Interstitial Cystitis (IC)/Bladder Pain Syndrome (BPS) is a chronic disease characterized by pain, urgency, and frequency. Patient having severe symptoms experiences a very miserable life. Even after so many years of research exact etiopathology has not been determined. 

There  is no cure available and the treatment  is directed  toward  control  of symptoms.  Most of the physicians believe that it is very difficult to treat IC/BPS and patients continue to suffer. Patients  present  in different  permutations  and combinations  of symptoms.  In spite of increased awareness IC/BPS patients still have to move from one physician to other  for years  before diagnosis is made.

In 2025 there is an international consensus regarding the name and definition of the disease IC/BPS. Bladder diary, urine routine examination and culture and sensitivity, ultrasonography of kidney -ureter -bladder and cystoscopy are commonly performed  investigations, but no test can diagnose IC/BPS.

Based on findings of cystoscopy patients can be divided in Hunner’s lesion (HL -IC/BPS) and non -Hunner’s lesion (NHL -IC/BPS)  depending on the presence or absence of Hunner’s lesion. Therapeutic hydrodistention and treatment of HL can be done at the time of diagnostic cystoscopy.  IC/BPS is considered as heterogenous disease so here is an attempt to identify different phenotypes of IC/BPS in order to treat individual patient in best possible way.

A policy  of staged  treatment is adopted  where  various  treatment  modalities  are applied  to the patient  one after other, starting with less invasive and progressing to more invasive. 

Lifestyle  changes,  biofeedback  physical  therapy  and diet also play a part in management of IC/BPS.

Orally amitriptyline, hydroxyzine hydrochloride, pentosan polysulfate sodium (PPS), gabapentin, etc., a represcribed. PPS has a black box warning from United States Food and Drug Administration (USFDA) for the development of retinal maculopathy and patients should be cautioned about it. Dimethylsulfoxide (DMSO), intravesical cocktail, and intravesical tacrolimus are used after failure of oral therapy. Oral cyclosporine A, intravesical Botox injection, neuromodulation, and reconstructive surgery are reserved for nonresponsive patients. The results of surgery are good but should be used as last resort because of surgical morbidity  and there  is a fear of persistence  of symptoms  in few patients.  International consensus guidelines, biomarker for diagnosis and effective  oral treatment are the most important unmet needs of IC/ BPS and efforts should be made  to achieve that in near future. 

Treatment:

Introduction

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a  neglected debilitating chronic, inflammatory disorder of the  urinary  bladder characterized  by variable  degree  of bladder  pain,  frequency,  and urinary  urgency. There  are still many  physicians  worldwide  who do not believe  in existence  of this disease. There is a consensus all over the world that IC/BPS  is difficult  to diagnose  and treat.  The worst  scenario  is that there  are no diagnostic  symptoms, signs,  or investigations. 

In last 35 years all the over the world, particularly  in USA,  in spite of spending unlimited money and effort, there is no clear direction toward pathology and treatment even at distance.  But these efforts have helped in increasing the awareness about the disease.  It is a unique disease with no clue to etiology, its pathology is unknown, and no specific treatment exists to affect a cure.

History

In early 19th century this disease was defined as a painful bladder inflammatory disease producing the symptoms same as bladder stone. However, the term interstitial cystitis was mentioned for the first time in 1886.

 In 1918 Guy Hunner described the term elusive ulcer of the bladder which was later named as Hunner’s ulcer. Cystoscopes in 1918 had primitive design and limited vision. Now it is realized that what he said as ulcer are not true ulcers but red lesion.

In 1951, JP Bourque from Canada used the term “painful bladder”—sometimes also referred to as “painful bladder disease”—not as a synonym for IC, but as an umbrella term for all disorders causing pain in the bladder. For the first time in 1978 one full chapter was devoted to interstitial cystitis in Campbell’s Urology, 4th edition and for the first time word glomerulations was coined for dot-like bleedings.

In 1987, Magnus Fall et al., described two types of IC as ulcerative and nonulcerative with different clinical picture. In the same year the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) formed a consensus definition of IC which was later revised in 1988. The aim of drawing these guidelines was to have an international standard to compare patients of different geographical areas. Unfortunately, these NIDDK guidelines were very rigid and diagnosed only 40% patients of IC/BPS.

 In 2002 International Continence Society used the term painful bladder syndrome. European Society for the Study of Interstitial Cystitis (ESSIC) was founded in Copenhagen in 2004. ESSIC changed the name to bladder pain syndrome in 2006 to meet the taxonomy criteria.

In 2009 hypersensitive bladder syndrome was the term used in Japanese guidelines as there is no word like pain in Japanese language.

 In 2010 ESSIC changed the name to the International Society for the Study of Bladder Pain syndrome but decided to continue to use the acronym ESSIC.

American Urological Association (AUA) for the first time framed the guidelines for interstitial cystitis in 2011 used the term IC/BPS.

 It is to be noted that all the terms IC, BPS/ IC, BPS, and HBS are used for the same syndrome. AUA guidelines were amended in 2014 and 2022.

2017 Bone, Reproductive, and Urological Drugs Advisory Committee (BRUDAC) criteria for IC/BPS were framed by USFDA.

The 2022 European Association of Urology (EAU) guidelines for chronic pelvic pain added the word “primary” to BPS, making it primary bladder pain syndrome (PBPS).

In 2024 we can write that though there is no consensus internationally on the name, IC/BPS is used by a good majority of physicians.

Symptoms of Interstitial Cystitis/Bladder Pain Syndrome [IC/BPS]

Triad of pelvic discomfort urinary urgency and frequency is most common presentation of IC/BPS. Pain is most important cause of pelvic discomfort but patients also complain of unusual pressure sensation, burning, throbbing or, piercing or childbirth like pain. Urinary discomfort is related to micturition meaning increases with bladder filling and decreases on voiding. In severe cases pelvic discomfort is continuous.

It is felt in the suprapubic, retropubic, infrapubic, urethral, genital, rectal region, and/or deep pelvic area. Most of the patients pass urine >8 times in a day. Once the patient gets desire to pass urine, they cannot postpone it because of increasing discomfort. Patient has urgency but not urge incontinence. This is an important point to differentiate IC/BPS from overactive bladder (OAB).

In IC/ BPS patients has severe urinary discomfort but urine does not leak. In IC/BPS patient’s urgency is fear of pain but in OAB there is fear of leak. To start with patient may have only one symptom initially but develop fully fledged syndrome over next 4–5 years. Some of the patients find it difficult to perceive the organ of origin of pain, i.e., bladder and they simply mention that is comes from pelvis depicts the common symptoms with which the patients presented in our series. Total number of patients included here is 92.

In a very severe presentation patient prefers to stay home and not travel. When there is need to travel, they prefer to move by train and not by road as toilets are available in train. There is no quality of life for the patients of severe IC/BPS.

Unusual Symptoms

Interstitial cystitis/bladder pain syndrome is basically a disease of sensation. In spite of little urine in the bladder patients feel that bladder is full and they cannot evacuate it totally. In severe cases patients sit in the toilet for hours as they feel that bladder is full and there is continuous urge to pass urine.

Patients may present with unusual obstructive symptoms such as thin stream, incomplete evacuation, dribbling, obstruction and straining, and desire to pass urine immediately after micturition. This is why sometimes presentation is like urethral stricture.

Even with minimal urine in the bladder patients feel they have full bladder. Irritative symptoms are hall mark of IC/BPS but it should be realized that around 50% of patients present with unusual obstructive and sensory symptoms.

Unusual Non Urinary Symptoms of Interstitial Cystitis/Painful Bladder Syndrome 

Patients complain of anal discomfort, vulvar and penile glans pruritis and burning, dyspareunia, painful ejaculation, and difficulty in walking and sitting. In both male and female some patients complain of flare up after intercourse. Increased tone of pelvic muscles or inability to relax pelvic muscles may be responsible for some of these symptoms.

Investigations:

Frequency Volume Chart

• Very useful investigation 
• Patients are instructed to make a chart mentioning the time and amount of urine passed each time. 
• IC/BPS patients void small amounts of urine frequently. 
• The average urinary volume per void is around 50 mL.
•  A 3-day log preferred. 

This type of log is especially useful when there is suspicious of IC/BPS but patients do not have frequency.

Urine Routine and Culture

• Urine culture may not be done if urine routine and microscopic test is totally normal.
•  If any suspicious of infection, then urine culture is a mandatory investigation.
•  In patients with IC/BPS urine culture does not show any growth.
• If culture positive diagnosis of urinary tract infection is made and treated with adequate antibiotics.
• Consider IC/BPS if patient does not improve with adequate treatment and symptoms persist.

Role of expanded qualitative urine culture (EQUC), urinary polymerase chain reaction (PCR), and next generation sequencing (NSG) is not clear and not recommended in clinical use. Both of these EQUC and NGS provide a plethora of information.

However, the clinical applicability of these data is unclear as the presence of a microbe does not render it causative of symptoms or necessarily indicate pathogenicity. Further research will throw light on use of these new technologies in clinical use.

Ultrasound of Kindney Ureter and Bladder with Postvoid with Residual

Upper tract normal, normal bladder wall and no or minimal postvoid residue.

Some patients will have small capacity bladder as they are not able to hold more urine.

In patients with small capacity bladder with normal bladder wall thickness and normal upper tracts IC/BPS should be first differential diagnosis.

Tuberculous small capacity thimble bladder has thick bladder wall with upper tract changes. This point is very important in differentiating tuberculosis from IC/BPS.

Cystoscopy

Cystoscopy is important investigation and has a diagnostic, management, and prognostic role. It should always be done under general or spinal anesthesia. Office cystoscopy under local anesthesia has minimal role and should be discouraged as it is painful. I do not believe that Hunner’s lesion can be diagnosed by performing flexible cystoscopy under local anesthesia as mentioned in BRUDAC criteria. 

