nutrition 411 Interstitial Cystitis: Recognizing and Caring for a Wounded Bladder A coming from the bladder. Many patients report their pain is urethral, with varying degrees of pelvic pain. Other patients report back pain, shooting pain down the legs, and pain that is positional — for example, sitting in one place too long can trigger symptoms. In addition, both men and women report pain with intercourse. Men with IC often experience penile pain at the moment of ejaculation; women can experience pelvic pain up to 24 hours after intercourse. Women’s symptoms also may increase premenstrually and at ovulation.8 Brookoff9 explains that IC is primarily visceral. The messages for visceral pain travel to the same area of the brain where emotions are generated, so IC patients may appear to be highly emotional. In addition, IC pain can be neuropathic; the person is in pain for so long, the nerves become damaged, resulting in more intense pain signals over time. Patients considering cystectomy need to weigh the perceived and potential benefits of bladder removal with fact that many continue to experience neuropathic pain after surgery. The other two cardinal symptoms of IC are frequent urination and an unexpected urge to get to the bathroom immediately. Patients have reported having to use the bathroom up to 60 times a day. Nocturia and the resultant sleep disruption become a major cause of distress for patients. Although knowing clinical descriptions of the disease is valuable, no definition of IC is complete without the vivid comments IC patients use to explain how they feel. Often patients will describe the pain as if they have “razor blades or battery acid” in their bladders. Patients may be frustrated because they are fine one moment and doubled over in unbearable pain the next. Common comorbidities include irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, vulvodynia, and various allergies, all suggesting a connection with the immune system. Patients also may experience a variety of mood or mental health disorders related to their disease. People living with chronic pain often experience a tremendous amount of stress, suffering emotionally as well as physically. Social lives may be disrupted and intimate relations strained. The despair and disability of many with IC is very real; nearly half of all IC patients cannot hold fulltime jobs, and many patients become depressed. Suicidal thoughts are not uncommon, and frequently, patients act on those thoughts.10 D U PL IC A ccording to the Interstitial Cystitis Association (ICA),1 interstitial cystitis (IC), a painful and puzzling bladder disorder, “is a condition that consists of recurring pelvic pain, pressure, or discomfort in the bladder and pelvic region, often associated with urinary frequency and urgency.” The RAND Interstitial Cystitis Epidemiology study2 reported in 2009 that approximately 3 to 8 million women and 1 to 4 million men suffer from IC. Historically, IC was considered a chronic pelvic pain syndrome originating in the bladder, but epidemiological studies comparing IC with similar conditions belie the simplicity of this statement. International researchers working to describe what is happening to an IC bladder are including other syndromes similar to IC; hence, IC is referred to alternatively as painful bladder syndrome (PBS), bladder pain syndrome (BPS, used primarily in Europe), and hypersensitive bladder syndrome (HBS, used primarily in Asia). Men also may be diagnosed with chronic prostatitis (CP), which shares similar symptom characteristics with IC. For the purpose of simplicity, in this article the condition will be called IC. TE Julie Beyer, MA, RD D O N O T Clinical Presentation Patients with IC experience urinary pain, frequency, urgency, and nocturia that cannot be attributed to other causes; thus, diagnosis frequently is by exclusion.3-5 Although symptoms of IC can be confused with a urinary tract infection, urine from an IC patient does not show any bacteria when cultured. The fundamental pathophysiology of IC is a damaged or wounded bladder lining. Both the glycosaminoglycans (GAG) layer (the protective mucous coating on the surface of the bladder) and the urothelial layer (the skin-like barrier that transmits the messages of pain and urgency to the brain) can be damaged in a bladder, causing IC symptoms. Diagnosticians may observe glomerulations, or petechial hemorrhages, when a patient undergoes a cystoscopy under anesthesia; however, there is some concern this damage could be caused by the procedure itself. Approximately 7% to 9% of patients actually have ulceration (Hunner’s ulcers) in the bladder lining.6 Mastocytosis (akin to having hives in the bladder) is also a common finding.7 Assessing Bladder/Urethral Symptoms For diagnostic purposes, IC pain generally worsens as the bladder fills with urine and is relieved upon emptying the bladder. The pain may or may not be perceived as Julie Beyer, MA, RD, is a registered dietitian and interstitial cystitis patient. You may contact her at: www.ic-diet.com. This article was not subject to the Ostomy Wound Management peer-review process. 