Primary hypertrophic osteoarthropathy: an update

Abstract

Digital clubbing, which has been recognized as a sign of systemic disease, is one of the most ancient diseases. However, the pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood. The study of a clinically indistinguishable idiopathic form (primary hypertrophic osteoarthropathy, PHO) provides an opportunity to understand the pathogenesis of hypertrophic osteoarthropathy. Current advances in the study of PHO are discussed. The impaired metabolism of prostaglandin E2 (PGE2) plays a central role in its pathogenesis.

Keywords

digital clubbing / primary hypertrophic osteoarthropathy / prostaglandin E2 (PGE2)

References

[1] Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update. Clin Genet2005; 68(6): 477-486

[2] Friedreich N. Hyperostose des gesammten skelettes. Virchows Arch1868; 43(1): 83-87

[3] Touraine A, Solente G, Gole L. Un syndrome nosteodermopathique: la pachydermie plicaturee avec pachyperiostose des extremites. Presse Med1935; 43: 1820-1824

[4] Jajic I. Epidemiology of hypertrophic osteoarthropathy. Clin Exp Rheumatol1992; 10(Suppl 7): 13

[5] Oikarinen A, Palatsi R, Kylmäniemi M, Keski-Oja J, Risteli J, Kallioinen M. Pachydermoperiostosis: analysis of the connective tissue abnormality in one family. J Am Acad Dermatol1994; 31(6): 947-953

[6] Harbison JB, Nice CM Jr. Familial pachydermoperiostosis presenting as an acromegaly-like syndrome. Am J Roentgenol Radium Ther Nucl Med1971; 112(3): 532-536

[7] Rimoin DL. Pachydermoperiostosis (Idiopathic Clubbing and Periostosis): genetic and physiologic considerations. N Engl J Med1965; 272(18): 923-931

[8] Currarino G, Tierney RC, Giesel RG, Weihl C. Familial idiopathic osteoarthropathy. Am J Roentgenol Radium Ther Nucl Med1961; 85: 633-644

[9] Chamberlain DS, Whitaker J, Silverman FN. Idiopathic Osteoarthropathy and Cranial Defects in Children (Familial Idiopathic Osteoarthropathy). Am J Roentgenol Radium Ther Nucl Med1965; 93: 408-415

[10] Guyot-Drouot MH, Solau-Gervais E, Cortet B, Deprez X, Chastanet P, Cotten A, Delcambre B, Flipo RM. Rheumatologic manifestations of pachydermoperiostosis and preliminary experience with bisphosphonates. J Rheumatol2000; 27(10): 2418-2423

[11] Martinez-Lavin M. Miscellaneous non-inflammatory musculoskeletal conditions. Pachydermoperiostosis. Best Pract Res Clin Rheumatol2011; 25(5): 727-734

[12] Sinha GP, Curtis P, Haigh D, Lealman GT, Dodds W, Bennett CP. Pachydermoperiostosis in childhood. Br J Rheumatol1997; 36(11): 1224-1227

[13] Uppal S, Diggle CP, Carr IM, Fishwick CW, Ahmed M, Ibrahim GH, Helliwell PS, Latos-Bieleńska A, Phillips SE, Markham AF, Bennett CP, Bonthron DT. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet2008; 40(6): 789-793

[14] Zhang Z, Xia W, He J, Zhang Z, Ke Y, Yue H, Wang C, Zhang H, Gu J, Hu W, Fu W, Hu Y, Li M, Liu Y. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet2012; 90(1): 125-132

[15] Diggle CP, Parry DA, Logan CV, Laissue P, Rivera C, Restrepo CM, Fonseca DJ, Morgan JE, Allanore Y, Fontenay M, Wipff J, Varret M, Gibault L, Dalantaeva N, Korbonits M, Zhou B, Yuan G, Harifi G, Cefle K, Palanduz S, Akoglu H, Zwijnenburg PJ, Lichtenbelt KD, Aubry-Rozier B, Superti-Furga A, Dallapiccola B, Accadia M, Brancati F, Sheridan EG, Taylor GR, Carr IM, Johnson CA, Markham AF, Bonthron DT. Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis. Hum Mutat2012; 33(8): 1175-1181

