BACKGROUND:

In the last decade there has been a significant expansion in the body of knowledge on the effects of rheumatoid arthritis (RA) on the foot and the management of these problems. Aligned with this has been the development of specialist clinical roles for podiatrists. However, despite being recommended by national guidelines, specialist podiatrists are scarce. In order to inform non-specialist podiatrists of the appropriate interventions for these foot problems, management guidelines have been developed and disseminated by a group of specialist podiatrists. The aim of this survey was to investigate the use of these guidelines in clinical practice.

METHOD:

Following ethical approval an online questionnaire survey was carried out. The questions were formulated from a focus group and comprised fixed response and open response questions. The survey underwent cognitive testing with two podiatrists before being finalised. An inductive approach using thematic analysis was used with the qualitative data.

RESULTS:

245 questionnaires were completed (128 -- non-specialist working in the private sector, 101 non--specialists working in the NHS and 16 specialist podiatrists). Overall, 97% of the non-specialists (n = 222) had not heard of the guidelines. The non-specialists identified other influences on their management of people with RA, such as their undergraduate training and professional body branch meetings. Three main themes emerged from the qualitative data: (i) the benefits of the foot health management guidelines, (ii) the barriers to the use of guidelines generally and (iii) the features of useable clinical guidelines.

CONCLUSIONS:

This study has revealed some crucial information about podiatrists' level of engagement with the foot health management guidelines and the use of guidelines in general. Specifically, the non-specialist podiatrists were less likely to use the foot health management guidelines than the specialist podiatrists. The positive aspects were that for the specialist practitioners, the guidelines helped them to identify their professional development needs and for the few non-specialists that did use them, they enabled appropriate referral to the rheumatology team for foot health management. The barriers to their use included a lack of understanding of the risk associated with managing people with RA and that guidelines can be too long and detailed for use in clinical practice. Suggestions are made for improving the implementation of foot health guidelines.

Dyslipidaemia is commonly observed in patients with active rheumatoid arthritis (RA), with lower total cholesterol levels as well as lower levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) reported in these patients than in individuals without RA. This pattern is mirrored in sepsis and other inflammatory states, suggesting systemic inflammation has the general effect of lowering circulating lipid levels. In line with such observations, suppressing inflammation with DMARDs, biologic therapies and small-molecule Janus kinase inhibitors seems to elevate levels of lipid fractions in RA, albeit in a variable manner dependent presumably upon the mechanism of action of the different agents. In addition, limited epidemiological data in patients with RA suggest increased cardiovascular disease (CVD) risk at relatively low cholesterol levels, a pattern contrasting with that observed in the population without RA. Our understanding of the potential mechanisms behind these inflammation-associated lipid changes remains suboptimal and requires further study. In clinical terms, however, use of the total cholesterol to HDL-C ratio as the lipid component of CVD risk scoring in patients with RA would seem appropriate given that these lipid parameters generally change in parallel with inflammation and suppression of inflammation. Whether alternative lipid or lipoprotein measures (or simple markers of inflammation) could improve stratification of CVD risk in RA beyond the established risk factors requires future investigation.

OBJECTIVE:

In rheumatoid arthritis (RA), anti-tumor necrosis factor (anti-TNF) treatment is shown to reduce but not to arrest the rate of hand bone loss. This has not been assessed in psoriatic arthritis (PsA). Our objective was to examine changes in cortical hand bone density in patients with PsA treated with placebo or infliximab (IFX).

METHODS:

Patients in IMPACT II (Induction and Maintenance Psoriatic Arthritis Clinical Trial 2) were randomized to placebo or IFX. After Week 24, all received IFX. In a subset of 120 patients, cortical hand bone density was assessed at Weeks 0, 24, and 54 by digital X-ray radiogrammetry (dxr-BMD) on the same radiographs scored for joint damage.

RESULTS:

Changes from baseline to 24 weeks in dxr-BMD were -0.30% (SD 1.1%) in the placebo group and -0.08% (SD 1.4%) in the IFX group (p = 0.63). Between baseline and 54 weeks the changes were -0.71% (SD 2.1%) in the placebo group and 0.15% (SD 1.7%) in the IFX group (p = 0.07), and between 24 and 54 weeks -0.41% (SD 1.4%) and 0.23% (SD 0.8%), respectively (p = 0.05). No significant correlation was found between change in dxr-BMD and radiographic damage.

