A general thorough medical history should be taken with emphasis paid to:
- previous pelvic operations
- previous urinary tract infections
- bladder history/urological diseases
- location of pelvic pain (referred pain) and relation to bladder filling/emptying
- characteristics of pain: onset, correlation with other events, description of pain
- previous pelvic radiation treatment
- autoimmune diseases

A common physical examination should be performed including palpation of the lower abdomen for bladder fullness and tenderness:
- standing: kyphosis, scars, hernia
- supine: abduction/adduction of the hips, hyperaes­thetic areas

In females physical examination should include a vaginal examination with pain mapping of the vulvar region and vaginal palpation for tenderness of the bladder, urethra, levator and adductor muscles of the pelvic floor. Tenderness might be graded as mild, moderate or severe.

Pain mapping Inspection:

• vulva
  - exclusion of vulvar/vestibular diseases (vulvitis, dermatosis etc.)
  - evaluation of introital area (endometriosis)
  - tenderness of vestibular glands or vulvar skin (Touch Test: use wet cotton stick or fingertip)

• vagina
  - tenderness during insertion and opening of speculum
  - cervical pathology
  - vaginal fornices (endometriosis)

• bimanual physical examination
  - tenderness of urethra, trigone and bladder
  - superficial/deep vaginal tenderness
  - tenderness of pelvic floor muscles (levator, adductor)
  - tenderness in adnexal areas

- urine dipstick (ABS, pH, leukocytes, nitrate), urine culture in all; if sterile pyuria culture for Mycobacterium tuberculosis
- urine cytology in risk groups
- investigations for vaginal Ureaplasma and Chlamydia in females and prostatitis in men are optional

• voiding diary with volume intake and output for 3 days at initial evaluation; patient sensation at voiding might be recorded
• at follow-up only number of voidings during day and night time is necessary; morning volume might be recorded as a help to monitor highest functional capacity
• the O’Leary-Sant Symptom Score supplemented with a sex score (suitable sex score to be constructed) should be used as basic symptom score supplemented with the Quality of Life Score from the International Prostate Symptom Score
•  pain should be recorded using a Visual Analogue Scale (VAS) for pain during the last 24 hours (to match the voiding diary); separate scores for the average, mildest and worst pain should be obtained:
  - average pain during the last 24 hours: no pain intolerable pain
  - worst pain during the last 24 hours: no pain intolerable pain
  - least pain during the last 24 hours: no pain intolerable pain

Filling cystometry is helpful in overactive bladder (OAB) for diagnosing detrusor instability as IC and OAB may coexist. This might have implications for treatment. In males, bladder outlet obstruction (BOO) can be a differential diagnosis. It is therefore recommended to perform filling cystometry with a filling rate of 50 ml/s (to comply with the revised Potassium Test—see below) to look for instability, volume at first desire to void and cystometric capacity. In females, flowmetry, post void residual urine volume and pressure-flow study are optional. In males, a flowmetry should be done in all, and if maximum flow rate <20 ml/s a pressure-flow study and measure of residual urine volume should be done.

The revised Potassium Test has shown prognostic value in bladder irrigation studies, but is considered optional. If performed it should be performed according to Daha et al. (J Urol 2003;170:807-9)

Modified KCl test: comparative assessment of maximum bladder capacity
A Foley balloon catheter (14F) is inserted and the bladder drained. Instill into the bladder 500 ml saline (0.9%) at a rate of 50 ml/min via an infusion set until the maximum capacity is reached. Drain the bladder and measure the saline filling volume. Repeat the instillation and measurement with 500 ml 0.2 M potassium chloride at a rate of 50 ml/min (taking care that filling lines are emptied of all saline before KCl instillation), and calculate the filling volume difference.
A difference in bladder capacity > 30% is considered positive. Besides reduction in bladder capacity by 0.2 M KCl, there is a stronger feeling of urgency in IC patients compared to the saline filling, which is also clinically relevant.

Cystoscopy under local anaesthesia might be part of the general urological workup to exclude diagnoses other than IC.
Cystoscopy under anaesthesia, either spinal or gen­eral, is mandatory in cases with suspected IC.

