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Clinical and epidemiological research
Concise report
Tendon involvement in the feet of patients with gout: a dual-energy CT study
  1. Nicola Dalbeth1,
  2. Ramanamma Kalluru1,
  3. Opetaia Aati1,
  4. Anne Horne1,
  5. Anthony J Doyle2,
  6. Fiona M McQueen3
  1. 1Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  2. 2Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  3. 3Department of Molecular Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  1. Correspondence to Dr Nicola Dalbeth, Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New Zealand; n.dalbeth{at}auckland.ac.nz

Abstract

Objectives To examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT).

Methods Ninety-two patients with tophaceous gout had DECT scanning of both feet. Two readers scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites).

Results MSU crystal deposition was observed by both readers in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons), followed by the peroneal tendons (18.1%). Tibialis anterior and the extensor tendons were involved less commonly (7.6–10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the enthesis alone was more common in the Achilles tendon (OR (95% CI) 74.5 (4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR (95% CI) 6.8 (3.6 to 13.0), p<0.0001).

Conclusions Tendons are commonly affected by MSU crystal deposition in patients with tophaceous gout. The patterns of MSU crystal deposition suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.

  • Gout
  • Tendinitis
  • Inflammation

https://doi.org/10.1136/annrheumdis-2012-202786

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    Gout is a disorder characterised by deposition of monosodium urate (MSU) crystals. In advanced gout, collections of MSU crystals within tophi become clinically apparent within both subcutaneous tissues and articular structures. Owing to the widespread availability of plain radiography, involvement of bone and joints is widely recognised in chronic gout.1 Advanced imaging studies using ultrasonography, MRI and CT have suggested that tendons and ligaments may also be affected by MSU crystal deposition,2–4 but the involvement of these structures has not been systematically characterised. Dual-energy CT (DECT) is a recently developed technology that enables excellent visualisation of soft tissue structures, such as tendons and ligaments, and detection of MSU crystal deposits.5 The aim of this study was to examine the frequency and patterns of tendon and ligament involvement in the feet of patients with gout using DECT.

    Patients and methods

    Ninety-two patients with tophaceous gout were prospectively recruited from rheumatology clinics in Auckland, New Zealand. All patients had a history of gout according to American College of Rheumatology classification criteria6 and at least one subcutaneous tophus on clinical examination. Women of childbearing age were excluded from the study. The Northern Regional Ethics Committee approved the study. All patients provided written informed consent before inclusion in the study.

    Clinical data recorded included demographic details (age, sex, ethnicity), gout history (disease duration, frequency of gout flares, gout treatments), medication, physical examination (including tophus count), Health Assessment Questionnaire (HAQ)-II, and laboratory tests including serum urate concentration. Plain radiographs of the hands and feet were scored using the gout-modified Sharp–van der Heijde score.1

    DECT scans of the feet were performed at the same study visit on a dual x-ray tube 128 detector row scanner (Somatom Definition Flash; Siemens Medical, Erlangen, Germany), and analysed as previously described.7 For the 80 kV images, fluid was set at 50 Hounsfield units (HU), the ratio for urate at 1.28, minimum HU 150 and smoothing range 5. For the 140 kV images, fluid was set at 50 HU and maximum HU at 500. Radiation exposure related to the DECT scan was calculated at 0.05 mSv (natural background radiation levels in New Zealand is 2 mSv/year).

    Two readers (RK and OA) scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites). Examples of bone and tendon involvement are shown in online supplementary figure S1. For affected tendons and ligaments, involvement was recorded as entheseal and/or non-entheseal (entheseal involvement was defined as MSU crystal deposition at the point of tendon/ligament insertion into bone).

    Data were analysed using SPSS software v20. Means with SD and percentages were used to describe the clinical characteristics of patients. Reliability was assessed using agreement statistics including κ values. Pearson's correlation tests were used to describe the associations between variables. Differences between groups were analysed using t tests and χ2 analysis with calculation of OR with 95% CI. All tests were two tailed, and p values <0.05 were considered significant.

    Results

    Clinical characteristics and DECT findings: patient level analysis

    The clinical characteristics of the patients are shown in online supplementary table S1. Patients were predominantly middle-aged men, with over half of Maori or Pacific ethnicity. All patients had at least one clinically apparent subcutaneous tophus, and mean disease duration was more than 20 years.

    Inter-reader agreement for DECT involvement was 94.7% at all bone sites and 88.0% at all tendon/ligament sites, and the respective Cohen's κ was 0.77 and 0.58. For a stringent analysis, MSU crystal deposition was considered present at each site only if reported by both readers.

    The DECT scans showed MSU crystal deposition involving bone in 66/92 (72%) patients and involving tendons/ligaments in 55/92 (65%) patients. Of the 66 patients with bone involvement, 52 (79%) also had tendon/ligament involvement. Of the 55 patients with tendon/ligament involvement, 52 (95%) also had bone involvement. Tendon involvement was more common if bone involvement was also present (OR (95% CI)=28.5 (7.5 to 108.8), p<0.0001). The mean (SD) number of involved bones was 5.4 (6.9), and the mean (SD) number of involved tendons/ligaments was 3.4 (4.0). There was a high correlation between mean number of affected bones and tendons, r=0.92, p<0.0001. The number of affected bones and tendons correlated with radiographic damage scores, serum urate concentrations and clinical tophus count (see online supplementary table S2 and supplementary text).

