OBJECTIVE: To review current knowledge about the epidemiology, etiology, diagnosis, and treatment of interstitial cystitis, with special emphasis on management of this condition by family physicians. QUALITY OF EVIDENCE: Articles were identified through MEDLINE and review of abstracts presented at Urology and Interstitial Cystitis meetings during the last decade. Recent reviews were further searched for additional studies and trials. Data were summarized from large epidemiologic studies. Etiologic theories were extracted from current concepts and reviews of scientific studies. Diagnostic criteria described in this review are based on clinical interpretation of National Institutes of Health (NIH) research guidelines, interpretation of data from the NIH Interstitial Cystitis Cohort Study, and recent evidence on use of the potassium sensitivity test. Treatment suggestions are based on six randomized placebo-controlled clinical treatment trials and best available clinical data. MAIN MESSAGE: Interstitial cystitis affects about 0.01% to 0.5% of women. Its etiology is unknown, but might involve microbiologic, immunologic, mucosal, neurogenic, and other yet undefined agents. The diagnosis of interstitial cystitis is a diagnosis of exclusion. It is impossible to provide a purely evidence-based treatment strategy, but review of available evidence suggests that conservative supportive therapy (including diet modification); oral treatment with pentosan polysulfate, amitriptyline, or hydroxyzine; and intravesical treatments with heparinlike medications, dimethyl sulfoxide, or BCG vaccine could benefit some patients. CONCLUSION: Family physicians should have an understanding of interstitial cystitis and be able to make a diagnosis and formulate an evidence-based treatment strategy for their patients.

ANTECEDENTES: La cistitis aguda no complicada es una de las infecciones bacterianas más frecuentes en adultos. Se estima que el porcentaje de mujeres que presenta al menos un episodio de cistitis aguda se encuentra entre el 40% y el 50%. Las quinolonas se recomiendan para la cistitis aguda en regiones donde el nivel de resistencia a otros antimicrobianos, principalmente el cotrimoxazol, es alto. Sin embargo, se deben investigar la eficacia, seguridad y tolerancia de las quinolonas. OBJETIVOS: Comparar la eficacia, la seguridad y la tolerancia de las diferentes quinolonas para las mujeres con cistitis aguda no complicada. ESTRATEGIA DE BÚSQUEDA: Se realizaron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL, en Número 3, 2003), MEDLINE (desde 1966 hasta septiembre de 2003), EMBASE (desde 1988 hasta septiembre de 2003), en las listas de referencias de los artículos y los resúmenes de congresos, sin restricción de idiomas. Listas de referencias de libros de texto de urología, enfermedades infecciosas y nefrología, artículos de revisión y estudios pertinentes. CRITERIOS DE SELECCIÓN: Se seleccionaron los ensayos controlados aleatorios y cuasialeatorios que compararon dos o más quinolonas diferentes para tratar mujeres (= 16 años) con cistitis aguda no complicada. RECOPILACIÓN Y ANÁLISIS DE DATOS: Dos revisores de forma independiente evaluaron la calidad de los ensayos y extrajeron los datos. Los análisis estadísticos se realizaron según un modelo de efectos aleatorios, y los resultados se expresaron como el riesgo relativo (RR) para las medidas de resultado dicotómicas, con intervalos de confianza (IC) del 95%. RESULTADOS PRINCIPALES: Se identificaron 11 estudios, que reclutaron a 7 535 mujeres. No hubo ninguna diferencia significativa en la eficacia clínica o microbiológica entre las quinolonas. Se observaron con mayor frecuencia reacciones de fotosensibilidad con la esparfloxacina comparada con la ofloxacina. Cualquier evento adverso, aquellos que causaron el retiro o afectaron la piel y las reacciones de fotosensibilidad fueron más frecuentes con la lomefloxacina, en comparación con la norfloxacina. Cualquier evento adverso, las reacciones adversas a los fármacos o los eventos adversos del sistema nervioso central (SNC) fueron más frecuentes con la ofloxacina, en comparación con la ciprofloxacina. Los eventos adversos del SNC y el insomnio se informaron con más frecuencia con la rufloxacina comparada con la pefloxacina. Las reacciones adversas al fármaco resultaron más frecuentes con la ofloxacina que con la levofloxacina. El insomnio se informó más veces con la enoxacina que con la ciprofloxacina. CONCLUSIONES DE LOS AUTORES: No se encontraron diferencias significativas en la eficacia clínica o microbiológica entre las quinolonas, pero sí algunas en la presentación el espectro de las reacciones adversas (seguridad) de las quinolonas.

