Nonbacterial cystitis is a catchall term that comprises various medical disorders, including nonbacterial infectious (viral, mycobacterial, chlamydial, fungal, schistosomal) and noninfectious (radiation cystitis, chemical, autoimmune, hypersensitivity) cystitis, as well as painful bladder syndrome/interstitial cystitis (PBS/IC). PBS/IC describes a syndrome of pain and genitourinary symptoms, such as frequency, urgency, pain, dysuria, and nocturia, for which no etiology can be found.
Candidal infection the bladder is shown below.
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Gross pathology, bladder with candidal infection and hemorrhage.
General symptoms of cystitis include urgency, frequency, dysuria, and, occasionally, hematuria, dyspareunia, abdominal cramps, and/or bladder pain and spasms. Establishing or excluding a specific diagnosis often requires recurrent cultures and various urologic procedures, including cystoscopy with bladder biopsies, various bladder tests, and immune system function examinations.
Some conditions, such as carcinoma in situ, bladder calculi, and urethral foreign bodies, may result in symptoms that mimic those of nonbacterial cystitis.
The frequency of viral and herpetic cystitis is unclear because culture results can be falsely negative. A large number of people have been suggested to have asymptomatic infections initially with both herpes simplex viruses (HSV), HSV-1 and HSV-2, so the incidence of herpetic cystitis may be higher than culture-positive results indicate. Hemorrhagic cystitis due to adenoviral infections is common in immunocompromised hosts, especially bone marrow transplant recipients or those with AIDS. Hemorrhagic cystitis due to infection with adenoviruses or BK polyoma virus has been reported in 20% and 8% of pediatric bone marrow transplant patients, respectively.
The frequency of chlamydial genitourinary infections may also be higher than cultures indicate. A study of 130 patients aged 14-25 years in an urban outpatient clinic demonstrated a 21% frequency of Chlamydia trachomatis infection; one third were asymptomatic. Risk factors for Chlamydia infection in this group included younger age, more than one sexual partner, and international travel. In another study of 36 cases of bladder biopsies performed to evaluate cystitis, antigen from C trachomatis was detected by immunochemistry in one third of the specimens.
Mycobacterial cystitis or urogenital tuberculosis is more common in underdeveloped countries and continues to be a major urologic problem in places such as North Africa, mainly because of diagnosis delays. The tuberculosis vaccine, bacillus Calmette-Guérin (BCG), which may be instilled into the bladder to treat bladder tumors, has also been reported to cause cystitis.
Fungal cystitis is more common in immunocompromised hosts, such as those with diabetes mellitus, those who have received chemotherapy, and those with indwelling catheters who have received multiple courses of antibiotics.
Schistosomiasis most frequently occurs in the developing world, although it is estimated that 400,000 cases exist in the United States.
Noninfectious cystitis
Radiation cystitis has been reported to occur in 6.5% of 1784 patients treated with a combination of external beam and intracavitary radiotherapy for stage Ib carcinoma of the cervix. Perez et al reported moderate-to-severe cystitis occurring in 12% of 738 patients treated with definitive irradiation therapy for prostate cancer after 10 years.[1]
Autoimmune disease related to cystitis is another entity that may be more common than previously realized. A review in Sweden demonstrated that 17% of all patients diagnosed with interstitial cystitis had rheumatoid arthritis, 47% had hypersensitivity reactions or allergies, and 2.3% had either ulcerative colitis or Crohn disease, a rate of more than 30 times the prevalence rate in the general population.
Both Sjögren syndrome and systemic lupus erythematosus (SLE) have been associated with urinary symptoms. In one study by Haarala et al of 121 patients and 121 age- and sex-matched controls, more than 60% of patients had some urinary symptoms, compared to 20% of controls.[2]
Painful bladder syndrome/interstitial cystitis
The exact number of people with PBS/IC or related diagnoses in the United States is unclear but may be as high as 450,000. Held and associates estimated that, for every patient diagnosed with PBS/IC, 5 cases of PBS/IC are undiagnosed.[3] Recent data from the Nurses Health Studies suggest that the frequency of PBS/IC is higher than previously reported, around 60 cases per 100,000 population.
Lipsky has suggested that the frequency of nonbacterial prostatitis and chronic pelvic pain syndrome is more common than prostatitis.[4] In general, this condition occurs in whites (>90% of cases) and females (>80% of cases). One author estimated that as many as 60% of men with chronic pelvic pain syndrome/prostadynia are found to have interstitial cystitis when cystoscopy is performed under anesthesia.
Many patients currently being treated for prostatitis in whom therapy fails may actually have undiagnosed interstitial cystitis.
Population studies have suggested that the incidence and prevalence of the disease in other countries, such as Finland and the Netherlands, which had previously been reported to be lower than in the United States, was, in fact, significantly higher. Leppilahti and colleagues in Finland randomly selected subjects and evaluated urinary symptoms; women with moderate-to-severe scores underwent clinical evaluation. The prevalence of clinically confirmed PBS/IC in this study was 530 per 100,000.[5]
Nonbacterial cystitis may have an acute, subacute, or chronic course. Some types of nonbacterial cystitis, such as viral or mycobacterial cystitis, can involve other systems or may depend on the degree of host immunosuppression. Improved molecular detection techniques have allowed the recognition of viral infections, such as the BK polyoma virus infections, cytomegalovirus (CMV) infections (associated with hemorrhagic cystitis after bone marrow transplant[6, 7] ), and adenoviral infections.[8]
Herpes and chlamydial nonbacterial cystitis is sexually transmitted, while other types, such as fungal cystitis, occur mainly in immunocompromised hosts.[9, 10]Corynebacterium urealyticum has been associated with a very rare chronic inflammatory disorder, encrusted cystitis, which is characterized by precipitation and incrustation of phosphate ammonium magnesium salts on the bladder mucosa.[11] Yeast infiltration of the bladder is shown in the image below.
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Infiltration of yeast in the bladder wall.
Schistosomiasis (shown in the image below) can cause severe cystitis and lower urinary tract symptoms due to an inflammatory reaction to Schistosoma eggs embedded in the host's bladder.
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Schistosomiasis of the ureter.
Noninfectious etiologies
Cystitis may occur following radiation therapy to the pelvis for cancer treatment. The average time from the beginning of radiation therapy to initial symptoms can be several months to several years. Symptoms can include anything from mild bleeding to severe recurrent bleeding and pain requiring hospitalization for treatment.
Autoimmune diseases such as SLE or Sjögren syndrome can also be associated with irritative bladder symptoms, such as frequency or pain. Eosinophilic cystitis is a rare pathologic condition characterized by transmural inflammation of the bladder predominantly by eosinophils and fibrosis, with or without muscle necrosis.[12]
Cystitis may also be caused by chemicals and medications. Both intravenous and oral cyclophosphamide, used to treat malignancies and vasculitides (eg, SLE, Wegener granulomatosis) can cause hemorrhagic cystitis.[13] Low-dose methotrexate, used to treat rheumatoid arthritis, has also been reported to cause hemorrhagic cystitis.[14]
Recent reports have documented cystitis arising after the recreational abuse of ketamine, an anesthetic agent. Such cases are characterized by marked frequency, urgency, and dysuria and display cystoscopic evidence of inflammation throughout the bladder.[15]
Painful bladder syndrome/interstitial cystitis
The etiology of PBS/IC is unknown. PBS/IC is believed to be a syndrome with numerous etiologies. Suggested possible etiologies include an as-yet-unidentified infectious agent or autoimmune diseases. For example, Van de Merwe and associates demonstrated an association between PBS/IC and various connective-tissue diseases such as Sjögren syndrome and SLE.[16] Multiple studies have examined the question of an infectious etiology for PBS/IC, but no single organism has been found consistently by culture, biopsy, or scanning electron microscopy. However, the idea of cryptic bacterial infections and/or the role of antecedent bacterial urinary tract infections (UTIs) causing urothelial damage continues to be evaluated.
One recent theory has suggested that the bladder-wall lining in persons with PBS/IC is "leaky" or defective, allowing toxic substances to enter the bladder and to produce symptoms, possibly due to defects in the protective glycosamine glycan layer of the apical membrane or a defect in the epithelial cell layer. Normally, the bladder wall is nearly impervious to water, protons, and small molecule reabsorption, partly because of the tight junctions between the apical membranes of the epithelial cells. Adding a toxic agent, such as nystatin, or sensitizing the bladder wall to an antigen disrupts the tight junctions and increases the permeability of normal bladder epithelium.
Another theory suggests that mast cells play an important role in the etiology of PBS/IC. Mast cells contain or can synthesize a large number of inflammatory mediators, including cytokines, chemotactic factors, histamine, vasoactive peptides, cenogeneses, leukotrienes, and prostaglandins. These compounds can cause pain, tissue damage, and changes in vascular regulation and can lead to infiltration of other inflammatory cells. Although mast cells are found in many tissues, the number of mast cells in the muscle layers (detrusor) is often higher in individuals with interstitial cystitis than in other kinds of cystitis. Many factors can trigger mast cell secretion, including chemotactic factors, drugs, hormones, solar and other radiation, bacterial toxins, and viruses.
Medications such as hydroxyzine (Atarax), which inhibit the inflammatory mediators found in mast cells, have been used with varying success in the treatment of interstitial cystitis. One suggestion involves using the relative number of mast cells found in the bladder biopsies of patients with interstitial cystitis to help select those who are most likely to benefit from mast cell inhibitors. When high numbers of mast cells are found, mast cell inhibitors are used.
Nitric oxide synthase, which regulates the production of nitric oxide in cells and is important in vascular regulation, has also been found to be decreased in the urine of patients with interstitial cystitis as compared to controls. The role of nitric oxide in interstitial cystitis is unknown.
Yet another theory suggests that PBS/IC is related to pelvic muscle hyperirritability and increased tension, leading to hypersensitivity of the peripheral and central nerves in the area. The muscles of the pelvic floor are chronically contracted, and urination requires relaxation of the pelvic floor muscles. Chronically increased stress or increased muscle tension, which causes the pelvic muscles to contract further, pulls the pelvic organs up against the pubic bone and causes further discomfort.
According to this theory, the resulting chronic stimulation of the spinal cord and central nerves in the brain leads to an abnormal state of hypersensitivity and chronic pain. Recent studies in subjects with complex regional pain syndromes (eg, reflex sympathetic dystrophy) have shown abnormal neuron growth in the dorsal horns of the spinal canal, leading to activation of the slow (type C) nerves when the fast (type A, light touch, pinprick) nerves are stimulated. This leads to the perception of pain after stimulus that is normally nonpainful.
Consistent with this idea of neuron cross-talk is a recent report by Pezzone et al of increased electromyography (EMG) activity in the colons of rats with induced bladder-wall irritation and increased bladder EMG activity in rats with acute colonic irritation.[17]
Jasmin and associates also demonstrated that infecting the CNS of rats with pseudorabies virus led to a localized immune response and bladder inflammation, which was not noticed when the bladder was denervated.[18]
Abnormalities in the recently described vanilloid receptors (VRs) responsible for activation of the unmyelinated C-fibers that conduct thermal and noxious stimuli to the CNS may be involved. VR1 is a nonselective cation channel with 6 transmembrane domains related to the transient receptor potential (TRP) channel family. Noxious temperatures (>43°C) and chemicals, such as capsaicin (the primary active ingredient in hot peppers), cause the ion channel to open and the nerve to be stimulated. The presence of even small quantities of hydrogen ions appears to lower the degree of heat or amount of capsaicin needed to activate the channel. The role of this receptor in pain stimulation is currently an area of active research.
Yet another recent theory suggests a genetic component to PBS/IC. In a prospective study that compared patients with PBS/IC and their first-degree relatives with a cohort of patients without PBS/IC, both the patients with PBS/IC and their family members had significantly higher lifetime prevalences of panic disorder, which has been linked to a genetic marker, D13S779 on chromosome 13.
In some patients, all of these etiologies may play a part in the disease process that produces the symptoms now termed PBS/IC. Interest in this subject has increased in recent years, leading to more research into the pathophysiology.
Cytopathologic viruses, such as HSV-1 and HSV-2, live integrated into the host genome in the nervous system. Impairment of immune surveillance, which can be caused by comorbid diseases, drugs, or chronic activation of the neuroendocrine pathways involved with corticosteroid production, allow the virus to activate, travel down the peripheral nerves, and cause an outbreak of the disease. Viruses normally do not cause cystitis in immunocompetent adults; whether the infections are due to primary infection or reactivation of latent virus is unclear.
Chlamydiae are obligate intracellular parasites with a unique reproductive cycle that involves two forms—an extracellular form adapted to survival in the environment, which allows the infection to be transmitted from one person to another, and an intracellular form that replicates and produces more extracellular forms. C trachomatis is the organism most commonly identified and is associated with symptoms of urethritis, cervicitis, pelvic inflammatory disease, proctitis, and epididymitis.
Initial infection with mycobacteria generally elicits a mild inflammatory response with few or no symptoms. Weeks after the primary infection with continued replication of the bacilli, development of cell-mediated immunity leads to macrophage infiltration and ingestion of the pathogen. While mycobacteria can persist within macrophages, replication usually ceases, and spread of the disease is contained. Individuals with disturbances in cell-mediated immune responses are therefore at higher risk for dissemination of the infection.
While fungal infections can occur in immunocompetent hosts, they are more likely to occur in individuals with abnormal immune systems. Species of fungi associated with urogenital fungal infections include Blastomyces dermatitidis, Candida species , and Torulopsis glabrata.
Schistosomiasis can cause symptoms of cystitis, including frequency, urgency, and dysuria. Chronic human schistosomiasis can eventually result in small bladder capacity, obstructive uropathy, and bladder cancer. Schistosoma eggs are deposited within the bladder wall as part of their life cycle. An eosinophilic immune reaction is generated in response to the eggs, leading to chronic inflammation.
Noninfectious cystitis
Radiation cystitis is presumably due to the ionizing radiation administered for treatment for pelvic and urogenital cancers. In a study by Perez et al,[1] both the volume of space irradiated and the total dose of radiation were important factors that influenced morbidity. Patients treated with stationary radiation portals that delivered higher doses of radiation to the bladder had an 18% incidence of morbidity compared to those treated with rotating portals (5%, P < 0.1).
Eosinophilic cystitis has been associated with various etiologic factors, such as allergies, bladder tumors, and parasite infections, which stimulate antigen formation, leading to antigen-antibody complexes that stimulate inflammatory cascades. This, in turn, leads to eosinophil infiltration and chemokine release, causing fibrosis.[12]
Chemical cystitis, which is due to chemotherapy with alkylating agents such as cyclophosphamide, is thought to be due to metabolites excreted in the urine. The effects appear to be related to the dose and duration of therapy.
Interstitial cystitis
The pathophysiology of interstitial cystitis is unknown. Because it may be a syndrome rather than a disease, the pathophysiology may differ depending on the exact etiology. However, data from animal and human studies demonstrate pathophysiologic changes, including urothelial dysfunction, mast cell stimulation and activation, sensory nerve upregulation, spinal cord imprinting, and pelvic floor dysfunction.
As mentioned above, the symptoms of cystitis include urgency, frequency, and dysuria and, in some cases, hematuria, dyspareunia, abdominal cramps, and/or bladder pain and spasms.
In a recent study of patients with herpes virus infection confirmed by HSV-2 antibody testing, a wide range of symptoms were exhibited, varying from transient dysuria that occurred only rarely to frequent prolonged attacks of dysuria, frequency, and pain.[10]
Clinical features of fungal infections can range from asymptomatic urinary tract colonization (the most common finding), to cystitis, pyelonephritis, or even sepsis with fungemia.[19] In rare cases, candidal infections also can cause pneumaturia.[20]
Chlamydial genitourinary infections may or may not produce symptoms but may have an associated mucopurulent cervical or urethral discharge.
Tuberculosis of the genitourinary system often has a more indolent onset, with fevers and mild nonlocalized abdominal pain, but typically produce sterile (ie, for bacteria) pyuria and ongoing infection that eventually damage the entire urinary tract. Adrenal insufficiency, renal failure, obstructive uropathy, and chronic cystitis are not uncommon.[21] Tuberculous peritonitis is occasionally reported in patients with renal disease.
Noninfectious etiologies
Radiation cystitis is graded depending on the presentation.
Grade 1: Single episode of mild transient bleeding occurs.
Grade 2: Recurrent minor bleeding occurs.
