Transcript Diapositiva 1

Clinical cases
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Case report n. 1
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Patient
• Woman, aged 78 years
• Affected by polyarticular pain and swelling of the distal
interphalangeal joints for 10 years
• First diagnosis: osteoarthritis of the hand, Heberden’s nodes with
recurrent inflammatory reactions
– Treatment: NSAIDs for flares (3-4 per year)
– Response: good
• Five years later psoriasis at elbow and on scalp
• New diagnosis: psoriatic arthritis
– Treatment: chronic therapy with NSAIDs + omeprazole
– Response: unsatisfactory (continuous pain)
• Three years later: atrial fibrillation (warfarin)
– Treatment: NSAIDs stopped → prednisone 5 mg/daily
– Response: moderate
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• After 2 years, she presented at the emergency room with painful
swelling of her second distal interphalangeal joints, bilaterally;
the joints were also red, warm and tender
By kind permission of L. Punzi, Rheumatology Unit, University of Padua
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When pressure was
applied, a toothpaste-like,
white, chalky substance
was easily expressed
By kind permission of L. Punzi,
Rheumatology Unit,
University of Padua
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• When analysed by polarised light microscopy, this chalky substance was
found to consist of needle-shaped, highly birefringent crystals (Figure A)
• Using a first order red compensator, these crystals had a negative optical
appearance typical of urate crystals (Figure B)
• Thus, a definitive diagnosis of gout was made
Figure A. Polarised light
Figure B. First order red compensator
By kind permission of L. Punzi, Rheumatology Unit, University of Padua
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• Laboratory investigations indicated normal renal and hepatic function;
serum uric acid 600 μmol/l (10mg/dl)
– Colchicine at low dose (0.5 mg x 2 daily) was added to prednisone 5 mg/daily
• The acute symptoms subsided rapidly after 1 week
– Allopurinol was then introduced at a low dose (50 mg/daily for 2 weeks, then
100 mg daily) together with colchicine at prophylactic doses (0.5 mg daily) and
prednisone 5 mg daily
• After 1 month, serum uric acid was 400 μmol/l (6.7 mg/dl)
– Allopurinol was increased to 150 mg daily, while continuing with colchicine
0.5 mg daily and prednisone 5 mg daily
• After another month, the serum uric acid was 320 μmol/l (5.4 mg/dl)
– Colchicine was continued and prednisone was reduced to 2.5 mg daily
– Three months later the patient stopped prednisone and after 1 month also
stopped the colchicine treatment
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Case report n. 2
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• A man, aged 50 years, presented with acute inflammatory polyarthritis
characterised by painful swelling, redness, warmth and tenderness of
many joints, including those of the hands and wrists bilaterally, shoulders,
knee and feet. He had never experienced such an episode before
By kind permission of L. Punzi, Rheumatology Unit, University of Padua
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• Serum urate was 625 μmol/l (10.5 mg/dl), serum creatinine clearance
90 ml/min and clearance of uric acid was 6.5 ml/min. An overproduction
mechanism rather than decreased elimination is supposed to be involved
in inducing hyperuricaemia
• A synovial fluid examination revealed urate crystals, so gout was
diagnosed
– Colchicine 0.5 mg x 2 daily and allopurinol in increasing doses from
100 up to 300 mg/day in 3 months was started
• After 3 months serum urate levels were still above the therapeutic target:
380 μmol/l (6.4 mg/dl)
- Allopurinol was further increased to 450 mg/day
• Serum urate levels of 291 mol/l (4.9 mg/dl) have been reached but the
patients complained malaise and a slight increase in eosinophils to 600/µl
- The allopurinol night dose of 150 mg was withdrawn
• At an allopurinol dose of 300 mg/day, the patient’s serum urate returned
to 380 μmol/l (6.4 mg/dl) and he still had chronic complaints and suffered
gout flares
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• Allopurinol was stopped and febuxostat was
introduced at a dose of 80 mg/day
• Serum urate levels lowered to 320 μmol/l (5.4 mg/dl)
and gout attacks ceased
• After three months the patient continued to stay well
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Case report n. 3
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• Man, aged 57 years, presented at our emergency room with a
2-day exacerbation of a painful, swollen elbow
• He had a history of some years of classical gout for which he had
been successfully treated with NSAIDs
• On examination, the patient was febrile and had an inflamed
olecranon bursa at the left elbow
By kind permission of
L. Punzi, Rheumatology Unit,
University of Padua
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• Purulent-looking fluid was aspirated from his swollen elbow and
sent for microbiological studies
• The synovial fluid analysis revealed a white blood cell content of
60,000/mm3 and many intra- and extra-cellular urate crystals
• The microbiological cultures grew group C haemolytic streptococci
• Other investigations included a haemoglobin of 9 g/dl, urea of
28.5 mmol/l and creatinine of 221 mmol/l. His creatinine clearance
was 20 ml/min, erythrocyte sedimentation rate 130 mm/h and
C-reactive protein 150 g/l, urate 357 μmol/l (6.0 mg/dl)
• He was taking enapril for hypertension and had recently had an
NSAID introduced for treatment of his gout. This and the infection
had presumably precipitated the patient’s renal failure
• He was treated with i.v. benzylpenicillin, and both enapril and
NSAID were discontinued
• On this treatment, his pyrexia settled
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• His serum creatinine improved to the normal range and creatinine
clearance to 44 ml/min
– Allopurinol 100 mg/day and colchicine 0.5 mg/day were introduced.
