Differences in Achilles tendon stiffness in people with gout: a pilot study

Gout occurs as a result of a metabolic inefficiency to fully metabolise purines and is considered to be the most common inflammatory arthritis [1, 2]. The resultant production of highly insoluble monosodium urate crystals located in joints and tendons causes a range of symptoms [1, 2]. Gout has an increasing prevalence both in the UK and worldwide [1‐4]. While estimates vary, up to 6.8% of some populations are affected [3]. Gout is associated with acute attacks of severe joint pain and swelling, particularly affecting the foot [4]. Pain and impairment often do not entirely normalise after a gout flare-up has subsided [5], leading to general and foot-specific pain and disability, reduced ankle joint angular velocity and resulting in altered walking patterns [6‐8]. Taken together, pain, time off work, limitations in ones’ ability to move or undertake exercise and subsequent loss of participation in social activities all reduce quality of life for those with gout [6, 9, 10].

The Achilles tendon (AT) is a common location for the deposit of monosodium urate crystals, forming subcutaneous palpable bodies known as tophi [11]. These structures are located within the tendon and will affect the structural arrangement of the tendon fibres impacting on the mechanical properties and function of the AT [12]. In gout, there are also measurable signs of inflammation in the AT (e.g. intra tendinous power Doppler signals) [13]. Inflammatory markers are generally considered to be a hallmark of rheumatic disorders such as gout. Inflammatory processes alter the tissue composition, increasing water content, and can result in changes to tissue structure and tissue stiffness (or elasticity). While the AT is the strongest tendon in the body, it is frequently injured, and the pathology of those injuries is heterogeneous [14, 15]. The mechanical properties of tendons are key to the transmission of muscle tension to the skeleton, elastic energy storage and to limiting load stress on muscles [16]. Consequently, measurement of the structural properties of the tendon is an important part of understanding the changes that may occur and affect the background pathogenesis [17]. Clinicians commonly use ultrasound imaging (US) to visualise tendon structure in AT disorders, since the technique is minimally invasive, quick and often easily available for use [18]. Shear wave elastography (SWE) is a non-invasive and dynamic method of quantifying changes in tendon elasticity, involving application of a focused ultrasound pulse to the tissue being imaged [19‐21]. SWE is a type of US elastography that uses shear waves generated by a remote radiation force of focused ultrasonic beams to assess tissue elasticity. It measures the velocity of shear waves (in metres per second) moving through tissue, and displays these in a quantitative manner via a real-time elastogram, in which elasticity is portrayed as a colour-coded representation over a B-mode image. In SWE images stiffer tissues are red, while softer tissues are blue [22‐24]. Importantly in ultrasonography, previous work indicates SWE is more independent of user skill than other modes of US imaging [25]. A systematic review of SWE as a diagnostic tool indicated good correlation with conventional ultrasound results, MRI and clinical examination [26]. More recently, SWE per se has received attention with regard to conditions involving tendons. Compared to other methods commonly used, it has been shown to be a simple way to measure tendon stiffness and identify pathology with good precision and increased diagnostic accuracy [27]. A review of imaging modalities in gout has highlighted the value of ultrasound for monitoring monosodium urate deposition and damage associated with inflammation, but SWE was not reported upon [28]. We aimed to utilise SWE to identify differences in Achilles tendon stiffness in people with gout compared to controls (non-gout). We hypothesised that stiffness of the AT would be reduced by the inflammatory processes and the consequences of monosodium urate crystal deposits affecting the structure and function of the AT.

In total, 40 people with gout were recruited with 24 subsequently participating (60%). Of those not taking part, 8 declined and 5 subsequently excluded, two were subsequently not contactable and one did not attend their appointment. A population of 26 age/sex matched non-gout subjects were simultaneously recruited from the same clinical population.