CONCLUSION:

This pilot study indicates that hand bone loss in PsA patients treated with anti-TNF can be arrested. Assessment of hand bone density may thus be a potential outcome measure for bone involvement and a response variable to treatment in PsA.

Granuloma annulare (GA) is classified as localized, generalized÷disseminated, subcutaneous, and perforating types. The studies show connection with diabetes mellitus, lipidic metabolic disorders, malignant diseases, thyroid disorders, infections (HBV, HCV, HIV). We performed a retrospective study between 2010-2011, regarding disseminated GA (GAD), and the relationship between GAD and other comorbidities. We clinically and histologically diagnosed eight cases of GAD. The patients were also investigated for the diagnosis of associated diseases. The treatment included topical corticosteroids, antihistamines, Calcipotriol÷Betamethasone, Tacrolimus 0.03%, Pentoxifylline, Hydroxychloroquine. Therapeutic response was assessed one month and three months after hospitalization. Our patients were five women and three men, aged 46-68 years, mean age 57.25 years, with a disease history of one year and a half (between three months and four years). The lesions occurred in the upper extremities (eight cases), distal extremities (three cases), cervical area (two cases), and trunk (five cases). In seven cases, we found annular appearance and one patient had disseminated small papules eruption. Associated pathology was diabetes mellitus type II (five cases), overweight and obesity (five cases), dyslipidemia (three cases), hypothyroidism (one case), rheumatoid arthritis (one case), external ear canal basal carcinoma (one case). Although there is controversy regarding the relationship between GAD and associated diseases, it is accepted that it is significantly associated with diabetes mellitus, also found in our study in five out of eight cases. We noticed obvious improvements after local and general treatment. It is confirmed that GAD is prevalent in women, over 40-year-old. GAD is often associated with diabetes and dyslipidemia, therefore it is necessary to investigate patients in this direction. The histopathological exam is essential for an accurate confirmation of GA.

Since their discovery in 1948, glucocorticoids have been widely used clinically to treat inflammatory disorders like rheumatoid arthritis. However, their usefulness, especially in rheumatoid arthritis therapy, is hampered by severe side effects on bone leading to glucocorticoid-induced osteoporosis. The molecular and cellular mechanisms mediating the beneficial and adverse effects remain poorly understood. Nevertheless, advanced molecular biological analyses and in vivo approaches using conditional mutant mice have helped to unravel in part the underlying mechanisms of immunosuppression and side effects of glucocorticoid therapy in arthritis, thereby contributing to an improved understanding of these therapeutically important hormones.

Chronic constipation is highly frequent in the general population (a prevalence of 14%). An underlying organic cause is usually absent, this type of constipation being known as chronic idiopathic constipation (CIC). Although usually considered banal, this disorder has a substantial personal, social and healthcare impact. Several studies have associated CIC with high rates of absenteeism in the workplace and disruption of routine activities. All these factors lead to high direct and indirect healthcare expenditure. Physically, the impact on patients with CIC, who require specialized care, is higher than that of ulcerative colitis or stable Crohn's disease. The psychological impact exceeds that caused by rheumatoid arthritis or hemodialysis. Appropriate treatment can improve HRQL in affected individuals. Recently, prucalopride, a highly selective 5-HT4 receptor agonist has been shown to improve the symptoms of CIC and to have a beneficial effect on HRQL.

OBJECTIVE:

Rheumatoid arthritis (RA) is a complex disorder with many genetic and environmental factors to account for disease susceptibility. Individual genetic association studies usually suffer from small sample size leading to biased results of polymorphisms association with RA liability. Therefore, meta-analyses seem to resolve this limitation, up to a point, increasing the power of statistical analyses. In this review, we summarize the current knowledge of non-HLA genetic factors contributing to RA predisposition based on meta-analyses.

METHODS:

Using the key words: rheumatoid arthritis, meta-analysis, and polymorphism, we searched the PubMed database for the associated articles. Up to the middle of November 2012, seventy-nine articles fulfilled the criteria and highlighted the current findings on the genetic factors contributing to RA susceptibility.

