Diagnosis of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)

The diagnosis of interstitial cystitis/painful bladder syndrome (IC/PBS) is challenging for a number of reasons:

• Currently available diagnostic criteria were developed for research rather than clinical use. The use of these restrictive research-based criteria has been shown to miss many patients with the condition.¹
• Painful, invasive techniques have been used for diagnosis, which some experts believe to be inaccurate and unnecessary.²
• To date, there are no biological markers for use in diagnosis, although one, antiproliferative factor (APF), is under investigation as a potential diagnostic marker.³
• Although there are hallmark cystoscopic findings often associated with IC/PBS, namely, glomerulations (superficial pinpoint hemorrhages) and Hunner's ulcers (discrete areas of inflammation involving deeper layers of the bladder), the diagnosis of IC/PBS remains one of exclusion.^4,5

Diagnostic Criteria

In 1987 the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) put forth a definition of IC/PBS to provide researchers with guidelines for selecting comparable study populations.⁶ The NIDDK criteria include 18 exclusion requirements, one of which is "lack of frequency," and three inclusion requirements:

• Pain associated with the bladder or urinary urgency
• Hunner's ulcer or glomerulations on cystoscopic exam
• Hydrodistention under anesthesia showing diffuse glomerulations, present in at least four quadrants of the bladder, with at least 10 lesions per quadrant

The criteria were purposely designed to be restrictive, to ensure that only patients with clearly defined cases of IC/PBS were included in research studies. However, because of a lack of other published criteria, the NIDDK criteria have been used for clinical diagnosis, especially outside the United States.

One study found that use of these criteria in the clinical setting misses 60 percent of patients with IC/PBS.¹ Not only are the NIDDK criteria purposely restrictive but also they require the use of operating room-based diagnostic procedures that are not generally necessary in the clinical setting.

Although these criteria may have a place in the research setting (some experts believe they are in need of updating even for this setting), they are not recommended for use in diagnosing individual patients. NIDDK has recognized that its research criteria need to be updated to reflect the knowledge gained in the past two decades about IC/PBS, and it has begun the process of updating these criteria with input from many IC/PBS experts.

General Approach to Diagnosis

Because of the lack of criteria appropriate for use in the clinical setting, the general approach to diagnosis of IC/PBS in the United States tends to be empirical. Once other conditions are excluded, patients with characteristic signs and symptoms generally are treated for presumed IC/PBS. In certain circumstances, some clinicians may choose to evaluate further, with cystoscopy with hydrodistention under general anesthesia, urodynamic studies, or lidocaine instillation. These techniques will be discussed further later in this chapter.

The potassium chloride challenge, or Parsons' test, also has been used for diagnosis. This test involves instillation of potassium chloride into the bladder; a positive result is pain and reproduction of IC/PBS symptoms. Because it tests for epithelial permeability, the potassium chloride challenge is not specific for IC/PBS and provides a positive result in other disorders that involve epithelial leakage.² The result is positive in virtually all patients with radiation cystitis and bacterial cystitis.² The test also misses up to 25 percent of patients with IC/PBS as defined by NIDDK criteria.⁷ The potassium chloride challenge is not widely used in this country because of low sensitivity and specificity, and because it is a painful test to undergo that also requires invasive urinary catheterization. Nevertheless, some experts feel it may be helpful in the subset of patients who have minimal pain.

Basic Diagnostic Assessment

In the United States, clinicians tend to use six tools for the basic diagnostic assessment of IC/PBS:^2,8

• History
• Physical examination
• Urinalysis
• Urine culture
• Cystoscopy with hydrodistention under anesthesia
• Cytology (when indicated)

If necessary, imaging and urodynamic testing are conducted.² In contrast, European-based clinicians often require urodynamic testing, cystoscopy with hydrodistention under anesthesia, and bladder biopsy for diagnosis.⁸

Because IC/PBS is currently underdiagnosed and its diagnosis is empirical, supplemented by a basic diagnostic assessment, it is important for clinicians to consider the condition when evaluating patients with persistent urinary symptoms. Specifically, clinicians should consider IC/PBS in:^9,10

• The patient treated for overactive bladder who continues to experience persistent urge with associated suprapubic/ pelvic discomfort or pain
• The patient who does not respond to empirical antibiotics for "recurrent urinary tract infection," especially if bacterial cystitis is not present and the patient has mounting discomfort with bladder filling
• The female patient who continues to have pelvic pain after endometriosis therapy (medical and/or surgical), especially if she has urinary frequency or change in pain or discomfort with bladder filling or emptying
• The male patient who has been treated for "prostatitis" with therapies such as antibiotics, alpha blockers, or NSAIDs but continues to have pelvic pain perceived to be associated with the bladder and possibly irritative voiding symptoms

History

Clinicians should elicit a detailed history of voiding symptoms, pelvic pain or discomfort, urinary frequency and urgency, and nocturia. A voiding log can be very helpful for assessing urinary frequency. It is important to note that some patients with IC/PBS do not complain of pelvic pain but, if asked, will admit to discomfort or pressure that is relieved by voiding. Also, clinicians should inquire about the timing and course of symptoms. A distinguishing characteristic of IC/PBS is progressive bladder pain or discomfort with increased bladder filling.