    Sites of involvement: site-by-site analysis

    MSU crystal deposition was observed in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The frequency of MSU crystal deposition at each assessed site is shown for tendons/ligaments in table 1 and for bones in table 2. The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons) followed by the peroneal tendons (18.1%) (figure 1). Tibialis anterior and the extensor tendons were involved less commonly (7.6–10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the Achilles tendon was present at a similar frequency to involvement at the first metatarsal (MT) head (38% of all first MT heads).

    View this table:
    Table 1

    Sites of tendon/ligament involvement (1840 sites assessed)

    View this table:
    Table 2

    Sites of bone involvement (3864 sites assessed)

    Figure 1
    Figure 1

    Representative dual-energy CT images showing involvement of tendons in two patients with tophaceous gout. (A) and (B) show three-dimensional volume-rendered images demonstrating monosodium urate (MSU) crystal deposition in the Achilles and peroneal tendons in both patients. (C) and (D) Two-dimensional sagittal images confirming MSU crystal deposition (green) at (C) the Achilles enthesis and (D) within the body of the Achilles tendon.

    Patterns of tendon/ligament involvement: site-by-site analysis

    In the 72 Achilles tendons with MSU crystal deposition, 27 (38%) had only non-entheseal involvement, 29 (40%) had both entheseal and non-entheseal involvement, and 16 (22%) had only entheseal involvement. In contrast, entheseal involvement was less common at the other 127 affected tendon/ligament sites; 102 (80.3%) had only non-entheseal involvement, 25 (19.9%) had both entheseal and non-entheseal involvement, and 0 (0%) had only entheseal involvement. Involvement of the enthesis alone was more common in the Achilles tendon (OR 74.5 (95% CI 4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR 6.8 (95% CI 3.6 to 13.0), p<0.0001).

    Discussion

    These data show that MSU crystal deposition within tendons is common in patients with longstanding tophaceous gout. As with bone and joint involvement, MSU crystal deposition occurs preferentially within tendons at certain sites in gout. The body and enthesis of the Achilles tendon are major sites of involvement. The finding of preferential MSU crystal deposition at certain anatomical sites raises interesting questions about the pathogenesis of gout, and suggests that biomechanical strain or other local factors may contribute to formation of MSU crystals. It is possible that microtrauma at sites of increased load may lead to release of matrix proteins or alterations in tissue pH, which promote crystal nucleation and growth in the context of elevated tissue MSU crystal concentrations.8

    Tendons play an important role in joint stability, flexibility and efficiency. The impact of tendon MSU crystal deposition on musculoskeletal function is currently uncertain. Tendon rupture due to tophus infiltration has been described in patients with chronic gout, although this would appear to be an uncommon event.3 ,9 ,10 Many parameters of gait are impaired in patients with chronic gout even in the absence of a flare.11 Elucidation of the impact of tendon involvement on musculoskeletal function may be technically challenging in gout, particularly given the concomitant involvement of bone.

    Although some studies have reported sites of tophus deposition and bone erosion in gout,12 ,13 systematic analysis of sites of MSU crystal deposition in patients with gout has not previously been possible. This study highlights the potential of DECT in characterising disease and understanding the pathogenesis of disease. In addition to providing high-definition images of bone and soft tissue structures, this technique detects the chemical composition of urate, and allows specific visualisation of urate. It should be noted that the imaging acquisition protocol used in this study was limited to 5 cm proximal from the ankle joint. Therefore, not all of the Achilles tendon was captured, and it is possible that our data may underestimate involvement of the proximal Achilles tendon. Although agreement was very good for bone sites, it was moderate for tendon sites. Importantly, the analysis specified that urate involvement was present only if observed by both observers.

    This study has shown lower rates of MSU crystal deposits at the first MT head than previous US studies.14 ,15 Our previous DECT analysis has shown marked variation in the urate content within tophi,7 and this observation may explain the slightly lower MSU crystal deposition at this site using DECT. DECT is able to accurately visualise uric acid stones of ≥3 mm.16 To date, the reliability and resolution of DECT have not been compared with other advanced imaging in gout, and it is possible that very small MSU crystal deposits were not detected using this method. We also acknowledge that the cross-sectional nature of this study does not allow us to determine the temporal sequence of MSU crystal deposition in patients with gout. Longitudinal DECT studies in patients with shorter disease duration will be of great interest in further understanding the natural history of this condition.

    In summary, soft tissue structures are often affected by MSU crystal deposition in patients with tophaceous gout. The Achilles tendon and enthesis are major sites of involvement in gout. The patterns of involvement at certain tendon sites suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.

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    View Abstract

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

      Files in this Data Supplement:

    Footnotes

    • Handling editor Tore K Kvien

    • Contributors ND (the guarantor) accepts full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish. ND conceived of the study, contributed to the data interpretation, and drafted the manuscript. RK contributed to the study design and analysed the DECT scans. OA recruited patients, analysed the DECT scans and managed the data entry. AH contributed to patient recruitment and data management. FMM and AJD contributed to the study design, data interpretation and manuscript drafting. All authors read and approved the final manuscript.

    • Funding This study was funded by the Health Research Council of New Zealand (Grant number 09/111D).

    • Competing interests None.

    • Patient consent Obtained.

    • Ethics approval Northern Regional Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.