Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Psoriatic disease—from skin to bone

Nature Clinical Practice Rheumatology volume 3, pages 698–706 (2007)Cite this article

Abstract

Psoriatic arthritis is an inflammatory joint disease that is heterogeneous in presentation and clinical course. Evidence that this disease is distinct from rheumatoid arthritis and other spondyloarthropathies is based on data derived from characteristic clinical features, histopathologic analyses, immunogenetic associations and musculoskeletal imaging. Emphasis has centered previously on a dominant role for the T lymphocyte in the inflammatory process; however, studies provide support for a major contribution from monocyte–macrophages in the initiation and perpetuation of joint and skin inflammation. The occurrence of arthritis in the absence of psoriasis in a minority of patients with psoriatic arthritis, coupled with divergent genetic risk factors, indicates that psoriatic arthritis is distinct from psoriatic skin inflammation. A new terminology, psoriatic disease, has emerged that encompasses the various manifestations of tissue and organ involvement observed in many psoriasis patients, including inflammation in the joint, eye and gut. Moreover, adverse cardiovascular and metabolic outcomes in patients with psoriasis or psoriatic arthritis might be directly linked to the cutaneous and musculoskeletal manifestations of these diseases via subsets of circulating monocytes and tissue macrophages activated by inflammatory cytokine networks that arise in the skin and possibly the joint.

Key Points

  • Psoriatic arthritis can be distinguished from rheumatoid arthritis and other forms of spondyloarthropathy on the basis of epidemiological data, clinical manifestations, histopathology, immunogenetic associations and imaging studies

  • Psoriasis is a systemic disorder that can involve many tissues in the musculoskeletal system and extra-articular sites, including the gastrointestinal tract and the eye

  • Monocyte effector cells (osteoclasts, dendritic cells and macrophages) have been implicated in inflammatory events that occur in psoriatic skin, joints, eye and intestinal tissues

  • Adverse metabolic and cardiovascular outcomes in psoriasis patients highlight an important link between cutaneous inflammation, adipocytes and vascular remodeling that might be mediated by subsets of inflammatory monocytes

  • Therapies directed at pivotal cytokines (tumor necrosis factor, interleukin-23) or specific subpopulations of monocytes or T lymphocytes might not only limit joint damage and skin inflammation but also lessen adverse metabolic outcomes and cardiovascular events

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Osteitis in psoriatic arthritis.
Figure 2: Psoriatic disease.
Figure 3: The psoriasiform phenotype of affected CD18hypo mice improves following depletion of macrophages by weekly local injection with clodronate liposomes.

Similar content being viewed by others

References

  1. Alibert J (1818) Precis theorique et pratique sur les maladies de la peau. Paris: Calle et Ravier

    Google Scholar 

  2. Bourdillon C (1888) Psoriasis et Arthropathies [MD thesis]. Paris: A Davy

    Google Scholar 

  3. Blumberg BS et al. (1964) ARA nomenclature and classification of arthritis and rheumatism (tentative). Arthritis Rheum 7: 93–97

    Article  CAS  Google Scholar 

  4. Moll JM and Wright V (1973) Psoriatic arthritis. Semin Arthritis Rheum 3: 55–78

    Article  CAS  Google Scholar 

  5. Moll JM (1974) Psoriatic spondylitis: clinical radiological and familial aspects. Proc R Soc Med 67: 46–50

    CAS  PubMed  PubMed Central  Google Scholar 

  6. O'Neill T and Silman AJ (1994) Psoriatic arthritis. Historical background and epidemiology. Baillieres Clin Rheumatol 8: 245–261

    Article  CAS  Google Scholar 

  7. Taylor W et al. (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54: 2665–2673

    Article  Google Scholar 

  8. Fitzgerald O and Dougados M (2006) Psoriatic arthritis: one or more diseases. Best Pract Res Clin Rheumatol 20: 435–450

    Article  Google Scholar 

  9. Hellgren L (1969) Association between rheumatoid arthritis and psoriasis in total populations. Acta Rheumatol Scand 15: 316–326

    Article  CAS  Google Scholar 

  10. Ho P et al. (2004) Genetic epidemiology of psoriatic arthritis. Mod Rheumatol 14: 91–100

    Article  Google Scholar 

  11. Baker H (1966) Prevalence of psoriasis in polyarthritic patients and their relatives. Ann Rheum Dis 25: 229–234

    Article  CAS  Google Scholar 

  12. Harrison BJ et al. (1997) Presence of psoriasis does not influence the presentation or short-term outcome of patients with early inflammatory polyarthritis. J Rheumatol 24: 1744–1749

    CAS  PubMed  Google Scholar 

  13. Madland TM et al. (2005) Prevalence, disease manifestations, and treatment of psoriatic arthritis in Western Norway. J Rheumatol 32: 1918–1922

    PubMed  Google Scholar 

  14. Jones SM et al. (1994) Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumatol 33: 834–839

    Article  CAS  Google Scholar 

  15. Olivieri I et al. (2002) Fast spin echo-T2-weighted sequences with fat saturation in dactylitis of spondylarthritis. No evidence of entheseal involvement of the flexor digitorum tendons. Arthritis Rheum 46: 2964–2967

