eMedicine Specialties > Urology > Interstitial Cystitis

Interstitial Cystitis

Author: Eric S Rovner, MD, Professor, Department of Urology, Medical University of South Carolina
Coauthor(s): Colin Murrah Goudelocke, MD, Fellow in Pelvic Surgery, Department of Urology, Medical University of South Carolina College of Medicine
Contributor Information and Disclosures

Updated: Feb 11, 2010

Introduction

Interstitial cystitis (IC) 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 undefined diagnostic criteria. Despite considerable research, universally effective treatments do not exist for interstitial cystitis, and therapy usually consists of various supportive, behavioral, and pharmacological 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. To clarify the criteria for diagnosis, some clinicians prefer the term painful bladder syndrome or interstitial cystitis, defined as a syndrome of chronic pain, pressure, or discomfort associated with the bladder, usually accompanied by urinary frequency in the absence of any identifiable cause.

An international consensus panel sponsored by the Society for Urodynamics and Female Urology was able to generally agree on a definition of bladder pain syndrome/IC: 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.

History of the Procedure

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 epidemiological description of interstitial cystitis is credited to Hand (1949), who described the widespread, small, submucosal bladder hemorrhages and the significant variation in bladder capacity characteristic of the condition.

Problem

Despite years of intensive research, no specific clinical or urinary markers; radiographic, laboratory, or serologic findings; or biopsy patterns are pathognomonic for interstitial cystitis. Interstitial cystitis is a diagnosis of exclusion. One obstacle in the diagnosis and management of interstitial cystitis is the lack of a consensual clinical definition. No universally accepted clinical criteria exist for the diagnosis of interstitial cystitis.

The differential diagnoses of urinary frequency, urgency, and/or pain includes the following:

• Infectious or inflammatory conditions - Recurrent urinary tract infection (UTI), urethral diverticulum, infected Bartholin gland or Skene gland, vulvovestibulitis, tuberculous/eosinophilic cystitis, vaginitis (eg, bacterial, viral [eg, herpes]), or schistosomiasis
• Gynecologic causes - Pelvic malignancy or mass (eg, fibroid, endometrioma), endometriosis, mittelschmerz, pelvic inflammatory disease, or genital atrophy
• Urologic causes -Bladder cancer or carcinoma in situ (CIS), radiation cystitis, overflow incontinence, acontractile detrusor, prostatodynia, chronic pelvic pain syndrome, bladder outlet obstruction (eg, urinary retention with overflow incontinence), large postvoid residual volume, or open bladder neck (eg, intrinsic sphincteric deficiency, urolithiasis, urethritis)
• Neurologic causes - Detrusor overactivity, Parkinson disease, lumbosacral disk disease, spinal stenosis, spinal tumor, multiple sclerosis, or cerebrovascular accident
• Other possible diagnoses - Dysfunctional voiding, vulvodynia, pelvic floor myalgia, degenerative joint disease, hernia, inflammatory bowel disease, gastrointestinal neoplasm, diverticulitis, or adhesions from prior surgery

Clinically, the practitioner is somewhat obligated to consider these potential alternative diagnoses prior to diagnosing interstitial cystitis. The implications of a diagnosis of interstitial cystitis are profound in that it is a chronic condition without universally effective therapy.

Frequency

• Prevalence: 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, whereas reports from Europe indicate a prevalence of 18 cases per 100,000 women and only 3-4 cases per 100,000 women in Japan. These marked differences 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. The incidence rate of interstitial cystitis is 2.6 cases per 100,000 women per year in the United States.
• Race: Of patients with interstitial cystitis, 94% are white. Interstitial cystitis appears to be slightly more common in Jewish women.
• Sex: Approximately 90% of patients with interstitial cystitis 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.
• Age: Median age at presentation is 40 years. However, Close et al from Seattle 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.²
• Family history: Although interstitial cystitis has not traditionally been considered a hereditable condition, a recent study from the University of Maryland reports a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition.³
• Associated medical conditions: Patients with interstitial cystitis are more likely to have undergone prior gynecologic surgery and/or to have a history of UTIs 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. In addition, several psychiatric conditions have been associated with interstitial cystitis, including anxiety disorder, depression, and adjustment reactions.