Grade 3: Bleeding requires hospitalization for medical management. More severe bleeding can be associated with clot retention and pain.
Both Sjögren syndrome and SLE have been associated with urinary symptoms. One tertiary referral center for assessment of vulval disease reported that 7 of 11 women with chronic dyspareunia had tissue and serologic evidence of Sjögren disease.[22] These women had vaginal symptoms for an average of 7 years (range, 1-20 y) before diagnosis.
Min et al found 10 cases of urinary involvement among 413 patients with SLE. All of the patients also had gastrointestinal manifestations, including abdominal pain, nausea, and vomiting and diarrhea, in addition to the urinary symptoms of frequency, dysuria, and incontinence.[23]
Eosinophilic cystitis often causes frequency, hematuria, dysuria, and suprapubic pain.[12]
Chemical cystitis due to chemotherapy can be acute and fulminant or even fatal but more often is delayed and mild to moderate. Atypical bladder epithelial cells may appear in the urine.
While these symptoms may be acute or chronic in patients with nonbacterial cystitis, patients with interstitial cystitis often have severe, recurring, or unremitting symptoms.
Interstitial cystitis
Interstitial cystitis is often diagnosed only after the patient has experienced repeated, frequent bouts of pain, frequency, and urgency without being able to identify a specific cause or any significant symptom relief from simple prescribed remedies. Held and associates, in their epidemiologic survey in 1987, found that the average duration of symptoms is 4.5 years and that patients see an average of 5 doctors before a correct diagnosis is reached.[3]
Symptoms of interstitial cystitis usually begin in persons aged 20-50 years (median age of onset, 40 y), although interstitial cystitis is occasionally diagnosed in children. The mean age of patients is reported as 50-60 years. The exact number of people with this diagnosis in the United States is unclear because many cases are either undiagnosed or misdiagnosed, but one study estimates the number of people with interstitial cystitis in the United States at 450,000.
In a 1975 study by Oravisto et al in Finland, disease onset was subacute and full development of the classic symptom complex occurred over a relatively short time.[24] However, as many as half the patients reported spontaneous remission of symptoms lasting an average of 8 months (range, 1-80 mo).
Patients often have a history of allergies to medications and environmental stimuli, asthma, or arthritides such as SLE or other immunopathologic abnormalities with a presumed autoimmune component such as inflammatory bowel disease or fibromyalgia. Patients with interstitial cystitis are also much more likely to report childhood bladder problems than other people.
In a study of 565 patients with interstitial cystitis by Koziol et al, urgency and frequency were reported in nearly all of them.[25] With reduced bladder capacity and decreased bladder contractions, individuals with interstitial cystitis urinate as often as every 1-2 hours throughout the day and night, with increasing frequency as the duration of the disease increases. Up to 40% of patients experience one or more episodes of hematuria.
Half of the patients reported being awakened in the middle of the night because of pain. Two thirds of the patients reported pelvic pain or pressure, with more than one half reporting pain during intercourse and one third reporting pain for days after intercourse.
More than one half of the patients reported excessive fatigue, difficulties concentrating, and an inability to enjoy their usual activities. Almost all patients found travel to be difficult to impossible, and two thirds of the patients found employment or working at the job for which they were qualified difficult or impossible.
The images below demonstrate the anatomy of the female and male pelvis and bladder and the muscles of the pelvic floor that may be involved in nonbacterial cystitis.
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Gross anatomy of the female pelvis.
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Gross anatomy of the bladder.
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Female perineal anatomy. The urogenital diaphragm and levator ani muscles have been removed, revealing the internal pudendal nerves and vessels, the r....
Viral infections are often difficult to diagnose. Viral culture results can be falsely negative. Some viruses can be detected by polymerase chain reaction (PCR) or by detection of antibodies to the virus.
Chlamydia can also be difficult to grow, and chlamydial culture results may be falsely negative. Chlamydia infection can also be diagnosed by cell cytology, enzyme-linked immunoassays, and PCR. Of all of these tests, PCR is probably the most reliable.[26]
Prior mycobacterial infection, such as Mycobacterium tuberculosis, can be detected by intracutaneous injection of a dose of intermediate-strength tuberculin-purified protein derivative. The test is considered positive if an induration of at least 10 mm develops at the injection site within 48-72 hours. More recently, an assay has been developed that quantifies interferon-gamma released from T cells sensitized to tuberculosis antigens (the QuantiFeron test); the second-generation assay uses antigens almost completely specific for M tuberculosis and can be performed using whole blood samples.
Mycobacteria can also be detected with examination of tissue stained with the acid-fast dye carbol fuchsin as slender, curved, polychromatic beaded rods in pairs or small clumps. Growing the bacteria on highly selective media allows cultivation within 1-2 weeks, although identification and antibiotic sensitivity testing may take longer. Finally, mycobacterial infection can be detected with PCR. In a study by Moussa et al, the sensitivity of acid-fast bacilli (AFB) staining was 52% versus 96% for PCR when compared with cultures.[27]
Fungal infection can be indicated by the findings of hyphae and/or spores on microscopic evaluation of wet smears or histopathologic sections or by culture. Microbiologic diagnosis of funguria is based on a fungal concentration of more than 103/µL in the urine.[19] Some fungi, such as Candida species, grow on many media, while others, such as B dermatitidis, require specialized culture techniques. More recently, DNA probes for detection of numerous fungal infections by PCR have also become available.[28]
Schistosomal infection is detected by searching for terminally spined eggs in urinary sediment. Histopathologic analysis can also be performed with a squash preparation on a glass slide.
