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PubMed2000

Recruitment, distribution and phenotypes of mast cells in interstitial cystitis.

PURPOSE: Interstitial cystitis (IC) is a chronic disabling condition of unknown etiology. One of its major characteristics is an increase in mast cells (MC) showing signs of activation. It has been suggested that the proteinase content defines two MC types: MC(TC), containing chymase and tryptase, and MC(T), which contains tryptase but lacks chymase. Here, we investigated the MC distribution and the MC proteinase expression in IC together with the tissue expression of the major MC growth factors, stem cell factor (SCF) and interleukin-6 (IL-6). MATERIALS AND METHODS: MC were enumerated in bladder specimens from patients with classic IC, nonulcer IC and controls. MC were visualized in terms of metachromasia, reflecting glycosaminoglycan content, and immunohistochemically, visualizing tryptase, chymase and IL-6 as well as the surface markers CD117 and SCF. RESULTS: Classic IC displayed a 6 to 10-fold increase of MC identified by proteinase content while in nonulcer IC there were twice as many MC as in controls. In contrast to nonulcer IC and controls, classic IC displayed an abundance of epithelial MC. Fewer CD117+ than proteinase+ MC were detected in IC but not in controls. Classic IC coexpressed SCF and IL-6 in the epithelium and displayed numerous SCF and IL-6+ cells in the mucosa and detrusor muscle, many of which were MC. CONCLUSIONS: Redistribution of MC into the epithelium and a high bladder wall MC density distinguish classic IC from nonulcer IC. Our findings suggest an SCF/IL-6-driven MC response in IC. They also indicate a downregulation of the SCF receptor in IC.

Aged↗
PubMed1986

[Autoimmune aspects of a case of chronic interstitial cystitis].

Chronic interstitial cystitis is a disease characterized by clinical recurring cystitis with histopathological aspects of a chronic aspecific inflammation of the bladder. Etiopathogenesis is still unknown, even if autoimmunity has been hypothesized in some cases. In this paper we report an immunopathologic and immunohistochemical study on a case of chronic interstitial cystitis. The inappropriate immunologic behaviour of the lymphocyte populations, the inhibition of leukocytes migration with bladder extracts and the immunofluorescent findings of IgG and C3 deposits in the mucosa support the hypothesis of an autoimmune pathogenesis of the disease.

Adult↗
PubMed2005

Interstitial cystitis in the UK: results of a questionnaire survey of members of the Interstitial Cystitis Support Group.

PURPOSE: To examine the site, severity, and duration, of symptoms in patients with interstitial cystitis. To examine the treatments offered. MATERIALS AND METHODS: Postal questionnaire administered to members of the Interstitial Cystitis Support Group, based in the United Kingdom. RESULTS: 736 of 1148 (64%) questionnaires were returned. 696 (94.6%) patients were women. 471 patients (64%) described daily pain when symptoms were at their worst, and 273 (37%) described daily pain at the time of survey. Most patients reported frequency, urgency and nocturia. A wide range of treatments had been offered, but drugs of proven efficacy were offered to less than a third of patients: cimetidine (36%); antihistamines (5%); pentosan polysulphate (12%); DMSO (33%); and anticonvulsants (2%). 495 patients (67%) reported "considerable impact" or more on their lifestyle and 346 (46%) reported moderate depression or worse. 364 (49%) reported at least considerable difficulties with sexual intercourse. CONCLUSIONS: This survey supports the work of others about the nature of symptoms and their impact upon quality of life. The data highlight the continuing difficulty in making a prompt diagnosis. We recommend that a European survey or registry of interstitial cystitis patients would help to establish a minimum standard of care. A suggested treatment algorithm is provided.

Anticonvulsants↗
PubMed1996

Tiaprofenic acid: an uncommon cause of cystitis often misdiagnosed as interstitial cystitis.

OBJECTIVE: To bring to the attention of Urologists that the medication tiaprofenic acid (Surgam, Albert-tiafen), a non-steroidal anti-inflammatory drug has been found to cause chemical cystitis. METHODS: Patients presenting between November 1994 and November 1995 with a confirmed or presumed diagnosis of interstitial cystitis and who were taking tiaprofenic acid are reported. RESULTS: Thirty-six patients presented with a confirmed or presumed diagnosis of interstitial cystitis. One woman without irritative symptoms presented with an abnormal ultrasound finding of a thickened bladder. Eight of these 37 patients were diagnosed with chemical cystitis from tiaprofenic acid. These eight patients (one man and seven women) with ages ranging between 46 and 79 (mean 67 years), were taking tiaprofenic acid from 22 to 84 months (mean 41.8 months), for the treatment of osteoarthritis. All eight patients had findings of inflammation at cystoscopy. Symptoms resolved from two to eight weeks (mean 5.3 weeks) in six out of the eight patients (one patient was asymptomatic and one is awaiting resolution two weeks after discontinuation), and persistence of bladder inflammation (as seen on cystoscopy) lingered greater than three months in two patients and five months one patient, after the medication was stopped. CONCLUSION: Symptoms of frequency, nocturia and suprapubic pain are associated with long term ingestion of tiaprofenic acid. Simple discontinuation of the drug will relieve symptoms usually within six weeks. The mechanism of inflammation is unknown.

Journal Article↗
PubMed2001

Clinical highlights of the National Institute of Diabetes and Digestive and Kidney Diseases/Interstitial Cystitis Association scientific conference on interstitial cystitis.

In October 2000, the National Institute of Diabetes and Digestive and Kidney Diseases and the Interstitial Cystitis Association held a joint meeting in Minneapolis, Minnesota. Clinical highlights from this meeting are reviewed. The general state of interstitial cystitis from the vantage point of the clinician is discussed, as well as epidemiologic advances, new concepts in markers for interstitial cystitis, and new treatment strategies. Although there are no breakthroughs in finding a cure for this disorder, potential major changes in methods of diagnosis and new forms of therapy are in the offing.

Cystitis, Interstitial↗
PubMed1994

Relationships between bladder inflammation and other clinical features in interstitial cystitis.

OBJECTIVES: Interstitial cystitis (IC) has been considered possibly to represent more than one disease process. If so, patients would be expected to form distinct subgroups. The degree of mononuclear inflammation on bladder biopsy can be objectively quantified and might be a useful parameter for subgroup division. The hypothesis of this study was that patients with mild versus severe inflammation would differ with regard to other clinical features of IC. METHODS: Sixteen patients who met the original National Institute of Diabetes, Digestive and Kidney Diseases criteria for IC underwent cystoscopy with bladder distention and biopsy. The degree of mononuclear inflammation on bladder biopsy was classified as mild, with less than 100 mononuclear cells/high power field (HPF), or severe (100 or more mononuclear cells/HPF or lymphoid aggregates). Associations were sought between degree of inflammation and other subjective and objective clinical features. RESULTS: Five patients had severe inflammation and 11 had mild inflammation. The major finding was that the patients with severe inflammation experienced better symptom relief after cystoscopy with bladder distention under anesthesia. This difference was highly significant (Fisher's exact test, p = 0.0014). For the other clinical features studied, these two groups did not differ significantly. CONCLUSIONS: Two distinct IC patient groups were identified by bladder biopsy findings. These two groups had significantly different treatment responses. If this difference is confirmed with a larger number of patients, it would suggest that these two patient groups may have different underlying disease processes.

Adult↗
PubMed1985

Subcutaneous heparin in the treatment of interstitial cystitis.

Chronic interstitial cystitis (IC) is an inflammatory condition of the bladder of unknown aetiology. Clinically, IC is difficult to handle. Previously, we reported that administration of subcutaneous heparin has an immediate, ameliorating effect. We have now followed eight of the patients for one year or more, during which period they received subcutaneous heparin in doses varying from 5000 IU per day to 5000 IU 2-3 times a week. This treatment was found to have a long-term beneficial effect. No side effects were observed.

Adult↗
PubMedDate not supplied

Increased expression of intercellular adhesion molecule 1 in relation to mast cells in the bladder of interstitial cystitis patients.

