Interstitial cystitis

Interstitial cystitis (bladder pain syndrome) is a chronic pelvic pain syndrome characterized by bladder pain and irritative lower urinary tract symptoms in the absence of infection or other identifiable causes. Interstitial cystitis is most common in female individuals aged ≥ 40 years. The etiology is not known. Clinical features include pain with bladder filling that is relieved with voiding, urinary urgency, urinary frequency, nocturia, and suprapubic and pelvic tenderness on examination. Interstitial cystitis is a diagnosis of exclusion, based on ≥ 6 weeks of symptoms, a negative urinalysis and urine culture, and the absence of identifiable causes such as infection, malignancy, or urological abnormalities. Management is based on symptoms. All patients benefit from nonpharmacological therapy, which may include avoidance of triggers (e.g., alcohol, coffee, citrus), behavioral modification (e.g., fluid intake management, bladder training, stress management), and management of comorbidities (e.g., IBS, depression). Patients with pelvic floor tenderness or high-tone pelvic floor dysfunction may also benefit from manual therapy to relax tissues. Pharmacological treatment (e.g., oral analgesia, pentosan polysulfate) may also be considered. Specialist referral is indicated for presumed Hunner lesions and/or refractory symptoms or if an alternative diagnosis is suspected.

• Uncommon condition (0.6–2% of women in the US)
• Sex: ♀ > ♂
• Peak age: ≥ 40 years

Epidemiological data refers to the US, unless otherwise specified.

• Pain with bladder filling that is relieved by voiding (most common feature)
• Suprapubic and/or perineal pain, pressure, or discomfort
• Increased urinary urgency and/or urinary frequency ^[1]
• Nocturia
• Genitourinary tenderness of the:
  • Urethra and bladder base
  • Scrotum and penis
  • Lateral and anterior vaginal wall
• Symptoms are typically:
  • Gradual in onset
  • Exacerbated by sexual intercourse, exercise, prolonged sitting, certain foods or drink ^[2]
• Patients may have a history of UTI. ^[1]

Interstitial cystitis is a diagnosis of exclusion made in patients with symptoms lasting ≥ 6 weeks and a negative urine culture. ^[1][2]

Approach ^[1]

• Diagnosis is clinical.
• Perform an initial assessment to evaluate for alternative diagnoses.
• Refer to urology or urogynecology for advanced studies (e.g., cystoscopy and/or urodynamic studies) if:
  • There is diagnostic uncertainty
  • Hunner lesions are suspected (e.g., age > 50 years, comorbid autoimmune diseases) ^[2]

Initial assessment ^[1]

• Voiding diary: to characterize symptoms and establish a baseline
• Physical examination
  • Abdominal examination to assess for masses
  • Pelvic examination including vaginal examination of the pelvic floor musculature (or digital rectal examination for male patients) ^[3]
  • Brief neurological examination
• Urinalysis with microscopy and urine culture: to rule out bacterial cystitis ^[1]
• Postvoid residual volume: to evaluate for urinary retention ^[1]
• Depending on risk factors, consider: ^[1]
  • Pregnancy test
  • STI testing for patients with risk factors for STIs
  • HbA1c if there are indications for diabetes screening ^[2]
  • Diagnostics for prostatitis
  • Hematuria diagnostics; consider also for patients without hematuria who use tobacco.

Low voiding frequency and/or high volume suggest an alternative diagnosis. ^[1]

Advanced studies ^[1]

Cystoscopy ^[1]

• Indications
  • Concern for Hunner lesions, e.g.: ^[2]
    • Patients > 50 years of age
    • Comorbid autoimmune disease
  • Concern for differential diagnosis of interstitial cystitis (e.g., clinical features of urinary tract cancer)
• Findings
  • Hunner lesions: acute inflamed, friable, denuded stellate-shaped lesions and ulcers on the bladder wall ^[1]
  • Findings in interstitial cystitis are nonspecific and include:
    • Diffuse glomerulations
    • Mastocytosis on biopsy ^[2]