Resiniferatoxin, a treatment based on a physiopathological concept (the involvement of C fibers and transient receptor potential vanilloid 1 in the transmission of pain) is undergoing evaluation for interstitial cystitis. We evaluated the current evidence from relevant studies identified in PubMed and Scopus databases. Six studies provided contradictory results regarding the effectiveness of resiniferatoxin treatment. The largest study showed no improvement of overall symptoms following a single administration of resiniferatoxin. Three other articles that studied the effectiveness of a single dose of resiniferatoxin gave contradictory results. However, the other two studies, those that examined the effect of multiple or prolonged administration schemes, gave more encouraging results. The use of the regimen is generally well tolerated although mild adverse events such as increase of bladder pain during instillation were sometimes reported by patients and serious adverse events rarely occur. In conclusion, the effectiveness of resiniferatoxin in the treatment of interstitial cystitis remains unknown.

ANTECEDENTES: El síndrome de vejiga dolorosa/cistitis intersticial (SVD/CI) ocurre predominantemente en mujeres. Es una afección poco conocida con síntomas de dolor vesical, polaquiuria, tenesmo vesical y nicturia. El tratamiento del SVD/CI incluye intervenciones en la alimentación/el estilo de vida, fármacos orales, instilaciones intravesicales y, en algunos casos, intervención quirúrgica. Las tasas de éxito son generalmente bajas y hay poco consenso sobre el tratamiento más adecuado de esta afección. OBJETIVOS: Evaluar la efectividad del tratamiento intravesical del SVD/CI. ESTRATEGIA DE BÚSQUEDA: Se realizaron búsquedas en el registro de ensayos especializado del Grupo Cochrane de Incontinencia (Cochrane Incontinence Group specialised trials register) (30 de mayo de 2006) así como en las listas de referencias de todos los ensayos seleccionados. Se estableció contacto con investigadores reconocidos en el tema en busca de cualquier material pertinente adicional. CRITERIOS DE SELECCIÓN: Se incluyeron en la revisión los ensayos controlados aleatorios o cuasialeatorios que reclutaron participantes con un diagnóstico clínico de SVD/CI si al menos un brazo del ensayo era el tratamiento con una preparación para uso intravesical. Las medidas de resultado se determinaron con anterioridad, las primarias eran el efecto sobre el dolor y la capacidad vesical. Otras medidas incluían la respuesta sintomática al tratamiento, la evaluación de la calidad de vida, los factores económicos y los eventos adversos. RECOPILACIÓN Y ANÁLISIS DE DATOS: Dos revisores evaluaron de forma independiente la elegibilidad de los ensayos y la calidad, luego extrajeron los datos pertinentes de los estudios. RESULTADOS PRINCIPALES: Se identificaron nueve ensayos elegibles, seis con diseño de grupos paralelos, un ensayo cruzado (crossover) incompleto y dos ensayos cruzados (crossover), con un total de 616 participantes. Seis ensayos compararon una instilación "activa" con una instilación placebo, dos compararon tipos diferentes de instilación, y uno era una comparación de una instilación más entrenamiento vesical versus entrenamiento vesical solo. En total, la revisión incluyó ensayos de seis diferentes tipos de instilación intravesical: Resiniferatoxina, dimetil sulfóxido, BCG, pentosanpolisulfato, oxibutinina y alcalinización del pH de la orina. Los intervalos de confianza fueron generalmente amplios. La resiniferatoxina no se asoció con diferencias mantenidas en los resultados informados en la revisión, pero el dolor durante la instilación y la retirada del tratamiento fue significativamente más frecuente. Los datos disponibles acerca del dimetil sulfóxido (DMSO) fueron muy limitados, pero sin diferencias manifiestas con el placebo. Los grupos tratados con BCG tendieron a informar menos dolor y menos síntomas generales. Aunque frecuentemente se informaron eventos adversos, no fueron más frecuentes después del BCG que después de la instilación de placebo. Los pocos datos acerca del pentosanpolisulfato tendieron a favorecer el tratamiento activo, pero con intervalos de confianza amplios; había poca información sobre los eventos adversos. La instilación de oxibutinina se asoció con mayor capacidad vesical, menor polaquiuria, mejores puntuaciones de calidad de vida y menos abandonos. La alcalinización del pH de la orina no logró diferencias claras, pero con intervalos de confianza potencialmente amplios. CONCLUSIONES DE LOS AUTORES: En términos generales, la base de la evidencia para tratar el SVD/CI con preparaciones intravesicales es limitada y hay poca posibilidad de realizar metanálisis por la diversidad de las medidas de resultado usadas. La calidad de los informes de los ensayos era desigual y en algunos casos impidió extraer datos significativos. El BCG y la oxibutinina se toleran razonablemente bien y las pruebas de su efectividad son las más alentadoras. La resiniferatoxina no mostró pruebas de efecto en la mayoría de los resultados y causó dolor, que disminuyó el cumplimiento del tratamiento. Hay pocas pruebas sobre los otros tratamientos incluidos en esta revisión. Se necesitan más ensayos controlados aleatorios y el diseño de los estudios debe incorporar las medidas de resultado más pertinentes para los pacientes con SVD/CI, las cuales deben ser estandarizadas.