Interstitial cystitis (IC) is a sterile, painful bladder disorder, often associated with inflammation. A defective urothelium and activated mast cells have been implicated in the pathophysiology of IC. Mast cells have been reported to induce the expression of intercellular adhesion molecules (ICAM) that are considered a necessary first step for the initiation of inflammation. We investigated the presence of ICAM-1 and its association with bladder mast cells in IC patients and controls in order to further understand their role in the pathophysiology of IC. Bladder tissue was fresh frozen and 7m section were cut using a cryostat. Immunocytochemical detection was carried out with monoclonal antibodies directed against anti-ICAM1 and tryptase. Twenty-one biopsies from women with IC and two from normal tissue from radical cystectomies (control) were analyzed. All IC samples were strongly positive for ICAM-1, exclusively in capillaries. Control samples were only faintly positive in fewer capillaries. Numerous mast cells were identified in the positive regions with toluidine blue or tryptase immunocytochemistry. This work may help explain why many IC patients develop sterile inflammation. It may also provide evidence further explaining the role of bladder mast cells in the pathophysiology of IC.

Journal Article↗
PubMed1992

Stimulated release of urine histamine in interstitial cystitis.

The diagnosis of interstitial cystitis is primarily made based on clinical and cystoscopic findings with exclusion of other bladder diseases. Despite all of the efforts at definitive identification, interstitial cystitis lacks universal objective findings. Mast cell activation with associated histamine release has been postulated as an etiological factor leading to the symptom complex associated with interstitial cystitis. To investigate this hypothesis, a 3-step controlled prospective study was conducted. In step 1 reliability of urine histamine assay was critically examined, and the assay was established to be simple, reliable and valid. In step 2 random spot urine histamine levels (basal state) were measured in 25 noninterstitial cystitis and 15 interstitial cystitis patients (22.1 +/- 0.95 ng./ml. versus 19.2 +/- 1.19 ng./ml.). There was no significant difference in the random urine histamine levels between the 2 groups (p greater than 0.05). In step 3 urine histamine levels were measured before and after hydrodistention (acute stimulation) in 7 noninterstitial cystitis controls and 6 newly diagnosed interstitial cystitis patients under general anesthesia. The urine histamine-to-creatinine ratio was used to correct for the dilutional effect of normal saline used during hydrodistention. The urine histamine-to-creatinine ratios of the control group showed no significant difference before and after hydrodistention. However, the difference in the urine histamine-to-creatinine ratios of the interstitial cystitis group compared to the controls before and after hydrodistention was highly significant (p less than 0.001). Although measurement of random spot urine histamine alone (basal state) was not found useful to make the diagnosis of interstitial cystitis, measurement of urine histamine before and immediately after hydrodistention (acute stimulation) may become an important objective parameter to assist in the diagnosis of interstitial cystitis.

Adult↗
PubMed1996

Interstitial cystitis in men.

Interstitial cystitis is an uncommon disease reported predominantly in females. Recently we were involved in the management of 4 men who had the clinical, endoscopic and pathological features consistent with the diagnosis of interstitial cystitis. The rarity of occurrence of the disease in males prompted us to report these cases.

Cystitis, Interstitial↗
PubMed2000

Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis.

PURPOSE: The etiology of interstitial cystitis is unknown. Urine from patients with interstitial cystitis has been shown to inhibit urothelial proliferation through a putative antiproliferative factor and to contain decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) compared to controls. Stretch of detrusor smooth muscle cells is known to stimulate HB-EGF production. Because bladder hydrodistention sometimes alleviates the symptoms of interstitial cystitis, we determined whether the stretch stimulus of hydrodistention alters antiproliferative factor activity and/or HB-EGF in interstitial cystitis urine specimens. MATERIALS AND METHODS: Urine was collected immediately before, and 2 to 4 hours and 2 weeks after hydrodistention from 15 patients with symptoms and cystoscopic findings compatible with interstitial cystitis and 13 controls. Hydrodistention was performed with the subject under general or regional anesthesia and bladders were distended to 80 cm. water 3 times. Urinary HB-EGF was measured by enzyme-linked immunosorbent assay and urinary antiproliferative factor activity was determined by measuring 3H-thymidine uptake by normal human bladder urothelial cells. RESULTS: Hydrodistention significantly increased urinary HB-EGF in patients with interstitial cystitis toward normal control values (before distention p = 0.003, 2 weeks after distention p = 0.67). Urine antiproliferative factor activity decreased significantly after hydrodistention in patients with interstitial cystitis. However, antiproliferative factor activity in interstitial cystitis and control specimens was still statistically different 2 weeks after distention (before distention p = 0.0000004, 2 weeks after distention p = 0.04). CONCLUSIONS: Bladder stretch increased HB-EGF and conversely reduced antiproliferative factor activity in urine from patients with interstitial cystitis but not controls up to 2 weeks after distention. These results provide additional evidence for the possible role of antiproliferative factor and decreased HB-EGF in the pathophysiology of interstitial cystitis. To our knowledge this is also the first human study to show that in vivo bladder stretch can alter urinary factors that regulate cell growth.

Cystitis, Interstitial↗
PubMed2003

Recent developments in the management of interstitial cystitis.

PURPOSE OF REVIEW: Interstitial cystitis, a great enigma of urology today, is a chronic sterile inflammatory disease of the bladder of unknown etiology characterized by urinary frequency, urgency, nocturia and suprapubic pain. Although there are plenty of theories, the etiology of the condition remains obscure. This review focuses on recently published literature on interstitial cystitis. RECENT FINDINGS: Several pathophysiological mechanisms have been proposed in the past few years including epithelial dysfunction, activation of mast cells, neurogenic inflammation, autoimmunity and occult infection. Evidence indicates that it is a heterogeneous syndrome and that the two subtypes, classic and nonulcer disease, represent different entities. The diagnosis is made by clinical and cystoscopic evaluation with hydrodistension and often with biopsy when other disorders are excluded. The National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases has developed criteria for clinical studies. There is a need for a noninvasive marker of interstitial cystitis. Antiproliferative factor as a urinary marker has shown promising results. The value of the bladder permeability test in interstitial cystitis needs further investigation. Many gynecologic conditions mimic the symptoms of interstitial cystitis. Multiple forms of therapy are available including self-care and dietary changes, medical and intravesical treatments, neuromodulation, multimodality treatment and surgical intervention. It is recommended that the most conservative treatments are used first and surgery should be regarded as the last resort. SUMMARY: Interstitial cystitis is a challenging disease of urology today. While causative factors remain unknown, treatment is based on empiricism. Intensive research may result in new and hopefully more effective treatments in the future.

Biomarkers↗
PubMed1987

A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease.

Painful bladder disease, sensory bladder disease, chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis, and, therefore, they are without any rational therapy. Pathogenetic theories concerning defects in the epithelium and/or mucous surface coat (including glycosaminoglycans) of the bladder, and theories concerning immunological disturbances predominate. Sodium pentosanpolysulfate (Elmiron) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes. We compared sodium pentosanpolysulfate versus placebo in a prospective double-blind, clinically controlled multicenter trial of 115 patients with painful bladder disease. Two protocols were used. Protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2), and protocol B included 72 patients with a painful bladder and unspecific histological findings. The patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months. Before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies. The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found. We conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease.

Adult↗
PubMed1993

Sjögren's syndrome in patients with interstitial cystitis.

OBJECTIVE: Patients with interstitial cystitis, a chronic nonbacterial inflammation of the bladder, were investigated for the presence of systemic autoimmune diseases, in particular for Sjögren's syndrome (SS). METHODS: Ten patients were included in the study on the basis of a diagnosis of interstitial cystitis according to usual criteria. They underwent clinical and laboratory investigations including those for keratoconjunctivitis (KCS) and focal lymphocytic sialoadenitis (FLS). RESULTS: In 2 patients both KCS and FLS were present allowing the diagnosis of primary SS according to classification criteria. Additionally, in 6 patients one of the 2 hallmarks of primary SS was present, KCS in 3 and FLS in 3. CONCLUSION: Interstitial cystitis is a new example of a disease that occurs in association with SS, supporting the concept that interstitial cystitis is an autoimmune cystitis. The clinical relevance of the finding is that a high index of suspicion for SS is indicated in patients with interstitial cystitis.

Adult↗