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We report a 74‐year‐old man with acute on chronic tophaceous gout in whom conventional treatments failed but who responded to treatment with the interleukin‐1 receptor antagonist, anakinra. The patient presented in February 2004 with a severe flare of gout. Multiple joints were swollen, including the right fifth proximal interphalangeal (PIP), the left fourth PIP, and the first metatarsophalangeal (MTP) joints bilaterally. Apart from chronic tophaceous gout, he also had a history of membranous glomerulonephritis (for which he was on prednisolone 5 mg/day), hypertension, and ischaemic heart disease. Allopurinol had previously induced a severe anaphylactic reaction and his renal impairment was exacerbated by non‐steroidal anti‐inflammatory drugs.
On examination, the above mentioned joints were swollen with associated tenderness and erythema, and there were multiple tophi. Investigations revealed a raised C reactive protein (CRP) of 72 mg/l (normal <10 mg/l), a raised urate of 0.6 mmol/l (0.20–0.42 mmol/l), urea of 13.9 mmol/l, and creatinine of 155 μmol/l, with creatinine clearance reduced to 54 ml/min. The patient could only tolerate colchicine 0.5 mg daily and probenicid 1 g daily, both of which were continued throughout anakinra therapy. A prednisolone dose of up to 40 mg daily was used but his symptoms worsened whenever steroids were tapered. This inadequate control resulted in foot deformities with dropping of the right metatarsal arch, associated with radiographic osteopenia and erosions of the left first interphalangeal joint. Febuxostat, benzbromarone, and uricase inhibition were considered but were not used because of lack of availability or concerns about toxicity.1,2,3 However, recent data show that uric acid activates the NALP3 inflammasome, leading to release of interleukin‐1 (IL‐1β), which provides a novel theoretical basis for anti‐IL‐1β treatment.4,5,6,7,8,9
The patient was prescribed anakinra 100 mg daily subcutaneously, and outcomes were assessed regularly thereafter. The joints involved were photographed before and after therapy (fig 11)) with the patient's consent. Pre‐therapy, the total swollen joint count (SJC) was 14 and the tender joint count (TJC) 24. The CRP and erythrocyte sedimentation rate (ESR) were normal pre‐therapy (<1 mg/l and 13 mm/h, respectively), probably reflecting the effect of the steroid treatment. The patient improved within two weeks, with the global assessment score falling from 65 mm to 20 mm on a visual analogue scale (VAS 0–100 mm), and SJC improving from 14 to 3. The physician global assessment score fell from 80 mm to 50 mm. The patient received a continuous daily dose of anakinra during the follow up as he had residual joint tenderness, and maintained the benefit from this treatment at six months. Prednisolone 5 mg daily was continued for the glomerulonephritis. We plan to wean the patient off anakinra if symptoms resolve.
There is surprisingly little information about the management of “intractable” gout, and treatment options remain empirical. So et al have recently shown the efficacy of anakinra in resistant gout in a small pilot study.9 In contrast to other reports, our patient was at the most severe end of the disease spectrum but nevertheless improved significantly. There has been one report on the successful use of anti‐tumour necrosis factor in severe gout.10 It remains to be determined whether anakinra is especially effective in gout or whether antagonism of other key cytokine pathways is also effective.