Interstitial Cystitis Part V

Treatment Modalities: Probiotics

Contrary to popular belief, the bladder is not sterile, a concept relatively recently presented as truth.⁴² In a detailed article regarding the history and current discoveries of the urinary microbiome, authors displayed evidence for the validity of a microbiome housed in the bladder.⁴² Not only is the urinary microbiome in existence, but in most people, it plays a protective role much like the microbiomes found in the rest of the body.⁴² It has been postulated that disturbances in the urinary microbiome may contribute to the symptomatology that accompanies urgency urinary incontinence.⁴² The authors of the review stated that future work is needed to better understand the intricate world of the urinary microbiome as well as what contributes to its development and healthy maintenance.⁴² Though this review does not pertain directly to IC, it does bring up questions as to whether or not the use of probiotics to ensure healthy microbiota would be warranted in IC patients.

Though not a well-referenced site, the Interstitial Cystitis Association (ICA) has presented the potential benefit of probiotics for IC patients, stating that adding this supplement may provide support for general wellness.⁴³ The ICA states that probiotics initiate growth of good bacteria that will in turn help to boost he body’s natural immune defenses, thus encouraging whole-body wellness.⁴³ Further, the ICA site reports that some IC patients have found benefit to taking probiotics, therefore presenting the possibility of positive effect.⁴³

In a cross-sectional study, researchers compared variance between the urinary microbiome and the cytokine levels of IC-diagnosed women and healthy controls.⁴⁴  Results demonstrated that the urinary microbiome of IC participants was less diverse, less likely to be colonized with lactobacillus, and linked with higher levels of proinflammatory cytokines.⁴⁴ These results present the assumption that the microbiome of IC patients is damaged or altered and would perhaps benefit from the introduction of probiotics as an adjunctive treatment option.

A systematic review was performed on the topic of the microbiome in the urinary tract  and the use of prebiotics and probiotics as useful treatment for various urological disprders.⁴⁵ Eighty-nine studies were included in the review and focused on a variety of urologic disorders including urinary incontinence, urologic cancers, interstitial cystitis, neurogenic bladder dysfunction, sexually transmitted infections, and chronic prostatitis/chronic pelvic pain syndrome.⁴⁵ Following an assimilation of the data and subsequent investigation of the study outcomes, the authors concluded that the microbiome in healthy individuals likely changes from a healthy one to a damaged one with the presence of urologic disorders.⁴⁵ Authors posed the hypothesis that the use of prebiotics and probiotics may provide a useful modality in the treatment of urologic disorders but the need for further study is apparent.⁴⁵ Again, though the accumulation of data regarding the proven benefit of using prebiotics and probiotics to treat urologic disorders has not yet been widely collected, enough evidence exists to support the assumption that this may offer a promising therapy for those suffering from these disorders.

Treatment Modalities: Dietary Intervention

Dietary intervention has been widely suggested as a possible way to reduce flare ups and symptoms of IC.³ Though dietary changes do not appear to provide a curative effect, studies reveal that the elimination of certain foods may be helpful in the management of symptoms. One study on dietary triggers and IC was performed to determine which foods most exacerbated symptoms.^46.Three hundred forty-four foods were considered in regard to problematic potential to effect urinary frequency, urgency and/or pelvic pain symptoms.⁴⁶ Researchers discovered that out of the 598 responses submitted, 95.8% of the participants answered affirmatively that certain foods and beverages contributed to their IC symptoms.⁴⁶ The majority of food and beverages tested posed no effect on symptoms but the items most frequently identified as problematic were citrus fruits, tomatoes, coffee, tea, carbonated and alcoholic beverages, spicy foods, artificial sweeteners, and vitamin C.⁴⁶ In addition, calcium glycerophosphate (a calcium salt) and baking soda offered symptom relief in some participants.⁴⁶ Researchers concluded that though IC diets do not necessarily need to be significantly restricted, it would behoove patients to abstain from the above-listed foods in order to provide preventative measures as well as alleviate symptoms.⁴⁶  

In a survey of 374 IC patients, the affect of certain beverages was tested in regard to IC symptomatology.⁴⁷ Researchers discovered that the inclusion of acidic, alcoholic or carbonated beverages, and coffee or tea caused an increase in overall pain in more than 50% of the participants, thus suggesting that the elimination of such liquids would be beneficial to IC patients.⁴⁷

In a study of 104 IC patients, researchers investigated the effect of 175 different foods and beverages.⁴⁸ Out of those surveyed, 90.2% reported that the consumption of particular foods irritated their symptoms, though no correlation was found between allergic reactions and the effect of certain foods on symptoms.⁴⁸ The foods and beverages most widely identified as problematic in terms of increased symptoms were caffeinated, carbonated and alcoholic beverages, certain fruits and juices, artificial sweeteners and spicy foods.⁴⁸ Looking at a compilation of the data, it appears fairly apparent that certain groups of foods cause an increase in symptom presentation and IC patients have potential benefit from eliminating such foods from the diet.

References

42. Thomas-White K, Brady M, Wolfe AJ, Mueller ER. The bladder is not sterile: history and current discoveries on the urinary microbiome. Current Bladder Dysfunction Reports. 2016; 11(1): 18-24. 

43. Interstitial Cystitis Association. Do probiotics work? Available at: https://www.ichelp.org/diagnosis-treatment/treatments/ic-diet-self-management/do-probiotics-help-ic/. Accessibility verified July 18, 2018.

44. Abernethy MG, Rosenfeld A, White JR, Mueller MG, Lewicky-Gaupp C, Kenton K. Urinary  microbiome and cytokine levels in women with interstitial cystitis. Obstetrics and Gynecology. 2017; 129(3): 500-506.

45. Aragón IM, Herrera-Imbroda B, Queipo-Ortuño MI, et al. The urinary tract microbiome in health and disease. European Urology Focus. 2018; 4(1): 128-138.

46. Bassaly R, Downes K, Hart S. Dietary consumption triggers in interstitial cystitis/bladder pain syndrome patients. Female Pelvic Medicine and Reconstructive Surgery. 2011; 17(1): 36-39.

47. Koziol JA, Clark DC, Gittes RF, Tan EM. The natural history of interstitial cystitis: a survey of 374 patients. The Journal of Urology. 1993; 149(3): 465-9.

48. Shorter B, Lesser M, Moldwin RM, Kushner L. Effect of comestibles on symptoms of interstitial cystitis. The Journal of Urology. 2007; 178(1): 145-152.

Interstitial Cystitis Part IV

Treatment Modalities: Yoga

Due to the fact that IC is a disorder oftentimes associated with poor musculoskeletal, neural and myofascial function of the back and/or pelvis, yoga has been shown to be an effective tool in the amelioration of IC symptoms as well as the accompanying psychological challenges.³⁴ It has been suggested that programs formulated to sustain balance of the main contributing muscles which affect the pelvic structure and lower back should be used in IC patients to help with symptom management.³⁴

In a small randomized controlled trial of 20 women, researchers looked at the use of mindfulness-based stress reduction (MBSR), combining the modalities of meditation and yoga, and its effect on IC.³⁵ Researchers stated that because stress exacerbates the symptoms of IC significantly, this treatment method is highly warranted due to its strong stress-reducing effects.³⁵ Women in the study were divided into two groups, one receiving usual care (UC) and the other receiving UC as well as engaging in MBSR.³⁵ Though the MBSR group did not exceed symptom amelioration on all measures when compared to the UC group, significant improvement was seen in the women engaged in MBSR.³⁵ More MBSR patients reported post-treatment symptom improvement when compared to the UC group (87.5% of MBSR group versus 36.4% of UC group).³⁵ Though some of the MBSR group improvement was not statistically significant, it still provides insight into the therapy method and its potential effect on IC.³⁵ Researchers concluded that the results of this study provide evidence to reinforce the role of MBSR as a significantly useful tool for the treatment of IC and should be incorporated into the care plan of IC patients.³⁵ Limitations presented by small sample size should also be taken into consideration.

