MINNEAPOLIS — Early recognition of interstitial cystitis/painful bladder syndrome by the primary care physician can prevent this common and debilitating condition from becoming refractory, Dr. Robert Moldwin said at the annual meeting of the Association of Reproductive Health Professionals.
This is an invisible condition, and there often is a lag time of 5–7 years between symptom onset and diagnosis, with patients being given multiple diagnoses, improper treatments such as antibiotics, and referrals to psychiatrists, he said.
The hallmarks of interstitial cystitis/painful bladder syndrome (IC/PBS) are pelvic pain, pressure, or discomfort, typically associated with a persistent urge to void or urinary frequency. Frequent nocturnal voiding is typical, and symptoms do not relate to infection or other pathology.
Although the precise etiology of IC/PBS remains unknown, it is now considered to be a hypersensitivity condition of the bladder wall, and increased understanding of the changes seen in the bladder urothelium are beginning to permit targeted therapies, explained Dr. Moldwin of the urology department at Albert Einstein College of Medicine, New York, and director of the Pelvic Pain Center at Long Island Jewish Medical Center, New Hyde Park, N.Y.
The normal bladder surface is coated with impermeable mucin; in patients with IC/PBS this layer is disrupted, permitting noxious substances such as potassium in urine access to nerves and muscles in the bladder. This sets off an inflammatory response with mast cell activation and the release of histamine, substance P, and other mediators, which results in neurogenic upregulation and a pain response.
In early stages of IC/PBS the symptoms tend to be intermittent, but with increasing duration the pain can become centralized and once that happens, even if the bladder is removed, the pain may remain. This is similar to phantom limb pain, Dr. Moldwin said. “The key is identifying these patients when they still have intermittent symptoms.”
The differential diagnosis includes overactive bladder, endometriosis, and bladder cancer. IC/PBS can be differentiated from overactive bladder by the pattern of urinary urge, with overactive bladder characterized by sudden sporadic urges, whereas IC/PBS is characterized by a steadily and sometimes exponentially increasing sense of discomfort that eases with voiding, he said.
“Of course you don't want to miss bladder cancer, but a 30-year-old nonsmoker is unlikely to have bladder cancer. If there's any hematuria or you are especially concerned you can send off a urine specimen for cytology,” he said.
Otherwise, the diagnosis is empiric, and diagnostic tests such as hydrodistention under anesthesia are not routinely done. In a patient for whom infection has been ruled out, and particularly with pronounced nocturia, it's reasonable to begin empiric therapy, Dr. Moldwin said.
Management encompasses both nonpharmacologic and pharmacologic strategies. Dietary changes often help, and many patients benefit from avoidance of carbonated and caffeinated beverages, alcohol, and citrus fruits. Behavior modification, with gentle exercise, stress reduction, and muscle relaxation, also can help, he added. “I'm a big believer in having patients become empowered, taking control of their own care.”
Oral medications used for IC/PBS include pentosan polysulfate sodium, amitriptyline, and hydroxyzine. Pentosan polysulfate, the only Food and Drug Administration-approved oral medication for this condition in doses of 100 mg three times per day, coats the bladder wall and decreases sensitivity. The drug can take several months to work, and is effective in up to 60% of patients.
The tricyclic antidepressant amitriptyline is useful in helping patients troubled with nocturia sleep at night, and it also has pain reduction properties, probably through inhibition of norepinephrine reuptake in the central and peripheral nervous systems, he said. Amitriptyline can be given in low doses of 10–50 mg per day, preferably at 7 p.m. to avoid a morning hangover effect, he said.
The H1 histamine antagonist hydroxyzine inhibits the mast cell degranulation and histamine release characteristic of the hypersensitive inflammatory response in the bladder wall. The drug is usually given at night, beginning in doses of 25 mg, but response can take a couple of months.
Intravesical agents that are used include dimethylsulfoxide, which is FDA-approved, and unapproved agents such as lidocaine and heparin.
Increased recognition of the importance of IC/PBS, which afflicts 1.2 million women and 82,000 men in the United States, along with an improved understanding of the associated pathologic events, is allowing the development of many new treatments, including antiproliferative factor, liposomes, and intravesical botulinum toxin type A.
Patients often experience comorbid conditions such as allergies, sensitive skin, irritable bowel syndrome, fibromyalgia, and pelvic floor dysfunction. “There are a lot of comorbidities with IC/PBS, but there probably is a common thread running through these patients. When we find that, we should have some better therapies,” he said.