Clinical Rheumatology

, Volume 15, Issue 5, pp 435–439 | Cite as

Hypertrophic osteoarthropathy: Endothelium and platelet function

  • F. Silveri
  • R. de Angelis
  • F. Argentati
  • D. Brecciaroli
  • S. Muti
  • C. Cervini


Hypertrophic osteoarthropathy (HOA) is characterized by finger clubbing, periostosis and arthritis. The pathogenesis of hypertrophic osteoarthropathy is still uncertain. Earlier studies have been focused on the potential role of platelet and endothelium in the pathogenesis of HOA.

The aim of this study was to evaluate the circulating levels of endothelin-1 (ET-1), β-thromboglobulin (β-TG) and platelet-derived growth factor (PDGF) in 21 HOA patients.

The circulating levels of ET-1, β-TG were significantly higher in HOA patients vs healthy controls, but not vs controls with lung diseases. On the contrary, PDGF was significantly higher in HOA patients vs healthy controls and vs subjects with lung diseases.

These findings suggest that “endothelium/platelet unit” may play a role in the pathogenesis of HOA, and PDGF could induce the changes observed in HOA.

Key words

Hypertrophic Osteoarthropathy Finger Clubbing Platelet Endothelium Endothelin-1 β-thromboglobulin Platelet-derived Growth Factor 


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  1. 1.
    Pineda, C. Diagnostic imaging in hypertrophic osteoarthropathy. Clin Exp Rheumatol 1992, 10 (suppl 7), 27–33.PubMedGoogle Scholar
  2. 2.
    Braude, S., Kennedy, H., Hodson, M., Batte, N.J. Hypertrophic osteoarthropathy in cystic fibrosis. Br Med J 1984, 288, 822–823.Google Scholar
  3. 3.
    Matthay, M.A., Matthay, R.A., Mills, D.M., Lakshmina-Rayan, S., Cotton, E. Hypertrophic osteoarthropathy in adults with cystic fibrosis. Thorax 1976, 31, 572–575.PubMedGoogle Scholar
  4. 4.
    Cohen, A.M., Yulish, B.S., Wasser, K.B., Vignos, P.J., Jones, P.K., Sorin, S.B. Evaluation of pulmonary hypertrophic osteoarthropathy in cystic fibrosis: a comprehensive study. AJDC 1986, 140, 74–77.PubMedGoogle Scholar
  5. 5.
    Suter, S., Schaad, U.B., Roux-Lombard, P., Girardin, E., Grau, G., Dayer, J.M. Relation between tumor necrosis factor-alpha and granulocyte elastase-alpha-1 proteinase inhibitor complexes in the plasma of patients with cystic fibrosis. Am Rev Respir Dis 1989, 140, 1640–1644.PubMedGoogle Scholar
  6. 6.
    Silveri, F., Carlino, C., Cervini, C. The “endothelium/platelet unit” in hypertrophic osteoarthropathy. Clin Exp Rheumatol 1992, 10 (suppl 7), 61–66.PubMedGoogle Scholar
  7. 7.
    Dickinson, C.J. Lung diseases associated with digital clubbing. Clin Exp Rheumatol 1992, 10 (suppl 7), 23–25.PubMedGoogle Scholar
  8. 8.
    MacDonald, T.T., Hutchings, P., Choy, M.Y., Murch, S., Cooke, A. Tumor necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 1990, 81, 351–355.Google Scholar
  9. 9.
    Taillandier, J., Alemanni, M., Samuel, D. Ostéoarthropathie hypertrophiante et rejet de greffe hépatique. Rev Rhum 1990, 57, 477–479.PubMedGoogle Scholar
  10. 10.
    Epstein, O., Ajdukiewicz, A.B., Dick, R., Sherlock, S. Hypertrophic hepatic osteoarthropathy: clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature. Am J Med 1979, 67, 88–97.PubMedGoogle Scholar
  11. 11.
    Scuderi, P., Sterling, K.E., Lam, K.S. Raised serum levels of tumor necrosis factor in parasitic infections. Lancet 1986, 2, 1364–1365.PubMedGoogle Scholar
  12. 12.
    Cooper, E.S., Bundy, D.A.P. Trichuris is not trivial. Parasitol Today 1988, 4, 301–306.PubMedGoogle Scholar
  13. 13.
    Martinez-Lavin, M., Bobadilla, M., Casanova, J. Attié, F., Martinez, M. Hypertorphic osteoarthropathy in cyanotic congenital heart disease: its prevalence and relationship to bypass of the lung. Arthritis Rheum 1982, 25, 1186–1193.PubMedGoogle Scholar
  14. 14.
    Martinez-Lavin, M. Cardiogenic hypertrophic osteoarthropathy. Clin Exp Rheumatol 1992, 10 (suppl 7), 19–21.Google Scholar
  15. 15.
    Matucci-Cerinic, M. Le sindromi paraneoplastiche reumatologiche. Il Reumatologo 1988, 9, 192–196.Google Scholar
  16. 16.
    Gosney, M.A., Gosney, J.R., Lye, M. Plasma growth hormone and digital clubbing in carcinoma of the bronchus. Thorax 1990, 45, 545–547.PubMedGoogle Scholar
  17. 17.
    Marinez-Lavin, M. Digital clubbing and hypertrophic osteoarthropathy: a unifying hypothesis. J Rheumatol 1987, 14, 6–8.PubMedGoogle Scholar
  18. 18.
    Rimoin, D.L. Pachydermoperiostosis (idiopathic clubbing and periostosis): genetic and physiologic considerations. N Engl J Med 1965, 272, 923–931.PubMedGoogle Scholar
  19. 19.
    Keber, R., Vogl, A. Pachydermoperiostosis: peripheral circulatory studies. Arch Intern Med 1973, 132, 245–248.Google Scholar
  20. 20.
    Jajic, I., Pecina, M., Krstulovic, B., Kovacevic, D., Pavicic, F., Spaventi, S. Primary hypertrophic osteoarthropathy and changes in the joints. Scand J Rheumatol 1980, 9, 89–96.PubMedGoogle Scholar
  21. 21.
    Fam, A.G., Chin-Sang, H., Ramsay, C.A. Pachydermoperiostosis: scintigraphic, thermographic, plethismographic and capillaroscopy observations. Ann Rheum Dis 1983, 42, 98–102.PubMedGoogle Scholar
  22. 22.
    Dickinson, C.J., Martin, J.F. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987, 2, 1434–1435.PubMedGoogle Scholar
  23. 23.
    Yanagisawa, M., Kurihara, H., Kimura, S. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988, 332, 411–415.PubMedGoogle Scholar
  24. 24.
    Economos, K., MacDonald, P.C., Casey, M.L. Endothelin-1 gene expression and protein biosynthesis in human endometrium: potential modulator of endometrial blood flow. J Clin Endocrinol Metab 1992, 74, 14–19.PubMedGoogle Scholar
  25. 25.
    Inoue, A., Yanagisawa, M., Kimura, S. et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 1989, 86, 2863–2867.PubMedGoogle Scholar
  26. 26.
    Editorials. Endothelins. Lancet 1991, 337, 79–81.Google Scholar
  27. 27.
    Kaplof, K.L., Brockman, M.J., Cherkoff, A. et al. Platelet alfagranule proteins: studies of release and subcellular localization. Blood 1979, 53, 604–618.PubMedGoogle Scholar
  28. 28.
    Rosove, M., Hocking, W., Harwing, S., Perloff, J. Studies of β-thromboglobulin, platelet factor-4 and fibrinopeptide-A in erythrocytosis due to cyanotic congenital heart disease. Thromb Res 1983, 29, 225–235.PubMedGoogle Scholar
  29. 29.
