UROLOGICAL SURVEY   ( Download pdf )

 

INVESTIGATIVE UROLOGY

Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis
Logadottir Y, Ehren I, Fall M, Wiklund NP, Peeker R, Hanno PM
From the Department of Urology, Sahlgrenska University Hospital, Göteborg (YL, MF, RP), and Department of Urology, Karolinska University Hospital, Stockholm (IE, NPW), Sweden
J Urol. 2004; 171:1148-51

  • Purpose: Interstitial cystitis (IC) is one of the most bothersome conditions in urological practice. There are 2 subtypes, classic and nonulcer IC, with similar symptoms but different outcomes with respect to clinical course and response to treatment. Histologically there are fundamental differences between the 2 subtypes, classic IC presenting a severe abnormality of the urothelium and characteristic inflammatory cell infiltrates while inflammation is scant in nonulcer IC. Regulation of urinary nitric oxide synthase activity has been proposed to be of importance for immunological responses in IC. We present evidence of a profound difference between the 2 subtypes concerning nitric oxide production, mirroring the differences in inflammatory response in IC.
  • Materials and Methods: A total of 17 patients with both subtypes and active disease as well as patients with disease in remission were included in the study, all diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria. Luminal nitric oxide was measured in the bladder of patients using a chemiluminescence nitric oxide analyzer.
  • Results: All patients with classic IC had high levels of NO. None of the other patients had any significant increase in NO levels in the bladder. The NO level in patients with classic IC was not related to symptoms but rather to the assignment to this specific subgroup of IC. The highest levels of NO were found in patients in the initial phase of classic IC.
  • Conclusions: The difference in NO evaporation between classic and nonulcer IC allows for subtyping of cases meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria without performing cystoscopy. The findings in the present series together with previous findings clearly demonstrate that the 2 subtypes of IC represent separate entities. This separation further emphasizes the need to subtype all cases included in all scientific matters, ensuring that the 2 subtypes are evaluated separately in clinical studies.

  • Editorial Comment
    Interstitial cystitis (IC) is often subdivided into 2 different subtypes: the classic “ulcerous” form of interstitial cystitis and the “early” or “nonulcer” form. The differences between the 2 subtypes are reflected in clinical manifestation and age distribution. It has also been demonstrated that the 2 subtypes respond differently to many treatment procedures (1). The main tool for differential diagnosis between the 2 forms of disease has been cystoscopy.
    Classic IC presents at endoscopy with reddened mucosal areas. These are often associated with small vessels radiating towards a central scar that ruptures with increasing bladder distension. Histological specimens obtained from lesions demonstrate that classic IC is a destructive inflammation and some patients eventually develop a small capacity fibrotic bladder. Outflow obstruction of the upper urinary tract may also occur in the final stage of classic IC.
    In nonulcer IC, the bladder mucosa is normal at initial cystoscopy. The development of glomerulations after hydrodistension is considered to be a positive diagnostic sign. Histologically, there are no or scant inflammatory signs in nonulcer disease (1).
    In the present pioneer study, the authors demonstrated that all patients with classic IC showed high or very high levels of NO. None of the other patients had any significant increase in NO in the bladder. The NO level in patients with classic IC was not related to symptoms but rather to the assignment to this specific subgroup of IC. However, disease stage seemed to influence NO levels with the highest levels of NO found in patients in the initial phase of classic IC. The difference in NO levels between classic and nonulcer IC allows for subtyping of cases without performing cystoscopy.

Reference
1. Peeker R, Fall M: The impact of heterogeneity on the diagnosis and treatment of interstitial cystitis. Int Braz J Urol. 2002; 28: 10-19.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil