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.