Using shear wave elastography, we have for the first time, demonstrated that people with gout exhibit significantly lower stiffness in the AT compared with age/sex matched non-gout participants. Previously, Aubrey and colleagues [45] reported that those with mid-portion AT tendinopathy demonstrated significantly lower mean SWE velocities than did those with a non-pathological AT. The loss of Achilles tendon stiffness we identified in those with gout was often greater than that demonstrated using a similar protocol in otherwise healthy runners with known Achilles tendinopathy [34]. The mean SWE values determined by Payne et al. [34] ranged from 7.91 m/s-9.56 m/s compared with mean SWE values in our participants with gout of 4.75 m/s-10 m/s. Recent work [46] suggests Achilles tendinopathy in healthy subjects involves both thickening of the tendon and softening (as reflected in lower SWE values), however our participants with gout did not report symptoms of AT.

Tendon pathology in the lower limbs has been shown to be more frequent in those with gout than in those with either osteoarthritis or healthy controls [13, 47]. A systematic review and meta-analysis revealed that abnormal ultrasound findings (i.e. tendon thickening, increased vascularity, hypoechogenicity) in the AT were predictive of tendinopathy [48]. However in our findings from those with gout, tendon thickening did not appear to be present, nor were considerably higher intra-tendon power Doppler readings noted, possibly suggesting a different pathological model from standard tendinopathy. A previous US study [13] demonstrated a much higher prevalence of intra-tendinous tophi (73%) than in non-gout participants. MSU deposition has been reported in 15–48% of the AT using dual energy CT scanning techniques [18, 49]. Our conventional ultrasound findings were toward the upper end of these results, but not as high as Carroll et al. [13], which may reflect different population sampling strategies. Previously, Chhana et al. [12] reported that MSU crystals directly interact with tenocytes to reduce cell viability and function, which may contribute to tendon damage. We did not identify any correlation between the number of tophi and SWE measures, which may further support a different pathological model. None of the studies reviewed above have reported SWE measurements. However currently, the lack of agreed and validated SWE values for tendinopathy may limit its use in the formal assessment of tendon damage [50].

Previous clinical and laboratory-based studies have reported weaker foot/leg muscles in those with gout than in non-gout participants [51, 52]. This muscle weakness was also associated with greater levels of foot pain [53]. Those with gout also exhibited slower walking speeds than control participants [53]. Current international recommendations for gout management [54] highlight the importance of diet together with lifestyle changes such as increased levels of physical activity. In 2008 the UK National Institute for Health and Care Excellence (NICE) [55] produced management recommendations for osteoarthritis that focused on the lower limb and emphasized that muscle strengthening should be undertaken before increasing aerobic activity. While we did not measure muscle strength, our contention here is that those participants with considerable loss of tendon stiffness might find that some types of increased load-bearing exercise have the potential to hasten the end stages of the continuum model of tendon pathology [56].

A key strength of our work is that we recruited people from a community-based outpatient clinic, and as such our participants were broadly representative of patients with gout treated in primary care. None were experiencing symptoms of an acute gout flare, nor Achilles tendinosis, yet significant loss of tendon stiffness was demonstrated. The primary limitation of our study was that the researcher (SO) undertaking US scans and SWE readings was not blinded to participant diagnosis, which may have led to inadvertent bias. Pathologies consistent with gout when seen on ultrasound are highly characteristic, typically with excellent inter-rater reliability [13]. Consequently, it is difficult to completely blind sonographers to the underlying diagnosis, but the addition of a second sonographer may add to the reliability of SWE measures in future work. The US machine we used for SWE readings also has a limitation where a maximum SWE value of 10 m/s can be recorded, after which a value of HIGH is given. Consequently, there may be a ceiling effect to some of the measurements leading to a possible underestimation of the differences in AT stiffness. Moreover, there has been limited use of SWE to assess soft tissue stiffness in other inflammatory arthropathies, making direct comparisons difficult. For example, in Ankylosing Spondylitis significant structural impairment of the Achilles tendon was noted using sonoelastography [57]. However, rather than reporting SWE values, areas of the AT were simply colour coded into normal or pathological, making direct comparison impossible.

Subjects with gout demonstrated significantly reduced Achilles tendon stiffness compared to non-gout controls. From a clinical standpoint, our SWE findings for the AT in those with gout were similar to SWE measurements in subjects with Achilles tendinopathy who did not have gout. This finding suggests the AT in people with gout may be less effective at transmitting muscle force and potentially more susceptible to further pathology and injury.