If Hunner lesions are detected on cystoscopy, simultaneous treatment can be provided (e.g., fulguration and/or intralesional triamcinolone injection). ^[1]

Urodynamic studies ^[1]

• There are no established urodynamic criteria for interstitial cystitis.
• Studies are indicated for refractory symptoms to evaluate for:
  • Lower urinary tract obstruction
  • Atonic bladder

• Neurological condition
  • Multiple sclerosis
  • Parkinson disease
  • Urinary retention
• Infections
  • Urinary tract infection
  • Chronic bacterial prostatitis
  • Genital herpes
• Overactive bladder
• Bladder stones
• Vulvovaginitis
• Malignancy
  • Urinary tract cancer
  • Ovarian cancer
  • Endometrial cancer
  • Vaginal cancer

The differential diagnoses listed here are not exhaustive.

Approach ^[1][2][4]

• Advise patients that there is no standard approach; treatment is highly individualized.
• Initiate treatment using nonpharmacological management and/or oral pharmacological treatment.
• Treat common coexisting conditions, e.g.:
  • Chronic pain syndromes ^[5]
  • Depression and anxiety disorders ^[5][6][7]
• Monitor symptom response to treatment using a validated tool (e.g., Interstitial Cystitis Symptom Index).
• Refer to a specialist (e.g., urogynecology, urology) for:
  • Evaluation and treatment of Hunner lesions
  • Refractory symptoms
  • Advanced therapy

Patients with Hunner lesions should be referred to a specialist promptly for definitive treatment. ^[1]

Nonpharmacological management ^[1][2]

• Behavioral modifications, e.g.:
  • Avoidance of triggers (e.g., alcohol, coffee, citrus)
  • Fluid intake management based on symptoms
  • Bladder training
  • Heat or cold applied to trigger points and hypersensitive areas (e.g., bladder, perineum)
• Stress management (e.g., cognitive behavioral therapy, meditation) ^[5]
• Manual therapy (e.g., trigger point therapy, tissue release) for patients with pelvic floor tenderness and/or high-tone pelvic floor dysfunction

Behavioral modifications and stress reduction are recommended for all patients with interstitial cystitis. ^[1]

Pelvic floor strengthening exercises (e.g., Kegel exercises) are contraindicated in interstitial cystitis as they may worsen symptoms. ^[1]

Oral pharmacological treatment ^[1][4]

There is no standardized management algorithm. Use shared decision-making.

• Management of acute flares
  • Phenazopyridine ^[8]
  • Short courses of glucocorticoids ^[1]
• Long-term symptom management ^[4]
  • Pentosan polysulfate ) ^[1]
  • Amitriptyline (off-label) ^[1][2][4]
  • Cimetidine (off-label) ^[1][2]
  • Hydroxyzine (off-label) ^[2]
• Oral analgesia (e.g., NSAIDs) can be used for both short- and long-term pain relief.

Patients with complex or uncontrolled pain may require referral to a pain management specialist. ^[1]

Long-term oral antibiotic or glucocorticoid treatment is not indicated for interstitial cystitis. ^[1]

Advanced treatments

Advanced treatments are performed by a specialist in urology or urogynecology and is typically reserved for patients with refractory symptoms and/or Hunner lesions.

Management of refractory interstitial cystitis ^[1]

• Intravesicular therapy (e.g., dimethyl sulfoxide, lidocaine, heparin)
• Procedural interventions, e.g.:
  • Hydrodistension
  • Neuromodulation
  • Intradetrusor botulinum toxin injection
• Surgery (e.g., substitution cystoplasty, urinary diversion)

Management of Hunner lesions ^[1]

• First-line: fulguration and/or intralesional triamcinolone injection
• Refractory lesions: oral cyclosporin A

Hunner lesions typically respond well to treatment. ^[1]