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Comparison of dual-energy CT, ultrasound and surface measurement for assessing tophus dissolution during rapid urate debulking

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Abstract

Tophaceous gout is painful and impairs quality of life. The optimal modality for assessing tophus resolution in response to urate-lowering treatment remains poorly defined. Using pegloticase as a model system for resolving tophi, we compared multiple imaging and physical diagnostic strategies for assessing tophus resolution. A 32-year-old subject with chronic refractory tophaceous gout was enrolled and received 6 months of pegloticase treatment. Measurements of tophi using vernier calipers (monthly), photographs and musculoskeletal ultrasound (MSK-US; every 3 months), and dual-energy CT (DECT) were compared. Pegloticase persistently lowered the patient’s sUA to <0.5 mg/dl. After 6 months, caliper measurements revealed 73, 60, and 61% reductions of three index tophi, while MSK-US revealed 47, 65, and 48% reductions. In contrast, DECT revealed 100% resolution of monosodium urate deposition in all three index tophi, and resolution or improvement of all other tophi identified. On caliper and MSK-US measurement, index tophus size fluctuated, with some lesions enlarging before ultimately contracting. Correlation between assessment modalities during tophus resolution may be poor. DECT identifies urate deposits invisible to physical exam and reveals that some urate deposits completely resolve even as their physically/sonographically measurable lesions persist. Recognition of urate resorption during the urate-lowering process may be confounded by fluctuating lesion volumes during initial tophus breakdown. While DECT was superior for identifying total (including occult) urate deposition, and assessing volume of deposits, other modalities may permit better assessment of non-urate tophus components.

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References

  1. Zhu Y, Pandya BJ, Choi HK (2011 Jul 28) Prevalence of gout and hyperuricemia in the US general population. Arthritis Rheum

  2. Zhu Y, Pandya BJ, Choi HK (2012 Jul) Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med 125(7):679–687 e671

  3. Keenan RT, O'Brien WR, Lee KH, Crittenden DB, Fisher MC, Goldfarb DS et al (2011 Feb) Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med 124(2):155–163

    Article  PubMed  Google Scholar 

  4. Becker MA, Schumacher HR, Benjamin KL, Gorevic P, Greenwald M, Fessel J et al (2009 May) Quality of life and disability in patients with treatment-failure gout. J Rheumatol 36(5):1041–1048

    Article  PubMed  Google Scholar 

  5. Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E (2014 Jan) Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis 73(1):177–182

    Article  CAS  PubMed  Google Scholar 

  6. Khanna P, Khanna D, Storgard C, Baumgartner S, Morlock R (2016 Jan) A world of hurt: failure to achieve treatment goals in patients with gout requires a paradigm shift. Postgrad Med 128(1):34–40

    Article  PubMed  Google Scholar 

  7. Perez-Ruiz F, Herrero-Beites AM, Carmona L (2011 Dec) A two-stage approach to the treatment of hyperuricemia in gout: the “dirty dish” hypothesis. Arthritis Rheum 63(12):4002–4006

    Article  CAS  PubMed  Google Scholar 

  8. McQueen FM, Doyle A, Dalbeth N (2011) Imaging in gout—what can we learn from MRI, CT, DECT and US? Arthritis Res Ther 13(6):246

    Article  PubMed  PubMed Central  Google Scholar 

  9. Baraf HS, Becker MA, Gutierrez-Urena SR, Treadwell EL, Vazquez-Mellado J, Rehrig CD et al (2013) Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther. 15(5):R137

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dalbeth N, McQueen FM, Singh JA, MacDonald PA, Edwards NL, Schumacher HR Jr et al (2011 Jul) Tophus measurement as an outcome measure for clinical trials of chronic gout: progress and research priorities. J Rheumatol 38(7):1458–1461

    Article  PubMed  Google Scholar 

  11. Suh YS, Cheon YH, Kim JE, Kim JM, Kim SH, Lee WS et al (2016 Nov) Usefulness of plain radiography for assessing hypouricemic treatment response in patients with tophaceous gout. Int J Rheum Dis 19(11):1183–1188

    Article  CAS  PubMed  Google Scholar 

  12. Araujo EG, Manger B, Perez-Ruiz F, Thiele RG (2016 Aug) Imaging of gout: new tools and biomarkers? Best Pract Res Clin Rheumatol 30(4):638–652

    Article  PubMed  Google Scholar 

  13. Howard RG, Pillinger MH, Gyftopoulos S, Thiele RG, Swearingen CJ, Samuels J (2011 Oct) Reproducibility of musculoskeletal ultrasound for determining monosodium urate deposition: concordance between readers. Arthritis care & research 63(10):1456–1462

    Article  CAS  Google Scholar 

  14. Perez-Ruiz F, Martin I, Canteli B (2007 Sep) Ultrasonographic measurement of tophi as an outcome measure for chronic gout. J Rheumatol 34(9):1888–1893

    PubMed  Google Scholar 

  15. Choi HK, Al-Arfaj AM, Eftekhari A, Munk PL, Shojania K, Reid G et al (2009 Oct) Dual energy computed tomography in tophaceous gout. Ann Rheum Dis 68(10):1609–1612

    Article  CAS  PubMed  Google Scholar 

  16. Artmann A, Ratzenbock M, Noszian I, Trieb K (2010 Mar) Dual energy CT—a new perspective in the diagnosis of gout. Rofo 182(3):261–266

    Article  CAS  PubMed  Google Scholar 

  17. Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C (2009 Jun) Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol 36(6):1273–1282

    Article  CAS  PubMed  Google Scholar 

  18. Crittenden DB, Pillinger MH (2013) New therapies for gout. Annu Rev Med 64:325–337

    Article  CAS  PubMed  Google Scholar 

  19. Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL et al (2011 Aug 17) Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 306(7):711–720

    Article  CAS  PubMed  Google Scholar 

  20. Araujo EG, Bayat S, Petsch C, Englbrecht M, Faustini F, Kleyer A et al (2015) Tophus resolution with pegloticase: a prospective dual-energy CT study. RMD Open 1(1):e000075

    Article  PubMed  PubMed Central  Google Scholar 

  21. Perez-Ruiz F, Calabozo M, Pijoan JI, Herrero-Beites AM, Ruibal A (2002 Aug) Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum 47(4):356–360

    Article  CAS  PubMed  Google Scholar 

  22. Dalbeth N, Schauer C, Macdonald P, Perez-Ruiz F, Schumacher HR, Hamburger S et al (2011 Apr) Methods of tophus assessment in clinical trials of chronic gout: a systematic literature review and pictorial reference guide. Ann Rheum Dis 70(4):597–604

    Article  PubMed  Google Scholar 

  23. Thiele RG, Schlesinger N (2007 Jul) Diagnosis of gout by ultrasound. Rheumatology (Oxford) 46(7):1116–1121

    Article  CAS  Google Scholar 

  24. Choi HK, Burns LC, Shojania K, Koenig N, Reid G, Abufayyah M et al (2012 Sep) Dual energy CT in gout: a prospective validation study. Ann Rheum Dis 71(9):1466–1471

    Article  PubMed  Google Scholar 

  25. Chhana A, Dalbeth N (2015 Mar) The gouty tophus: a review. Curr Rheumatol Rep 17(3):19

    Article  PubMed  Google Scholar 

  26. Martillo MA, Nazzal L, Crittenden DB (2014) The crystalization of monosodium urate. Current Rheumatology Reports In press

Download references

Acknowledgments

We thank Ms. Margaret Andrews, RN, for coordinating this study, Ms. Ranit Shriky for administrative support, and Drs. Cheongeun Oh, PhD, and David Goldfarb, MD, for helpful input into study design and interpretation. This study was supported in part by an investigator-initiated grant from Savient/Crealta, to Dr. Pillinger. Neither Savient nor Crealta played any role in the design or execution of the study, or the preparation or review of the manuscript. Dr. Krasnokutsky receives support from an Investigator Award from the Rheumatology Research Foundation. Dr. Pillinger receives support from NYU CTSA grant 1UL1TR001445 from the National Center for the Advancement of Translational Science (NCATS), NIH.

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Author notes

  1. Dodji V. Modjinou and Svetlana Krasnokutsky contributed equally to this manuscript.

Authors and Affiliations

  1. The Crystal Diseases Study Group, New York University School of Medicine, New York, NY, USA

    Dodji V. Modjinou, Svetlana Krasnokutsky, Soterios Gyftopoulos, Virginia C. Pike, Elaine Karis, Robert T. Keenan, Kristen Lee, Daria B. Crittenden, Jonathan Samuels & Michael H. Pillinger

  2. Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, USA

    Dodji V. Modjinou, Svetlana Krasnokutsky, Virginia C. Pike, Elaine Karis, Robert T. Keenan, Kristen Lee, Daria B. Crittenden, Jonathan Samuels & Michael H. Pillinger

  3. Division of Rheumatology, Department of Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA

    Dodji V. Modjinou

  4. Division of Musculoskeletal Radiology, Department of Radiology, New York University School of Medicine, New York, NY, USA

    Soterios Gyftopoulos

  5. Division of Rheumatology, Duke University Medical Center, Durham, NC, USA

    Robert T. Keenan

  6. Division of Rheumatology, NYU Hospital for Joint Diseases, 301 East 17th Street, Room 1410, New York, NY, 10003, USA

    Michael H. Pillinger

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  1. Dodji V. Modjinou
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  2. Svetlana Krasnokutsky
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  3. Soterios Gyftopoulos
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  5. Elaine Karis
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  7. Kristen Lee
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  8. Daria B. Crittenden
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  9. Jonathan Samuels
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  10. Michael H. Pillinger
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Corresponding author

Correspondence to Michael H. Pillinger.

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Conflict of interest statement

Dr. Pillinger is currently or has recently been a consultant for Crealta, Horizon, AstraZeneca, SOBI and Ironwood, serves as a study site investigator for Takeda. Dr. Krasnokutsky is currently or has recently been a consultant for Crealta, Horizon, AstraZeneca and Ironwood. Dr. Keenan is a consultant for Horizon, Ironwood and AstraZeneca. Dr. Crittenden is currently employed by Amgen. Dr. Karis has served on a speakers bureau for Takeda. No other author has any disclosures.

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Modjinou, D.V., Krasnokutsky, S., Gyftopoulos, S. et al. Comparison of dual-energy CT, ultrasound and surface measurement for assessing tophus dissolution during rapid urate debulking. Clin Rheumatol 36, 2101–2107 (2017). https://doi.org/10.1007/s10067-017-3729-z

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  • DOI: https://doi.org/10.1007/s10067-017-3729-z

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