Urinary, urethral, and/or vaginal or prostatic cultures can also be performed. Special stains or PCR for viruses, chlamydia, fungi, and mycobacteria should be included in selected patients.
Noninfectious etiologies
The diagnosis of cystitis due to radiation therapy, chemicals, or autoimmune disease can be established in part by obtaining the relevant history. In patients with radiation cystitis, associated UTIs are not uncommon. Cystoscopy may be required to exclude other causes of bleeding, such as recurrent tumor, a new primary tumor, or benign prostatic hyperplasia.
Diagnosis of autoimmune diseases relies on a compatible history supported by serologic or tissue confirmation. Detection of antinuclear antibodies (ANA) is often used as a screening test for connective-tissue disease; positive test results are subjected to assays that are more specific.
Cystoscopy with biopsy is the criterion standard for diagnosing eosinophilic cystitis.[12] Some patients may also have peripheral eosinophilia.
Serologic tests likely to be positive in patients with SLE include low C3, anti–double stranded (ds) DNA, anti-Smith (Sm), and antiribonucleoprotein (anti-RNP) antibodies.
Biopsy of affected organs may show vasculitis. Tests likely to have positive results in patients with Sjögren syndrome include the Schirmer tear test, anti-Ro(SS-A) and anti-La(SS-B), and minor lacrimal gland biopsy. Urine cytology can be a useful first step in the diagnosis of genitourinary malignancies.
Possible imaging tests include abdominal ultrasonography, CT scanning, or MRI for stones, tumors, or endometriosis or dye studies to evaluate for bladder or ureteral strictures and obstruction. Example radiographs of genitourinary tuberculosis can be found in the article Tuberculosis, Genitourinary Tract.
In patients with SLE and bladder involvement, abdominal CT scanning demonstrated thickening of the bladder wall, hydronephrosis, ascites, and bowel-wall thickening.[23]
Treatment of nonbacterial cystitis depends on the etiology, when it can be determined.
Infectious Etiologies
If the host is immunocompromised, treatment regimens may need to be adjusted. Some medications, such as acyclovir, also require dose adjustment for patients with a decreased glomerular filtration rate.
Herpes simplex
In recent years, several antiviral agents chemically related to acyclovir have been shown to be effective against HSV-1 and HSV-2. Treatment for immunocompetent adults includes acyclovir 400 mg 5 times/day for 7 days or valacyclovir 500 mg bid for 5-10 days.
Viral-associated hemorrhagic cystitis
Ganciclovir and vidarabine have been used in some cases of CMV or adenoviral-associated hemorrhagic cystitis in patients who have undergone bone marrow transplantation.[29, 30] Valganciclovir is an oral prodrug with greater intestinal absorption than ganciclovir. Cystitis due to BK polyoma virus reportedly resolved without treatment in 9 pediatric patients. However, in adults who have undergone renal transplantation, cidofovir and a decrease in the dose of immunosuppressants is usually recommended because of the concern of renal parenchymal damage from the virus. Mycophenolate mofetil has been associated with more adenoviral infections than azathioprine.
Chlamydia
Chlamydia can be treated with doxycycline 100 mg bid for 7 days, azithromycin 1 g orally as a single dose, erythromycin 500 mg qid for 7 days, or one of the fluoroquinolones, such as ofloxacin 300 mg bid for 7 days. Erythromycin, azithromycin, and amoxicillin can also be used in pregnant women.
Mycobacteria
Mycobacterial treatment begins with 3 or 4 agents, generally starting with isoniazid (INH) and rifampin (RIF) and another 1 or 2 agents, depending on the probable sensitivities of the organism and the underlying state of the immune system. Standard treatment regimens include INH 300 mg/d, RIF 600 mg qd, ethambutol (EMB) 15 mg/kg, and pyrazinamide 2 g/d. Other drugs that can be used include streptomycin 0.75-1 g/d, ethionamide (ETH) 1 g/d, or one of the fluoroquinolones. Treatment regimens are modified when the actual drug sensitivities are determined. Drug toxicities sufficient to require a change in regimen occur in up to 5% of patients.
Schistosomiasis
The current recommended treatment for schistosomiasis is two oral doses of praziquantel 40 mg/kg for 1 day, resulting in cure rates of 83%-100%. All patients with schistosomiasis should be treated, regardless of disease severity.[31]
Funguria
Treatment is recommended only when the funguria is symptomatic or in cases of fungal colonization when host factors increase the risk of fungemia.[19] Fungal cystitis in immunocompetent patients with indwelling catheters may simply respond to removal of the catheter without further treatment of the infection. If removal of the catheter is not an option, treatment with oral azole antifungal agents or bladder irrigations containing amphotericin B 50 mcg/mL for 5 days can be instituted. In immunosuppressed patients, another option may be intravenous amphotericin B, depending on the degree of dissemination of the infection. Susceptibility testing to antifungal agents may be necessary if patients have previously received therapy for fungal infections. Measures to reduce risk factors include removing urinary catheters, limiting antibiotic treatment, and optimizing diabetes management.[19]
Recently, several new antifungal agents called echinocandins that are active against azole and polyene-resistant pathogens have been developed. One trial that compared one of these newer agents, caspofungin, with amphotericin B for invasive candidiasis demonstrated similar efficacy and markedly fewer side effects for caspofungin. Some infectious disease specialists consider caspofungin to be first-line therapy against invasive non-albicans candidal species. Micafungin, a newly approved echinocandin, can often be used against fungi that are resistant to azole antifungal agents.
Noninfectious Etiologies
Noninfectious etiologies include radiation cystitis, chemical cystitis, autoimmune cystitis, and interstitial cystitis.
Radiation cystitis
While minor bleeding episodes due to radiation treatment stops without treatment, severe bleeding may require hospitalization for therapy. Clot evacuation and continuous bladder irrigation are the standard treatment for heavy bleeding.
A small number of patients with severe bleeding require further treatment. Methods that have been tried include hyperbaric oxygen therapy and chemical therapy. The long-term results of hyperbaric oxygen in 11 patients was reported by Del Pizzo—3 had complete resolution of symptoms, 3 had persistent symptoms, and 5 had initial improvement but then relapsed.[32] In a more recent review by Chong et al of 60 patients with radiation cystitis, 80% had complete or partial resolution of the hematuria, and 96% (27 of 28) of patients treated within 6 months of the onset of hematuria had complete resolution of symptoms.[33]
Srisupundit and colleagues reported good short-term results (follow-up, 1-9 mo) in 13 of 20 patients treated with an intravenous infusion of a chemically stabilized chlorite matrix tetrachlorodecaoxygen (TCDO).[34]
Urinary diversion surgery is presently the surgical treatment of choice in patients whose symptoms fail to resolve.
Chemical cystitis
Chemical cystitis from chemotherapy agents, such as cyclophosphamide, may resolve with hydration or with discontinuation of the drug. Another alternative is mesna, a semisynthetic sulfhydryl compound that reacts chemically with drug metabolites, detoxifying them in a manner similar to the physiologic cysteine-cystine system. Recently, Ballen and colleagues have suggested that extremely aggressive hydration with intravenous fluids and diuretics to maintain a urine output greater than 150 mL/h may be as effective a therapy as mesna, as well as being much less expensive.[35]
Autoimmunecystitis
Treatment of autoimmune diseases generally relies on a combination of symptomatic relief, anti-inflammatory, and immunosuppressive agents. In the last several years, monoclonal antibodies to tumor necrosis factor (TNF)–alpha and several of the interleukins have markedly improved symptoms in some of the rheumatic diseases. The greater variety of immunologic targets amenable to treatment modification has allowed rheumatologists to tailor combinations of drugs that yield improved efficacy with fewer symptoms.
At present, no therapy for eosinophilic cystitis is curative. Treatments that have been tried include anti-inflammatory therapies with nonsteroidal anti-inflammatory drugs and steroids and transurethral resection of the bladder lesion.[12]
Painful bladder syndrome/interstitial cystitis
Please see Interstitial Cystitis for treatment options.
Medications
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
Antimicrobial agents
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Rifampin (Rifadin, Rifadin IV, Rimactane) inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription. The dosage in adults is 600 mg PO qd for 6 mo. Rifampin induces microsomal enzymes, which may decrease effects of other drugs. Blood pressure may increase with coadministration of enalapril. Coadministration with isoniazid or pyrazinamide may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur).
Obtain CBC counts and baseline clinical chemistries prior to and throughout rifampin therapy. In liver disease, weigh benefits against risk of further liver damage. Interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur. Rifampin is a pregnancy category C drug.
Isoniazid (Laniazid, Nydrazid) is an isonicotinic acid hydrazide (INH), which is part of a triple-drug regimen. The adult dosage is 300 mg PO qd for 6 mo. Previous isoniazid-associated hepatic injury or other severe adverse reactions are contraindications. Daily alcohol ingestion may predispose to isoniazid-related hepatitis. Aluminum salts may decrease isoniazid serum levels (administer 1-2 h before taking aluminum salts). Isoniazid may increase anticoagulants effects with coadministration and may inhibit metabolic clearance of benzodiazepines. Carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function). Coadministration with cycloserine may increase CNS side effects (eg, dizziness). Acute behavioral and coordination changes may occur with coadministration of disulfiram. Coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy.
Isoniazid may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin. Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur. Isoniazid is a pregnancy category C drug.
Pyrazinamide’s mechanism of action is unknown. It is well absorbed from GI tract and hydrolyzed to active metabolite in liver. Note that 70% is excreted in urine within 24 h. Treat patients with drug-resistant disease with individualized regimens. The adult dose is 2 g PO qd for 2 months. Contraindications include severe hepatic damage and acute gout. Coadministration with rifampin may result in higher rate of hepatotoxicity than with either agent alone (discontinue if alterations in LFTs occur). Use only in combination with other effective antituberculous agents. Pyrazinamide inhibits renal excretion of urates and may result in hyperuricemia (usually asymptomatic). Perform baseline serum uric acid determinations and discontinue drug upon signs of hyperuricemia with acute gouty arthritis. Perform baseline LFTs (closely monitor in liver disease) and discontinue drug if signs of hepatocellular damage appear. Caution in history of diabetes mellitus. Pyrazinamide is a pregnancy category C drug.
Ethambutol (Myambutol) diffuses into actively growing mycobacterial cells, such as tubercle bacilli. It impairs cell metabolism by inhibiting synthesis of one or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with previously unadministered second-line drugs. The adult dose is 15 mg/kg PO qd for 2 mo. Optic neuritis is a contraindication, unless clinically indicated. Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose). Reduce dose in impaired renal function. Ethambutol may have reversible visual adverse effects if promptly discontinued. Ethambutol is a pregnancy category C drug.
Antifungal agents
Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Amphotericin B, conventional (Amphocin, Fungizone) is produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules.
A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes. The adult dose is 0.5 mg/kg IV qd for 7-14 d; 50 mcg/mL bladder irrigation continuously for 5 days.
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension. Corticosteroids, digitalis, and thiazides may potentiate hypokalemia. The risk of renal toxicity is increased with cyclosporine. Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC counts, and hemoglobin concentrations. Resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d. Hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion). Fever and chills are not uncommon after first few administrations of drug. Rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock. Amphotericin B is a pregnancy category B drug.
