Kate H. Moore1
(1)
Department Obstetrics & Gynaecology, St George Hospital, Kogarah, New South Wales, Australia
Abstract
Unlike the other conditions considered in this text which are very common, interstitial cystitis (IC) is quite rare. This chapter is a short summary of a great deal of research and clinical studies that have been directed at this fascinating problem. Appropriate textbooks are recommended.
Unlike the other conditions considered in this text which are very common, interstitial cystitis (IC) is quite rare. This chapter is a short summary of a great deal of research and clinical studies that have been directed at this fascinating problem. Appropriate textbooks are recommended.
How to Diagnose It
IC is a chronic pain syndrome characterized by the following:
· Recurrent episodes of suprapubic pain/pelvic pain. Pain is worse when the bladder is full. The symptom of urgency is actually painful (in 92 % of cases).
· Severe frequency (can void 60 times per day or more).
· Generally, severe nocturia (ten times per night or more, in 51 % of cases).
· Leakage of urine is not typical (but can occur).
Less common symptoms include the following:
· Chronic pelvic pain or pressure symptoms (64–69 %)
· Dysuria (61 %)
· Dyspareunia (55 %)
· Pain for days after sexual intercourse (37 %)
· Hematuria (22 %)
· IC is more common in women (ratio 9:1).
Large studies indicate prevalence of about 18 per 100,000 women Ho et al. [3]. The annual estimated incidence is 2.6 per 100,000 total US population. The average IC patient sees three or four urologists or gynecologists before diagnosis.
The diagnosis of IC is based on:
The classic symptoms of pain with frequency/urgency/nocturia. The Frequency Volume Chart (FVC) shows severe frequency/ nocturia. FVC usually shows small volumes/small bladder capacity. Urodynamic testing is painful and just shows small bladder capacity (although in some cases detrusor contractions are seen). Voiding function is usually normal (flow rate and residual urine). Urine cultures are generally sterile (by definition must be sterile for 3 months). Cystoscopy must be performed under general anesthesia (GA).
· Mucosa often fairly normal during first fill.
· Capacity under GA is reduced, for example, 400–600 ml.
· Refill exam must be performed: shows petechial hemorrhages and small punctate red dots scattered over the mucosa.
· In severe cases, may see Hunner’s ulcers—red splits or cracks in the mucosa.
Bladder biopsy is recommended. Biopsy needs special stains for mast cells (see Fig. 12.1). It often but not always reveals excess mast cells in the detrusor muscle.
Figure 12.1
Mast cells in the detrusor muscle from a biopsy taken from patient with classic features of IC
Etiology
The etiology of IC remains unknown, although several theories have been put forward.
The Defective Epithelial Barrier Theory: The bladder mucosa is lined by a chemical layer of glycosaminoglycans (GAGs) which are thought to render the urothelium impermeable to harmful solutes (such as urea). Early histological studies suggested that the urothelium of IC patients was more readily penetrated, but later functional radioisotope studies showed no significant differences between IC patients and controls.
The Detrusor Mastocytosis Theory: Because mast cells release histamine, which causes pain, hyperemia, and fibrosis, an excess of mast cells in the detrusor muscle could explain the pathophysiology of IC. An early study of 115 IC patients suggested that a finding of >28 mast cells per mm [2] in the detrusor muscle (on biopsy) indicated “true” IC and a lower mast cell count indicated early disease. Although this basic concept is still probably true, high mast cell counts can be seen in patients with prostate cancer, so the finding is not pathognomonic. Later studies showed that high mast cell counts in the lamina propria are also a marker of “classic IC.” For review, see Theoharides et al. [6].
The Autoimmune Theory: Several studies have shown that patients with severe IC are more likely to have antinuclear antibodies. Thus, IC has been likened to scleroderma (fibrosis) but the data are inconsistent. Coexistence of IC with Sjogren’s disease, rheumatoid arthritis, SLE, and Hashimoto’s thyroiditis has been reported in large prevalence studies.
In the United States, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which is part of the National Institutes of Health (NIH), has a major interest in funding research into IC. The NIDDK has established a national database of patients with IC, to study the long-term natural history of the disease. So far as we know at present, IC tends to wax and wane over time, but is not “curable.”