[16] Seifert W, Kühnisch J, Tüysüz B, Specker C, Brouwers A, Horn D. Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing. Hum Mutat2012; 33(4): 660-664

[17] Busch J, Frank V, Bachmann N, Otsuka A, Oji V, Metze D, Shah K, Danda S, Watzer B, Traupe H, Bolz HJ, Kabashima K, Bergmann C. Mutations in the prostaglandin transporter SLCO2A1 cause primary hypertrophic osteoarthropathy with digital clubbing. J Invest Dermatol2012; 132(10): 2473-2476

[18] Bergmann C, Wobser M, Morbach H, Falkenbach A, Wittenhagen D, Lassay L, Ott H, Zerres K, Girschick HJ, Hamm H. Primary hypertrophic osteoarthropathy with digital clubbing and palmoplantar hyperhidrosis caused by 15-PGHD/HPGD loss-of-function mutations. Exp Dermatol2011; 20(6): 531-533

[19] Sinibaldi L, Harifi G, Bottillo I, Iannicelli M, El Hassani S, Brancati F, Dallapiccola B. A novel homozygous splice site mutation in the HPGD gene causes mild primary hypertrophic osteoarthropathy. Clin Exp Rheumatol2010; 28(2): 153-157

[20] Diggle CP, Carr IM, Zitt E, Wusik K, Hopkin RJ, Prada CE, Calabrese O, Rittinger O, Punaro MG, Markham AF, Bonthron DT. Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy. Rheumatology (Oxford)2010; 49(6): 1056-1062

[21] Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD⁺ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC). J Med Genet2009; 46(1): 14-20

[22] Sasaki T, Niizeki H, Shimizu A, Shiohama A, Hirakiyama A, Okuyama T, Seki A, Kabashima K, Otsuka A, Ishiko A, Tanese K, Miyakawa S, Sakabe J, Kuwahara M, Amagai M, Okano H, Suematsu M, Kudoh J. Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype-genotype correlation in Japanese patients with pachydermoperiostosis. J Dermatol Sci2012; 68(1): 36-44

[23] Ursing B. Pachydermoperiostosis. Acta Med Scand1970; 188(3): 157-160

[24] Cantatore FP, Mancini L, Ingrosso AM, Carrozzo M. Pachydermoperiostosis: dermatological, neurological and radiological observations. Clin Rheumatol1995; 14(6): 705-707

[25] Jajic I, Jajic Z, Grazio S. Minor but important symptoms and signs in primary hypertrophic osteoarthropathy. Clin Exp Rheumatol2001; 19(3): 357-358

[26] Saigal R, Kansal A, Mittal M, Singh Y, Ram H. Pachydermoperiostosis with myelofibrosis and empty sella. J Assoc Physicians India2010; 58: 253-255

[27] Martinez-Lavin M. Exploring the cause of the most ancient clinical sign of medicine: finger clubbing. Semin Arthritis Rheum2007; 36(6): 380-385

[28] de Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci2010; 1192(1): 269-277

[29] Narayanan S, Mohamed Gani VM, Sundararaju V. Primary hypertrophic osteoarthropathy with hypertrophic gastropathy. J Clin Rheumatol2010; 16(4): 190-192

[30] Martínez-Lavín M. Digital clubbing and hypertrophic osteoarthropathy: a unifying hypothesis. J Rheumatol1987; 14(1): 6-8

[31] Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet1987; 2(8573): 1434-1435

[32] Watanabe O, Arimura K, Kitajima I, Osame M, Maruyama I. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet1996; 347(9002): 702

[33] Soubrier M, Dubost JJ, Serre AF, Ristori JM, Sauvezie B, Cathebras P, Piette JC, Chapman A, Authier FJ, Gherardi RK. Growth factors in POEMS syndrome: evidence for a marked increase in circulating vascular endothelial growth factor. Arthritis Rheum1997; 40(4): 786-787

