Diagnosis and prevalence of IC/BPS: double difficulty

Despite many efforts taken to find any marker, so far nothing has been discovered that can be inarguably associated with IC/BPS.¹ There are no alterations either that would refer to IC/BPS, without doubt, so using the most known imaging methods in themselves do not provide a precise diagnosis. The image of the healthy bladder and the disrupted one may be identical. On the other hand, the insufficiency of the GAG-layer can refer to other diseases, too. Excluding malignant processes and infections is necessary, but even the presence of any other condition cannot rule out IC/BPS. Therefore, IC/BPS can sometimes only be diagnosed after the successful treatment of the easily identifiable, coincident condition.

The Typical Symptoms of IC/BPS

The usual symptoms of IC/BPS can be divided into two major groups.²

Pain

Not only the urethra and the bladder can be affected, but also the lower abdomen, the pelvic or perineal area (moreover, in women the vagina, in men the scrotum and the penis)
Its intensity may correlate with the filling of the bladder, whereas voiding may temporarily reduce it
Assuming the urethra is affected, sexual intercourse may be painful
Its level varies from mild discomfort to severe, excruciating pain
In the beginning, the sparse and short painful periods are separated with long, symptomless intervals. As IC/BPS progresses, pain becomes permanent, and it can occur without any correlation to voiding
Even during long lasting symptom-free, stable condition, patients may experience flare-ups from time to time.

Voiding

In the beginning, the frequency is slightly higher than normal. In severe cases 60–80 urination a day is possible, too
Sudden urgency may occur, followed by spasms and pain
In mild cases, the abnormal frequency of voiding shows up only in daytime. With progression nocturia develops, the need for voiding can occur several times at night.
The voided volume (the urine portion) is very small and correlates to the amount of liquid consumed.
In severe cases, the need for voiding persists after urinating too.

The presence of these symptoms varies by patients and is affected by several factors. Namely, consuming certain foods and drinks, the amount of physical and/or mental stress, digestive disorders, urinary infections (UTIs) and (in women) their menstrual cycle (the symptoms are usually worse after ovulation).

Diagnosing IC/BPS – Then and Now

Most urologists define a condition as IC/BPS if the characteristic symptoms persist for a certain period (1.5–6 months) given that every disease of similar symptoms can be excluded. Filling out questionnaires can identify the presence of symptoms; the O’Leary-Sant Symptom Index is one of the most frequently used ones.³ However, because no lab tests or any other kind of examination can unequivocally confirm IC/BPS, the condition can never be diagnosed with a 100% certainty. Fortunately, not only are there a handful of supplemental examinations that can be used for refining the diagnosis, but also the medical practice has improved significantly in this field in recent years.

The most important tool for diagnosing IC/BPS used to be the Potassium Sensitivity Test (aka. Parsons-test or PST). This confirmed the insufficiency of the GAG-layer by the pain generated by potassium-chloride instilled into the bladder.⁴ (In case of a healthy GAG-layer there is no significant pain observed). This tool, however, was not only unnecessarily invasive but unpleasant, too, given that the patients had severe pain due to the solution itself. The Parsons-test did not provide information for a quantitative analysis either. In a later version of this sensitivity test (modified Parsons test) the bladder was filled with diluted potassium-chloride solution to determine its maximum capacity, and then the same process was repeated with physiological salt solution. The proportion of the two values referred to the sensitivity of the bladder wall for the concentration of the urine. Although the modified Parsons test could be used for quantitative measurements as well, it was just as invasive, time-consuming, and its accuracy was not higher than that of the original version. Due to these issues, neither tests are recommended in the recent guidelines.^5,6

The lidocaine test works oppositely. This substance is to moderate bladder pain, so given that the source of the pain is the bladder itself, the instilled lidocaine lessen the symptoms in case of IC/BPS.^[7] This tool is definitely more comfortable than the potassium sensitivity test, but it is just as invasive and does not enable quantitative analyses either.

A new diagnostic tool is the GAG-layer Integrity Test, which uses a two days' voiding diary, and it is non-invasive and painless too. This test is based on the fact that for observing the correlation between the urine concentration and the bladder capacity, nothing need be instilled; the solution of dissolved salts is already present – in the form of urine itself. The concentration of urine substances – salts included – depends on the amount of consumed liquid. The volume of each voiding can be measured for a day on which the patient consumes the least liquid they can, then the same thing can be done on the second day on which the patient consumes as much liquid as they can. In case of a healthy bladder wall, there is no correlation between the mean voided volumes and the liquid intake. In the early phase of IC/BPS, the higher liquid consumption results in 30–50% higher urine portions. As the disease progresses, the difference increases to 50–100%; in severe cases, it can be 300–500%. Therefore, not only does the 2-day Voiding Diary indicate the damaged bladder wall, but also it describes the amount of damage, numerically. Thus, the GAG-layer Integrity Test enables quantitative analysis, too.

The correlation between the mean of the daytime urine portion and the total amount of daytime urine, in case of healthy people and IC/BPS patients.

There are certain diseases which occur significantly more likely together with IC/BPS; their presence may support the diagnosis. This group consists of allergic symptoms, migraine, irritable bowel syndrome, endometriosis, vulvodynia, chronic fatigue syndrome, Sjögren-syndrome, panic disorder, and many more conditions.^[8]

Low-pressure cystoscopy is recommended if there is blood in the urine, or urine cytology refers to the chance of a malignant process (or there is an unambiguously positive result), or the patient's condition becomes worse despite the combined therapy they get, to examine whether bladder cancer or another disease of similar symptoms are present. The biopsy of the bladder mucosa is performed only if the cystoscopic image reveals areas that may refer to malignancy. If cystoscopy does not raise suspicion of malignancy, urine cytology should be performed, which is the most sensitive non-invasive method.

Recording the patient's anamnesis provide useful information, too. This should include not only the current symptoms but also the history of their earlier infections, other diseases they suffer in (mainly focusing on autoimmune diseases and digestive disorders), medicines and/or antibiotics being taken or were taken before, the patients' diet and other lifestyle characteristics and the correlation between the symptoms and any of the information described above.

How Many IC/BPS Patients are there?

The occurrence of disease can usually be described by two kinds of data. Incidence means the newly registered cases during a certain period (usually a year). Prevalence, on the other hand, means the total amount of people affected by the disease at a certain point of time. In the case of IC/BPS, which appears to be a life-long condition, the latter data is relevant.

The international estimations of prevalence are based on the presence of symptoms, filling in questionnaires, and data on patients having been diagnosed with IC/BPS. The number of people affected by IC/BPS is usually referred to as 100,000 people.

However, neither the questionnaires nor the way of their evaluation is standardized. Certain studies that used only the data gathered from doctors focusing on the diagnosed IC/BPS cases concluded a prevalence of 45–197/100,000.^[9] On the other hand, a survey in which households had been contacted by phone estimated 1,900–4,200/100,000 men and 2,750–6350/100,000 women affected by IC/BPS. A mere 10% of the latter group had been diagnosed.^[10],[11] According to another research based on self-reporting via e-mail, IC/BPS can affect 258–13,114/100,000 people, depending on the way of calculations.^[12]

In 2017 Interstitial Cystitis Association (ICA) reported that alone in the USA, there are 3–8 million women and 1–4 million men affected by IC/BPS.^[13] In recent years, this estimation seems to have been accepted by many relevant papers and organizations.^[14],[15] Considering the mean of both values, a prevalence of 2,400/100,000 appears to be a reasonable calculation.

The mean age of patients appears to be 40 years, but IC/BPS can show up at younger or older age, too.

That said, the diagnosis rate of IC/BPS is less than 5–10%, even in the countries with the most advanced healthcare. There is no other disorder of this seriousness, which has a lower diagnostic rate.