Neue Erkenntnisse zur Differenzialdiagnostik des Bladder-Pain-Syndroms

 

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Zusammenfassung

Die Diagnostik des BPS / IC (Bladder Pain Syndrom / Interstitielle Zystitis) stellt eine besondere Herausforderung dar, da nicht nur die Pathoge­nese des Syndroms sondern auch die Definition klinisch relevanter Parameter noch in lebhafter Diskussion sind. Die kürzlich von der ESSIC (European Society for the Study of IC / BPS) vorgeschlagenen Kriterien definieren, basierend auf dem Leitsymptom Blasenschmerz, eine Patientengruppe, die in sich heterogen ist und damit einer ein­heitlichen Therapie nicht zugeführt werden kann. Eine erweiterte Diagnostik auf molekula­rer Basis erscheint uns daher indiziert, um einerseits eine individualisierte Pharmakotherapie zu ermög­lichen und andererseits zur Aufklärung der Pathogenese des BPS / IC beizutragen. Dazu sehen wir eine Biopsienahme als unerlässlich. Die Diagnostik des BPS / IC sollte auf 3 „Säulen“ basieren: (1) Klinische Diagnostik, (2) Histopathologie, (3) Molekulardiagnostik / Proteinexpression. Da eine Beteiligung aller 3 zellulären Funk­tionseinheiten der Harnblase an der Pathogenese wahrscheinlich ist, sollten die Untersuchungen idealer Weise Urothel, Lamina propria und Detrusormuskulatur einschließen. Die Erstellung von Rezeptorprofilen der Detrusormuskulatur ist ein erster Ansatz für ein diagnostisches Tool, mit dem eine Individualisierung der Pharmakothe­rapie möglich erscheint. Andere Faktoren, wie etwa die Expression von beta-hCG im Urothel, ­bedürfen der weiteren Evaluation. Die Durchführung der erweiterten BPS / IC-Diagnostik könnte im Rahmen eines Klinik / Labornetzwerks realistisch in die urologische Routineversorgung integriert werden.

Abstract

The diagnosis of bladder pain syndrome / inter­stitial cystitis (BPS / IC) is challenging, since pathogenetic mechanisms and the definition of clini­cal relevant parameters are still under lively dis­cus­sion. The criteria recently proposed by the ­European Society for the Study of Interstitial Cystitis (ESSIC) define a collective of patients based on the cardinal symptom of bladder pain which is heterogeneous, and therefore cannot receive standardised consistent therapy. Thus an ex­tend­ed diagnosis based on molecular markers seems to be indicated to render individual pharmacotherapy possible, and to contribute to elucidation of BPS / IC pathogenesis. For this purpose we feel the vital need for taking a bladder biopsy. The ­diagnosis of BPS / IC should rely on 3 “columns”: (1) clinical diagnostics; (2) histopatho­logy; (3) molecular diagnostics / proteinexpres­sion. Since a significant contribution of the 3 functional units of the bladder to the pathophysiology is most evident, the examinations should ideally include urothelium, lamina propria, and detrusor mus­culature. Generation of receptor profiles of the ­detrusor muscle represents a first attempt to ­define a diagnostic tool for the individ­ualisation of BPS / IC pharmacotherapy. Other factors, e. g., beta-hCG expression in the urothelium, need ­further evaulation. Extended BPS / IC diagnostics could be realistically integrated into rou­tine pa­tient care within a clinic / laboratory network.

Literatur

• 1 van de Merwe J P, Nordling J, Bouchelouche P et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal.  Eur Urol. 2008;  53 60-67
  CrossrefPubMedGoogle Scholar
• 2 Fall M, Baranowski A P, Elneil S et al. EAU Guidelines on chronic pelvic pain.  Eur Urol. 2009;  ,  [Epub ahead of print]
  CrossrefPubMedGoogle Scholar
• 3 Binder I, van Ophoven A. [The complexity of chronic pelvic pain exemplified by the condition currently called interstitial cystitis. Part 1: Background and basic principles].  Aktuelle Urol. 2008;  39 205-214
  Article in Thieme ConnectPubMedGoogle Scholar
• 4 Hanno P M, Landis J R, Matthews-Cook Y et al. The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study.  J Urol. 1999;  161 553-557
  CrossrefPubMedGoogle Scholar
• 5 Gillenwater J Y, Wein A J. Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial ­Cystitis, National Institutes of Health, Bethesda, Maryland, August 28–29, 1987.  J Urol. 1988;  140 203-206
  PubMedGoogle Scholar
• 6 Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society.  Neurourol Urodyn. 2002;  21 167-178
  CrossrefPubMedGoogle Scholar
• 7 Rosamilia A, Igawa Y, Higashi S. Pathology of interstitial cystitis.  Int J Urol. 2003;  10 Suppl 11-15
  CrossrefPubMedGoogle Scholar
• 8 Kelada E, Jones A. Interstitial cystitis.  Arch Gynecol Obstet. 2007;  275 223-229
  CrossrefPubMedGoogle Scholar
• 9 Messing E M, Stamey T A. Interstitial cystitis: early diagnosis, pathology, and treatment.  Urology. 1978;  12 381-392
  CrossrefPubMedGoogle Scholar
• 10 Johansson S L, Fall M. Clinical features and spectrum of light microscopic changes in interstitial cystitis.  J Urol. 1990;  143 1118-1124
  PubMedGoogle Scholar
• 11 Gillespie L, Said J, Sostrin S et al. Immunofluorescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis.  Br J Urol. 1990;  66 265-273
  CrossrefPubMedGoogle Scholar
• 12 Lynes W L, Flynn S D, Shortliffe L D et al. Mast cell involvement in interstitial cystitis.  J Urol. 1987;  138 746-752
  PubMedGoogle Scholar
• 13 Shear S, Mayer R. Development of glomerulations in younger women with interstitial cystitis.  Urology. 2006;  68 253-256
  PubMedGoogle Scholar
• 14 Tomaszewski J E, Landis J R, Russack V et al. Biopsy features are associ­ated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study.  Urology. 2001;  57 67-81
  CrossrefPubMedGoogle Scholar
• 15 Smith B H, Dehner L P. Chronic ulcerating interstitial cystitis (Hunner’s ulcer). A study of 28 cases.  Arch Pathol. 1972;  93 76-81
  PubMedGoogle Scholar
• 16 Irwin P, Galloway N T. Impaired bladder perfusion in interstitial cys­titis: a study of blood supply using laser Doppler flowmetry.  J Urol. 1993;  149 890-892
  PubMedGoogle Scholar
• 17 Pontari M A, Hanno P M, Ruggieri M R. Comparison of bladder blood flow in patients with and without interstitial cystitis.  J Urol. 1999;  162 330-334
  CrossrefPubMedGoogle Scholar
• 18 Larsen S, Thompson S A, Hald T et al. Mast cells in interstitial cystitis.  Br J Urol. 1982;  54 283-286
  CrossrefPubMedGoogle Scholar
• 19 Theoharides T C, Sant G R. The mast cell as a neuro-immunendocrine ­effector in interstitial cystitis. In: Sant G, editor. Interstitial cystitis. Phil­adelphia: Lippincott-Raven; 1997: 101–108
  PubMedGoogle Scholar
• 20 Kastrup J, Hald T, Larsen S et al. Histamine content and mast cell count of detrusor muscle in patients with interstitial cystitis and other types of chronic cystitis.  Br J Urol. 1983;  55 495-500
  CrossrefPubMedGoogle Scholar
• 21 Peeker R, Aldenborg F, Dahlstrom A et al. Increased tyrosine hydroxylase immunoreactivity in bladder tissue from patients with classic and nonulcer interstitial cystitis.  J Urol. 2000;  163 1112-1115
  CrossrefPubMedGoogle Scholar
• 22 Keay S, Zhang C O, Chai T et al. Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome.  Urology. 2004;  63 22-26
  CrossrefPubMedGoogle Scholar
• 23 Meyers K E, Pfieffer S, Lu T et al. Genitourinary complications of sys­temic lupus erythematosus.  Pediatr Nephrol. 2000;  14 416-421
  CrossrefPubMedGoogle Scholar
• 24 Linardou H, Dahabreh I J, Kanaloupiti D et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer.  Lancet Oncol. 2008;  9 962-972
  CrossrefPubMedGoogle Scholar
• 25 Greenbaum D, Colangelo C, Williams K et al. Comparing protein abundance and mRNA expression levels on a genomic scale.  Genome Biol. 2003;  4 117
  CrossrefPubMedGoogle Scholar
• 26 Hohlbrugger G. Urinary potassium and the overactive bladder.  BJU Int. 1999;  83 Suppl 2 22-28
  PubMedGoogle Scholar
• 27 Parsons C L. The role of the urinary epithelium in the pathogenesis of interstitial cystitis / prostatitis / urethritis.  Urology. 2007;  69 9-16
  CrossrefPubMedGoogle Scholar
• 28 Slobodov G, Feloney M, Gran C et al. Abnormal expression of molecular markers for bladder impermeability and differentiation in the uro­thelium of patients with interstitial cystitis.  J Urol. 2004;  171 1554-1558
  CrossrefPubMedGoogle Scholar
• 29 Lavelle J P, Meyers S A, Ruiz W G et al. Urothelial pathophysiological changes in feline interstitial cystitis: a human model.  Am J Physiol ­Renal Physiol. 2000;  278 F 540-F 553
  PubMedGoogle Scholar
• 30 Zimmermann G, Ackermann W, Alexander H. Epithelial human chori­onic gonadotropin is expressed and produced in human secretory ­endometrium during the normal menstrual cycle.  Biol Reprod. 2009;  80 1053-1065
  CrossrefPubMedGoogle Scholar
• 31 Alexander H, Biesold C, Weber W et al. [Immunohistochemical evidence of immuno-reactive hCG in the secretory endometrium in women].  Zentralbl Gynakol. 1997;  119 Suppl 1 17-22
  PubMedGoogle Scholar
• 32 Neuhaus J, Scholler U, Freick K et al. [Myofibroblasts and afferent signalling in the urinary bladder: A concept].  Urologe A. 2008;  47 1085-1090
  PubMedGoogle Scholar
• 33 Roosen A, Datta S N, Chowdhury R A et al. Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neuro­toxin type a treatment.  Eur Urol. 2009;  55 1440-1448
  CrossrefPubMedGoogle Scholar
• 34 Mukerji G, Yiangou Y, Grogono J et al. Localization of M2 and M3 muscarinic receptors in human bladder disorders and their clinical correlations.  J Urol. 2006;  176 367-373
  CrossrefPubMedGoogle Scholar
• 35 Faussone-Pellegrini M S. Histogenesis, structure and relationships of ­interstitial cells of Cajal (ICC): from morphology to functional interpretation.  Eur J Morphol. 1992;  30 137-148
  PubMedGoogle Scholar
• 36 Mansfield K J, Liu L, Moore K H et al. Molecular characterization of M2 and M3 muscarinic receptor expression in bladder from women with refractory idiopathic detrusor overactivity.  BJU Int. 2007;  99 1433-1438
  CrossrefPubMedGoogle Scholar
• 37 Hinata N, Shirakawa T, Okada H et al. Quantitative analysis of the levels of expression of muscarinic receptor subtype RNA in the detrusor muscle of patients with overactive bladder.  Mol Diagn. 2004;  8 17-22
  PubMedGoogle Scholar
• 38 Pontari M A, Braverman A S, Ruggieri M RS. The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction.  Am J Physiol Regul Integr Comp Physiol. 2004;  286 R 874-R 880
  PubMedGoogle Scholar
• 39 Stevens L A, Chapple C R, Chess-Williams R. Human idiopathic and neurogenic overactive bladders and the role of M2 muscarinic receptors in contraction.  Eur Urol. 2007;  52 531-538
  CrossrefPubMedGoogle Scholar
• 40 Mansfield K J, Liu L, Mitchelson F J et al. Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing.  Br J Pharmacol. 2005;  144 1089-1099
  CrossrefPubMedGoogle Scholar
• 41 Hampel C, Gillitzer R, Pahernik S et al. [Changes in the receptor profile of the aging bladder].  Urologe A. 2004;  43 535-541
  CrossrefPubMedGoogle Scholar
• 42 O’Reilly B A, Kosaka A H, Knight G F et al. P2X receptors and their role in female idiopathic detrusor instability.  J Urol. 2002;  167 157-164
  CrossrefPubMedGoogle Scholar
• 43 Apostolidis A, Dasgupta P, Fowler C J. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity.  Eur Urol. 2006;  49 644-650
  CrossrefPubMedGoogle Scholar
• 44 Rudick C N, Bryce P J, Guichelaar L A et al. Mast cell-derived histamine mediates cystitis pain.  PLoS ONE. 2008;  3 e 2096
  PubMedGoogle Scholar
• 45 Bouchelouche K, Bouchelouche P. Cysteinyl leukotriene d(4) increases human detrusor muscle responsiveness to histamine.  J Urol. 2006;  176 361-366
  CrossrefPubMedGoogle Scholar
• 46 Neuhaus J, Weimann A, Stolzenburg J U et al. Histamine receptors in ­human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.  World J Urol. 2006;  24 202-209
  CrossrefPubMedGoogle Scholar
• 47 Dasgupta P, Sharma S D, Womack C et al. Cimetidine in painful bladder syndrome: a histopathological study.  BJU Int. 2001;  88 183-186
  CrossrefPubMedGoogle Scholar
• 48 Theoharides T C, Sant G R. Hydroxyzine therapy for interstitial cystitis.  Urology. 1997;  49 108-110
  PubMedGoogle Scholar
• 49 Parsons J K, Parsons C L. The historical origins of interstitial cystitis.  J Urol. 2004;  171 20-22
  CrossrefPubMedGoogle Scholar
• 50 Ueda T, Sant G R, Hanno P M et al. Interstitial cystitis and frequency-urgency syndrome (OAB syndrome).  Int J Urol. 2003;  10 Suppl 39-48
  CrossrefPubMedGoogle Scholar
• 51 Hanno P, Keay S, Moldwin R et al. International Consultation on IC – Rome, September 2004 / Forging an International Consensus: progress in painful bladder syndrome/interstitial cystitis.  Report and abstracts, Int Urogynecol J Pelvic Floor Dysfunct. 2005;  16 Suppl 1 2-34
  PubMedGoogle Scholar
• 52 Hanno P, Baranowski A P, Fall M et al. Painful bladder syndrome (including interstitial cystitis). In: Abrams P, Wein A, Cardozo L, editors. Incontinence. Paris: Health Publication Limited; 2005: 1465–1520
  PubMedGoogle Scholar

1 gleichberechtigte Erstautoren

Dr. med. T. Schwalenberg

Klinik und Poliklinik für Urologie · Universitätsklinikum Leipzig AöR

Liebigstr. 20

04103 Leipzig

Email: thilo.schwalenberg@uniklinik-leipzig.de

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