Carole Cranford, age 52, comes to the outpatient clinic complaining of pain and pressure in the bladder area, which she rates as a 10 on a 1-to-10 scale, as well as urinary urgency and frequency. She says she has been voiding 20 or more times per day for the past year. She reports pain during and after sexual intercourse, which at times has deterred her from having sex. The pain increases when her bladder is full, isn’t relieved when she voids, and isn’t cyclic or timed with her menstrual cycle.

Which condition would you suspect as the cause of Ms. Cranford’s symptoms? Most likely, you’d place interstitial cystitis (IC) at the top of your list. Also called painful bladder syndrome, IC is marked by pelvic and bladder pain of varying severity and lasting for an extended time, along with urinary frequency. Many patients with IC have pain on bladder filling and urination, as well as with sexual intercourse. They void frequently to decrease pain by eliminating urine in the bladder. Pain commonly occurs in the general pelvic region, inguinal area, inside of the thighs, in the labia or vaginal lips, deep inside the vagina, urethra, clitoris, and in the perineum.

The cause of IC remains unknown. Diagnosis and treatment can be controversial, and for many patients, the treatment is complicated. New research indicates IC is more prevalent than originally thought. According to the RAND IC Epidemiology (RICE) Study, the largest IC epidemiology study undertaken, about 3 to 8 million women in the United States (roughly 3% to 6% of all women) may have IC. Findings from the Boston Area Community Health (BACH) survey show that roughly 1 to 4 million men have IC. However, that number is probably lower than the true rate because IC in men may be mistaken for another disorder, such as chronic prostatitis or chronic pelvic pain syndrome. IC can start in childhood, although studies haven’t been done to establish its prevalence in this age group.

Pathophysiology

Several pathogenic mechanisms have been proposed to explain IC. According to one theory, injury to the bladder’s inner protective mucous lining causes leakage of urinary chemicals (such as potassium) into surrounding tissues, resulting in pain and bladder irritation. Many studies show that IC patients have bladder-lining abnormalities, which may appear in biopsies. Experts don’t know whether these abnormalities are primary or arise secondary to another (unrecognized) condition.

A second theory involves the glycosaminoglycan (GAG) layer, which normally coats the surface lining of the bladder, making it impermeable to solutes. According to this theory, defects in the GAG layer may allow urinary irritants to penetrate and activate underlying nerve and muscle tissues. This process may promote further tissue damage, pain, and hypersensitivity. Bladder mast cells also may play a role in proliferation of ongoing bladder damage after the initial injury.

A third theory involves antiproliferative factor (APF)—a unique protein found in urine in the bladder of IC patients. This protein may prevent growth of healthy new bladder cells and prevent bladder cells from repairing the damaged bladder lining.

Assessment and diagnosis

IC diagnosis rests on characteristic signs and symptoms and exclusion of other possible causes. (See Conditions that may mimic IC by clicking on the PDF icon above.) IC always causes pain associated with bladder filling or emptying, usually accompanied by urinary frequency, urgency, and nocturia. The pain, which originates from the bladder, usually is felt suprapubically. Urinary frequency occurs because voiding partially or completely relieves the pain caused by bladder filling; thus, patients prefer to maintain low bladder volumes.

IC patients commonly have several diagnoses, such as irritable bowel syndrome, endometriosis, vulvodynia, migraine, fibromyalgia, dyspareunia, increased pain during the luteal phase of the menstrual cycle, or dysmenorrhea. When one of these comorbid conditions flares or causes symptoms, the patient also may have a flare or exacerbation of IC.

Many clinicians use the Pelvic Pain, Urgency, and Frequency (PUF) questionnaire as a screening and diagnostic tool. A score of 10 or greater suggests IC. Patients may describe the pain as ranging from a mild burning sensation to severe and debilitating. They may report sitting on the toilet for hours at a time to let urine dribble from their bladders more or less continuously, to keep the bladder as empty as possible and thus minimize pain.

Potassium sensitivity test

Although the American Urological Association’s preliminary IC Clinical Guidelines don’t recommend the potassium sensitivity test to help
diagnose IC, many clinicians find it helpful. In this procedure, 40 mL of sterile water is instilled into the bladder via sterile technique, and the patient is asked if she has bladder pain. The bladder is drained and 40 mL of 0.4% potassium chloride is instilled. Increased pain on potassium instillation indicates bladder hypersensitivity and suggests IC.

Cystoscopy with hydrodistention

This test may be done in the office or in the operating room under general anesthesia. With the patient’s bladder filled to capacity with normal saline solution, the practitioner examines the epithelium with a telescopic fiber inserted through the urethra to the bladder. Glomerulations (tiny hemorrhages—the telltale signs of IC) appear only while the bladder is distended. These hemorrhages are found in 95% of IC patients.

Cystoscopy also may reveal bladder calculi, which can cause symptoms similar to those of IC. Less frequently, cystoscopy reveals epithelial ulcerations (Hunner’s ulcers), lesions, and scars. Hunner’s ulcers indicate IC, though hydrodistention isn’t needed to see them.

Tissue biopsy

A biopsy can distinguish between epithelial ulcers and cancerous lesions, as well as detect mast cells in the bladder, which sometimes are abundant in IC. But some IC sufferers lack epithelial glomerulations or ulcers.

Treatment

Treatment aims to decrease or eliminate bladder and urethral discomfort and relieve urinary frequency and urgency. Modalities include drugs, bladder instillation, various procedures, and dietary modification.

Pharmacologic options

Pentosan polysulfate (Elmiron)—the only oral drug approved to treat IC—is given as 100 mg three times daily to reconstitute the deficient GAG layer over the bladder lining. Other pharmacologic options include: