NATIONAL QUALIFICATIONS CURRICULUM SUPPORT
Human Biology
Autoimmune Disorders
Case Study on Rheumatoid Arthritis
Teacher’s Notes
[HIGHER]
The Scottish Qualifications Authority regularly reviews
the arrangements for National Qualifications. Users of
all NQ support materials, whether published by
Learning and Teaching Scotland or others, are
reminded that it is their responsibility to check that the
support materials correspond to the requirements of the
current arrangements.
Acknowledgement
Learning and Teaching Scotland gratefully acknowledges this contribution to the National
Qualifications support programme for Human Biology.
The publisher gratefully acknowledges permission to use the following sources: image Joints
frequently affected by rheumatoid arthritis, reproduced with kind permission of Arthritis
Research UK; table Rheumatoid arthritis patient demography, treatment and disease activity
from Nature Medicine, Vol 2, No 2, February 1996, p 176, reprinted by permission from
Macmillan Publishers Ltd, Nature Medicine © 1996; image and table from ‘The Role of
interleukin-15 in T-cell migration and activation in rheumatoid arthritis’, Nature Medicine, Vol
2, No 2, February 1996, p 177, reprinted by permission from Macmillan Publishers Ltd, Nature
Medicine © 1996; a hand affected by rheumatoid arthritis © James Heilman, MD
Every effort has been made to trace all the copyright holders but if any have been inadvertently
overlooked, the publishers will be pleased to make the necessary arrangements at the first
opportunity.
© Learning and Teaching Scotland 2011
This resource may be reproduced in whole or in part for educational purposes by educational
establishments in Scotland provided that no profit accrues at any stage.
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Contents
Information for the teacher
4
Part 1: Background
8
Part 2: Analysis of clinical data
22
Scenario
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Information for the teacher
Rationale
This resource is designed to provide materials for use when delivering Unit 4
of the Higher Human Biology course. It is intended that this material will
provide adequate challenge to students studying Higher Human Biology.
Furthermore, it is hoped that it will provide opportunities to investigate areas
of interest related to autoimmunity, as specified by the SQA Arrangements
Document (Unit 4). In more detail, this resource has been designed to
complement the following section of the course:
Unit 4: Immunology and Public Health
1.
Immune System in Health and Disease
(b) Specific Cellular Defences
(iii) T and B lymphocytes
Recognition of self and non-self
Failure in regulation of the immune system leads
to an immune response to self-cells (autoimmune
disease).
Prerequisite knowledge for students
It is expected that students will have knowled ge of relevant sections of the
Higher Human Biology course in sufficient detail such that they will have
understanding of:
 non-specific immune response cell types, ie knowledge of mast cells,
macrophages and other phagocytes, and their role in the activat ion of
lymphocytes
 immune surveillance, ie tissue damage leading to inflammation at the site
of damage
 cytokines as chemical messengers, produced by immune cell types;
essential for communication between immune system cells and integral to
inflammation
 specific immune response cells: activation and proliferation of B and T
lymphocytes in response to cytokines and/or antigen -presenting cells (eg
macrophages)
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 autoimmunity: failure to distinguish self antigens from foreign ant igens.
Any further necessary knowledge or information is provided within the
resource.
Suggested use of the resource
This study should ideally be divided into 2-3 x hour long lessons or carried
out as an individual and independent project.
Part 1: Background
It is important that students have a basic knowledge of immunology and so
the purpose of this part of the materials is to revise the basic concepts and
definitions associated with the immune system and autoimmunity. It also
provides the opportunity for students to research and d iscuss the symptoms
and lifestyle effects of rheumatoid arthritis. Emphasis should be placed on the
reality and incidence of the disease. Should time allocation for this resource
be limited, the background study could be carried out as a homework task
prior to the analysis stage.
The time allocation and choice of individual activities could be selected to
suit the demands of the actual class involved.
