Successful Treatment With Rasburicase of a Tophaceous Gout in a Patient Allergic to Allopurinol

Pascal Richette; Thomas Bardin

Disclosures

Nat Clin Pract Rheumatol. 2006;2(3):338-342. 

In This Article

Summary and The Case

Background A 56-year-old white woman was referred to our institution with a 16-month history of severe, gouty, recurrent, acute polyarthritis involving the finger joints. She also had numerous small subcutaneous tophi in her hands. The patient was intolerant to allopurinol and had mild renal insufficiency attributed to uric-acid nephrolithiasis and interstitial nephropathy.
Investigations Physical examination, laboratory testing, X-rays of the hands, feet and pelvis, CT of the pelvis, microscopic analysis of an aspirate from a finger tophus.
Diagnosis Tophaceous gout associated with urate nephropathy in a patient intolerant to allopurinol.
Management Acute polyarthritis was successfully managed by intravenous bolus methylprednisolone combined with codeine, diclofenac and low-dose colchicine. Rasburicase infusions combined with fenofibrate and sodium bicarbonate achieved to maintain serum acid uric below 360 µmol/l.

A 56-year-old white woman had a 16-month history of severe recurrent acute polyarthritis involving the finger joints. Her general practitioner diagnosed gouty arthritis because of a high serum uric-acid level (600 µmol/l; normal range 270–380 µmol/l) coexistent with tophi in her hands, and initiated allopurinol 100 mg daily. A few days after the introduction of allopurinol, the patient developed severe urticaria/angioedema, and allopurinol therapy was discontinued. The patient was hospitalized 7 months after allopurinol discontinuation, in order to manage subintrant articular crisis that was resistant to colchicine therapy.

The patient's past medical history included a duodenal ulcer, hypertension, ischemic heart disease, hyperlipidemia and moderate, chronic renal insufficiency, which was previously attributed to uric-acid nephrolithiasis and interstitial nephropathy. She had also been suspected of anorectic behaviour and of intermittently taking diuretics for several years. Upon admission to hospital, her therapy consisted of acetaminophen 3 g daily, colchicine 1 mg daily, omeprazol 20 mg daily and bisoprolol 10 mg daily. Her height was 151 cm and her weight was 40 kg (BMI 17).

Physical examination revealed swelling and tenderness in both wrists and in many metacarpophalangeal joints, numerous small tophi in the subcutaneous tissue of the palmar aspect of her fingers, and severe finger flexor tenosynovitis. Laboratory evaluations showed a slightly raised uric-acid level of 445 µmol/l, an elevated C-reactive-protein level of 50 mg/l (normal level <4 mg/l) and renal impairment with creatinine clearance of 29 ml/min (normal range 80–120 ml/min). The 24 h uric acid excretion rate was 1.09 mmol/day (normal range 2.4–4.8 mmol/day). Serum total cholesterol and triglycerides were 5.73 mmol/l (normal range 4.4–6.1 mmol/l) and 2.74 mmol/l (normal range 0.5–1.4 mmol/l), respectively. Glycemia was normal. A pelvic CT scan revealed intraparenchymatous renal calcifications with normal kidney size. X-rays of the hands, feet, pelvis and knees did not demonstrate features of urate arthropathy but revealed CHONDROCALCINOSIS in her knees and pubic symphysis. The chondrocalcinosis was asymptomatic, as the patient did not complain of arthritis in her knees.

A needle aspiration of a subcutaneous tophus located on the palmar aspect of the left forefinger allowed demonstration of needle-shaped, negatively birefringent monosodium urate (MSU) crystals by COMPENSATED POLARIZED-LIGHT MICROSCOPY (Figure 1).

Microscopic analysis of an aspirate from a tophus. Numerous negatively birefringent needle-shaped monosodium urate crystals are detected by compensated polarized-light microscopy (original magnification ×40). Monosodium urate crystals are strongly birefringent when observed under polarized light, and negatively birefringent, appearing yellow when parallel, and blue when perpendicular, to the axis of slow vibration from the compensator.

The patient was given 1 mg colchicine every 4 h (maximum of 4 mg/day), but she developed diarrhea, so the colchicine dose was reduced to 1 mg daily, as was given previously. Despite concurrent treatment with diclofenac 75 mg daily and codeine 30–60 mg daily, her acute arthritis did not improve. Four days later, methylprednisolone 100 mg was administered intravenously, leading to a major improvement in joint inflammation. Sodium bicarbonate was prescribed in order to obtain a urinary pH of less than 6, and fenofibrate 160 mg daily was introduced in order to decrease uric-acid level and to manage hypertriglyceridemia. Following 1 month of treatment with fenofibrate, the patient's uric-acid level persisted above 360 µmol/l, although triglycerides normalized. Intravenous therapy with recombinant urate oxydase rasburicase 0.20 mg/kg (Fasturtec®, Sanofi-Aventis, Paris, France) was then added. A total of 10 infusions were performed during a 16-month period. The patient's serum uric-acid level dramatically decreased in the days following rasburicase infusions, but progressively increased during the subsequent weeks, before the next infusion. After the third infusion, serum uric-acid level was maintained below 360 µmol/l until the next infusion (Figure 2). Rasburicase treatment was well tolerated, without allergic side effects. The first three infusions were marked by recurrent, acute attacks, although these were successfully treated with oral prednisolone 20–40 mg day. No gout attack has occurred since the sixth infusion, and dramatic regression of hand synovitis was observed, with restoration of the patient's functional capacity of both hands. Gout tophi totally disappeared and renal function remained stable. The patient continues to receive rasburicase treatment.

Course of serum uric-acid levels during long-term rasburicase treatment. Rasburicase infusions are indicated as F. A total of ten infusions were performed between May 2004 and October 2005.

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