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Obscure diagnosis – painful bladder syndrome

bladder pains consultation 3x2

Case history

Mrs M is a 36-year-old lady and mother of a 15-year-old. She was suffering from severe bladder irritation symptoms for seven months before she attended the urogynaecology clinic. She had excruciating pain each time she emptied her bladder and felt as if her ‘bladder was on fire.’ She also had increased frequency – up to 25 times a day – and nocturia.

She had five courses of antibiotics from her GP on suspicion of a UTI and all culture sensitivity tests of her urine were negative. She had no other medical problems and took no medications. She used to drink socially, smoked 20 cigarettes a day and drank four to five caffeinated drinks.

On examination, she had mild tenderness over her suprapubic region. Gynaecological examination was normal, as was pelvic ultrasound. A differential diagnosis of PBS was made.

A cystoscopy and bladder biopsy was organised. During cystoscopy, the bladder mucosa looked normal and the bladder biopsy was normal. A diagnosis of PBS was confirmed. We discussed the diagnosis and pathophysiology of PBS with the patient, and the role of bladder irritants. We recommended lifestyle modification to reduce smoking, caffeine, alcohol intake, and bladder training.

Other treatment options, such as medical and intravesical therapy, were discussed, but she was encouraged to try lifestyle modifications first. Three months later, having made the lifestyle changes, her bladder symptoms had completely gone.

Painful bladder syndrome (PBS), or interstitial cystitis, is a condition of chronic pelvic pain associated with irritative voiding symptoms.

Management of PBS has been an ongoing challenge for physicians, owing to a lack of consensus on its definition, incomplete understanding of its pathophysiology, and lack of reliable evidence for its treatment.

Better understanding of the pathophysiology of PBS and the management principles will enable you to initiate management in the community, reducing the number of referrals and waiting time.

A large number of these patients can improve by simple lifestyle measures.



The International Incontinence Society diagnosis of PBS is based on suprapubic pain related to bladder filling, day- or night-time frequency, and the absence of other obvious pathology. The term interstitial cystitis should be reserved for those affected by PBS who also have specific cystoscopic findings.1,2



PBS has a female to male ratio of 10:1. The mean age of those affected is in the 40s, although rare cases have been reported in children. Prevalence varies widely across the world, from one to four per 100,000 in Japan to 18 per 100,000 in Finland.1,3


Clinical features


Patients typically present with a constellation of bladder, urethral or pelvic pain associated with urgency or frequency and, less commonly, nocturia or dysuria.

The similarity between PBS and overactive bladder syndrome has led some experts to believe these conditions lie on the same disease spectrum.

The principal differentiation is the persistent pain of PBS, where pain starts with the filling of the bladder. Patients may also present with associated conditions, including allergy, IBS, vulvodynia, systemic lupus erythematosus, endometriosis, fibromyalgia and depression.1,4,5


Examination findings will vary. Some patients may not have obvious findings, but most have suprapubic tenderness.


Basic investigations include urine analysis and a culture and sensitivity to rule out UTI. Ultrasound scans of the pelvis, kidneys, ureter and bladder will be useful to rule out a pelvic or renal mass. Investigation by the specialist team will include cystoscopy to rule out bladder pathology and confirm the diagnosis of PBS, especially if there is haematuria.

Differential diagnosis

Differential diagnosis will include all causes of pelvic pain, such as recurrent UTI, endometriosis, pelvic congestion syndrome, fibroid uterus, vulvodynia, vaginal or vulval infection, uterovesical prolapse, bladder-neck obstruction, vaginal atrophy, fibromyalgia, IBS and psychosomatic disorders. Cancer is rare in these cases, especially in the absence of haematuria.


The exact pathogenesis of PBS is not understood but it is likely to be multifactorial.6 One of the numerous theories is that the factors most likely to play a significant role include infection, autoimmune inflammation, mast cell activation, bladder epithelial permeability, neurogenic inflammation and antiproliferative factor. One hypothesis is that an initial bladder injury leads to epithelial damage, resulting in leakage of potassium into the interstitium, which triggers mast cell activation and leads to further bladder damage and neuropathic pain.

How can GPs diagnose with certainty?

Patients will report chronic pelvic pain and irritable bladder symptoms. Once chronic UTI is ruled out by microscopy and bacteriology, there are few causes of chronic pelvic pain that have the irritable bladder component as well.



Many management options for PBS exist – non-pharmacological, oral, intravesical and hydrodistension – but the best approach has yet to be determined.

Management should start with lifestyle measures, which include:

• Diet and behaviour modification.

• Bladder training exercises.

• Management of comorbidities.

• Patient support and empowerment.

Dietary regimens typically restrict caffeine, alcohol, citrus, carbonated beverages and acidic foods, which are all believed to trigger histamine release and thereby exacerbate symptoms. Behavioural adaptations emphasise controlled fluid intake, abstention from exacerbating activities, stress reduction through exercise and breathing and relaxation techniques, and bladder training.

Bladder training aims to decrease frequency of voiding and is best for those with mild to moderate pain.1,7


Pharmacological therapy

The most commonly used oral agents are amitriptyline and hydroxyzine. There has been evidence to suggest symptom improvement with oral agents. The trial of the oral agent should be three to six months. If the response is adequate, therapy should be continued and reviewed in six to 12 months.1,7,8


This procedure is performed under anaesthesia and consists of filling the bladder with water or saline until 70mmHg pressure is reached. Dilatation is maintained for up to half an hour, and then the fluid is released. It is suggested that this aggressive ‘stretching’ disrupts the sensory nerves in the bladder wall, resulting in pain relief. Only small observational studies of hydrodistension as a treatment are available, with one showing that 9% undergoing the treatment were good responders (symptom relief lasted for more than three years without further treatment) and 58% were moderate responders (relief maintained for three to 12 months). Hydrodistension appears to be a viable treatment, but the risk of anaesthesia and the variable duration of relief should be discussed.9

Intravesical therapy

Dimethyl sulfoxide – an anti-inflammatory analgesic with muscle-relaxing and mast-cell inhibiting properties – is the only FDA-approved intravesical agent. Intravesical BCG – the tuberculosis vaccine that is believed to work immunologically – has been shown to benefit some cases. There is no robust evidence to support the success of intravesical therapy.1,10,11

When to refer

Early referral should be considered in the presence of haematuria, any palpable abdominal mass or persistent symptoms in spite of conservative management. An ultrasound scan before referral is useful, as this will facilitate early management. Referral to hospitals with urogynaecology facilities will be beneficial as units with this capacity can arrange specialised investigation.

Key points


• PBS is a combination of chronic pelvic pain and irritative voiding symptoms


• Basic investigations include urinalysis, MSU and pelvic and renal-tract ultrasound

• Cancer is rare with these symptoms, especially in the absence of haematuria


• Conservative measures include diet and bladder training exercises

• Pharmacological options include amitriptyline and hydroxyzine


Miss Sayanti Ghosh is an ST7 in obstetrics and gynaecology, and Mr Fabian Imoh-Ita is a consultant urogynaecologist, both based at West Middlesex University Hospital, London.



1 Lau TC, Bengtson JM. Management strategies for Painful Bladder Syndrome. Rev Obstet Gynecol 2010;3:42–8

2 Warren JW, Meyer WA, Greenberg P et al. Using the International Continence Society’s definition of painful bladder syndrome. Urology 2006;67:1138–42

3 Alagiri M, Chottiner S, Ratner V et al. Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes. Urology 1997;49(suppl 5A):52–7

4 Chung MK, Chung RP, Gordon D. Interstitial cystitis and endometriosis in patients with chronic pelvic pain: The “Evil Twins’ syndrome. JSLS 2005;9:25-9

5 Curhan GC, Speizer FE, Hunter DJ et al. Epidemiology of interstitial cystitis: a population based study. J Urol 1999;161:549–52

6 Hanno PM. Painful bladder syndrome/interstitial cystitis and related disorders. In: Wein AJ, editor. Campbell-Walsh Urology. 9th ed. St Louis: Elsevier Health Sciences; 2006.

7 Parsons CL, Koprowski PF. Interstitial cystitis: successful management by increasing urinary voiding intervals. Urology 1991;37:207-12

8 Dimitrakov J, Kroenke K, Steers WD et al. Pharmacologic management of painful bladder syndrome/interstitial cystitis: a systematic review. Arch Intern Med 2007;167:1922-9

9 Yamada T, Murayama T, Andoh M. Adjuvant hydrodistension under epidural anaesthesia for interstitial cystitis. Int J Urol 2003;10:463-8

10 Dawson TE, Jamison J. Intra-vesical treatments for painful bladder syndrome/interstitial cystitis. Cochrane Database Syst Rev, 2007;4:CD006113

11 Perez-Marrero R, Emerson LE, Feltis JT. A controlled study of dimethyl sulfoxide in interstitial cystitis. J Urol 1988;140:36-


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