Continuing professional development

Pathophysiology of rheumatoid arthritis: nature or nurture?

PHC636 Clancy J, Hasthorpe H (2011) Pathophysiology of rheumatoid arthritis: nature or nurture? Primary Health Care. 21, 9, 31-38. Date of acceptance: September 13 2011.

Abstract
Rheumatoid arthritis (RA) is associated with homeostatic processes in the body and its origins have long intrigued healthcare professionals; does nature or nurture determine its development? This article explores theories associated with RA development and reviews the necessary work of nurses as they help patients to deal with the symptoms of the disease. It will discuss interactions associated with the chronic, systemic, inflammatory disease which reflects an autoimmune imbalance of cells in the synovial joints and their tissues. The work highlights that the multiple roles of the healthcare practitioner are analogous to the components that sustain homoeostasis and practitioners may be considered external agents for homeostatic control. However, because of the progressive nature of RA, the authors conclude that practitioners are limited in this control as they can only manage signs and symptoms to improve the patients quality of life and not restore the homeostatic status. HEALTH IS often cited in the literature as being synonymous with homoeostasis and ill-health with homeostatic imbalances. The nurse may be cast as an external agent of homeostatic control, restoring the homeostatic status for the patient or, at least, minimising the signs and symptoms to improve the patients quality of life (Clancy and Smith 2010, Clancy et al 2011a, 2011b, Clancy and McVicar 2011a, 2011b, 2011c, 2011d, Clancy and Newell 2011). This work is especially important in rheumatoid arthritis (RA) a chronic, inflammatory and often progressive disease, which untreated may lead to joint destruction, deformity, disability and increased mortality rates (Clancy et al 2011b). Research has highlighted a 60 per cent increased risk of cardiovascular disease mortality associated with RA in comparison with the general population (Meune et al 2009). observed. After reading this article and completing the time out activities you should be able to: Briefly explore the debates regarding the origins of RA to connect genetic and environmental influences. Reflect on presenting signs and symptoms to better understand the theory of RAs inflammatory/ destructive process. Revisit explanations of RA shared with patients to determine how understanding and support might be enhanced. Monitor the patient more effectively, identifying additional cardiovascular or anaemia problems that might present in the future.

John Clancy is senior lecturer in physiology applied to health, School of Nursing and Midwifery, University of East Anglia Heather Hasthorpe is rheumatology nurse practitioner, Norfolk and Norwich University Hospital Trust Correspondence

j.clancy@uea.co.uk
Conflict of interest

None declared

Keywords
Homoeostasis, nature, nurture, rheumatoid arthritis
These keywords are based on the subject headings from the British Nursing Index. This article has been subject to double-blind review. For related articles visit our online archive and search using the keywords

Introduction
Estimates suggest the worldwide prevalence of RA is around 0.5 to 1.5 per cent (Kobelt and Jnsson 2008); the UK prevalence is 1 per cent with 26,000 cases being diagnosed annually (National Institute for Health and Clinical Excellence (NICE) 2009). Incidence increases with age, onset, however, most commonly occurs between 50 and 60 years, but can occur at any age, usually from about 30 years of age (Oliver and Silman 2009). The common prevalence in females suggests a link between the development of RA and female hormones (Oliver and Silman 2009). It is nearly 20 years since it was reported that there is a

