PDF herunterladen
Aktuelle Urol 2003; 34(6): 387-391
DOI: 10.1055/s-2003-43172
Übersichtsarbeit
© Georg Thieme Verlag Stuttgart · New York

Neue Aspekte zur Ätiopathogenese der Induratio penis plastica

New Insights into the Etiological Pathogenesis of Peyronie's DiseaseE.  W.  Hauck1 , A.  Hauptmann1 , S.  M.  Haag1 , W.  Weidner1
  • 1Justus-Liebig-Universität Gießen, Klinik und Poliklinik für Urologie und Kinderurologie
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
27. Oktober 2003 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Dieser Beitrag gibt eine Übersicht über den aktuellen Kenntnisstand zur Ätiopathogenese der Induratio penis plastica. De la Peyronie vermutete einen Zusammenhang mit venerischen Erkrankungen. Neben infektiösen werden traumatische, vor allem (auto-)immunologische und genetische Ursachen diskutiert. Eine wichtige Hypothese ist Beeinflussung durch wiederholte Mikrotraumen in der Tunica albuginea, die beim Geschlechtsverkehr zu Läsionen mit anschließender Aktivierung von Wundheilungsprozessen und Entwicklung des fibrotischen Plaques führen. Eine Assoziation mit den Antigenen des HLA-System kann nach neuesten Studien ausgeschlossen werden. Transforming Growth Factor beta (TGF-β) scheint einen entscheidenden Einfluss zu spielen, da er vermehrt im Plaque exprimiert wird und im Tiermodell durch intratunikale Injektion von Zytomodulin - einer Substanz mit TGF-β ähnlicher Aktivität - IPP-ähnliche Veränderungen erzeugt werden können. Wie bei anderen fibrotischen Erkrankungen scheint eine Verschiebung des Verhältnisses Nitridoxid (NO) zu reaktiven Sauerstoffspezies (ROS) einen Einfluss zu haben. Die wichtigsten neuen Aspekte wurden in der Untersuchung von Zellkulturmodellen gewonnen, in denen eine vermehrte Expression von Basic Fibroblast Growth Factor (bFGF), eine Änderung der Zellzyklusregulation sowie zytogenetische Instabilität beobachtet wurden.

Abstract

This paper reviews the current knowledge of the etiological pathogenesis of Peyronie's disease. De la Peyronie himself supposed a connection with venereal diseases. Herein, infectious, traumatic, autoimmune and genetic causes are discussed. An important hypothesis is that the recurrent microtraumatisation of the tunica albuginea during sexual intercourse leads to small lesions that activate processes of wound healing and development of fibrotic plaque. According to recent data, an association with the antigens of the HLA-system could be ruled out. Transforming growth factor beta (TGF-β) seems to have an important impact due to its increased expression in the plaque. Furthermore it is possible to induce a condition similar to Peyronie's disease by intratunical injection of cytomodulin - a substance with TGF-β-like activity - in an animal model. As in other fibrotic diseases, an imbalance between nitric oxide (NO) and reactive oxygen species (ROS) seems to be of importance. The most important new insights were gained from cell-culture models in which increased expression of basic fibroblast growth factor (bFGF), as well as a change in cell cycle regulation (p53) and cytogenetic instability were observed.

Schlüsselwörter

Induratio penis plastica - Ätiopathogenese - HLA-System - TGF-β - NO/ROS - Zellkultur - zytogenetische Instabilität

Key words

Peyronie's disease - etiological pathogenesis - HLA-system - TGF-β - NO/ROS - cell culture - cytogenetic instability

