Current Rheumatology Reviews - Volume 12, Issue 3, 2016

Methotrexate (MTX) was synthesised as a folate antagonist for use in treating childhood leukaemia in 1940s. Gubner and colleagues in 1953 used several log-order lower doses of MTX that mimicked the anti-inflammatory properties of cortisone. They used it successfully in treating rheumatoid arthritis (RA). Their work was however overlooked because the Nobel Prize winning drug cortisone held sway in those days. With increasing awareness of the adverse effects of cortisone, interest was rekindled in discovering ‘steroid-sparing’ drugs. Hoffmeister and Willkens used low-dose MTX (LD-MTX) in treating RA patients in 1960s with impressive results. Pivotal trials in 1984-5 established the efficacy and safety of LD-MTX in treating RA that gained FDA approval in 1988. LD-MTX at doses <25-30 mg weekly as mini-pulses, is presently the standard-of-care for the treatment of RA. Its toxicities and adverse effects are rarely if ever life-threatening. This is in contrast to the high-dose methotrexate (HD-MTX) for treating malignancies at doses that are several log-orders higher and usually cause serious toxicities. While LD-MTX acts mainly as an anti-inflammatory drug by increasing tissue adenosine levels besides other mechanisms, HD-MTX has anti-proliferative cytotoxic action with different toxicity profile and adverse effects. In practical terms LD-MTX and HD-MTX are 2 different therapeutic agents. However, in developing countries like India the stigma attached to MTX as a cytotoxic ‘cancer drug’ still persists and most non-rheumatologists fear its use in RA. This review aims to allay such anxiety attached to LD-MTX so that they start using it in appropriate doses for treating RA.

Osteoarthritis (OA) is a multifaceted disorder defined by the alteration of homeostasis and degradation in articular cartilage. Recently mounting evidence suggests that OA should be conceived as an inflammatory disease rather than a simple wear-and-tear problem. Bradykinin (BK) and B2 receptors play a role in the pathogenesis of OA. The aim of this paper is to analyze preclinical and clinical studies examining the potential role of BK and of B2 receptor blockade in OA pathogenesis. We analyzed the data about the effects of BK in synoviocytes, endothelial cells and chondrocytes cultures and described the action of B2 receptor antagonists (Icatibant and Fasitibant). In conclusion, the BK is an endogenous proinflammatory molecule that is involved in the pathophysiology of OA, and B2 receptor antagonists are believed to be considered as a potential symptomatic therapy for this disease. There is a need for further preclinical and clinical trials to better explain the mechanisms of action and the efficacy and tolerability of the B2 receptor antagonists in OA.

The pre-operative assessment is used to clarify issues prior to surgery that can change management provided by a multidisciplinary team. A high proportion of rheumatoid arthritis patients are elderly requiring orthopaedic surgery which requires further investigations, assessment of risk through functional capacity and several anaesthetic considerations. Rheumatoid arthritis patients often provide a variety of medical issues that can be found on careful and thorough pre-assessment that can be accommodated for by the surgical and anaesthetic team, however aspects of holistic management is an important considerations for efficient and effective management.

Background: Thyrotoxic periodic paralysis (TPP) is a rare disease entity highlighted by hypokalemia, flaccid paralysis, and thyrotoxicosis. It usually presents as sudden profound muscle weakness manifested as almost complete immobility and can affect proximal and distal limb muscles, respiratory musculature as well as the cardiac conduction system. Methods: A comprehensive review of Thyrotoxic periodic paralysis from 1885 to date was carried out by an extensive and thorough literature research including but not limited to Pubmed, Medline and EMBASE. Objective: This review emphasizes the etiology, pathogenesis, management and prognosis of TPP and aims to highlight clinical awareness of early diagnosis and rapid initiation of treatment. Conclusion: It is extremely important to diagnose this condition as early as possible as it is potentially reversible and prompt treatment leads to rapid resolution with no residual weakness. Missing the diagnosis can result in possible fatal complications such as hypercapneic respiratory failure and ventricular fibrillation.

