Classic Interstitial Cystitis Research Articles

Clinical Phenotyping Does Not Differentiate Hunner Lesion Subtype of Interstitial Cystitis/Bladder Pain Syndrome: A Relook at the Role of Cystoscopy

Identifying Hunner lesions in patients with interstitial cystitis/bladder pain syndrome presents an opportunity for objective classification into Hunner lesion interstitial cystitis/bladder pain syndrome (classic interstitial cystitis) and nonHunner lesion bladder pain syndrome. While currently the former diagnosis requires cystoscopy, limited data suggest that these subtypes can be distinguished without endoscopy based on the degree of bladder focused centricity and the infrequent association with generalized pain conditions. Patients in a prospective, single center database of interstitial cystitis/bladder pain syndrome who had documented cystoscopic findings were categorized with Hunner lesion interstitial cystitis/bladder pain syndrome or nonHunner lesion bladder pain syndrome. Demographics, pain and symptom scores, voiding symptoms, irritable bowel syndrome and clinical UPOINT (urinary, psychosocial, organ specific, infection, neurological and tenderness) scoring were comparatively analyzed. We reviewed the records of 469 patients, including 359 with documented local anesthetic cystoscopic findings, 44 (12.3%) with Hunner lesion interstitial cystitis/bladder pain syndrome and 315 (87.7%) with nonHunner bladder pain syndrome. Patients with Hunner lesions were older (p = 0.004) and had greater urinary frequency (p = 0.013), more nocturia (p = 0.0004) and higher ICSI (Interstitial Cystitis Symptom Index) scores (p = 0.017). Hunner lesion prevalence was significantly lower in those younger than 50 years vs those 50 years old or older (7.8% vs 14.9%, p = 0.0095). There was no difference in the number of UPOINT phenotype domains reported, overall UPOINT scores or the prevalence of irritable bowel syndrome between the groups. A subtype of interstitial cystitis with Hunner lesions has worse bladder centric symptoms but did not show a distinct bladder centric phenotype. Given the management implications of distinguishing classic interstitial cystitis from nonHunner lesion bladder pain syndrome, we recommend cystoscopy with local anesthesia in patients diagnosed with interstitial cystitis/bladder pain syndrome.

Classic Interstitial Cystitis: Unrelated to BPS

When first recognized, more than one hundred years ago, the term interstitial cystitis (IC) was reserved for subjects with a special type of deep inflammation of the bladder wall. Later, the scope of IC widened, including all kinds of bladder pain syndromes (BPS), giving rise to a lot of confusion and difficulties in research as well as in clinical practice. Herein, recent progress in the understanding of the BPS/IC complex will be discussed, emphasizing the fact that the classic Hunner disease (BPS type 3C according to the European Society for the Study of Interstitial Cystitis (ESSIC) classification) is a well-defined condition that fulfills the requirements of the denomination interstitial cystitis. The paper will also discuss recent research on diagnostics, markers, genetics, and various types of remedies for classic IC. For the benefit of our patients, in BPS/IC, it is time for a final separation of the concepts BPS and IC. Classic IC is a well-defined entity with multiple unique characteristics, those characteristics having a potential for development of a specific rational, pharmacological, and surgical treatment algorithm if further investigated. BPS, on the other hand, seems to include a heterogenic composition of conditions calling for broad attempts to be more closely explored.

Inflammation characteristics in bladder pain syndrome ESSIC type 3C/classic interstitial cystitis

Interstitial cystitis is regarded as a heterogenous syndrome with two distinguishable forms: the non-ulcer and the classic form of interstitial cystitis, the latter with Hunner's lesions; or bladder pain syndrome type 3C and non-Hunner bladder pain syndrome, respectively. A cohort of 379 patients diagnosed with interstitial cystitis was studied. Nitric oxide release from the bladder was measured using a chemiluminescence nitric oxide analyzer. Bladder biopsies from the patients and healthy controls were analyzed by routine histopathological examination. Biopsies from a subset of patients and controls were also analyzed by immunohistochemistry and cytokine gene expression by real-time polymerase chain reaction. Patients with bladder pain syndrome type 3C/classic interstitial cystitis had considerably higher levels of nitric oxide as compared with non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients and healthy individuals, and showed histologically a chronic inflammation in the bladder mucosa, with abundant mast cell infiltration in all layers of the bladder wall. No inflammation was noted in non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients. The isoenzymes inducible nitric oxide synthase, the catalyst in the nitric oxide production, was strongly expressed in the inflammatory cells in the bladder mucosa of bladder pain syndrome type 3C/classic interstitial cystitis patients. In addition, the expression of the pro-inflammatory cytokines interleukin-6 and interleukin-17A messenger ribonucleic acid, and of anti-inflammatory interleukin-10 messenger ribonucleic acid showed significantly increased levels in bladder pain syndrome type 3C/classic interstitial cystitis compared with healthy controls. Bladder pain syndrome type 3C/classic interstitial cystitis is a distinct inflammatory disease and in many aspects shares features of inflammatory autoimmune diseases. These findings could open up novel research avenues with expectations for new targets for pharmacological treatment.

