Interstitial Cystitis

Interstitial Cystitis, or bladder pain syndrome (also IC/BPS), is a chronic condition and diagnosis of exclusion of unknown cause characterized by bladder pain. It may be associated with urinary urgency, urinary frequency, waking at night to urinate (nocturia), and sterile urine cultures. Those with interstitial cystitis may have symptoms that overlap with other urinary bladder disorders such as: urinary tract infection (UTI), overactive bladder, urethritis, urethral syndrome, and prostatitis. IC/BPS can result[quantify] in a quality of life comparable to that of a patient with rheumatoid arthritis, chronic cancer pain, or a patient on kidney dialysis.

Symptoms

The symptoms of IC/BPS are often misdiagnosed as a “common” bladder infection (cystitis) or a UTI. However, IC/BPS has not been shown to be caused by a bacterial infection and antibiotics are an ineffective treatment. The symptoms of IC/BPS may also initially be attributed to prostatitis and epididymitis (in men) and endometriosis and uterine fibroids (in women).

  • The most common symptoms of IC/BPS are pain, frequency, painful sexual intercourse, and nocturia.
  • Painful urination
  • Pain that is worsened with bladder filling and/or improved with urination.
  • Pain that is worsened with a certain food or drink.
  • Some patients report dysuria (burning sensation in the urethra when urinating).
  • Urinary frequency (as often as every 10 minutes), urgency, and pressure in the bladder and/or pelvis.

Some patients report nocturia (waking at night to urinate), urinary hesitancy (needing to wait for the stream to begin, often caused by pelvic floor dysfunction and tension), pain with sexual intercourse, and discomfort and difficulty driving, travelling or working.

During cystoscopy, 5-10% of patients are found to have Hunner’s ulcers. Patients may have discomfort only in their urethra, while others struggle with pain in the entire pelvis. Interstitial cystitis patients often exhibit their symptoms in one of two patterns: significant suprapubic pain with little frequency or a lesser amount of suprapubic pain but with increased urinary frequency.

Resources

Resources •National Institute of Diabetes and Digestive and Kidney Diseases (2012). “Interstitial Cystitis/Painful Bladder Syndrome”. National Institutes of Health. Retrieved 25 October 2012. •Peters, Dr. Jill. “”Interstitial Cystitis” Paul Perry, MD, Chairman, Obgyn.Net Editorial Advisory Board, Chronic Pelvic Pain interviews Jill Peters, MD”. OBGYN.net. Obgyn.Net Conference Coverage from International Pelvic Pain Society — Simsbury Connecticut — April/May, 1999. Retrieved 10 April 2011. •Butrick, CW (2007). “Patients with Chronic Pelvic Pain: Endometriosis or Interstitial Cystitis/Painful Bladder Syndrome?”. Journal of the Society of Laparoendoscopic Surgeons 11 (2): 182–189. PMID 17761077. •Dimitrakov, J; Guthrie, D (2009). “Genetics and Phenotyping of Urological Chronic Pelvic Pain Syndrome”. Journal of Urology 181 (4): 1550–1557. doi:10.1016/j.juro.2008.11.119. PMID 19230927. •PubMed Health (2011). “Prostatitis-nonbacterial-chronic”. U.S. National Library of Medicine. Retrieved 25 October 2012. • Eric S., Rovner, MD. “Interstitial Cystitis: Etiology”. MedScape Reference. Retrieved 1 April 2011.

 

Treatments

AUA Treatment Guidelines

In 2011, the American Urological Association released the first consensus based guideline for the diagnosis and treatment of IC in the USA. The authors note their goal of providing insights for both healthcare providers and patients about managing this chronic condition. The Guideline outlines principles of clinical care—with the ultimate goal of improving the quality of life for IC patients.

The AUA Treatment Guidelines include a treatment protocol ranging from conservative treatments to more invasive interventions with lower numbers representing less invasive methods:

1. First-line treatments – Patient education, self care (diet modification), stress management

2. Second-line treatments – Physical therapy, oral medications (amitryptiline, cimetidine or hydroxyzine, pentosan polysulfate), bladder instillations (DMSO, heparin or lidocaine)

3. Third-line treatments – Treatment of Hunner’s ulcers (laser, fulguration or triamcinolone injection), hydrodistention (low pressure, short duration)

4. Fourth-line treatments – Neuromodulation (sacral or pudendal nerve)

5. Fifth-line treatments – Cyclosporine A, Botulinum Toxin (BTX-A)

6. Sixth-line treatments – Surgical intervention (urinary diversion, augmentation, cystectomy)

The AUA Guideline also listed several discontinued treatments, including: long term oral antibiotics, intravesical Bacillus Calmette Guerin (BCG), intravesical resiniferatoxin (RTX), high pressure & long duration hydrodistention, and systemic glucocorticoids.

As recently as a decade ago, treatments available were limited to the use of astringent instillations, such as chlorpactin (oxychlorosene) or silver nitrate, designed to kill “infection” and/or strip off the bladder lining. In 2005, understanding of IC/BPS improved dramatically and these therapies are now no longer used. Rather, IC/BPS therapy is typically multi-modal, including the use of a bladder coating, an antihistamine to help control mast cell activity and a low dose antidepressant to fight neurogenic inflammation. Oral pentosan polysulfate is believed to provide a protective coating in the bladder, but studies have encountered mixed results when attempting to determine if the effect is statistically significant compared to placebo.

Amitriptyline has been shown to be effective in reducing symptoms in many patients with IC/BPS with a median dose of 75 milligrams daily.  In one study, the antidepressant duloxetine was found to be ineffective as a treatment, although a patent exists for use of duloxetine in the context of IC, and is known to relieve neuropathic pain.