[34] Silveira LH, Martínez-Lavín M, Pineda C, Fonseca MC, Navarro C, Nava A. Vascular endothelial growth factor and hypertrophic osteoarthropathy. Clin Exp Rheumatol2000; 18(1): 57-62

[35] Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev2004; 25(4): 581-611

[36] Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J1999; 13(1): 9-22

[37] Towler DA. Vascular biology and bone formation: hints from HIF. J Clin Invest2007; 117(6): 1477-1480

[38] Olán F, Portela M, Navarro C, Gaxiola M, Silveira LH, Ruiz V, Martínez-Lavín M. Circulating vascular endothelial growth factor concentrations in a case of pulmonary hypertrophic osteoarthropathy. Correlation with disease activity. J Rheumatol2004; 31(3): 614-616

[39] Vazquez-Abad D, Martinez-Lavin M. Macrothrombocytes in the peripheral circulation of patients with cardiogenic hypertrophic osteoarthropathy. Clin Exp Rheumatol1991; 9(1): 59-62

[40] Nomura T, Lu R, Pucci ML, Schuster VL. The two-step model of prostaglandin signal termination: in vitro reconstitution with the prostaglandin transporter and prostaglandin 15 dehydrogenase. Mol Pharmacol2004; 65(4): 973-978

[41] Schuster VL. Prostaglandin transport. Prostaglandins Other Lipid Mediat2002; 68- 69: 633-647

[42] Endo S, Nomura T, Chan BS, Lu R, Pucci ML, Bao Y, Schuster VL. Expression of PGT in MDCK cell monolayers: polarized apical localization and induction of active PG transport. Am J Physiol Renal Physiol2002; 282(4): F618-F622

[43] Cattral MS, Altraif I, Greig PD, Blendis L, Levy GA. Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease. Am J Med1994; 97(4): 369-373

[44] Coggins KG, Latour A, Nguyen MS, Audoly L, Coffman TM, Koller BH. Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the ductus arteriosus. Nat Med2002; 8(2): 91-92

[45] Chang HY, Locker J, Lu R, Schuster VL. Failure of postnatal ductus arteriosus closure in prostaglandin transporter-deficient mice. Circulation2010; 121(4): 529-536

[46] Martínez-Lavín M, Pineda C, Navarro C, Buendía A, Zabal C. Primary hypertrophic osteoarthropathy: another heritable disorder associated with patent ductus arteriosus. Pediatr Cardiol1993; 14(3): 181-182

[47] Harada S, Nagy JA, Sullivan KA, Thomas KA, Endo N, Rodan GA, Rodan SB. Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. J Clin Invest1994; 93(6): 2490-2496

[48] Fabre JE, Nguyen M, Athirakul K, Coggins K, McNeish JD, Austin S, Parise LK, FitzGerald GA, Coffman TM, Koller BH. Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation. J Clin Invest2001; 107(5): 603-610

[49] Nguyen S, Hojjati M. Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy. Clin Rheumatol2011; 30(1): 7-13

[50] Jayakar BA, Abelson AG, Yao Q. Treatment of hypertrophic osteoarthropathy with zoledronic acid: case report and review of the literature. Semin Arthritis Rheum2011; 41(2): 291-296

[51] Tanaka H, Maehama S, Imanaka F, Sakai A, Abe K, Hamada M, Yamashita J, Kimura A, Imamura N, Fujimura K, Kuramoto A. Pachydermoperiostosis with myelofibrosis and anemia: report of a case of anemia of multifactorial causes and its improvement with steroid pulse and iron therapy. Jpn J Med1991; 30(1): 73-80

[52] Ninomiya S, Hara T, Tsurumi H, Kanemura N, Kasahara S, Ogawa Y, Seishima M, Hirose Y, Moriwaki H. Myelofibrosis successfully treated with prednisolone in a patient with pachydermoperiostosis. Intern Med2011; 50(19): 2207-2211

[53] Monteiro E, Carvalho P, Silva A, Ferraro A. Frontal rhytidectomy: a new approach to improve deep wrinkles in a case of pachydermoperiostosis. Plast Reconstr Surg2003; 112(4): 1189-1191

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg