JSUR Journal

Introduction

Bladder Pain Syndrome (BPS) is an entity which Painful Bladder Syndrome (PBS) or Interstitial Cystitis (IC) fall under, and is a form of chronic pelvic pain [1]. It has been defined by the International Society of Bladder Pain Syndrome (ESSIC) as suprapubic pain accompanied by other symptoms including urinary urgency, frequency, nocturia, in the absence of any Urinary Tract Infection (UTI) or obvious pathology [2]. IC is defined similarly to PBS, though requires cystoscopic and/or histological features typical of the disease (glomerulations and Hunner’s ulcers) [3]. Its diagnostic criteria remain elusive and is often used to describe a constellation of symptoms, resulting in few consistently reliable treatment options. It is a debilitating condition leading to high rates of depression, anxiety, sleep disturbances and social life interference, impacting both physical and mental quality of life [4]. This article provides an overview of the current understanding of and management strategies for PBS. A Medline literature search was performed, and relevant clinical guidelines summarized. We make a practical set of recommendations applicable to the general practice setting.

Clinical Assessment

Diagnosis is complex and partly based on the exclusion of other diseases. Pertinent differentials must be considered and excluded prior to a diagnosis of PBS. Prostatic/gynaecological/urethral/ bladder disease, genitourinary infections, and pelvic floor disease are all considerations. Urothelial carcinoma is of particular concern, as it can often present with irritative voiding symptoms and dysfunction, with or without macroscopic haematuria. Patients with macroscopic haematuria should be referred promptly for exclusion of urothelial carcinoma [5,6].

Clinical History

A comprehensive history and examination of the urogenital system remains integral the work-up of BPS. Burden of disease on patient quality-of-life, pain history (if present) and past medical history are important. Clinical features include pelvic pain – often described as “pressure” – related to bladder filling, with common sites being suprapubic, urethral, vulval, vaginal and rectal. A history of recurrent culture-negative UTIs is often described by the patient. Irritative voiding symptoms such as urgency, frequency, urge/stress incontinence and nocturia may be associated (defined in Table 1) [7,8].

Table 1: Definition of symptoms.

Potential risk factors and triggers that may exacerbate symptoms should be explored. Validated questionnaires can aid in establishing baseline characteristics and assessment of treatment efficacy (Table 2) [7,9-12].

Table 2: Relevant history taking.

Physical Examination

Examination should be of the lower abdomen, followed by assessment of bladder fullness and suprapubic tenderness. A vaginal exam is recommended in females, with documentation of vulval, vaginal and surrounding organ pain. Digital rectal exam is recommended for males, with appropriate documentation of scrotal-anal region pain [7].

Laboratory Testing

Initial investigations consist of urinalysis and urine culture to exclude infective causes, with consideration of urine cytology if haematuria is present, or if there is a history of smoking. “Sterile pyuria” should be cultured for exclusion of tuberculosis and fastidious organisms [13]. Antiproliferative factor may be used as a biomarker for the diagnosis of PBS, though its specificity is low and is often confounded by other factors [14]. A bladder diary may prove useful in providing objective information regarding fluid volume intake, triggers (alcohol, caffeine), incontinence episodes and determination of nocturnal polyuria. Ultrasonography of the urinary tract including pre-void and post-void residuals can be considered.

Management Strategies

Management strategies are listed in Table 3. BPS management should be based on a bio-psychosocial model and should be performed in a holistic patient-centred approach, with active patient involvement. Treatment can be approached in a stepwise fashion, from conservative behavioral and lifestyle modification, to medical, to minimally invasive surgical, and finally radical surgical treatments. Expectation management in chronicity of disease and the lack of efficacy of any single treatment regimen is important on initial diagnosis [15-17]. Current guidelines and literature indicate multi-modal, tailored approaches are key in ongoing control [15-21]. Treatments should be periodically reassessed, and ineffective treatments stopped [15]. Multidisciplinary team input with urologists, gynaecologists, pain specialists and mental health practitioners may also be considered.

Table 3: Key points on management strategies.

Conservative Management

Conservative measures are a cost-effective and risk-free strategy on initial diagnosis, forming sustainable and accessible options for long-term management. Physical therapy has shown symptom improvement in over 50% of patients [19]. These strategies include [15-20]:

• Stress reduction techniques including psychotherapy, hypnotherapy
• Dietary changes to avoid food triggers (e.g. reducing caffeine, spicy foods, alcohol, citrus fruits) including elimination diets and weight loss
• Exercise regimens
• Smoking cessation
• Urinary concentration/volume alteration by fluid restriction/hydration
• Social support: early involvement and education of family members, support group education
• Physical therapy – hot/cold packs, pelvic floor muscle relaxation, trigger point myotherapy, connective tissue release, muscle coordination training, Thiele massage, acupuncture, reflexology, bladder training

Simple analgesics like nonsteroidal anti-inflammatories can ease the burden of symptoms.

Pharmacotherapy

Pharmacotherapy agents have variable success rates, and are associated with significant non-compliance or discontinuation rates due to minimal long-term efficacy [21]. However, they form the mainstay of ongoing management if conservative measures fail. Current guidelines indicate several agents with varying recommendations across multiple guidelines (Table 4) [15-20].

Table 4: Agents available in Australia with varying supporting recommendations across multiple guidelines.

Pentosan polysulfate is a mainstay oral therapeutic, being the most-studied oral medication for PBS. Effectiveness is variable. Some trials report no differences in symptom improvement, but others show improvement compared to placebo [15]. Its mechanism of action is thought to reduce urothelial permeability by reinforcing the Glycosaminoglycan (GAG) layer in urothelium, allowing restoration of the urothelial layer and reducing noxious stimulation of the sub-mucosal nerves [15-20]. Antihistamines are thought to reduce bladder symptoms by inhibiting mast cell histamine release [22]. Tricyclics may act in a similar way, however there is limited robust evidence [20]. There is emerging evidence for low-dose Cyclosporin A as a treatment option, with studies showing a greater efficacy than pentosan polysulfate in patients with Hunner’s ulcers or active bladder inflammation [15-19]. However, there are significant adverse effects associated, leaving it as a relatively last-line treatment option often requiring urological input.

Surgical

Minimally Invasive: Instillations

Multiple instillation agents can be used with varying efficacy for varying time periods, ultimately attempting to restore the architecture of the GAG layer and thus natural protection provided. They are often used in combination with each other [15-20] Table 5.

Table 5: Intravesical instillation agents.