Clinical case 1

You are asked to see a 75 year old lady because of arthritis in her right knee and ankle, but she also complains of
soreness in both wrists and hands. She has no family history of arthritis, and does not suffer from psoriasis. Examination
shows a painful knee with an effusion, and tender and modestly swollen ankle and modestly painful wrists and MCP
joints in her right hand. Hips show limited motion but are painless. Her joint symptoms started a few years back and she
most often feels unwell with pains which have affected feet, knees, elbows, wrists or hands although the joint distribution
of painful joints has varied; she also has some pain and limitation in shoulders and pelvic girdle with morning stiffness
lasting over one hour.

1. Indicate whether the following statements in relation to the diagnosis of this lady's disease are true or not
true
a. This clinical presentation is highly suggestive of a chronic polyarthritis which requires further diagnostic work-up
True. joint pain and some swelling of such duration with a current joint exam showing swollen and tender joints are
suggestive of a chronic polyarthritis, but there are several diagnostic possibilities.
b. FBC, ESR, C reactive protein, liver and kidney function tests and urine analysis will provide data of diagnostic
significance
False. although it should be done to evaluate the general status of the patient, likely it will only show the presence of an
acute phase reaction with high CRP and sedimentation rate, and possibly some anaemia consequent to chronic disease
and higher than expected platelet count.
c. The macroscopic appearance and cell count of synovial fluid will help the diagnosis
False. In this lady the chances are that the fluid will show inflammatory characteristics between 2,000 and 50,000
cells. Cell counts above 50,000 can be seen in uninfected joints suffering from psoriatic arthritis, spondylo-arthropathies
or crystal arthritis. The appearance will be cloudy/turbid the degree of cloudiness/turbidity generally being
proportional to the cell count. But these characteristics will not help distinguish between the different possibilities.
d. A radiograph of the hands may help
True. The symptoms are quite long standing and changes suggesting rheumatoid arthritis or psoriatic
arthritis/spondyloarthopathy are possible. CPP crystal arthritis is also a possibility.
e. Determination of rheumatoid factor, anti-citrullinated antibodies and ANA must be done
True. Rheumatoid arthritis is a clear possibility and a connective tissue disease is also possible.
Tests show: Hg 11.2 g/dl with otherwise normal FBC. Sedimentation rate: 48mm in 1st hour; CRP 2.8 mg/dl. Liver and
kidney function are normal; a serum uric acid value is 4.5 mg/dl. Rheumatoid factor, anti citrullinated antibodies and
ANA are negative. Synovial fluid was cloudy with a cell count of 34,000 cells/-l. Hand radiographs do not show joint
erosions although at the right hand there is isolated narrowing of the trapezio-scaphoid joint with sclerosis of the
subchondral bone. A few bone cysts are seen in carpal bones.
2. Consider whether the following statements are correct or not:
a. A definitive diagnosis has now been reached
False. The data does not allow a concrete diagnosis; elevation of acute phase reactants and data from the synovial fluid
merely confirm the existence of an inflammatory arthritis; from her history we already know that this is a chronic
inflammatory arthritis.
b. Treatment with NSAID should be started
False. This approach is symptomatic and although it may have a place in the short term it is not a reasonable choice for
a chronic arthritis.

