Urate-Lowering Therapy Reduces Non-Episodic Foot Pain in Patients Without Gout Diagnosis
Non-episodic foot pain in hyperuricemia was associated with ultrasound features of monosodium urate deposition.
In hyperuricemic individuals who did not qualify for a gout diagnosis according to 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, urate lowering therapy (ULT) reduced persistent foot pain, according to study findings published in the Annals of the Rheumatic Diseases. Positive ultrasound findings, including the double contour sign, predicted this effect.
Even without a history of a clearly-defined episode, which is needed for a definitive gout diagnosis, normally asymptomatic patients with hyperuricemia may still have monosodium urate (MSU) crystal deposition in their joints, presenting with an alternative form of non-episodic foot pain. This presentation may indicate an earlier pathophysiologic phase that could benefit from ULT despite current recommendations and a lack of formal ACR/EULAR classification.
A case-control study enrolled hyperuricemic participants with non-episodic persistent foot pain (n=16; mean pain duration, 28 months) who did not meet ACR/EULAR 2015 gout criteria and compared them to asymptomatic controls with hyperuricemia (n=15). Bilateral ultrasound of the first metatarsophalangeal joint was performed in all participants, looking for MSU deposition indicators, including tophi, erosion, and the double contour sign. Individuals with foot pain were prescribed febuxostat 80 mg once per day for 3 months. Serum urate and pain measured using a 0 to 100 visual analogue scale (VAS) were assessed at baseline and at 1 and 3 months.
On ultrasound, tophi, erosion, and the double contour sign were seen in 37%, 37%, and 44% of patients with foot pain, respectively; there were no positive ultrasound findings in controls. Baseline serum urate levels were similar in patients with foot pain (mean, 450 mg/dL) and controls (mean, 426 mg/dL). In patients with foot pain, serum urate was significantly reduced at 1 and 3 months (200 mg/dL and 223 mg/dL, respectively; P <.001 for both). The 24-hour and 7-day VAS pain scores in patients with foot pain at baseline were 65 and 70, respectively. Both measures were significantly reduced at 1 month (VAS score, 41; P =.001; and VAS score, 44; P <.001) and 3 months (VAS scores 33 and 38, respectively; P <.001 for both).
When patients with foot pain were stratified by presence (n=7) or absence (n=9) of the double contour sign, there were no significant differences in baseline pain VAS scores. However, after ULT the double contour-positive patients displayed significantly lower 24-hour pain scores compared with double contour-negative patients at 1 month (26 vs 52; P =.046) and 3 months (14.3 vs 49; P =.009). In a similar fashion, the double contour-positive individuals also fared better compared with double contour-negative participants on 7-day VAS scores at 1 month (27 vs 57; P =.011) and 3 months (17.7 vs 56; P =.01).
“These findings indicate that persistent, non-episodic foot pain in hyperuricemia is both associated with [ultrasound] features of MSU deposition and is responsive to ULT,” concluded the authors. They suggested that symptomatic hyperuricemia without a history of a classic gout episode may represent an alternative or early disease presentation, and that patients might benefit from classification changes that would improve treatment strategies and outcomes in those with positive ultrasound findings.
Alammari YM, Gheta D, Flood RM, Boran G, Kane DJ, Mullan RH. Urate-lowering therapy (ULT) reduces non-episodic foot pain in patients who fail to meet ACR/EULAR 2015 gout classification criteria: an effect predicted by ultrasound and potential rationale for reclassification [published online October 29, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214305