Histamine content and mast cell count of detrusor muscle in patients with interstitial cystitis and other types of chronic cystitis

The quantitative mast cell count in the detrusor muscle, the histamine content and the degree of collagen staining material in the bladder wall have been evaluated in order to elucidate their value in distinguishing between patients with interstitial cystitis and other types of chronic cystitis. The number of mast cells in the detrusor muscle was statistically significantly increased in patients with interstitial cystitis compared with the control group (P less than 0.0001). With a proposed level of greater than 20 mast cells/sq mm of muscle tissue the diagnostic specificity was 88% and the diagnostic sensitivity 95%. The histamine content in the bladder wall was significantly increased in patients with interstitial cystitis (P less than 0.05) but not useful as a diagnostic test. The amount of collagen staining material was significantly increased in the intra- and inter-fascicular muscle tissue of the bladder in patients with interstitial cystitis (P less than 0.0005, P less than 0.001) and might be used as a support for the histological diagnosis, even in patients with uncontracted bladders.     

Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis

OBJECTIVE: To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. MATERIALS AND METHODS: We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, FcepsilonRIalpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera. RESULTS: Oral administration of BXL628 significantly reduced the expression of interleukin-13, FcepsilonRIalpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo. CONCLUSIONS: Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.     

Pathology and pathophysiology of painful bladder diseases

Painful bladder disease is an ill-defined disease presenting with chronic cystitis symptoms, despite sterile urine. This report includes only patients with painful bladder diseases of unknown etiology and pathogenesis. We have chosen to classify these patients pathoanatomically as follows: interstitial cystitis, detrusor myopathy, chronic unspecific cystitis and eosinophilic cystitis. The pathoanatomical appearance of the four groups of patients are described in details and certain clinical differences appear between the groups. The etiology and pathogenesis to the inflammatory reactions and muscle changes found in the detrusor biopsies are unknown, but many theories exist. It is suggested that something in the urine gains access to the bladder wall and initiates the pathoanatomical changes through a defective urothelium and glycosaminoglycans layer. In the interstitial cystitis patients, the inflammatory process and mast cell degranulation might be monitored by the urinary excretion of 1,4-methyl-imidazole-acetic acid and eosinophil cationic protein. It is concluded that no specific therapy for the disease exists, since etiology and pathogenesis are still unknown and therefore future research in this field is very important.     

Bladder epithelial cells from patients with interstitial cystitis produce an inhibitor of heparin-binding epidermal growth factor-like growth factor production

PURPOSE: The etiology of interstitial cystitis is unknown. We previously identified an interstitial cystitis urine factor, antiproliferative factor, that inhibits proliferation of bladder epithelial cells in vitro and complex changes in epithelial growth factor levels, including profound decreases in heparin-binding epidermal growth factor-like growth factor (HB-EGF). Bladder and renal pelvic catheterization of patients with interstitial cystitis indicated that the antiproliferative factor is made and/or activated in the distal ureter or bladder. Therefore, we determined whether bladder epithelial cells from interstitial cystitis cases produced the antiproliferative factor and whether purified antiproliferative factor could alter production of growth factors known to be abnormal in interstitial cystitis. MATERIALS AND METHODS: Antiproliferative factor activity was determined by 3H-thymidine incorporation into primary bladder epithelial cells. The antiproliferative factor was purified by size fractionation followed by sequential chromatography involving ion exchange, hydrophobic interaction and high performance liquid chromatography. HB-EGF, epidermal growth factor, insulin-like growth factor and insulin-like growth factor binding protein 3 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Bladder epithelial cells from patients with interstitial cystitis produced a single antiproliferative factor with the same purification profile as that purified from interstitial cystitis urine. Purified antiproliferative factor specifically inhibited HB-EGF production by bladder epithelial cells in vitro, and the effect of interstitial cystitis urine or purified antiproliferative factor on bladder cell proliferation was inhibited by recombinant human HB-EGF in a dose dependent manner. Similar to urine HB-EGF, serum HB-EGF was also significantly lower in interstitial cystitis cases than in controls. CONCLUSIONS: Bladder epithelial abnormalities in interstitial cystitis may be caused by a negative autocrine growth factor that inhibits cell proliferation by down-regulating HB-EGF production. Furthermore, decreased levels of urine and serum HB-EGF indicate that interstitial cystitis may be a urinary tract manifestation of a systemic disorder.     