Though not specifically referring to IC, the results of a meta-analysis may shed light on the possibility of the benefit of using yoga for IC patients.³⁶ Though small, the study further supports the use of yoga in those who suffer from prolonged pain.³⁶ Researchers concluded that the use of yoga as a complementary approach for those suffering from pain is a useful tool that produces moderate effect sizes on pain-ridden individuals.³⁶ This finding can indirectly be applied to the possibility of yoga providing similar benefit to those suffering from the pain associated with IC.³⁶

Treatment Modalities: Physical Therapy

Physical therapy (PT) has been used to treat IC patients and shown benefit.²⁶ PT for IC patients frequently centers around soft tissue manipulation and rehabilitation that can help facilitate scar reduction and pain improvement.²⁶ Exercises oftentimes focus on pelvic floor relaxation rather than strengthening pelvic floor muscles.²⁶

In a randomized, multicenter clinical trial of 81 women suffering from IC, researchers looked at the benefit of myofascial physical therapy (MPT) when compared to global therapeutic massage (BTM).³⁷ Though results displayed superior benefit of the MPT when compared to the GTM (59% improvement in the MPT group versus 26% in the GTM group), both categories experienced amelioration of some symptoms.³⁷ In addition, the sample size was small, thus presenting the need for caution in regard to drawing broad conclusions.³⁷

A pilot study of 16 female IC-diagnosed patients who suffered from high-tone pelvic floor dysfunction were monitored following manual PT.³⁸ Therapy included several techniques including direct myofascial release, joint mobilization, muscle energy techniques, strengthening, stretching, and neuromuscular reeducation.³⁸ Patients were tested for symptoms before and after treatment to determine levels of improvement.³⁸ Greatest improvement was seen in frequency of pain and suprapubic pain, while improvement in urgency and nocturia showed smaller changes.³⁸ Researchers concluded that manual PT may be a positive therapeutic tool in the treatment of IC.³⁸

Forty-five women and seven men with IC or urgency-frequency syndrome were followed in a study to determine the effects of manual PT on the symptoms of these disorders.³⁹ Researchers stated that, “The rationale was based on the hypothesis that pelvic floor myofascial trigger points are not only a source of pain and voiding symptoms, but also a trigger for neurogenic bladder inflammation via antidromic reflexes”, thus attempting to reach a deeper part of the problem.³⁹ PT centered around the pelvic floor and was conducted one to two times per week for eight to twelve weeks.³⁹ Results demonstrated that the specific manual PT employed was highly effective in symptom amelioration for both groups of patients.³⁹

Treatment Modalities: Acupuncture

Acupuncture has long been known for its beneficial effect on pain. A study involving a small sample of IC-diagnosed female patients examined the usefulness of acupuncture on symptom reduction.⁴⁰ All twelve participants received ten acupuncture administrations twice a week and evaluations of symptoms were completed in the 1^st, 3^rd, 6^th and 12^th months.⁴⁰ Results showed a statistically significant decrease in all measures in the first month.⁴⁰ Improvement scores varied at different points in the study, with positive effect demonstrated in differing areas during all evaluations.⁴⁰ Despite the small sample size, based upon the study results, researchers concluded that acupuncture displays a promising, non-invasive and efficacious treatment option for those suffering with IC.⁴⁰

A systematic review of complementary therapies for bladder pain syndrome looked at 11 studies, all of which were evaluated for quality based on the Cochrane risk of bias scale prior to their inclusion.⁴¹ Several key interventions were discussed amongst the studies including acupuncture, relaxation therapy, physical therapy, hydrogen-rich therapy, diet and nitric oxide synthetase.⁴¹ Following careful evaluation, researchers concluded that dietary management, acupuncture and physical therapy had the highest potential for providing benefit to patients with bladder pain syndrome.⁴¹ Researchers advised caution in regard to these results due to the limited study sizes included in the review.⁴¹

References

34. Ripoll E, Mahowald D. Hatha Yoga therapy management of urologic disorders. World Journal of Urology. 2002; 20: 306–309.

35. Kanter G, Komesu YM, Qaedan F, et al. Mindfulness-based stress reduction as a novel treatment for interstitial cystitis/bladder pain syndrome: a randomized controlled trial. International Urogynecology Journal. 2016; 27(11): 1705-1711. 

36. Büssing A, Ostermann T, Lüdtke R, Michalsen A. Effects of yoga interventions on pain and pain-associated disability: a meta-analysis. Translational Andrology and Urology. 2015 4(6); 653-661. 

37. FitzGerald M, Payne C, Lukacz E, et al. Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome (IC/PBS) and pelvic floor tenderness. The Journal of Urology. 2012; 187(6): 2113-2118. 

38. Lukban J1, Whitmore K, Kellogg-Spadt S, Bologna R, Lesher A, Fletcher E. The effect of manual physical therapy in patients diagnosed with interstitial cystitis, high-tone pelvic floor dysfunction, and sacroiliac dysfunction. Urology. 2001; 57(6)(1): 121-122.

39. Weiss JM. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome. The Journal of Urology. 2001; 166(6): 2226-2231.

40. Sönmez MG1, Kozanhan B. Complete response to acupuncture therapy in female patients with refractory interstitial cystitis/bladder pain syndrome. Ginekologia Polska. 2017; 88(2): 61-67.

41. Verghese TS, Riordain RN, Champaneria R, Latthe PM. Complementary therapies for bladder pain syndrome: a systematic review. International Urogynecology Journal. 2016; 27: 1127-1136. 

Interstitial Cystitis Part III

Treatment Modalities: Medications

When it comes to treatment options for IC, the list of possibilities is lengthy. However, it is important to note the risks and benefits of the suggested treatments prior to the engagement of any one modality. Treatments range from prescribed and over-the-counter medications to so-called natural interventions, diet and lifestyle modifications.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen sodium are sometimes used for IC patients. The reasoning behind these types of prescriptions is based upon the premise that inflammation plays an integral part in the pathophysiology of IC.²³ With the use of these drugs, prostaglandin production is blocked and reportedly leads to control of inflammatory pain.²³ Challenges may arise, however, due to the increased risk of serious gastrointestinal and cardiovascular adverse effects with NSAID use.²³ Some researchers go so far as to say that IC can be caused by NSAID use, a condition known as drug-induced interstitial cystitis (DIC).²⁴ In a review on DIC and the effects of particular drugs on the development or exacerbation of symptoms, researchers found that NSAIDs may contribute to the initiation or worsening of symptoms.²⁴ Authors were bold enough to state:

“Although there is no clear association between other NSAIDs and cystitis, there is sufficient evidence to suspect strongly that they do occasionally induce cystitis…Unless drugs are essential and cannot be replaced by suitable alternatives, they should be stopped in sequence, starting with obvious candidates such as NSAIDs…New drugs are being introduced all the time and as urologists, we need to raise our level of awareness. It seems that many urologists do not read Current Problems in Pharmacovigilance or The British Medical Journal.”²⁴

Tricyclic antidepressants are another class of drug frequently prescribed for IC. These drugs such as amitriptyline or imipramine work by aiding in the relaxation of the bladder which in turn facilitates blockage of pain.³ The mechanism of action lies in the drug’s ability to inhibit the reuptake of norepinephrine and serotonin from the brainstem to the spinal cord.²⁵ However, though in theory these drugs may suggest benefit, some research has shown that this class of drugs is useless for pain unless the patients taking them are simultaneously suffering from depression.²⁵ Therefore, researchers conclude that in regard to pain, “if the patient is not depressed, the SSRIs are virtually useless”.²⁵