c. Determining HLA-B27 can help with the diagnosis

False. If positive it only implies that this lady is in the group with a risk of suffering a spondyloarthropathy, if negative it
makes this diagnosis less likely but in the absence of a more suggestive clinical presentation to support this diagnosis
HLA-B27 determination has little use.
d. Glucose determination in the synovial fluid would have been of help
False. Low glucose in synovial fluid is a feature of infectious arthritis. Nothing in the patient's presentation suggests this.
e. Start treatment with methotrexate
False. It implies that we have decided to treat this lady as a seronegative rheumatoid arthritis hoping that she will
respond. And this may be fine if we consider that the diagnostic work up is already complete. But is it?
f. Do a crystal search in synovial fluid
True. The serum urate level is quite low and polyarticular gout is highly unlikely, but chronic CPP crystal arthritis is a
possibility.
You take a new synovial fluid sample from the swollen knee, and look at it using the ordinary microscope in the
Emergency room laboratory. You see abundant cells and what appear to you as crystals, intra and extracellular, many
acicular, but others are rhomboidal or parallelepipedic. You have already read the In Depth Discussion of this On Line
Course on crystal analysis and may also have done the Crystal Workshop at EULAR but have little experience in
crystal analysis and still feel insecure. How would you make a decision about what these crystals are?
3. In relation to your identification of the crystals indicate whether these statements are True or Not true
a. The findings as described suggest coexistence of urate and CPP crystals
False. Acicular CPP crystals are usual and seen in most/all synovial fluid samples containing CPP crystals. Fluids
containing both types of crystals are very unusual and most often, when using the ordinary light microscope there are
both acicular crystals and rhomboidal and parallelelipedic crystals, all of them are CPP crystals. But the answer is
partially true: coexistence of both crystal types in this particular sample cannot be discounted with only the ordinary light
microscope.
b. In the pathology department there is a simple polarized microscope which will allow better detection of CPP crystals
by birefringence
False. Only about 1/5th of the crystals show any birefringence when observed by means of a simple polarized
microscope, without a compensator. Crystal detection of CPP crystals (confirming that there are crystals in the synovial
fluid preparation) is better carried out with the ordinary light microscope. Those CPP crystals that show birefringence,
show a weaker birefringence than urate crystals and their shine on the dark background of the microscope field is most
often faint.
c. If there are urate crystals in the synovial fluid, the simple polarized microscope will help with detection and
identification
True. Urate crystals are highly birefringent and shine brightly over the dark background when observed by means of a
simple polarized microscope. This allows an easy detection even when crystal numbers are few. All urate crystals are
acicular.
d. Rhomboidal or parallelelipedic crystals cannot be taken for urate crystals
True.
e. In this patient, examining a synovial fluid sample of the currently not inflamed knee (but previously inflamed) will also
show crystals
True. This is true for gout and also for CPP arthritis (although for CPP there are fewer published data). This is of
importance when there are not currently inflamed joints but there is a history of arthritis, allowing a diagnosis of crystal
arthritis during intercritical periods.

f. Observation under a compensated polarized microscope will help in the identification of crystals as urate or CPP
crystals
True. Crystal identification under the compensated polarized microscope is the current standard procedure. Examiners
with experience can accurately identify the crystal type by means of the ordinary light (the best examining tool for CPP
crystals, their shape facilitating detection and identification by this mean) and the simple polarized microscope (best for
urate crystals, all acicular and of strong light intensity in this system). But the negative birefringence of urate and positive
birefringence of CPP crystals allows a more definitive identification and is the standard tool for crystal identification
g. The first tool for beginners to start their training in crystal analysis is the compensated polarized microscope
False. This is the most difficult tool to master, and it is a more difficult starting tool for learning. It is easier 1) start looking
at fluids with known diagnosis by means of an ordinary light microscope and identify crystals by shape. 2) then try the
simple polarized microscope and see the presence/absence and intensity of the birefringence of urate and CPP crystals.
After mastering these systems, a compensated polarized microscope is easier to use.
The rhomboidal, parallelepipedic and acicular crystals of the synovial fluid of the patient showed only faint birefringence,
and by means of the compensated polarized microscope positive birefringence establishes the diagnosis of chronic CPP
crystal arthritis in your patient. Some data provided so far indicate that this could be so.
4. Indicate which of the following statements are true or not true:
a. The hand X ray findings that were described suggested the diagnosis
True. Isolated osteoarthritis of the trapezioscaphoid joint and carpal bone cysts are both features seen in CPP crystal
arthritis (Donich AS, Lektrakul N, Liu CC, Theodorou DJ, Kakitsubata Y, Resnick D. Calcium pyrophosphate dihydrate
crystal deposition disease of the wrist: trapezioscaphoid joint abnormality. J Rheumatol. 2000;27:2628-34).
b. The pattern of arthritis may have suggested the diagnosis
True. The patient referred to a changing pattern of joint inflammation. This is less characteristic (though possible) with
other chronic inflammatory arthritides, and may have prompted a search for CPP crystal in synovial fluid or
radiological chondrocalcinosis elsewhere.
c. The restriction of movement of the hips is worth an X Ray that may have suggested the diagnosis of CPP arthritis
True. In this case it showed osteoarthritis of the hips. Chondrocalcinosis can often be seen in radiographs at the hip
joint. Also this lady had chondrocalcinosis at the symphysis pubis.
d. Shoulder and hip girdle pain with morning worsening of some duration does not suggest crystal arthritis, but rather
rheumatoid arthritis or associated polymyalgia rheumatica in addition to her crystal arthritis.
False. A polymyalgia rheumatica like clinical picture has been described in chronic CPP crystal arthritis (Pego-Reigosa
JM et al. Calcium pyrophosphate deposition disease mimicking polymyalgia rheumatica: a prospective follow up study of
predictive factors for this condition in patients presenting with polymyalgia symptoms. Arthritis Rheum.
2005;15;53:931-8. This is also the experience of the authors of this review and any joint effusion in these patients should
be examined for crystals.
Conclusion : Here we describe a lady presenting with chronic arthritis, and although her presentation does not fit the
most characteristic one for any of the "major" chronic inflammatory arthritides, she could easily have been diagnosed
and managed as having one of them. As stated in the EULAR recommendations for the diagnosis of gout and also for
the diagnosis of CPP crystal arthritis, a synovial fluid sample from any undiagnosed (or diagnosed with uncertainty)
arthritis should be examined for crystals. When this is a regular practice, CPP chronic arthritis and atypical gout
become less unusual, these diseases more attractive, and patients thankful!
Clinical case 2
You are consulted from the surgical ward of your hospital to evaluate a 69 year old man whose right knee suddenly
became painful and swollen five days after coronary bypass surgery. He does not recall any previous joint problem.
Besides the signs of recent heart surgery, his physical exam only shows a large effusion in his right knee; active and