Aims and intended learning outcomes

This article aims to promote further understanding of the origins and pathological process of RA, reflecting on what nurses have already noted in patients they care for. Although robust explanations of RA are not yet available, it is important to speculate about the nature of the disease, and for practitioners to share with researchers what they have
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reduction in the incidence and severity of the disease with oral contraceptive use (James 1993). Practitioners often report that female patients with RA experience remission in pregnancy, speculatively associated with a surge in hormones. Following birth when hormones decline, practitioners report a significant flare up of RA symptoms requiring immediate attention. Such observations provoke reflections on the origins of RA and the influence of nature and nurture influences. If there is a genetic base to RA, can nurture events, beyond pregnancy, also influence whether the disease flares up? To date, there has been insufficient research in these areas and it has been difficult to recruit people to studies, so the debate continues. blood supply of the uterine-placental tissue, and for the preparation of the mammary glands for postnatal lactation, inhibit the production of autoantibody producing B-lymphocytes associated with RA. In summary, pregnancy reduces the disease activity and temporarily during gestation restores normal function to the joint capsule (Temprano et al 2011). International studies indicate an ethnic prevalence, with increased incidence in Native Americans in comparison with inhabitants of the African continent (Alamanos et al 2006). Further studies acknowledging psychosocial, cultural and financial influences on the development of RA in individuals are essential to lead to a greater understanding of the significant environmental impact on the expression and non-expression of the susceptible genes for the development of RA. The authors predict that following the successful completion and linkage of the human genomics and proteomic research findings, the government will focus its finances on a project researching the impact of environmental risk factors associated with diseases, and this will be a major advancement to enhance the understanding of the aetiology and potential treatment options.

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Time out

Personal experience
Speculate on your experience of the incidence of RA, either experienced personally or seen in patients you care for. Do you confirm the pattern of presentation associated with pregnancy and beyond alluded to above? Have you noticed any other associations with life events or stages of ageing that seem to influence the incidence of the disease and/or the distress evoked? While speculations are not research, they are often later formulated into imaginative research questions.

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Research
Consider the part that theories of RA play in your discussion with patients. While there may be no definitive explanation of RA, do you use theories to help patients make sense of what they are dealing with? If so, how do you present the theories and set them against the continuing quest for answers to the illness? To what degree do they seem helpful? Reflect on how you conclude such discussions, perhaps directing them to sources of ongoing RA research.

There are many credible ageing theories associated with the onset of RA and it is outside the scope of this article to discuss all of them. However, the free radical theory of ageing has become increasingly popular (Harman 2009). This surmises that free radicals accumulate over a lifespan and that the bodys immune system works to limit these. Various lifestyle choices, associated with diet and exercise are believed to further help limit the negative effects of free radicals. However, the entire significance of the free radicals in the ageing process and their association with chronic diseases, such as, RA may never be uncovered. As the ageing population increases against a constantly changing environment that might also affect the incidence and progression of disease, ongoing research on biological processes of decline is fundamental to promote healthy, productive individuals and maximum longevity. A further theoretical explanation for the development of RA has been associated with low levels of oestrogens and progesterone in women who have infertility problems, since they seem to develop RA more frequently than women who have normal levels of oestrogens and progesterone (Hazes 1991). Conversely, during pregnancy the higher levels of oestrogen and progesterone required to develop the 30 November 2011 | Volume 21 | Number 9

Aetiology and pathogenesis

RA is a homeostatic imbalance commonly referred to as an autoimmune disease of unknown aetiology, diverse in its severity and progressiveness (Clancy et al 2011b). We hypothesise that the rationale behind the development of RA is no different from any disease, due to an individuals predisposition arising through the inheritance of susceptibility genes for RA and their expression when exposed to environmental risk factors. These factors are constantly changing and evolving, as is the environment we live in. It is this dynamism which explains why it is so difficult to understand the aetiology of RA. Evidence from 20 years ago suggests strong familial and hereditary genetic links and studies revealed a 10 per cent greater incidence of RA among monozygotic twins (of single origin egg) than among dizygotic
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Figure 1 The pathology of rheumatoid arthritis NORMAL RHEUMATOID ARTHRITIS Periosteum Articulating bone Articular cartilage Synovial or joint cavity (fluid filled) Synovitis

Bone erosion

Articular capsule

Fibrous capsule Synovial membranes

Pannus

Articulating bone Periosteum

Cartilage degradation (joint space narrowing)

