Chapter 51: Interstitial Cystitis/Bladder Pain Syndrome

DEFINITION

Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), is a condition associated with bladder inflammation and pain. Originally described in 1887 with discrete bladder ulcerations termed Hunner lesions, IC has evolved into the broader IC/BPS syndrome, characterized by:

Bladder and/or pelvic pain
Urinary storage symptoms (frequency, urgency)
Negative urine cultures
No specific identifiable causes

Accepted definitions generally agree on:

Chronic nature
Pain perceived to be bladder-related
Pain with lower urinary tract symptoms (LUTS)
Pain beyond bladder common (pelvis, perineum, genitals, abdomen)

The contemporary definition includes an unpleasant sensation (pain, pressure, discomfort) related to the bladder, associated with LUTS >6 weeks, excluding infection or other causes.

The urologic chronic pelvic pain syndrome (UCPPS) umbrella includes IC/BPS (in men and women) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, men only). Overlapping symptoms and pathophysiology exist, but this chapter focuses on IC/BPS.

ETIOLOGY AND PATHOGENESIS

The etiology of IC/BPS is uncertain, likely representing a syndrome of interrelated processes beyond the bladder.

INFECTION AND THE URINARY MICROBIOTA

Bacterial infection once suspected but never definitively shown.
Many IC/BPS patients report prior UTIs but often with negative cultures and limited antibiotic response.
Advanced culture-independent studies reveal subtle urinary microbiota differences between patients and controls, possibly indicating dysbiosis driving flares.

AUTOIMMUNITY

Some patients show anti-urothelial antibodies and bladder inflammation.
Immune disturbances may cause IC/BPS in subsets (e.g., with Sjögren’s syndrome).
Clinical relevance remains unclear.

INFLAMMATION

Subset with Hunner lesions have clear inflammatory bladder lesions.
Other subtle inflammatory patterns include lymphoplasmacytic infiltrates, stromal edema, fibrosis, urothelial denudation, and mastocytosis.
Toll-like receptor stimulation correlates with symptom severity and widespread pain.

UROTHELIAL DYSFUNCTION

Urothelial Permeability and the Glycosaminoglycan (GAG) Layer

Bladder urothelium is a stratified epithelium with a GAG layer and tight junctions protecting underlying tissue.
Disruptions in GAG or epithelial layers hypothesized to cause pain, but evidence is inconclusive.

Antiproliferative Factor (APF)

APF found in IC/BPS patient urothelial cells, slowing growth.
Proposed biomarker role but not widely adopted clinically.

PELVIC ORGAN CROSSTALK

Symptoms often extend to gastrointestinal, gynecologic, genital organs.
Neural sensitization and autonomic abnormalities reported.
Applicability to entire patient population unclear.

NEUROBIOLOGIC CONTRIBUTIONS AND CENTRAL SENSITIZATION

Brain structural/functional differences identified in UCPPS patients.
Quantitative sensory testing shows generalized pain hypersensitivity.
Central sensitization likely contributes to symptomatology.

EPIDEMIOLOGY

Prevalence estimates vary widely due to evolving definitions.
Estimated 2.7–6.5% of North American women have symptoms consistent with IC/BPS.
Female-to-male ratio ~10:1; likely underreported in men.
Childhood disorders and adverse experiences may increase risk.
High prevalence of chronic overlapping pain conditions (COPCs) like fibromyalgia, IBS, chronic fatigue syndrome in IC/BPS patients.

CLINICAL MANIFESTATIONS

Bladder-related pain and urinary symptoms (frequency, urgency).
Pain may extend beyond bladder (pelvis, genitals, abdomen).
Pain phenotypes: bladder-only (~20%) vs. pelvic + extra-pelvic pain (~80%).
Associated conditions: IBS, pelvic floor dysfunction, vulvodynia, fibromyalgia, chronic fatigue.
Symptoms fluctuate; flares triggered by diet, stress, infection, hormones.

APPROACH TO THE PATIENT

Initial evaluation by primary care includes history, physical exam, symptom scoring, and urine studies (see Table 51-1).
Avoid siloing patients by symptoms; consider UPOINT domains: Urinary, Psychosocial, Organ-specific, Infection, Neurologic, Tenderness.
Categorize patients as pelvic-pain-only vs. pelvic pain + COPCs.
Psychosocial factors (depression, anxiety) important in management.

DIAGNOSIS

Diagnosis of exclusion; history and physical examination paramount.
Urine studies to rule out infection, cytology for cancer suspicion.
Imaging, cystoscopy (for Hunner lesions), and urodynamics as needed.
Intravesical anesthetic challenge and hydrodistension can aid diagnosis.
Symptom questionnaires (ICSI, ICPI, GUPI) aid in baseline and monitoring.

TREATMENT OF CLINICAL PHENOTYPING

Multimodal, phenotype-directed therapy guided by UPOINT.
Conservative measures first: patient education, diet, pelvic floor physiotherapy, psychological support.
Medical therapies:
Pentosan polysulfate sodium (PPS): FDA-approved oral agent, but recent vision risks reported.
Dimethyl sulfoxide (DMSO): FDA-approved intravesical agent, with variable efficacy.
Off-label oral agents: amitriptyline, hydroxyzine, cimetidine, gabapentinoids, cyclosporin A.
Intravesical agents: heparin, lidocaine, hyaluronic acid, chondroitin sulfate.
Trigger point injections for pelvic floor tenderness.
Surgical therapies: Hunner lesion ablation, hydrodistension, onabotulinum toxin A, sacral neuromodulation, radical surgery reserved for refractory cases.

COMPLICATIONS AND PROGNOSIS

IC/BPS causes significant disability, reduced quality of life, and mental health morbidity.
Suicidal ideation reported in 11–23% of patients.
Symptoms often wax and wane, with some progressing to end-stage bladder.
Multimodal and interdisciplinary care recommended.

GLOBAL CONSIDERATIONS

Prevalence varies globally but believed to be similar worldwide.
Diagnosis and treatment based largely on history and physical examination, making management feasible even in resource-poor settings.