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.
John Clancy is senior
Abstract lecturer in physiology
applied to health, School
Rheumatoid arthritis (RA) is associated with homeostatic processes in the body and its origins have long of Nursing and Midwifery,
University of East Anglia
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 Heather Hasthorpe is
with the symptoms of the disease. It will discuss interactions associated with the chronic, systemic, inflammatory rheumatology nurse
practitioner, Norfolk
disease which reflects an autoimmune imbalance of cells in the synovial joints and their tissues. The work and Norwich University
highlights that the multiple roles of the healthcare practitioner are analogous to the components that sustain Hospital Trust
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 Correspondence
manage signs and symptoms to improve the patient’s quality of life and not restore the homeostatic status. j.clancy@uea.co.uk

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 patient’s 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).
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
observed. After reading this article and completing Conflict of interest
the time out activities you should be able to: None declared
■■ Briefly explore the debates regarding the origins of
RA to connect genetic and environmental influences.
■■ Reflect on presenting signs and symptoms to Keywords
better understand the theory of RA’s inflammatory/ Homoeostasis, nature,
destructive process. nurture, rheumatoid
■■ Revisit explanations of RA shared with patients to arthritis
determine how understanding and support might
be enhanced. These keywords are based on
■■ Monitor the patient more effectively, identifying the subject headings from
the British Nursing Index.
additional cardiovascular or anaemia problems that This article has been subject
might present in the future. to double-blind review. For
related articles visit our
Introduction online archive and search
using the keywords
Estimates suggest the worldwide prevalence of RA
is around 0.5 to 1.5 per cent (Kobelt and Jönsson
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

PRIMARY HEALTH CARE November 2011 | Volume 21 | Number 9 29

 Continuing professional development
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.
1 Personal experience
Speculate on your experience of the incidence
Time out
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.
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 body’s 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
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.
2 Research
Consider the part that theories of RA play
Time out
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.
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 individual’s 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
PRIMARY HEALTH CARE
Figure 1 The pathology of rheumatoid arthritis
NORMAL
Periosteum
Articulating bone
Articular cartilage
Synovial or
joint cavity
(fluid filled)
{
Fibrous
capsule
Articular
capsule
Synovial
membranes
Articulating bone
Periosteum
(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
PRIMARY HEALTH CARE
RHEUMATOID
ARTHRITIS
Synovitis
Bone erosion
Pannus
Cartilage
degradation
(joint space
narrowing)
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
November 2011 | Volume 21 | Number 9 31
 Continuing professional development
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).
3 Diagrams
Consider the discussions you have with
Time out
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
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 body’s 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.
4 Treatments
Given the information here about the
Time out
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
PRIMARY HEALTH CARE
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.
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
PRIMARY HEALTH CARE
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
November 2011 | Volume 21 | Number 9 33
 Continuing professional development
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).
5 Cardiovascular disease
Consider whether your patients with a long
Time out
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
author’s 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
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 individual’s 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
PRIMARY HEALTH CARE
irritation causing ulceration and bleeding. Presenting
anaemia should, therefore, be investigated.
6 Anaemia
Identify an RA patient you have cared for
Time out
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 body’s 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.
PRIMARY HEALTH CARE
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
November 2011 | Volume 21 | Number 9 35
 Continuing professional development
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
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Synovial fluid proteomic fingerprint: S100A8,
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36 November 2011 | Volume 21 | Number 9
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 Practice profile
Time out
Now that you have completed the article,
you might like to write a practice profile.
Guidelines to help you are on page 38.
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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.
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