Skip to main content

Advertisement

SpringerLink
Log in

Treatment of Enthesitis, Dactylitis and Nail Lesions in Psoriatic Arthritis

  • Seronegative Arthritis (N Haroon, Section Editor)
  • Published:
Current Treatment Options in Rheumatology Aims and scope Submit manuscript

Abstract

Purpose of review

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with the skin disease, psoriasis. It is a highly heterogeneous disorder, not only in the musculoskeletal phenotype but also in its cutaneous manifestations. Enthesitis, dactylitis, and nail changes are the hallmark of the disease, and experts in the field believe that the initiating process of PsA is a deep Koebner phenomenon which triggers enthesitis and the subsequent disease process and progression. We aim to discuss the most recent advances in the treatment of enthesitis, dactylitis, and nail changes in psoriatic arthritis.

Recent findings

Various treatment regimens have been used to control the above manifestations of PsA, including conventional synthetic disease-modifying agents (csDMARDs), biologic disease-modifying agents (bDMARDs), and newer therapies which include interleukin (IL)-12/23 antagonist (ustekinumab), IL-17 antagonists (secukinumab and ixekizumab), as well as small molecules including the Janus kinase (JAK) inhibitors and phosphodiesterase-4 inhibitor (apremilast). The csDMARDs include methotrexate, sulphasalazine, leflunomide, as well as cyclosporine.

Summary

These modalities of treatment are further discussed in this review. Rapid escalation of therapy in patients who have an inadequate response to conventional therapy results in better outcomes. Future research includes specific antibodies against the p19 subunit of IL-23.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum. 1973;3:55–78.

    Article  PubMed  CAS  Google Scholar 

  2. McGonagle D. Enthesitis: an autoinflammatory lesion linking nail and joint involvement in psoriatic disease. J Eur Acad Dermatol Venereol. 2009;23:9–13.

    Article  PubMed  CAS  Google Scholar 

  3. Farber EM, Nall L. Nail psoriasis. Cutis. 1992;50:174–8.

    PubMed  CAS  Google Scholar 

  4. Elkayam O, Ophir J, Yaron M, et al. Psoriatic arthritis: interrelationships between skin and joint manifestations related to onset, course and distribution. Clin Rheumatol. 2000;19:301–5.

    Article  PubMed  CAS  Google Scholar 

  5. • Williamson L, Dalbeth N, Dockerty JL, et al. Extended report: nail disease in psoriatic arthritis—clinically important, potentially treatable and often overlooked. Rheumatology. 2004;43:790–4. This report outlines the importance of nail disease assessment and treatment in PSA.

    Article  PubMed  CAS  Google Scholar 

  6. • Helliwell PS, Firth J, Ibrahim GH, et al. Development of an assessment tool for dactylitis in patients with psoriatic arthritis. J Rheumatol. 2005;32:1745–50. This paper outlines an important assessment tool for dactylitis in the ongoing management of PsA.

    PubMed  Google Scholar 

  7. Ritchlin CT. Pathogenesis of psoriatic arthritis. Curr Opin Rheumatol. 2005;17:406–12.

    Article  PubMed  Google Scholar 

  8. Rich P, Scher R. Nail psoriasis severity index: a useful tool for evaluation of nail psoriasis. J Am Acad Dermatol. 2003;49:206–12.

    Article  PubMed  Google Scholar 

  9. • Chandran V, Gottlieb A, Cook RJ, et al. International multicenter psoriasis and psoriatic arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis. Arthritis Rheum. 2009;61:1235–42. This paper discusses the assessment of the various components of PsA.

    Article  PubMed  Google Scholar 

  10. Cassell SE, Bieber JD, Rich P, et al. The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis. J Rheumatol. 2007;34:123–9.

    PubMed  Google Scholar 

  11. Mander M, Simpson JM, McLellan, et al. Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis. Ann Rheum Dis. 1987;46:197–202.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003;62:127–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Maksymowych WP, Mallon C, Morrow S, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68:948–53.

    Article  PubMed  CAS  Google Scholar 

  14. Ibrahim G, Groves C, Chandramohan M, et al. Clinical and ultrasound examination of the Leeds enthesitis index in psoriatic arthritis and rheumatoid arthritis. Rheumatology(Oxford). 2011;2011:731917.

    CAS  Google Scholar 

  15. Freeston JE, Coates LC, Helliwell PS, et al. Is there subclinical enthesitis in early psoriatic arthritis? A clinical comparison with power doppler ultrasound. Arthritis Care Res (Hoboken). 2012;64:1617–21.

    Article  CAS  Google Scholar 

  16. Husic R, Gretler J, Felber A, et al. Disparity between ultrasound and clinical findings in psoriatic arthritis. Ann Rheum Dis. 2014;73:1529–36.

    Article  PubMed  Google Scholar 

  17. Brenner M, Molin S, Ruebsam K, et al. Generalized pustular psoriasis induced by systemic glucocorticosteroids: four cases and recommendations for treatment. Br J Dermatol. 2009;161:964–6.

