Although this was the second patient conference to be held in Belgium for PBS/IC patients, it was the first official conference and annual general meeting of the new patient support group Interstitiële Cystitis Patiëntenvereniging België. On 18 February in Vilvoorde, the acting chairman, Josee de Raa, and her committee were formally confirmed by the members. Since part of Belgium speaks Dutch and part speaks French, the ICPB - which is currently a Dutch-language organisation for Flemish patients - is now hoping to set up a French section for the French-speakers in Belgium. This means of course that everything will have to be translated into French. All patient organisations in Belgium have to deal with this language problem. The ICPB is also planning to organise informal regional meetings for small groups of patients. They believe that this will give patients the opportunity to talk about their specific problems, exchange experiences and thereby help each other. The ICPB already has a twice yearly magazine for PBS/IC patients: Atlantis. The main problem faced by the ICPB at the moment is the usual one of "funding"!

Presentation by Professor J.J. Wyndaele

Professor J-J Wyndaele, urologist, of Antwerp University Hospital was the speaker of the day. He began by explaining to the patients in simple terms the complex neurological background to pain, the difference between acute pain and chronic pain and the long-term effects of chronic pain. The nervous system of the body is divided into the peripheral nervous system, comprising a network of nerve fibres that branch off from the spinal cord and radiate all over the body, and the central nervous system which comprises the brain, spinal cord and peripheral nerves. The brain plays an important role in pain with messages passing to and from the brain and other parts of the body, including the bladder. Neurotransmitters send nerve impulses from one cell to another. Specialised nerve cells called nociceptors at the end of nerve fibres are activated by external events such as pain or injury to body tissues and relay this information via peripheral nerves to the central nervous system where it is interpreted as pain.

Limbic system

The brain’s limbic system, which includes the hypothalamus, hippocampus and amygdala, lies on both sides of and below the thalamus. The thalamus forwards the pain signals to the cerebral cortex and the limbic system. The cerebral cortex is the place where thought processes take place and which tells you to remove your hand quickly if you have just burnt it on the oven, while the limbic system is the oldest part of the brain dating from the earliest days of the human species. It plays a role in controlling emotions, emotional responses, mood, pain and pleasure sensations. It is the limbic system which produces emotions on pain, including the physiological signs of emotion such as palpitations, stress and anxiety or a child crying when grazing a knee. This means that there is a very close relationship in the brain between pain sensation, emotion and stress.

Limbic system in the brain

Long-term effects of chronic pain

One of the problems of chronic pain is that it can eventually become imprinted in the brain and the origin of the pain is no longer necessary for the pain to be felt. The pain lives a life of its own. When this occurs in the case of PBS/IC, the patient may continue to feel pain even if the bladder is removed. Just like the phantom pain felt by amputees in limbs that no longer exist. In a similar way, a traumatic experience in life can become imprinted in the brain and continue to cause anxiety and panic attacks throughout life. Professor Wyndaele explained that recurrent, severe, chronic pain can cause changes in your whole body, changes in your emotions and feelings and changes in the body’s response to pain. It has also been shown how it affects muscles, skin and other parts of the body by mechanisms which are not as yet understood. Less pain stimulus and lower levels of pain are needed to trigger off the same sensation of strong pain. There is an increase in the intensity of the pain signals which reach the brain and the subjective perception of pain increases.

Chronic Pelvic Pain Syndrome (CPPS)

Chronic pelvic pain syndrome (CPPS) can originate in many different systems located within the pelvic area: the reproductive system, gastrointestinal system, urinary tract, nervous system, musculoskeletal system and systemic, autoimmune diseases. So there are many possible causes and the question is to find the right cause or combination of causes (overlapping chronic pelvic pain disorders). Painful bladder syndrome/interstitial cystitis is one of these possibilities. Systemic diseases such as Systemic Lupus Erythematosus or Sjögren’s syndrome can cause pelvic pain, but so can irritable bowel syndrome (IBS) or endometriosis. Professor Wyndaele spoke of the possibility of neuronal cross-talk between systems (with irritation in the one system perhaps influencing another system).

Prevalence PBS/IC

The true prevalence of PBS/IC is unknown since studies around the world have produced greatly conflicting data and depend on what basis or criteria patients have been diagnosed. However, Professor Wyndaele estimates that there could be some 4000-5000 patients in Belgium. It is mainly diagnosed in patients between the ages of 40 and 45 years, but 25% of patients are under the age of 30 years. It also occurs in children. At the present time the ratio women to men is 10:1. But it is possible that many men are receiving the wrong diagnosis. It may take an average of 5 years for a patient to obtain a correct diagnosis. Nobody yet knows how or why PBS/IC starts. There have been many theories, one being the concept of a leaky GAG-layer whereby the urine and its toxic elements can seep through into the inner linings of the bladders, and another being that an increased number of mast cells plays an important role. Some patients relate the start of their PBS/IC to a bladder infection or the use of drugs.