Interstitial cystitis is bladder pain syndrome with Hunner's lesion.

The contents and understanding of the term, interstitial cystitis, have undergone major changes during the past 100 years, moving from a chronic, true inflammatory bladder disorder to an extensive syndrome with lower urinary tract pain. Comments on this development are presented. From examples in the literature, some important features of classic interstitial cystitis are outlined. The more inclusive attitude of later decades has drawn desirable attention to the entire spectrum of disorders resulting in bladder pain. The wish to include all of them into one handy entity has unfortunately resulted in much scientific and clinical confusion, though. It is noted that originally interstitial cystitis represented the Hunner type of disease. Today, there is agreement that the classic type of interstitial cystitis with Hunner's lesions, bladder pain syndrome type 3C according to current terminology, stands out as a well-defined phenotype; it has to evaluated separately in clinical studies and practice, as treatment requirements differ importantly between this and other phenotypes.

Increased mRNA Expression of Genes Involved in Pronociceptive Inflammatory Reactions in Bladder Tissue of Interstitial Cystitis

We assayed mRNA expression of the TRP family of channels and ASIC1 in bladder tissue from patients with interstitial cystitis. Bladder biopsies of 1) nonclassic interstitial cystitis, 2)nonulcerative portions of classic interstitial cystitis, 3) ulcerative portions of classic interstitial cystitis and 4) noncancerous portions of bladder cancer as the control were placed immediately in ice-cold RNAlater® and subjected to real-time reverse transcriptase-polymerase chain reaction. We compared the mRNA expression of TRP channels, ASIC1, NGF, CXCL9 and UPK3A with that of controls, and correlated expression with symptom severity. We analyzed specimens from 17 patients with nonclassic interstitial cystitis, 22 with classic interstitial cystitis and 11 controls. In nonclassic interstitial cystitis samples TRPV2 and NGF showed significantly increased expression. In classic interstitial cystitis samples nonulcerative portions demonstrated asignificant increase in the expression of TRPA1, TRPM2 and 8, TRPV1 and 2, ASIC1, NGF and CXCL9, and a significant decrease in UPK3A and TRPV4. Ulcerative portions showed similar changes for TRPM2, TRPV1, 2 and 4, CXCL9 and UPK3A. Increased expression of TRPM2, first noted in interstitial cystitis tissue, was the most pronounced one of the TRP family. All symptom measures correlated with TRPM2 and TRPV2 expression, and partially with that of the other genes. This study showed increased expression of the genes involved in pronociceptive inflammatory reactions in interstitial cystitis, including TRPV1, 2and 4, ASIC1, NGF and CXCL9, and to our knowledge TRPM2 for the first time. The different expression patterns suggest distinct pathophysiologies for classic and nonclassic interstitial cystitis. The genes and their products are potential candidates for use as biomarkers or novel therapy targets.

Fulguration for Hunner Ulcers: Long-Term Clinical Outcomes

Cystoscopic fulguration of Hunner ulcers in patients with interstitial cystitis/bladder pain syndrome is a recommended therapy because it has the potential to rapidly ameliorate symptoms. We reviewed our experience with Hunner ulcer fulguration. We retrospectively reviewed the records of patients with interstitial cystitis/bladder pain syndrome treated with Hunner ulcer fulguration who were seen at our pelvic pain referral center between 1993 and 2011. Patient demographics, clinical characteristics, intraoperative findings and long-term clinical outcomes were assessed. The Kaplan-Meier product limit method was used to evaluate time to the first repeat procedure. Potential risk factors associated with repeat procedures were examined using the log rank test. A total of 106 procedures were performed in 59 patients. The mean history of illness before first fulguration was 5 years and overall median followup was 44.8 months (IQR 52.2), as calculated from the time of the first fulguration. There were no significant associations between time to the first repeat procedure and any demographic criteria analyzed, patient reported interstitial cystitis/bladder pain syndrome associated conditions or the number of Hunner ulcers fulgurated at the initial session. A total of 27 patients (45.8%) required repeat fulguration. Time to event analysis demonstrated that 12 months after the initial fulguration 13.1% of patients required repeat treatment. This rate increased to 57.2% at 48 months, when it plateaued. Fulguration of Hunner ulcers can be an effective treatment for patients with interstitial cystitis/bladder pain syndrome and focal Hunner ulcers involving less than 25% of the bladder who have symptoms refractory to other therapies. However, a significant subset requires repeat treatment and some patients may even go on to require cystectomy.

Gene Expression Analysis of Urine Sediment: Evaluation for Potential Noninvasive Markers of Interstitial Cystitis/Bladder Pain Syndrome

We determined whether gene expression profiles in urine sediment could provide noninvasive markers for interstitial cystitis/bladder pain syndrome with and/or without Hunner lesions. Fresh catheterized urine was collected and centrifuged from 5 controls, and 5 Hunner lesion-free and 5 Hunner lesion bearing patients. RNA was extracted from pelleted material and quantified by gene expression microarray using the GeneChip® Human Gene ST Array. Three biologically likely hypotheses were tested, including 1) all 3 groups are distinct from each other, 2) controls are distinct from the 2 types combined of patients with interstitial cystitis/bladder pain syndrome and 3) patients with Hunner lesion-interstitial cystitis/bladder pain syndrome are distinct from controls and patients with nonHunner-lesion interstitial cystitis/bladder pain syndrome combined. For statistical parity an unlikely fourth hypothesis was included, that is patients with nonHunner-lesion interstitial cystitis/bladder pain syndrome are distinct from controls and patients with Hunner lesion-interstitial cystitis/bladder pain syndrome combined. Analysis supported selective up-regulation of genes in the Hunner lesion interstitial cystitis/bladder pain syndrome group (hypothesis 3), which were primarily associated with inflammation. The inflammatory profile was statistically similar to that reported in a prior Hunner lesion interstitial cystitis/bladder pain syndrome bladder biopsy study. Gene expression analysis of urine sediment was feasible in this pilot study. Expression profiles failed to discriminate nonHunner-lesion interstitial cystitis/bladder pain syndrome from controls and they are unlikely to be a noninvasive marker for nonHunner-lesion interstitial cystitis/bladder pain syndrome. In contrast, patients with Hunner lesion had increased proinflammatory gene expression in urine sediment, similar to that in a prior microarray study of bladder biopsies. If these preliminary results are validated in future research, they may lead to a noninvasive biomarker for Hunner lesion-interstitial cystitis/bladder pain syndrome.

120: Nitric Oxide as a Marker for Evaluation of Treatment Efficacy of Ciclosporin in Patients with Classic Interstitial Cystitis

120: Nitric Oxide as a Marker for Evaluation of Treatment Efficacy of Ciclosporin in Patients with Classic Interstitial Cystitis

Critical appraisal of dimethyl sulfoxide treatment for interstitial cystitis discomfort, side-effects and treatment outcome

To evaluate the discomfort and long-term efficacy associated with instillation of dimethyl sulfoxide (DMSO). A total of 28 patients, 13 (11 females, 2 males) with classic interstitial cystitis (IC) and 15 (13 females, two males) with non-ulcer disease, who had received at least one series of six instillations of DMSO were studied. In addition to studying micturition diaries before and after the treatment, the evaluation included assessments of pain using a visual analog scale and of side-effects after each instillation in every series. Data were obtained by surveying the clinical records. A follow-up telephone interview was conducted for those patients who were treated with DMSO and in whom the treatment was considered successful. DMSO instillations were considered successful if the patient reported symptom amelioration and chose to continue with the treatment. Side-effects were not more common or pronounced in patients with classic compared to non-ulcer IC. For classic IC a significant difference could be seen when comparing side-effects experienced during the first three instillations and the three subsequent instillations. After DMSO instillations, a residual treatment effect lasting 16-72 months could be seen. Intravesical instillation therapy with DMSO appears to be a feasible treatment option for both subtypes of IC and is associated with a reasonably low degree of discomfort.

The prevalence of interstitial cystitis, endometriosis, adhesions, and vulvar pain in women with chronic pelvic pain

To estimate the prevalence of bladder-origin pain, intraperitoneal pathology, and vulvar pain in patients undergoing laparoscopy for chronic pelvic pain (CPP). Prospective, observational one-site (Canadian Task Force classification II-2). Referral gynecology specialty private practice. Sixty-four patients undergoing laparoscopy for CPP were prospectively assessed to establish the source of their CPP over a 12-month period. All patients received an intravesical potassium sensitivity test (PST), cystoscopy with double-fill hydrodistension, a physical examination for vulvar pain, and laparoscopy to assess the presence of peritoneal pathology. The validated pelvic pain/urgency/frequency (PUF) screening questionnaire was given to all patients to assess symptoms. Forty-four patients (69%) were found to have a positive PST indicating pain of bladder origin due to bladder epithelial dysfunction. Cystoscopic findings diagnosed only seven cases of classic interstitial cystitis (11%). Laparoscopic findings revealed biopsy-proven endometriosis in 28% and adhesions in 64%. Vulvar pain was diagnosed on examination in 20%. Assessment of intraperitoneal pathology and bladder-origin pain accurately diagnosed 95% of patients. There was no statistical difference in the prevalence of endometriosis, adhesions, or vulvar pain when groups were stratified to PST-positive or -negative groups. Bladder pain, peritoneal pathology, and vulvar pain are independent risk factors of CPP although a trend of severity was noted in patients who had worse symptoms (increased voids per day, urgency, pain, and PUF scores). Patients with increased symptoms had a higher likelihood of having pain from bladder epithelial damage and intraperitoneal pathology. The etiology of CPP may arise from multiple sites in the pelvis including the bladder, pelvic peritoneum, and vulva. This study demonstrated that in a group of women undergoing a comprehensive work-up for CPP, the bladder was the predominant pain generator. A work-up for CPP should include an assessment of bladder epithelial function and an assessment for intraperitoneal pathology.

NITRIC OXIDE AS AN OBJECTIVE MARKER FOR EVALUATION OF TREATMENT RESPONSE IN PATIENTS WITH CLASSIC INTERSTITIAL CYSTITIS

Nitric oxide (NO) has previously been shown to be a marker for inflammatory disorders in the bladder. We investigated if the measurement of NO can be used to evaluate the treatment response in classic interstitial cystitis (IC). A total of 15 patients diagnosed with classic IC were included. The patients were treated with oral prednisolone for 8 weeks. We evaluated patient symptoms/problems with the IC index, and we measured NO formation in the bladder. Seven patients were classified as responders with a 4 point or more decrease in symptom score after 8 weeks of treatment. In this group the mean symptom score was +/- SEM decreased from 15 +/- 1 to 7 +/- 2 at the end of therapy (p <0.05). The problem score was also significantly reduced. Responders showed a clear decrease in bladder NO. The 8 nonresponders did not show any improvement in symptom/problem score and there was no change in bladder NO during steroid treatment. Furthermore, the study showed a statistically significant correlation between changes in symptom/problem score and changes in luminal bladder NO in each patient. The study shows that NO can be used not only to measure inflammation in patients with IC, but also to evaluate objectively the treatment response in individuals. This makes NO formation a useful marker in the assessment of classic interstitial cystitis.

Intravesical Nitric Oxide Production Discriminates Between Classic and Nonulcer Interstitial Cystitis

Interstitial cystitis (IC) is one of the most bothersome conditions in urological practice. There are 2 subtypes, classic and nonulcer IC, with similar symptoms but different outcomes with respect to clinical course and response to treatment. Histologically there are fundamental differences between the 2 subtypes, classic IC presenting a severe abnormality of the urothelium and characteristic inflammatory cell infiltrates while inflammation is scant in nonulcer IC. Regulation of urinary nitric oxide synthase activity has been proposed to be of importance for immunological responses in IC. We present evidence of a profound difference between the 2 subtypes concerning nitric oxide production, mirroring the differences in inflammatory response in IC. A total of 17 patients with both subtypes and active disease as well as patients with disease in remission were included in the study, all diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria. Luminal nitric oxide was measured in the bladder of patients using a chemiluminescence nitric oxide analyzer. All patients with classic IC had high levels of NO. None of the other patients had any significant increase in NO levels in the bladder. The NO level in patients with classic IC was not related to symptoms but rather to the assignment to this specific subgroup of IC. The highest levels of NO were found in patients in the initial phase of classic IC. The difference in NO evaporation between classic and nonulcer IC allows for subtyping of cases meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria without performing cystoscopy. The findings in the present series together with previous findings clearly demonstrate that the 2 subtypes of IC represent separate entities. This separation further emphasizes the need to subtype all cases included in all scientific matters, ensuring that the 2 subtypes are evaluated separately in clinical studies.

