients with psoriatic arthritis (PsA) not responding to conventional therapy with NSAIDs and conventional synthetic DMARDs, therapeutic options are more diverse. In addition to TNFα inhibitors and secukinumab, another IL-17A inhibitor ixekizumab, IL-12/23 blocker ustekinumab, phosphodiesterase-4 inhibitor apremilast, T-cell-mediated pathway inhibitor abatacept, and Janus kinase (JAK) inhibitor tofacitinib are the approved treatment. Nevertheless, there is still an unmet need for further treatment options in both axSpA and PsA. Further therapeutics, such as the dual IL-17A and F inhibitor bimekizumab, IL-17 receptor blocker brodalumab, and JAK inhibitors baricitinib, filgotinib and upadacitinib are in development for these indications. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab are further emerging drugs for PsA. Thus, the number of treatment options in SpA is likely to be increased over the next few years that make identification of optimal treatment strategies essential.     

The triggering role of physical injury in the onset of peripheral arthritis in seronegative spondyloarthropathy

Summary Three more cases of B27-positive patients who developed peripheral arthritis immediately after trauma are reported. The first had an exacerbation of arthritis in the right hip after falling from her motor-bike. The second had arthritis of the distal interphalangeal (DIP) joint of the right forefinger after shutting his finger in the door of his car. The third had arthritis of the right sternoclavicular joint after a road-accident while fastening her safety belt.     

Ultrasonographic evaluation of tendons and enthesal sites in rheumatoid arthritis: comparison with ankylosing spondylitis and healthy subjects

The objective of this study was to determine tendon involvements and enthesal abnormalities in patients with rheumatoid arthritis (RA) using high-resolution ultrasonographic images and to compare the findings with those seen in patients with ankylosing spondylitis (AS) and healthy controls. A total of 24 patients with RA, 18 with AS, and 20 healthy controls matched by age and body mass index (BMI) were included in the study. All of the patients and controls underwent clinical and ultrasonographic examinations of both lower limbs at five enthesal sites (superior and inferior pole of the patella, tibial tuberosity, Achilles tendon, and plantar aponeurosis) and both upper limbs at two tendon sites (tendons of m. biceps brachii and supraspinatus at the shoulder). High-resolution ultrasonographic examinations were performed to detect bursitis, structure thickness, bony erosion, and enthesophyte. An ultrasonographic score of lower limb enthesitis was calculated using the Glasgow Ultrasound Enthesitis Scoring System (GUESS) in all patients. Tendon involvements and enthesal abnormalities were found significantly more often in the RA group than in controls (p<0.05 to <0.001), but were not found to be different from the AS group (p>0.05). On clinical examination 67 of 336 (19.9%) tendon and enthesal sites were abnormal and on ultrasonographic examination 130 of 336 (38.2%) sites were abnormal in RA patients. The most frequently affected enthesal sites in the lower limbs were suprapatellar, infrapatellar, and Achilles tendon in both the RA and AS groups. The tibial tuberosity was less affected in both groups, and involvement of the plantar aponeurosis was not different from the controls. A statistically significant correlation was found between the Ritchie articular index and GUESS (r=0.578, p=0.008). Tendon involvements and enthesal abnormalities in RA patients were found more often than had been estimated. Further studies are required to validate our results.