    Article  Google Scholar 

  16. Brockbank JE et al. (2005) Dactylitis in psoriatic arthritis: a marker for disease severity. Ann Rheum Dis 64: 188–190

    Article  CAS  Google Scholar 

  17. Salvarani C et al. (1997) Isolated peripheral enthesitis and/or dactylitis: a subset of psoriatic arthritis. J Rheumatol 24: 1106–1110

    CAS  PubMed  Google Scholar 

  18. Tan A et al. (2007) The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis: a high-resolution MRI and histology study. Rheumatology (Oxford) 46: 253–256

    Article  CAS  Google Scholar 

  19. Gladman DD et al. (1999) HLA-C locus alleles in patients with psoriatic arthritis (PsA). Hum Immunol 60: 259–261

    Article  CAS  Google Scholar 

  20. Ho P et al. (2007) HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis. Ann Rheum Dis 66: 807–811

    Article  CAS  Google Scholar 

  21. Gonzalez S et al. (1999) The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis. Arthritis Rheum 42: 1010–1016

    Article  CAS  Google Scholar 

  22. Kruithof E et al. (2005) Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis. Arthritis Res Ther 7: R569–R580

    Article  CAS  Google Scholar 

  23. Salvador G et al. (2005) p53 expression in rheumatoid and psoriatic arthritis synovial tissue and association with joint damage. Ann Rheum Dis 64: 183–187

    Article  CAS  Google Scholar 

  24. van Kuijk AW et al. (2006) Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis 65: 1551–1557

    Article  CAS  Google Scholar 

  25. Reece RJ et al. (1999) Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis. Arthritis Rheum 42: 1481–1484

    Article  CAS  Google Scholar 

  26. Veale D et al. (1993) Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis. Arthritis Rheum 36: 893–900

    Article  CAS  Google Scholar 

  27. Canete J et al. (2007) Ectopic lymphoid neogenesis in psoriatic arthritis. Ann Rheum Dis 66: 720–726

    Article  CAS  Google Scholar 

  28. McGonagle D et al. (1998) Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy. Arthritis Rheum 41: 694–700

    Article  CAS  Google Scholar 

  29. Jevtic V et al. (1995) Distinctive radiological features of small hand joints in rheumatoid arthritis and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA) magnetic resonance imaging. Skeletal Radiol 24: 351–355

    Article  CAS  Google Scholar 

  30. McQueen FM et al. (2003) Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis. Arthritis Rheum 48: 1814–1827

    Article  Google Scholar 

  31. Bollow M et al. (2000) Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis—cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis 59: 135–140

    Article  CAS  Google Scholar 

  32. Lories RJ et al. (2004) Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Ann Rheum Dis 63: 595–598

    Article  CAS  Google Scholar 

  33. Diarra D et al. (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13: 156–163

    Article  CAS  Google Scholar 

  34. Lories RJ et al. (2007) Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum 56: 489–497

    Article  Google Scholar 

  35. Frediani B et al. (2002) Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis. Clin Rheumatol 21: 203–206

    Article  Google Scholar 

  36. McGonagle D et al. (2001) An enthesitis based model for the pathogenesis of spondyloarthropathy. Additive effects of microbial adjuvant and biomechanical factors at disease sites. J Rheumatol 28: 2155–2159

    CAS  PubMed  Google Scholar 

  37. Mease PJ (2004) Recent advances in the management of psoriatic arthritis. Curr Opin Rheumatol 16: 366–370

    Article  Google Scholar 

  38. Scarpa R et al. (2003) Clinical and genetic aspects of psoriatic arthritis “sine psoriasis”. J Rheumatol 30: 2638–2640

    PubMed  Google Scholar 

  39. Ritchlin C (2006) Newer therapeutic approaches: spondyloarthritis and uveitis. Rheum Dis Clin North Am 32: 75–90

    Article  Google Scholar 

  40. Lowes MA et al. (2007) Pathogenesis and therapy of psoriasis. Nature 445: 866–873

    Article  CAS  Google Scholar 

  41. Segre JA (2006) Epidermal barrier formation and recovery in skin disorders. J Clin Invest 116: 1150–1158

    Article  CAS  Google Scholar 

  42. Nestle FO et al. (2005) Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 202: 135–143

    Article  CAS  Google Scholar 

  43. Boyman O et al. (2007) The pathogenic role of tissue-resident immune cells in psoriasis. Trends Immunol 28: 51–57

    Article  Google Scholar 

  44. Scarpa R et al. (2006) Psoriasis, psoriatic arthritis, or psoriatic disease. J Rheumatol 33: 210–212

    PubMed  Google Scholar 

  45. Schatteman L et al. (1995) Gut inflammation in psoriatic arthritis: a prospective ileocolonoscopic study. J Rheumatol 22: 680–683

    CAS  PubMed  Google Scholar 

  46. Scarpa R et al. (2000) Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel symptoms. J Rheumatol 27: 1241–1246

    CAS  PubMed  Google Scholar 

  47. Mielants H et al. (2005) Gut inflammation in the spondyloarthropathies. Curr Rheumatol Rep 7: 188–194

    Article  CAS  Google Scholar 

  48. Michaelsson G et al. (1997) Psoriasis patients have highly increased numbers of tryptase-positive mast cells in the duodenal stroma. Br J Dermatol 136: 866–870