Etiology

The etiology of interstitial cystitis remains unknown and is likely multifactorial. 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 urine⁴
• 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

Pathophysiology

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 pathological 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 intraoperative findings at cystoscopy and bladder overdistension. These categories are the ulcerative (ie, classic) and nonulcerative (ie, Messing-Stamey) types.

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

The nonulcerative type of interstitial cystitis is characterized by similar clinical symptoms (ie, frequency, urgency, pelvic pain), but the cystoscopic findings noted above are absent. However, following overdistension, these patients demonstrate glomerulations that are discreet, tiny, raspberrylike 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 compared to those found in patients with classic interstitial cystitis.

Presentation

Because interstitial cystitis is a poorly defined entity of unknown etiology, the clinical presentation is often not uniform and the symptoms vary in severity and nature.

The onset of symptoms is often but not invariably acute, and the patient is sometimes able to describe the moment at which symptoms began. Patients often associate the onset of symptoms with a specific UTI, catheterization, or bladder or pelvic surgery.

Patients with interstitial cystitis have a high incidence of associated conditions, including allergies, irritable bowel syndrome, fibromyalgia, and focal vulvitis.

Interstitial cystitis is characterized by periods of exacerbation followed by variable periods of remission. Symptoms of frequency, urgency, pain, and dysuria may vary daily or weekly or may be constant and unrelenting for months or years and then resolve spontaneously with or without therapy. In females, symptoms may fluctuate relative to the ovulatory cycle. In addition, recent data suggest that some pregnant patients may experience periods of remission during the second and third trimester.

Patients with interstitial cystitis may describe pressure, discomfort or pain in the pelvis, a vague sense of incomplete bladder emptying, or a constant sensation or compulsion to void. Furthermore, a substantial emotional and psychological overlay to the complaints due to the duration and severity of symptoms may or may not be present, and patients may have had an incomplete response to prior therapies.

Spontaneous remission occurs in as many as 50% of patients at a mean of 8 months. Patients may experience complete and spontaneous relief from the symptoms, may undergo a waxing and waning course, may be completely asymptomatic with intermittent flares, or may have a chronically progressive course of increasing symptoms over several years.

The most prevalent feature of interstitial cystitis is irritative lower urinary tract symptoms, including urinary frequency. The exact number of micturitions, daytime or nighttime, is not important; however, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria, more than 8 micturitions per day is considered adequate for inclusion into clinical studies. Daytime frequency in the absence of nocturia is not characteristic of interstitial cystitis. The absence of significant nocturia may suggest an alternative diagnosis (eg, sensory urgency).

Pain with bladder filling is a common finding that may be reproduced urodynamically or with cystography. Patients may complain of constant pelvic pain or pain related to a full bladder. Dyspareunia is common in as many as 50% of women. Men with interstitial cystitis may report perineal, groin, penile, or scrotal pain; the diagnosis of prostadynia or nonbacterial prostatitis (chronic pelvic pain syndrome) should be entertained. Urinary incontinence is quite rare. Patients with a primary complaint of incontinence may require further evaluation, including urodynamic studies.

Patients with interstitial cystitis have a high incidence of associated conditions, including allergies, irritable bowel syndrome, fibromyalgia, and focal vulvitis. Dyspareunia, sex-related distress, and decline in libido and orgasm frequency are also common.

The diagnosis of interstitial cystitis is most often made when the long-standing symptoms of urinary frequency, urgency, and pelvic pain exist in the absence of a readily identifiable etiology such as UTI. Urinalysis and urine culture are mandatory. A voiding diary is helpful in establishing baseline voiding frequency. Cystoscopy is considered by some clinicians to be mandatory in order to diagnose interstitial cystitis; however, this is somewhat controversial because of the lack of specific or pathognomonic findings (except perhaps the very rare finding of a Hunner ulcer). Urodynamic evaluation is optional, and finding detrusor overactivity or pelvic floor dysfunction may suggest an alternative diagnosis.

Validated questionnaires may serve as an aid in clinical diagnosis, as a means of tracking symptom response to therapy in clinical practice, or as an assessment of response to treatments in study populations. However, despite the usefulness of these metrics, interstitial cystitis remains a diagnosis of exclusion. The Wisconsin Interstitial Cystitis Scale was initially validated in a small population³⁸ but has been shown in subsequent larger studies to be valid and easy to implement.³⁹ It has also been show to correlate well with other validated interstitial cystitis questionnaires.⁴⁰

The Interstitial Cystitis Symptom and Problem Index (O’Leary-Sant Interstitial Cystitis Symptom and Problem Index) are self-administered questionnaires that were found to be valid and reliable and serve as a useful adjunct to aid in diagnosis. They were not designed to be used as a screening tool.⁴¹ Theses indices have also been shown to be responsive to changes in interstitial cystitis symptoms⁴² and may therefore be useful in measuring response to therapy in both clinical and research settings.

Because no pathognomonic criteria exist for the diagnosis of interstitial cystitis, the modified NIDDK criteria for the inclusion of patients in interstitial cystitis basic and clinical research studies can be used. These criteria, initially developed in 1987, became the de facto definition of the disease; however, a significant number of patients with interstitial cystitis do not meet these criteria.

National Institute of Diabetes and Digestive and Kidney Diseases criteria

One of the following cystoscopic findings after distension under anesthesia for 1-2 minutes at 80-100 cm water:

• Glomerulations in at least 3 quadrants of the bladder and at least 10 glomerulations per quadrant
• Classic Hunner ulcer

One of the following subjective symptoms:

• Pain associated with the bladder
• Urinary urgency

Absence of any of the following criteria, which would exclude the diagnosis:

• Cystometric bladder capacity larger than 350 mL in a conscious patient with either gas or liquid filling
• Intense urge to void when patient's bladder has been filled with 100 mL of gas or 150 mL water during cystometry at a fill rate of 30-100 mL/min
• Demonstration of phasic involuntary bladder contractions on cystometry findings at a fill rate of 30-100 mL/min (Note that, although this is an exclusion criterion as per the NIDDK, detrusor instability may be present in as many as 14% of patients with a clinical diagnosis of interstitial cystitis.)
• Duration of symptoms less than 9 months
• Nocturia
• Symptoms relieved by antimicrobials, urinary antiseptics, anticholinergics, or antispasmodics
• Frequency of micturition of less than 8 times per day
• Diagnosis of bacterial prostatitis or cystitis within a 3-month period
• Presence of ureteral or bladder calculi
• Active genital herpes
• Uterine, cervical, vaginal, or urethral cancer
• Urethral diverticulum
• Cyclophosphamide or other chemical cystitis
• Tuberculous cystitis
• Radiation cystitis
• Benign or malignant bladder tumors
• Vaginitis
• Patient younger than 18 years

Indications

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 serological, physical, or histopathological findings. Conservative measures and oral or intravesical treatments are considered first-line treatment.

Indications for surgical intervention in interstitial cystitis (IC) are limited to (1) cystoscopy for both diagnosis and therapeutic purposes, (2) neuromodulation for urgency or frequency symptoms, and (3) urinary reconstruction, (4) urinary diversion, or both for the rare patient who may benefit from these procedures. Botulinum toxin type A is an emerging therapy for many urologic diseases associated with frequency, urgency, and urge incontinence but is still considered investigational in the treatment of interstitial cystitis.^5,6,7

Although somewhat controversial, cystoscopy under anesthesia and bladder overdistension, with or without bladder biopsy, is used by many physicians as an initial diagnostic procedure. A diminished bladder capacity under anesthesia and/or a Hunner ulcer (very rare) are suggestive (and some feel diagnostic) of interstitial cystitis. Furthermore, relief of urinary frequency, urgency, and pain has been reported, at least temporarily, in as many as 60% of patients following bladder overdistension. However, note that, initially, many patients find that their symptoms are transiently exacerbated following this procedure.

Bladder biopsy is performed to evaluate for CIS and the presence of mast cells. Some authors have proposed a pathophysiological role for mast cells in the genesis of interstitial cystitis and have suggested that an increased density of mast cells may be present in patients with interstitial cystitis. Furthermore, the finding of mast cells may suggest a potential role for antihistamine compounds in the treatment of the condition.

Direct sacral nerve root stimulation, or neuromodulation, has been shown to be effective in treating frequency and urgency associated with interstitial cystitis. In patients taking chronic narcotics for refractory pain associated with interstitial cystitis, sacral neuromodulation has been shown to decrease (but not eliminate) narcotic requirements after implantation.

Indications for urinary tract reconstruction or diversion are very limited in patients with interstitial cystitis. Candidates for these procedures should have exhausted all reasonable and available medical, pharmacological, and behavioral therapies for their condition. They should also understand that even technically successful urinary tract reconstruction or urinary diversion still may not relieve the underlying symptoms of pain and urinary urgency. These are large surgical undertakings and, for the most part, are irreversible. Only limited success has been reported, thus, patients should be extensively counseled prior to undergoing this type of surgical therapy for interstitial cystitis.

Relevant Anatomy

Abdominal, pelvic, and directed neurologic examinations should be performed in all patients with voiding dysfunction; nevertheless, the findings from these examinations are often unrevealing in patients with interstitial cystitis (IC). Women with interstitial cystitis may express some discomfort with palpation over the urethra and bladder base. A correlation has been noted between urethral tenderness and the finding of a Hunner ulcer after cystoscopic examination.

Pain upon urethral palpation in the presence of an anterior vaginal wall mass may suggest urethral diverticulum, whereas cervical motion tenderness may suggest pelvic inflammatory disease. Examination with a speculum may reveal prolapse; masses; and evidence of vaginitis, herpes, vestibular adenitis, vulvovestibulitis, vulvodynia, or other pathology. These findings suggest a diagnosis other than interstitial cystitis.

Palpation for a full bladder and bimanual examination evaluating for adnexal masses should be part of the complete examination. Rectal examination should always be performed to evaluate for masses, tenderness, and assessment of rectal and pelvic floor (levator) muscle tone.

Neurologic examination findings are usually unremarkable, but abnormalities of motor function, sensation, or reflexes may indicate spinal cord or nerve root dysfunction and should prompt further evaluation for other diagnoses.

Male patients commonly have no abnormalities upon examination. In male patients with irritative lower urinary tract symptoms, bladder outlet obstruction and chronic nonbacterial prostatitis are important diagnostic considerations.

Contraindications

Contraindications to cystoscopy and bladder hydraulic distension include anesthetic risk, history of prior rupture during distension, pregnancy, and UTI.

• Search for CME/CE on This Topic »

• Cystitis, Nonbacterial (Urology)
• Bladder, Cystitis (Radiology)
• Gynecologic Pain (Obstetrics and Gynecology)
• Cystectomy, Partial (Urology)

• Kidneys and Urinary System Center
• Urinary Tract Infection Causes
• Urinary Tract Infection Symptoms
• Urinary Tract Infections Treatment
• Urinary Tract Infections Overview

• More Favorable Results With Tanezumab for Various Pain Types
• Childhood Maltreatment Linked to Migraine and Other Pain Disorders

• Clinical Phenotyping in Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Interstitial Cystitis: A Management Strategy for Urologic Chronic Pelvic Pain Syndromes
• Primary Care Physician Practices in the Diagnosis, Treatment and Management of Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome
• Pelvic Floor Disorders and Quality of Life in Women with Self-reported Irritable Bowel Syndrome