(Adapted from Feldmann et al 1996)

twins (Deighton and Walker 1991). Genome wide meta-analyses (Etzel et al 2006) of susceptibility genes associated with RA provide strong evidence linking RA to chromosomes six, eight and 16. The Human Genome Project continues to uncover vital information regarding the understanding of mechanisms involved in cellular function in health and disease; the emergence of new genes and their relationships in protein/enzyme production and inhibition which has implications for future treatments (Klareskog et al 2006). A leading genetic association in RA is with a large group of human leukocyte antigen (HLA) genes linked to immune response (Farragher et al 2008). It is widely accepted in genomic studies that HLA genes contribute to development of autoimmune disease, conditions caused by the immune system fighting the body it is supposed to protect. Other genes (called RA susceptibility genes), in addition to
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the HLA also are suspected of being major factors in the evolution of rheumatoid arthritis (Eustice 2007). There has also been much speculation about viruses being causative agents in RA the Epstein Barr Virus (EBV) is one of the main ones. Saal et al (1999) isolated higher levels of EBV in the synovial fluid aspirated from patients with RA establishing HLA-DRB1 as a significant risk factor gene in RA. A study by Birkenfeld et al (1990) found T-helper cell receptors are influenced by HLA to produce antibodies from B-plasma cells against the synovial fluid proteins which are linked to RA. Such results may be highly significant when considering the inflammatory nature of this illness, and the propensity of the body to worsen the effect of disease through an enhanced inflammatory response. It could be hypothesised with the discovery of the susceptibility genes for RA via the Human Genome
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Project that the connection lies with these leucocytes and their response to a virus. This could possibly lead to a genetic response creating a homeostatic imbalance associated with the synovial joints triggering the development of the signs and symptoms of RA. Additional environmental risk factors must be involved as it is still not understood why individuals who have inherited the susceptibility genes do not all develop RA. The pathogenesis of the disease is characterised by an onset of usually symmetrical inflammation with stiffness and pain predominantly in the small joints of the hands and feet, although any cartilage-covered bone and synovial joint can be affected (Figure 1 page 33). The process begins with inflammation of the lining of the joint capsule, leading to excessive synovial fluid accumulation containing the enzyme metalloproteinase which attacks and erodes the cartilage (Clancy et al 2011b). phagocytosis to destroy pathogens and antigens and to control the immune response. However, in RA there is a localised invasion of macrophages at the cartilage surface leading to a thickened hyperplastic tissue mass known as pannus. This is created due to a homeodynamic imbalance of messenger RNA (mRNA) encoding for excess levels of the destructive matrix enzyme - metalloproteinases, which attack the joint surfaces leading to irreversible destruction. Galligan et al (2010) suggest the disease process in RA may be influenced by fibroblast-like synovial (FLS) cells. These cells can function as immune cells, but also secrete an enzyme to attract leucocytes to the synovium and may be responsible for pannus formation. Fibrocytes could be the homeostatic control centres for the regulation and function of FLS cells and their activity, therefore, could be potentially used as biomarkers in blood taken to identify patients with RA. There has been much debate regarding the role of cytokines in the pathophysiology and treatment regimens of RA, in particular their role in synovitis. These chemicals control the immune responses responsible for cell growth, tissue repair and remodelling, and also inflammation, as they have pro- and anti-inflammatory effects. They are divided into two groups: Th1: promotes T-cell mediated immunity. Th2: determines B-cell humeral (antibody) response. The bodys immune system is reliant on self-regulating the levels of these cytokines, which are essential for a healthy operational immune system. The levels are controlled by the expression of genes which are influenced by environmental factors, such as pathogens in the joints. An excess or inadequate production of interleukins (a type of cytokine) and interferon (such as an anti-viral biomarker) which make up Th1 and Th2, leads to a failure in the homeostatic roles of cytokines resulting in synovitis associated with RA. The homeostatic levels of these cytokines are essential for a healthy operational immune system and the levels are controlled genetically and influenced by the environmental factors, such as pathogenic antigenic insults in the joints.

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Diagrams
Consider the discussions you have with patients as you inspect their swollen hands and joints. What do patients typically understand about the process of inflammation? What other information would be useful? Diagrams may be helpful; do they play a part in your explanations?

Clancy and McVicar (2009) acknowledge that all body systems are fundamental to the maintenance of intracellular metabolic homoeostasis. This becomes apparent in the inflammatory process in the synovium with a complexity of interactions involving the immune, endocrine, and central nervous systems leading to inflammation of the joint capsule (synovitis). Synovial tissue acts as a homeostatic regulator in the joint environment. An imbalance leads to changes to the synovium, triggering the inflammatory process to promote joint space narrowing, excess tissue growth and high levels of synovial fluid. These are factors which mark the onset of the disease and can lead to joint destruction. Synovial tissue has two linings; macrophages and fibroblast cells are contained in its intimal lining. The sub-lining comprises mainly fibroblasts and fat cells. It is the activation of the synovial macrophages and their over-expression of the folate receptor gene that is responsible for the progressive nature of the disease, in which synovial tissue thickens due to the excessive infiltration of macrophages, T-helper cells and B-plasma cells. Under normal circumstances T-helper cells act as homeostatic control centres in immune response by assisting B-plasma cells to produce the antibodies to activate the phagocytes, to promote 32 November 2011 | Volume 21 | Number 9

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Time out

Treatments
Given the information here about the potential role of cytokines in RA destructive processes, what treatments, in your experience, make use of this theory? Are there specific treatments you work with that rely on insights into this altered physiology?

Biologic treatment for RA targets a pivotal cytokine in the inflammatory response, reducing inflammation
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and potential joint destruction. However, treatment of RA is not always deemed to be successful, in that total remission is not achieved and joint destruction continues. It is possible that the reason for this is that the complex pathology of RA is individual to each patient based on the complexities of nature-nurture interactions for each. There have been major treatment advancements through greater understanding of these subjective interactions which have led to the development of further biologic therapies targeting specific cytokines, for example, rituximab. Through targeting specific aspects of the disease this may improve efficacy and reduce potential side effects. However, we propose that pharmacogenomics, or tailor-making drugs for patients with varying degrees of severity of the condition according to their individual needs, is possibly over-optimistic at this time. The pharmaceutical companies will continue to focus on the mass production of general drugs to treat patients, rather than producing specific drugs for individuals, which is less profitable.

are regulated by the receptor activator of NF-kB ligand (RANKL), a gene associated with TNF cytokines and with links to the immune system. T-helper cells express the gene to produce RANKL, which is involved in the development of the immune cells of the body. A homeodynamic imbalance occurs when there is hyperactivity of the T-cells resulting in over-expression of the RANKL gene. Failure to re-establish levels to an optimum range results in a mass production of osteocytes, known as osteoclastogenesis. This causes bone matrix degradation, re-absorption, bone loss and subsequent erosions. Advancements to the present biologic treatments recognised in RA and for future treatment in erosive bone disorders could hypothetically be heavily dependent on information derived from proteomics on these protein-based cells and their interaction and regulation of TNF cells.

Cardiovascular disease
The cardiovascular system plays a vital role in maintaining intracellular homoeostasis by transporting chemicals to enable cells to sustain homeodynamic metabolism. For example, cellular respiration utilises the transported oxygen to transfer the energy from food, usually glucose, to the chemical adenosine triphosphate (ATP), which provides the energy to drive metabolism. Other end products of cellular respiration are heat energy, which thermoregulates the cell, and carbon dioxide and water which sustain the acid-base balance of the cell. Thermoregulation and acid-base balance are necessary to optimise enzymatic action in accordance with a healthy metabolism (Clancy and McVicar 2009). Atherosclerosis has a well documented interrelated genetic and environmental aetiology which arises due to a failure to maintain optimum homeostatic parameters in arterial walls. This results in increased deposition of calcium, fibrin and cholesterol, causing mass narrowing of the lumen of the artery (Clancy and McVicar 2009). In an attempt to re-establish homeostasis in atherogenesis, which is essentially an inflammatory condition, the immune system releases macrophages to absorb oxidised low-density lipoproteins (LDLs) a causative factor in arterial wall damage. Fatty streaks develop due to the inability of the cells to repair the arterial wall. This continual process leads to hardening and narrowing of the lumen giving rise to hypertension and risk of an intravascular thrombotic event. Patients with RA have a significant increased risk of cardiovascular disease (CVD) due to an accelerated and often premature rate of atherosclerosis (Han et al 2006). It is suspected that the rheumatoid inflammatory
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Proteomics research
Proteomics is the study of the identification of metabolic pathways involved in the production of proteins (enzymes). It investigates the transcription of deoxyribonucleic acid (DNA) into messenger ribonucleic acid (RNA) and the translation of messenger RNA by transfer RNA in the synthesis of enzymes, such as metalloproteinase. Scientists focus on the complex environment of synovial fluid and its tissue in patients with RA (Tilleman et al 2005), and as such any successful identification of abnormal enzymes associated with RA may lead to exciting opportunities in the treatment of this condition. Baillet et al (2010) identified specific enzymes in the synovial fluid of patients with RA, which are not found in the synovial fluid from that of other types of inflammatory arthritis. I agree with their conclusions that their enzyme findings could be used as biochemical markers in the definitive diagnosis of RA. It can be hypothesised that if drugs are developed to block the transcription of RA susceptibility genes or block the translation of messenger RNA involved in metalloproteinase synthesis, this would be a major breakthrough in treating patients with RA. Uncontrolled synovitis in the joints of patients with RA lead to a destructive process resulting in loss of structure, deformity and impaired function. This destruction can be rapid and is often evident in the first year. McQueen et al (1998) reported that magnetic resonance imaging (MRI) scans revealed erosions in 45 per cent of patients within four months. Bone cells (osteoclasts) have a significant role in bone degradation; their activity and numbers
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process decreases the production of high density lipoprotein cholesterol (HDL-C) metabolism, resulting in a greater risk of atherosclerosis in RA patients. In its normal homeodynamic range, HDL-C has powerful anti-atherogenic properties because it eliminates excess cellular lipids through a reverse cholesterol pathway to restore optimum cellular environment. Future proteomic studies may identify the inflammatory enzymes which decrease HDL-C and provide potential target areas for treatment of these pathological conditions. Links have been associated with radiological evidence of destructive joint disease attributed to uncontrolled systemic inflammation. Persistent elevation in citrullinated reactive protein (CRP), an acute phase protein, produced by the liver has been shown to be a predictor of atherosclerotic CVD (Ridker et al 2001) and of premature mortality (Maradit-Kremers et al 2005). Life expectancy of patients with RA is reduced by five to ten years as a result of CVD risk factors compared with that of the general population (Brady et al 2009). increase associated with CVD in patients with RA. However, the authors of this article hypothesise that the chronic elevation in inflammatory status could be linked to increased secretion of cytokines at the site. This would identify a positive feedback link which results in the signs and symptoms of RA, including immobility and disability, and exposure to environmental triggers, such as diet and smoking, as well as the individuals susceptibility to these nature-nurture interactions, predisposing this group of people to greater risk of developing RA.

Healthcare professionals
Assessment and diagnosis The diagnosis of RA is derived from a skilled clinical evaluation and examination of the individual in secondary care, including a concise history of signs and symptoms and visual assessment of the distribution of swollen painful joints supported by radiographic, haematological and biochemical investigations. Systemic inflammation is often detected by an elevation in acute phase proteins, such as CRP. This is useful in diagnostics and to determine efficacy of treatment and disease progression. The elevation in CRP arises due to an increase in interleukin-6 (IL-6), an anti-inflammatory cytokine secreted by the T-killer cells in response to a pathogenic presence or injury which triggers the inflammatory response, and a failure to re-establish levels within the normal range. The current generation of drugs used to treat RA, such as tocilizumab, act directly by blocking interleukin-6 receptors. Evidence suggests that CRP is an important predictor for cardiovascular disease and of greater value than LDL-C (Ridker et al 2002). Boilard et al (2010) isolated platelet microparticles from synovial fluid aspirated from patients with RA and suggest platelets may have a role in inflammatory joint disease and potential for non-immunosuppressant treatment which would specifically target platelet activation and inhibit microparticle secretion in RA. Although CRP and erythrocyte sedimentation rate (ESR) inflammatory indices are the most common biomarkers used to detect systemic inflammation, this work has exciting possibilities as the side effect profile currently experienced in immunosuppressant regimens could be significantly reduced. RA is associated with several types of anaemia, including iron deficiency, vitamin B12, and folic acid anaemia; all of which are responsible for decreasing the production of erythrocytes (Wilson et al 2004). Anaemia of chronic disease due to inflammation relating to bone marrow suppression is also often evident in RA patients with poorly controlled disease. Vigilance in monitoring these patients is required, because long-term steroid and non-steroidal anti-inflammatory drug use can lead to gastric
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Time out

Cardiovascular disease
Consider whether your patients with a long history of RA demonstrate a significant incidence of cardiovascular disease and hypertension. Given what you know about the local treatment of swollen and painful joints, and the side effects of corticosteroids, are there any additional considerations you might need to take into account when monitoring patients?

Painful rheumatoid joints are often treated with corticosteroid injections to reduce inflammation via stabilising membranes of cellular lysosomes. This decreases the secretion of the destructive enzymes lysozymes (Clancy and McVicar 2009) which causes less cellular destruction in the joints, alleviating pain and stiffness. However, corticosteroids can potentially increase risk factors associated with atherosclerosis, including hyperglycaemia leading to type 2 diabetes, obesity and hypertension in genetically susceptible patients (Clancy and Newell 2011). It is, therefore, the authors belief that the results of proteonomic research may identify improved treatments in the future. It has been suggested that impaired endothelial function and greater arterial stiffness as a result of the pathophysiology of RA has a significant role in the development of CVD (Metsios et al 2008). Increased levels of vascular adhesion molecules attributed to carotid atherosclerosis have been identified in patients with RA (Dessein et al 2005). There is no definitive explanation given for the significant atherosclerotic 34 November 2011 | Volume 21 | Number 9

irritation causing ulceration and bleeding. Presenting anaemia should, therefore, be investigated.

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Anaemia
Identify an RA patient you have cared for who demonstrated a type of anaemia. How was the anaemia managed? What would you emphasise to patients asked to play a role in helping to monitor their condition after treatment for anaemia?

Care planning The care of patients with RA requires a multidisciplinary approach. It begins in primary care and requires recognition, vigilance and prompt referral to secondary care. Clancy et al (2011b) state that RA must not be treated in isolation, this is a mind-body (pathopsychophysiological) homeostatic imbalance and requires pharmacological intervention and sensitivity, recognition and support for the sociopsychological impact the disease has on patient and family. The provision of holistic care has been publicised widely in nursing and medical care for some time, but the authors of this article argue that in reality this is not delivered. Healthcare professionals often fail to recognise that illness is a result of a nature-nurture interaction leading to a cellular-only static imbalance which results in presenting signs and symptoms. The disease may be a result of a predetermined inherited gene or susceptibility genes triggered by environmental risk factors. Practitioners must consider that disease is part of a health-illness-death continuum, where health is maintaining the body in a normal homeostatic status, although subclinical signs may be apparent but not experienced by the individual, and illness is a result of the bodys inability to maintain the homeostasis. This results in an imbalance with signs and symptoms that may require clinical or pharmaceutical intervention. Death is a result of a complete failure to re-establish homoeostasis, but also a failure to manage other fatal conditions associated with RA. We would argue that practitioners cannot consider acting as effective homeostatic control agents for patients if they do not fully understand the rationale behind intervention and education. There is no cure for RA so treatment is to achieve remission, control symptoms, preserve structure and function of joints to prevent irreversible damage and resultant deformities, and improve and maintain quality of life for patients. The recognition of CV mortality associated with RA requires interventions that target reducing these risks. As discussed in this article, uncontrolled systemic inflammation is the driver for destruction and the main cause of accelerated atherosclerotic changes leading to CVD.
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According to Clancy et al (2011b) the aim of treatment is to reduce inflammation as joint destruction occurs early in the disease process, making early intervention vital. An early aggressive approach to the management of RA is widely accepted as the optimum approach, with evidence to support this through improved symptoms and reduction of radiological progression (Emery 2006). Treatment is recommended within the first three months of unabated symptoms to control disease activity (NICE 2009). Treatment of RA begins with disease-modifying antirheumatic drugs (DMARDs). These drugs act on the immune system to alleviate symptoms caused by inflammation and to slow down disease progression to avoid joint destruction and potential disability associated with uncontrolled inflammation. Methotrexate is classified as a DMARD and is the most widely used drug of choice in initial treatment of RA, either as a monotherapy, combination or triple therapy, and generally always alongside biologic treatments. Rapid escalation and addition of further DMARDs is recommended if disease is not suppressed (Luqmani et al 2006). Patients escalate to biologic drugs when they fail to respond to first line treatment. Methotrexate is a folate antagonist developed in the 1940s and is used in comparatively low doses in the treatment of RA to control inflammation through its anti-proliferative and immunosuppressive effects and also its influence on reducing cytokine production. Adenosine, which is an active metabolite of methotrexate with anti-inflammatory properties, suppresses the expression of inflammatory cytokines. T-killer cell activation is inhibited resulting in suppression of the adhesion molecules secreted by the B-plasma cells. Individuals require close haematological and biochemistry monitoring while on this drug due to a risk of toxicity. Physiotherapists and occupational therapists provide aids and supports to patients, helping them in activities of daily living (Roper et al 1980). The inclusion of a podiatrist in the multidisciplinary team approach to patient care is essential because 90 per cent of patients with RA have expressed foot pain or discomfort at some stage of their disease (Michelson et al 1994). Disorders of the foot in RA are a result of chronic inflammation resulting in increased mechanical stressors and altered gait (Woodburn et al 2005).

Conclusion
There is a lot still to be discovered regarding RA and its origins and effects physiologically within the body but there is sufficient information to begin to help patients make some sense of their illness. The information gained from human genomic and proteonomic projects has led to a better
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understanding of the aetiology and pathogenesis of the disease and major advances in its treatment. RA is an autoimmune condition characterised by inflammation of the joints, most commonly the smaller ones, such as those in the hand. It is intimately associated with homeostatic balances, the way in which the body regulates the cellular environment and helps it to respond to infection or injury. It appears to be influenced by a genetic predisposition and may be strongly affected by hormone changes. Understanding of the nature-nurture influences on individuals with RA and their effects on health and illness are important to aid the planning and delivery of care so patients enjoy improved symptom management and an enhanced quality of life. While References
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a cure is not available, there are treatments that will help to achieve remission and limit joint destruction. In the meantime, the nurse has a role in providing psychological support and helping the patient to profile what seems to exacerbate their illness and monitor indications of deterioration in the body, particularly the cardiovascular system.

7
Time out

Practice profile
Now that you have completed the article, you might like to write a practice profile. Guidelines to help you are on page 38.

Acknowledgement The authors are grateful to Karl Gaffney MB, BCh, FRCPI, FRCP, Department of Rheumatology, Norfolk & Norwich University Hosptals NHS Foundation Trust, Norwich for checking the accuracy of the content of this paper.

36 November 2011 | Volume 21 | Number 9

PRIMARY HEALTH CARE

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