    Article  CAS  Google Scholar 

  49. Lindqvist U et al. (2006) Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris. J Rheumatol 33: 924–927

    PubMed  Google Scholar 

  50. Queiro R et al. (2002) Clinical features and predictive factors in psoriatic arthritis-related uveitis. Semin Arthritis Rheum 31: 264–270

    Article  Google Scholar 

  51. Paiva ES et al. (2000) Characterisation of uveitis in patients with psoriatic arthritis. Ann Rheum Dis 59: 67–70

    Article  CAS  Google Scholar 

  52. Durrani K and Foster CS (2005) Psoriatic uveitis: a distinct clinical entity. Am J Ophthalmol 139: 106–111

    Article  Google Scholar 

  53. Mallbris L et al. (2006) Metabolic disorders in patients with psoriasis and psoriatic arthritis. Curr Rheumatol Rep 8: 355–363

    Article  CAS  Google Scholar 

  54. Neimann AL et al. (2006) Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol 55: 829–835

    Article  Google Scholar 

  55. Mallbris L et al. (2006) Psoriasis is associated with lipid abnormalities at the onset of skin disease. J Am Acad Dermatol 54: 614–621

    Article  Google Scholar 

  56. Henseler T and Christophers E (1995) Disease concomitance in psoriasis. J Am Acad Dermatol 32: 982–986

    Article  CAS  Google Scholar 

  57. Gelfand JM et al. (2006) Risk of myocardial infarction in patients with psoriasis. JAMA 296: 1735–1741

    Article  CAS  Google Scholar 

  58. Zenz R et al. (2005) Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 437: 369–375

    Article  CAS  Google Scholar 

  59. Wang H et al. (2006) Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. J Clin Invest 116: 2105–2114

    Article  CAS  Google Scholar 

  60. Stratis A et al. (2006) Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation. J Clin Invest 116: 2094–2104

    Article  CAS  Google Scholar 

  61. Massey HM and Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106: 167–170

    Article  CAS  Google Scholar 

  62. Zhou LJ and Tedder TF (1996) CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 93: 2588–2592

    Article  CAS  Google Scholar 

  63. McGonagle D et al. (2002) Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis 61: 534–537

    Article  CAS  Google Scholar 

  64. Taccari E et al. (1987) Phenotypic profile of major synovial cell populations in longstanding psoriatic arthritis. J Rheumatol 14: 525–530

    CAS  PubMed  Google Scholar 

  65. Ritchlin CT et al. (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111: 821–831

    Article  CAS  Google Scholar 

  66. Boyle WJ et al. (2003) Osteoclast differentiation and activation. Nature 423: 337–342

    Article  CAS  Google Scholar 

  67. Baeten D et al. (2002) Macrophages expressing the scavenger receptor CD163: a link between immune alterations of the gut and synovial inflammation in spondyloarthropathy. J Pathol 196: 343–350

    Article  CAS  Google Scholar 

  68. Baeten D et al. (2004) Association of CD163+ macrophages and local production of soluble CD163 with decreased lymphocyte activation in spondylarthropathy synovitis. Arthritis Rheum 50: 1611–1623

    Article  Google Scholar 

  69. Sonoda KH et al. (2003) Immunoregulatory role of ocular macrophages: the macrophages produce RANTES to suppress experimental autoimmune uveitis. J Immunol 171: 2652–2659

    Article  CAS  Google Scholar 

  70. Rader DJ and Pure E (2005) Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell. Cell Metabol 1: 223–230

    Article  CAS  Google Scholar 

  71. Gordon S (2007) Macrophage heterogeneity and tissue lipids. J Clin Invest 117: 89–93

    Article  CAS  Google Scholar 

  72. Swirski FK et al. (2007) Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 117: 195–205

    Article  CAS  Google Scholar 

  73. Lumeng CN et al. (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117: 175–184

    Article  CAS  Google Scholar 

  74. Kanda H et al. (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116: 1494–1505

    Article  CAS  Google Scholar 

  75. Fitch E et al.: Pathophysiology of psoriasis. Curr Rheumatol Rep, in press

  76. Clark RA and Kupper TS (2006) Misbehaving macrophages in the pathogenesis of psoriasis. J Clin Invest 116: 2084–2087

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA christopher_ritchlin@urmc.rochester.edu

Authors and Affiliations

  1. C Ritchlin is a Professor of Medicine and Director of the Clinical Immunology Research Center at the University of Rochester Medical Center, NY, USA.,

    Christopher Ritchlin

Authors
  1. Christopher Ritchlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

Christopher Ritchlin is a consultant for Abbott, Amgen, Bristol Myers-Squibb, Centocor, Roche and Wyeth, and has received grant/research support from Centocor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ritchlin, C. Psoriatic disease—from skin to bone. Nat Rev Rheumatol 3, 698–706 (2007). https://doi.org/10.1038/ncprheum0670

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0670

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing