Journal Mobile Options
Table of Contents
Vol. 221, Suppl. 1, 2010
Issue release date: August 2010
Dermatology 2010;221(suppl 1):15–22

Nailing down the Genetic and Immunological Basis for Psoriatic Disease

McGonagle D. · Palmou Fontana N. · Tan A.L. · Benjamin M.
aSection of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds and Chapel Allerton Hospital, Leeds, and bSchool of Biosciences, Cardiff University, Cardiff, UK; cRheumatology Department, Complejo Hospitalario Universitario A Coruña, La Coruña, Spain

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Psoriatic disease encompassing skin, joint and nail involvement is largely viewed as autoimmune – a finding supported by data from animal models, the human leucocyte antigen (HLA)-Cw6 disease association in man, T-lymphocyte infiltration in lesional skin and the favourable skin response to T-cell-directed therapies. However, this immunopathogenetic model only applies to the skin, as recent studies failed to demonstrate a HLA-Cw6 association with the nails or joints. Furthermore, the nails and joints are intimately associated with inflammation at points of ligament or tendon insertion (i.e., enthesitis), so it is now appreciated that both of these sites also share a common microanatomical basis. Moreover, inflammation at insertion sites and nails does not appear to be associated with a particular antigenic territory but is quite diffuse in nature. This suggests that an aberrant response to tissue stressing of the integrated nail-joint apparatus, rather than autoimmunity, is driving the inflammatory process. Therefore, HLA-Cw6-associated type 1 psoriasis is more closely linked to autoimmunity, whereas nail and joint disease may be linked to tissue-specific factors, including tissue biomechanical stressing and microtrauma, that lead to activation of aberrant innate immune responses. These observations that stem from nail disease point toward a relative differential involvement of adaptive and innate immunity in the psoriatic disease spectrum and offer a fresh perspective on the pathophysiology of psoriatic disease and how it can be classified along the immunological disease continuum of self-directed inflammation.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Wright V: Psoriasis and arthritis. Ann Rheum Dis 1956;15:348–356.
  2. Gisondi P, Tinazzi I, El-Dalati G, et al: Lower limb enthesopathy in patients with psoriasis without clinical signs of arthropathy: a hospital-based case-control study. Ann Rheum Dis 2008;67:26–30.
  3. Scarpa R, Ayala F, Caporaso N, Olivieri I: Psoriasis, psoriatic arthritis, or psoriatic disease? J Rheumatol 2006;33:210–212.
  4. Jiaravuthisan MM, Sasseville D, Vender RB, Murphy F, Muhn CY: Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy. J Am Acad Dermatol 2007;57:1–27.
  5. Zaias N: Nail in Health and Disease, ed 2. London, Appleton and Lange, 1990.
  6. de Berker DA, Andre J, Baran R: Nail biology and nail science. Int J Cosmet Sci 2007;29:241–275.
  7. Fleckman P: Structure and function of the nail unit; in Scher RK, Daniel CR III (eds): Nails: Diagnosis, Therapy, Surgery, ed 3. Philadelphia, Elsevier, 2005, pp 13–26.
  8. Martin BF, Platts MM: A histological study of the nail region in normal human subjects and in those showing splinter haemorrhages of the nail. J Anat 1959;93:323–330.
  9. Frenz C, Fritsch H, Hoch J: Plastination histologic investigations on the inserting pars terminalis aponeurosis dorsalis of three[-]sectioned fingers. Ann Anat 2000;182:69–73.
  10. Tan AL, Benjamin M, Toumi H, et al: The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis – a high-resolution MRI and histological study. Rheumatology (Oxford) 2007;46:253–256.
  11. McGonagle D, Tan AL, Benjamin M: The nail as a musculoskeletal appendage – implications for an improved understanding of the link between psoriasis and arthritis. Dermatology 2009;218:97–102.
  12. Tan AL, Grainger AJ, Tanner SF, Emery P, McGonagle D: A high-resolution magnetic resonance imaging study of distal interphalangeal joint arthropathy in psoriatic arthritis and osteoarthritis: are they the same? Arthritis Rheum 2006;54:1328–1333.
  13. McGonagle D, Gibbon W, O’Connor P, Green M, Pease C, Emery P: Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy. Arthritis Rheum 1998;41:694–700.
  14. Jevtic V, Watt I, Rozman B, Kos-Golja M, Demsar F, Jarh O: Distinctive radiological features of small hand joints in rheumatoid arthritis and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA) magnetic resonance imaging. Skeletal Radiol 1995;24:351–355.
  15. McGonagle D: Imaging the joint and enthesis: insights into pathogenesis of psoriatic arthritis. Ann Rheum Dis 2005;64:ii58–ii60.

    External Resources

  16. Benjamin M, McGonagle D: The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. J Anat 2001;199:503–526.
  17. Benjamin M, McGonagle D: Histopathologic changes at ‘synovio-entheseal complexes’ suggesting a novel mechanism for synovitis in osteoarthritis and spondylarthritis. Arthritis Rheum 2007;56:3601–3609.
  18. Benjamin M, Toumi H, Suzuki D, Redman S, Emery P, McGonagle D: Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders. Arthritis Rheum 2007;56:224–233.
  19. McGonagle D, Lories RJ, Tan AL, Benjamin M: The concept of a ‘synovio-entheseal complex’ and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 2007;56:2482–2491.
  20. Raychaudhuri SP, Jiang WY, Raychaudhuri SK: Revisiting the Koebner phenomenon: role of NGF and its receptor system in the pathogenesis of psoriasis (comment). Am J Pathol 2008;172:961–971.
  21. Baker BS, Powles AV, Lambert S, Valdimarsson H, Fry L: A prospective study of the Koebner reaction and T lymphocytes in uninvolved psoriatic skin. Acta Derm Venereol 1988;68:430–434.
  22. Sahin GO, Akyol M, Ozcelik S: An unusual Koebner phenomenon secondary to PPD with pustular and arthropathic psoriasis. Eur J Dermatol 2007;17:446.
  23. Fawcett RS, Linford S, Stulberg DL: Nail abnormalities: clues to systemic disease. Am Fam Physician 2004;69:1417–1424.
  24. Marcilly MC, Balme B, Haftek M, et al: Sub-total hereditary leukonychia, histopathological and electron microscopy study of ‘milky’ nails. Ann Dermatol Venereol 2003;130:50–54.
  25. Samman PD, Fenton DA (eds): The Nail in Disease. London, William Heinemann, 1986.
  26. Baran R, Dawber RPR (eds): Diseases of the Nail and Their Management. Oxford, Blackwell Scientific Publications, 1984.
  27. Lewin K, DeWit S, Ferrington RA: Pathology of the finger nail in psoriasis: a clinicopathological study. Br J Dermatol 1972;86:555–563.
  28. Namey TC, Rosenthall L: Periarticular uptake of 99mtechnetium diphosphonate in psoriatics: correlation with cutaneous activity. Arthritis Rheum 1976;19:607–612.
  29. McGonagle D, Marzo-Ortega H, Benjamin M, Emery P: Report on the Second International Enthesitis Workshop. Arthritis Rheum 2003;48:896–905.
  30. Mahoney JM, Scott R: Psoriatic onychopachydermoperiostitis (POPP): a perplexing case study. J Am Podiatr Med Assoc 2009;99:140–143.
  31. Resnick D, Broderick TW: Bony proliferation of terminal toe phalanges in psoriasis: the ‘ivory’ phalanx. J Can Assoc Radiol 1977;28:187–189.
  32. McGonagle D, Conaghan PG, Emery P: Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum 1999;42:1080–1086.
  33. Jury CS, Fleming C, Kemmett D: Severe nail dystrophy associated with painful fingertips. Diagnosis: psoriatic onychopachydermoperiostitis (POPP). Arch Dermatol 2000;136:925–930.
  34. Srivastava M, Solomon G, Strober B: Psoriatic onycho-pachydermo periostitis. Dermatol Online J 2007;13:20.

    External Resources

  35. Bongartz T, Harle P, Friedrich S, et al: Successful treatment of psoriatic onycho-pachydermo periostitis (POPP) with adalimumab. Arthritis Rheum 2005;52:280–282.
  36. Marzo-Ortega H, McGonagle D, Rhodes LA, et al: Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis. Ann Rheum Dis 2007;66:778–781.
  37. Elder JT: Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis. Genes Immun 2009;10:201–209.
  38. Gudjonsson JE, Karason A, Antonsdottir AA, et al: HLA-Cw6-positive and HLA-Cw6-negative patients with psoriasis vulgaris have distinct clinical features. J Invest Dermatol 2002;118:362–365.
  39. Fan X, Yang S, Sun LD, et al: Comparison of clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population. Acta Derm Venereol 2007;87:335–340.
  40. Ho PY, Barton A, Worthington J, Thomson W, Silman AJ, Bruce IN: HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis. Ann Rheum Dis 2007;66:807–811.
  41. Filer C, Ho P, Smith RL, et al: Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum 2008;58:3705–3709.
  42. McGonagle D, McDermott MF: A proposed classification of the immunological diseases. PLoS Med 2006;3:e297.
  43. McGonagle D, Georgouli T: The importance of ‘Mechnikov’s thorn’ for an improved understanding of 21st century medicine and immunology: a view from the eye. Scand J Immunol 2008;68:129–139.
  44. Lawry M: Biological therapy and nail psoriasis. Dermatol Ther 2007;20:60–67.
  45. Rigopoulos D, Gregoriou S, Stratigos A, et al: Evaluation of the efficacy and safety of infliximab on psoriatic nails: an unblinded, nonrandomized, open-label study. Br J Dermatol 2008;159:453–456.
  46. Rich P, Griffiths CEM, Reich K, et al: Baseline nail disease in patients with moderate to severe psoriasis and response to treatment with infliximab during 1 year. J Am Acad Dermatol 2008;58:224–231.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50