Interstitial cystitis.

Deborah L. Myers, MD Interstitial cystitis (IC) is a chronic condition of urinary urgency, frequency, and suprapubic pain in the absence of bacteruria. It is part of the painful bladder syndrome whose known causes are tuberculosis, stones, malignancy, previous chemotherapy of the bladder, and pelvic radiation. Interstitial cystitis is a diagnosis of exclusion when no known cause of painful bladder can be identified. It has classically been diagnosed by the presence of “Hunner’s ulcers”, a lesion noted on cystoscopy in 1915.1 The word “ulcer” has proven to be a misnomer; the lesion is actually a coalescence of vessels. IC is a chronic illness for which we do not have a full understanding in terms of etiology or management. IC occurs predominantly in women between 40-60 years, and in a ratio of 9:1 of women to men. With newer diagnostic techniques and less stringent criteria, the estimated prevalence of IC in the United States is approximately 1.5 million to 25 to 30 million women. Practitioners involved in women’s health should know about this condition.2 The pathophysiology of IC remains unknown, but two integrated theories, the (1) “leaky epithelium” and (2) “neurogenic up-regulation” are proposed. The bladder uroepithelium has a protective mucous coat layer, the glycosaminoglycan (GAG) layer, which, when injured, becomes deficient, or “leaky”, thus allowing potassium and toxins in the urine to penetrate into the underlying bladder and causing inflammation and pain. In response to this bladder insult, detrusor mast cells release substance P, histamines and prostaglandins which cause vasodilatation and pain. The sensory C afferent nerve fibers of the bladder can become “up-regulated.” (Figure 1) Studies have shown increased nerve fiber density including sympathetic nerves in bladders of patients with IC. IC could be a type of reflex sympathetic dystrophy with abnormal spinal sympathetic activity.4 The cause of the “leaky epithelium” still remains unknown. Work by Keay et al has identified proteins in the urine which affect the ability of the uroepithelium to regenerate and repair. Patients with IC have increased levels of Anti-proliferative factor (APF). APF inhibits the growth of the bladder lining. IC patients have lower levels of other proteins HB-EGF (heparin binding epidermal growth factor-like), required for epithelial growth.5 In summary, the damaged epithelium leads to a complex cascade of interactions involving urinary cations, activated mast cells, sensory nerves, detrusor muscle overactivity, and spinal cord sensitization.