Part 2: Analysis of clinical data
This provides the opportunity for students to:
 get some insight into the types of tests that may be carried out during a
clinical trial
 analyse a table of results
 practice and apply skills, eg to construct a pie chart ca lculation of mean
values etc
 look at information and form conclusions from a research scientist’s poin t
of view
 carry out further research on the effect of different drugs and their modes
of action (this may be suitable for more able and interested students)
 read and extract information from an original scientific paper (this would
only be suitable for the most able students).
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Scenario
The scenario provides the opportunity to apply and develop the students’
overall understanding of the topic. It is especially valuable to any potential
medical students since it is uses the common strategy of problem-based
learning.
Example plan
Introduction
 Issue all students with the Background information for students sheets.
 Recap session (questions and answers) on autoimmunity, to check for
understanding of previously taught knowledge, in particular the
prerequisite knowledge listed above. Questions may also be designed to
probe for existing knowledge of particular autoimmune diseases.
Main activity
 After students have finished reading the background information they
should be split into (mixed-ability) research groups. In this activity the
students are going to experience the role of a group of scientific
researchers, working in the field of autoimmunity.
 Both groups should be separately provided with resources , including
computer (and internet) access, in order to:
- analyse the data
- design conclusions
- prepare graphs of raw data for presentation
- prepare a presentation of the research findings
- draw conclusions on the scenario.
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Images of rheumatoid arthritis
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Part 1: Background
All the images on page 7 have one thing in common: they illustrate a range of
different physical deformities that are caused by rheumatoid arthritis (RA).
You may know someone who suffers from this disease . Although the severity
of the symptoms varies enormously between individuals, the lifestyle of any
person suffering from any of the symptoms will be affected to some extent. .
Rheumatoid arthritis does not discriminate, although more women are
affected than men.
Task 1
Examine the images on page 4 and give thought to how these deformities
would cause difficulties for both the individual and their immediate families.
Within your group, discuss and list any examples of how daily life could be
adversely affected and what support could be provided to overcome any of
these problems. You should remember to take age, gender and different
lifestyles into consideration. A useful website can be accessed at:
http://www.umm.edu/patiented/articles/what_lifestyle_changes_can_help_ma
nage_rheumatoid_arthritis_000048_10.htm
Rheumatoid arthritis is an example of an autoimmune disease. This case study
will illustrate the symptoms and possible, although still unclear, causes of the
disease. The first part of the study requires a good understanding of both the
immune system and autoimmunity. The second part involves you carrying out
analysis on real data acquired from subjects who have been diagnosed with
the disease.
Task 2
In pairs, construct a mind map to revise the immune system and
autoimmunity
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Main points:
The immune system
The inflammatory response
The immune system
The inflammatory response
This kind of defence attacks all invading organisms, ie it is not specific.
When organisms damage tissue, pain and swelling results, b lood flow is
increased and special cells called neutrophils (most abundant white
blood cells in mammals) are brought to the site of infection. The
neutrophils then engulf and destroy the invading organisms by the
process of phagocytosis. If infection is not overcome, then specific
immune responses can be activated.
Specific Immune responses
T- lymphocytes and B- lymphocytes
Bone marrow produces lymphocytes. A population of these, the T lymphocytes,
enter the thymus and the lymph nodes. Others remain in the bone marrow,
becoming B lymphocytes.
What do B lymphocytes do? When B cells are stimulated by the
presence of an antigen, they will rapidly multiply. Some of them will
become memory cells or mass produce antibodies. The antigens then
combine with the antibodies at the receptor sites and the whole complex
is engulfed by phagocytes.
What do the T- lymphocytes do? When a cell becomes infected,
microbial proteins are released by the host cell, move to the cell surface
and act as antigens. A type of T lymphocyte called a killer T cell
recognises the antigen and destroys the infected cell. A chemical is
released that perforates the membrane. This is called the cell -mediated
response.
Helper T cells (another type of T lymphocytes) patrol the body and
when they recognise antigens they activate the B lymphocytes , killer T
cells and macrophages, as illustrated in Figure (1).
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Figure 1 The immune response
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Autoimmunity
The principal function of the immune system is to defend against infe ction by
attacking and eliminating harmful pathogens, whilst not attacking the body’s
own cells and tissues.
