Preliminary results of bladder syndrome associated with Sjögren syndrome

Background information

Painful bladder syndrome, ie interstitial cystitis (IC), is a very rare bladder inflammatory disease whose cause is still completely unclear. 

Interstitial cystitis (painful bladder syndrome / interstitial cystitis; PBS/IC) is a persistent pain syndrome affecting the urinary bladder with symptoms including urinary frequency, bladder pain and nocturia (excessive urination at night).

The diagnosis of this disease is based on clinical observation (urinary tract symptoms, night urination, joint pain and abdominal pain that worsens when the bladder is filled).

The diagnosis is largely based on the exclusion of other known diseases; benign and malignant tumors, kidney stones, bacterial or fungal inflammation, urinary tuberculosis, bladder nerve disorders and gynecological causes such as endometriosis. 

Some patients have been thought to have some autoimmune disease underlying the symptoms. Also, Sjögren's syndrome (SS) has been suspected to be associated with painful bladder syndrome, IC's.

Possible cause for the deterioration of the function of Sjögren's cells is the formation of the body's antibodies. In a patient with Sjögren's syndrome, the body forms an adverse antibody that identifies the so-called " muscarinic receptor and binds therein, thus preventing normal regulation through the receptor. The receptor-attached antibody also activates another immune defense system which then attacks the antibody-identified cells and attempts to destroy them." 

Muscarinic receptors are located at many places in the body. They are located in the smooth muscles of the blood vessels, as well as in the lungs. M₃ receptors typically cause contraction of smooth muscle, such as that observed during bladder emptying.

Muscarinic receptors play a key role in the regulation of bladder muscle activity. Specifically, the receptor types M₂ and M₃ are central to the initiation of the urine reflex. Also, the receptors of spinal cord, M₁ , block the start of the urine reflex. 

Overall, bladder function is subject to many regulatory systems, and the disruption to the balance of these systems can then lead to varying degrees of problems.

Possible disruption of bladder function in connection with Sjögren's syndrome has been neglected in the past. Some indications have previously been obtained from the adherence of Sjögren's syndrome to painful bladder syndrome, ie interstitial cysts, but the findings have been related to individual patients. A wide-ranging study of SS and Bladder Disorders has not been done before.

Research results

In spring 2000, a questionnaire was sent to all members of the Sjögren Association, where a variety of urinary disorders were detected. In order to evaluate the significance of the findings, an identical survey was also carried out simultaneously with 2000 Finnish women who were selected as a comparative population and randomly selected from the Population Register Center. 

Participation in the questionnaire was commendable in both groups. As many as 81% of Sjögren members answered the questionnaire, and 67% of these respondents were interviewed.

In the interviews, an interstitial cystitis syndrome formulation was used, to monitor the disease. In the survey, it was particularly desirable to find out whether Sjögren's syndrome is significantly related to the ICs.

The prevalence of urinary symptoms in Sjögren patients was strikingly common. 12% of those surveyed suffered from severe bladder symptoms and, in addition, half the patients had mild to moderate symptoms. 

Moderate and severe symptoms were 3-4 times more common in SS than in women of comparable population and the mean or severe disadvantages caused by these symptoms were 4-5 times more common in Sjögren patients. Pain, which is the central symptom of interstitial cystitis (IC), was 8 times more common in Sjögren patients.

In smoking Sjögren patients, moderate to severe bladder symptoms were twice as common as non-smokers. There was no correlation in the control population. However, the number of pregnancies had no effect on the prevalence of the urinary symptoms in either study group.

5% of Sjögren patients had received an antibiotic for urinary tract infection in the last month. In the control population, this was less than half. Based on the questions, 5% of Sjögren patients met the IC criteria. This prevalence was almost 20 times more common in Sjögren than in the control group (without Sjögren's syndrome). It was also interesting to note that a third in the patients of the comparison population who met the IC criteria were SS.

Conclusions

The study provides for the first time strong evidence that interstitial cystitis is significantly associated with Sjögren syndrome. However, this questionnaire still does not allow for more precise interpretations of possible underlying mechanisms.

Muscarinic receptor agents can play an important role.  Also, hormonal factors may have a significant effect. Interestingly, both Sjögren patients and 90% of IC patients are women. The female hormone (estrogen) can affect the many inflammatory mechanisms in the body and enhance the response of various inflammatory mediators. Probably a number of different factors can trigger an inflammatory process in the bladder wall, resulting in painful bladder syndrome.

Mikael Leppilahti 
Urology, Department Officer 
Seinäjoki Central Hospital, Finland 

Translated from Finland Sjögren's Syndrome Association