OBJECTIVES: To determine the efficacy of pentosan polysulfate (Elmiron) compared to placebo in the treatment of interstitial cystitis. METHODS: The data sources used were MEDLINE, Excerpta Medica, and International Pharmaceutical Abstracts databases, and the manufacturer. Bibliographies of articles obtained were reviewed. The keywords used were pentosanpolysulfate, pentosanpolysulfate sodium, and pentosan. Inclusion criteria were blinded selection of English language, prospective, randomized, placebo-controlled comparative trials; > or = 8 weeks' duration; > or = 300 mg daily; adult humans with > or = 1 symptoms including pain, urgency, frequency, and nocturia; symptoms for > or = 12 months; normal urinalysis; negative findings for urine culture and cytology. Exclusion criteria were hemorrhagic cystitis; drug-, microbial-, or radiation-induced cystitis; carcinoma in situ; other influencing diseases. The outcome of success was defined as a > or = 50% decrease in pain, urgency, frequency, and nocturia. The number of successes was extracted by blinded investigators, treating withdrawals as failures. The percentage difference in success rates of pentosan polysulfate and placebo, and the number needed to treat (NNT) were determined for each variable; P values and 95% confidence intervals (CIs) were determined for combined data. Homogeneity of effect was determined by calculating Q (chi-squared). Article quality was assessed using the Chalmers scale to determine if quality affected outcome. Effective inter-rater reliability was determined using Rosenthal's method. Significance was set at P < 0.05. RESULTS: Four studies were included. Data were extracted from all four studies for pain (n = 398), three for urgency (n = 306), two for frequency (n = 160), and one study for nocturia (n = 106). The differences (95% confidence limits) were pain: 16.6% (95% CI 8%, 25%), NNT = 7; urgency: 13.0% (1.0%, 25%), NNT = 7.5; frequency: 16.7% (2.3%, 31.1%), NNT = 6; nocturia: -1% (-19.8%, 21.8%). P values from homogeneity tests were not significant. Mean quality scores were 63.8%, 48.1%, 50.4%, and 65.6%, respectively, in the four studies; the effective inter-rater reliability was 0.96. Results did not differ when weighted by quality score. CONCLUSIONS: Pentosan polysulfate is more efficacious than placebo in the treatment of pain, urgency, and frequency associated with interstitial cystitis. Pentosan polysulfate is not significantly different from placebo in treating nocturia associated with interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness. METHODS: A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale. RESULTS: Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary-Sant questionnaire. CONCLUSION: Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed.

RECORD STATUS: None CITATION: Palylyk-Colwell E. Chondroitin sulfate for treatment of interstitial cystitis. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH). Issues in Emerging Health Technologies Issue 84. 2006

To evaluate the effectiveness of dimethyl sulfoxide in the treatment of patients with biopsies suggestive of interstitial cystitis, 33 patients underwent a controlled crossover trial. Patients were allocated randomly to receive 50 per cent dimethyl sulfoxide or placebo (saline). The medication was administered intravesically every 2 weeks for 2 sessions of 4 treatments each. Response was assessed urodynamically and symptomatically. Thirty women and 3 men (mean age 48 years and mean duration of symptoms 5.5 years) were entered into the study. No significant side effects to dimethyl sulfoxide were noted. When assessed subjectively, 53 per cent of dimethyl sulfoxide treated patients were markedly improved compared to 18 per cent of the placebo treated patients. Of the dimethyl sulfoxide group 93 per cent had objective improvement versus 35 per cent of the placebo group. Thus, dimethyl sulfoxide proved to be superior to placebo in the objective and subjective improvement of patients with interstitial cystitis.

The efficacy of single dose treatment with trimethoprim compared to a 5-day course with the same drug was investigated in 100 children, 3-12 years, with isolated episodes of symptomatic non-febrile urinary tract infection. Cure, defined as sterile urine during the first week after treatment, was achieved in 74% (37/50) in the single dose group compared to 86% (43/50) in the 5-day treatment group. The difference was not statistically significant (chi 2 = 2.25, p = 0.134 two-tailed). The cure rates in relation to P-fimbriation of the infecting E. coli strains were similar in the two groups. During the 6 month follow-up, six children in each treatment group had one or more reinfections. Extended studies are needed to conclude if single dose and conventional treatment courses are equally effective.

PURPOSE: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS: The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.