Treatment
Cystodistension is often performed as part of the initial cystoscopy. Up to 60 % of patients obtain benefit for 3–6 months. At cystodistension, Hunner’s ulcers/mucosal splitting areas should be diathermied.
Dimethyl sulfoxide (DMSO) installation is usually first-line therapy and is the only intravesical treatment approved by the FDA in the United States. After catheterization, a 50 ml solution of DMSO is instilled into the bladder; the patient is encouraged to retain it for 15–30 min. Weekly or biweekly treatments are given for 6–12 weeks. Response is usually noted after 3–4 weeks. An initial worsening of symptoms for 1–2 weeks may occur. A garlic-like taste and skin odor are often noted for up to 3 days. Marked reduction in pain and frequency occur in 50–90 % of patients; relapse occurs in about 40 %, but repeat treatment is usually effective. The drug is cheap and has no major side effects.
Amitriptyline, 25–75 mg daily, is useful in patients who can tolerate its sedative effects, with major benefit in 70–80 % in such cases.
Pentosan polysulfate sodium (Elmiron) is an expensive oral drug, 100 mg TDS, for at least six months. Clinical improvement may not start until after 2–4 months, so therapy is recommended for 6 months. In open trials, up to 80 % of patients note 80 % reduction in pain. In placebo-controlled RCTs, the drug has about double the effect of placebo (32 % vs. 16 % objective benefit; see Giannantoni [2] and Mahmoud [5] for review).
Transcutaneous nerve stimulation (TENS) has been used successfully to inhibit the perception of suprapubic pain. The electrodes are placed suprapubically; the stimulus is 10 Hz, in keeping with other chronic pain therapy (see Chap. 7 for methodology).
Oxalate-free diet has been used with some success. Patients avoid acidic foods such as tomatoes, strawberries, chilies, citrus fruits, tea, coffee, vinegar, and alcohol. A further modification of this diet involves avoiding foods high in tyrosine, tyramine, tryptophan, aspartate, and phenylalanine. Several studies show substantial benefit Friedlander [1].
Surgical resection of Hunner’s ulcers by endoscopic resectoscope was originally practiced, but other treatments have superseded this because of the risk of postoperative scarring, fibrosis, and reduction of bladder capacity.
Clam cystoplasty, as described for refractory detrusor overactivity (Chap. 7), is a useful procedure to enlarge bladder capacity and reduce pain but has major morbidity.
Continent diversion can be used in end-stage disease (for review, see Hohenfellner et al. [4]).
The NIDDK operates a useful Web site for patient information; a very good leaflet can be downloaded: http://www.niddk. nih.gov/health/urolog/pubs/cystitis/cystitis.htm. In the United States, an IC patient support group is run, with a useful newsletter that is available worldwide; details are at www.ichelp.org.
References
1.
Friedlander JI, Shorter B, Moldwin RM. Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions. BJU Int. 2012;11. doi:10.111/j.1464-410x.2011.10860.x [Epub ahead of print].
2.
Giannantoni A, Bini V, Dmochowski R, et al. Contemporary management of the painful bladder: a systematic review. Eur Urol. 2012;61:29–53 [Epub 2011 Sep 9].PubMedCrossRef
3.
Ho N, Koziol JA, Parsons CL. Epidemiology of interstitial cystitis. In: Sant GR, editor. Interstitial cystitis. Philadelphia: Lippincott-Raven; 1997. p. 9–16. Chapter 2.
4.
Hohenfellner M, Linn J, Hampel C, Thuroff JW. Surgical treatment of interstitial cystitis. In: Sant GR, editor. Interstitial cystitis. Philadelphia: Lippincott-Raven; 1997. p. 223–33. Chapter 28.
5.
Mahmoud MS. Bladder pain syndrome/interstitial cystitis: a reappraisal for the clinician. J Reprod Med. 2011;56:405–9.PubMed
6.
Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a seeker of human and experimental evidence. Urology. 2001;57:47–55.PubMedCrossRef