RESULTS:

The association with RA was confirmed for 32 gene polymorphisms, being population specific in some cases. However, meta-analyses did not confirm an association in case of 16 gene variants, previously studied in individual studies for their association with RA.

CONCLUSIONS:

The use of bioinformatics tools and functional studies of the summarized implicated genes in RA pathogenesis could shed light on the molecular pathways related to the disorder, helping to the development of new drug targets for a better treatment of RA.

Rheumatoid arthritis (RA) is a chronic systemic disease that leads to increases in health system economic burden through direct and indirect costs, including chronic treatment, reduced productivity and premature mortality. Anti-TNF agents have represented a major advance in the treatment of RA. The most commonly used (adalimumab, etanercept and infliximab) have demonstrated their cost-effectiveness at label doses. However, physicians may need to adapt the treatment by increasing the dose when a drug is not effective enough or by reducing it when there is a sustained effectiveness. In a cross-sectional study conducted in our hospital in which information from RA patients treated with anti-TNF drugs under conventional and modified doses were collected, the authors analyzed the costs of the medication in order to estimate the mean patient-year cost, the annual costs related to clinical efficacy and the cost per responder patient to anti-TNF treatment when dosage modification is undertaken in daily clinical practice.

Although oral bisphosphonates (BP) are highly effective in preventing fractures, some patients will fracture while on treatment. We identified predictors of such fractures in a population-based cohort of incident users of oral BP. We screened the SIDIAP database to identify new users of oral BP in 2006-2007. SIDIAP includes pharmacy invoice data and primary care electronic medical records for a representative 5 million people in Catalonia (Spain). Exclusion criteria were: Paget disease, <40 years of age, and any anti-osteoporosis treatment in the previous year. A priori defined risk factors included age, gender, body mass index, vitamin D deficiency, smoking, alcohol drinking, pre-existing comorbidities, and medications. Fractures were considered if they appeared after at least 6 months after treatment initiation. Fractures while on treatment were defined as those occurring among participants persisting for at least 6 months and with an overall high compliance (medication possession ratio ≥ 80%). Fine and Gray survival models accounting for competing risk with therapy discontinuation were fitted to identify key predictors.

RESULTS:

Only 7,449/21,385 (34.8%) participants completed >6 months of therapy. Incidence of "fracture while on treatment" was 3.4/100 person-years [95%CI 3.1-3.7]. Predictors of these among patients persisting and adhering to treatment included: older age (sub-hazard ratio (SHR) for 60 to <80 years 2.18 [1.70-2.80]; for ≥80years 2.5 [1.82-3.43]), previous fracture (SHR 1.75 [1.39-2.20] and 2.49 [1.98-3.13] in the last 6 months and longer respectively), underweight (SHR 2.11 [1.14-3.92]), inflammatory arthritis (SHR 1.46 [1.02-2.10]), use of proton pump inhibitors (PPI) (SHR 1.22 [1.02-1.46]) and vitamin D deficiency (SHR 2.69 [1.27-5.72].

CONCLUSION(S):

Even among high compliers, 3.4% of oral BP users will fracture every year. Older age, underweight, vitamin D deficiency, PPI use, previous fracture and inflammatory arthritides increase risk. Monitoring strategies and/or alternative therapies should be considered for these patients.

Abstract There is an urgent need for identifying novel serum biomarkers that can be used to improve diagnosis, predict disease progression or response to therapy, or serve as therapeutic targets for rheumatic diseases. Synovial fluid (SF) is secreted by and remains in direct contact with the synovial membrane, and can reflect the biochemical state of the joint under different physiological and pathological conditions. Therefore, SF is regarded as an excellent source for identifying biomarkers of rheumatologic diseases. The use of high-throughput and/or quantitative proteomics and sophisticated computational software applied to analyze the protein content of SF has been well-adopted as an approach to finding novel arthritis biomarkers. This review will focus on some of the potential pitfalls of biomarker studies using SF, summarize the status of the field of SF proteomics in general, as well as discuss some of the most promising biomarker study approaches using proteomics. A brief status of the biomarker discovery efforts in rheumatoid arthritis, osteoarthritis and juvenile idiopathic arthritis is also provided.