Background: The use of simulation-based learning in the medical field has many benefits, including patient safety, health care professional confidence, accelerating diagnostic and therapeutic procedures, meeting the unfulfilled demand for medical personnel, and lowering of medical errors. Developing of interactive learning tools for teaching a simulated clinical case studies program, is highly needed to improve specialist nurses and middle grade health care professionals skills and competency. Aim: Assess the outcomes of a simulated problem-based learning educational activity for scoring the Psoriasis Area and Severity Index (PASI). Methods: 33 training health care professionals took part in the simulation activity. Before commencing the teaching program, every participant answered a pre-simulation activity confidence and competence levels questionnaire. The simulation activity was carried out in 3 phases: Phase 1: interactive instructor-learner format; Phase 2: Peer-led tutorial; Phase 3: completely independent student led learning adopting a “Problem solving” approach. At the end, every participant completed a questionnaire for post-simulation activity confidence and competence levels. Results: The percentage of agreement with the reference PASI score was progressively improving which reflects improvement of the learners’ skills after adopting the repetitive learner engagement approach. All participants expressed positive attitudes toward the simulation-based course. The overall mean for the student satisfaction subscale was 4.33/5, whereas the overall mean for the selfconfidence subscale was 4.15/5. Conclusion: Simulation-based teaching is an effective way to teach health care professionals. This approach led to improving attitudes, behaviors, interaction, confidence and overall performance leading to potential increased patient safety and better clinical outcomes. The next step is to implement simulation-based training effectively and efficiently in standard teaching.

The chronic diseases, rheumatoid arthritis (RA) and periodontal disease (PD) lead to confined destruction of soft and hard tissues as a result of inflammatory processes. Their pathogenesis is dictated by a network of inflammatory cells and its mediators. They also share some etiological risk factors and therapeutic alternatives. The evolution of focal infection theory is summarized in this review, with special reference to PD and its relationship to RA. Foci of chronic infections exist in the oral cavity and may result in anatomically distant disease in certain individuals. Recent cumulative evidences document the influence of inflammatory diseases such as RA on the development of PD. Historical evidences and new theories on the interrelationship between the two diseases have the potential to identify novel mechanisms and therapy to improve patient outcomes. This review focuses on not only the association of focal infection theory and RA, but also on the reciprocal effects of RA and PD.

Objectives: Rheumatoid arthritis (RA) is strongly associated with cardiovascular morbidity and mortality. Previous studies have demonstrated that TNFα-inhibitors may reduce cardiovascular events (CVE) in patients with RA. Thus, the purpose of this systematic review was to evaluate the ability of TNFα-inhibitors to reduce the risk of CVE in patients with RA. This study will update the findings of two earlier systematic reviews that synthesized the data up until 2010. Methods: A search of Medline, Embase, Medline In-Process and Other Non-Indexed Citations, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials was conducted for observational studies reporting on CVE in RA patients since 2009. Conference proceedings for the Canadian Rheumatology Association, American College of Rheumatology, and European League against Rheumatism were also searched between 2009 and 2014. Abstracts were assessed for inclusion by two reviewers and studies identified by either reviewer were brought forward to full-text review. Studies undergoing full-text review were further assessed based on predefined inclusion and exclusion criteria and the quality of selected papers was evaluated using the Newcastle-Ottawa Scale. Results: The search identified 6089 abstracts and 14 articles were included in the final systematic review. Of the studies included, 8 reported on the effect of TNFα-inhibitors on overall CVE, 10 reported on coronary artery disease (CAD), 6 reported on cerebrovascular disease (CVD), and 5 reported other clinical cardiovascular outcomes. Conclusion: TNFα-inhibitors appear to reduce the likelihood of overall CVE in individuals with RA. The reduction is not as pronounced in the individual outcome measures. These results are consistent with two previous systematic reviews suggesting that TNFα-inhibitors are likely useful in the prevention of cardiovascular complications of RA.

