Differences in Clinical Features and Histopathology in BPS/IC with and without Hunner Lesions

  • Christina Kåbjörn-GustafssonEmail author
  • Ralph Peeker


The understanding of interstitial cystitis (IC) has changed a lot since the term was first introduced by Skene as early as in 1887 [1]. Guy L. Hunner described a symptom complex of bladder pain associated with an elusive cystoscopic feature, the Hunner ulcer, almost exactly 100 years ago [2]. A couple of decades later things became a lot more confusing when John Hand presented a large series of IC patients noticing that IC did not comprise just one single entity [3]. Some 40 years ago Messing and Stamey believed that there might be an early form of the disease, displaying the so-called submucosal glomerulations, potentially progressing into the well-known classic disease [4]. This notion has subsequently been considered unrealistic since progression from the so-called ‘early form’ to the classic ulcerous form or end stage disease (bladder contracture) actually never has been reported. Conversely, during the recent decades it has become increasingly clear that the different forms of IC indeed represent completely different pathological entities, despite sharing similar symptomatology and the same chronic course [5–8]. In a recent report, Killinger et al. failed to reveal any significant differences in pain patterns between the two subtypes [9].The differences between the two subtypes are reflected in clinical manifestation and age distribution [7, 8]. It has also been reported that the two subtypes respond differently to many treatment procedures [8]. Koziol et al. supported the contention of heterogeneity of interstitial cystitis by observations based on epidemiological data relating to demographics, risk factors, symptoms, pain and psychosocial factors [6], and, more recently, Peters et al. demonstrated notable differences between the two subtypes in the number of comorbid diagnoses as well as symptoms [10]. In these reports, subjects with Hunner disease were significantly older.



We would like to thank Ulric Pedersen for his contribution to the preparation of included figures.


  1. 1.
    Skene AJC. Diseases of bladder and urethra in women. New York: Wm Wood; 1887. p. 167.Google Scholar
  2. 2.
    Hunner GL. A rare type of bladder ulcer in women; report of cases. Boston Med Surg J. 1915;172:660–4.CrossRefGoogle Scholar
  3. 3.
    Hand JR. Interstitial cystitis: report of 223 cases (204 women and 19 men). J Urol. 1949;61:291–310.CrossRefPubMedGoogle Scholar
  4. 4.
    Messing EM, Stamey TA. Interstitial cystitis: early diagnosis, pathology and treatment. Urology. 1978;12:381–92.CrossRefPubMedGoogle Scholar
  5. 5.
    Fall M, Johansson SL, Aldenborg F. Chronic interstitial cystitis: a heterogeneous syndrome. J Urol. 1987;137(1):35–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Koziol JA, Adams HP, Frutos A. Discrimination between the ulcerous and the nonulcerous forms of interstitial cystitis by noninvasive findings. J Urol. 1996;155(1):87–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Logadottir Y, Fall M, Kabjorn-Gustafsson C, Peeker R. Clinical characteristics differ considerably between phenotypes of bladder pain syndrome/interstitial cystitis. Scand J Urol Nephrol. 2012;46(5):365–70.CrossRefPubMedGoogle Scholar
  8. 8.
    Peeker R, Fall M. Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. J Urol. 2002;167(6):2470–2.CrossRefPubMedGoogle Scholar
  9. 9.
    Killinger KA, Boura JA, Peters KM. Pain in interstitial cystitis/bladder pain syndrome: do characteristics differ in ulcerative and non-ulcerative subtypes? Int Urogynecol J. 2013;24(8):1295–301.CrossRefPubMedGoogle Scholar
  10. 10.
    Peters KM, Killinger KA, Mounayer MH, Boura JA. Are ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome 2 distinct diseases? A study of coexisting conditions. Urology. 2011;78(2):301–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Parsons CL. Interstitial cystitis: clinical manifestations and diagnostic criteria in over 200 cases. Neurourol Urodyn. 1990;9:241–50.CrossRefGoogle Scholar
  12. 12.
    Waxman JA, Sulak PJ, Kuehl TJ. Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation. J Urol. 1998;160(5):1663–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Johansson SL, Ogawa K, Fall M. The pathology of interstitial cystitis. In: Sant GR, editor. Interstitial cystitis. Philadelphia: Lippincott-Raven; 1997. p. 143–52.Google Scholar
  14. 14.
    Hunner GL. A rare type of bladder ulcer: further notes, with a report of eighteen cases. JAMA. 1918;70:203–12.CrossRefGoogle Scholar
  15. 15.
    Lepinard V. Interstitial cystitis. Ann Urol (Paris). 1998;32(6–7):349–51.Google Scholar
  16. 16.
    Johansson SL, Fall M. Clinical features and spectrum of light microscopic changes in interstitial cystitis. J Urol. 1990;143(6):1118–24.CrossRefPubMedGoogle Scholar
  17. 17.
    Collan Y, Alfthan O, Kivilaakso E, Oravisto KJ. Electron microscopic and histological findings on urinary bladder epithelium in interstitial cystitis. Eur Urol. 1976;2(5):242–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Dixon J, Holm-Bentzen M, Gilpin C. Electron microscopic investigation of the bladder urothelium and glycocalyx in patients with interstitial cystitis. J Urol. 1986;135:621–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Anderstrom CR, Fall M, Johansson SL. Scanning electron microscopic findings in interstitial cystitis. Br J Urol. 1989;63(3):270–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Elbadawi A, Light JK. Distinctive ultrastructural pathology of nonulcerative interstitial cystitis. Urol Int. 1996;56:137–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Hunt LW, Colby TV, Weiler DA, Sur S, Butterfield JH. Immunofluorescent staining for mast cells in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase. Mayo Clin Proc. 1992;67(10):941–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Qu Z, Liebler JM, Powers MR, Galey T, Ahmadi P, Huang XN, et al. Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am J Pathol. 1995;147:564–73.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Stevens LR, Austen KF. Recent advances in the cellular and molecular biology of mast cells. Immunol Today. 1989;10:381–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Williams RM, Bienenstock J, Stead RH. Mast cells: the neuroimmune connection. Chem Immunol. 1995;61:208–35.PubMedGoogle Scholar
  25. 25.
    Keith IM, Jin J, Saban R. Nerve-mast cell interaction in normal guinea pig urinary bladder. J Comp Neurol. 1995;363(1):28–36.CrossRefPubMedGoogle Scholar
  26. 26.
    Naukkarinen A, Harvima IT, Aalto ML, Harvima RJ, Horsmanheimo M. Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique. Arch Dermatol Res. 1991;283(7):433–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Newson B, Dahlstrom A, Enerback L, Ahlman H. Suggestive evidence for a direct innervation of mucosal mast cells. Neuroscience. 1983;10(2):565–70.CrossRefPubMedGoogle Scholar
  28. 28.
    Peeker R, Enerbäck L, Fall M, Aldenborg F. Recruitment, distribution and phenotypes of mast cells in interstitial cystitis. J Urol. 2000;163:1009–15.CrossRefPubMedGoogle Scholar
  29. 29.
    Ochs RL, Stein T Jr, Peebles CL, Gittes RF, Tan EM. Autoantibodies in interstitial cystitis. J Urol. 1994;151(3):587–92.CrossRefPubMedGoogle Scholar
  30. 30.
    Oravisto KJ. Interstitial cystitis as an autoimmune disease. A review. Eur Urol. 1980;6:10–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Silk MR. Bladder antibodies in interstitial cystitis. J Urol. 1970;103:307–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Mattila J, Pitkanen R, Vaalasti T, Seppanen J. Fine-structural evidence for vascular injury in patients with interstitial cystitis. Virchows Arch A Pathol Anat Histopathol. 1983;398(3):347–55.CrossRefPubMedGoogle Scholar
  33. 33.
    Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151.CrossRefPubMedGoogle Scholar
  34. 34.
    Harrington DS, Fall M, Johansson SL. Interstitial cystitis: bladder mucosa lymphocyte immunophenotyping and peripheral blood flow cytometry analysis. J Urol. 1990;144(4):868–71.CrossRefPubMedGoogle Scholar
  35. 35.
    Maeda D, Akiyama Y, Morikawa T, Kunita A, Ota Y, Katoh H, et al. Hunner-type (classic) interstitial cystitis: a distinct inflammatory disorder characterized by pancystitis, with frequent expansion of clonal B-cells and epithelial denudation. PLoS One. 2015;10(11):e0143316.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Akiyama Y, Morikawa T, Maeda D, Shintani Y, Niimi A, Nomiya A, et al. Increased CXCR3 expression of infiltrating plasma cells in hunner type interstitial cystitis. Sci Rep. 2016;6:28652.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ehren I, Hosseini A, Herulf M, Lundberg JO, Wiklund NP. Measurement of luminal nitric oxide in bladder inflammation using a silicon balloon catheter: a novel minimally invasive method. Urology. 1999;54:264–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Logadottir Y, Ehren I, Fall M, Wiklund NP, Peeker R. Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis. J Urol. 2004;171:1148–50.CrossRefPubMedGoogle Scholar
  39. 39.
    Koskela LR, Thiel T, Ehren I, De Verdier PJ, Wiklund NP. Localization and expression of inducible nitric oxide synthase in biopsies from patients with interstitial cystitis. J Urol. 2008;180:737–41.CrossRefPubMedGoogle Scholar
  40. 40.
    Logadottir Y, Hallsberg L, Fall M, Peeker R, Delbro D. Bladder pain syndrome/interstitial cystitis ESSIC type 3C: high expression of inducible nitric oxide synthase in inflammatory cells. Scand J Urol. 2013;47:52–6.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of BiomedicineGothenburg UniversityLandvetterSweden
  2. 2.Department of Urology, Institute of Clinical SciencesSahlgrenska Academy at the University of GothenburgGöteborgSweden

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