A state of autoimmunity may develop when the immune system recognises
and reacts to one or more of the body’s proteins. When this happens, the
immune reaction that develops may have a serious impact on health.
The immune system distinguishes only between ‘self’ and ‘non-self’. Proteins
that are produced by the body are self and trigger a state of immunological
tolerance; proteins from viruses, bacteria, parasites, plants, animals and other
humans are non-self and can potentially trigger an immune response.
In simple terms, when autoimmunity develops, the immune system will attack
the body’s own cells and tissues.
A faulty immune system can initiate the development of chronic, disabling
autoimmune diseases. More than 80 clinically distinct autoimmune diseases
have been discovered and diagnosed to date.
Task 3
Name at least six examples of autoimmune diseases.
Task 4
Find out about the incidence of autoimmune disease in Scotland
All autoimmune diseases are chronic, disabling disorders that have the ability
to inflict a poor quality of life. The range of more than 80 identified diseases
comprises a heterogeneous family of disorders exhibiting a wide variety of
clinical symptoms.
It is well known that T cells play an important role in cell-mediated
autoimmunity. T cells are known to mediate tissue damage in type I diabetes
and multiple sclerosis. Cytokines and chemokines are biological mediators
secreted by immune cells. They influence the type of immune response
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generated in autoimmunity. Pro-inflammatory cytokines, such as Tumour
Necrosis Factor Alpha( TNFa) have a well-established role in the mediation
of autoimmune disease.
This knowledge has been used to design therapy for some autoimmune
diseases, for example TNFa blocking treatments have led to a reduction in
inflammation in some RA patients.
Arthritis is a group of conditions involving joints in the body. There are
more than 100 forms of arthritis but this study will involve two commonly
known types, namely osteoarthritis (OA) and RA.
What are the differences between OA and RA?
 OA is a much more common condition than RA.
 OA is a degenerative joint disease caused by the breakdown of cartilage. It
can result from injury or simply be a side effect of increasing age, ie wear
and tear.
 RA is a chronic inflammatory autoimmune condition that causes stiffness
in joints and difficulties in movement. In RA, the body’s own immune
system starts to attack its own tissues. Many parts of the body can be
affected.
Task 5
What is a chronic disease?
Answer
A persistent medical condition that causes long -term deterioration in the
body.
 OA patients tend to be older; their condition mainly a consequence of
ageing.
 In contrast, RA can afflict people of all ages, although the most common
age of onset is 30–50 years. RA can also affect children (juvenile RA).
 The synovial fluid contained in the synovi um is responsible for the
lubrication of a joint and allows smooth movement. In people who suffer
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from RA, antibodies are produced against the synovial tissue and this
ultimately results in inflammation in and around the joints.
 Patients suspected of having arthritis, whether OA or RA need to be tested
to find out which form of the disease they have and are, ,therefore,
required to provide biopsy samples of their joint tissue and synovial fluid
Task 6
What is a biopsy?
Answer
A medical test that involves the removal of cells/tissues for examination from
a living subject to determine the presence/extent of a disease.
In clinical research, as illustrated in the analysis section of this study,
synovial joint samples from OA patients are often used for co mparison with
samples from RA patients. This is because clinicians have access to biopsy
samples from OA patients, whereas it would be very invasive and ethically
difficult to acquire samples of this kind from normal, healthy individuals.
Rheumatoid arthritis-some background to the disease
RA is an inflammatory autoimmune disorder characterised by symmetrical
inflammation of freely moveable joints. In addition to the observed external
features of this disease, systemic inflammation is commonly exhibited i n RA.
Task 7
Find out about systemic inflammation and write a brief description of it in
your own words.
Answer
An infectious organism can escape the confines of the immediate tissue via
the circulatory system or lymphatic system, where it may spread to other
parts of the body. When inflammation overwhelms the host, systemic
inflammatory response syndrome is diagnosed.
With the discovery of interleukins, the concept of systemic inflammation
developed. Although the processes involved are identical to tissue
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inflammation, systemic inflammation is not confined to a particular tissue b ut
involves the endothelium and other organ systems.
Systemic inflammation is the result of pro-inflammatory cytokines being
released from immune-related cells and the chronic activation of the immune
system.
A booklet called Target Rheumatoid Arthritis, produced by the Association of
the British Pharmaceutical Industry, is a particularly useful and appropriate
resource for background information on this disease (abpi@abpi.org.uk,)
http://www.abpi.org.uk).
Introductory video: the following websites give an overview of the sympt oms
and basic understanding of how RA affects the joints in a human body.
http://www.arthritisresearchuk.org/arthritis_informatio n/arthritis_types__sym
ptoms/rheumatoid_arthritis.aspx
http://www.goldagegroup.com/rheumatoid_arthritis.htm
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Synovial joints
A joint is where two bones meet. Joints allow the movemen t and flexibility of
various parts of the body.
Revise the structure of the Synovial Joint by labelling Figure 2
Muscle
Bone
Synovial
membrane
Synovial
fluid
Cartilage
Capsule
Bone
Tendon
Figure 2 A normal synovial joint.
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How does the disease develop?
The progression of RA is not the same in every person. Common symptoms
include joint pain and swelling, stiffness (especially in the morning or after
sitting for long periods) and fatigue
The development of the disease can be divided into three stages:
 the inflammatory stage: pain, swelling, stiffness and early bone l oss
 the proliferative stage: tissues around the joint thicken and form pannus
 the destructive stage: cartilage and bone degenerate, giving the physical
symptoms of RA.
 Figure 3 shows a comparison of a healthy joint with one showing typical
signs of RA.
Figure 3 A healthy joint (left) and one showing typical signs of RA (right) (Target
Rheumatoid Arthritis).
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Figure 4 shows the joints frequently affected by RA.
50–60%
80%
80%
80%
90%
Figure 4 Joints affected by RA. The figures represent the frequency of distribut ion
of affected joints. Adapted from: Arthritis Research UK. Figures from Target
Rheumatoid Arthritis
In approximately 20% of RA patients the disease develops very rapidly, with
pain and inflammation in several joints, severe morning stiffness and great
difficulty doing everyday tasks.
Although arthritis means ‘inflammation of the joints’, it’s not just the joints
that are affected. Along with pain and swelling in the joints , patients may feel
tired, depressed or irritable, even with mild arthritis. Fati gue can be one of
the most difficult aspects of RA for people to deal with.
Current immunological understanding of RA
RA is characterised by a chronic inflammation of the synovial joints and
infiltration by T cells, macrophages and plasma cell s (antibody-producing B
cells).
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Because of its chronically disabling pathology and relatively high prevalence
(approximately 1%), RA has been a major focus of biomedical research for
many years.
RA has been found to be induced by a strong T cell -mediated inflammatory
immune response. The inflammation exhibited in RA is associated with
enhanced circulating levels of activated immune cells and pro -inflammatory
cytokines.
Task 8
Find out about cytokines and write a brief description of them in your own
words.
http://arthritis.about.com/od/inflammation/f/cytokines.htm
Answer
Cytokines are small, cell-signalling protein molecules that are released by
cells of the nervous/immune system either into the circulatory system or
directly into tissue. They locate target cells and interact with receptors on the
target immune cell, which triggers a response by the target immune cell.
Overproduction/inappropriate production of certain cytokines by the b ody can
result in disease. In RA, particular cytokines, eg interleukins and TNFa, are
known to be produced.
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Task 9
Find out about interleukins and write a brief description of them in your own
words.
Answer
Interleukins are a group of cytokines that were first seen to be expressed by
white blood cells (leukocytes). It has since been found that interleukins are
produced by a wide variety of body cells. They stimulate the growth and
activity of certain white blood cells and so the function of the immune system
depends largely on the production of interleukins.
Many different forms of interleukin are now known. The properties and
action of particular interleukins play an important role in the research of RA.
The majority of interleukins are synthesised by helper CD4+ T lymphocytes,
as well as through monocytes, macrophages and endothelial cells. They
promote the development and differentiation of T cells B cells and
hematopoietic cells.
Task 10
Find out about interleukin-15 (IL-15) and write a brief description of it in
your own words.
Answer
IL-15 is an inflammatory cytokine first described 15 years ago. It is not
produced by T cells but is a potent chemical attractor (chemo attractor) of T
cells.
It is thought that IL-15 may have a role to play in the pathogenesis of
rheumatoid arthritis.
IL-15 has been shown to be produced by several cell types, including
mononuclear cells, macrophages and dendritic cells.
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Task 11
What is a pannus? Write a brief description of it in your own words.
Answer
In RA, pannus tissue forms in the joint affected by the disease, causing loss
of bone and cartilage.
Chronic stages of the disease typically show formation of a pannus. A pannus
is a membrane of granulation tissue.
Formation of the pannus ultimately causes cartilage destruction and bone
erosion.
Task 12
Briefly describe the significance of the following blood tests, which are used
in the detection and diagnosis of RA.
(a)
Erythrocyte sedimentation rate.
(b)
CRP blood test.
http://arthritis.about.com/od/arthqa/f/arthbloodtests.htm.)
Answer
(a)
The erythrocyte sedimentation rate (ESR) is a blood test based on the
production of many different proteins produced during inflammat ion. It
measures how fast the red blood cells take to settle at the bottom of a
test tube. Inflammation causes the red blood cells to clump together,
therefore a high ESR rate indicates a high level of inflammation.
(b)
The CRP blood test specifically measures the level of C-reactive
protein. This is also used as an indicator of inflammation.
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Task 13
What is meant by rheumatoid factors?
Answer
Rheumatoid factors are circulating autoantibodies made by B cells. They
stimulate inflammation and play an important role in the normal immune
reaction. In RA, production is persistent and occurs in joints. Eighty per cent
of patients will test positive for rheumatoid factors in their blood serum, but
100% test positive in synovial joint fluid. It is unknown why rheumatoid
factors are made in RA. Their presence is used as an indicator of the disease
but RA cannot be ruled out by a negative serum test result. A high level of
rheumatoid factors usually represents greater severity of RA. It can take
many months for rheumatoid factors to be detected in some patients.
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Part 2: Analysis of clinical data
The next stage of this case study will focus on the analysis of actual results
obtained from patients who have been diagnosed with RA. The data are real
and have been extracted from a paper (McInnes Iain B et al (1996) The Role
of IL-15 in T-cell migration and activation in Rheumatoid Arthritis,Nature2
(2)pp175-182)
Most importantly, this paper shows how detailed and highly scientific the line
of research into RA is. However, the paper is extremely technical and
demanding, and is certainly above the requirements of knowledge at Higher
level. Even so, it could be a worthwhile reference for an overview of both the
content and presentation of a scientific report. It is only appropriate for use
with the most able students, who may have a personal desire to get involved
in medical research. More likely it could prove to be a useful resource to the
teacher for more detailed information on the data. A separate file is attached.
A second paper, ‘Cutting Edge: Mast cells Express IL-17 in Rheumatoid
ArthritisSynovium published in the Journal of Immunology illustrates how
another proinflammotory cytokine is thought to play an important role in RA.
This study found greater expression of this particular cytokine in the mast
cells rather than the T cells. Again this paper is particularly special ised and
highly technical in the field of immunology.
A final paper by authors in Glasgow and America, ‘State-of-the-art:
rheumatoid arthritis’, This paper was published on 10 November 2010 and
therefore provides an up-to-date review and update of the main advances in
RA.
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Table 1 shows the data provided by 17 subjects who have had RA for
different periods of time. Your job is to analyse thi s data and form valid
conclusions from the information provided.
Table 1 RA patient demography, treatment and disease activity
Patient
Age
Disease
duration
(years)
Rheumatoid
factor (+ or
–)
ESR
(mm/h)
Drug
profile
4
CRP
levels
(mg
ml –1 )
10
RA1
89
6
+
RA2
36
5
+
36
58
Gold
RA3
34
4
+
28
57
SASP
RA4
44
9
+
15
14
SASP
RA5
44
10
+
16
5
Pred,MTX
RA6
57
3
+
46
50
SASP
RA7
60
8
+
51
39
Gold
RA8
59
33
+
89
161
MTX
RA9
75
50
+
30
74
SASP
RA10
49
11
+
46
59
MTX
RA11
56
16
+
8
30
Gold
RA12
65
7
+
71
66
SASP
RA13
74
20
+
22
44
SASP
RA14
73
3
+
58
86
Gold
RA15
54
25
–
23
66
SASP
RA16
31
5
+
45
16
Gold
RA17
57
15
+
80
93
Gold
ESR, erythrocyte sedimentation rate; CRP, C -reactive protein.
 Clinical details and blood samples of RA patients were collecte d at the
time of synovial fluid collection.
 ESR is a test that indirectly measures how much inflammation is in the
body (<20 mm h –1 is normal).
 Blood levels of CRP are normally <10 mg ml –1 .
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Task 14
Examine the data in Table 1 and answer the following questions.
(a)
What conclusion can be made on the basis of the se rheumatoid factor
results?
(b)
What steps could be taken to support this conclusion?
Use two different colours to identify any patients in Table 1 whose results
were higher than normal for either ESR rates or CRP levels.
Answer
(a)
The rheumatoid factor may not always be detected in a patient who has
been diagnosed with the disease.
(b)
Increase the sample size. Repeat the test at a later point and compare
with the results of previous tests and recorded symptoms.
Task 15
Construct a bar chart based on the age of patients diagnosed with RA
Answer
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Task 16
(a)
Calculate the mean age of the patients.
(b)
What is the range of ages?
(c)
Construct a suitable chart to illustrate the age of each patient along with
the duration of the disease.
(d)
From this data, can you conclude that there is a direct relationship
between the age of the patient and the duration of the disease? Give
evidence to support your conclusion.
Answer
(a)
56
(b)
31–89
(c)
100
90
80
70
Series1
60
age
50
40
Series2
30
20
duration
of disease
10
0
0
(d)
5
10
15
20
patient
The graph shows that there is no direct relationship between the age of
the patient and the duration of the disease. The oldest patient age (89)
had been diagnosed for 6 years compared to the youngest (31) who had
had the disease for 5 years. The graph shows no direct correlation.
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Figure 5 compares the ESR with the levels of CRP in RA patients as shown in
Table (1).
Figure 5 A comparison of ESR and CRP levels in RA patients .
Task 17
(a)
Using the data in Figure (5) calculate the mean ESR rate of the RA
patients.
(b)
Calculate the mean CRP level of the RA patients .
(c)
What valid conclusions can be made from these results?
(d)
Can you suggest any ways in which the survey of these patients could
be improved to provide more valid conclusions?
Answer
(a)
39.3 mm h –1
(b)
54.6 mg ml –1
(c)
From these results, there is no direct relationship between the levels of
CRP and ESR in this sample of patients.
(d)
A larger sample size; data from control patients who do not suffer from
RA.
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The next stage of the analysis involves a comparison of IL -15 levels in
synovial fluid from OA and RA patients as shown in Figures (6) and (7)
Figure 6 IL-15 levels in OA patients
Figure 7 IL-15 levels in RA patients
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Task 18
Compare Figures 6 and 7 and write down what conclusions can be drawn
from them.
Answer
IL-15 was detected in some, but not all, OA patients. The average
concentration of IL-15 was much higher in samples taken from RA patients
compared to OA patients.
Quantification of IL-15 in synovial tissues
Figure 8 Image of synovial tissue. Sections of synovial tissue were stained to show
the presence of IL-15. Positive staining is shown in red.
Task 19
What does the slide shown in Figure 8 confirm?
Comment on the distribution of the red stained area.
Answer
IL-15 is present in this sample of synovial tissue.
IL-15 is not uniformly distributed. It is clearly more concentrated in one
particular area of the tissue sample.
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CASE STUDY ON RHEUMATOID ARTHRITIS
The data were quantified for each patient sample and the summarised results
are shown in Table 2.
Table 2
Percentage(%) of positively stained cells were counted
in different areas of the synovial tissue
Diagnosis
Area 1
Area 2
Area3
RA (n = 9)
54 ± 13.1
24 ± 12.3
12 ± 7.7
OA (n = 5)
6.5 ± 4.5
2 ±1.1
Table (2) A comparison of Synovial Tissue samples in OA and RA patients
Task 20
Construct a pie chart to show the distribution of positively stained cells in the
RA patients.
What does this pie chart show?
Answer
The greatest percentage of IL-15 was found in area 1 of the sample. The pie
chart also illustrates that IL-15 is not evenly distributed through the synovial
tissue.
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CASE STUDY ON RHEUMATOID ARTHRITIS
Figure 9 A second sample of synovial tissue was stained to show the presence
of CD68, a macrophage antigen.Positively stained cells are shown in red.
Task 21
Would you expect this sample to represent a patient with RA or OA? Provide
a full explanation to support your view.
Answer
The presence of the macrophage antigen is shown by a concentrated area of
red-stained cells. This indicates obvious activity of the autoimmune reaction
and so it is expected that this sample represents a patient with RA rather than
OA.
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CASE STUDY ON RHEUMATOID ARTHRITIS
Scenario
Read the following scenario and answer the questions.
A 37-year-old woman gradually developed painful wrists over 3 months . She
consulted her doctor only when the pain and early morning stiffness stopped
her from gardening.
Question 1
What questions should the doctor ask the woman?
Answer
How long has she had the symptoms? Apart from stiffness and pain is she
aware of any differences to her general health? Is there any history of arthritis
in the family? How severe is the pain? Does the pain subside as th e day
progresses? Is her sleep pattern disturbed?
The doctor suspects that the woman may have developed RA.
Question 2
What physical signs should he look for?
Answer
Swelling and tenderness of joints, including the hands, wrists, shoulders,
elbows, knees and ankles. Limitation of movement and muscle wasting.
Warmth of tissue. Any sign of deformities.
On examination, the doctor found that the wrists and joints of both the
woman’s hands were swollen and tender but not deformed .
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CASE STUDY ON RHEUMATOID ARTHRITIS
Question 3
From what you have learned through this study, can you suggest what clinical
tests should be carried out at this stage?
Answer
A general blood count to check for anaemia.
ESR and CRP levels to be checked.
Test for rheumatoid factor.
X-rays to be arranged.
The results of blood tests showed that the woman had a raised CRP level (27
mg –1 , normal <10) but a normal haemoglobin and white-cell count. A test for
rheumatoid factor was negative and antinuclear antibodies were not detected.
Question 4
Based on the result of the rheumatoid factor test, can the doctor assume that
the woman does not have RA? Explain you answer.
Answer
No. Non-detection of rheumatoid factor does not mean that the patient does
not have RA (rheumatoid factor is only present in 80% of cases ).
The clinical diagnosis was early RA and ibuprofen was prescribed. Despite
some initial improvement in the pain, the stiffness and swelling of the hands
persisted and 1 month later both knees became similarly affected. The woman
was referred to a rheumatologist.
Six months after initial presentation, the woman developed two nodules on
the left elbow; these were small, painless, firm and immobile , but not tender.
A test for rheumatoid factor was now positive .
At this point she was sent to the local hospital for further tests.
X-rays of the hands showed bony erosions in the metacarpals (Figure 10). She
still had a raised CRP (43 mg l –1 ). A biopsy showed that a pannus had
developed.
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CASE STUDY ON RHEUMATOID ARTHRITIS
Figure 10 X Ray image of Rheumatoid Arthritis in hands
There was now definite X-ray evidence of RA in the patient. If one
metacarpal joint (MCP) is involved with RA, then typically all of the joints
are involved. The X Ray image figure (10) shows that every MCP joint is
affected.
The doctor recommended that treatment should be a weekly low dose of
methotrexate.
Question 5
How does the methotrexate work? What other drugs are available and how do
they work? What other forms of treatment are available and how successful
are they likely to be?
(Target Rheumatoid Arthritis)
The good news for this particular woman is that the drug has controlled the
arthritis for several years and no further symptoms have developed.
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