DMSO, a wood pulp extract, is the only approved bladder instillation for IC/BPS yet it is much less frequently used in urology clinics. Research studies presented at recent conferences of the American Urological Association by C. Subah Packer have demonstrated that the FDA approved dosage of a 50% solution of DMSO had the potential to create irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long term use of DMSO is questionable as its mechanism of action is not fully understood though it is thought that DMSO can inhibit mast cells and may have anti-inflammatory and analgesic effects.

More recently, the use of a “rescue instillation” composed of pentosan polysulfate or heparin, sodium hyaluronate, lidocaine and sodium bicarbonate, has generated considerable excitement in the IC/BPS community because it is the first therapeutic intervention that can be used to reduce a flare of symptoms. Published studies report a 90% effectiveness in reducing symptoms. Sometimes these rescue instillations are given on a regular basis for treatment. It is important to note that this is off-label use for both pentosan polysulfate and heparin, as neither medicine has been approved to be used this way.

Other bladder coating therapies include Cystistat (sodium hyaluronate) and Uracyst (chondroitin). These treatments are believed to replace the deficient GAG layer on the bladder wall. Like most other intravesical bladder treatments, this treatment may require the patient to lie for 20 – 40 minutes, turning over every ten minutes, to allow the chemical to ‘soak in’ and give a good coating, before it is passed out with the urine. Cystistat is not currently available in the United States or Canada, though testing has recently started in Canada. Testing has also begun for Uracyst in both Canada and the United States. Uracyst is available in Canada.

Interstitial cystitis patients often experience an increase in symptoms when they consume certain foods and beverages, especially caffeine-containing beverages such as coffee, tea, and soda. Dietary triggers may also include alcoholic beverages, citrus fruits and juices, artificial sweeteners and hot peppers. The challenge with diet triggers is that they vary from person to person: the best way for a person to discover his or her own triggers is to use an elimination diet. Patients may be able to reduce sensitivity to trigger foods if they consume calcium glycerophosphate and/or sodium bicarbonate. The foundation of therapy is a modification of diet to help patients avoid those foods which can further irritate the damaged bladder wall.

Anecdotal evidence has linked gluten intolerance to UCPPS symptoms. Studies are lacking in this area. The mechanism by which dietary modification benefits patients with IC is unclear. Researchers hypothesize that integration of neural signals from pelvic organs mediates the effects of diet on symptoms of IC.

Bladder distension (a procedure which stretches the bladder capacity while under general anaesthesia) has shown some success in reducing urinary frequency and giving pain relief to patients. However, many experts still cannot understand precisely how this procedure causes pain relief.[36] Recent studies showing that pressure on pelvic trigger points can relieve symptoms may be connected. The relief achieved by bladder distensions is only temporary (weeks or months) and consequently, is not viable as a long-term treatment for IC/BPS.

Surgical interventions are rarely used for IC/BPS. Surgical intervention is very unpredictable for IC/BPS, and is considered a treatment of last resort when all other treatment modalities have failed and pain is severe. Some patients who opt for surgical intervention continue to experience pain after surgery. Surgical interventions for IC/BPS include transurethral fulguration and resection of ulcers, using electricity/laser; bladder denervation, where some of the nerves to the bladder are cut (Modified Ingelman-Sundberg Procedure); bladder augmentation; bladder removal (cystectomy); electrical nerve stimulation, similar to TENS, where an electrical unit is implanted in the body and provides continuous or intermittent electrical pulses to the affected areas (Interstim); spinal cord stimulation (SCS), where an electrical unit is implanted that provides electrical stimulation to the spinal cord, interfering with pain reception to the brain (ANS/Advanced Neuromodulation Systems spinal Cord Stimulator); and the implantation of the intrathecal pain pump, where very small amounts of medication, like morphine sulfate, dilaudid, or baclofen are released into the cerebrospinal fluid via a catheter stemming from the small electrical pump, requiring only about 1/100 to 1/300 the amount of medication needed orally for the same therapeutic benefit, but with significantly fewer side effects.

Research by Wise and Anderson has shown that urologic pelvic pain syndromes, such as IC/BPS and CP/CPPS, are characterized by pelvic muscle tenderness and that symptoms may be reduced with pelvic myofascial physical therapy. This is theorized to leave the pelvic area in a sensitized condition resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up). This is a form of Myofascial pain syndrome. Current protocols largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress.

Pelvic floor dysfunction is a fairly new area of specialty for physical therapists worldwide. The goal of therapy is to relax and lengthen the pelvic floor muscles, rather than to tighten and/or strengthen them as is the goal of therapy for patients with urinary incontinence. Thus, traditional exercises such as Kegel exercises, can be helpful as they strengthen the muscles, however, they can provoke pain and additional muscle tension. A specially trained physical therapist can provide direct, hands on, evaluation of the muscles, both externally and internally.

Neuromodulation can be successful in treating IC/BPS symptoms, including pain. One electronic pain-killing option is TENS. PTNS stimulators have also been used, with varying degrees of success. Percutaneous sacral nerve root stimulation (PNS) was able to produce statistically significant improvements in several parameters, including pain.

A 2002 review study reported that acupuncture alleviates pain associated with IC/BPS as part of multimodal treatment. While a small 1987 study showed that 11 of 14 (78%) patients had a >50% reduction in pain, a 1993 study found no beneficial effect. A 2008 review found that despite a scarcity of controlled studies on alternative medicine and IC/BPS, “rather good results have been obtained” when acupuncture is combined with other treatments. Biofeedback, a relaxation technique aimed at helping people control functions of the autonomic nervous system, has shown some benefit in controlling pain associated with IC/BPS as part of a multimodal approach that may also include medication or hydrodistention of the bladder

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