According to Harvard Health, tricyclic antidepressants have the ability to relax the bladder, slow the release of neurochemicals that initiate bladder pain and inflammation and may also enhance sleep.²⁶ With most medications, however, these drugs also carry with them side effect profiles that are less than desirable.²⁶

                    In a study of 94 patients, the long term use of tricyclic antidepressants was examined to determine safety and efficacy.²⁷ Though the researchers concluded that patient satisfaction overall was highly positive (46% of patients), several limitations are of note.²⁷ Not only did 84% of the patients experience negative side effects, but the dropout rate was 31%, a fairly large percentage of the original group.²⁷ Perhaps of even greater significance was the fact that nonresponse to treatment was the leading explanation for dropout with side effects contributing to 86% of those who exited the study.²⁷ With these factors in mind, the so-called “feasible, safe and effective” use of tricyclic antidepressants as a treatment for IC is questionable.²⁷

Antihistamines are another class of frequently prescribed medication in the management of IC. The assumption is that these drugs will reduce issues of urgency and frequency and in turn, relieve additional symptoms.³ In a study of 90 participants, researchers observed the effects of using hydroxyzine as a treatment for IC.²⁸ Results demonstrated a positive and useful effect of the drug for IC patients.²⁸  Side effects such as sedation, increased appetite, urinary retention and nightmares were reported.²⁸ Further, researchers commented that the reasoning as to why hydroxyzine shows positive effect remains unclear, stating that the antihistamine action is not enough to explain positive action.²⁸ Some postulate that since hydroxyzine is a histamine antagonist and inhibits mast cell (found in connective tissue, responsible for releasing histamine and contributing to inflammatory and allergic reactions) degranulation, a reduction in the release of histamine occurs.²⁹ As histamine release is decreased, there may be a benefit for IC patients due to the assumption that increased histamine release appears to be present in the pathophysiology of IC.²⁹

In a prospective, randomized, double-blind placebo-controlled trial, researchers looked at the effectiveness of cimetidine, an oral histamine antagonist, for IC patients.³⁰ Of the 34 patients who completed the study,  significant improvement of symptoms, pain and sleep disturbance due to voiding urgency was observed  in those taking the cimetidine.³⁰ However, researchers also noted that no qualitative change was observed in the bladder mucosa as a result of treatment and further, the mechanism of action for symptom relief was unidentifiable.³⁰

Pentosan polysulfate sodium (PPS), marketed as Elmiron and approved specifically for the amelioration of IC symptoms, is also frequently used in the treatment regimen of IC.³ However, the mechanism of action is unknown.³ Another factor worthy of mention is the reality that pain reduction may take two to four months and improvement in urinary frequency may take up to six months, creating a significant challenge for many patients who have lived with the disorder for extended periods of time.³  In a randomized, double-blind, placebo controlled study, researchers examined the efficacy of using a third of the recommended daily dose of PPS in IC patients.³¹ When compared to a placebo, results demonstrated that there was no statistically significant improvement between the study group and the placebo group.³¹ Further, researchers concluded that despite the broad population of symptomatic patients involved in the study, no treatment effect was revealed.³¹

Retrospectively reviewing the charts of 260 IC patients, authors of another study evaluated the efficacy and safety of PPS.³² Observations demonstrated that symptoms of both groups improved over time but symptom improvement was greater in terms of statistical significance in the treatment group compared to the control group.³² Nocturia was unchanged in the treatment group when compared with the control group.³² Authors concluded that though some areas of symptomatology were unchanged between groups and 15% of patients experienced negative side effects, that PPS remains an efficacious option for symptom reduction in IC patients.³² A systematic review of pharmacologic treatment of IC was performed to determine efficacy of the wide variety of medication options.

