Interstitial Cystitis 

Interstitial cystitis is a clinical syndrome characterized by daytime and nighttime urinary frequency, urgency, and pelvic pain of unknown etiology. Interstitial cystitis has no clear etiology or pathophysiology, and diagnostic criteria for the syndrome remain undefined. Despite considerable research, universally effective treatments do not exist; therapy usually consists of various supportive, behavioral, and pharmacologic measures. Surgical intervention is very rarely indicated.

The International Continence Society has coined the term painful bladder syndrome (suprapubic pain with bladder filling associated with increased daytime and nighttime frequency, in the absence of proven urinary infection or other obvious pathology) and reserves the diagnosis of interstitial cystitis for patients with characteristic cystoscopic and histologic features of the condition.

An international consensus panel was able to generally agree on the following definition of bladder pain syndrome/interstitial cystitis: unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder and associated with lower urinary tract symptoms of more than 6 weeks’ duration, in the absence of infection or other identifiable causes.

In 1887, Skene initially described a condition characterized by inflammation that destroyed the urinary bladder "mucous membrane partly or wholly and extended to the muscular parietes." Guy Hunner popularized the disease with the description of characteristic bladder wall ulcers.^[1] The first comprehensive epidemiologic description of interstitial cystitis is credited to Hand, who in 1949 described the widespread, small, submucosal bladder hemorrhages and the significant variation in bladder capacity characteristic of the condition.

Despite years of intensive research, there are no specific clinical or urinary markers; no radiographic, laboratory, or serologic findings; and no biopsy patterns that are pathognomonic for interstitial cystitis. Interstitial cystitis is a diagnosis of exclusion (see Differentials, Presentation, and Workup.)

The most important element in treating patients with interstitial cystitis is education and emotional support. Periodic exacerbations are managed as they occur because no long-term therapy has been shown to prevent or delay recurrent episodes. Therefore, the purpose of treatment is to palliate and alleviate symptoms.

Because no discrete pathognomonic pathologic criteria exist for assessing and monitoring disease severity, indications and goals for treatment are based on the degree of patient symptoms. Assessing patient response to treatment is also complicated because of the subjective nature of symptoms and the lack of objective serologic, physical, or histopathologic findings. Conservative measures and oral or intravesical treatments are considered first-line treatment. (See Treatment.)

The pathophysiology of interstitial cystitis is poorly understood. Various etiologies have been proposed, none of which adequately explains the variable presentations, clinical courses, or responses to therapies. This may indicate that interstitial cystitis represents a number of as yet undefined, disparate pathologic conditions that, over time, ultimately present as the clinical syndrome of urinary frequency, urgency, and pelvic pain.

Clinically, interstitial cystitis is often divided into 2 distinct subgroups based on findings at cystoscopy and bladder overdistention. These categories are the ulcerative (ie, classic) and nonulcerative (ie, Messing-Stamey) types.

Ulcerative

The hallmark of classic interstitial cystitis is a diffusely reddened appearance to the bladder surface epithelium associated with 1 or more ulcerative patches surrounded by mucosal congestion (ie, Hunner ulcer) on the dome or lateral walls of the bladder upon cystoscopic examination. These ulcers may become apparent only after overdistention, because discrete areas of mucosal scarring rupture during the procedure. Overdistention in this type of interstitial cystitis results in fissures and cracks that bleed in the bladder epithelium.

In the United States, the ulcerative type is rare (< 10% of cases), and some authors consider this type to be more resistant to therapy. Biopsy findings show that the ulcerative lesion can be transmural, associated with marked inflammatory changes, granulation tissue, mast cell infiltration, and, in some cases, fibrosis. This classic form of interstitial cystitis can be associated with progressively smaller bladder capacity over time.

Nonulcerative

The nonulcerative type of interstitial cystitis is characterized by similar clinical symptoms (ie, frequency, urgency, pelvic pain), but the cystoscopic findings noted for the ulcerative lesion are absent. Instead, after overdistention, these patients demonstrate glomerulations that are discreet, tiny, raspberry-like lesions appearing on the dome and lateral walls of the bladder and tiny mucosal tears and submucosal hemorrhages. Bladder biopsy findings in these patients often are unremarkable, as compared with those found in patients with classic interstitial cystitis.

The etiology of interstitial cystitis remains unknown and is likely multifactorial.^{[2, 3]} Proposed etiologies include the following:

• Pathogenic role of mast cells in the detrusor and/or mucosal layers of the bladder
• Deficiency in the glycosaminoglycan layer on the luminal surface of the bladder, resulting in increased permeability of the underlying submucosal tissues to toxic substances in the urine^[4]
• Infection with a poorly characterized agent (eg, a slow-growing virus or extremely fastidious bacterium)
• Production of a toxic substance in the urine
• Neurogenic hypersensitivity or inflammation mediated locally at the bladder or spinal cord level
• Manifestation of pelvic floor muscle dysfunction or dysfunctional voiding
• Autoimmune disorder

Although interstitial cystitis has not traditionally been considered a heritable condition, a 2005 study from the University of Maryland reported a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition.^[5]

Patients with interstitial cystitis are more likely to have undergone prior gynecologic surgery and/or to have a history of urinary tract infections and are 10-12 times more likely to report childhood bladder problems. Interstitial cystitis is associated with several chronic illnesses, including inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome, fibromyalgia, and atopic allergy. Psychiatric conditions associated with interstitial cystitis include anxiety disorder, depression, and adjustment reactions.

Reports on the prevalence of interstitial cystitis conflict, depending on the country of origin and the criteria used for diagnosis. In the United States, Curhan et al showed a prevalence of 60-70 cases per 100,000 women. The incidence rate of interstitial cystitis is 2.6 cases per 100,000 women per year in the United States.

Reports from Europe indicate a prevalence of 18 cases per 100,000 women and only 3-4 cases per 100,000 women in Japan. The marked differences between these countries and the United States are likely due to differences in diagnostic criteria, varying from all-encompassing clinical criteria (eg, those from the National Institute of Diabetes & Digestive & Kidney Diseases [NIDDK] of the US National Institutes of Health) to very strict criteria based on a pathologic diagnosis.

Race-, sex-, and age-related differences in incidence

Of patients with interstitial cystitis, 94% are white, and approximately 90% are female. Household size, marital status, number of male sexual partners, educational status, and parity are not statistically different between patients with interstitial cystitis and healthy controls. Interstitial cystitis appears to be slightly more common in Jewish women.

Median age at presentation is 40 years. However, Close et al have shown that interstitial cystitis may occur in children. In their series, the median age of onset was 4.5 years, with a mean age of diagnosis of 8.2 years. The children had diffuse glomerulations and terminal hematuria. Of the 16 children in the study, 15 improved after bladder hydrodistention.^[6]

Interstitial cystitis is a chronic condition with a variable course characterized by intermittent periods of exacerbations and remissions. Unfortunately, the disorder responds poorly to treatment in many cases. No treatment to date has been shown to decrease disease progression; therefore, the purpose of treatment is to palliate and alleviate symptoms. Although rare, classic interstitial cystitis may lead to bladder wall scarring that results in a contracted, small-capacity bladder. These patients often require augmentation cystoplasty or some form of urinary diversion.

Because of the chronic nature of interstitial cystitis and the significant impact on the patient's quality of life, the psychological impact of the condition can be enormous. Ongoing emotional support is essential.^{[7, 8]}

More information about interstitial cystitis and support information for patients can be obtained from the following associations:

• Interstitial Cystitis Association
• 51 Monroe St. Suite 1402
• Rockville, MD 20580
• Telephone toll-free: 1-800-help ICA
• Email: ICAmail@ichelp.com
• www.ichelp.org
• American Foundation for Urologic Disease, Inc.
• 300 West Pratt St. Suite 401
• Baltimore, MD 21201
• Telephone toll-free: 1-800-242-2383
• HealthlinkUSA
• Cystitis Support Group - United Kingdom
• Interstitial Cystitis Network: The Interstitial Cystitis Network is a large archive of information on the Web for interstitial cystitis, including patient materials, a research library, and physician referrals
• The National Institutes of Health maintains a patient information site for Interstitial Cystitis
• Urology Channel, which is a source of general health information about urologic subjects, has a review of interstitial cystitis

For patient education information, see Urinary Tract Infections (UTIs).