Symptoms

The hallmark symptoms of PBS/IC – bladder pain with urgency/frequency, pain increasing as the bladder fills and alleviated when the bladder is emptied - cause a change in the normal pattern of urination. The patient urinates small amounts frequently. In other words, the bladder can no longer store urine in the normal way. Many patients may experience pain with sexual relations. And some patients have pain throughout the pelvic floor. Although painful urination is considered to be typical of bacterial cystitis, PBS/IC patients may also experience burning pain as urine comes into contact with irritated urethral or vulvar tissues.
A study of 589 patients (Fitzgerald et al ICDB Study group ICS/IUGA 2004 abstract 417) showed that patients also had intermittent, moderately severe pain in places other than the bladder as follows:

• 74 % urethra
• 51 % vagina
• 53 % perineum
• 65 % lower back
• 80 % lower abdomen
• 24 % rectum
• 27 % elsewhere

Diagnosis

Diagnosis is currently based on:

• the exclusion of other possible diseases causing the symptoms
• urine tests
• symptoms
• cystoscopy under anaesthesia
• biopsies

A biopsy may reveal mast cells in the detrusor muscle, lamina propria and epithelium.

There are currently two categories of PBS/IC: ulcerative and non-ulcerative. The ulcerative form (Hunner’s ulcer or lesion) is only seen in around 10% of patients.

Treatment

There are many different facets to treatment of PBS/IC patients. It is essential for the doctor to take time to listen to the patient, explain everything carefully and provide the patient with support. PBS/IC patients take a lot of time. Patient support groups can help here with patient to patient counselling.
It is usual to start with conservative treatment and only progress to more invasive treatment if the conservative treatment fails. PBS/IC is not a curable disease, but sometimes subsides of its own accord.
Treatment goes in stages: general medication, specific medication, followed by the less commonly used methods.

Basic medication comprises the following:

• anticholinergics/antispasmodics to reduce the overactivity of the bladder (Ditropan, Detrusitol, Vesicare, Daricon et al)
• anti-inflammatory agents
• analgesics (painkillers)

Oral treatment includes:

• amitriptyline (Redomex ®)
• cimetidine (Tagamet ®)
• pentosanpolysulfaat (Elmiron®)

Intravesical treatment includes:

• heparin (sulfated polysaccharide)
• chondroitin sulfate 0.2 % (Uracyst®)
• hyaluronic acid (Cystistat®)
• DMSO Dimethyl sulfoxide 0.2 %
• BCG – experimental, results of studies awaited

Intravesical treatment which is now rarely used is Chlorpactin (Sodium oxychlorosene) 0.4%. A very old treatment, silver nitrate, is considered outdated but nevertheless still occasionally used.

A new treatment is Botulinum Toxin (Botox). Trials are in progress with PBS/IC patients.

TENS electrical stimulation helps the pain in some patients and can be used at home. Modified Thiele massage and other forms of pelvic floor relaxation can be tried once the pain is under control.

Hyperbaric oxygenation is similar to the type of treatment given to divers who develop the bends and comprises breathing pure oxygen in a special chamber.

Neuromodulation is an expensive form of treatment involving implantation of devices usually reserved for patients who have failed all other treatments.

Hydrodistension under anaesthesia is used for both diagnostic purposes and as a treatment. The beneficial effects are short-term.

Laser treatment is used to seal ulcerated or raw patches in the bladder. It is temporary but can be repeated.
Other surgery can be used to remove ulcers. Partial or complete removal of bladder is a last resort treatment.

Long-term prognosis

PBS/IC is a chronic disease and patients should not expect it to be cured, although in some cases it might spontaneously subside. PBS/IC is characterised by exacerbation and remission, so-called “flares”.

Impact on the patient

PBS/IC has a significant impact on the lives of patients: on their partnerships, family, friends and work. Patients need frequent treatment by their doctor and will frequently change doctor in the hope of finding a better solution.

Another question was on whether hydrodistension damaged the bladder. Professor Wyndaele said that it causes minimal cracks in the bladder wall, breaking off nerve endings. It should be emphasised that it does not work on all patients and is a temporary measure, but can be repeated.

Does catheterisation cause a risk of infection? Yes, said Professor Wyndaele. Everything introduced into the bladder increases the risk of a bacterial infection.

Responding to a question on bladder augmentation, Professor Wyndaele said that this was not advisable in PBS/IC patients. It consists of placing a piece of bowel on the lower part of the bladder. This part of the original bladder will continue to give pain.

Does the patient’s emotional state of mind have an effect on the IC? According to Jane Meijlink, there are two aspects to this: first the PBS/IC itself has an emotional impact on the patient, causes the patient stress and anxiety. PBS/IC can turn a perfectly normal person into a very stressed, emotional person. Stress can also exacerbate diseases such as PBS/IC – this can be either physical or emotional stress. Typical of PBS/IC patients is to have a flare at the beginning of a vacation because they have spent days running around making preparations, packing cases, cleaning the house and have generally become exhausted. This can trigger off an attack. Students taking examinations may also experience flares due to the build-up of stress.

A question on how to maintain a good partner relationship (sexual relationship) led to some discussion. The panel believed that the difficulties experienced are very individual because every patient has a different level of pain. It can create difficulties in a relationship because the partner does not like the patient to be in pain, while the patient feels guilty that he/she cannot be a normal sexual partner. Sex is an important and intimate aspect of most people’s lives and sexual difficulties can cause cracks to appear in a partnership. It is essential that the partner is given adequate information about the disease. Advice can be sought from sex counsellors. This is a topic that could be discussed in small regional meetings.