The effects of cold-restraint stress on urinary bladder wall compared with interstitial cystitis morphology

Stress is associated with many diseases of unknown aetiology. This study demonstrates the effects of cold-restraint stress on the morphology of the urinary bladder. Additionally, it compares the results obtained with the morphology of the interstitial cystitis. The animals were subjected to three hours of cold-restraint stress and then starved for 48 h. The morphology and histochemistry of the urinary bladder was investigated with light and electron microscopy. The proliferative activity was analysed via flow cytometry. Increased and degranulated mast cells in the mucosa, leucocyte infiltration in the lamina propria, vacuole formation in the urothelial cells, loose tight junction, dilated intercellular spaces and altered proliferative activity were observed in the stress group when compared with the control. The increase in the number of mast cells and especially degranulated mast cells and vacuole formation and the loose tight junction of the urothelium correlated with the histopathological findings of interstitial cystitis. Received: 12 December 1998 / Accepted: 25 June 1999     

INCREASED URINARY LEUKOTRIENE E4 AND EOSINOPHIL PROTEIN X EXCRETION IN PATIENTS WITH INTERSTITIAL CYSTITIS

PURPOSE: The role of cysteinyl containing leukotriene C4, D4 and E4, and eosinophil protein X in interstitial cystitis is unknown. Leukotriene E4, the end product of cysteinyl containing leukotrienes, and eosinophil protein X are markers of the activation of mast cells and eosinophils, respectively. Cysteinyl containing leukotrienes are potent and specific chemoattractants for eosinophils. We compared the urinary excretion of leukotriene E4 and eosinophil protein X in patients with interstitial cystitis and in healthy controls. MATERIALS AND METHODS: Morning spot urine samples from nine patients with interstitial cystitis who fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria were collected on the day of cystoscopy with biopsies. Aliquots of urine specimens were immediately centrifuged and the supernatants were stored at -80C until use. Urine samples from 9 healthy women served as controls. Urinary leukotriene E4 and eosinophil protein X were measured by enzyme immunoassay and radioimmunoassay, respectively. All determinations were performed in duplicate and normalized to urine creatinine. RESULTS: Leukotriene E4 and eosinophil protein X were significantly increased in the morning urine of patients with interstitial cystitis compared with controls. The mean urinary excretion of leukotriene E4 plus or minus standard deviation was 148.8 +/- 62.5 and 62.2 +/- 17.5 ng./mmol. creatinine in patients and controls (p = 0.003), while the mean urinary excretion of eosinophil protein X was 109.7 +/- 70.4 and 43.7 +/- 22.0 microg./mmol. creatinine, respectively (p = 0.01). All urine cultures were negative. The mean mast cell count in detrusor biopsies in the interstitial cystitis group was 41 cells per mm.2 (range 5 to 84). Eosinophilic granulocytes were occasionally observed in the submucosa but not in the detrusor. CONCLUSIONS: Our study shows that patients with interstitial cystitis and detrusor mastocytosis have increased urinary leukotriene E4 and eosinophil protein X. It is possible that cysteinyl containing leukotrienes and eosinophil protein X are involved in the pathogenesis of interstitial cystitis. Urinary leukotriene E4 and eosinophil protein X may be useful markers for assessing the grade of activation of mast cells and eosinophils in patients with interstitial cystitis and/or for confirming the diagnosis. However, it remains to be investigated whether the increase in urinary leukotriene E4 and eosinophil protein X correlates with interstitial cystitis symptoms.     

Urinary excretion of a metabolite of histamine (1,4-methyl-imidazole-acetic-acid) in painful bladder disease

Thirteen patients with interstitial cystitis (detrusor mastocytosis) and 12 other patients with painful bladder disease without mastocytosis collected 24-h urine specimens that were analysed for the major metabolite of histamine, 1,4-methyl-imidazole-acetic-acid (1,4-MIAA), by reversed phase ion-pair high performance liquid chromatography. The median urinary excretion of 1,4-MIAA was 3.34 mg/24 h (range 1.47-4.66) in the patients with detrusor mastocytosis and 1.75 mg/24 h (range 0.18-4.30) in the other patients with a painful bladder (P less than 0.01). It was concluded from this study that patients with a painful bladder and detrusor mastocytosis had a significantly elevated urinary excretion of 1,4-MIAA compared with other painful bladder patients without mastocytosis, whose urinary excretion of 1,4-MIAA was within the normal range (0.72-2.34 mg/24 h). We suggest that the urinary excretion of 1,4-MIAA might be useful in the diagnosis of interstitial cystitis.     

ACTIVATION OF THE KALLIKREIN KININ SYSTEM IN INTERSTITIAL CYSTITIS

PURPOSE: We investigated whether the kallikrein kinin system is activated in interstitial cystitis by measuring urinary excretion rates of kinin peptides, active and total kallikrein, and the kininase neutral endopeptidase in women with interstitial cystitis. We compared these excretion rates to a control group of women with stress incontinence and normal bladder function. MATERIALS AND METHODS: Catheter urine was collected from subjects during a water diuresis (approximately 10 ml. per minute) before and after distention of the bladder with 100 ml. water. The contribution of the bladder wall to urinary kinins was assessed by measuring the change in kinin levels after 2 minutes of bladder stasis before and after distention. RESULTS: Absolute bradykinin and kallidin excretion rates were similar in women with interstitial cystitis and control subjects. Two minutes of bladder stasis after bladder distention increased urinary bradykinin (p = 0.02) but not kallidin excretion rates. Active and total kallikrein excretion rates were similar in patients with interstitial cystitis and control subjects. Neutral endopeptidase excretion rates were reduced in the initial urine collection from subjects with interstitial cystitis but were similar in both groups during later collection periods. CONCLUSIONS: These data provide evidence for increased bradykinin levels in the bladder wall of subjects with interstitial cystitis, which may be due in part to reduced neutral endopeptidase levels. These increased bradykinin levels may participate in the pathogenesis and symptomatology of interstitial cystitis.     

Urinary levels of substance P and its metabolites are not increased in interstitial cystitis

OBJECTIVES: To determine whether interstitial cystitis is associated with the increased release of substance P from the bladder wall into urine, by measuring urinary excretion rates of substance P and its metabolites in women with interstitial cystitis and in a control group of women with stress incontinence and normal bladder function. PATIENTS AND METHODS: Catheter urine was collected from 13 patients and 10 controls during a water diuresis ( approximately 10 mL/min) before and after instilling the bladder with 100 mL of water. The contribution of the bladder wall to urinary substance P peptides was assessed by measuring the change in substance P peptide levels after 2 min of bladder stasis before and after instillation. RESULTS: Absolute substance P excretion rates were similar in patients with interstitial cystitis and controls; 2 min of bladder stasis reduced the substance P excretion rate (P = 0.03) and increased the excretion rate of substance P metabolites (P = 0.01). CONCLUSIONS: The release of substance P from the bladder wall was not increased in patients with interstitial cystitis.     

Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis

PURPOSE: Mast cells are ubiquitous cells derived from the bone marrow and are responsible for allergic reactions as they release numerous vasodilatory, nociceptive and pro-inflammatory molecules in response to immunoglobulin E (IgE) and specific antigen. Mast cell secretion is also triggered by a number of peptides, such as bradykinin and substance P, and may also be involved in the development of inflammatory responses. An example is interstitial cystitis, which is a sterile painful bladder disorder that has been associated with a defective glycosaminoglycan bladder mucosal layer and an increased number of activated mast cells. Pentosanpolysulfate is a synthetic, sulfated polysaccharide that has been approved for the treatment of interstitial cystitis on the premise that it may replenish the defective glycosaminoglycan layer. We hypothesize that pentosanpolysulfate may also have an additional or alternate action on bladder mast cells. We report that pentosanpolysulfate has a powerful dose dependent inhibitory effect on mast cell release of histamine induced by the mast cell secretagogue compound 48/80. MATERIALS AND METHODS: Inhibition of mast cell secretion was documented by light and electron microscopy and extended to stimulation by substance P or IgE and antigen. RESULTS: The inhibition was more potent than that seen with the clinically available mast cell stabilizer disodium cromoglycate (cromolyn). Maximal inhibition by pentosanpolysulfate was apparent within 1 minute, was unaffected by the length of pre-incubation and persisted after the drug was washed off. In contrast, the effect of cromolyn was limited by rapid tachyphylaxis. In addition, while cromolyn has no effect on mucosal or rat basophilic leukemia cells, pentosanpolysulfate inhibited histamine secretion from both. Confocal microscopy using a calcium indicator dye showed that pentosanpolysulfate decreased intracellular calcium ion levels. CONCLUSIONS: Pentosanpolysulfate appears to be a potent inhibitor of allergic and nonimmune mast cell stimulation, which is an alternative explanation of its benefit in interstitial cystitis.     

Do women with idiopathic sensory urgency have early interstitial cystitis?

Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics. Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity, with both early and late forms of the disease being described. Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist. We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis). No control patient showed such an increase. Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency.     

Detrusor mast cells in refractory idiopathic instability.

The diagnosis of interstitial cystitis (IC) is not usually considered in patients with idiopathic instability. Because histamine provokes detrusor contractions in vitro, we assessed detrusor mast cell counts in 29 females with refractory instability. Raised mast cell counts (greater than 28/mm2 of detrusor muscle, consistent with a histological diagnosis of IC) were found in 29% of such cases. Thus cystoscopy and bladder biopsy should be considered in patients with idiopathic instability which fails to respond to anticholinergic drugs, as alternative therapy may be useful. Patients with refractory instability and normal detrusor mast cell counts often gave a history of prolonged childhood nocturnal enuresis (55% of cases); in contrast, patients with intractable instability and abnormally high mast cell counts seldom gave such a history (12%). These trends may give some insight into the aetiology of idiopathic instability--"congenital" or acquired?     

Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis.

An analysis was made of the numbers and characteristics of mast cells in lateral bladder wall biopsies from 22 patients with interstitial cystitis, 6 with bacterial cystitis and 8 normal controls, using toluidine blue stains and computerised video image analysis techniques. A significantly greater number of mast cells were found within the detrusor muscle in interstitial cystitis than in bacterial cystitis or normal controls. Within the urothelium and submucosa, mast cell numbers were significantly greater than in normal controls in both interstitial and bacterial cystitis. In interstitial cystitis mast cells were significantly larger within the detrusor than in the urothelium/submucosa and they appeared to degranulate predominantly within the superficial layers. Differential staining techniques, using long and short toluidine blue stains, failed to reveal statistically significant evidence of mast cell heterogeneity within the bladder wall in interstitial cystitis.     

The clinical significance of eosinophils in urine]

The clinical significance of eosinophils in urine was examined. Eosinophils were found in 9 out of 10 cases of interstitial cystitis, and there were more than 50 eosinophils in 50 fields in 6 of these cases. Although the number of eosinophils almost correlated with the number of leucocytes, the relationship between eosinophils and leucocytes in interstitial cystitis was different in acute and chronic cystitis. Since urinary eosinophils could be observed in cases of interstitial cystitis in which leucocytes were as low as 3 to 10 per field and the number of eosinophils was not decreased by chemotherapy, the urinary eosinophils in interstitial cystitis may be of allergic significance and reflect eosinophilic infiltration into the bladder wall.     