Spinal anesthesia is preferred as it keeps the pelvis muscles relaxed for 60–90 minutes keeping patient comfortable after the procedure while in general anesthesia post procedure after waking up patient feels severe pelvic pain and desire to pass urine and cannot tolerate Foley’s urethral catheter. Post procedure the catheter is removed as soon as patient starts moving legs.

Advantage of Cystoscopy

To rule out any other disease as cause of symptoms, e.g., bladder carcinoma, carcinoma in situ, tuberculosis, and uroepithelial dysplasia.

To biopsy any suspicious lesion present before the bladder is distended. There is no need to biopsy red petechial hemorrhage and ecchymosis that develop as the bladder is distended or after bladder is evacuated.

To measure capacity of bladder. If bladder capacity is 701 mL have good prognosis and We do not distend the bladder >800 mL for fear of rupture. Foley catheter is retained in all the cases.

Important Points about Cystoscopy

Patients with normal capacity under anesthesia can also have IC/BPS. Figure 5 shows distribution of IC/BPS patients as per cystoscopy capacity under anesthesia. Around 10% of patients will have small capacity bladder.

Bladder mucosa can be normal in around 20% cases of IC/BPS Prevailing concept that normal bladder on cystoscopy rules out IC/BPS is wrong. In my series 17% of patients had normal bladder mucosa and 17% patients had grade 4 lesion HL.

There are no pathognomic changes on bladder biopsy to diagnose IC/BPS. Bladder biopsy can be absolutely normal in IC/BPS. The belief that a normal bladder biopsy rules out IC/BPS is false. Cold cup biopsy will mostly show changes of inflammation.

Staged Treatment Policy

The problem with IC/BPS is its uncertainty in treatment response. There is no way to know which patient will respond to which treatment. Multiple treatment options are available. We follow staged treatment policy in all our patients for last 30 years and all the patients are subjected to same protocol. Protocol is modified depending on advances in our understanding of the disease, the response of the patient and the availability of the therapeutic agent.

Though AUA Guideline 2011 recommended managing patients based on 1–6 lines of treatment starting from simple therapy and moving toward more invasive one, but the recent amendment to the guidelines (2022) has not mentioned any lines of treatment recommendation. The protocol developed and followed at our center from last 30 years is represented.

All the patients are advised about lifestyle and diet modifications and stress management at the first consultation and it is followed throughout the treatment duration. We do not have specialist available for biofeedback and special physical therapy so do not recommend it to the patients.

We do not follow AUA guidelines as only 6 out of 26 guideline statements are evidence based and others are either option, clinical principle or expert opinion. There is evidence for what not to do rather than what to do. This is because there is very less evidence available for management of IC/BPS in literature.

Staged Therapy Protocol 

Stage 1: Cystoscopy hydrodistension with oral therapy

Stage 2: Intravesical therapy

Stage 3: Reconstructive surgery

Staged Interstitial Cystitis/Bladder Pain Syndrome in Children

The diagnosis of IC in children is controversial. About 25% of IC patients report that they had chronic urinary tract problems in childhood. Children do indeed present with dysfunctional voiding. There is no theoretical reason why IC cannot exist in children and should be suspected in a child who presents with irritative symptoms and pelvic pain and has no definite diagnosis and has not responded to symptomatic treatment.

The presentation and treatment of IC/BPS in children is similar to Adults PPS, amitriptyline, hydroxyzine, and gabapentin are options for oral therapy. Dose has to be adjusted for pediatric patient intravesical options are anesthetic cocktail or DMSO in reduced doses.

 I am an adult urologist and have seen only four patients who would fit in the pediatric IC/BPS presentation in my 35 years of practice. I believe that most of these patients are managed as dysfunctional voiding by pediatricians.

A separate condition of extraordinary urinary frequency has been reported in children. This condition is described as abnormally increased diurnal frequency in a completely toilet-trained child with normal urinalysis. Onset is sudden and there is complete resolution in few months. I have seen one patient like this.

What Not To Do while Managing IC/BPS Patients

• Long term oral antibiotics
• Systemic (oral) long-term steroid administration 
• Intravesical BCG
• Long duration high pressure hydrodistention (>10 minutes)
• Repeat HD under anesthesia at short interval like 1– 3 months 
• Hydrodilatation by raising the height of reservoir at the time of cystoscopy under anesthesia
•  Oral steroids 
• Painful procedure such as potassium test, office cystoscopy, and urodynamics

     (The first four are also mentioned in AUA guidelines on IC/BPS.)

Conclusion

In 2024 there is consensus regarding name of disease and definition of IC/BPS. Etiopathology is elusive and no standard management protocol is defined yet. We have positive results in treating IC/BPS in long run. Introduction of intravesical tacrolimus and good results of surgery has given us confidence in managing IC/BPS patients. Immediate future need is to unlock etiopathology and prepare a simple and effective management algorithm.

There is unmet need to develop drugs for curing IC/BPS. I hope that scientist all over the world will work harder to give IC/BPS patients very good quality of life.

The author [Dr. Nagendra Nath Mishra, Sr. Consultant Urologist] has more than 35 years of experience in diagnosing, managing and treating IC/BPS across the world.

 Note: For more details, please go through the below attached document.

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