Researchers looked at randomized controlled trials in regard to pharmacological options for IC patients with the intention of evaluating the efficacy of medications, examine the effect size of the trials and to begin to develop a clinical consensus in terms of efficacious treatment options.³³ Twenty-one randomized controlled trials were used in the review, including 1470 patients.³³ Though PPS showed modest treatment benefit, researchers concluded that there is an insufficient amount of evidence available for any other pharmacological treatments.³³ Authors stated, “ A consensus on standardized outcome measures is urgently needed”.³³

It is clear that many questions and limitations remain in terms of pharmacological treatment options. Challenges such as unknown mechanisms of action, significant side effects, and lengthy waits for symptom reduction all point to the use of caution prior to the utilization of these medications. It would perhaps be useful to examine what alternatives exist for those suffering from this debilitating issue.

References

23. Gardella B, Porru D, Allegri M, et al. Pharmacokinetic considerations for therapies used to treat interstitial cystitis. Expert Opinion on Drug Metabolism and Toxicology. 2014; 10(5): 673-684.

24. Bramble FJ, Morley R. Drug-induced cystitis: the need for vigilance. British Journal of Urology. 1997; 79: 3-7.

25. Medscape. Symptomatic treatment of neuropathic pain: a focus on the role of anticonvulsants: tricyclic antidepressants (TCAs) for the treatment of neuropathic pain. Available at: https://www.medscape.org/viewarticle/413110_3. Accessibility verified July 17, 2018.

26. Harvard Health Publishing. Diagnosing and treating interstitial cystitis. Available at: https://www.health.harvard.edu/diseases-and-conditions/diagnosing-and-treating-interstitial-cystitis. Accessibility verified July 17, 2018.

27. van Ophoven A, Hertle L. Long-term results of amitriptyline treatment for interstitial cystitis. The Journal of Urology. 2005;174(5): 1837-1840.

28. Theoharides TC, Sant GR. Hydroxyzine for interstitial cystitis. Urology. 1997; 49(5): 108-110.

29. Association of Reproductive Health Professionals. Screening, treatment, and management of IC/PBS. Available at: http://www.arhp.org/Publications-and-Resources/Clinical-Proceedings/Screening-Treatment-and-Management-of-ICPBS/Management. Accessibility verified July 18, 2018.

30. Thilagarajah R, Witherow ON, Walker MM. Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double‐blind placebo‐controlled trial. BJU International. 2001; 87(3): 207-212.

31. Nickel JC, Herschorn S, Whitmore KE, et al. Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: insights from a randomized, double-blind, placebo-controlled study. The Journal of Urology. 2015; 193(3): 857-62.

32. Waters MG, Suleskey JF, Finkelstein LJ, Van Overbeke ME, Zizza VJ, Stommel M. Interstitial cystitis: a retrospective analysis of treatment with pentosan polysulfate and follow-up patient survey. The Journal of the Osteopathic Association. 2000; 100(3): S13-8.

33. Dimitrakov J, Kroenke K, Steers WD, et al. Pharmacological management of painful bladder syndrome/interstitial cystitis: a systematic review. Archives of Internal Medicine. 2007; 167(18): 1922-1929.

Interstitial Cystitis Part II

Comorbidities

Those suffering from IC frequently present with multiple other maladies, creating an even more challenging set of symptoms to manage. In a population-based study of 9,269 IC patients and 46,345 randomly selected comparison subjects, researchers examined the prevalence of 32 comorbidities ranging from cardiovascular, pulmonary and neurological conditions to rheumatological, gastrointestinal and psychological conditions.⁹ Results displayed a significantly higher prevalence of all comorbidities when compared to the control group, with the exception of metastatic cancer.⁹

A small cross-sectional study of 132 subjects was studied in regard to interstitial cystitis and comorbidities.¹⁰ Researchers determined that multiple comorbidities existed in physician and questionnaire diagnosed patients.¹⁰ Findings coincided with previous outcomes that showed comorbidities with conditions such as migraines, irritable bowel syndrome, and overall bodily pain.¹⁰ However, results also showed several new apparent comorbidities such as symptoms related to dyspepsia as well as orthostatic intolerance (disorders with symptoms emerging during periods of standing upright that are alleviated when reclining).¹⁰