Intercurrent autoimmune conditions in classic and non-ulcer interstitial cystitis.

Interstitial cystitis (IC) is known to be one of the most bothersome conditions encountered in urological practice. It is frequently divided into two subtypes: classic and non-ulcer. Several authors have reported on autoantibodies in patients with IC and clinical and histopathological findings show similarities with those in some autoimmune disorders. Furthermore, IC has been shown to be associated with autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome and autoimmune diseases of the thyroid gland. Our aim was to study the occurrence of associated autoimmune conditions in patients with IC diagnosed according to the National Institutes of Health/National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria. Our sample of IC patients consisted of 129 with classic IC and 93 with non-ulcer IC. Clinical records, including micturition charts, were surveyed, and a more in-depth interview was obtained by means of a telephone call. Autoimmune disorders, diagnosed by Swedish clinicians according to acknowledged diagnostic criteria, were registered. Allergy was the most common IC-associated condition, 41% of all patients with classic IC and 47% of all patients with non-ulcer IC having some type or degree of hypersensitivity/allergy. Rheumatoid arthritis occurred in 13% of patients with classic IC and in 4% with non-ulcer IC. Inflammatory bowel disease was not diagnosed in any of the patients with non-ulcer IC whereas 2.3% of the patients with classic IC had either ulcerative colitis or Crohn's disease, approximately 33 times the prevalence seen in the general population. It appears that systemic and autoimmune disorders are more prevalent in the IC population than in the general population.

Toward a Precise Definition of Interstitial Cystitis: Further Evidence of Differences in Classic and Nonulcer Disease

Interstitial cystitis is a bothersome condition in urological practice. There is continuous discussion on the extent and demarcation of this syndrome. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. Today it is often divided into classic and nonulcer disease. Compared with classic interstitial cystitis the nonulcer type appears different in terms of demographic, endoscopic and histological findings as well as in the response to various types of treatment. However, in clinical series subdivision is not always performed, which makes it difficult to draw conclusions. We determined whether there are additional dissimilarities in clinical presentation in the 2 subtypes of interstitial cystitis. We evaluated 130 patients with classic and 101 with nonulcer interstitial cystitis diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria by surveying the clinical records, including voiding diaries. Patients with nonulcer disease were younger at diagnosis (p <0.0001) and at symptom onset. Furthermore, there was a marked and significant difference in bladder capacity while patients were under general anesthesia (p <0.0001). The current findings together with previous findings clearly demonstrate that the 2 subtypes of interstitial cystitis represent separate entities. We suggest refining the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria, so that subtyping scientific materials is considered mandatory, hence, ensuring that the 2 subtypes are evaluated separately in clinical studies.

Mast cell involvement in interstitial cystitis: a review of human and experimental evidence

Interstitial cystitis (IC) is a heterogeneous syndrome of unknown etiology. Altered bladder glycosaminoglycans lining and bladder mastocytosis have been documented in IC. The objective of this article is to critically examine the published data on bladder mastocytosis in clinical, experimental, and animal studies, with particular emphasis on morphologic evidence of mast cell increase and activation. The literature on bladder mastocytosis and mast cell activation in IC is critically reviewed with particular reference to staining methodology, tryptase immunoreactivity, and electron microscopy. Data from humans and animal models of IC are included. Mastocytosis in IC is best documented by tryptase immunocytochemical staining. Standard surgical stains such as Giemsa and toluidine blue routinely underestimate the degree of mastocytosis. Mast cells are 6- to 8-fold higher in the detrusor compared with controls in “classic IC,” and 2- to 3-fold higher in “nonulcerative” IC. Detrusor mastocytosis occurs in both classic and nonulcer IC. Mucosal mast cell increase is present in nonulcerative IC. Mast cell activation without typical exocytosis occurs in the mucosa and submucosa. Activation of mast cells, irrespective of bladder location or degree of mastocytosis, is significant. Mast cell-derived vasoactive and proinflammatory molecules may contribute to the pathogenesis of IC.

