nm5250: the way we've structured this afternoon is we're going to consider a 
couple of cases prepared from a clinic and er a case on the ward er from the 
unit at Warwick and use that to discuss one of the two common problems er in 
rheumatology that you need to understand for your level a-, a-, at this stage 
in your career so the sort of clinical problems that you'll face in finals er 
will be relatively straightforward and that means that you need to have a a 
clear understanding of the er basic differential diagnosis of a polyarthritis a 
monoarthritis and then some understanding of generalised systemic disease like 
S-L-E but you don't really need to know a great deal about S-L-, er the details 
of S-L-E but you need to have a a good understanding of things like 
osteoarthritis rheumatoid arthritis spondyloarthropathies and things like gout 
given that this is taught at the end of the day i think we can reasonably cover 
a proportion of that er now and so what what i'd like to do is start off with a 
description of a a case presented by er er one one of you which will describe 
someone with polyarthritis and we can then briefly er discuss the clinical 
aspects of that which pointed towards a diagnosis and briefly discuss the sort 
of investigations which were helpful we won't be dealing with a great deal of 
information it's largely to give you a flavour of the pattern of two or three 
er of the main diagnoses in my subject so that you have a good flavour of those 
and that should act as a foundation to build up a clinical skill in making a 
rou-, in making a a stab at a diagnosis when you do a clerking er we're not 
expecting you to be rheumatologists but the sort of skill that we'll be 
assessing in I-C-E the sort of skill that we would assess in finals would be to 
make a diagnosis of rheumatoid arthritis the skill that we'd expect at I-C-E is 
to make a diagnosis of an inflammatory arthritis as distinct from er 
osteoarthritis et cetera er and then to have some sort of outli-, er idea of 
the management for instance we wouldn't expect you to know about anti-tumour 
necrosis factor alpha antibodies but you might need to know about anti-
inflammatories and physio's and O-T an-, an-, and those sorts of elements so 
we'll try and cover some of that this afternoon so i i'd like to hand over now 
to
sf5251: Gail
nm5250: Gail Gail do you want to present the first case
sf5251: hi Aimie and i are going to present the first case which is one of er 
chronic polyarthritis and we chose patient B who is a sixty-seven year old 
woman with a twenty-four year history of rheumatoid arthritis and the 
presenting complaint we saw her at the clinic er and the presenting complaint 
was pain in the groin which was dull and continuous she'd had the pain for over 
a month it was worse on the right side but was present on both sides and sort 
of radiated around the whole pelvic area it was associated with stiffness and 
intensified by movement but relieved by simple analgesia in nineteen-seventy-
nine er this patient was diagnosed with rheumatoid arthritis after she 
presented with hot and fiery joints and it's a progressive disease with 
increasing joint involvement deformity and disability and she's previously been 
treated with er gold injections and sulphasalazine and these are disease 
modifying drugs her current painful joints include knees elbows neck and her 
jaw and she has pa-, morning stiffness that lasts over an hour but she's only 
had that for the last six months and so for twenty-three and a half years or 
whatever she's reported no morning stiffness which is which is quite unusual 
and she often suffers from tiredness and fatigue this patient also has extra 
articular involvement so she has had an and has presently several rheumatoid 
nodules on her knees and elbows and she also has vasculitis and there was an 
ulcer on the anterior surface of her left leg and there's also a possibility of 
having secondary Sjogren's syndrome er which is associated with rheumatoid 
arthritis and she has a dry mouth and eyes which are symptoms of this and 
occasionally er the eyes become gritty and red past medical history of our 
patient is that she's un-, undergone carpal tunnel s-, surgery and she had a 
forefoot arthroplasty of the right foot er she also has osteoporosis and this 
has resulted in a fracture of of the humorous the wrist and a comminuted of the 
pelvis and it's i think it's important to keep that in mind because that was 
sort of what they were investigating with the the pain in the in the groin and 
radiating around around the pelvis i think that maybe you know she she might 
have a a fracture there this time as well she also has osteoarthritis and has 
had type one diabetes for the last forty-eight years functionally she enjoys 
keeping as as fit and active as possible and er she enjoys gardening she has 
reduced mobility so it's difficult to for her to sort of get out and about too 
much but she does manage and she has difficulty in dressing as Aimie will 
discuss later she has some quite marked er ulnar deviation which makes 
buttoning things and tucking things in difficult and er she has difficulty in 
showering so she's what happens now is she has stool that she places next to 
the bath tub and she has to sort of climb on top of this to get into the into 
the bath and that's really dangerous for her with her osteoporosis and her 
history and her unsteadiness so she's applying for a grant er to have that 
renovated and because she has difficulty in meal preparations she relies on a 
microwave for her meals she lives alone in a bungalow and she receives daily 
social service's support er two ladies come in and help her get ready in the 
morning and she has one daughter in Germany that er comes back if there's a a 
flare up of the rheumatoid arthritis and she has many friends and family er 
that come by and visit and take her out places her mother had rheumatoid 
arthritis and that's actually how she sort of when she had these hot and fiery 
joints she sort of knew that she probably had rheumatoid arthritis and er her 
mother and sister died of breast cancer
sf5252: okay er her current drug history is that she takes er methotrexate 
which is a disease modifying drug along with folic acid which you have to take 
in combination she's on fosamax for her osteoporosis meloxicab for pain er if 
her pain's severe she can also take either co-proxamol or paracetamol er as 
required and she's also found that glucosamine has helped er some of her 
movement problems in the past she's also taking insulin and rinitidine er on 
examination er there was marked ulnar deviation of the M-C-Ps of the hand she 
had flexion of the elbow joints at rest and er she had gross deformity of the 
joints of the feet she actually had to wear specially made shoes er there was 
visible rheumatoid nodules on her P-I-P's of the hand elbow and knee joints and 
there was also the ulcerated area on the the leg she also had erythematous skin 
around the ankles a swollen right knee and she was obviously er suffering from 
generalised muscle wasting er examination of her left knee and right elbow 
found them to be warm they weren't tender to the touch er but the whole joint 
was swollen and it felt boggy to the touch er there was no crepitus with 
regards to her movement er she had decreased range of movement and on hands 
elbows shoulders knee and ankle joints er there was tenderness on extension 
internal and external rotation of her right hip and tenderness on movement of 
the left knee and right elbow the investigations er were performed just purely 
on attendance at the clinic so this isn't a diagnostic investigation but er a 
full blood count's performed to check for the anaemia that can go along with 