Technique
A rigid cystoscope is preferred to facilitate taking of adequate biopsies. Glycine or corresponding filling fluid should be used to allow for coagulation after biopsies. Infusion height should be approximately 80 cm above the symphysis pubis. A dripping chamber is used and the bladder is filled until fluid dribbling stops. If necessary, a digital block is applied around the urethra to prevent leakage. Pre-distension inspection includes observation for radiating vessels, coagulum or fibrine deposits, white spots, hyperaemia, oedema, cracks, scars or any other mucosal changes. Continuous inspection while filling the bladder is advised.

When maximum capacity is reached, the distension is maintained for 3 minutes. The bladder is emptied and the colour of the fluid checked for the degree of bleeding. The total volume drained is the measured maximum bladder capacity.
During a second filling, the bladder is filled to approximately 1/3rd to 2/3rd of the bladder capacity to achieve optimal vision for inspection and biopsies. The bladder should not be filled to maximum capacity or distended again to avoid further provocation of changes with doubtful reproducibility.

Inspection
Describe lesions in anterior wall, posterior wall, lateral quadrants and fundus. At the fundus one should be alert for possible artefacts if there is blind introduc­tion of the scope. Bladder mapping by drawing is mandatory. Photographs are recommended but optional.

Classification
grade 0: normal mucosa
grade I: petechiae in at least two quadrants
grade II: large submucosal bleeding (ecchymosis)
grade III: diffuse global mucosal bleeding
grade IV: mucosal disruption, with or without bleeding/oedema

The highest grade is to be reported and the observations should be detailed. It is recommended to take the biopsies including muscle under good visibility and not at full bladder capacity. A minimum of three biopsies are taken plus a biopsy from an area with maximum post-distension reaction.

Biopsies
During cystoscopy the bladder is distended to full capacity. After draining the bladder, bladder biopsies are taken at roughly half-full bladder capacity: Biopsy procedures should be performed by using large forceps and include detrusor muscle; alternatively double punch biopsies or resections of lesions can be used.

Biopsy handling
Biopsies are treated conventionally according to routine procedure at the Department of Pathology. Six adjacent 3 um sections are cut and placed with 3 specimens on each of two specimen slides. The first slide is stained with H&E, the next with a connective tissue stain suitable for the individual institute. Twenty-four 10 um sections are then cut and every third section is mounted on a specimen slide for mast cell counting (see below). The specimens are stained by Leder­stain (naphtolesterase) according to routine procedures. Finally, a 3 um section is obtained to ensure the presence of detrusor muscle in the specimens.

Mast cell counting
The use of a measuring grid (Leitz periplan 6F 10N ocular containing a standardized grid) is neces­sary. Previous standardized measurements have been done on a grid containing 25 squares each square measuring 0.21 mm2. The counting of mast cells in the detrusor is preferably made in 20 squares but at least 7 squares should be counted on a magnification of 25. If less than 7 squares with detrusor are represented, the biopsy is insufficient. Only mast cells containing nucleus are included. When counting the cells, those covering or touching the bottom - and a right line - should be excluded whereas those covering the upper and left line are included. In this way a maximum of 20 squares may be encounted in the total counting i.e. 20 squares: 20 x 0.21 mm2 = 4.2 mm2 . At least 3 biopsies must be the subject of mast cell counting and if possible one including a lesional area.

The total number of mast cells per mm2 is:

the total number of mast cells
-------------------------------------------------------------------------
the number of squares included in the counting x 0.21

If biopsies for mast cell counting do not contain detrusor muscle, new biopsies must be obtained.

The pathology report

• epithelium
  - not present / present
  - dysplasia with grading
  - abnormal but no dysplasia: description is mandatory.

• propria
  - normal
  - inflammation: description with a grading
  - other findings are described

• detrusor muscle. abnormal muscle cells: describe

• intrafascicular fibrosis
  - not present / present

• mast cell count: at least three biopsies should be included in the counting; only the biopsy with the highest number of mast cells per mm2 should be reported

The enzymatic (naphtolesterase) staining is, for the time being, recommended since standardized values are available:

• < 20 mast cells/mm2 : no detrusor mastocytosis
• 20-28 mast cells/mm 2 : grey zone
• > 28 mast cells/mm 2 : detrusor mastocytosis

The use of immunohistochemical stainings (i.e. anti-tryptase) is not at the present time recommended since no reference material employing standardized cutting procedures and counting procedures exist. However, it is the aim of this study group to collect a reference/normal material for immunohistochemical staining and, when available, cutting and staining procedures will be changed accordingly.