INTRAVESICAL BACILLUS CALMETTE-GUERIN AND DIMETHYL SULFOXIDE FOR TREATMENT OF CLASSIC AND NONULCER INTERSTITIAL CYSTITIS:: A PROSPECTIVE, RANDOMIZED DOUBLE-BLIND STUDY

We conducted a prospective, double-blind study with a crossover design of intravesical bacillus Calmette-Guerin (BCG) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis, respectively, might benefit from either regimen. A total of 21 patients, including 11 with classic and 10 with nonulcer interstitial cystitis, randomly underwent treatments with intravesical BCG or dimethyl sulfoxide and, if not improved, were treated with the other substance after a washout period. All 21 patients were evaluated with symptom questionnaires, including a visual analog pain scale and voiding diaries. Regardless of regimen, there was no improvement in maximal functional capacity. There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype (p <0.05), whereas no reduction was seen following BCG in either subtype. A substantial pain decrease was noted in classic (p <0.05) as well as nonulcer (p <0.05) interstitial cystitis following dimethyl sulfoxide. Intravesical BCG has been presented as a promising new option for treatment of interstitial cystitis. We failed to demonstrate benefit from this treatment. Dimethyl sulfoxide had no positive effect on maximal functional capacity but resulted in a significant reduction in pain and urinary frequency, although only in patients with classic interstitial cystitis.

Complete transurethral resection of ulcers in classic interstitial cystitis.

Interstitial cystitis (IC) is a chronic disease of obscure etiology. It commonly affects females, who present with symptoms of pain on bladder filling and urinary frequency. There are two types of IC: classic and non-ulcer disease, which differ in many respects, including response to different therapies. In this retrospective study we evaluated the hitherto largest series of patients with classic IC treated by transurethral resection (TUR) of visible ulcers. Altogether 259 TURs of Hunner ulcers were performed on 103 patients: 92 experienced amelioration, and in 40% symptom relief lasted more than 3 years. In the remaining patients, although symptom recurrence was common, the majority responded well to subsequent TUR. In conclusion, TUR has a good outcome in patients with classic interstitial cystitis, and we suggest it as first-line treatment in this patient group.

INCREASED TYROSINE HYDROXYLASE IMMUNOREACTIVITY IN BLADDER TISSUE FROM PATIENTS WITH CLASSIC AND NONULCER INTERSTITIAL CYSTITIS

Interstitial cystitis is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer subtype appears different than classic interstitial cystitis in regard to symptoms, and endoscopic and histological findings as well as response to various treatments. We further explore the neurogenic nature of this disease using indirect immunofluorescence to evaluate the presence and density of various autonomic and sensory nerve fibers. Specimens from the bladder wall of 6 patients with classic interstitial cystitis, 7 with nonulcer interstitial cystitis and 6 controls were evaluated to determine the presence and density of nerve fibers containing tyrosine hydroxylase, calcitonin gene-related peptide, neuropeptide Y and substance P using specific antibodies, and the general presence of nerve fibers using a mixture of antibodies against nerve filament, neuron specific enolase and S-100 protein. Increased density and number of nerve fibers immunoreactive for tyrosine hydroxylase were noted in interstitial cystitis cases compared to controls. Furthermore, there was a difference between classic and nonulcer disease in the overall density of nerves using the antibody mixture. Our findings indicate an altered peripheral sympathetic innervation in interstitial cystitis cases, which may be an indication of primary neurogenic etiology. The difference in nerve density observed after incubation with the antibody mixture between classic and nonulcer interstitial cystitis supports the hypothesis that the 2 forms represent separate entities.

RECRUITMENT, DISTRIBUTION AND PHENOTYPES OF MAST CELLS IN INTERSTITIAL CYSTITIS

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). 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. 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. 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.

Treatment guidelines for classic and non-ulcer interstitial cystitis.

Interstitial cystitis (IC) is a chronic disease of as yet unknown etiology. It commonly affects females, presenting with symptoms of pain on bladder filling, and urinary frequency. Accumulated evidence indicates that IC is a heterogeneous syndrome. Compared to classic IC, the non-ulcer type appears different concerning symptomatic, endoscopic and histological findings, as well as the response to various forms of treatment. This review gives an introduction to the syndrome of IC, concerning epidemiology, clinical characteristics, diagnostic criteria and etiological considerations. A variety of treatment modalities have been suggested and are assessed and reviewed, such as hydrodistension of the bladder, intravesical instillation therapy, oral medication, transcutaneous electrical nerve stimulation, transurethral resection of diseased bladder tissue, and supratrigonal cystectomy followed by enterocystoplasty and urinary diversion. Our algorithm on non-surgical and surgical treatment for classic and non-ulcer IC is presented.