Fibromyalgia and painful bladder syndrome/Interstitial Cystitis (PBS/IC) are two diseases both with chronic pain. About 17.7% of the PBS/IC will have fibromyalgia by previous study.  These two diseases have similar common characteristics, such as demographic characteristics; comorbidities; past history; risk factors; difficult to treat. However, the exact pathogeneses are still unknown. This study assumes that there is a causal relationship between the two diseases, and design a cohort study to explore if the risk of PBS/IC in fibromyalgia patients is higher than those patients without fibromyalgia in Taiwan.

The cohort study used longitudinal health insurance database (LHID2010) of the Taiwan National Health Insurance in 2010. We define those who are first-time diagnosed of fibromyalgia during 2002 to 2013 fibromyalgia cohort. Patients without fibromyalgia were matched with age, sex and ten comorbidities acquired the non-fibromyalgia cohort. Prospective observe and compare the risk of PBS/IC during study period in these two cohorts. In addition, to analysis the duration from diagnosis of fibromyalgia to the occurrence of PBS/IC in these cases

In unmatched group, including 1,403 FM and 368,507 non-FM patients, the PBS/IC HR was 1.064 (95% CI, 0.813-1.393; p=0.651) in the FM cohort compared with non-FM cohort. In matched group, there were 23,751 patients in both FM and non-FM cohorts and the PBS/IC HR was 1.373 (95% CI, 0.866-2.177; p=0.178). The average year of developing PBS/IC in FM cohort and non-FM cohort were 3.71±2.53 (n=33) and 5.85±3.32 (n=50) years, respectively

In this study, the propensity score method to match the control interference factors, the period of the tracking period was up to 12 years, representing the credibility and internal and external validity of the study.
2.	In 1997, Clauw showed that PBS/IC and FM have many similarities between the symptoms and possible pathogenesis, such as increased sensitivity of pain stimulation in the CNS and increased sensitivity of pain in surrounding tissues, it is only inferences and lack of sufficient evidence.
3.	In 2010, Nickel conducted a questionnaire survey of 205 PBS/IC and 117 age-matched general populations. Patients with interstitial cystitis were significantly more likely to have fibromyalgia at the same time (17.7% vs 2.6%, p < 0.001), and 20.2% of patients had multiple comorbidities at the same time, and their symptoms were more severe, also may be two way evolution
4.	The results of this program show that "fibromyalgia" does not increase the risk of "interstitial cystitis". Therefore, there should be no common cause or pathogenesis in the two; at the same time, there is no two-way evolution between the two.
5.	The study also found that the diagnosis of fibromyalgia patients is greatly variable. There were 326,732 patients with "fibromyalgia" diagnosed with incidence rate was about 30% or more by doctors from all departments, however, 31,565 were diagnosed by medical specialists, with an incidence of about 3.1%, similar to epidemiological investigations (2-8%). Therefore, this study only used patients with "fibromyalgia" diagnosed by medical specialists, which can increase the reliability of the research results, and can also be used as a reference for future research.
6.	In this study, the risk of "interstitial cystitis" was compared between the two generations before and after pairing by CoX analysis. The number of samples before pairing was larger (n=695,239), which was close to the mother group. The analysis result of the step can represent the characteristics of the whole sample, that is, the external validity is better. However, because of the influence of the interference factor, the second step was performed and then the survival analysis was performed. Although the number of samples was relatively small (n=47,520), the pairing control of age, sex and 10 comorbidities due to the propensity score. It can avoid the influence of interference factors, that is, the inherent validity is higher, which can represent the causal relationship between real diseases.
7.	The results of this program show that "fibromyalgia" is not a risk factor for "interstitial cystitis" and has no causal relationship. However, the two diseases may still be affected by other "Mediator", and the relationship between "interstitial cystitis" and other comorbidities still needs more research to confirm.
8.	Limitation of study: ICD coding based for the dependent and confounding factors that maybe a diagnosis bias. PBS/IC patients may not go to undertake the treatment which is a detection bias. There may be a different results using another one million sample.

FM has no causal effect on PBS/IC in this twelve years’ cohort study. The average year from diagnosis of FM to PBS/IC was 3.71±2.53 years

Lee MH, Chang KM, Tsai WC,  Morbidity rate and medical utilization in interstitial cystitis/painful bladder syndrome. International Urogynecology Journal, 2018 Jul;29(7):1045-1050
Clauw, Daniel J. Fibromyalgia. JAMA. 2014-04-16, 311 (15): 1547–55
Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, et al. Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. The Journal of urology. 2010;184(4):1358-63