Literatur

  • 1 Davis C J. The microscopic pathology of Peyronie's disease.  J Urol. 1997;  157 282-284
    PubMedGoogle Scholar
  • 2 Vande Berg J S, Devine C J, Horton C E, Somers K D, Wright G L, Leffell M S, Dawson D M, Gleischman S H, Rowe M J. Mechanisms of calcification in Peyronie's Disease.  J Urol. 1982;  127 52-54
    PubMedGoogle Scholar
  • 3 Brock G, Hsu G L, Nunes L, von Heyden B, Lue T F. The anatomy of the tunica albuginea in the normal penis and Peyronie's disease.  J Urol. 1997;  157 276-281
    CrossrefPubMedGoogle Scholar
  • 4 Somers K D, Sismour E N, Wright G L, Devine C J, Gilbert D A, Horton C E. Isolation and characterization of collagen in Peyronie's disease.  J Urol. 1989;  141 629-631
    PubMedGoogle Scholar
  • 5 Vande Berg J S, Devine C J, Horton C E, Somers K D, Wright G L, Leffell M S, Dawson D M, Gleischman S H, Rowe M J. Peyronie's disease: an electron microscopic study.  J Urol. 1981;  126 333-336
    PubMedGoogle Scholar
  • 6 Somers K D, Dawson D M. Fibrin deposition in Peyronie's disease plaque.  J Urol. 1997;  157 311-315
    PubMedGoogle Scholar
  • 7 van der Water L. Mechanisms by which fibrin and fibronectin appear in healing wounds: implications for Peyronie's disease.  J Urol. 1997;  157 306-310
    PubMedGoogle Scholar
  • 8 Iacono F, Barra S, de Rosa G, Boscaino A, Lotti T. Microstructural disorders of tunica albuginea in patients affected by Peyronie's disease with or without erection dysfunction.  J Urol. 1993;  150 1806-1809
    PubMedGoogle Scholar
  • 9 Weidner W, Schroeder-Printzen I, Weiske W H, Vosshenrich R. Sexual dysfunction in Peyronie's disease: an analysis of 222 patients without previous local plaque therapy.  J Urol. 1997;  157 325-328
    PubMedGoogle Scholar
  • 10 Lindsay M B, Schain D M, Grambsch P, Benson R C, Beard C M, Kurland L T. The incidence of Peyronie's disease in Rochester, Minnesota, 1950 through 1984.  J Urol. 1991;  146 1007-1009
    PubMedGoogle Scholar
  • 11 Sommer F, Schwarzer U, Wassmer G, Bloch W, Braun M, Klotz T, Engelmann U. Epidemiology of Peyronie's disease.  Int J Impotence Res. 2002;  14 379-383
    PubMedGoogle Scholar
  • 12 Gelbard M K, Dorey F, James K. The natural history of Peyronie's disease.  J Urol. 1990;  144 1376-1379
    PubMedGoogle Scholar
  • 13 Kadioglu A, Tefekli A, Erol B, Oktar T, Tunc M, Tellaloglu S. A retrospective review of 307 men with Peyronie's disease.  J Urol. 2002;  168 1075-1079
    PubMedGoogle Scholar
  • 14 Hauck E W, Heitz M, Schreiter F, Weidner W. Induratio penis plastica.  Akt Urol. 1999;  30 386-404
    PubMedGoogle Scholar
  • 15 Levine L A, Lenting E L. A surgical algorithm for the treatment of Peyronie's disease.  J Urol. 1997;  158 2149-2152
    PubMedGoogle Scholar
  • 16 Hauck E W, Weidner W. François de la Peyronie and the disease named after him.  Lancet. 2001;  357 2049-2051
    CrossrefPubMedGoogle Scholar
  • 17 de la Peyronie F. Sur quelques obstacles qui s'opposent à l'éjaculation naturelle de la semence.  Mem Acad Roy Chir. 1743;  1 318-333
    PubMedGoogle Scholar
  • 18 Gholami S S, Lue T F. Peyronie's disease.  Urol Clin N Am. 2001;  28 377-390
    PubMedGoogle Scholar
  • 19 Hellstrom W JG, Bivalacqua T J. Peyronie's disease: Etiology, medical, and surgical therapy.  J Androl. 2000;  21 347-354
    PubMedGoogle Scholar
  • 20 Rompel R, Weidner W, Mueller-Eckhardt G. HLA association of idiopathic Peyronie's disease: an indication of autoimmune phenomena in etiopathogenesis?.  Tissue Antigens. 1991;  38 104-106