    Vazquez-Abad, D., Martinez-Lavin, M. Macrothrombocytes in the peripheral circulation of patients with cardiogenic hypertrophic osteoarthropathy. Clin Exp Rheumatol 1991, 9, 59–62.PubMedGoogle Scholar
  30. 30.
    Fox, S.B., Day, C.A., Gatter, K.C. Association between platelet microthrombi and finger clubbing. Lancet 1991, 2, 313–314.Google Scholar
  31. 31.
    Martinez-Lavin, M., Pineda, C., Valdez, T. et al. Primary hypertrophic osteoarthropathy. Semin Arthritis Rheum 1988, 17, 156–162.PubMedGoogle Scholar
  32. 32.
    Blanke, H., Praetorius, G., Leschke, M., Seitz, R., Egbring, R., Strauer, B.E. Die Bedeutung des Thrombin-Anti-thrombin III-Komplexes in der Diagnostik der Lungenembolie und der tiefen Venenthrombose: vergleich mit Fibrinopeptid A, Plattchenfaktor 4 und β-thromboglobulin. Klin Wochenschr 1987, 65, 757–763.PubMedGoogle Scholar
  33. 33.
    Kaplan, K.L., Owen, J. Plasma levels of β-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood 1981; 57, 199–202.PubMedGoogle Scholar
  34. 34.
    Matucci-Cerinic, M., Marinez-Lavin, M., Rojo, F., Fonseca, C., Kahaleh, B.M. Von Willebrand factor antigen in hypertrophic osteoarthropathy. J Rheumatol 1992, 19, 765–767.PubMedGoogle Scholar
  35. 35.
    Matucci-Cerinic, M., Lotti, T., Jajic, I., Di Lollo, S., Brunetti, L., Urlic, D. Cutaneous fibrinolytic activity in primary hypertrophic osteoarthropathy. Scand J Rheumatol 1987, 16, 205–212.PubMedGoogle Scholar
  36. 36.
    Matucci-Cerinic, M., Cinti, S., Morroni, M. et al. Pachydermoperiostosis (primary hypertrophic osteoarthropathy): report of a case with evidence of endothelial and connective tissue involvement. Ann Rheum Dis 1989, 48, 240–246.PubMedGoogle Scholar
  37. 37.
    Gow, J.F., Jones, D.B., Billet, J., France, A.J., Edwardscr, W. Platelet serotonin concentration in patients with finger clubbing. Lancet 1988, 2, 579–9.Google Scholar
  38. 38.
    Matucci-Cerinic, M., Lotti, T., Jajic, I., Pignone, A., Bussani, C., Cagnoni, M. The clinical spectrum of pachydermoperiostosis (Primary hypertrophic osteoarthropathy). Medicine 1991, 70, 208–214.PubMedGoogle Scholar
  39. 39.
    Fonseca, C., Martinez-Levin, M. Circulating plasma levels of platelet-derived growth factor in patients with hypertrophic osteoarthropathy. Clin Exp Rheumatol 1992, 10 (suppl 7), abstr 6.Google Scholar
  40. 40.
    Heldin, C.H., Wasteson, A., Westermark, B. Platelet-derived growth factor. Mol Cell Endocrinol 1985, 39, 169–187.PubMedGoogle Scholar
  41. 41.
    Ross, R., Raines, E.W., Bowen-Pope, D.F. The biology of platelet-derived growth factor. Cell 1986, 46, 155–169.PubMedGoogle Scholar
  42. 42.
    Ross, R. Platelet-derived growth factor. Lancet 1989, 1, 1179–1182.PubMedGoogle Scholar
  43. 43.
    Xu, W., LeRoy, E.C., Smith, E.A. Fibronectin release by systemic sclerosis and normal dermal fibroblasts in response to TGF-β. J Rheumatol 1991, 18, 241–246.PubMedGoogle Scholar
  44. 44.
    Roberts, A.B., Sporn, M.B., Assoian R.K. et al. Transforming growth factor type β: rapid induction of fibrosis and angiogenesisin vivo and stimulating of collagen formationin vitro. Proc Natl Acad Sci USA 1986, 83, 4167–4171.PubMedGoogle Scholar
  45. 45.
    Soma, Y., Grotendorst, G.R. TGF-β stimulates primary human skin fibroblast DNA synthesis via an autocrine production of PDGF-related peptides. J Cell Physiol 1989, 140, 246–253.PubMedGoogle Scholar
  46. 46.
    Yamakage, A., Kikuchi, K., Smith, E.A., LeRoy, E.C., Trojanowska, M. Selective upregulation of platelet-derived growth factor-α receptors by transforming growth factor β in scleroderma fibroblasts. J Exp Med 1992, 175, 1227–1234.PubMedGoogle Scholar
  47. 47.
    Matucci-Cerinic, M., Sacerdoti, L., Perrone, C. et al. Pachydermoperiostosis (primary hypertrophic osteoarthropathy):in vitro evidence for abnormal fibroblast proliferation. Clin Exp Rheumatol 1992, 10 (suppl 7): 57–60.Google Scholar
  48. 48.
    Padula, S.J., Broketa, G., Sampieri, A., Arakawa, M., Matucci-Cerinic, M., Downie, E., Korn, J.H. Increased collagen synthesis in skin fibroblasts from patients with primary hypertrophic osteoarthropathy. Arthritis Rheum 1994, 37, 1386–1394.PubMedGoogle Scholar
  49. 49.
    Assoian, R.K., Grotendorst, G.R., Miller, D.M., Sporn, M.B. Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature 1984, 309, 804–806.PubMedGoogle Scholar
  50. 50.
    Esch, F., Baird, A., Ling, N. et al. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acid FGF. Proc Natl Acad Sci USA 1985, 82, 6507–6511.PubMedGoogle Scholar
  51. 51.
    Cobral, R., Ortiz-Freyre, R., Halfger-Marcet, C. Studies on the mechanisms of connective tissue proliferation in primary and secondary hypertrophic osteoarthropathy. Arthritis Rheum 1988, 31 (suppl 4), abstr B22.Google Scholar

Copyright information

© Clinical Rheumatology 1996

Authors and Affiliations

  • F. Silveri
    • 1
  • R. de Angelis
    • 1
  • F. Argentati
    • 2
  • D. Brecciaroli
    • 1
  • S. Muti
    • 1
  • C. Cervini
    • 1
  1. 1.Department of RheumatologyAncona University, Ospedale “A. Murri”Jesi (Ancona)Italy
  2. 2.Radioimmunology ServiceJesi HospitalJesi (Ancona)Italy

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