Alternate Occurrence of Allergic Disease and an Unusual Form of Interstitial Cystitis

Background : It has been postulated that interstitial cystitis can be induced by an allergy. This is partly based on the observation that many patients with interstitial cystitis also have allergic diseases. In this study, an allergic evaluation was conducted on patients with interstitial cystitis complicated by bronchial asthma, a typical allergic disease.
Methods : Clinical histories were obtained and biopsy specimens from the vesical walls of the study patients were examined histologically. Cutaneous tests and IgE radioallergosorbent tests (RAST) were performed. Further, intravesical provocation tests were carried out using IgE RAST-positive antigens, and histamine release assays were performed on the vesical biopsy specimens using anti-lgE antibodies.
Results : Five of 6 patients alternately exhibited symptoms of allergic disease and bladder symptoms. The eosinophil and mast cell counts in the vesical biopsy specimens of these 5 patients were increased. Furthermore, an intravesical provocation test performed using the IgE RAST-positive antigen was positive in 4 patients. The mean vesical biopsy specimen histamine release was 1 7.7% for patients with interstitial cystitis with bronchial asthma which was significantly higher than that for interstitial cystitis patients without bronchial asthma (8.9%) or the control group (4.5%). The prognosis of patients with interstitial cystitis with allergic complications was relatively good.
Conclusion : Patients with bronchial asthma exhibited hypersensitivity both generally and locally in the bladder. The alternation phenomenon was observed between the hypersensitive organs.     

Tumor necrosis factor promotes differential trafficking of bladder mast cells in neurogenic cystitis

PURPOSE: IC is often considered neurogenic cystitis, in which mast cells are involved in a positive feedback loop that results in sustained urothelial inflammation. To characterize these processes we developed a murine model of neurogenic cystitis using Bartha's strain of PRV based on a similar model in the rat. MATERIALS AND METHODS: Female C57BL/6 mice (National Cancer Institute, Bethesda, Maryland) were used in the study. Neurogenic cystitis was induced by the injection of Bartha's strain of PRV (2.2 x 10 pfu) into the abductor caudalis dorsalis tail base muscle. Bladder inflammation was assessed by leukocyte influx and Evans blue dye extravasation. Mast cells were visualized in bladder tissue by staining with 0.1% toluidine blue. RESULTS: Inoculation with PRV in the abductor caudalis dorsalis resulted in cystitis within 3 days. Coincident with the induction of cystitis mast cells accumulated in the lamina propria due to mast cell trafficking from the proximal detrusor (relative to the lumen), whereas mast cells from the distal detrusor were unchanged and total mast cell counts were not increased. Degranulated mast cells increased approximately 20-fold in the lamina propria of infected mice relative to controls. In TNF receptor 1/2 deficient mice (Jackson Laboratory, Bar Harbor, Maine) mast cell trafficking was not observed in response to PRV and mast cells were not degranulated. CONCLUSIONS: These data indicate that neurogenic cystitis is associated with the differential trafficking and activation of distinct mast cell pools in the bladder. Since TNF mediates these events, anti-TNF therapy may mitigate the pathogenesis of neurogenic cystitis.     

Acute renal failure resulting from huge inguinal bladder hernia

We report a novel entity of plasma cell bladder infiltration without other demonstrable disease. The patient had severe irritative voiding symptoms, hematuria, and a diffuse mucosal infiltrate with 90% plasma cells. Although the patient demonstrated some clinical and pathologic evidence consistent with interstitial cystitis and eosinophilic cystitis, a predominant finding of focal plasma cell infiltration of the urinary bladder suggests a new or previously unrecognized clinical entity.     

BLADDER MICROVASCULATURE IN WOMEN WITH INTERSTITIAL CYSTITIS

PURPOSE: A cardinal cystoscopic finding in women with interstitial cystitis is mucosal small vessel hemorrhage or glomerulations after hydrodistention. We quantified and compared microvascular density and endothelial proliferation in the bladder biopsies of women with interstitial cystitis and a control group of women who were undergoing incontinence or prolapse surgery. MATERIALS AND METHODS: We performed computer assisted image analysis and immunohistochemical studies to compare differences in the blood vessel count, and proportional area in the bladder suburothelium and deeper submucosa of bladder biopsies of 52 women, including 26 with interstitial cystitis. Routine light microscopy features were examined and correlated with microvascular density. RESULTS: In the bladder biopsies of women with interstitial cystitis there was a lower blood vessel count (p = 0.01), and a lower proportion of the total image consisted of blood vessel wall (p = 0.03) in the suburothelium than in control biopsies. We noted no difference in the blood vessel count of the deeper submucosa or in the degree of endothelial cell proliferation. Suburothelial blood vessel differences correlated with the degree of histological change, such as edema, inflammatory infiltrate and vascular congestion. CONCLUSIONS: We found decreased microvascular density in the suburothelium but not in the deeper submucosa in bladder biopsies of women with interstitial cystitis.     

Intravesical suplatast tosilate (IPD-1151T) inhibits experimental bladder inflammation

PURPOSE: Interstitial cystitis is a painful bladder disease characterized by urgency, frequency and variable inflammation but there is no curative therapy. Suplatast tosilate (IPD-1151T) is an immunoregulatory compound that decreases interstitial cystitis symptoms but to our knowledge its mechanism of action is unknown. We investigated the effect of intravesical IPD-1151T on mediator release from bladder explants in experimental cystitis. MATERIALS AND METHODS: A catheter was inserted into the bladder of female mice. After urine was emptied normal saline, carbachol (100 nM) or lipopolysaccharide (10 mg/ml) was introduced with or without 10-minute pretreatment with IPD-1151T. Urine was removed after 45 minutes for histamine and tumor necrosis factor-alpha assays. The bladder was removed after 4 hours, minced into 1 mm2 pieces and cultured with or without triggers overnight for mediator release. The effect of IPD-1151T was also tested on rat skin vascular permeability as well as on purified rat peritoneal mast cells and human cord blood derived mast cells. RESULTS: Carbachol significantly increased histamine release in urine (61.3% in 8 preparations, p<0.05) but not in explant medium. IPD-1151T inhibited this effect by 77%. Lipopolysaccharide induced a 350% urine histamine increase in 9 preparations (p<0.05) and a 300% tumor necrosis factor-alpha increase in explant medium. IPD-1151T inhibited the lipopolysaccharide induced medium tumor necrosis factor-alpha increase by 95% in 5 preparations (p<0.05). IPD-1151T did not inhibit rat skin vascular permeability or purified rat peritoneal mast cell activation by compound 48/80 or human cord blood derived mast cells by anti-IgE. CONCLUSIONS: IPD-1151T inhibits bladder release of histamine and tumor necrosis factor-alpha through a mechanism that does not appear to involve direct mast cell inhibition. These findings may justify a beneficial effect of IPD-1151T in interstitial cystitis.     

Is interstitial cystitis an allergic disorder?: A case of interstitial cystitis treated successfully with anti-IgE

Interstitial cystitis (IC) is a chronic disorder diagnosed by symptomatology of pelvic pain and urinary frequency, which are extremely variable and unpredictable fluctuating among patients. IC has recently been found combined with some allergic disorders and histopathologic abnormalities resembling that of allergic disorders, including mast cell activation, histamine release and eosinophil infiltration. Therefore, it could be cautiously postulated that IC is one of the allergic disorders of the urogenital system. A 28-year-old Caucasian female patient, who was diagnosed with asthma and allergic rhinitis, suffered from bladder symptoms of frequency, urgency and pelvic pain for the past 3 years. The symptoms disturbed her every day and were intractable for treatment. Urologists concluded that she had interstitial cystitis. Specific immunotherapy (SIT) was recommended for her allergic symptoms. While taking specific immunotherapy, she had anaphylaxis. She still had the reaction even with the 1000-fold diluted shot of SIT. Omalizumab was used for her allergic symptoms and possible prevention of anaphylactic reaction to SIT. Interestingly, she reported that her urogenital symptoms had subsided since omalizumab had been started. According to the published literature, we postulate that interstitial cystitis might be one of the IgE mediated, mast cell driven allergic disorders of the urogenital system. Therefore, in this case, the patient's bladder symptoms are successfully controlled primarily by anti-IgE therapy and the improvement could be maintained by SIT. We report, for the first time, a case of interstitial cystitis with allergic rhinitis and asthma, successfully treated by anti-IgE therapy and specific immunotherapy.