12 ostomy wound management december 2011 www.o-wm.com nutrition 411 • Consider treatments from least to most conservative depending on initial presentation of the patient. Pain management is important at every level. • Consider multimodal treatments to control the various aspects of the condition. • Second-line treatments include pelvic floor physical therapy, and both oral and intravesical medications. • Third-line treatments include cystoscopy under anesthesia and treatment/excision of Hunner’s ulcers if indicated. PL • Fourth-line treatments include neuromodulation and continued pain management. IC A • First-line treatments include patient education, stress management, and self-care including dietary modification. Current IC Treatments Previously, experts had considered IC to be a disease with little, if any, chance of improvement regardless of treatment.13 Although IC still does not have a cure, the outlook is much brighter. A variety of lifestyle changes, medications, and medical treatments are available to ease symptoms, improve quality of life, and possibly provide relief in the form of a remission. As a result, an individualized treatment plan often involves patients working with a multidisciplinary team that includes urologists, gynecologists, nurse practitioners, counselors, physical therapists, and dietitians.11 In 2011, The AUA11 published the most comprehensive treatment guidelines to date (see Table 1), establishing a plan based on individual patients’symptoms presentation, beginning with the least invasive treatments (lifestyle modifications) and graduating to various medical and surgical interventions. Medications. Currently, pentosan polysulfate (PPS, Elmiron™ Janssen Pharmaceuticals, Inc, Titusville, NJ) is the only oral medication approved by US Food and Drug Administration (FDA) for use in IC. PPS is believed to help rebuild the damaged GAG layer of some patients. Because an objective assessment of PPS effectiveness would require secondary invasive procedures, evaluation of PPS efficacy is still primarily dependent on the subjects’ self-evaluation of symptoms. Reports of efficacy vary, with between 32% and 50% of patients on PPS reporting improvement in their symptoms. The primary drawback of PPS is its low bioavailability; only 10% of PPS is absorbed in the digestive tract.14 However, PPS now has received attention in the scientific community when used as an intravesical instillation combined with other drugs, specifically lactose-bound heparin. Although researchers still are not certain how this process works, it is thought that the PPS instilled in the bladder assimilates into the GAG layer more effectively than when used as an oral treatment.15 Other oral medications used to treat IC symptoms in patients include urinary anesthetics, tricyclic antidepressants such as amitriptyline (for pain relief ), anti-convulsants, immunosuppressants, opiates, and nonsteroidal anti-inflammatory agents.16 Antihistamines (hydroxyzine HCL or hydroxyzine pamoate) can successfully reduce symptoms in patients who have demonstrated high mast cell distribution. Antihistamines also can reduce anxiety and act as a sleep aid for patients. Antibiotic and antifungal therapy are controversial treatments, but occasionally considered if an infection is suspected to be present despite sterile urine. With the advent of anticholinergic therapies used in cases of overactive bladder (detrusor overactivity), it is important to note that IC is not the same as overactive bladder and generally does not respond to anticholinergic therapy.17 Medical interventions. Allergy testing and treatment may seem like an unusual therapy for IC, but a large number of IC patients present with allergies, and many report some relief of symptoms when they undergo allergy treatment. Botulinum toxin A (BTX-A) shows promise in early trials as an intramuscular injection.18 Researchers also are evaluating TE Table 1. A summary of American Urological Association treatment guidelines for interstitial cystitis/ bladder pain syndrome • Fifth-line treatments include treatment with cyclosporine A and intradetrusor botulinim toxin. U • Bladder removal and urinary diversion are considered “last resort” unless patient’s bladder structure warrants earlier intervention. D Adapted from Interstitial Cystitis Treatment Algorithm (American Urological Association)11 D O N O T Diagnosing IC The primary diagnostic challenges are for patients to convey their unusual bladder symptoms to their medical care providers and the ability of those providers to recognize patients’ bladder symptoms as something requiring further investigation. Diagnostic methodologies have been hotly debated in the past 10 years. The 2011 guidelines developed by the American Urological Association (AUA)11 recommend using tests and questionnaires that create the least amount of trauma to the patient or bladder.11 Of course, the least invasive medical procedure would entail a measurement biomarker unique to IC patients, the most promising of which is the antiproliferative factor (APF) discovered by Keay et al12 and reported in 2002. As previously stated, getting an appropriate diagnosis relies on educating patients and physicians to the possibility of IC while increasing the awareness of newer tools and diagnostic resources among primary care providers. Until more universal diagnostic criteria are developed, IC remains a disease of exclusion, and clinicians and researchers alike generally follow a systematic, multifactorial diagnostic pathway. 