rheumatoid arthritis and er C reactive protein is used to monitor the disease 
er it's often raised in rheumatoid arthritis and it can indicate if there's 
flares or if the disease is er progressing aggressively er kidney and liver 
functions predominantly assessed just for er drug side effects and she also er 
had a pelvic x-ray ordered to investigate the pain in her hip the management 
carried out in the clinic was that she had an intramuscular steroid injection 
now normally if you've got er joint pain they'll actually inject directly into 
the joint but because she had an elbow and knee involved they used er the 
intramuscular action so that it could get to both joints at once without er 
increasing her dose of steroid it was also discussed that er if she wanted to 
she could increase her methotrexate dose in two weeks if she didn't notice 
improvement and she would be followed up er in the rheumatolology clinic in six 
months time she also had access to a rheumatolology helpline and that means 
that she can phone them up without actually attending her G-P to increase her 
methotrexate and also if there's any change in her symptoms at present okay 
nm5250: er i think that's a case that's worth discussing in a little bit of 
detail and thought i'd just go round what we want first of all when you see a 
case like that er is a problem list so from the audience what are the problems 
that this lady has so first of all her mobility and what's the main problem 
affecting her mobility yes anybody well there's her in fact is this er bright 
enough i'll get a let me just get a darker pen better still a pen better 
contrast i think black would be better so with her mobility there's an acute 
problem and a chronic problem isn't there so what's the chronic problem 
su: rheumatoid arthritis
nm5250: yeah her R-A for twenty years what else
su: osteoporosis 
nm5250: there's her osteoporosis now in terms of her rheumatoid in terms of the 
chronic disease er there's there's two elements that you need to consider in 
terms of that effect on her mobility there's the damage that's been done and 
it's whether that it's active so even the rheumatoid arthritis er has an acute 
and a chronic component which you'll need to consider what's the acute 
component to her loss of mobility what did she actually present with okay what 
was the main presenting problem right so she had groin pain was actually what 
she complained of was groin pain er so would anybody like to say what they 
think the most likely diagnosis of the groin pain is considering the 
examination findings so just to remind people what people found on examination 
was that her right hip was painful on internal and external rotation what do 
you think the most likely finding on that pelvic x-ray is anyone stick hands up 
or what would be the critical thing when you're doing er investigations is that 
it's a series of questions and answers and so the clinical symptoms the 
problems the problem list are the questions some of them are straightforward er 
the patient may just tell you their rheumatoid is active and then it's a matter 
of deciding what you're going to do er but but er i-, it's not always 
straightforward and sometimes you do a test and the test is asking often a very 
simple question what was that pelvic x-ray what question was that pelvic x-ray 
asking so in other words what would be the what could be the findings if you er 
it was covering in a sheet stuck up on er er a a light box what would be the 
three possibilities that you would find 
nm5250: a fracture because she's got osteoporosis pelvic fractures are actually 
very difficult to see er o-, o-, on x-ray but people with significant 
osteoporosis particularly people with rheumatoid arthritis particularly people 
on steroids meloxicam analgesics et cetera er can fracture their necks of femur 
er and have relatively little pain it's not terribly likely but even a 
fractured neck of femur is possible what's the most likely diagnosis would you 
say 
nm5250: osteoarthritis and here it's osteoarthritis partly related to her age 
but mostly related to her rheumatoid so it's a final common pathway so i think 
you're right i i'd expect to see er right hip O-A what do you think the most 
likely solution to that's going to be
nm5250: yeah i i suspect what we're looking at there is a hip replacement so 
that's her mobility her osteoporosis is treated and they've x-rayed the pelvis 
looking for a O-A maybe just seeing erosions or an effusion as part of her 
rheumatoid that's possible because the rheumatoid was quite active now what 
were the features of her history that would tell you that the rheumatoid was er 
active what were the key features that distinguished the rheumatoid for 
instance from other disease 
nm5250: say again at the back
nm5250: er yeah that they're they're good descriptions of inflammation but 
that's not what she complained of
su: morning stiffness
nm5250: yeah how long did that morning stiffness last for
nm5250: sort of an hour and a half er in fact after er a C-R-P or er after the 
pressure that you can exert by compressing er er a little actuator the len-, 
the length the number of minutes of morning stiffness correlates very well with 
the degree of activity of this disease and we use morning stiffness and as sort 
of the key features to distinguish inflammatory joint failure from mechanical 
joint failure mechanical typically being worse with exertion and she does say 
that some of her pains were worse with exertion the mechanical element but more 
than twenty minutes of morning stiffness you would regard as moderate er 
disease activity i must admit er i think if her C-R-P was elevated i wouldn’t 
hesitate to increase her methotrexate er so that’s one problem was her mobility 
er any other problems her pain i to some extent that could be c-, considered 
separately er again that needs to be addressed either through analgesia or 
treating her illness so that’ll be treating the rheumatoid arthritis itself and 
perhaps query a hip replacement er any any any other problems
su: activities and daily living showering
nm5250: there’s the consequences er and although we won’t i won’t dwell on this 
case too long er what you get actually people with chronic illness er is they 
get used to having things which are present for a long time the patient gets 
sort of er used to them er what you find is that the the world constricts 
around their symptoms and they get used to the idea that they use the microwave 
she might even have been quite a good cook at some time er so they start buying 
food that can be microwaved er but they are not able to wash find washing and 
things very difficult they get round it my various precarious er er stools and 
climbing in and out of er showers er and often they can recruit the carers 
around them to adapt to those circumstances that’s why it’s very important in 
these circumstances to actually get something like an occupational therapist 
some external profession allied to medicine to go to the house and in someone 
with a chronic disease like this once a year or twice a year to just stand back 
as an external judge and view what’s going on and see if it makes any sense and 
often what you’ve found is there’s a drift into a corner and what this lady 
might well require is a hip replacement some quite aggressive physiotherapy 
some er devices er into her house like a chair in the shower et cetera that can 
then transform her life it may be that she actually needs to be seen in the 
upper limb clinic to sort out her hand function so that she’s able to return to 
washing herself and cooking for herself er in terms of the degree of disability 
that she has that really reflects her diagnosis and when it was made in the 
