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Adham Ahmed

on 12 June 2018

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Transcript of PBS

Clinical syndrome defined by symptoms of urgency, frequency and/or pain, in the absence of any other reasonable cause.
Clinical Manifestations
Adham M. Awad, Feisal Idrees
Amr Gaber, Mostafa Abdel-Karim,
Sameh Nassar, M. Salah

Painful Bladder Syndrome
A diagnosis of IC can be made when patients have (1) bladder pain or urinary urgency AND (2) glomerulations or Hunner's ulcer during cystoscopy/hydrodistension AND (3) none of the exclusions listed below:
Awake cystometric capacity >350 mL using a fill rate of 30-100 mL/minute
Absence of intense urge to void at 100 mL gas or 150 mL liquid
Involuntary detrusor contractions on cystometry
Urinary frequency less than 8 voids per day
Absence of nocturia
Duration of symptoms less than 9 months
Age less than 18 years
Cystitis (bacterial, chemical, post-irradiation), prostatitis, vulvitis (herpes) or vaginitis
Bladder, uterine, cervical, vaginal or urethral cancer
Cyclophosphamide or any type of chemical cystitis
Tuberculous cystitis
Radiation cystitis
Bladder or lower ureteral calculi
Urethral diverticulum
"Painful bladder syndrome is the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology.... The ICS believes this to be a preferable term to 'interstitial cystitis'. Interstitial cystitis is a specific diagnosis and requires confirmation by typical cystoscopic and histological features."
"A diagnosis of Bladder Pain Syndrome (BPS) is made of the basis of the symptom of chronic pain related to the urinary bladder accompanied by at least one other urinary symptom such as daytime and nighttime frequency, AND exclusion of confusable diseases as the cause of the symptoms, AND cystoscopy with hydrodistension and biopsy if indicated (to document the type of BPS/IC). Results of hydrodistension are denoted grades 1-3 with increasing grade of severity in appearance, and a second symbol of A,B or C indicating increasing grade of severity at biopsy findings. A symbol 'X' indicates hydrodistension or biopsy not done. For example, BPS-2C indicates a patient with BPS symptoms who demonstrated glomerulations during hydrodistension and had a positive biopsy."
Physical examination
Urine analysis
Urine culture
Cystoscopy with hydrodistention under anesthesia
Cytology (when indicated)
If necessary, imaging and urodynamic testing are conducted

The clinical evaluation should begin with a complete history and physical examination.

The diagnosis of IC/PBS is one of exclusion. There are a number of conditions that must be considered in the differential diagnosis of a patient with possible IC/PBS, including:
Urinary tract infection
Overactive bladder
Bladder carcinoma
Drug effects: cyclophosphamide, aspirin, NSAIDs, allopurinol
Urinary tract infection (UTI), endometriosis, and overactive bladder (OAB) are relatively common conditions; the other conditions listed are rare but should be considered in patients with relevant findings, such as microhematuria on cystoscopy. Note that cyclophosphamide, aspirin, NSAIDs, and allopurinol are associated with a nonbacterial cystitis that resolves when the drugs are discontinued.5 Of course, two or more of these conditions can occur concurrently.

Differential Diagnosis

detailed history of voiding symptoms,
pelvic pain or discomfort,
Frequency, urgency, and nocturia. A voiding diary can be very helpful for assessing urinary frequency.
some patients with IC/PBS do not complain of pelvic pain but, if asked, will admit to discomfort or pressure that is relieved by voiding. Also, clinicians should inquire about the timing and course of symptoms. A distinguishing characteristic of IC/PBS is progressive bladder pain or discomfort with increased bladder filling.


Urinalysis is normal, and urine culture is negative in both women.

Sandra Smith is a 38-year-old mother of two. She presents with persistent symptoms that include urinary urgency, urinary frequency, nocturia, and discomfort in the bladder area that is reduced with voiding.

Jennifer Jones is a 38-year-old mother of three. She presents with persistent symptoms that include urinary urgency, urinary frequency, and occasional urinary incontinence.

Case Study

The clinician should ask the women whether the urgency arises due to concern about impending incontinence or increasing pain and discomfort.
Jennifer Jones has urgency caused by concern about impending incontinence, which is suggestive of OAB.
Sandra Smith has urgency caused by progressive bladder pain, which is suggestive of IC/PBS.

What should the clinician ask?

O’Leary-Sant (OLS) questionnaires are useful symptom screeners for IC

During the past month …
Q1. … how often have you felt the strong need to urinate with little or no warning?
0. ____ Not at all
1. ____ Less than 1 time in 5
2. ____ Less than half the time
3. ____ About half the time
4. ____ More than half the time
5. ____ Almost always
Q2. … how often have you had to urinate less than 2 hours after you finished urinating?
0. ____ Not at all
1. ____ Less than 1 time in 5
2. ____ Less than half the time
3. ____ About half the time
4. ____ More than half the time
5. ____ Almost always
Q3. … how often did you most typically get up at night to urinate?
0. ____ None
1. ____ Once
2. ____ 2 times
3. ____ 3 times
4. ____ 4 times
5. ____ 5 times
Q4. … have you experienced pain or burning in your bladder?
0. ____ Not at all
2. ____ A few times
3. ____ Fairly often
4. ____ Usually
5. ____ Almost always
Add the numerical values of the checked entries.
Total score: _______


During the past month how much has each of the following been a problem for you:
Q1. Frequent urination during the day
0. ____ No problem
1. ____ Very small problem
2. ____ Small problem
3. ____ Medium problem
4. ____ Big problem
Q2. Getting up at night to urinate?
0. ____ No problem
1. ____ Very small problem
2. ____ Small problem
3. ____ Medium problem
4. ____ Big problem
Q3. Need to urinate with little warning?
0. ____ No problem
1. ____ Very small problem
2. ____ Small problem
3. ____ Medium problem
4. ____ Big problem
Q4. Burning, pain, discomfort, or pressure in your bladder?
0. ____ No problem
1. ____ Very small problem
2. ____ Small problem
3. ____ Medium problem
4. ____ Big problem
Add the numerical values of the checked entries.
Total score: _______

pelvic exam in women and a digital rectal exam in men. Although there are no physical findings specific to IC/PBS.
many patients with the condition have exquisite tenderness at the perineum between the anus and scrotum in men, and at the anterior vaginal wall near the urethral meatus in women.

Physical Examination

To exclude infection.

Urine analysis & Culture

The bladder is instilled with two separate intravesical solutions, one containing 40 mL of sterile water and one containing 40 mL of potassium chloride (40 mEq per 100 mL of water). After three to five minutes, patients are asked to rate their individual response to water and potassium and also to compare the two. Urgency, pain symptoms, or both are interpreted to indicate damaged urothelium.

Potassium sensitivity test


After overdistention, these patients demonstrate glomerulations that are discreet, tiny, raspberry-like lesions appearing on the dome and lateral walls of the bladder and tiny mucosal tears and submucosal hemorrhages.
Bladder biopsy findings in these patients often are unremarkable, as compared with those found in patients with classic interstitial cystitis.

Non-ulcerative type of interstitial cystitis

The hallmark of classic interstitial cystitis is a diffusely reddened appearance to the bladder surface epithelium associated with 1 or more ulcerative patches surrounded by mucosal congestion (ie, Hunner ulcer) on the dome or lateral walls of the bladder upon cystoscopic examination.
These ulcers may become apparent only after overdistention, because discrete areas of mucosal scarring rupture during the procedure. Overdistention in this type of interstitial cystitis results in fissures and cracks that bleed in the bladder epithelium.

Ulcerative type of interstitial cystitis

A biopsy helps to exclude bladder cancer. It also may confirm the presence of mast cells or inflamation of the bladder wall that are consistent with a diagnosis of PBS/IC.
Nevertheless, there is nothing on the biopsy that can make an absolute diagnosis of PBS/IC.


An exaggeration of normal sensations of urge to void and discomfort necessitating a trip to the bathroom
“It resembles a constellation of stars; its components are real enough but the pattern is in the eye of the beholder” (Makela and Heliovaara, 1991).
The Aunt Minnie description of IC

(she is hard to define, but you know her
when you see her)
“We have all met, at one time or another, patients who
suffer chronically from their bladder; and we mean the ones who
are distressed, not only periodically but constantly, having to
urinate often, at all moments of the day and of the night, and
suffering pains every time they void. We all know how these
patients are unhappy, and how those distressing bladder
symptoms get finally to influence their general state of health
physically at first, and mentally after a while” (Bourque, 1951).
All patients with PBS/IC have
, which is associated with bladder filling and/or emptying, and usually accompanied by
urinary frequency, urgency, and nocturia
. The pain that is thought to be of bladder origin is usually described as being suprapubic or urethral, although patterns such as unilateral lower abdominal pain or low back pain with bladder filling are common
Increased urinary frequency arises because the pain of bladder filling is partially or completely relieved by voiding, so patients prefer to maintain low bladder volumes. Clinically, it is useful to ask patients why they void frequently to help distinguish PBS/IC from other causes of frequency. As an example, patients with overactive bladder syndrome void frequently to avoid urinary urge incontinence, whereas in PBS/IC they void frequently to avoid discomfort.
Affected patients may also describe chronic pelvic pain that is distinct from their bladder pain, as well as other ongoing, distinct pain symptoms. These patients often carry several diagnoses, such as irritable bowel syndrome (another visceral pain syndrome), dysmenorrhea, endometriosis, vulvodynia, migraine, or fibromyalgia . They may also describe exacerbation of their PBS/IC symptoms during times when other pain symptoms are at their worst (eg, "flares" of PBS/IC when irritable bowel syndrome is symptomatic)
The character of symptoms may vary from one day to the next in a single patient. Exacerbation of PBS/IC symptoms may occur after intake of certain foods or drinks (eg, strawberries, oranges, beer, coffee), or during the luteal phase of the menstrual cycle, stressful times, or after activities such as exercise, sexual intercourse, or being seated for long periods of time (eg, a plane trip).
The majority of patients describe symptoms that are of gradual onset, with worsening of discomfort, urgency and frequency over a period of months. A smaller subset of patients describes symptoms that are severe from their onset. Symptoms of PBS/IC begin suddenly, with some patients able to name the exact date on which symptoms began. In other patients, symptoms begin after an apparently uncomplicated urinary tract infection or surgical procedure, episode of vaginitis or prostatitis, or after a trauma, such as a fall onto the coccyx.
Psychosocial support
Correction of uroepithelial abnormalities
Pentosan polysulfate sodium
Neuromodulating therapies
Somatic therapy
Physical therapy
Therapies directed at mast cells
Proponents of the theory that mast cells play a critical role in the development and/or maintenance of IC symptoms favor therapies directed at mast cells and allergic phenomena. These include:
Pentosan polysulfate sodium
PPS is the only oral medication approved by the United States Food and Drug Administration (FDA) for treatment of IC. The medication is a protein that is supposed to be filtered by the kidneys and appear in the urine so that it can reconstitute the deficient glycosaminoglycan (GAG) layer over the urothelium. In fact, only a tiny proportion of the drug is absorbed by the gastrointestinal tract and excreted in the urine.
A systematic review of randomized trials assessing pharmacologic treatments of PBS/IC found that PPS was more effective than placebo in overall improvement of patient-reported symptoms (pain, urgency, frequency)
Intravesical heparin and lidocaine
Intravesical dimethyl sulfoxide (DMSO)
Intravesical dimethyl sulfoxide (DMSO)
Its action is thought to be nonspecific, including antiinflammatory, analgesic, smooth muscle relaxing, and mast cell inhibiting effects.
Small randomized trials initially suggested benefit , but adverse effects, including pain and significant exacerbation of symptoms, limited its use.
DMSO is currently less commonly used than in the past, as other, less painful treatments have become available
Intravesical botulinum toxin
Hydrodistension is usually used as a
diagnostic aid
for PBS/IC. It has also been used as a
because some patients report prolonged relief of symptoms after the procedure, possibly due to disruption of sensory nerves within the bladder wall. However, it is usually
, and many patients experience worsening of their symptoms; thus, many clinicians feel that the risk-benefit ratio of hydrodistension therapy is not appropriate for their patients. It may be appropriate to reserve use of repetitive therapeutic hydrodistension for patients who generally obtain significant and prolonged relief. Risks of hydrodistension include bleeding (from ruptured vessels) and, rarely, rupture of the bladder wall.
Proponents of the theory that urothelial abnormalities are responsible for symptoms favor use of therapies directed at the urothelium. These include:
Proponents of the theory that PBS/IC represents a neurological hypersensitivity disorder tend to favor use of neuromodulating treatments. These include:
Electrical stimulation therapy
Proponents of the theory that bladder symptoms are caused or maintained by somatic (body wall) abnormalities favor somatic therapies.
Immunomodulatory treatments
In one trial, Cyclosporine A was superior to PPS in all clinical outcome parameters measured: micturition frequency in 24 hours was significantly reduced (-6.7 +/- 4.7 versus -2.0 +/- 5.1 times) and the clinical response rate (according to global response assessment) was significantly higher for cyclosporine than PPS (75 versus 19 percent). Adverse effects of cyclosporine A include hair growth, gingival hyperplasia, paresthesias, abdominal pain, flushing and muscle pain.
Surgical therapy
When all fails,
Diversion with or without
Substitution cystoplasty
can be considered
Implanted sacral neuromodulation
This device is FDA
approved for treatment of urinary urgency and frequency, but not specifically for treatment of PBS/IC
. The device consists of an implanted lead that lies along a sacral nerve root and is attached to an implanted pulse generator. An uncontrolled study from a single center showed that mean daytime and nighttime voiding frequencies decreased as well as average pain.

A less-expensive and noninvasive alternative to sacral nerve stimulation is percutaneous posterior tibial nerve stimulation. One study reported 44% of patients showed positive results after tibial nerve stimulation was applied twice weekly.
Behavioral therapy
Avoidance of activities associated with flares
Treatment of comorbid conditions
Referral to pain management specialists
Until recently, the antihistamine hydroxyzine was a mainstay of IC treatment. However, a randomized controlled trial found hydroxyzine had no benefit over placebo.
One small study showed that after one month of montelukast treatment, there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain. No side effects were observed during treatment. Further investigation of this modality is required.
Common sense dictates that the following components are part of all treatment programs:
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