Background:Emerging evidence that the joints of asymptomatic hyperuricaemic individuals contain monosodium urate (MSU) deposits and that alternative presentations of foot pain occur in hyperuricaemia suggests that preclinical phases may occur prior to a first episodic gout attack. (1) This case–control study evaluates urate deposition in hyperuricaemic individuals not fulfilling the current gout classification criteria, as well as a potential therapeutic role for urate lowering therapy (ULT).Objectives:To investigate whether ULT reduces non-episodic foot pain in patients who fail to meet ACR/EULAR 2015 gout classification criteria.Methods:Following informed consent, hyperuricaemic individuals with persistent, non-episodic foot pain (n=53) not fulfilling ACR/EULAR 2015 gout classification criteria, were compared with asymptomatic hyperuricaemic controls (n=18). Ultrasound (US) of bilateral first metatarsophalangeal (MTP) joints and features of MSU deposition including double contour (DC) sign, tophus and juxta-articular erosion were recorded. Cases only were treated with febuxostat or allopurinol daily for 6 months. Serum urate, 24-hour and 7-day visual analogue score (VAS) 0–100 mm pain scales and the Manchester Foot Pain and Disability Index (MFPDI) were recorded before treatment and after 3 and 6 months. MTP Ultrasound was repeated after a minimum of 6 months on treatment.Results:53 hyperuricaemic individuals with persistent, non-episodic foot pain not meeting the ACR/EULAR 2015 gout classification criteria were recruited. At baseline MTP US DC sign, erosion and tophus occurred in 62.5%, 20.8% and 49% of cases, respectively. No US features of gout occurred in controls. No significant difference was seen in baseline serum urate between cases (481±14 mg/dL) versus controls (437±14; p=NS). Serum urate in cases fell at 3 months (325±25; p<0.01) and 6 months (248±19; p<0.01). For cases, baseline 24-hour pain VAS (46±3.9) reduced at 3 months (32±4.1; p<0.05) and 6 months (21±5.2; p<0.05) of ULT. The 7-day pain VAS (59±3.9) decreased at 3 months (35±4.5; p<0.05) and 6 months (30±5.3; P<0.05). MFPDI (17±1.4) decreased at 3 month (13±1.8; p=<0.05) and 6 months (11±2.2; p=<0.05). When cases were grouped according to the presence (N=33) or absence (N=18) of DC sign on baseline US, no differences were observed for baseline pain scores. Following ULT however, 24-hour pain VAS were significantly lower in DC positive patients at 3 months (22±4.48 DC positive vs 42±6.14 DC negative; p<0.05) and 6 months (12.±5.4 vs 33±8.4; p<0.05). The 7-day pain VAS were significantly lower in DC positive patients at 3 months (23±4.6 vs 47±6.6; p<0.05) and MFDPI were significantly lower in DC positive patients at 3 months (10±1.9 DC positive vs 19±2.9 DC negative; p<0.05).Conclusion:These findings indicate that persistent, non-episodic foot pain in hyperuricaemia is both associated with US features of MSU deposition and is responsive to ULT. Symptomatic hyperuricaemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation. Changes to the ACR/ EULAR classification criteria to include non-episodic foot pain in the presence of US features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.References:[1]Stewart S, Dalbeth N, Vandal AC, Rome K. Characteristics of the first metatarsophalangeal joint in gout and asymptomatic hyperuricaemia: A cross-sectional observational study. J Foot Ankle Res. 2015;8(1):1–8.Disclosure of Interests:None declared