Identifying and managing interstitial cystitis

Clinical case scenario

Lucinda, a cisgender 44-year-old, arranges a GP consultation due to continued abdominal pain and increased frequency of voiding.

Over the past 6 weeks Lucinda has requested two telephone GP appointments where she reported abdominal pain, dysuria, and increased frequency of voiding. She has subsequently been treated with two courses of antibiotics (nitrofurantoin and trimethoprim). Urine dips and culture were negative.

Lucinda consults her GP for a third time and reports ongoing discomfort prior to voiding urine. Voiding relieves her symptoms. She has a medical history of irritable bowel syndrome, denies urinary incontinence and is not currently at risk of pregnancy or sexually transmitted infections.

Abdominal examination reveals tenderness in the suprapubic region; internal pelvic examination elicits generalised discomfort with no significant findings. As the urine dipstick was normal again, she was encouraged to drink more fluids, recommended over-the-counter pain relief and advised to re-attend in 1 week if her pain did not improved. Lucinda’s pain improved, but after 3 months had returned to the same level of severity. The GP referred Lucinda to the Urology Department for investigations and review.

The urology consultant concluded that her symptoms and history were consistent with interstitial cystitis. Lucinda asks what this is and what will happen …

Background and definitions

Interstitial cystitis (IC) is a urological condition known additionally as painful bladder syndrome (PBS) or bladder pain syndrome (BPS). The variety of names used for the condition reflects its disputed aetiology.

The World Health Organisation (WHO) International Classification of Diseases 11 (WHO, 2019) distinguishes IC, as a disease of the genitourinary tract, from BPS, which is classified as a chronic primary visceral pain condition. Conversely, the European Society for the Study of Interstitial Cystitis (ESSIC) argues that the diagnoses are mutually interchangeable and that multiple names may hinder patients seeking health-related benefits (Van de Merwe et al., 2008). In this review, we use the combined term interstitial cystitis/bladder pain syndrome (IC/BPS), as agreed by ESSIC (Van de Merwe et al., 2008).

IC/BPS encompasses a spectrum of urological presentations (Clemens, 2021), most typically chronic bladder pain and painful urinary symptoms that improve on voiding. A variety of symptoms are reported including increased urinary frequency and nocturia. However, IC/BPS is a diagnosis of exclusion after organic causes have been ruled out. Despite lacking a definitive cause, IC/BPS results in significant distress to patients and has resource implications for general practice and the NHS.

Epidemiology

The true prevalence of IC/BPS is difficult to ascertain, although different national studies place prevalence between 1 and 7% (Berry et al., 2011; Homma et al., 2020; Suskind et al., 2013). The best UK data (albeit poor quality) from broad population surveys suggests an estimated UK prevalence of 400 000 (The Urology Foundation, 2021).

IC/BPS is most commonly associated with female sex and age over 40 years. It is believed that women are 5:1 more affected than men (Berry et al., 2011). It is also co-prevalent with other common chronic diseases including endometriosis, rheumatoid arthritis, irritable bowel syndrome (IBS) and fibromyalgia (Clemens, 2021).

The burden of IC/BPS has been shown to worsen quality of life for patients. These patients tend to seek and use healthcare resources more often and report their work productivity and general activity to be diminished (Hakimi et al., 2017).

Pathophysiology

The exact pathophysiology of IC/BPS is poorly understood, with various aetiologies being described in the literature. Parsons (2007) proposed the mechanism of the breakdown of the urothelial lining, due to changes of the insoluble glycosaminoglycan layer on epithelial cells, which normally acts as a barrier to urological toxins. Birder (2019) reviews additional proposed aetiologies including: changes across central and peripheral neurological signalling pathways, changes in visceral pain receptor sensitivity, and localised autoimmune-mediated inflammatory reactions.

Symptoms

Clinical assessment in general practice

Like other chronic pain conditions, patients who are eventually diagnosed with IC/BPS may present with longstanding urinary complaints to healthcare professionals. Patients may understandably express frustration with repetitive unsuccessful therapy or failure to receive an accurate diagnosis (Clemens, 2021). Good communication skills are the key to managing chronic pain conditions, and taking time to listen to the patient’s symptoms and their own thoughts about causation are linked to better management outcomes (Tirlapur et al., 2016).

Clinical suspicion of a diagnosis of IC/BPS should generally arise in a patient with multiple attendances with chronic urological symptoms. It may be further raised where previous treatment has been tried without success, such as repeat prescriptions of antibiotics for urinary tract infections (UTIs), or where further investigation has been inconclusive.

Symptom evaluation can be formally assessed with the validated O’Leary Sant questionnaire specific for IC/BPS (outlined in Box 1). This may help to accurately document symptoms and provide a severity score which can be used to guide treatment (Lubeck et al., 2001). Box 1.

The questions and numerical scoring systems of the O’Leary–Sant questionnaire. Repeated survey of patients may identify if therapeutic interventions are successful.

Symptoms:

During the past month, how often have you felt the strong need to urinate with little or no warning? (0–5)

During the past month, have you had to urinate less than 2 hours after you finished urinating? (0–5)

During the past month, how often did you most typically get up at night to urinate? (0–6)

During the past month, have you experienced pain or burning in your bladder? (0–5)

Problems:

During the past month, how much has each of the following been a problem for you?

1. Frequent urination during the day? (0–4)

2. Getting up at night to urinate? (0–4)

3. Need to urinate with little warning? (0–4)

4. Burning, pain, discomfort, or pressure in your bladder? (0–4)

Differential diagnosis

Since IC/BPS is a diagnosis of exclusion, differential diagnoses should be considered through a systems approach during the history (outlined in Table 1; Van de Merwe et al., 2008). Considering the broad symptom overlap between IC/BPS and other genitourinary conditions, patients will likely have already been investigated or referred for these investigations. However, in patients who present with new symptoms, it is important to solely consider IC/BPS once the appropriate investigations have ruled out conditions listed in Table 1.

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Table 1.

Key differential diagnoses when suspecting IC/BPS. A structured systems approach may help GPs to cover the variety of possible alternatives.

Urological	Gynaecological	Other
Carcinoma	Carcinoma	Iatrogenic
UTIUrolithiasisBladder • Bladder neck obstruction • Neurogenic obstruction • Urinary retention • Overactive bladderProstate • Benign/malignant obstruction • Prostatitis	• Cervical • Uterine • OvarianSTIUrethral diverticulumUrogenital prolapseEndometriosisVaginal candidiasis	• Chemotherapy • Radiotherapy • Biological therapy • Anti-inflammatory • Recreational Drugs e.g. ketaminePudendal nerve entrapmentPelvic floor muscle-related painIBS

Adapted from ESSIC guidelines (Van de Merwe et al., 2007).

It is important to exclude malignancy (Table 1). Urological malignancy with red flag features include: unexplained haematuria, systemic features such as loss of weight or appetite, or unprovoked deep vein thrombosis. In men, other presentations that may require investigating include penile symptoms; new onset LUTs or erectile dysfunction.

Gynaecological malignancy also needs consideration. In addition to the systemic features of malignancy described above, female patients reporting symptoms such as dysmenorrhoea or vaginal bleeding (particularly intermenstrual or post-coital) require the necessary appropriate investigation to rule this out.

Chronic pelvic pain syndrome and, in men, chronic prostatitis are further differentials to consider. Patients suffering from chronic pelvic pain syndrome do not experience relief on bladder emptying, which assists with narrowing the differential. Validated tools such as UPOINT and INPUT may be used to classify these patients with chronic pain and to guide management approaches (Crane et al., 2018).

Genitourinary infections, including UTIs, sexually transmitted infections (STIs) and pelvic inflammatory disease (PID), may also present with pain. Accompanying infective symptoms include bloody or purulent genital discharge, systemic features of infection or a history of risk factors for immuno-compromise. If necessary, patients should be referred via the appropriate local pathways to their local sexual health clinic. Iatrogenic causes of abdominal pain are also important to rule out, the most common being oncological therapy (Table 1).

Examination

Examination findings for IC/BPS are typically non-specific. Patients may present with a varying degree of tenderness on abdominal examination, with some authors describing characteristic band-like hip girdle pain (Clemens, 2021).

Pelvic examination including speculum and bimanual examination may be helpful for completion to rule out vulval/vaginal/cervical pathology, such as dermatoses, malignancy and PID. Digital rectal examination in male patients should distinguish prostatic causes of abdominal pain. Typically carried out by secondary care specialists, urethral and pelvic floor examination can identify urethral tenderness in patients with IC/BPS.