14 ostomy wound management december 2011 www.o-wm.com nutrition 411 IC A TE titis, and epididymitis in outpatient urological practice: The Canadian PIE Study. Urology. 2005;66:935–940. 6. Kanai A, de Groat W, Birder L, Chai S, Hultgren S, Fowler C, et al. Symposium report on urothelial dysfunction: pathophysiology and novel therapies. J Urol. 2006;175:1624–1629. 7. Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology. 2001;57(suppl 6A):47–55. 8. Warren JW, Diggs C, Brown V, Meyer WA, Markowitz S, Greenberg P. Dysuria at onset of interstitial cystitis/painful bladder syndrome in women. Urology. 2006;68:477-481. 9. Brookoff D. Interstitial Cystitis and Pain Management. Presentation at the Northern California Summit on Chronic Pain, Santa Rosa, CA. 1997. Available at: www.ic-network.com/handbook/brookoff.pdf. Accessed September 15, 2011. 10.Ratner V. Current controversies that adversely affect interstitial cystitis patients. Urology. 2001;57(suppl. 6A):89–94. 11.Hanno PM, Burks DA, Clemens JQ, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. American Urological Association (AUA) Guideline 2011. Available at: www.auanet.org/content/guidelinesand-quality-care/clinical-guidelines/main-reports/ic-bps/diagnosis_and_ treatment_ic-bps.pdf. Accessed September 15, 2011. 12.Keay S, Zhang CO, Shoenfelt JL, Chai TC. Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis. Urology. 2003;61:1278–1284. 13.Propert KJ, Schaeffer AJ, Brensinger CM, Kusek JW, Nyberg LM, Landis JR, and The Interstitial Cystitis Data Base Study Group. A prospective study of interstitial cystitis: results of longitudinal follow up of the interstitial cystitis database cohort. J Urol. 2000;163:1434–1439. 14.Erickson DR, Sheykhnazari M, Bhavanandan VP. Molecular size affects urine excretion of pentosan polysulfate. J Urol. 2006;175(3 Pt 1):1143–1147. 15.Muthusamy A, Erickson DR, Sheykhnazari M, Bhavanandan VP. Enhanced binding of modified pentosan polysulfate and heparin to bladder—a strategy for improved treatment of interstitial cystitis. Urology 2006;67:209–213. 16.Nickel JC. Opioids for chronic prostatitis and interstitial cystitis: lessons learned from the 11th World Congress on Pain. Urology. 2006;68:697–701. 17.Minaglia S, Ozel B, Bizhang R, Mishell DR. Increased prevalence of interstitial cystitis in women with detrusor overactivity refractory to anticholinergic therapy. Urology. 2005;66:702–706. 18.Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB. Botulinum toxin A has antinociceptive effects in treating interstitial cystitis. Urology. 2004;64(6):871–875. 19.Oyama IA, Rejba A, Luknan JC, Fletcher E, Kellogg-Spadt S, Holzberg AS, Whitmore, KE. Modified Thiele massage as therapeutic intervention for female patients with interstitial cystitis and high-tone pelvic floor dysfunction. Urology. 2004;64(5):862–865. 20.Beyer JA, The IC Diet and Food List 2011. Available at: http://ic-diet.com/ IC%20Diet%20and%20Food. PL pelvic floor physical therapy with validated instruments, providing evidence of efficacy of a therapy that has been used successfully for years in many patients.19 Instillations. Intravesical instillations can be helpful for some patients and include dimethyl sulfoxide (DMSO), heparin, lidocaine, and the previously mentioned offlabel use of PPS dissolved in a solution. External and surgically placed sacral neuromodulation devices have been used successfully in some patients, although overall results have been mixed. Much more invasive surgical procedures can be used, with bladder removal considered a last resort.11 Diet and lifestyle changes. Diet and other lifestyle modification techniques are very helpful in helping IC patients take control of their symptoms. Patients often suspect that certain foods trigger their symptoms long before they are diagnosed. For most IC patients, the worst offenders are tomato products, cranberry juice, citrus fruits, soy, coffee, tea, sodas, alcoholic beverages, chocolate, and spicy foods.20 A wellconstructed elimination diet plan including symptom and food intake journals can help uncover other individual food sensitivities. Stress management education can be nearly as important in diet to modify the effects of stress hormones on the urinary system.11 n References D O N O T D U 1. Interstitial Cystitis Association. What Is IC? 2009. Available at: www. ichelp.org/Page.aspx?pid=327. Accessed September 15, 2011. 2. Barry SH, Stoto MA, Elliott M, et al. Prevalence of interstitial cystitis/painful bladder syndrome in the United States. J Urol. 2009;181:20–21. 3. Hanno PM. Interstitial cystitis—epidemiology, diagnostic criteria, clinical markers. Rev Urol. 2002;4(suppl 1):53–58. 4. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Interstitial Cystitis/Painful Bladder Syndrome. 2005. Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/interstitialcystitis/. Accessed September 15, 2011. 5. Nickel JC, Teichman MH, Gregoire M, Clark J, Downey J. Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cys- 16 ostomy wound management december 2011 www.o-wm.com