Etiology

It is widely accepted that the specific cause of IC is still unknown, though several factors appear to be influential. Some researchers state that furtherance of knowledge in regard to the causes of IC may be limited due to the central focus on the bladder and lower urinary tract as the genesis of symptoms without examining other pelvic influences and systemic factors.¹¹ Research has also shown the possible influence of other illnesses on the contraction of IC (rather than simply a comorbidity as discussed above) such as fibromyalgia, irritable bowel syndrome and chronic fatigue syndrome, suggesting that IC may entail systemic pathophysiology.¹¹ Therefore, researchers hypothesize that a plethora of causes and contributing factors are likely involved in IC symptoms which in turn lead to many sub-types of the disease.¹¹ Likewise, additional sources infer that multiple components are involved in the development of IC such as an autoimmune reaction, hereditary factors, infection or allergies.³ However, these possible instigating factors have remained unproven.³  Similarly, in a review of the literature, researchers studied possible causes of IC and came up with a multitude of potential contributing factors including the suggestion of infection and autoimmune response.¹² Certain studies have shown a connection between bacterial infection in the bladder and IC as a causal factor, but recent research contradicts this finding and no longer assumes that infection is the main etiology from which IC stems.^{12, 13, 14} In regard to the autoimmune connection, results have been contradictory.

Researchers evaluating lymphocyte populations in the blood and bladder tissue of IC patients discovered that lymphocyte populations were normal and thus not supportive of the theory that autoimmune disorders are an initiating factor.¹⁵ In a different review of the literature, researchers looked at the intertwining of IC and systemic autoimmune disease and postulated that there is a possible association between IC patients and autoimmune diseases.¹⁶ However, researchers stated “direct evidence clearly showing autoimmune mechanisms is lacking”.¹⁶ A connection between IC and Sjogren’s syndrome has shown a more significant connection, according to the researchers involved, and may warrant additional studies.¹⁶ Questions still remain as to the causal or reactionary effect of autoimmune response in regard to the etiology of IC and further research is necessary in this area.¹⁵

Research in some studies has pointed to the hereditary nature of IC as a causal variable. Researchers looked at a small group of monozygotic and dizygotic twins to determine incidence of interstitial cystitis within this population.¹⁷  Results showed that in the monozygotic twin group, five out of eight monozygotic twin respondents had probable or confirmed IC as compared to the group of 26 dizygotic twin respondents who showed no signs of IC.¹⁷ Researchers concluded that based on this finding, a genetic contribution is likely.¹⁷ It appears somewhat obvious, however, that basing statements upon one finding is ill-advised.

A pilot study examining the prevalence of IC within groups of first-degree relatives with an IC diagnosis was performed with a total number of 2,581 respondents.¹⁸ Out of those who responded, 101 participants reported an incidence of 107 first-degree relatives with IC.¹⁸ Researchers reported more detailed findings, stating that not only is there a genetic component involved but adult female first-degree relatives of those diagnosed with IC may have as high as 17 times higher prevalence rate than that found within the general population.¹⁸ Concluding comments stated that, “This, together with previously reported evidence showing a greater concordance of IC among monozygotic than dizygotic twins, suggests, but does not prove, a genetic susceptibility to IC”.¹⁸

The connection between allergies and IC has been examined and some studies indicate that 40-80% of patients experience allergies.¹⁹ The nature of causation versus correlation is not clear, however, and could be a comorbidity as easily as it could be a predictive element.

Several popular, but weakly referenced, IC blogs and websites suggest that leaky gut may be a causal component of IC.^{20, 21} However, finding credible research that points to causation, correlation or comorbidity does not appear easily accessible. Due to the fact that there seems to be a possible connection between IC and autoimmune disorders, it would make sense if leaky gut showed up in IC patients (due to the role leaky gut plays in autoimmune disorders). Despite this fact, little formal research has been done in this area.

Several risk variables have been suggested that may contribute to the contraction of the illness. Some articles state that risk factors range from heightened stress, sex of the individual, fair skin, red hair, or having an existing chronic pain disorder.³ However, most of the research in these areas is, at best, lacking. One report on the epidemiology, risk factors, and impact of interstitial cystitis clearly stated that the only decisive risk factor for IC is female gender.²²

Many other hypotheses for the causal factors of IC have been postulated, but the bottom line to the question of causation is the frustrating yet simple conclusion that the cause of IC is still unknown.³ Though this does not provide concrete data on what initiates the disorder, it may provide patients with a clear understanding of the fact that a specific cause is not known, suggesting time would be better spent on the prevention and treatment of IC.

References

9.     Keller JJ1, Chen YK, Lin HC. Comorbidities of bladder pain syndrome/interstitial cystitis: a population-based study. BJU International. 2012; 110(11): 903-909.

10.  Chelimsky G, Heller E, Buffington CAT, Rackley R, Zhang D, Chelimsky T. Co-morbidities of interstitial cystitis. Frontiers in Neuroscience. 2012; 6: 1-6.

11.  Mullins C, Bavendam T, Kirkali Z, Kusek JW. Novel research approaches for interstitial cystitis/bladder pain syndrome: thinking beyond the bladder. Translational Andrology and Urology. 2015; 4(5): 524-533.

12.  Grover S, Srivastava A, Lee R, Tewari AK, Te AE. Role of inflammation in bladder function and interstitial cystitis. Therapeutic Advances in Urology. 2011;3 (1): 19-33.

13.  Domingue GJ1, Ghoniem GM, Bost KL, Fermin C, Human LG. Dormant microbes in interstitial cystitis. The Journal of Urology. 1995; 153(4): 1321-1326.

14.  Wilkins EG1, Payne SR, Pead PJ, Moss ST, Maskell RM. Interstitial cystitis and the urethral syndrome: a possible answer. British Journal of Urology. 1989; 64(1): 39-44.

15.  MacDermott JP1, Miller CH, Levy N, Stone AR. Cellular immunity in interstitial cystitis. The Journal of Urology. 1991; 145(2): 274-278.

16.  Van de Merwe JP. Interstitial cystitis and systemic autoimmune diseases. Nature Clinical Practice – Urology. 2007; 4(9): 484-91.

17.  Warren JW, Keay SK, Meyers D, Xu J. Concordance of interstitial cystitis in monozygotic and dizygotic twin pairs. Urology. 2001; 57(6): 22-25.

18.  Warren JW, Jackson TL, Langenberg P, Meyers DJ, Xu J. Prevalence of interstitial cystitis in first-degree relatives of patients with interstitial cystitis. Urology. 2004; 63(1): 17-21.

19.  Van de Merwe JP, Yamada T, Sakamoto Y. Systemic aspects of interstitial cystitis, immunology and linkage with autoimmune disorders. International Journal of Urology. 2003; 10: S35–S38.

20.  Stop UTI Forever. Can a leaky gut cause IC (Interstitial Cystitis)? Available at: https://www.stoputiforever.com/interview/leaky-gut-and-ic/. Accessibility verified July 13, 2018.

21.  Eat Beautiful. How I healed my interstitial cystitis. Available at: https://eatbeautiful.net/2015/10/04/how-i-healed-my-interstitial-cystitis/. Accessibility verified July 13, 2018.

22.  Association of Reproductive Health Professionals. Screening, Treatment, and Management of IC/PBS. Available at: http://www.arhp.org/Publications-and-Resources/Clinical-Proceedings/Screening-Treatment-and-Management-of-ICPBS/Epidemiology. Accessibility verified July 13, 2018.