Investigations

These should follow clinical suspicion of the other pathologies identified in Table 1. Mid-stream urine analysis is important to exclude UTIs and renal tract stones. Specialists may request urine cytology to exclude malignancy (Clemens, 2021). STI testing may also be warranted. A pelvic ultrasound scan can help exclude common pelvic, ureteric and gynaecological pathologies (Colemeadow et al., 2020).

Patients should be advised to keep a bladder diary and food diary to identify triggering features and this will be useful information for later specialist review. Patients with IC/BPS typically void small volumes, so a bladder diary may be useful to quantify the daytime and nocturnal voiding frequency and to assess functional bladder capacity through the voided volumes (Tirlapur et al., 2016). A bladder scan may be useful if increased urinary frequency is thought to be related to storage problems.

Referrals

If red flag symptoms are present, a 2-week-wait referral should be submitted to the appropriate service. GPs should consider urology referrals via the regular local pathway if a patient’s symptoms reoccur or are not adequately controlled in primary care after 3-6 months. Patients may be counselled about the possibility of further investigation. Typical first line Urology Clinic investigations include uroflowmetry and cystoscopy, which is particularly useful in excluding urological pathology and identifying Hunner lesions if present (Colemeadow et al., 2020).

Clinical case scenario (continued)

At the urology clinic Lucinda was given the diagnosis of IC/BPS, cystoscopy showed no Hunner lesions, she is still awaiting biopsy results and was advised that she will need to see her GP if the pain worsens in the future. She was given information leaflets on IC/BPS and informed about online support groups. Lucinda is still struggling.

Management options

Patients often undergo multiple secondary care reviews before a diagnosis of IC/BPS is made. Management of patients is usually instigated by urology following investigations to exclude other causes, with GPs providing regular review and ongoing collaboration if patients require repeat specialty input. There is a role for a multi-disciplinary team in providing non-pharmaceutical therapy which may help, including physiotherapists, pain teams and clinical psychologists (Tirlapur et al., 2016).

At the initial diagnosis, patients should be counselled on the possibility of frequent flares that will require managing, and the advice that almost half of all patients with IC/BPS experience long term resolution with conservative treatment. It is also useful to signpost to patient support groups (Colemeadow et al., 2020; Tirlapur et al., 2016).

There is no overall consensus regarding the single best therapy, although establishing each patient’s ESSIC phenotypes can be used to tailor approaches (Colemeadow et al., 2020; Van de Merwe et al., 2008). All patients should be advised of conservative measures including diets of exclusion, stress management, psychosocial self-care, lifestyle modification advice, and pelvic floor exercises. Female patients should be advised that pregnancy can have a variable effect on their symptoms (Tirlapur et al., 2016).

First line pharmacological treatments vary across the literature and guidelines. Pain symptoms should be managed with simple analgesia, preferably non-steroidal anti-inflammatories, with anti-muscarinics additionally useful for bladder pain symptoms (Tirlapur et al., 2016). The Royal College of Obstetricians and Gynaecologists (RCOG)/Urology Joint Green Top guideline on BPS (alone) recommends amitriptyline, although cimetidine and pentosan polysulfate sodium have also been used to some effect (Tirlapur et al., 2016). The use of these medications for IC/BPS is off-label, and thus, in practice requires specialist urology input for prescribing and follow up.

Second line therapies are managed by Urology and include intravesical therapies (including injection of lidocaine, botulinum toxin A, heparin, hyaluronic acid), cystoscopic fulguration (cautery of areas of inflammation of the bladder lining typically used in resistant UTIs) and laser treatment and neuromodulation (Colemeadow et al., 2020). Last line treatments include oral cyclosporin A and surgery, typically urinary diversion and/or cystectomy.

Conclusion

IC/BPS is varied in presentation, often overlooked and leads to significant health burden. Identification should begin with a careful history and involve key investigations to rule out other serious differentials. Managing the typically unexplained gynae-urological symptoms requires patience and time, and GPs should be prepared initially to counsel patients regarding diagnostic uncertainty. A firm diagnosis of IC/BPS with speciality input and support by the GP typically helps improve patient education and outcomes, particularly important when managing a patient's chronic pain or recurrent flares. As one of the many complex chronic pain conditions, trainees should consider IC/BPS as a key differential for chronic bladder pain, a step which would be supported by its inclusion in the RCGP (2020) curriculum.

Key points