Ankylosing spondylitis (AS) is a world-wide chronic inflammatory disease of the axial skeleton most likely caused by a microbial factor in genetically susceptible individuals. Over the last 40 years extensive data has been produced which shows that the majority of patients with AS possess the HLA-B27 genetic marker. Significantly elevated levels of Klebsiella antibodies have been demonstrated in 1556 AS patients in 16 different countries with various geographical locations. Other evidence for the link between Klebsiella and AS include increased fecal isolation rates of Klebsiella microbes in AS patients together with shared molecular and immunological cross-reactivity features existing between Klebsiella antigens and HLA-B27 and collagens I, III and IV. Anti-Klebsiella measures could possibly be included with the currently used medical treatment in the management of patients with AS.

Our goals were to describe the balance of social support to negative social interactions (i.e. social constraint) for autoimmune disease patients and determine whether support and constraint from spouses and non-spousal family and friends interact to influence patients’ psychological adjustment. Using crosssectional survey data from 109 married vasculitis and lupus patients, we found that patients reported that spouses and family/friends provided more social support than social constraint. In regression models, constraint from spouses (β= -0.45, p<0.01) and family/friends (β= -0.89, p<0.001) were associated with worse patient psychological adjustment. A significant 3-way interaction revealed that patients with low spousal support had worse psychological adjustment as the levels of family and friend support increased. In contrast, patients with high levels of spousal support reported better psychological adjustment as family and friend support increased. Future longitudinal studies may help to elucidate the complex interplay between constraint and support from spouses, family, and friends.

The literature evaluating external anatomical measurements and carpal tunnel syndrome (CTS) remains inconclusive. The purpose of this study was to compare hand- shape measurements of patients with and without (CTS). A retrospective case - control study of participants with suspected CTS (male/female ratio of 0.69) was performed. Nerve conduction tests (NCT) defined 65 involved hands (CTS) and 73 control hands. The relationship between 3 different hand index ratios (measuring palm length and width) and CTS (defined by NCT) was evaluated using Generalized Estimating Equations model (GEE) with the binary outcome of CTS. Palmar Length/Palmar Width index had the strongest and negative association with CTS with greatest sensitivity and specificity to detect CTS. Hands with more square shape had increased tendency to be diagnosed with CTS. Hand indices that include the shape of the palm may help identify patients with greater likelihood of developing CTS for early screening and prevention.

Introduction: Vertebral fragility fractures are the most common fragility fracture. A significant proportion of patients still present to hospital for treatment due to their underlying older age and frailty syndrome. We aim to describe the prevalence of frailty within a cohort of hospitalised patients with vertebral fragility fracture using clinical frailty scales and comparing this group of patients with those that have a fragility fracture of the hip, a well-recognised frail group of patients. Method: As part of a service improvement project, a prospective case series of all patients ≥50years admitted to hospital with a vertebral fragility fracture over a 6 week period (n=24) were screened for frailty. This was done using recognised clinical scales for frailty assessment (PRISMA-7, Groningen Frailty Index(GFI) and Edmonton Frail Scale (EFS)). Data was collected on patients’ mobility (timed-up-and-go test), activities of daily living (Barthel Index) and cognition (abbreviated mental test). Secondly, we performed a cross-sectional analysis of patient characteristics of those ≥50years admitted to hospital with a fragility fracture of the hip (n=30) and those with a vertebral fragility fracture using data from our local clinical service registries. Results: In the first study, frailty was identified in 70.8% of vertebral fracture patients using PRISMA-7 tool; 66.7% with the GFI; and 33.3% with the EFS. A further 20.8% were considered vulnerable to frailty on the EFS. Almost 30% were considered frail on all the three scales. Three quarters had a timed-up-and-go of >20seconds. Median Barthel Index was 18 (range 6-20); and the median abbreviated mental test was 9 (range 2-10), which suggests a cohort that is mostly independent with personal activities of daily living with good levels of cognition. In the second study, compared to patients with hip fracture, patients with vertebral fractures were younger; more likely to be living independently; less likely to have fallen in the last year; were taking more medication; and had equal number of co-morbidities as patients with hip fractures Conclusion: Frailty is prevalent in those admitted to hospital with a vertebral fragility fracture. Treatment of their acute fracture will need to include addressing their frailty issues.