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Treatment of the Bladder Pain Syndrome and Interstitial Cystitis

• Interstitial cystitis: definition, causes, symptoms and diagnosis
• Interstitial cystitis: medical treatment and surgical therapy

Conservative treatment of bladder pain syndrome/interstitial cystitis

The following interventions are used to alleviate the symptoms of bladder pain syndrome. There is only limited evidence from controlled trials availability:

• Pelvic floor relaxation exercises: with biofeedback and stress reduction, warm tub baths.
• Behavioral therapy (bladder training) to increase bladder capacity: a treatment option if frequency with only minor pain is present. Some authors presented satisfactory results (halving urinary frequency, increasing the functional bladder capacity)
• Acupuncture: sometimes leads to symptomatic improvement with no change in the objective parameters.
• Dietary restrictions: avoid caffeine, alcohol, artificial sweeteners, hot spices, and beverages that might acidify the urine.

Drug therapy of the bladder pain syndrome/Interstitial Cystitis

Pentosan polysulfate (PPS):

Pentosan polysulfate (PPS) is a plant-based artificial heparinoid. Dosage 100 mg p.o. 1-1-1, PPS is excreted via the kidneys, is deposited on the GAG layer, and is supposed to reduce the permeability of the urothelium. The treatment effect should be assessed after 3–6 months of therapy. Only minor efficacy was demonstrated in randomized trials; after six months, 30% of the patients improved (Sant et al., 2003). PPS has been approved in Germany since 2017.

Postmenopausal women:

Estrogen deficiency in postmenopausal women is a risk factor for recurrent urinary tract infections and chronic bladder symptoms; estrogen replacement therapy should be offered to all postmenopausal women. Local estrogen replacement therapy (vaginal cream or vaginal estrogen implants) is more successful and less harmful than oral hormone replacement therapy. Dosage: 0,03--0,5 mg intravaginal estriol once a week.

Hydroxyzine:

Hydroxyzine is an antihistamine (H1 antagonist) with a sedative effect. The dosage is 25 mg p.o. 0-0-1 for 1 week, then the dosage is increased to the dose to 25 mg in the morning and 50 mg at night. Good results were reported in patients with evidence of allergies. However, a randomized trial could not demonstrate efficacy (Sant et al., 2003).

Amitriptyline:

Amitriptyline is a tricyclic antidepressant used to treat neuropathic pain. The dosage is 25 mg 0-0-1 gradually increasing to 75 mg 0-0-1. The efficiency is based on the anticholinergic, antihistaminic, and adrenergic effects. One-third of the patients reported a persistent improvement in symptoms. Sedation is the main side effect. Caution: cardiac toxicity is possible.

Analgesics:

Pain medication is prescribed according to the WHO analgesic ladder: non-steroidal analgesic combined, if necessary, with an opioid.

Immunosuppressants:

Good responses are reported with cyclosporine. Problematic are the severe side effects of immunosuppressive drugs; thus, they are only an option if an autoimmune disease is also present.

Antibiotics:

Antibiotics are used if a positive urine culture is present. One empirical course of antibiotics may be given at the onset of bladder symptoms. Low effectiveness has been reported for antibiotics without proven urinary tract infection.

Miscellaneous drugs:

There are numerous studies with promising results for several drugs. However, the results were never confirmed by other authors or by prospectively randomized studies:

• L-Arginine (NO donor)
• Anticholinergics (only indicated for overactive bladder)
• Misoprostol (oral prostaglandine)
• Montelukast (leukotriene antagonist)
• Prednisolone
• Nifedipine (calcium antagonist)
• Cimetidine (H2 antihistamines)

Intravesical Therapy

Hydrodistention of the Bladder:

Hydrodistention of the bladder under anesthesia is usually the first treatment attempt, as it also has diagnostic significance. The bladder is filled with water to a pressure of 80–100 cm of water over 5–8 min. A symptom improvement can be expected in only a subset of patients (20%). The mechanisms are unclear and might involve damage to the mucosal afferent nerve endings.

Intravesical Instillations for the Regeneration of the GAG Layer:

The regeneration of the GAG layer is thought to improve the increased permeability of the urothelium. Pentosan polysulfate, heparin, chondroitin sulfate, or hyaluronic acid are used for intravesical instillations individually or in combination. The instillations are usually started with weekly intervals. After treatment response, the dosing interval can be increased to monthly instillations. Therapy is costly, depending on the product. Few randomized trials have demonstrated a limited or statistically insignificant effect (Nickel et al., 2012) (Madersbacher et al., 2012).

Miscellaneous Drugs for Intravesical Therapy:

• DMSO
• Lidocaine and dexamethasone combined with iontophoresis (EMDA), optionally followed by a bladder hydrodistention without anesthesia.
• Intradetrusor injections of botulinum toxin A

Surgical Treatment Options for Interstitial Cystitis

Endourological Treatment:

Transurethral resection or coagulation of Hunner's ulcers, with a loop fulguration or laser treatment. Initial good improvement, but high relapse rate in 1–3 years. Prospective studies do not exist.

Sacral Nerve Stimulation:

Sacral nerve stimulation improves subjective and objective symptoms; so far, only small uncontrolled studies with short follow-ups are available. This also applies to the transcutaneous electrical nerve stimulation (TENS).

Open surgical treatment for Interstitial Cystitis:

Open surgery remains the last resort after unsuccessful medical or interventional treatment. Surgical therapy is a good option for patients with unbearable urinary frequency due to diminished bladder capacity (less than 250 ml under anesthesia). Surgery is less reliable in eliminating chronic pain. Even after radical cystectomy and urinary diversion, some patients are not cured of their chronic pain syndrome.

Bladder augmentation (supratrigonal cystectomy):

The trigone of the bladder is kept, and the bladder wall is reconstructed with the bowel.

Complete cystectomy:

Surgical alternative to bladder augmentation. The entire bladder is removed as a possible symptom source; the disadvantage is the need for ureter-intestinal anastomosis.

References

Hanno, P. & Dmochowski, R. Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot.
Neurourol Urodyn, 2009, 28, 274-286.

Loch, A. & Stein, U. [Interstitial cystitis. Current aspects of diagnosis and therapy].
Urologe A, 2004, 43, 1135-1146.

Oberpenning u.a. 2000 OBERPENNING, F. ; OPHOVEN, A. van ; HERWIG, R. ; PIECHOTA, H. J.: [Diagnosis of interstitial cystitis].
In: Urologe A
39 (2000), Nr. 6, S. 530–4

Sant, G. R.; Propert, K. J.; Hanno, P. M.; Burks, D.; Culkin, D.; Diokno, A. C.; Hardy, C.; Landis, J. R.; Mayer, R.; Madigan, R.; Messing, E. M.; Peters, K.; Theoharides, T. C.; Warren, J.; Wein, A. J.; Steers, W.; Kusek, J. W. & Nyberg, L. M. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis
J Urol, 2003, 170, 810-5.

Sievert u.a. 2000 SIEVERT, K. D. ; EDENFELD, K. D. ; OBERPENNING, F. ; PIECHOTA, H. J.: [Oral therapy of interstitial cystitis].
In: Urologe A
39 (2000), Nr. 6, S. 535–8

  Deutsche Version: Interstitielle Zystitis