Physical Examination

The physical examination of a patient with possible IC/PBS should include a pelvic exam in women and a digital rectal exam in men. Although there are no physical findings specific to IC/PBS, many patients with the condition have exquisite tenderness at the bladder neck, at the perineum between the anus and scrotum in men, and at the anterior vaginal wall near the urethral meatus in women.¹¹ The physical exam also should include an assessment of pelvic floor muscle strength and pelvic floor muscle tenderness, as well as evaluation for vaginal vault, introital, or vestibular pathology and periurethral or urethral lesions.

Differential Diagnosis

As previously mentioned, the diagnosis of IC/PBS is one of exclusion. There are a number of conditions that must be considered in the differential diagnosis of a patient with possible IC/PBS, including:

• Urinary tract infection
• Overactive bladder
• Endometriosis
• Bladder carcinoma
• Drug effects: cyclophosphamide, aspirin, NSAIDs, allopurinol

Urinary tract infection (UTI), endometriosis, and overactive bladder (OAB) are relatively common conditions; the other conditions listed are rare but should be considered in patients with relevant findings, such as microhematuria on cystoscopy. Note that cyclophosphamide, aspirin, NSAIDs, and allopurinol are associated with a nonbacterial cystitis that resolves when the drugs are discontinued.5 Of course, two or more of these conditions can occur concurrently.

Clinicians should be wary of making a diagnosis of IC/PBS in patients who have OAB or a history of recurrent UTI unless adequate treatment of involuntary detrusor contractions (for OAB) or infection (for recurrent UTI) fails to resolve symptoms.² Also, clinicians should be aware that although urgency is a common symptom of IC/PBS, it also is characteristic of OAB, as illustrated by the above case study.

Diagnosis of Associated Conditions

As previously mentioned, experts now recognize that more overlap exists between IC/PBS and associated conditions than previously thought, and NIDDK-sponsored research is under way to better understand the relationship between IC/PBS and these conditions. Results of these studies may alter the recommended management of IC/PBS and its comorbid conditions. In the meantime, providers should be alert for the presence of such conditions in patients with IC/PBS or who present with symptoms suggestive of IC/PBS. Diagnosing and treating these conditions can reduce or eliminate a secondary source of pain for patients with IC/PBS.

References:

1. Hanno PM, Landis JR, Matthews-Cook Y, Kusek J, Nyberg L, The Interstitial Cystitis Database Study Group. The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database Study. J Urol. 1999;161:553-7.
2. Hanno PM. Painful bladder syndrome (interstitial cystitis). In: Hanno PM, Wein AJ, Malkowicz SB, editors. Penn Clinical Manual of Urology. Philadelphia: Saunders; 2007. pp. 217-34.
3. Keay SK, Szekely Z, Conrads TP, Veenstra TD, Barchi JJ, Jr, Zhang CO, et al. An antiproliferative factor from interstitial cystitis patients is a frizzled 8 proteinrelated sialoglycopeptide. Proc Natl Acad Sci USA. 2004;101:11803-8.
4. National Institute of Diabetes and Digestive and Kidney Diseases. Overcoming bladder disease: a report of the Bladder Research Progress Review Group. Chapter 8. August 2002. pp. 103-115.
5. Hanno PM. Painful bladder syndrome/interstitial cystitis and related disorders. In: Wein AJ, editor. Campbell-Walsh Urology. 9th ed. Philadelphia: Saunders; 2007. pp. 330-70.
6. Gillenwater JY, Wein AJ. Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987. J Urol. 1988;140(1):203-6.
7. Grégoire M, Liandier F, Naud A, Lacombe L, Fradet Y. Does the potassium stimulation test predict cystometric, cystoscopic outcome in interstitial cystitis? J Urol. 2002;168:556-7
8. Clemens JQ, Joyce GF, Wise M, Payne CK. Interstitial cystitis and painful bladder syndrome. In: Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007. NIH Publication No. 07-5512:125-154.
9. Clemons JL, Arya LA, Myers DL. Diagnosing interstitial cystitis in women with chronic pelvic pain. Obstet Gynecol. 2002;100:337-41.
10. Forrest JB, Nickel JC, Moldwin RM. Chronic prostatitis/chronic pelvic pain syndrome and male interstitial cystitis: enigmas and opportunities. Urology. 2007;69(Suppl 4A):60-3.
11. Rosenberg MT, Newman DK, Page SA. Interstitial cystitis/painful bladder syndrome: symptom recognition is key to early identification, treatment. Cleve Clin J Med. 2007;74(Suppl 1):S54-S62.