    PubMedGoogle Scholar
  • 21 Chen T YH, Zahran A R, Carrier S. Penile Curvature associated with Scleroderma.  Urology. 2001;  58 282XIX-282XX
    PubMedGoogle Scholar
  • 22 Yudkin J S. Peyronie's disease in association with metoprolol. Letter to the editor.  Lancet. 1977;  2 1355
    PubMedGoogle Scholar
  • 23 Leikin L B. Association of Peyronie's disease following petrochemical exposure - a case series. Letter to the editor.  JOEM. 2002;  44 105-106
    PubMedGoogle Scholar
  • 24 La Pera G, Pescatori E S, Boffini A, Calabrese M, Boffini A, Colombo F, Adriani E, Natali A, Vaggi L, Catugno C, Giustini M, Taggi F. and the SIMONA Group . Peyronie's disease: Prevalence and association with cigarette smoking.  Eur Urol. 2001;  40 525-530
    CrossrefPubMedGoogle Scholar
  • 25 Çulha M, Alici B, Acar O, Mutlu N, Gökalp A. The relationship between diabetes mellitus, impotence and venoocclusive dysfunction in Peyronie's disease patients.  Urol Int. 1998;  60 101-104
    PubMedGoogle Scholar
  • 26 Devine Jr C J, Somers K D, Jordan G H, Schlossberg S M. Proposal: Trauma as cause of Peyronie's lesion.  J Urol. 1997;  157 285-290
    PubMedGoogle Scholar
  • 27 Jarow J P, Lowe F C. Penile trauma: etiologic factor in Peyronie's disease and erectile dysfunction.  J Urol. 1997;  158 1388-1390
    PubMedGoogle Scholar
  • 28 Gefen A, Elad D, Chen J. Biomechanical aspects of Peyronie's disease in development stages and following reconstructive surgery.  Int J Impotence Res. 2002;  14 389-396
    PubMedGoogle Scholar
  • 29 Moreland R B, Nehra A. Pathophysiology of Peyronie's disease.  Int J Impotence Res. 2002;  14 406-410
    PubMedGoogle Scholar
  • 30 El-Sakka A I, Selph C A, Yen T SB, Dahiya R, Lue T F. The effect of surgical trauma on rat tunica albuginea.  J Urol. 1998;  159 1700-1707
    CrossrefPubMedGoogle Scholar
  • 31 Willscher M K, Cwazka W F, Novicki D E. The association of histocompatibility antigens of the B7 cross-reacting group with Peyronie's disease.  J Urol. 1979;  128 34-35
    PubMedGoogle Scholar
  • 32 Bias W B, Nyberg Jr L M, Hochberg M C, Walsh P C. Peyronie's disease: a newly recognized autosomal-dominant trait.  Am J Med Genet. 1982;  12 227-235
    CrossrefPubMedGoogle Scholar
  • 33 Leffell M S, Devine C J, Horton C E, Somers K D, Dawson D, Vande Berg J S, Bluemink G G, Wright G L. Non-association of Peyronie's disease with HLA B7 cross-reactive antigens.  J Urol. 1982;  128 1223-1224
    PubMedGoogle Scholar
  • 34 Nyberg L M, Bias W B, Hochberg M C, Walsh P C. Identification of an inherited form of Peyronie's disease with autosomal dominant inheritance and association with Dupuytren's contracture and histocompatibility B7 cross-reacting antigens.  J Urol. 1982;  128 48-51
    PubMedGoogle Scholar
  • 35 Ziegelbaum M, Thomas A, Zachary A A. The association of Peyronie's disease with HLA B7 cross-reactive antigens.  Cleveland Clin J Med. 1984;  57 427-430
    PubMedGoogle Scholar
  • 36 Deguchi T, Maeda S, Sakai S, Kuriyama M, Kawada Y, Nishiura T. HLA-A and B antigens in patients with Peyronie's disease.  Urology. 1984;  23 547-548
    CrossrefPubMedGoogle Scholar
  • 37 Rompel R, Mueller-Eckhardt G, Schroeder-Printzen I, Weidner W. HLA antigens in Peyronie's disease.  Urol Int. 1994;  52 34-37
    PubMedGoogle Scholar
  • 38 Nachtsheim D A, Rearden A. Peyronie's disease is associated with an HLA class II antigene, HLA-DQ5, implying an autoimmune etiology.  J Urol. 1996;  156 1330-1334
    PubMedGoogle Scholar
  • 39 Ralph D J, Schwartz G, Moore W, Pryor J P, Erbringer A, Bottazzo G F. The genetic and bacteriological aspects of Peyronie's disease.  J Urol. 1997;  157 291-294
    PubMedGoogle Scholar
  • 40 Noss M B, Day N S, Christ G J, Melman A. The genetics and immunology of Peyronie's disease.  Int J Impotence Res. 2000;  12 (suppl) S127-S132
    PubMedGoogle Scholar
  • 41 Hauck E W, Hauptmann A, Weidner W, Bein G, Hackstein H. Non-association of Peyronie's disease with the antigens of the human leukozyte antigen (HLA)-system. Eur Urol Supplements 2003 2 (Suppl 1): 123 abstract 484
    Google Scholar
  • 42 Cupples L A, Heeren T, Schatzkin A, Colton T. Multiple testing of hypotheses in comparing two groups.  Ann Intern Med. 1984;  100 122-129
    PubMedGoogle Scholar
  • 43 Curtin F, Schulz P. Multiple correlations and Bonferroni’s correction.  Biol Psychiatry. 1998;  44 775-777
    CrossrefPubMedGoogle Scholar
  • 44 Schiavino D, Sasso F, Nucera E, Alcini E, Gulino G, Milanoi A, Patriarca G. Immunologic findings in Peyronie's disease: a controlled study.  Urology. 1997;  50 764-768
    CrossrefPubMedGoogle Scholar
  • 45 Ralph D J, Mirakian R, Pryor J P, Bottazzo G F. The immunological features of Peyronie's disease.  J Urol. 1996;  155 159-162
    PubMedGoogle Scholar
  • 46 Stewart S, Malto M, Sandberg L, Colburn K K. Increased serum levels of anti-elastin antibodies in patients with Peyronie's disease.  J Urol. 1994;  152 105-106
    PubMedGoogle Scholar
  • 47 Lahme S, Feil G, Bichler K H. Untersuchungen zum Kollagenstoffwechsel bei Patienten mit Induratio penis plastica.  Akt Urol. 2001;  32 (suppl 1) 37-40
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 48 Kömpf J, Tomiuk J, Feil G, Lahme S, Bichler K H. Induratio penis plastica und genetische Variation des Alpha-1-Antitrypsin-Systems.  Akt Urol. 2001;  32 (suppl 1) 41-43
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 49 El-Sakka A I, Hassoba H W, Pillarisetty R J, Dahiva R, Lue T F. Peyronie's disease is associated with an increase in transforming growth factor-β protein expression.  J Urol. 1997;  158 1391-1394
    PubMedGoogle Scholar
  • 50 El-Sakka A I, Hassoba H M, Chui R M, Bhatnagar R S, Dahiya R, Lue T F. An animal model of Peyronie's like condition associates with an increase of transforming growth factor beta mRNA and protein expression.  J Urol. 1997;  158 2284-2290
    PubMedGoogle Scholar
  • 51 Hauck E W, Hauptmann A, Schmelz H U, Bein G, Weidner W, Hackstein H. Prospective analysis of single nucleotide polymorphisms of the transforming growth factor β-1 gene in Peyronie's disease.  J Urol. 2003;  169 369-372
    PubMedGoogle Scholar
  • 52 Awad M R, El-Gamel A, Hasleton P, Turner D M, Sinott P J, Hutchinson I V. Genotypic variation in the transforming growth factor-β1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation.  Transplantation. 1998;  66 1014-1020
    CrossrefPubMedGoogle Scholar
  • 53 El-Gamel A, Awad M, Sim E, Hasleton P, Yonan N, Egan J, Deiraniya A, Hutchinson I V. Transforming growth factor-beta1 and lung allograft fibrosis.  Eur J Cardiothorac Surg. 1998;  13 424-430
    CrossrefPubMedGoogle Scholar
  • 54 Bivalacqua T J, Diner E K, Novak T E, Vohra Y, Sikka S C, Champion H C, Hellstrom W JG. A rat model of Peyronie's disease associated with a decrease in erectile activity and an increase in inducible nitric oxide synthase protein expression.  J Urol. 2000;  163 1992-1998
    PubMedGoogle Scholar
  • 55 Bivalacqua T J, Champion H C, Leungwattanakij S, Yang D Y, Hyun J S, Abdel-Magdeed A B, Sikka S C, Kadowitz P J, Hellstrom W JG. Evaluation of nitric oxide synthase and arginase in the induction of a Peyronie's-like condition in the rat.  J Androl. 2001;  22 497-506
    PubMedGoogle Scholar
  • 56 Bivalacqua T J, Champion H C, Hellstrom W JG. Implications of nitric oxide synthase isoforms in the pathophysiology of Peyronie's disease.  Int J Impotence Res. 2002;  14 345-352
    PubMedGoogle Scholar
  • 57 Sikka S C, Hellstrom W JG. Role of oxidative stress and antioxidants in Peyronie's disease.  Int J Impotence Res. 2002;  14 353-360
    PubMedGoogle Scholar
  • 58 Ferrini M G, Vernet D, Magee T R, Shahed A, Qian A, Rajfer J, Gonzalez-Cadavid N F. Antifibrotic role of inducible nitric oxide synthase.  Nitric Oxide. 2002;  6 283-294
    CrossrefPubMedGoogle Scholar
  • 59 Gonzalez-Cadavid N F, Magee T R, Ferrini M, Qian A, Vernet D, Rajfer J. Gene expression in Peyronie's disease.  Int J Impotence Res. 2002;  14 361-374
    PubMedGoogle Scholar
  • 60 Nathan C. Inducible nitric oxide synthase: What difference does it make?.  J Clin Invest. 1997;  100 2417-2423
    PubMedGoogle Scholar
  • 61 Poli G, Parola M. Oxidative damage and fibrogenesis.  Free Radic Biol Med. 1997;  22 287-305
    CrossrefPubMedGoogle Scholar
  • 62 Burnett A L. Nitric oxide in the penis: physiology and pathology.  J Urol. 1997;  157 320-324
    CrossrefPubMedGoogle Scholar
  • 63 Magee T R, Qian A, Rajfer J, Sander F C, Levine L A, Gonzalez-Cadavid N F. Gene expression profiles in the Peyronie's disease plaque.  Urology. 2002;  59 451-457
    CrossrefPubMedGoogle Scholar
  • 64 Lin C S, Lin G, Whang Z, Maddah S A, Lue T F. Upregulation of monocyte chemoattractant protein 1 and effects of transforming growth-factor-β1 in Peyronie's disease.  Biochem Biophys Res Com. 2002;  295 1014-1019
    PubMedGoogle Scholar
  • 65 Ahuja S K, Sikka S C, Hellstrom W JG. Stimulation of collagen production in an vitro model for Peyronie's disease.  Int J Impotence Res. 1999;  11 207-212
    CrossrefPubMedGoogle Scholar
  • 66 Anderson M S, Shankey T V, Lubrano T, Mulhall J P. Inhibition of Peyronie's plaque fibroblast proliferation by biologic agents.  Int J Impotence Res. 2000;  12 (suppl 3) S35-S31
    PubMedGoogle Scholar
  • 67 Mulhall J P, Anderson M S, Lubrano T, Shankey T V. Peyronie's disease cell culture models: phenotypic, genotypic and functional analyses.  Int J Impotence Res. 2002;  14 397-405
    PubMedGoogle Scholar
  • 68 Mulhall J P, Thom J, Lubrano T, Shankey T V. Basic fibroblast growth factor expression in Peyronie's disease.  J Urol. 2001;  165 419-423
    CrossrefPubMedGoogle Scholar
  • 69 Mulhall J P, Branch J, Lubrano T, Shankey T V. Pertubation of cell cycle regulators in Peyronie's disease.  Int J Impotence Res. 2001;  13 (suppl 5) S21-S28
    PubMedGoogle Scholar
  • 70 Levine A J. p53, the cellular gatekeeper for growth and division.  Cell. 1997;  88 323-331
    PubMedGoogle Scholar
  • 71 Perinchery G, El-Sakka A I, Angan A, Nakajima K, Dharia A, Tanaka Y, Lue T F, Dahiya R. Microsatellite alterations and loss of heterozygosity in Peyronie's disease.  J Urol. 2001;  164 842-846
    PubMedGoogle Scholar

Prof. Dr. med. W. Weidner

Justus-Liebig-Universität Gießen · Klinik und Poliklinik für Urologie und Kinderurologie

Rudolf-Buchheim-Straße 7

35385 Gießen

Telefon: 0641-99 44 501

Fax: 0641-99 44 509

eMail: wolfgang.weidner@chiru.med.uni-giessen.de

      >