nineteen-seventies er when it was originally made er gold was the only 
substantial therapy for which there was evidence of disease control and in the 
Empire rheumatism trial it really depended on four or five patients we hardly 
use gold at all now although you know er not to be intending to be a pun it was 
the gold standard then it’s a pretty useless therapy really less than seven per 
cent of people will truly respond forty fifty per cent of people will their 
inflammation will get better but in terms of true disease control er it really 
doesn’t offer a great deal these days we would use methotrexate in combination 
with other agents er as one of the main line er therapies and the aim now 
really is complete disease control by which we mean no abnormal blood tests no 
erosions er and complete er normality for the patient apart from taking 
medication er so there’s been an enormous improvement really in the last ten to 
fifteen years and the success of treating this disease although we’re no quite 
at the point where we’re claiming to have cured it er there’s one other point 
what er significance do you think er was her family history there was two 
elements to her family history
nm5250: so there was her breast disease and her rheumatoid arthritis er what 
did you make of that in terms of your problem list how this lady what’s her er 
least probability of getting breast cancer has anybody any idea i mean the 
girls in the audience ought to know what the i think that’s something that you 
should have a er personal interest to some ex-, some extent what’s the 
background risk of getting breast cancer a life time risk for any lady
nm5250: yeah about eight per cent about one in eleven if you have a strong 
family history with two first degree relatives how much does it increase by 
anybody
su: is it one in three 
nm5250: it’s probably not quite er er as much as one in three it’ll depend upon 
the age if the age is less than fifty er it’s about one in six if it’s less 
than thirty yes it’s one in two to one in three it almost a proteus autosomal 
dominant almost a proteus mendelian er er er genetic er behaviour but but this 
lady’s er er breast cancer risk should be two to three times the background 
risk so that’s probably of the order of maybe one in twenty or one in thirty 
her lifetime risk becomes er and i can’t remember how old was she namex
sf5252: sixty-seven
nm5250: sixty-seven so actually in the clinic with with that you ought to just 
make sure that she’s having mammography because with her disability is she 
getting to the mammogram because this lady getting into hospital is probably a 
bit of a tor-, er er er er a difficulty for her what about the rheumatoid’s 
influence on er er cancer risk do you know about that
nm5250: yeah what would you say the all cause cancer ratings in someone with 
rheumatoid arthritis who’s active compared to the background risk at any given 
age it’s about two to three times the standardised age related risk if it’s 
active if it’s inactive it drops back to normal and that’s data we’ve only 
recently er er understood er long term follow up trials on methotrexate because 
er at one time there was immense debate about giving someone a chemotherapy 
agent for an agent that at the time wasn’t thought to kill you it was regarded 
as perhaps er aggressive therapy that can be justified what’s emerged is that 
if you don’t get side-effects on methotrexate there don’t seem to by any long 
term problems and the cancer risk drops back to the background risk in addition 
there’s some anti er endothelial action and being having rheumatoid arthritis 
and being on methotrexate has survival advantage you have a reduced heart 
attack and stroke risk that’s very small but never the less it’s it’s sort of 
reassuring er very reassuring to to people like myself with several hundred 
people on the drug that we’re not er adding to their problems er but tr-, 
active rheumatoid arthritis and that’s probably true of most active autoimmune 
disease you’ll slightly increase your cancer risk er if you have a family 
history of rheumatoid arthritis does that increase your risk at all anybody 
know the the risk is very marginally increased so although when you read your 
text books about rheumatoid arthritis it talks about class two antigens H-L-A-D-
R1 and D-R-4 er because there’s a particular motif er that er represents a 
particular peptide particular class two antigens er er in in those two groups 
that i mentioned they’re susceptibility markers whereas they’re very common in 
the population and if you look at the population risk those markers don’t 
increase your risk of rheumatoid arthritis er and therefore genetic studies are 
probably never going to be er er helpful er what i’d like to do before we do 
the next case is just show you some slides of someone with rheumatoid arthritis 
different cases to just talk through the characteristic features of rheumatoid 
arthritis i know these aren’t as crystal clear as they should be scan them in 
but er the number of images that without a couple of C-D burners i wasn’t going 
to be able to bring all all of these along today er what can people see on that 
slide what would be the features that you’d see so chap there what can you see
nm5250: yes characteristic feature of rheumatoid arthritis synovitis and this 
lady would present with morning stiffness er relative sudden onset of swelling 
of the wrists which would be painful they would be warm and swollen those sorts 
of features that would indicate an inflammatory disorder and the other thing 
about this is that it’s symmetrical so PIP’s and MCP’s and wrists on both sides 
and for the vast majority er of cases that will er represent rheumatoid 
arthritis tests which are most useful in these circumstances er are plain X-
rays and what you see commonly with that degree of synovitis is periarticular 
osteopenia and here is an early erosion and well i don’t think that comes out 
at all we’ll pass that that on that’s just to show the development of erosion 
the second thing er about this is rheumatoid arthritis is a systemic disease so 
er this is a chap who presented with rheumatoid arthritis er swelling of the 
joints swelling of an ankle er he’s developed anaemia marrow involvement and 
he’s got a very high ESR and CRP and when it presents aggressively it can give 
you fever although rarely is the reason for the fever not er fairly clear cut 
so inflammatory disorders er are typically have external features in addition 
to the er er joints and that’s particularly so of rheumatoid arthritis er the 
involvement of the disease is quite er wi-, widespread so it’s a multi-system 
disorder so when you assess someone with rheumatoid arthritis er there’s there 
isn’t an organ really apart from the central nervous system er and what i mean 
by that is the central part you can get peripheral neuropathy that doesn’t 
require some degree of assessment and in essence the characteristic features 
really are er synovitis affecting joints serositis affecting er pleura 
pericardium potentially vasculitis can affect the gut er and as a result of 
chronic illness you can getting thinning and wasting of the skin muscle wasting 
er et cetera amyloidosis is a very rare feature of chronic inflammatory disease 
and as a consequence of chronic persistent inflammation over many many years in 
which you can get deposition of proteins er in rheuma-, in rheumatoid arthritis 
typically AA amyloidosis the commonest amyloidosis in fact being er a 
manifestation of er myeloma er er not normally er associated with this disease 
what you see here really is er this is meant to be even pink er cartilage which 
is the surface er on which your bones are meant to move and underneath here is 
bone and here you can see chondrocytes little double cells and what is 
happening is that palisades of inflammatory cells are digesting this away and 
in addition er after digesting the articular surface they’ll digest the bone 
underneath so behaviour which has some features in common er with with 
malignancy and many of the er processes that are involved er were originally 
discovered in in examining tumours hence one of the agents that we block in 
severe disease is tumour necrosis factor alpha it’s primarily a an inflammatory 
marker but discovered er er in the field of oncology and this is a feature just 
showing joint destruction er the final common pathway of that erosion er is 
complete destruction of a joint but it isn’t only joints which are attacked so 
anywhere where these is a synovial surface rheumatoid arthritis can act and so 
the tendons these are tendons which have ruptured er are also a target so 
rheumatoid arthritis characteristic features are synovitis and that synovitis 
isn’t confined to the joint the other feature that’s characteristic is the 
formation of rheumatoid nodules not everyone with rheumatoid arthritis gets 
rheumatoid nodules er but a good proportion do and we would regard it as a 
severity marker so the first severity marker is erosions the next is the 
presence of rheumatoid factor er and then presence of nodules and this is a 
post-mortem specimen from someone with rheumatoid arthritis and vasculitis who 
who died and this is to show the extr-, extensive er fibrinoid er material over 
the surface of a m-, of a heart this is a whole heart preparation er and 
pericard-, pericarditis was part of the mode er that led to this patient dying 
although not the single er er problem but just to illustrate the serositis er 
here’s someone with small blood vessel vasculitis with rheumatoid arthritis so 
that’s the third characteristic so synovitis serositis vasculitis that’s small 
vessel vasculitis so this would be the lesions similar to the one that Gail 
described before on a lady’s leg er when you get lesions of this size er er we 
would regard that as quite a serious problem because that sort of vasculitis 
distinct from the previous vasculitis this vasculitis is small blood vessel 
vasculitis er the tissues that are involved will typically recover here is 
large vessel vasculitis necrotising vasculitis this has a high morality and is 
one of the triggers for more aggressive therapy including cyclophosphamide so 
vasculitis is a feature er here is a post-mortem specimen er from a decade or 
so ago before our more aggressive er treatments were used widely er and when 
not every person with rheumatoid arthritis was under a specialist er here’s 
someone was to a DGH with an illness very similar to the one that that slide of 
a man so a joint with a PUO with weight loss with a very high fever and the 
worry that the er physicians had with looking after him the diagnosis of 
rheumatoid arthritis wasn’t made pre-mortem er er they thought he might have 
SPE they were treating him er with antibiotics and so forth er and he died very 
quickly er with haemorrhage into his bowel as a result of his necrotising 
vasculitis that’s a rare feature of rheumatoid very rare these days because of 
the way we treat them er but was once a common mode of death prior to er modern 
therapy rheumatoid arthritis had the same mortality as grade three Hodgkin’s er 
in other words treat modern treated grade three Hodgkin’s in that there was a 
twenty per cent five mortality so these systemic diseases are quite nasty 
another manifestation of the vasculitis is involvement of the eyes and here’s 
someone with er scleritis so you can see inflammation in the scleral layer 
which is largely the vein the v-, veins and venulitis in the eye is a really a 
form of vasculitis so if you see someone with scleritis they should be assumed 
to have vasculitis till proved otherwise and that’s true of whatever sort of 
scleritis you’re dealing with and this can lead to thinning of the er scleral 
membrane er here’s someone with a more aggressive er form of that er sorry i 
beg your pardon er that could lead to thinning of the membrane and occasionally 
even to to blindness although that’s now extremely rare there’s a condition 
called the corneal melt syndrome where the scleritis is so aggressive that 
we’ll use chemotherapy similar to Hodgkin’s therapy and very high dose steroids 
treatment now here’s a more common er er a er a slide to just talk around dry 
eyes what’s happened to this eye is rose bengal dye has been dropped into the 
eye so it’s looking nice and red and then what’s happened is then you wash it 
out and what you’re left with is little rim of the rose bengal down here and 
what you can see is little patches of er keratitis where the rose bengal has 
been taken up and rose bengal is a non-vital dye basically it doesn’t touch 
things that are alive it gets taken up into bits that are dead and there 
shouldn’t be anything on the surface of the eye that’s in that condition you 
know the surface of your skin er is meant to have a lot of dead material on it 
as a protective layer the surface of your eye is meant to be alive and 
transparent and these are keratitic precipitates so where the eye is dried out 
the surface has dried out the skin has keratinised tried to become more like 
normal skin and as that eye lid passes over it peels that layer off giving that 
gritty horrible dry er symptom that the patient complains upon of and if this 
continues it can lead to scarring on the cornea an-, and a a number of 
difficulties and so that syndrome dry eyes as sometimes described in your text 
books is keratoconjunctivitis sicca so there is the keratoconjunctivitis the 
sicca being the pathology the dryness of of of the eye and you’d expect the 
majority of people with rheumatoid arthritis who are seropositive er to have 
that problem this lady did indeed have dry eyes here’s someone with some er 
pulmonary nodules er but there are other problems that can occur in the lung 
there’s a nodule er er in a lung that’s a post-mortem specimen there’s also 
some pleural er damage there as well now with a single nodule in a lung 
remember what we were talking before about rheumatoid arthritis that it 
increases your risk of cancer so a single nodule in a lung is still more likely 
to be a cancer then it is a rheumatoid nodule even if you have rheumatoid er 
arthritis er and so in general the a single nodule should be biopsied er as any 
other single nodule in the lung should be er on it’s own merits an example of 
serositis pleural effusion and here’s an example of a a different manifestation 
of lung disease er fibrosing alveolitis where you’re getting honeycombing and 
loss of volume of both lung bases again a mode of death in rheumatoid arthritis 
and any sort of involvement would indicate interstitial lung disease is an 
indication to increase therapy to a more the next aggressive level steroid with 
the trexate cyclophosphamide and a consequence of synovitis is initially 
deformity er and then loss of of function and here’s someone with muscle 
wasting who’s losing their mobility because of this disease which hasn’t been 
er controlled in in that case now neurological involvement in additional to 
peripheral neuropathy is largely a consequence of mass effects er on 
neurological structures and the most the the only one that you’d be expected to 
know in any detail is atlanto-axial subluxation and although this is rare why 
it’s very important i-, is that it’s often asymptomatic until it’s at quite a 
late stage and therefore if you encounter someone with rheumatoid arthritis er 
as a house officer in say surgery it’s important to have their neck X-rayed 
before they go to theatre et cetera so awareness of the problems in the neck is 
very important er because although it’s rare it’s a major problem so here’s a 
lady who had er i’ll tell you just about ten millimetres of atlanto-axial 
subluxation so because the transverse ligament around the front of the axis had 
been eroded by rheumatoid arthritis her skull slipped forward about just over a 
centimetre when she nodded forwards and as you know the spinal cord passes up a 
little canal here to then loop into the foramen magnum about there and er 
there’s an odontoid peg climbing up here that’s not such a good thing to occur 
so the odontoid peg at the back can be pulled forward onto the spinal cord as 
it tries to do a loop through here in fact this lady had no symptoms and we did 
an MR scan of here there was still er two or three millimetres to go and it was 
decided to treat her conservatively but a very small change in her atlanto-
axial subluxation is very likely then to have give-, taken her across that 
threshold and it wouldn’t be you wouldn’t want to be the anaesthetists who 
flexed her neck forward and back trying to get a difficult er er during a 
difficult intubation and what this lady that we described is likely to come to 
here’s in fact someone with an elbow with elbow damage er and even if you 
hopefully less often these days don’t win with the drugs there’s joint 
replacement er to consider but unfortunately joint replacement has it’s own 
problems this lady has thin bones er there’s a risk of infection and a 
percentage of them about three or four per cent of them become infected i’m 
going to show you a discitis there right and really just to go back over though 
so rheumatoid arthritis is a paradigm probably the one inflammatory arthritis 
you need to know in some detail so we’ve just gone over that in er a broad 
outline and remember you know you need to educate the patient there are drugs 
there’s their activities of daily living there’s protecting the joints surgical 
treatment and remember to you know treating the patient er er as far as 
possible holistically so th-, this this lady with her active rheumatoid 
arthritis requires a whole host of interventions with her long problem list she 
needs some aids at home she probably needs an O-T to see her she might need her 
osteoporosis assessed her rheumatoid is active and that probably requires more 
treatment the rheumatoid treatment will require monitoring her hip has probably 
failed and she’s likely to need to see the surgeons before that happens we need 
to assess her neck you probably might need to even assess her lung function 
although there’s no symptoms of of of lung involvement she might have some 
marrow problems if the disease remains active that might need to be corrected 
before er surgery her pain needs to be treated and also if she’s become trapped 
in her house and her activities are are restricted if life is becoming a 
smaller encompass for her people get depressed with this illness as you might 
expect so her psychological well-being might need to be er considered er very 
good what we’d do now is dis-, discuss the next case and then what i’ll do is 
i’ll take you through a series of slides er discussing differential diagnosis 
er er er in rheumatology so who is it who’s next 
nm5250: Tess do you want to come and er jus-, sorry just before we do that is 
there any questions anyone would like to ask about rheumatoid arthritis yes
sf5251: can i just ask when you were saying about the increased cancer risk was 
that due to the treatment or the condition itself
nm5250: er no it worried us that was a a very important question about the 
cancer risk of rheumatoid arthritis it’s worried rheumatologists for years that 
we are the cause of the increased cancer risk but in fact with with now careful 
follow up studies properly controlled er it looks to be it’s the active disease 
which is the main risk er now there is a slight caveat to that in that if you 
combine about a third of our patients are on combination therapy so what we 
know is that methotrexate alone in reality doesn’t increase your cancer risk in 
rheumatoid arthritis in fact it brings your cancer risk back to where it was 
before overall there might be in very large populations a small increased risk 
of lymphoma but that appears to be a very low risk we know from treating 
transplant patients that when you combine chemotherapy your cancer risk starts 
to go up again and so in people on double agents like leflunomide and 
methotrexate cyclosporine and methotrexate i think we can’t yet say that we’re 
not potential causers of trouble er because certainly the lymphoma risk in 
transplant patients on similar regimes are increased however they have a very 
much more aggressive er er immuno induction and we don’t know whether it’s 
exactly the same we are sort of approach maintenance er er treatments er in 
transplantation so the sort of d-, combination of and cyclosporine that you 
might get but you don’t have the induction therapy so i think there’s a slight 
question mark over it okay any other questions about rheumatoid arthritis 
pathology treatment i mean i i really just wanted to give you a a broad outline 
of the pattern of the illness yeah
sf5252: er in terms of the d-, deformity is there anything apart from treatment 
with drugs that can sort of slow it down or er 
nm5250: pretty much not no er people have come up with all sorts of fancy the 
reason the deformity occurs is purely anatomical so the ul-, well the joints 
become damaged but why you get ulnar drift is largely because your flexor 
compartment is seven or eight time stronger than your extensor compartment and 
so the balance between the extensors and the flexors is such that the flexors 
just pull fingers across so a great deal of the deformity is a consequence of 
joint destruction and the balance of forces in your your limbs a-, and 
essentially the stopping the disease is the only way proper way of stopping 
deformity that’s not to take away from the surgeons and what they can do to 
clear up the mess that that we’ve not been able to stop forming namex
sf5252: okay er we saw Mr M who’s eighty-three er and he presented with trouble 
in his joints er he had a three month history of intermittent swollen painful 
and inflamed hands knees and elbows which started suddenly er he also had 
reduced movement of the hands which Mui’s going to talk about in a minute er he 
had stiffness in the morning and at rest er which didn’t last that long and he 
had swelling and tenderness of the right big toe by and large for the past 
three months as well er in terms of past medical history he’s got er left 
ventricular failure chronic renal impairment er which i’m not sure what was it 
was caused by but he was given V-I-O-X-X er as pain relief and that sort of 
exacerbated it so that was stopped er he’s also got er atrial fibrillation and 
ischaemic heart disease he’s a sufferer of chronic obstructive pulmonary 
disease and he’s had three er M-Is er and he also had an episode of spondylous 
of the neck four months ago er which i think is sorted out now er in terms of 
functional history he’s got reduced mobility he uses a walking stick or a frame 
er he was recently taken into an intermediate care facility because he had 
problems sort of looking after himself and he was in there for a week er he has 
difficulty opening jars with his left hand but his right hand’s fine and he 
also has difficulty tying his shoe laces er again because of his left hand er 
social and family history he lives alone in a bungalow so he doesn’t have to 
worry about stairs or anything he’s a retired marker researcher er he has good 
support from his son daughter and his ex-wife who although they don’t live with 
him they live locally er he’s got no significant family history he’s an ex-
smoker and stopped smoking fourteen years ago but has got a fifty year pack 
history er and he doesn’t take any alcohol any more er and hasn’t done so for a 
while er drug history he’s on quite a few but the important ones are the 
prednisolone er which he was given to sort of reduce the inflammation and 
allopurinol er which is for the long term control of gout er and the others 
just for sort of his heart and things er Muireann’s going to talk about the 
examination and what investigations have been done
sf5252: his right knee and his left hand were slightly swollen he said they did 
they used to look like big sausages so when we saw him it had he had gone down 
quite a lot er his ankles were also swollen but there was no er gro-, gross 
deformity so there’s no ulnar deviation or anything like that er there was some 
erythema on the skin and both of his legs er no tophi was seen which er are 
collections of urate crystals we were looking for these on the ear lobes on the 
feet and the hand and it’s a clinical feature of of gout er er feeling he had a 
warm right knee and warm left hand er the proximal interphalangeal er proximal 
yeah proximal interphalangeal joint where er there was mild swelling in the 
left hand er and but there was no tenderness when we palpated it on either the 
hand or the knee er there was some crepitus on both knees and there was some er 
pitting oedema and tenderness on both ankles er movement well er on his left 
hand at the wrist there was decreased movement er and also he couldn’t make a 
fist so couldn’t make he couldn’t grip your finger with his left hand but his 
right hand was perfectly normal er there was also pain when you tried to extend 
the left hand er and there was some tenderness when he moved his right knee 
also his neck er there was some decreased movement and his neck was slightly er 
fe-, flexed and fixed er so our differential diagnosis were polyarticular gout 
rheumatoid and ankylosing spondylitis we did some do you want me to go onto the 
investigations okay
nm5250: no i was going to say we’re going to get people to do say what they 
would want to know the results of so do you want to ask what tests they’d ask
sf5252: so er with those differential diagnoses are there some investigations 
that you think you’d like to do 
nm5250: right so the story really is a short history the er two of the drugs 
were mentioned were only been started this morning in fact after a test result 
came back so the the story is of a chap with extensive ischaemic heart disease 
previous er er myocardial infarction a degree of renal impairment who’s now 
developed a rapid onset oligo arthritis oligo being er less than six joints so 
what tests would you want the results of
su: C-R-P
nm5250: right CRP is about sixty what’s the value of the CRP here so what 
question does that answer it’s a reasonable reasonable it’s a reasonable thing 
to ask for that’s a good it’s a g-, good thing to suggest but what what 
questions is it answering in this situation er not a lot actually what what it 
does is it it confirms that it’s inflammatory and it says that it’s probably 
quite a lot rather than very little er but diagnostically it doesn’t take you 
on any further really why is that the description really isn’t it is of a oligo 
arthritis with warm painful swollen joints with stiffness in the morning that’s 
come on relatively suddenly it’s not in the pattern that would suggest a 
mechanical joint failure so you’re really dealing with an inflammatory 
arthritis what forms of inflammatory arthritis do you know that might do this 
so the first thing what you you know what’s the differential diagnosis one’s 
been suggested i mean one’s been suggested as polyarticular gout rheumatoid 
arthritis and ankylosing spondylitis
su: osteoarthritis
nm5250: yeah o-, osteoarthritis could do that you’d expect really a a longer 
period of symptoms and a much smaller number of joints and also you wouldn’t 
expect the pain to move around in quite the way that it did so inflammatory 
osteoarthritis can certainly occur but it wouldn’t quite be in this 
distribution so the pattern of joints argues against inflammatory cause of O-A 
any other ideas
nm5250: yeah the the other thing is in fact we discussed this case earlier so 
er uric acid was measured and it was eight-hundred and eighty-nine micromoles 
per litre and we would expect anything in this above we’d expect it to be four-
hundred and twenty or less so do you think that’s significant it is it’s a 
record in my personal experience er the solubility product of uric acid is only 
three-hundred and sixty and you find it physically difficult to get much more 
than about seven-hundred micograms into a biological solution and eight-hundred 
and eighty-nine so is is close to a record i think people have seen thousands 
why do you think this chap has got gout 
nm5250: yeah he’s recently had a myocardial infarction and he’s been put on 
diuretics that’s one one answer one contribution what else 
nm5250: well he’s got renal failure absolutely the renal failure itself 
directly why do you think he’s had renal failure in a chap like this what are 
the causes of renal failure that you consider 
nm5250: in very very simple terms
su: drug induced
nm5250: so you think of drugs so what are the drugs that he’s on that might 
have done it
nm5250: well the N-S-A-I-Ds the N-S-A-I-Ds converted mild renal failure to 
acute renal failure with a creatinine of about five-hundred i think three or 
four-hundred anyway so non-steroidals in this situation especially dangerous
nm5250: yeah non-steroidals and ACE inhibitors are a nasty combination because 
the ACE inhibitors decrease renal blood flow and then non-steroidals decrease 
it further so prostacyclin’s are particularly important for capillary and 
papillary blood flow and so if you have any degree of renal artery stenosis 
that’s induced by the ramipril that he was put on for his last heart attack and 
then in addition you drop the plasma volume by putting him on a diuretic you 
dry him out a bit because he’s developed an illness he’s developed gout and his 
renal function’s getting worse and then you throw a non-steroidal on top er 
that’s quite quite a dangerous combination and why i particularly point that 
out is that in most people who develop very acute gout er with diuretics far 
far safer to put them on steroids everyone tells you about how dangerous 
steroids are are much safer in this situation than non-steroidals which are 
dangerous difficult tablets to use in people with chronic heart or renal 
disease so if you see heart failure put the non-steroidals to one side because 
the next thing is there’ll be a you know a proportion of them will end up being 
admitted with an exacerbation of their heart failure and they are er in the 
right circumstances quite strongly sodium retaining er so i would say that this 
chap’s polyarticular gout is probably mostly iatrogenic although i would 
suspect that with that he has a degree of hyperuricemia and then on top of it 
he developed chr-, acute renal failure which was drug induced plus he had 
reduced renal blood flow because of his previous treatments and he developed 
what’s actually although at the top of the differential diagnosis here er 
polyarticular gout actually that’s er er an uncommon presentation of gout er 
but never the less er er an important one are there any other differential 
diagnoses that you would consider in a chap like this any other arthritis’s you 
know at all
su: septic
nm5250: septic arthritis 
su: yes
nm5250: when you mean septic do you mean an infection in the joint itself yes i 
mean that that’s a reasonable thing to consider with a CRP of sixty in fact 
your C-R-Ps a hundred and fifty-seven er however you would expect a septic 
arthritis really to involve one or two joints and for him to be systemically 
unwell so it’s certainly something to consider but i would say that the pattern 
here of a septic arthritis er er it would be an unlikely presentation but 
infection and arthritis you’re on the right track does anyone know of any other 
yeah
su: gonococcal 
nm5250: a gonococcal arthropathy er on the same ward round we saw a sixty-t 
four year old with active syphilis serology and then when i rang the er GU 
physician they said could she have H-I-V we thought probably not er and she’s 
got a vasculitis that’s probably going to turn out to be related to yaws i 
guess she probably have a treponema yaws unusual so er gono-, age is no bar 
i’ve seen a sixty year old with HIV and certainly in the late fifties recently 
with gonococcal arthritis in fact this chap’s unlikely i i think having met him 
i think it’s unlikely it would be gonococcus but that be a in as a pattern of 
arthritis of an oligo arthritis that’s moving with relatively little systemic 
disease i think gnococcal arthritis is the right pattern but not quite that 
likely because of his age and other circumstances i i i don’t think he’s 
sexually active er you know he he’s functioning not at a very high level er sex 
would probably kill him actually although er any anything else any other any 
other links between infection and arthritis which would give you another 
diagnosis
su: no it wasn’t infection i just thought in er haemochromotosis you can get 
arthralgias
nm5250: er yes you can er that’s a rare cause of osteoarthritis which can 
present with an inflammatory oligo arthritis typically in your fifties bit bit 
younger with er a less dramatic inflammatory presentation er that’s not an 
arthritis that’s at all well understood because the gene frequency is vastly 
higher the homozygous gene frequency is vastly higher than either the liver 
disease or the joint disease okay the other ones i was thinking of was reactive 
arthritis so again a er mycoplasma chest infection a diarrhoeal illness er 
that’s er another possibility er so what what i’ll do now is i just want to go 
through a few slides which take you through er er different-, other 
differential diagnoses here’s a swollen joint it’s very acutely swollen very 
red and tender what would be the differential diagnosis 
ss: gout
nm5250: yes that’s the diagnosis is there anything else to consider so we 
consider so we think it could be gout what else infection anything else 
su: trauma
nm5250: trauma yes anything else
nm5250: er yes it could be yes it could be it could be sort of cellulitis er an 
allergic phenomenon that’s possible er or another inflammatory arthritis is 
there anything else apart from gout there is pseudo gout as well so to some 
extent we would t-, tend to say crystal arthropathy er as as the diagnosis 
there okay so how are you going to distinguish er between those features how 
are you going to make the diagnosis what would be the features in the history 
that might tell you that would allow you to distinguish between those 
differential diagnoses
su: been any recent trauma 
nm5250: yeah what would you expect with gout 
su: alcohol
nm5250: alcohol brilliant who said alcohol very good er a decent alcohol 
history’s a rare thing in history taking because er doctors as a bunch tend to 
be a sort of polite group on the whole and rather than you know getting down to 
the nitty gritty er and really getting a proper alcohol history the only way to 
get an alcohol history is to really get the patient to describe what they drink 
over two or three days and you often come to a surprising conclusion do it 
yourselves just on a piece of paper don’t or not if you’re too frightened but 
but alcohol as a predisposition to gout is quite important er so high alcohol 
intake family history the previous history with other forms of arthritis like 
rheumatoid arthritis the length of the history when a joints involved tends to 
be weeks or months what’s the typical length of history with gout of a swelling 
like that how long’s that likely to last for any idea hands up anybody anyone 
with personal experience family members no life time risk is one in a hundred 
someone here has got a family member with gout er typically it’s only a few 
days and in fact the polyarticular gout is unusual in that that chap’s had 
illness over several weeks and that’s just a manifestation of the severity er 
of the illness er typically only a few days and how if you get an attack of 
gout how typically if you say your first attack how long would you say it’s 
likely to be before you get your next attack hands up anybody
nm5250: typically up to a year so one of the things that's critical is just ask 
them if they've ever had it again and what you ought to try and see is what 
would you expect the natural history of multiple attacks of gout to do you know 
the background pathology is hyperuricemia so there's a number of er er er 
processes which lead to accumulation of uric acid in the body so your total 
body uric acid slowly rises what would you expect to do because what you expect 
i guess is what happens is you get an attack and then the period before the 
next attack is quite long we call that the inter-critical period and what 
happens is that the inter-critical period gets shorter and shorter and shorter 
until eventually you'd be get-, into the realms of polyarticular gout at which 
point you're often getting tophi and so forth so the pattern of gout is of 
attacks which are isolated short-lived typically ignored even though they must 
be they're dreadfully painful but you know going to see your doctor 
particularly in the N-H-S is even more painful i think so people often ignore 
these things for quite a while so typically you'll get a history of at least 
three or four attacks often over a two or three year period but the gap between 
the attacks getting less and if there's a major alcohol component then that's 
all accelerated right so acute monoarthritis trauma bacterial arthritis crystal 
arthropathies reactive arthritis they're the four things that you need to 
remember there are other things that do it but that's if you want to get 
honours and things of that sort or want to be er a rheumatologist but four 
things to remember trauma and crystal arthropathy being very common bacterial 
arthritis being very rare but you mustn't miss it now what are you going to do 
here's someone else with a monoarthritis what what are you going to do you've 
got a history the history has told you it's an inflammatory arthritis and er 
there isn't any trauma they're not an alcoholic they don't think it's happened 
before what might you do next 
nm5250: well you don't you haven't got a diagnosis at this point so probably 
you've examined them you've not found any tophi if you've found out that 
they're on diuretics you might then be suspicious of gout but how are you going 
to prove the diagnosis so at this point you've got a differential diagnosis 
what are you going to do to nail the diagnosis 
nm5250: absolutely most people say do an x-ray so here's a normal x-ray er 
mostly useless in acute monoarthropathy and absolutely right you'd aspirate the 
joint er we do x-rays of these acutely swollen joints but they're pretty 
useless just a waste of the country's money generally speaking the most 
important thing is a needle in and here's pus from a joint and importantly 
although we've put joint sepsis at the top that appearance could be caused by 
gout pseudo gout rheumatoid arthritis virtually any inflammatory disorder and 
so what would you do next to try and make a diagnosis microscopy and if it's 
gout the thing that's most helpful really is er light this is er polarised 
light microscopy and what you see is these these are er gout crystals about er 
a hundred microns along and to make the absolute diagnosis what's nice to see 
is a gout crystal in a neutrophil and strictly speaking that's the way you make 
the perfect diagnosis you demonstrate the gout crystal in the cell because a 
few background gout crystals are quite common and here's how difficult it is to 
see without light microscopy so you'd just see a smudge with a bit of a bar 
across it i don't think unless you were very very skilled down a microscope 
you'd be particularly er er taken with that appearance and there's the 
polarised er er view with the crystal clearly seen within the cell so not using 
polarised light microscopy makes seeing the crystals very very difficult 
probably the commonest reason the crystals are not often picked up er and as 
we've described here's someone with gout and it can look like cellulitis when 
it's very severe here's a little old lady with some renal impairment who had 
been put on diuretics bashed her hand er and got this very severe appearance 
which was in fact treated with antibiotics for a couple of days because 
everyone assumed that it had to be cellulitis here's someone else with chronic 
renal impairment who's got swelling of the toes and bilateral swelling of the M-
T-P's but in fact was polyarticular gout so although gout is a form of 
monoarthritis er it is one of the differentials of polyarthritis and so i'm 
sort of rather er labouring the polyarticular presentation here these are tophi 
and they're typically present really only after er two three four years of 
hyperuricemia but they're very distinctive there's a white appearance 
underneath red typically not at all painful er and it's best not to stick a 
needle into them because er you can get chronic er sinuses forming er and 
infection and here is a tophus on an ear and here is the sort of nineteenth 
century version of severe gout in someone who felt that they were allergic to 
the treatment and didn't try any other medications er so gout is a fairly nasty 
disease and i suppose untreated has a mortality because they tend to get 
worsening renal failure and er then heart failure which can be quite so the 
gout itself with a uric acid of eight eight-hundred nine-hundred can itself er 
add to renal failure by a urate nephropathy which is both affecting the 
glomerulus and er er caused by some crystallisation within the tubules and it 
can mimic rheumatoid nodules er er whereas this is in fact a tophus rather than 
a rheumatoid nodule and if you feel it it feels quite different er what i want 
to show you here really before we move onto er er something else er is the 
distribution of uric acid in normal people and also in people with er er gout 
and there's one bar mi-, this is a normal distribution which is meant to go 
down to here so a small proportion of people with gout don't try and read the 
numbers er have uric acids of only three or four-hundred sort of five per cent 
the average level here is around about three-hundred and eighty to four-hundred 
that's where most of us lie and up to er fifteen per cent of people with gout 
have value er of uric acid when you measure them at that length and this value 
here is six-hundred basically virtually no-one goes above six-hundred because 
of the physio-chemical properties of uric acid normal people without gout also 
drop up into the level up to here so you can have people with er levels of uric 
acid of four-hundred and forty four-hundred and fifty who've never had an 
attack of gout so those distributions cross over and the range of which they 
cross over will encompass almost fifty per cent of people with gout which is 
why uric acid is a very poor discriminator which is why er we you cannot use 
the presence of hyperuricemia er er t-, to diagnose gout although you can say 
that if you have a level of gout er a level of of uric acid below three-hundred 
and twenty gout becomes very very unlikely now here's someone else with a a 
monoarthritis which isn't gout and that was seen from their shoulder so does 
anybody know what the diagnosis is here yeah any i've heard the i've heard it 
mentioned in the audience anyone got an idea what that is so it was a 
monoarthritis affecting the shoulder someone who is systemically quite well er 
an elderly person about sixty-five er pus essentially was removed from their 
shoulder stuff very yellow high neutrophil count with a negative Gram stain so 
no infection and there were the crystals that were seen and it is yeah come on 
pseudo gout and these are little rhomboidal crystals that you see in pseudo 
gout and here's a sort of scanning electron microscope it's they're they're 
much smaller they're about a quarter of the length of gout and they have 
positive birefringence rather than negative birefringence and what can 
sometimes be seen on x-rays is a very faint line it's er probably faint on this 
projection to the point where it vanishes can you see a little line there maybe 
that's chondrocalcinosis and one of the hallmarks which on plain x-ray may give 
you a clue as to the presence of pseudo gout and i've just shown this in as er 
a monoarthritis in a young boy with a very high fever the one discriminating 
feature for septic arthritis normally is a fever and typically you get spiking 
temperatures above thirty-seven so not a low grade fever but a decent fever and 
that's a very marked indicator of septic arthritis and again it becomes 
critical that you aspirate the joint er critical that you aspirate the joint 
and do blood cultures before you put people er on antibiotics er here on this 
side is the result of joint destruction from a staphylococcal er arthritis 
compared to the relatively normal x-ray on that side someone we'd missed now 
chap in the blue shirt er what do you think er this lesion is
su: that's the gonococcal
nm5250: absolutely i'll pass on from that really now what do you think the 
diagnosis is here the features the swelling here and here 
nm5250: osteoarthritis Bouchard's nodes and Heberden's nodes again er the 
commonest arthritis but one that rarely gets er confused and here is the sort 
of appearance of osteophytes er er an-, and thinning of the joints here with 
osteoarthritis and here is the pathological appearance of a normal joint and a 
joint in which osteophytes are forming er there is some narrowing it's probably 
that's a more typical joint it's just the way that these slides have been 
prepared er damage to some of the subarticular surface loss of this material 
here big wide spaces so erosion of the bone underneath and in the production of 
osteophytes and apart from pain relief joint replacement is pretty much all we 
have to offer now here's someone who sta-, this is er a series of photographs 
which have been superimposed of the progress of a chap with the con-, er a 
particular condition anyone recognise the condition say again what are the 
features of ankylosing spondylitis
nm5250: another chap bending forward preservation of the lumbar lordosis so er 
here here's a condition which was the paradigm for a group of illnesses called 
the spondyloarthropathies which we'll just talk about er er er very briefly 
we've talked about polyarthritis briefly monoarthritis what i don't want to do 
is you know drive out i mean we what i hope you've learnt so far is rheumatoid 
is er er the main sort of features of rheumatoid arthritis the four main 
differential diagnoses of a monoarthritis and that you stick a needle in the 
joint if you go away remembering that i'll be very satisfied er do you want to 
stop at this point hands up who wants to continue i think we'll stop at that 
point because then we've covered enough material thank you very much