Most clinicians with outpatient practices see undiagnosed cases of interstitial cystitis/painful bladder syndrome (IC/PBS). This chronic condition is characterized by pain perceived to be from the urinary bladder, urinary urgency and frequency, and nocturia. As currently diagnosed, the great majority of cases occur in women. Symptoms wax and wane for months or years or possibly even for the patient's lifetime. The spectrum of symptom intensity is broad. The pain can be excruciating, urgency can be distressing, frequency can be up to 60 times per 24 h, and nocturia can be causative of sleep deprivation. These symptoms can be disabling in terms of daily activities, work schedules, and personal relationships; patients with IC/PBS report less life satisfaction than do those with end-stage renal disease. The etiology of IC/PBS is unknown. It is not a new disease, having first been described in the late nineteenth century in a patient with the symptoms described above and a single ulcer visible on cystoscopy (now called Hunner's ulcer after the urologist who first reported it). Over the ensuing decades, it became clear that many patients with similar symptoms had no ulcer. It is now appreciated that ≥10% of patients with IC/PBS have a Hunner's ulcer.
The definition of IC/PBS, its diagnostic features, and even its name continue to evolve. The International Continence Society, a body devoted to studying disorders of the lower urinary tract and pelvic floor, has defined PBS as "the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology." In practice, clinicians have interpreted this definition to include any chronic pelvic pain that increases with bladder filling and/or decreases with voiding and that cannot be explained by reference to another identifiable disease.
Many patients with IC/PBS also have other syndromes, such as fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, vulvodynia, and migraine. These syndromes collectively are known as functional somatic syndromes (FSSs): chronic conditions in which pain and fatigue are prominent features but laboratory tests and histologic findings are normal. Like IC/PBS, the FSSs often are associated with depression and anxiety. The majority of cases affect women, and more than one FSS can affect a single patient. Because of its similar features and comorbidity, IC/PBS sometimes is considered an FSS.
Contemporary population studies of IC/PBS in the United States indicate prevalences of 2–3% among women and 1–2% among men. For decades, it was thought that 90% of IC/PBS cases occurred in women. These prevalence findings, however, have generated research aimed at determining the proportion of men with symptoms usually diagnosed as chronic prostatitis (now known as chronic prostatitis/chronic pelvic pain syndrome) who actually have IC/PBS. Well-designed studies of the incidence of IC/PBS have not been reported.
Among women, the average age at onset of IC/PBS symptoms is the early forties, but the range is from childhood through the early sixties. Risk factors (antecedent features that distinguish cases from controls) primarily have been FSSs. Indeed, the odds of IC/PBS increase with the number of such syndromes present. Surgery was long thought to be a risk factor for IC/PBS, but analyses adjusting for FSSs refuted that association. A minority of patients have a bacterial urinary tract infection (UTI) at the onset of IC/PBS.
The natural history of IC/PBS is not known. Although studies from urology and urogynecology practices have been interpreted as showing that IC/PBS lasts for the lifetime of the patient, population studies suggest that some individuals with IC/PBS do not consult specialists and may not seek medical care at all, and most prevalence studies do not show an upward trend with age—a pattern that would be expected with incident cases throughout adulthood followed by lifetime persistence of a nonfatal disease. It may be reasonable to conclude that patients in a urology practice represent those with the most severe and recalcitrant IC/PBS.
For the ⩽10% of IC/PBS patients who have a Hunner's ulcer, the term interstitial cystitis may indeed describe the histopathologic picture. Most of these patients have substantive inflammation, mast cells, and granulation tissue. However, in the 90% of patients without such ulcers, the bladder mucosa is relatively normal, with scant inflammation.
Numerous theories about the pathogenesis of IC/PBS have been put forward. It is not surprising that most early theories focused on the bladder. For instance, IC/PBS has been investigated as a chronic bladder infection. Sophisticated technologies have not identified a causative organism in urine or in bladder tissue; however, the patients studied by these methods had IC/PBS of chronic duration, and the results do not preclude the possibility that infection may trigger the syndrome or may be a feature of early IC/PBS. Other inflammatory factors, including a role for mast cells, have been postulated, but as was noted above, the 90% of patients without a Hunner's ulcer have little bladder inflammation and do not exhibit a prominence of mast cells. Autoimmunity has been considered, but autoantibodies are low in titer, nonspecific, and thought to be a result rather than a cause of IC/PBS. Increased permeability of the bladder mucosa due to defective epithelium or glycosaminoglycan (the bladder's mucous coating) has been studied frequently, but the findings have been inconclusive.
Investigations of causes outside the bladder have been prompted by the presence of comorbid FSSs. Many patients with FSSs have abnormal pain sensitivity as evidenced by (1) low pain thresholds in body areas unrelated to the diagnosed syndrome, (2) dysfunctional descending neurologic control of tactile signals, and (3) enhanced brain responses to touch in functional neuroimaging studies. Moreover, in patients with IC/PBS, body surfaces remote from the bladder are more sensitive to pain than is the case in individuals without IC/PBS. All these findings are consistent with upregulation of ...