passive movement at the knee are restricted due to evident pain. There are no skin manifestations, though the skin of
the right knee feels warm. Body temperature is 38.7 C. Laboratory examinations performed this same morning show a
leukocyte count of 13.2 x 109/l; C reactive protein of 35 mg/l; ESR: 78mm/h; creatinine: 124 mol/l (1.4 mg/dl), uric
acid: 0.35 mmol/l (5.9 mg/dl).

1. In this setting your first and clinically most important step would be to:
a. Order a radiograph of the knee
False. A radiograph of a joint with acute arthritis will be of some, but limited help if chondrocalcinosis is seen, suggesting
the diagnosis of acute CPP crystal arthritis ("pseudogout"), but the positive and negative predictive values of
chondrocalcinosis are too low to predict or exclude an attack of acute CPP crystal arthritis in an individual.
Chondrocalcinosis occurs very frequently in the elderly, so its presence may not necessarily explain the patient's joint
problem. On the other hand, absence of chondrocalcinosis does not exclude acute CPP crystal arthritis. The radiograph
might show unrelated osteoarthritis, but will not show specific clues for other causes of acute arthritis.
b. Prescribe an NSAID
False. An NSAID may be the first step if this is crystal arthritis. But 1) the patient is febrile and may have a septic joint.
So a diagnosis has to be made 2) the patient is elderly and recently underwent heart surgery, and his creatinine is a bit
high: because of possible renal and cardiovascular side effects, an NSAID is relatively contraindicated.
c. Aspirate synovial fluid
True. The patient is febrile and joint infection is a real possibility, so a culture has to be made. Both gouty arthritis and
acute CPP crystal arthritis can also produce elevated body temperature (more likely if the affected joint is large, such in
this man). So the joint fluid should be cultured, and the fluid examined for crystals. This man's acute arthritis can be due
to gout (serum uric acid levels can decrease during the attacks, and be then within the normal range) or to acute CPP
crystal arthritis; also there could be crystal arthritis and coexisting bacterial arthritis.
d. Start appropriate antimicrobial treatment without delay
False. Even if the diagnosis is bacterial arthritis, treatment should never start without a previous synovial fluid culture, if
possible to perform. Otherwise, in case of poor response, it will be unclear whether the diagnosis is wrong, i.e. that this
patient doesn't have bacterial arthritis at all or whether the diagnosis is right, but the organism is resistant to the
antibiotic(s) administered.
Two days later neither the cultures of the joint fluid nor the blood cultures show any growth. The initial synovial fluid
analysis had shown 40,000 cells/l. and abundant monosodium urate crystals, but because a possible coexisting joint
infection could not be excluded, the decision had been made to start antibiotics and the joint has been drained, but it
remains swollen and painful.
2. For this situation at this time, which statement is true?
a. The cell count less than 50 x10 exp.9/l was not in the septic range: this finding implies antibiotics should not have
been given
False. The cell count less than 50 x10 exp.9/l as a cut-off between septic and inflammatory synovial fluids is only
suggestive and has not been critically evaluated. Exceptions are very common, and decisions should not be taken
based on this finding alone.
b. Local injection with glucocorticoids is an option
True. An intra-articular injection with glucocorticoids is reasonably free of systemic side effects and likely will result in
rapid resolution of the gout attack. Negative cultures make coexistent bacterial arthritis unlikely but do not discard it;
maintaining the antibiotics appears safe. An alternative option could be to stop the antibiotics, allowing the taking of
cultures again if arthritis nevertheless persists.
c. A change in antibiotics is the right approach for this patient

False. If there would be (severe suspicion of) coexisting bacterial arthritis, eventually the antibiotic should be stopped in
case of lack of effect and cultures should be taken again. However, 2 days is too short a period to be fully sure the
cultures eventually will be negative or to expect a full recovery of arthritis.
d. A full dose of an NSAID now is indicated
False. Due to the age of the patient and his co-morbidities, this is a poor option at any time. Furthermore: the most
important issue here is: did we make the right diagnosis?
e. It appears safer to proceed with an open drainage of the knee
False. The chances are that this patient has only gout (gouty flares are very common after surgery), and in this case this
procedure aimed at bacterial arthritis would be an unnecessary option with possible complications, such as bacterial
infection.
The patient refused an intra-articular injection with glucocorticoids and was treated with 30 mg prednisone orally for a
few days and antibiotics were maintained. Two days later his knee has markedly improved and his temperature is down
to normal; cultures remained negative.
3. At this time which strategy is best?
a. Antibiotics can be discontinued and prednisone rapidly taped down and stopped
False. These are two changes in treatment. Rapidly tapering down prednisone may likely result in a rebound attack of
gout. If antibiotics are discontinued now, it may become difficult to know if the rebound arthritis is due to crystals or to a
flare of infection.
b. Antibiotics should be maintained, and prednisone rapidly tapered down and stopped
False. Rapidly tapering down prednisone may likely result in a rebound attack of gout, which is not treated or prevented
anymore. The rapid response to prednisone suggest that gout may be the only problem; so the decision could be made
to stop the antibiotics (and to take cultures again if arthritis flairs).
c. Antibiotics can be discontinued and prednisone can be rapidly tapered down and stopped and allopurinol should be
started
False. Initiation of allopurinol without prophylaxis easily results in a gouty flare. In addition, a first attack of gout doesn't
need to be treated with uric acid lowering drugs, and certainly not as 'urgent treatment'.
d. Antibiotics can be discontinued and colchicine should be started at a dose of 0.5 to 1mg/daily and prednisone rapidly
tapered down and stopped
True. Colchicine offers a good protection against new gouty attacks, and reduces the chance of a rebound attack after
discontinuation of prednisone. The joint should be evaluated again if new symptoms emerge while on colchicine
prophylaxis. The rapid response to prednisone may suggest that gout probably is the only problem; the decision could
be made to stop the antibiotics and to take cultures again if arthritis flairs.
e. Prednisone should be tapered down and maintained at a dose below 7.5 mg/day
False. Prednisone should not be used for long-term prophylaxis of new gout attacks. Maintaining prednisone and
discontinuing antibiotics may masquerade the symptoms of infectious arthritis if present and is therefore also an
unsafe choice.
Colchicine was started at a dose of 0.5 mg b.i.d. because of his slightly elevated serum creatinine, prednisone was
rapidly tapered and stopped, and the antibiotics were discontinued. The knee became rapidly asymptomatic and by one
week the patient had forgotten this problem, and was recovering uneventfully from surgery. Now he recalled having had
attacks of acute arthritis for the last 7 years, affecting initially the first MTP joint of one or the other feet, but later he had
noticed tarsal, ankle and knee arthritis. He did recall 5 such attacks during the previous year, which he effectively treated
with colchicine (1mg followed 1 every two hours by 0,5 mgs until resolution of the attack), although almost always this
therapy was complicated by diarrhoea and abdominal cramps.
4. Which of the following two statements are true?

a. The colchicine scheme of 0.5 mg each two hours is fine, but it should be stopped at the beginning of diarrhoea or
abdominal cramps
False. Colchicine frequently results in side effects if used in the doses most often used for acute attacks of gout. Now
there is evidence that 1.2 mg followed 1 hour later by 0.6 is equally effective but with less side effects than the larger
doses which have been quite usual. In this patient with elevated serum creatinine, lower doses of colchicine seem more
appropriate.
b. He should receive an explanation about the nature of gout as a potentially reversible crystal deposit disease and the
clinical characteristics of the attacks related to it. He also should know the function of the different drugs used to treat
gout, the possibility of co-morbid conditions and the importance of lifestyle modifications.
True. Information about gout and its treatment, as well as about co-morbid conditions is considered essential by the
EULAR guidelines for gout treatment.
c. He should receive 0.5 to 1 mg/day of colchicine for at least six months.
False. This likely will avoid gouty attacks or reduce their number - during the period in which colchicine is
administered, but as serum uric acid remains high, crystals continue being deposited in joints and at other places, and
the patient will suffer from new attacks after discontinuation of colchicine
d. He should start allopurinol as continuous therapy.
False. If given without colchicine prophylaxis, the patient is likely to have new gouty attacks triggered by the rapid
decrease of serum uric acid resulting from allopurinol therapy. He may discontinue all medication (and consult another
doctor) if this is the case
e. He should start allopurinol as continuous therapy and use during at least during the first six months also colchicine 0.5
to 1 mg/day.
True. By reducing to normal serum uric acid levels allopurinol prompts dissolution of urate crystals. Gouty attacks tend
to occur at the initiation of allopurinol therapy; prophylaxis with colchicine helps to avoid them. The duration of colchicine
prophylaxis has not been critically ascertained, and six months appears a reasonable period of time. Attacks may occur
after discontinuation of colchicine if the joints still contain urate crystals.
f. Dietary and life habits modifications should be sufficient to control his gout.
False. Although very important for this patient's management, dietary and life style modifications are most frequently
insufficient to control long standing gout. In this specific patient with elevated serum creatinine, chances are very low
that life-style modification would be sufficient.
Now you have to plan the future management of this patient's gout.
5. Indicate whether the following statements are true or not true
a. This patient's gout and coronary disease may be related.
True. Gout associates with the metabolic syndrome, thus with atherosclerosis and hypertension. In addition gout has
been reported now to also be independently associated with myocardial infarction.
b. He should avoid his habit of drinking 1-2 glasses wine per day.
False. A moderate consumption of wine does not induce hyperuricemia.
c. The diuretics that he may need will raise the serum urate levels.
True. This has been shown for different diuretics
d. If Losartan is used for hypertension, it will help to reduce serum urate levels.
True. Losartan results in a modest rise of urate clearance, thus reducing uricaemia
e. Low dose aspirin may result in a modest rise in serum urate levels.
True. Low dose aspirin results in a modest decrease of urate clearance, increasing uricaemia

f. Even if properly treated, gout is a chronic disease and the patient will continue having attacks (milder and less
frequent) indefinitely.
False. Gout is a reversible monosodium urate crystal deposit disease. Prolonged reduction of serum uric acid levels
below a certain level results in complete crystal dissolution and complete absence of gout attacks. If serum uric acid is
allowed to rise again, new crystals will form and gout will return, however.