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A Clinical and Sonographic Investigation of the First Metatarsophalangeal Joint in Gout and Asymptomatic Hyperuricaemia: a Comparison with Normouricaemic Individuals

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A Clinical and Sonographic Investigation of the First Metatarsophalangeal Joint in Gout and Asymptomatic Hyperuricaemia: a Comparison with Normouricaemic Individuals A clinical and sonographic investigation of the first metatarsophalangeal joint in gout and asymptomatic hyperuricaemia: A comparison with normouricaemic individuals Sarah Stewart A thesis submitted to Auckland University of Technology in fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) 2016 School of Clinical Sciences 1 Abstract Background: Although hyperuricaemia is required for the development of symptomatic gout, many individuals with hyperuricaemia remain asymptomatic. However, ultrasonography has identified urate deposition in people with asymptomatic hyperuricaemia. Urate crystal deposition and gout-related features have a certain propensity for the first metatarsophalangeal joint (1MTP). Despite the importance of normal structure and function of the 1MTP, it is unclear how this joint is impaired in people with gout and asymptomatic hyperuricaemia and whether this relates to underlying sonographic pathology. This thesis aimed to (i) identify clinical characteristics and (ii) sonographic features of the 1MTP in participants with gout and participants with asymptomatic hyperuricaemia; and (iii) determine the association between clinical and sonographic characteristics of the 1MTP while accounting for the diagnostic group. Methods: This two-arm cross-sectional study involved participants with gout (n = 23), asymptomatic hyperuricaemia (n = 29), and age- and sex-matched normouricaemic controls (n = 34) without acute arthritis at the time of assessment. Clinically assessed characteristics included patient-reported outcomes related to foot and lower limb pain, disability and impairment; 1MTP structural and functional characteristics including joint range of motion (ROM), muscle force, hallux valgus severity and foot posture; neurovascular characteristics including temperature, vibration perception and protective sensation; and dynamic outcomes including spatiotemporal gait characteristics and barefoot plantar pressure measurements. Ultrasonography was used to assess 1MTPs for the double contour sign, tophus, erosion, effusion, synovial hypertrophy, snowstorm, synovitis and cartilage thickness. Results: All participants were middle-aged men. Compared to controls, participants with gout reported greater 1MTP pain (P = 0.014), greater foot pain and disability (MFPDI) (P < 0.001), decreased lower limb function for daily living (P = 0.002) and recreational (P<0.001) activities, increased activity limitation (P = 0.002), reduced ROM (P < 0.001), reduced plantarflexion force (P = 0.012), increased 1MTP temperature (P < 0.05), more loss of protective sensation (OR 15.6, P = 0.21) and more severe hallux valgus (OR 0.3 P = 0.041). Compared to controls, participants with asymptomatic hyperuricaemia had more disabling foot pain (OR 4.2, P = 0.013), increased activity limitation (P = 0.033), decreased lower limb function for daily living (P = 0.026) and recreational (P = 0.010) activities, increased 1MTP plantarflexion force (P = 0.004) and a more pronated foot posture (P = 0.036). Compared to controls, participants with gout demonstrated increased step time (P = 0.022) and stance time (P = 0.022), and reduced velocity (P = 0.050). Participants with gout also walked with decreased peak pressure at the heel (P = 0.012) and 2 hallux (P = 0.036) and increased peak pressure (P < 0.001) and pressure time integrals (P = 0.005) at the midfoot. Compared to controls, participants with asymptomatic hyperuricaemia demonstrated increased support base (P = 0.002), double support time (P < 0.001) and cadence (P = 0.028), and reduced swing time (P = 0.019) and single support time (P = 0.020), as well as increased pressure at the midfoot (P = 0.013), first metatarsal (P = 0.015) and second metatarsal (P = 0.007). Compared to controls, participants with gout and asymptomatic hyperuricaemia had more double contour sign (odds ratio [OR] 3.91, P = 0.011 and OR 3.81, P = 0.009, respectively). Participants with gout also had more erosion (OR 10.13, P = 0.001) and synovitis (OR 9.00, P < 0.001) and had greater tophus and erosion diameters (P = 0.035 and P < 0.001, respectively). The double contour sign was associated with higher MFPDI scores (P < 0.001). Tophus was associated with higher MFPDI scores (P < 0.001), increased temperature (P = 0.005) and reduced walking velocity (P = 0.001). Conclusions: This study has shown that urate deposition, synovitis and bone erosion are common at the 1MTP in participants with gout, even in the absence of acute arthritis. Participants with gout also demonstrated 1MTP-specific changes indicative of subclinical inflammation. Although individuals with asymptomatic hyperuricaemia lack ultrasound features of inflammation or bone changes, they demonstrate a similar frequency of urate deposition. They also report high levels of foot- and lower limb-related pain and disability. Sonographic features of urate deposition, rather than soft tissue inflammation or erosion, are associated with patient-reported foot pain and disability, while the presence of tophus is associated with impaired functional characteristics. 3 Table of contents Abstract ........................................................................................................................................ 2 List of tables................................................................................................................................ 10 List of figures .............................................................................................................................. 12 Attestation of authorship .......................................................................................................... 13 PhD research outputs ................................................................................................................. 14 Peer-reviewed publications .................................................................................................... 14 Refereed conference proceedings .......................................................................................... 14 Acknowledgements .................................................................................................................... 16 Chapter one: An introduction to gout and hyperuricaemia ..................................................... 18 1.1 Introduction ...................................................................................................................... 18 1.2 History ............................................................................................................................... 18 1.3 Epidemiology ..................................................................................................................... 19 1.3.1 Prevalence and incidence of gout and hyperuricaemia ............................................ 19 1.3.2 Risk factors ................................................................................................................. 20 1.3.2.1 Genetic factors .................................................................................................... 20 1.3.2.2 Dietary factors ..................................................................................................... 20 1.3.2.3 Comorbidities ...................................................................................................... 21 1.3.2.4 Medications ........................................................................................................ 22 1.4 Pathophysiology ................................................................................................................ 22 1.5 Microscopy ........................................................................................................................ 25 1.6 Classification of gout ......................................................................................................... 26 1.7 Clinical staging ................................................................................................................... 28 1.8 Clinical features of gout .................................................................................................... 29 1.8.1 Acute gouty arthritis .................................................................................................. 29 1.8.2 Chronic gouty arthropathy and tophaceous gout ..................................................... 31 1.9 The burden of gout ........................................................................................................... 32 1.10 Management ................................................................................................................... 34 1.10.1 Asymptomatic hyperuricaemia ................................................................................ 34 1.10.2 Acute gouty arthritis ................................................................................................ 35 1.10.2.1 Pharmacological ................................................................................................ 35 1.10.2.2 Non-pharmacological ........................................................................................ 37 1.10.3 Long-term management of gout.............................................................................. 37 4 1.10.3.1 Pharmacological therapy .................................................................................. 37 1.10.3.2 Patient and practitioner education ................................................................... 39 1.10.3.3 Diet and
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