    Article  PubMed  CAS  Google Scholar 

  18. Eder L, Chandran V, Ueng J, et al. Predictors of response to intra-articular steroid injection in psoriatic arthritis. Rheumatology (Oxford). 2010;49:1367–73.

    Article  Google Scholar 

  19. Montesinos MC, Desai A, Cronstein BN. Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis. Arthritis Res Ther. 2006;8(2):R53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Black RL, O’Brien WM, VanScott EJ, et al. Methotrexate therapy in psoriatic arthritis; a double-blind study on 21 patients. JAMA. 1964;189:743–7.

    Article  PubMed  CAS  Google Scholar 

  21. Willkens RF, Williams HJ, Ward JR, et al. Randomized, double-blind, placebo-controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum. 1984;27:376–81.

    Article  PubMed  CAS  Google Scholar 

  22. Espinoza LR, Zakraoui L, Espinoza CG, et al. Psoriatic arthritis: clinical response and side effects to methotrexate therapy. J Rheumatol. 1992;19:872–7.

    PubMed  CAS  Google Scholar 

  23. Abu-Shakra M, Gladman DD, et al. Long-term methotrexate therapy in psoriatic arthritis: clinical and radiological outcome. J Rheumatol. 1995;22:241–5.

    PubMed  CAS  Google Scholar 

  24. Kingsley GH, Kowalczyk A, Taylor H, et al. A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford). 2012;51:1368–77.

    Article  CAS  Google Scholar 

  25. •• Armstrong AW, Tuong W, Love TJ, et al. Treatments for nail psoriasis: a systematic review by the GRAPPA Nail Psoriasis Work Group. J Rheumatol. 2014;41:2306–14. Important and insightful review and recommendations by GRAPPA working groups.

    Article  PubMed  CAS  Google Scholar 

  26. •• Orbai AM, Weitz J, Siegel EL, GRAPPA Enthesitis Working Group, et al. A systematic review of treatment effectiveness and outcome measures for enthesitis in psoriatic arthritis. J Rheumatol. 2014;41:2290–4. Important and insightful review and recommendations by GRAPPA working groups.

    Article  PubMed  CAS  Google Scholar 

  27. •• Rose S, Toloza S, Bautista-Molano W, GRAPPA Dactylitis Study Group, et al. Comprehensive treatment of dactylitis in psoriatic arthritis. J Rheumatol. 2014;41:2295–300. Important and insightful review and recommendations by GRAPPA working groups.

    Article  PubMed  Google Scholar 

  28. Nash P, Lubrano E, Cauli A, et al. Updated guidelines for the management of axial disease in psoriatic arthritis. J Rheumatol. 2014;41:2286–9.

    Article  PubMed  Google Scholar 

  29. Farr M, Kitas GD, Waterhouse L, et al. Sulphasalazine in psoriatic arthritis: a double-blind placebo-controlled study. Br J Rheumatol. 1990;29:46–9.

    Article  PubMed  CAS  Google Scholar 

  30. Gupta AK, Grober JS, Hamilton TA, et al. Sulfasalazine therapy for psoriatic arthritis: a double-blind, placebo-controlled trial. J Rheumatol. 1995;22:894–8.

    PubMed  CAS  Google Scholar 

  31. Clegg DO, Reda DJ, Mejias E, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum. 1996;39:2013–20.

    Article  PubMed  CAS  Google Scholar 

  32. Clegg DO, Reda DJ, Abdellatif M. Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondyloarthropathies: a Department of Veterans Affairs cooperative study. Arthritis Rheum. 1999;42:2325–9.

    Article  PubMed  CAS  Google Scholar 

  33. Fox RI. Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol. 1998;53:20–6.

    CAS  Google Scholar 

  34. Scarpa R, Manguso F, Oriente P, et al. Leflunomide in psoriatic polyarthritis: an Italian pilot study. Arthritis Rheum. 2001;44:S92.

    Google Scholar 

  35. Behrens F, Finkenwirth C, Pavelka K, et al. Leflunomide in psoriatic arthritis: results from a large European prospective observational study. Arthritis Care Res (Hoboken). 2013;65:464–70.

    Article  CAS  Google Scholar 

  36. Steinsson K, Jonsdottir I, Valdimarsson H. Cyclosporin A in psoriatic arthritis: an open study. Ann Rheum Dis. 1990;49:603–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Sterry W, Ortonne JP, Kirkham B, et al. Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double-blind multicentre trial. BMJ. 2010;340:c147.

    Article  PubMed  Google Scholar 

  38. • Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: Results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52:1227–36.Shows data on the response of infliximab on PsA domains.

    Article  PubMed  CAS  Google Scholar 

  39. • Antoni CE, Krueger GG, de Vlam K, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 TRIAL. Ann Rheum Dis. 2005;64:1150–7. Shows data on the response of infliximab on PsA domains.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Mease PJ, Ory P, Sharp JT, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis. 2009;68:702–9.

    Article  PubMed  CAS  Google Scholar 

  41. Kavanaugh A, McInnes IB, Philip Mease P, et al. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial, the GO-REVEAL study. Ann Rheum Dis. 2014;0:1–6. https://doi.org/10.1136/annrheumdis-2013-204,902.

    Article  Google Scholar 

  42. Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73:48–55.

    Article  PubMed  CAS  Google Scholar 

  43. Ritchlin C, Rahman P, Kavanaugh A, PSUMMIT 2 Study Group, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Kavanaugh A, Puig L, Gottlieb AB, et al. Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). Ann Rheum Dis. 2016.

  45. McInnes IB, Kavanaugh A, Gottlieb AB, et al. PSUMMIT 1 Study Group Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1-year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382:780–9.

    Article  PubMed  CAS  Google Scholar 

  46. Jandus C, Bioley G, Rivals JP, et al. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58:2307–17.

    Article  PubMed  Google Scholar 

  47. Kagami S, Rizzo HL, Lee JJ, et al. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Investig Dermatol. 2010;130:1373–83.

    Article  PubMed  CAS  Google Scholar 

  48. Lin AM, Rubin CJ, Khandpur R, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Noordenbos T, Yeremenko N, Gofita I, et al. Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum. 2012;64:99–109.

    Article  PubMed  CAS  Google Scholar 

  50. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329–39.

    Article  PubMed  CAS  Google Scholar 

  51. Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693–700.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Mease PJ, van der Heijde D, Ritchlin CT, SPIRIT-P1 Study Group, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naïve patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2016.

  53. Mease PJ, Genovese MC, Greenwald MW, et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med. 2014;370:2295–306.

    Article  PubMed  CAS  Google Scholar 

  54. Mease P, Gottlieb AB, Berman A, et al. The efficacy and safety of clazakizumab, an anti-interleukin-6 monoclonal antibody, in a phase 2b study of adults with active psoriatic arthritis. Arthritis Rheum. 2016;

  55. Mease P, Genovese MC, Gladstein G, et al. Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial. Arthritis Rheum. 2011;63:939–48.

    Article  PubMed  CAS  Google Scholar 

  56. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73:1020–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75:1065–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Pathan E, Abraham S, Van Rossen E, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis. 2013;72:1475–80.

    Article  PubMed  CAS  Google Scholar 

  59. Kirkham BW, Kavanaugh A, Reich K. IL17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis, and rheumatoid arthritis. Immunology. 2014;141:133–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Novelli L, Chimenti MS, Chiricozzi A, et al. The new era for the treatment of psoriasis and psoriatic arthritis: perspectives and validated strategies. Autoimmun Rev. 2014;13:64–9.

    Article  PubMed  CAS  Google Scholar 

  61. O’Shea JJ. Jaks, STATs, cytokine signal transduction, and immunoregulation: are we there yet? Immunity. 1997;7:11–3.

    Google Scholar 

  62. Papp KA, Menter MA, Raman M, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016;174:1266–76.

    Article  PubMed  CAS  Google Scholar 

  63. •• Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016;75:499–510. This is an important consensus document by EULAR on the management and recommendations of PsA.

    Article  PubMed  CAS  Google Scholar 

  64. •• Ogdie A, Schwartzman S, Eder L, et al. Comprehensive treatment of psoriatic arthritis: managing comorbidities and extraarticular manifestations. J Rheumatol. 2014;41:2315–22. This is an important paper the deals comprehensively with extraarticular manifestations, the importance in management of PsA in totality.

    Article  PubMed  CAS  Google Scholar 

  65. •• Coates LC, Kavanaugh A, Ritchlin CT. GRAPPA Treatment Guideline Committee: Systematic review of treatments for psoriatic arthritis: 2014 update for the GRAPPA. J Rheumatol. 2014;41:2273–6. Important review on the guidelines and recommendations of treatment of PsA by GRAPPA.

    Article  PubMed  Google Scholar 

  66. •• Coates LC, Kavanaugh A, Mease PJ. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis. Arthritis Rheumatol. 2016;68:1060–71. Important update of the previous recommendations of GRAPPA to include new agents.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

    Ajesh B. Maharaj MBBS, H, DipInt, Med, FCP

  2. Department of Internal Medicine, Prince Mshiyeni Memorial Hospital and School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

    Ajesh B. Maharaj MBBS, H, DipInt, Med, FCP

  3. Department of General Medicine, Division of Internal Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

    F. Paruk MBChB (Natal), FCP (SA), PhD

Authors
  1. Ajesh B. Maharaj MBBS, H, DipInt, Med, FCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Paruk MBChB (Natal), FCP (SA), PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ajesh B. Maharaj MBBS, H, DipInt, Med, FCP.

Ethics declarations

Conflict of Interest

Ajesh B Maharaj, MB.BS, H. Dip.Int. Med, FCP, Cert in Rheumatology and Faranah Paruk, MBChB, FCP, Cert in Rheumatology, Ph.D. declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal studies performed by any of the authors.

Additional information

This article is part of the Topical Collection on Seronegative Arthritis

Electronic Supplementary Material

ESM 1

(DOCX 35 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maharaj, A.B., Paruk, F. Treatment of Enthesitis, Dactylitis and Nail Lesions in Psoriatic Arthritis. Curr Treat Options in Rheum 4, 183–196 (2018). https://doi.org/10.1007/s40674-018-0097-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40674-018-0097-z

Keywords

Search

Navigation