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Aetiology (under construction)

Associated diseases

Books

 

Campbell-Walsh Urology (to be published December 2006)
9th Edition by Saunders Elsevier, Chapter 10: Painful Bladder Syndrome/Interstitial Cystitis and Related Disorders by Philip M. Hanno MD

click here to go to the sample Chapter 10 

http://www.campbellsurology.com

 

Interstitial Cystitis
Grannum R. Sant 
Lippincott-Raven
September 1997

 

Campbells’ Urology
Eighth Edition, Volume One
Chapter 16: Interstitial Cystitis and Related Disorders
Philip Hanno
Saunders
 

Interstitial cystitis (in Japanese)
Dr Tomohiro Ueda
ISBN 4-87151-311-4

 

Intersticiální cystitida (in Czech) 
Tomáš Hanuš and Libor Zámecník 
Nucleus HK
ISBN 80-86225-30-5

 

Diagnosis and Treatment of Interstitial Cystitis in Women (in Russian)
O.B. Loran, A.W. Zaitcev, W.S. Lipsky
ISBN: 5-7633-0893-X

4

Confusable diseases

Diagnostic criteria and guidelines

  • Bladder pain syndrome international consultation on incontinence
    Hanno P, Lin A, Nordling J, Nyberg L, van Ophoven A, Ueda T, Wein A. Neurourol Urodyn 2010;29:191-8
    - the Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis; this included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research
    - the emphasis was on new information developed since the last consultation 4 years previously
    - the consultation decided to refer to the condition as "bladder pain syndrome" (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy
    - reasonable definitions of BPS include the definition of the ESSIC and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS
    - the initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture; urine cytology and cystoscopy are recommended if clinically indicated 
    - the consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder

  • Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome.
    Homma Y, Ueda T, Tomoe H, et al. Int J Urol 2009;16:597-615

  • Using the International Continence Society's definition of painful bladder syndrome.
    Warren JW, Meyer WA, Greenberg P, et al. Urology 2006;67:1138-42; discussion 1142-3
    • the authors conclude that the ICS definition identified only 91 (66%) of the 138 patients whom study investigators and caregivers diagnosed as having IC/PBS 
    • furthermore, those who met the ICS definition did not differ in important ways from those who did not 
    • these observations suggest that the ICS definition may not be sufficiently sensitive; minor modifications of the definition appeared to increase its sensitivity

  • Interstitial cystitis - epidemiology, diagnostic criteria, clinical markers
    Hanno PM. Rev Urol 2002;4 (Suppl 1):S3-S8

  • Etiology, pathogenesis, and diagnosis of interstitial cystitis
    Sant GR. Rev Urol 2002;4 (Suppl 1):S9-S15

  • Interstitial cystitis: characterization and management of an enigmatic urologic syndrome
    Nickel JC. Rev Urol 2001;4:112-21

Dissertations

  • Intravesical therapy of interstitial cystitis 
    P Tyagi. University of Pittsburgh, USA, 4 April 2005

Epidemiology

  • Epidemiologic issues in interstitial cystitis. 
    Parsons JK, Kurth K, Sant GR. Urology 2007;69(4 Suppl):5-8
    • the authors suggest that because IC is substantially underdiagnosed, its actual prevalence may affect as many as 1 in 4 to 5 women and 1 in 20 men

  • Prevalence and correlates for interstitial cystitis symptoms in women participating in a health screening project.
    Temml C, Wehrberger C, Riedl C, Ponholzer A, Marszalek M, Madersbacher S. Eur Urol 2006 Aug 30; PMID: 16979286

  • Prevalence of interstitial cystitis symptoms in women: a population based study in the primary care office.
    Rosenberg MT, Hazzard M. J Urol 2005;174:2231-4

  • Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland.
    Leppilahti M, Sairanen J, Tammela TL, et al. J Urol 2005;174:581-3

  • Incidence of physician-diagnosed interstitial cystitis in Olmsted County: a community-based study.
    Roberts RO, Bergstralh EJ, Bass SE, et al. BJU Int 2003;91:181-5

  • Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland. 
    Leppilahti M, Tammela TL, Huhtala H, Auvinen A. J Urol 2002;168:139-43

  • Interstitial Cystitis in Japan
    Ito T, Miki M, Yamada T. BJU Int 2000;86:634-7

  • Epidemiology of interstitial cystitis: a polulation based study.
    Curhan GC, Speizer FE, Hunter DJ, et al. J Urol 1999;161:549-52

  • Interstitial cystitis in the Netherlands: prevalence, diagnostic criteria and therapeutic preferences.
    Bade JJ, Rijcken B, Mensink HJ. J Urol 1995;154:2035-7; discussion 2037-8

  • Epidemiology of interstitial cystitis.
    Oravisto KJ. Ann Chir Gynaecol Fenn 1975;64:75-7

 

Genetics

  • Genetics and Phenotyping of Urological Chronic Pelvic Pain Syndrome
    Dimitrakov J, Guthrie D. J Urol 2009 Feb 19. [Epub ahead of print] 
    • a review on genetic risk factors for urological chronic pelvic pain syndromes

  • EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a genotype-phenotype correlation? 
    Maclean K, Holme SA, Gilmour E, et al. Am J Med Genet A 2007 Apr 12; [Epub ahead of print]
    • case report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation 
    • features common to both families were an ectodermal dysplasia principally affecting tooth, breast and nipple development, dacryostenosis and severe micturition difficulties; additional findings included post-axial digital hypoplasia, cleft uvula, anal stenosis, hypoplasia of the perineal body and biopsy-proven interstitial cystitis
    • unlike previous reports, the urinary symptoms were refractory to treatment with oral Fibrase and persisted into adulthood 
    • of the 6 cases/families now reported with EEC syndrome and Arg227Gln TP63 mutation, 4 have manifested this distinct urological abnormality, indicative of a genotype-phenotype correlation

  • A case of familial clustering of interstitial cystitis and chronic pelvic pain syndrome
    Dimitrakov JD. Urology 2001;58:281 
    • a case of familial clustering of interstitial cystitis (IC) and chronic pelvic pain syndrome (CPPS) is reported 
    • the proband was a 28-year-old woman with IC; IC was also diagnosed in the patient's mother and in two of her brothers, previously considered to have CPPS (category IIIB CPPS). A third brother was asymptomatic

Histopathology

Hunner's lesion (Hunner's "ulcer")

Hypotheses on aetiology and/or pathogenesis

International consultation

  • Bladder pain syndrome international consultation on incontinence
    Hanno P, Lin A, Nordling J, Nyberg L, van Ophoven A, Ueda T, Wein A. Neurourol Urodyn 2010;29:191-8
    - the Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis; this included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research
    - the emphasis was on new information developed since the last consultation 4 years previously
    - the consultation decided to refer to the condition as "bladder pain syndrome" (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy
    - reasonable definitions of BPS include the definition of the ESSIC and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS
    - the initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture; urine cytology and cystoscopy are recommended if clinically indicated 
    - the consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder

  • Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot
    Hanno P, Dmochowski R. Neurourol Urodyn. 2009 Mar 3. [Epub ahead of print] 
    • the Society for Urodynamics and Female Urology brought together thought leaders from Europe, Asia, and the United States to Miami, and a broad, structured discussion ensued which is the subject of this report
    • the most appropriate name of the disease remains an area of contention
    • a final "definition" of BPS/IC did garner substantial agreement among participants: an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes

 

Proceedings of the International Consultation on Interstitial Cystitis (ICICJ) - March 28-30, 2003. Kyoto, Japan. Int J Urol 2003;10(suppl:i-iv):S1-70

Mast cells

  • Interstitial cystitis in a woman with systemic mastocytosis
    Roth TM. Int Urogynecol J Pelvic Floor Dysfunct 2006 Nov 24; [Epub ahead of print] 
    • the author describes a patient with systemic mastocytosis who was confirmed to have detrusor mastocytosis and interstitial cystitis

  • Mast cells are essential intermediaries in regulatory T-cell tolerance
    Lu LF, Lind EF, Gondek DC, et al. Nature 2006;442:997-1002
    • it is known that T-regulatory cells, a subset of CD4+ T lymphocytes, are able to prevent other immune cells from attacking healthy tissues 
    • the authors demonstrate that the protective actions of T-regulatory cells depend on mast cells; so, mast cells do not only play a proinflammatory role in allergic disorders but also a physiological role to prevent immune-mediated tissue damage 
    • IL-9 from the T-regulatory cells is probably involved in the recruitment and activation of mast cells to perform this protecting role 
    • mast cells, like macrophages and dendritic cells, are thus not merely agents of destruction but ensure self-tolerance and tissue integrity through the maintenance of microenvironments where harmful immune responses are damped down

Pathophysiology (under construction)

Prevalence

  • Prevalence of interstitial cystitis symptoms in a managed care population
    Clemens JQ, Meenan RT, O'Keeffe Rosetti MC, et al. J Urol 2005;174:576-80
    • IC symptoms were defined in 2 ways, that is as 1) pelvic pain at least 3 months in duration plus urgency or frequency at least 3 months in duration and 2) the same criteria plus pain increasing as the bladder fills and/or pain relieved by urination
    • the prevalence of IC symptoms according to definitions 1 and 2 was 11.2% and 6.2% in women, and 4.6% and 2.3% in men, respectively 
    • the authors conclude that the prevalence of IC symptoms is 30 to 50-fold higher in women and 60 to 100-fold higher in men than the prevalence of a coded physician diagnosis of IC in the same population
    • these findings suggest that IC may be significantly under diagnosed

Prognosis

Can histological assessment predict the outcome in interstitial cystitis
MacDermott JP, Charpied GC, Tesluk H, Stone AR. Br J Urol 1991;67:44-7 
• in this retrospective study, the outcome of 39 patients with interstitial cystitis was compared to the histological findings at initial diagnostic bladder biopsy
• the degree of inflammation and fibrosis and the mast cell counts were assessed on each biopsy; the prognostic relevance of the clinical features of age, duration of symptoms, frequency, nocturia, pain and bladder capacity was assessed
• the study showed no statistical correlation between the severity of histological findings at diagnosis and the eventual outcome of the disease.

Urgency

Bladder pain syndrome/interstitial cystitis: a sense of urgency.
Hanno PM, Chapple CR, Cardozo LD. World J Urol 2009;27:717-21
- a review on bladder pain syndrome with special attention to urgency and overactive bladder

 VULVODYNIA

  • Vulvodynia. Definition, diagnosis and treatment
    Petersen CD, Lundvall L, Kristensen E, et al. Acta Obstet Gynecol Scand 2008;87:893-901 
    • this article describes the terminology and definition of the condition, theories on patho-physiological mechanisms underlying the disorder, methods of diagnosis and evidence and recommendations on clinical management

  • Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated factors
    Reed BD, Caron AM, Gorenflo DW, Haefner HK. J Low Genit Tract Dis 2006;10:245-51 
    • women with vulvodynia who were prescribed a tricyclic antidepressant in general (or amitriptyline, specifically) were more likely to have pain improvement compared with those women not taking these medications at follow-up
    • randomized, controlled studies of tricyclic antidepressants versus other treatments are needed to clarify the overall effectiveness of these drugs

TREATMENT

ORAL

  • Safety and Efficacy of the Use of Intravesical and Oral Pentosan Polysulfate Sodium for Interstitial Cystitis: A Randomized Double-Blind Clinical Trial
    Davis EL, El Khoudary SR, Talbott EO, et al. J Urol 2007 Nov 12; [Epub ahead of print]

  • A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. 
    van Ophoven A, Pokupic S, Heinecke A, et al. J Urol 2004;172:533-6
    • the authors conclude that amitriptyline therapy for 4 months is safe and effective for treating IC 
    • a statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed
    • anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC

  • see also: 
    Efficacy of tricyclic antidepressant is associated with beta2-adrenoceptor genotype in patients with interstitial cystitis
    Nishijima S, Sugaya K, Yamada T, et al. Biomed Res 2006;27:163-7 
    • the efficay of imipramine was studied in 55 IC patients and 113 controls in relation to the polymorphism of the beta2-adrenoreceptor (ADRB2)
    • the results suggest that the Arg16Gly polymorphism of ADRB2 is related to down-regulation of ADRB2 expression in the detrusor muscle and that the response of IC to tricyclic antidepressant therapy depends on the Arg16Gly polymorphism.

  • Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis
    Nickel JC, Barkin J, Forrest J, et al. Urology 2005;65:654-8
    • three dosages (300, 600, and 900 mg) of PPS in a randomized, double-blind, double-dummy, parallel-group, multicenter, 32-week study were studied in 380 IC patients
    • at study end, 27.5%, 56.9%, and 15.7% reported mild, moderate, and severe symptoms, respectively
    • for all three dosages of PPS, a clinically significant but similar response was demonstrated; the duration of therapy appears to be more important than the dosage

  • Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis
    Warren JW, Horne LM, Hebel JR, et al. J Urol 2000;163:1685-8
    • 50 patients with IC were randomized to receive 18 weeks of placebo or antibiotics, including rifampin plus a sequence of doxycycline, erythromycin, metronidazole, clindamycin, amoxicillin and ciprofloxacin for 3 weeks each. 
    • 12 of 25 patients (48%) in the antibiotic and 6 of 25 (24%) in the placebo group reported overall improvement (p = 0.14), while 10 and 5, respectively, noticed improvement in pain and urgency (p = 0.22). 
    • in the antibiotic group 20 participants (80%) had adverse effects compared with 10 (40%) in the placebo group (p = 0.009). 
    • the authors conclude that their findings suggest that these antibiotics alone or in combination may sometimes be associated with decreased symptoms in some patients but they do not represent a major advance in therapy for interstitial cystitis

  • A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis
    Cartledge JJ, Davies AM, Eardley I. BJU Int 2000;85:421-6 
    • the authors conclude that oral L-arginine produces a statistically significant improvement in the IC symptom index in patients with IC, but the effect is small; this effect may not be clinically significant as there were no improvements in the other variables assessed and no significant difference between the response to L-arginine and placebo
    • from these results the use of L-arginine cannot be recommended for treating IC

  • A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease
    Holm-Bentzen M, Jacobsen F, Nerstrom B, et al. J Urol 1987;138:503-7 
    • protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2) 
    • protocol B included 72 patients with a painful bladder and unspecific histological findings 
    • patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months 
    • before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies 
    • the results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. 
    • a significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found 
    • the authors conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease

Open studies and non-placebo-controlled studies

Case reports

Reviews

Questionnaires

  • Patient perceived outcomes of treatments used for interstitial cystitis
    Hill JR, Isom-Batz G, Panagopoulos G, et al. Urology 2008;71:62-6 
    • 750 patients with a diagnosis of IC completed a computerized survey that queried each patient about their demographics, symptoms, concomitant diagnoses, treatments, and their perceived treatment outcomes
    • the authors conclude that medical therapy is perceived to be superior to invasive therapy in the treatment and that several medications showed a large percentage of patients with improvement in symptoms
    • these medications were calcium glycerophosphate, phenazopyridine and pentosan polysulfate sodium
    comment: this study may be biased as the survey was a direct link from 3 websites, at least one of them being a commercial site

NEUROMODULATION(under construction)

  • Bilateral s3 stimulator in patients with interstitial cystitis
    Steinberg AC, Oyama IA, Whitmore KE. Urology 2007;69:441-3
    • this retrospective study demonstrated that 15 patients diagnosed with interstitial cystitis with the symptoms of frequency, urgency, and pain had a significant decrease in frequency and nocturia with bilateral stimulator placement

 

SURGICAL(under construction)

OTHER

Hyperbaric oxygen

Hydrodistension

SELECTED TOPICS & BOOKS