Nifedipine sustained release 20 mg bid was started as his new
antihypertensive treatment
• One month later, he developed a generalized florid rash for which he
was readmitted to hospital
• The rash disappeared after allopurinol was discontinued
• On admission, his serum urate had been 464 μmol/l (7.8 mg/dl)
– Probenecid was introduced but the patient was unable to tolerate it
because of dyspepsia
• Despite continuous treatment with colchicine 0.5 mg bid he suffered
frequent inflammatory episodes of gout with serum urate levels
varying from 450 to 900 μmol/l (87.5-15.1 mg/dl)(normal range,
160-420 μmol/l – 2.6-7.0 mg/dl)
• In recent months, he was noted to have proteinuria with a slightly
raised serum creatinine of 240 mmol/l
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• In view of persistent symptoms and concern over the
possibility of gouty nephritis, allopurinol was recommenced
in a desensitization regime
• After restarting allopurinol, the serum uric acid decreased
to a normal level
• The regime was tolerated well up to a dose of 200 mg daily,
when the patient developed a mild, macular rash. This
settled after allopurinol was discontinued
• Febuxostat at 80 mg daily was then introduced
• Six months later he was well, and colchicine has been
stopped
• The patient’s proteinuria has disappeared and his serum
urate levels have fallen to 300 μmol/l (5 mg/dl)
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Comments
• Severe allopurinol-induced toxic effects occur in less than 2% of
treated patients but can be life-threatening, with a mortality rate of
about 20%
• They also develop early and seem to arise mainly in patients with
renal failure, in those on high doses of allopurinol, in patients on
concomitant diuretic treatment and when the drug is reintroduced
after skin intolerance
• Patients with a history of severe skin rash induced by allopurinol
should, therefore, never be given the drug again. Several strategies
to control uricaemia in these patients have been proposed, including
the use of febuxostat and uricosuric drugs when not contraindicated
• In cases of mild skin reaction, allopurinol desensitisation might be
successful but it is recommended only if the alternatives fail
• Desensitisation should not be attempted in patients with severe
reactions or renal or hepatic failure
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Case report n. 4
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Patient
• A 68-year-old female with well-controlled type 2 diabetes,
chronic kidney disease, and chronic gout
• Experiencing increasingly frequent gout attacks
• She presented with sub-acute pain, swelling, redness and
tenderness in joints of the left foot, left hand and pre-patellar
bursa
• Symptoms resolved slowly following aspiration and steroid
injection into the pre-patella bursa
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• At examination the patient had polyarticular gout characterised by
acute pain, swelling, redness and tenderness of different affected
joints
By kind permission of L. Punzi, Rheumatology Unit, University of Padua
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• Diagnostic procedures
– A bursal aspirate revealed urate crystals and no
infection
– Laboratory investigations indicated poor renal function
(creatinine clearance 30 ml/min/1.73 m2) and elevated
serum urate levels (10 mg/dl - 595 μmol/l)
• Medical consideration
– Therapeutic options for symptomatic treatment of this
patient’s gout flares and for the management of her
chronic gout and hyperuricaemia required careful
consideration in view of her compromised renal function
and diabetes
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• The patient was treated with allopurinol, starting at a dose
of 100 mg/day, and with low dose colchicine for prophylaxis
of flares
• The allopurinol dose was adjusted according to the patient’s
creatinine clearance
• After 3 months of allopurinol treatment urate levels had
decreased only to 8.0 mg/dl (476 μmol/l) and the patient still
experienced flares.
• Allopurinol was stopped and benzbromarone was started at
a dose of 50 mg/day after the patient’s liver function had
been evaluated
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• Unfortunately, the patient developed an extensive skin rush and
benzbromarone was stopped immediately
By kind permission of L. Punzi, Rheumatology Unit, University of Padua
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• Febuxostat at 80 mg daily was then introduced and
colchicine prophylaxis was continued for 6 months
• After 1 month of treatment the patient’s serum urate
level had reached 6.1 mg/dl (363 μmol/l)
• After a further 3 months the serum urate level was
4.9 mg/dl (292 μmol/l) and the patients felt well and
had no further flares
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Comments
• Urate lowering therapy is strongly indicated in patients with frequent gout
flares and persistent hyperuricaemia
• Gout management can be difficult in patients with impaired renal function
(associated with diabetes in this case)
• NSAIDs should be avoided and colchicine and corticosteroids used with
caution for the symptomatic management of flares
• Since allopurinol and its metabolites are excreted by the kidney, the dose
must be reduced in patients with impaired renal function. Allopurinol
should be started at a low dose
• Since this patient had impaired renal function, low-dose colchicine was
more appropriate than NSAIDs for prophylaxis
• Benzbromarone is likely to be effective in patients with impaired renal
function, but carries a small risk of liver toxicity
• Febuxostat is an effective and well tolerated urate-lowering drug and can
be used with no dose adjustments in patients with mild and moderate
renal impairment
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