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Interstitial Cystitis: Urgency and Frequency Syndrome JULIUS F

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Interstitial Cystitis: Urgency and Frequency Syndrome JULIUS F Interstitial Cystitis: Urgency and Frequency Syndrome JULIUS F. METTS, M.D., University of California, Davis, School of Medicine, Davis, California Interstitial cystitis is a chronic, severely debilitating disease of the urinary blad- der. Excessive urgency and frequency of urination, suprapubic pain, dyspareunia, O A patient informa- chronic pelvic pain and negative urine cultures are characteristic of interstitial tion handout on inter- stitial cystitis, written cystitis. The course of the disease is usually marked by flare-ups and remissions. by the author of this Other conditions that should be ruled out include bacterial cystitis, urethritis, article, is provided on neoplasia, vaginitis and vulvar vestibulitis. Interstitial cystitis is diagnosed by cys- page 1212. toscopy and hydrodistention of the bladder. Glomerulations or Hunner’s ulcers found at cystoscopy are diagnostic. Oral treatments of interstitial cystitis include pentosan polysulfate, tricyclic antidepressants and antihistamines. Intravesicular therapies include hydrodistention, dimethyl sulfoxide and heparin, or a combi- nation of agents. Referral to a support group should be offered to all patients with interstitial cystitis. (Am Fam Physician 2001;64:1199-206,1212-4.) atients with irritative voiding The nonulcer type of interstitial cystitis symptoms and negative urine cul- occurs in about 90 percent of patients. The tures frequently present a diag- more severe form of the disease (in about 10 nostic challenge for primary care percent of patients) involves Hunner’s ulcers, physicians. Interstitial cystitis is a which are lesions that involve all of the layers Pseverely debilitating disease of the urinary of the bladder wall and appear as brownish- bladder. Symptoms of interstitial cystitis red patches on the bladder mucosa. include excessive urgency and frequency of Women make up 90 percent of patients urination, suprapubic pain, dyspareunia and with interstitial cystitis,1 while men comprise chronic pelvic pain.1 Interstitial cystitis inter- the remaining 10 percent. Children can also feres with employment, social relationships have interstitial cystitis.3 Urinary frequency, and sexual activity. The course of the disease is sensory urgency and lower abdominal pain usually marked by flare-ups and remissions. are common symptoms among children with Interstitial cystitis is a chronic disease that per- the disease. sists throughout the patient’s life. On clinical The onset of interstitial cystitis usually evaluation, patients with interstitial cystitis occurs between 30 and 70 years of age,4 with a should have no other definable pathology, median age of 43.5 The prevalence of the dis- such as urinary infections, carcinoma, or radi- ease appears to be increasing among young ation-induced or medication-induced cystitis and middle-aged women.6 (Parsons CL. Interstitial cystitis, new concepts Most patients consult at least five physi- in pathogenesis, diagnosis and management. cians, including psychiatrists, over a period of Presentation at 3rd annual meeting of the more than four years before interstitial cystitis American Urological Association, June 4, 1998, is diagnosed. Symptomatic patients require San Diego, Calif.). considerably more medical care than their age-matched cohorts.7 Epidemiology Interstitial cystitis may affect as many as Etiology 700,000 women in the United States.2 Data While the exact cause of interstitial cystitis from the Nurses’ Health Study suggest that the is not known, it is probably related to many prevalence of interstitial cystitis among women factors, including autoimmune, allergic and is about 67 per 100,000 and 52 per 100,000.3 infectious etiologies.2 OCTOBER 1, 2001 / VOLUME 64, NUMBER 7 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1199 ing inflammation, tissue irritation and injury, One common etiologic theory of interstitial cystitis is a defect mast cell degranulation and sensory nerve in the glycosaminoglycan component of the mucin layer that depolarization, which result in the urinary urgency, frequency and pain of interstitial cys- covers and protects the urothelium. titis.5,6,10 Glycosaminoglycans are highly hydrophilic and protective. They maintain a stable layer of water between the urothelium According to one widely held theory, the and the bladder lumen, and prevent adhesion symptoms of interstitial cystitis originate from to and invasion of the urothelium by bacteria, a defect in the glycosaminoglycan component microcrystals, ions, proteins and other sub- of the mucin layer that covers and protects the stances in the urine. bladder urothelium8 (Figure 1). A deficiency Another working theory of interstitial cysti- of this layer is thought to cause interstitial cys- tis etiology includes mast cell abnormalities. titis. Low rates of urinary glycosaminoglycan Mast cells are present in the bladder wall of excretion have been found in patients with many patients with interstitial cystitis. interstitial cystitis. The glycosaminoglycan Increased numbers of submucosal mast cells hypothesis is the basis for treating interstitial are found in these patients.11,12 Antigenic cystitis with glycosaminoglycan “replace- exposure of mast cells causes the release of ments,” such as sodium pentosan polysulfate pharmacologically active mediators (e.g., his- (an exogenous, oral glycosaminoglycan) and tamine, prostaglandins, leukotrienes and heparin or hyaluronic acid administered tryptases) that have a significant effect on intravesically.8,9 Irritating substances in the smooth muscle, vascular epithelium and urine may leak through the urothelium, caus- inflammation. Urinary bladder Bladder lumen . Bound water Mucin layer . molecules Endothelium on protein backbone Lamina propria Surface endothelium Smooth muscle ILLUSTRATION BY DAVID KLEMM Section of bladder wall Close-up of epithelial surface FIGURE 1. Normal bladder transitional epithelium with glycosaminoglycan (GAG) layer covering transitional cells. Small blue circles represent bound water molecules, and wavy lines represent the protein backbone. 1200 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 7 / OCTOBER 1, 2001 Interstitial Cystitis OTHER ETIOLOGIC FACTORS Persons with interstitial cystitis should avoid foods that can To date, no convincing evidence confirming cause irritation, including coffee, alcohol, carbonated drinks, a viral, bacterial or fungal cause of interstitial citrus fruits, tomatoes and chocolate. cystitis has been found.13,14 A psychologic etiology of interstitial cystitis has been mentioned, only to be condemned. Research has shown that definite objective evidence of Hunner’s ulcers. Strict application abnormalities are present in patients with of the NIDDK criteria would have misdiag- interstitial cystitis, including findings on blad- nosed more that 60 percent of patients who der biopsy and cystoscopy. The chronic pain, were diagnosed by researchers as definitely frequency, urgency and sleep deprivation having or likely to have interstitial cystitis.6 associated with interstitial cystitis may con- The most typical symptom of interstitial tribute to psychologic stress and secondary cystitis is pelvic pain. The pain is relieved by depression. Suicidal ideation is three to four voiding small amounts of urine from the times more common in patients with intersti- bladder, but soon recurs as the bladder fills. tial cystitis than in the general population.15 Another common symptom is an uncomfort- More than one half of symptomatic patients able, constant urge to void that does not go with interstitial cystitis have depression. away even after the patient has voided. Incon- Chronic bladder and pelvic pain is usually tinence is not typical of interstitial cystitis and, moderate to severe.1,8,16 if present, requires that other diagnoses be An unexplained association has been found diligently sought. Dyspareunia (on deep pen- between interstitial cystitis and other chronic etration) is not uncommon in patients with disease or pain syndromes such as allergies, interstitial cystitis. irritable bowel syndrome, skin sensitivity, The symptoms of interstitial cystitis typi- vulvodynia, fibromyalgia, migraine, endo- cally worsen in the week before menstruation metriosis and chronic fatigue syndrome.17 in contrast to the symptoms of endometriosis, Dyspareunia is not uncommon in persons which are worse during menses. Sometimes with interstitial cystitis and may be related to the symptoms of interstitial cystitis are exacer- the mechanical effects of intercourse on the inflamed bladder. TABLE 1 APPROACH TO DIAGNOSIS Diagnostic Criteria for Interstitial Cystitis Interstitial cystitis is often underdiagnosed or improperly diagnosed. A presumptive diag- Presence of urgency or frequency, or pelvic/perineal or bladder pain nosis may be made by looking for appropriate Presence of glomerulations (pinpoint submucosal hemorrhages) or ulcers clinical criteria. The National Institute of Dia- on cystoscopic examination with hydrodistention under anesthesia betes and Digestive and Kidney Diseases Negative urine culture (NIDDK) developed inclusion and exclusion Absence of genitourinary infections or prostatitis criteria for patients who are being considered Absence of neoplastic diseases or benign bladder tumor for interstitial cystitis research (Table 1).18 Absence of history of radiation, tuberculosis or chemical cystitis (e.g., following cyclophosphamide [Cytoxan] therapy) While the NIDDK criteria are useful for research, they are too restrictive to be used by Adapted with
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