Often confused with other conditions, this disorder is one of the most difficult to diagnose and treat in primary care. Two experts offer guidance.

The symptoms of interstitial cystitis (IC)—a chronic inflammation of the subepithelial connective tissue of the urinary bladder—are not always present at the same time. Moreover, they may come and go. There is even some disagreement about whether IC even exists. All of the above considerations add up to a challenging diagnosis for primary-care clinicians. The Clinical Advisor asked Amy Rejba, MSN, CRNP, a women’s health nurse practitioner at the Pelvic and Sexual Health Institute in Philadelphia, and Andrew J. Combs, RPA-C, clinical assistant professor in the Department of Urology at the State University of New York Downstate Medical Center in Brooklyn and a certified urologic physician assistant, to discuss what one textbook calls “an enigma in the urologic firmament.”

Q: Why is IC one of the most difficult diagnoses to make in primary care?
Ms. Rejba: The difficulty lies in that there is no consensus on what IC is, not even on the name (it is also sometimes called “painful bladder syndrome”). In addition, there’s no gold standard diagnostic test, and there is a lack of education. The word is just now getting out for primary care.
Mr. Combs: I would call it an elusive diagnosis. Clinicians really need to have their antennae up to detect it.

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Q: Who is most likely to get IC?
Ms. Rejba: For a long time, the typical picture was the 40-something, well-educated professional woman, but that may be because such women are able to see multiple clinicians. According to one estimate, up to one in 4.5 women and one in 11 men may have some form of IC. Clinicians are now seeing younger women and people referred earlier.
Mr. Combs: IC has been reported in men and children and crosses all races and economic backgrounds. It may be more common in younger people than previously suspected; the incidence may be related to how aggressively one looks to make the diagnosis.

Q: What symptoms should alert clinicians to the possibility of IC?
Mr. Combs: The first is irritative voiding symptoms—increased frequency and urgency, which is a heightened sensation of the need to void that is difficult to defer. The second is bladder pain and discomfort. The classic description is pain that increases in intensity with bladder filling and diminishes with voiding, but some people feel pain during urination itself; still others feel constant pelvic pain. These symptoms may wax and wane. The same person who needed to urinate every 20 minutes may later void more normally.
Ms. Rejba: Symptoms may not show up simultaneously. A small percentage of IC patients may present with only one of the classic symptoms at a time. Over time, especially without diagnosis and treatment, symptoms intensify.

Q: Is there an algorithm for diagnosis or a standard line of questioning?
Ms. Rejba: There are two questionnaires available, the O’Leary-Sant index and the pain/urgency/frequency (PUF) questionnaire. Both ask about frequency, urgency, burning, and pain, but the PUF was specifically designed as a screening tool, so it might be more helpful in a primary-care setting.
Mr. Combs: A voiding diary is very useful to delineate the actual degree of frequency, functional bladder capacity, and total daily output and can be useful in identifying abnormal voiding patterns. The diary includes the date, time, and amount of urine voided. One would also note the timing, duration, and intensity of pain if that were an associated complaint. If a patient has increased or large output confined to a certain time of day (e.g., at work), I would also ask her to keep a three- to four-day diary of the time, type, and amount of liquid consumed. I am often amazed by people who complain of urinary frequency but seem oblivious to their drinking several large bottles of water per day or five cups of coffee in a row. They may be making 3-5 L of urine a day when a more normal output is 1.5-2 L.

Q: Many other conditions can cause the symptoms of IC. In what order should clinicians rule these out, and how?
Mr. Combs: The biggest trap is making a diagnosis based solely on the patient’s symptomatology. IC is more a diagnosis of exclusion. To rule out other conditions, do a urinalysis and urine culture first. Urinalysis can reveal pH, concentration, and the presence of RBCs, WBCs, protein, and sugar. Patients with glucosuria produce a large volume of urine, as seen in diabetes, causing increased frequency and urgency. Protein in the urine may indicate renal disease, which can also increase urine output. Crystals might suggest stone disease. The urine culture can reveal UTI. Hematuria alone needs to be investigated further by a urologist as it may indicate a urinary tract neoplasm.

Q: Do other conditions sometimes appear concurrently? How can the clinician sort this out?
Ms. Rejba: About 15% of patients with IC have also been found to have overactive bladder (OAB), in which the bladder contracts involuntarily. Infection used to be an exclusion factor, but we do see patients who get infections in addition to IC.
Mr. Combs: There are reports of other diseases occurring with increased frequency in patients with IC (e.g., certain autoimmune connective tissue disorders), but whether they are related or merely a coincidence has yet to be determined. Infrequently, IC has been reported in multiple family members, suggesting a genetic component. However, the fact that IC affects around 700,000 to 1 million women means it, too, may be coincidental.

Q: Is misdiagnosis common?
Ms. Rejba: It is. For women, the easiest misdiagnosis is often an overlapping condition, such as endometriosis. Primary-care clinicians should know that IC flares often coincide with the menstrual cycle. We pay special attention to patients with “recurrent UTIs.” It is stunning how many patients are not having their urine cultured. Everybody is busy, and the prescription gets called in without a specimen, just the UTI-like symptoms. These may be IC flares rather than UTIs.
Another common misdiagnosis is OAB. In primary care, if you have prescribed an OAB medication and it has not resolved a patient’s urinary frequency, IC should be a consideration. With OAB, people urinate frequently because they are afraid they will leak; with IC, they feel discomfort or pain and sense that they could urinate at any moment.

Q: What would you like the primary-care clinician to have checked out before the patient comes to you?
Ms. Rejba: After the urine culture and urinalysis, one simple thing that makes a tremendous difference for many patients is identifying and cutting back on foods that irritate the bladder. Common ones are coffee, diet soda, citrus fruits, and alcohol but there are many more, and it is often an individual matter. The primary-care clinician can suggest this as an option: “Would you like to try to modify your diet for a few weeks?”
Mr. Combs: I also like the voiding diary to better delineate their complaint, particularly since patients who have irritating symptoms for a prolonged period often lose objectivity. A diary also becomes a useful baseline against which to compare relative change or response to therapy.

Q: What can happen if IC goes untreated?
Ms. Rejba: As symptoms progress, they become more difficult to treat. Once patients get into chronic pain and daily urgency, the nervous system is starting to get upregulated. In the late stages, even medications may fail.
Mr. Combs: IC symptoms can be debilitating and may severely impact quality of life. In some cases, IC can progress to the development of a small contracted bladder so fibrotic it holds only a few ounces of urine, essentially making the patient a bladder cripple. Fortunately, this is the exception rather than rule.

Q: When is it time to refer? To whom?
Ms. Rejba: The old criterion was that if the patient hasn’t had all of the symptoms constantly for six months, it’s not IC. However, if you strongly suspect IC, refer the patient as soon as possible. As previously noted, anyone with hematuria should see a urologist immediately.
Mr. Combs: If a patient presents with recent onset of frequency, urgency, and nocturia of several weeks’ or months’ duration and you’ve ruled out infection, urologic manifestation of systemic disease, or abnormalities in their voiding diary (e.g., excessive fluid intake or infrequent voiding), it is reasonable to prescribe an empiric course of anticholinergic medication. This is based on the presumptive diagnosis of OAB, which is far more common than IC. But if the patient has been having problems for years and you are the third clinician she has seen without achieving a successful diagnosis or resolution, it’s time for referral. Or refer any time you have reached the limits of your expertise and practice. Referral should be to someone who specializes in voiding dysfunction for further evaluation and management. The specialist will rule out such conditions as bowel dysfunction; new onset of such neurologic disease as multiple sclerosis; other types of voiding disorders, such as primary bladder neck dysfunction or dysfunctional voiding; and urinary tract neoplasm. Further decisions regarding the performance of urodynamic testing or cystoscopy are at the discretion of the consultant.

Q: What treatments are available?
Mr. Combs: Only two treatments have FDA approval: Pentosan polysulfate (Elmiron) tablets and dimethylsulfoxide for intravesical instillation. Nearly 140 different treatments have been described for IC. These include everything from dietary modification to various combinations of antispasmodic, anticholinergic, analgesic, anti-inflammatory, and antidepressant medications. There are also various intravesically instilled drug cocktails. More radical therapies have included implantable nerve stimulators, surgical enlargement of the bladder known as augmentation cystoplasty, or even total cystectomy and creation of a neobladder. There are so many different treatments because none works consistently well. While many approaches seem to work in at least some patients, under critical analysis, most hardly do better than placebo. Even following radical surgery, some patients have complained of persistent pelvic pain and discomfort.

Q: Is IC curable?
Mr. Combs: IC is controllable but not curable. Even when patients respond to therapy, their symptoms may wax and wane but never disappear permanently.
Ms. Rejba: It is manageable. Patients can remain symptom-free for years.

Q: What can the primary-care clinician do to make the patient’s life more bearable?
Ms. Rejba: UTI management. Many people live closer to their primary-care provider than their specialist. If patients can go in and drop off urine samples, the primary-care clinician can start to gather the information needed to distinguish between UTI and IC symptom flares.

Q: Is IC preventable?
Mr. Combs: No.
Ms. Rejba: Unfortunately, it is not. The most important thing to remember is to be proactive when the patient starts to have bladder complaints.

Q: Do patients have any misconceptions about IC that they bring to their clinician?
Ms. Rejba: Though the Internet offers wonderful resources, there are also postings from patients who are faring poorly. When you tell patients they might have IC, they can get very upset. Even patients with mild IC fear they will have to go on disability and won’t be able to care for their children because of what they have read online. Offer reassurance that most patients with IC are managing their lives, still working, and may not even be on medication.

Q: Are there any misconceptions about IC among clinicians?
Mr. Combs: Some practitioners are not aware of the existence of the disorder, and others question the legitimacy of the diagnosis.
Ms. Rejba: The most heartbreaking thing is seeing patients come in from urologists or other practitioners who do not believe in IC. By the time these patients get to our office, many have been told the symptoms are in their head and they think they’re going crazy.

Q: What new theories are researchers pursuing with regard to the cause of IC?
Ms. Rejba: Everyone’s been hoping to find a single cause of IC, but the more research conducted, the more complex we realize the whole syndrome is. There is cross-communication between nerves and different organs, and clinicians need to be open to the idea that patients may develop IC in many ways. It’s an expanding field.
Mr. Combs: Some researchers are looking at IC as a manifestation of an exaggerated autoimmune response. They’re also looking at certain types of protein serum markers (e.g., altered Tamm-Horsfall protein).

Q: Are there any new treatments for IC that clinicians should be aware of?
Mr. Combs: There hasn’t been anything new for some time, but there has been some recent success using either cyclosporine or BCG vaccine to treat IC patients.
Ms. Rejba: Treatment remains primarily a process of trial and error.

Ms. Lippert is a medical writer and editor in the New York City area.