Screening, Treatment, and Management of IC/PBS – Etiology

(Published May 2008)

Etiology and Associated Conditions of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)

Etiology

The exact cause of interstitial cystitis/painful bladder syndrome (IC/PBS) remains a mystery, but research has identified a number of different factors that may contribute to the pathogenesis of the condition. Investigators have proposed that a series of events lead to IC/PBS.¹ Figure 4 illustrates one possible etiology of IC/PBS.

Based on this model, the trigger for IC/PBS may be bladder damage caused by one or more inciting events, which include:¹

• Bladder trauma, including trauma related to pelvic surgery
• Bladder overdistention (anecdotal cases suggest onset after long periods without access to bathroom facilities)
• Pelvic floor muscle dysfunction
• An autoimmune disorder
• Bacterial infection (cystitis)
• Primary neurogenic inflammation: hypersensitivity or inflammation of pelvic nerve roots
• Spinal cord trauma

These triggers are believed to damage the bladder epithelium. Researchers speculate that normal repair of the epithelial lining of the bladder does not occur in patients who develop IC/PBS. In fact, recent research by Keay and colleagues at the University of Maryland indicates that a protein called antiproliferative factor (APF) is secreted by the bladder epithelial cells of patients with IC/PBS but not by the cells of healthy control subjects.² APF has been shown to inhibit the growth of bladder epithelial cells.² The bladder may be unable to repair itself in the presence of APF.¹

It is postulated that defects in the bladder epithelium allow urine contents, such as potassium, to leak into the bladder interstitium, which may lead to mast cell activation and the release of histamine.¹ These events are speculated to trigger the activation of C-fiber nerves and release of Substance P, as well as immunogenic and allergic responses.¹ The constellation of these events is believed to lead to progressive bladder injury, which may induce spinal cord changes in some patients, causing chronic neuropathic pain.¹

Associated Conditions

Anecdotal reports from patients and some population-based studies suggest that certain conditions, many of which have an immunologic or allergic basis, occur more commonly in patients with IC/PBS than in the general population. Figure 5 displays data from a study that examined the prevalence of diseases that had been previously associated with IC/PBS among patients with the condition and the general population.³ According to these data, allergies, irritable bowel syndrome, sensitive skin, vulvodynia, fibromyalgia, and migraine headaches were more common among patients with symptoms of IC/PBS than in the general population. In this study, the “Diagnosed” group was defined as patients diagnosed by their physician as having IC/PBS. The “Population” group was a comparison group from the general population.

Note that the comparator population for vulvodynia was a general gynecology practice, which may represent an overestimate of the prevalence in the general population (possibly explaining why the prevalence of vulvodynia in the comparator population was higher than the prevalence in patients with diagnosed IC/PBS). Also, although inflammatory bowel disease and systemic lupus erythematosus (SLE) have a relatively low prevalence in IC/PBS patients, in this study their prevalence was, respectively, 100 times and 30 times that seen in the general population.

Recognizing that more overlap exists between IC/PBS and these associated conditions in symptoms and prevalence than previously thought, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has initiated a significant research effort to better understand the relationship.⁴ At a workshop held in December 2007, experts in IC/PBS, as well as from related conditions fields, discussed a new approach to the condition that was “based on relationships with other pain syndromes.”⁵ This change in approach emphasizes the fact that the field is an emerging one and that recommended management of the condition may shift as more becomes known about IC/PBS and its comorbid conditions.

Pelvic floor dysfunction

Pelvic floor dysfunction (PFD) is myofascial dysfunction of the pelvic floor muscles (e.g., levator ani—the posterior portion of the pelvic floor muscle) and a frequent cause of chronic pelvic pain. PFD is another condition commonly seen in patients with IC/PBS.

One retrospective chart review found that the majority of 100 consecutive female IC/PBS patients had PFD.⁶ Common symptoms of PFD found in this retrospective review included:

• decreased force of urinary stream (75%)
• urinary hesitancy (75%)
• sense of incomplete void (73%)
• straining with urination (70%)
• constipation (68%)
• low-back pain (43%)
• dyspareunia (45%)

In addition, physical examination demonstrated tenderness of the levator ani muscle in 81% of patients. A statistically significant relationship existed between the severity of levator ani tenderness and findings of constipation, decreased force of the urinary stream, straining with urination, and urinary hesitancy. Identifying PFD (via pelvic or rectal exam) in patients with IC/PBS is important because therapy directed at PFD may help reduce IC/PBS symptoms in patients.⁶

References:

1. 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.
2. 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 protein-related sialoglycopeptide. Proc Natl Acad Sci USA. 2004;101:11803-8.
3. Alagiri M, Chottiner S, Ratner V, Slade D, Hanno PM. Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes. Urology. 1997;49(Suppl 5A):52-7.
4. National Institute of Diabetes and Digestive and Kidney Diseases. Multi-disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network [grant announcement].
5. International Painful Bladder Foundation. IPBF E-newsletter. December 2007. Available at: http://www.painful-bladder.org/pdf/2007_12_Newsletter.pdf. Accessed January 9, 2008.
6. Moldwin RM, Kaye J. Pelvic floor dysfunction in the painful bladder syndrome/ interstitial cystitis (PBS/IC) population. NIDDK International Symposium: Frontiers in Painful Bladder Syndrome and Interstitial Cystitis; 2006 Oct 26–27; Bethesda, MD.