Fluconazole (Diflucan) is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. It has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Fluconazole is available in tablet form for oral administration, as a powder for oral suspension, and as a sterile solution for IV use. It has fewer adverse effects and better tissue distribution than older systemic imidazoles. The adult dosage is 200 mg PO/IV qd for 7-14 d. Probenecid, zidovudine, or cimetidine coadministration prolongs half-life and increases CNS toxicity of valacyclovir. Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress.
Fluconazole may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications. It is not recommended for breastfeeding mothers. Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents. Fluconazole is a pregnancy category C drug.
Antiviral agents
Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.
Acyclovir (Zovirax) is a prodrug activated by phosphorylation by virus-specific thymidine kinase that inhibits viral replication. Guanylate kinase converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication. It has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. It inhibits activity of both HSV-1 and HSV-2. Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h from rash onset. It may prevent recurrent outbreaks. Early initiation of therapy is imperative. The adult dosage is 400 mg PO 5 times/day for 7 days. Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir. Caution in renal failure or when using nephrotoxic drugs. Acyclovir is a pregnancy category B drug.
Valacyclovir (Valtrex) is a prodrug rapidly converted to the active drug acyclovir. It is more expensive than acyclovir but has a more convenient dosing regimen. The adult dosage is 500 mg PO bid for 5-10 days. ACE inhibitors, cyclosporin, and potassium-sparing diuretics cause increased risk of hyperkalemia. Caution in renal failure (decrease dose) and coadministration of nephrotoxic drugs; it is associated with onset of hemolytic uremic syndrome. Valacyclovir is a pregnancy category B drug.
Valganciclovir (Valcyte) is an L-valyl ester prodrug of ganciclovir used for cytomegalovirus (CMV) disease prophylaxis in various solid organ transplants. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Viral activity is halted due to inhibition of viral DNA synthesis. It has the advantage of qd or bid PO administration. It achieves serum levels comparable to those obtained with IV ganciclovir. The adult dosage is 450 mg PO bid for 21 d. Contraindications include severe renal dysfunction or hemodialysis; pregnancy; breastfeeding; or an absolute neutrophil count < 500 cells/µL, a platelet count of < 25,000/µL, or hemoglobin level of < 8 g/dL.
Interactions with valganciclovir are similar to those reported with ganciclovir. Coadministration with cytotoxic drugs such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity of rapidly dividing cell populations including bone marrow, spermatogonia, germinal layers of skin and GI mucosa (coadminister only if benefits outweigh risks).
Coadministration with imipenem-cilastatin may cause generalized seizures (use only if benefits outweigh risks). Serum creatinine levels may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B. In presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir. Bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in the presence of ganciclovir.
Strict adherence to dosage guidelines of valganciclovir is essential to avoid overdose. Valganciclovir tablets may not be substituted for ganciclovir capsules on one-to-one basis; adjust dose according to CrCl in impaired renal function. Valganciclovir may cause granulocytopenia, anemia and thrombocytopenia. It is not indicated for CMV disease prevention in liver transplantation (higher CMV disease incidence in liver transplantation compared to prophylaxis with ganciclovir). Valganciclovir is a pregnancy category C drug.
Anthelmintic
Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.
Praziquantel (Biltricide) increases cell membrane permeability in susceptible worms, resulting in loss of intracellular calcium, massive contractions, and paralysis of musculature. In addition, it produces vacuolization and disintegration of schistosome tegument. This is followed by attachment of phagocytes to parasite and death. Tablets should be swallowed whole with some liquid during meals. Keeping tablets in mouth may reveal bitter taste, which can produce nausea or vomiting. The adult dosage is 40 mg/kg PO bid for 1 day. Ocular cysticercosis is a contraindication. Hydantoins may reduce serum praziquantel concentrations, possibly leading to treatment failures.
Destruction of parasite within eyes can cause irreparable lesions (ocular cysticercosis should not be treated with praziquantel). Caution while driving or performing other tasks requiring alertness on the day of and following treatment. Minimal increases in liver enzymes have been reported. When schistosomiasis or fluke infection is associated with cerebral cysticercosis, hospitalize the patient for duration of treatment. Praziquantel is a pregnancy category B drug.
Antidote
These agents counteract the toxic effects of drugs.
Mesna (Mesnex): In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. It inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. The adult dosage is 240 mg IV at 0, 4, 8 h after ifosfamide dose. It may increase warfarin effects. Mesna does not prevent hemorrhagic cystitis in all patients (monitoring for hematuria in the morning prior to ifosfamide or cyclophosphamide dose required). It does not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide. Common adverse effects include hypotension, headache, GI toxicity, and limb pain. Mesna is a pregnancy category B drug.
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Doxycycline (Bio-Tab, Doryx, Doxy, Periostat, Vibramycin, Vibra-Tabs) is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. The adult dosage is 100 mg PO bid. Severe hepatic dysfunction is a contraindication.
The bioavailability of doxycycline decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate. Tetracyclines can increase hypoprothrombinemic effects of anticoagulants and can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy. Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment. Reduce dose in renal impairment. Consider drug serum level determinations in prolonged therapy. Tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can permanently discolor teeth. Fanconi-like syndrome may occur with outdated tetracyclines. Doxycycline is a pregnancy category D drug.
Azithromycin (Zithromax) acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. It concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. It is used to treat mild-to-moderate microbial infections. The adult dosage is 1 g PO once.
Contraindications to azithromycin use include hepatic impairment. Do not administer with pimozide. Azithromycin may increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids. Nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine. Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use. It may increase hepatic enzymes and cholestatic jaundice. Caution in patients with impaired hepatic function or prolonged QT intervals. Azithromycin is a pregnancy category B drug.
Ofloxacin (Floxin) penetrates the prostate well and is effective against N gonorrhea and C trachomatis. It is a pyridine carboxylic acid derivative with broad spectrum bactericidal effect. The adult dosage is 300 mg PO bid for 7 d. Antacids, iron salts, and zinc salts may reduce serum levels. Administer antacids 2-4 h before or after taking fluoroquinolones. Cimetidine may interfere with metabolism of fluoroquinolones. Ciprofloxacin reduces therapeutic effects of phenytoin. Probenecid may increase ciprofloxacin serum concentrations. Ofloxacin may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels) and may increase effects of anticoagulants (monitor PT). In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic). Adjust dose in renal function impairment. Superinfections may occur with prolonged or repeated antibiotic therapy. Ofloxacin is a pregnancy category C drug.
Surgical treatment is rarely needed for nonbacterial cystitis. Most infectious etiologies are treated with systemic and, in some cases, local pharmacotherapy. If bladder outlet obstruction is suspected in the setting of severe funguria, a Foley catheter or suprapubic tube can be placed. After resolution of the infection, benign prostatic hyperplasia should be managed surgically.
Surgery is rarely needed to treat tuberculosis of the genitourinary system. When surgery is necessary, complex reconstruction is often required.
Schistosomiasis should be treated first with medical management, with surgery reserved for cases that do not respond to medical therapy or for patients with intractable gross hematuria. Obstructive uropathy due to ureteral strictures is the most common sequela. Ureteral stricture is managed based on the stricture length and location. Deep nonhealing bladder ulcers may require partial cystectomy, while biopsy-proven bladder cancer often requires radical cystectomy.
For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center, Women's Health Center, and Procedures Center. Also, see eMedicine's patient education articles Bladder Control Problems, Blood in the Urine, Cystoscopy, and Pain During Intercourse.
Many of the medications mentioned above have adverse effects. Some have been mentioned in the Treatment section. In this section, some other common adverse effects are listed.
Hepatic toxicity can be caused by many of the antituberculosis medications, including INH, RIF, pyrazinamide (PZA), and ETH. INH is metabolized primarily by acetylation; approximately 50% of whites and African Americans are slow acetylators, which can lead to higher blood levels and increased toxicity. Hepatocellular dysfunction severe enough to require changing regimens may occur in 3-5% of patients. Alcohol use increases the risk of INH-related hepatitis. The risk of developing fatal hepatitis increases with increasing age, from approximately 0 of 1000 patients younger than 20 years to 23 of 100 patients aged 50-64 years.
RIF induces cytochrome P450 metabolizing enzymes. Patients taking other medications (eg, anticonvulsants, antiarrhythmics, azole antifungal agents, calcium channel blockers, some antibiotics, anticoagulants) metabolized by these enzymes may have significant lowering of drug levels because of increased metabolic rates.
Cyclophosphamide use is associated with an increased risk for secondary leukemias and bladder cancer and may cause infertility in patients of reproductive age.
Intravenous dosing of amphotericin B usually requires pretreatment of the patient with Tylenol and Benadryl to minimize the fevers, chills, or allergic symptoms. Amphotericin B treatment often causes diarrhea (30%), electrolyte abnormalities (15-30%), elevations in liver enzymes (10-20%), and renal disease (20-40%). Intravesical instillation of amphotericin B is much better tolerated than intravenous infusion.
Radiation toxicity
Radiation of living tissues increases the risk of damage to the matrix and the cellular components and to DNA. The effect is dose and tissue dependent. Doses greater than 65 Gy have been associated with late bladder problems. Inability to adequately shield the surrounding tissues can lead to bladder and bowel complications after prostate or cervical radiation, including bleeding, scarring, and pain in 5-20% of patients. In one retrospective review of radiation treatment for prostate cancer, impotence was a common problem.[36]
Infectious causes of nonbacterial cystitis, such as HSV-1 or HSV-2, can now be treated; however, the treatment does not eliminate the dormant virus integrated into the host genome, so the disease can recur.
Both chlamydial and mycobacterial infections can be cured. For chlamydial disease, cure is not protective and the disease can be reacquired. In addition, while mycobacterial infections can generally be cured with regimens containing 3 or 4 drugs, in the review by Mnif et al of 60 cases of urogenital tuberculosis, only 2 were cured by medical therapy alone.[37] Fifty-four patients required surgical intervention, including nephrectomy (43), ureterovesical reimplantation (7), augmentation enterocystoplasty (11), or other ureteral diversions (5). Two patients whose medical and nutritional status was poor to begin with died despite aggressive therapy.
Fungal infections are usually curable, depending on the underlying health status of the patient. Because patients with severe immunosuppression (eg, those with untreatable malignancies, AIDS, poorly-controlled diabetes, transplant patients) are the ones most likely to develop these infections, some patients may require continued treatment to ensure that the infection does not recur.
Noninfectious etiologies
Radiation cystitis, when it does occur, is usually mild and does not require specific therapy.[36] The incidence of bleeding, scarring, and/or obstruction increases over time, and symptoms may occur for the first time many years after the radiation treatment. Some patients with heavy bleeding, strictures, or obstruction may require urinary diversion surgery for symptom relief.[38]
Chemical cystitis due to chemotherapy agents is generally mild, with no long-term consequences, and stops when the medications are stopped.
No known cures exist for autoimmune disease–associated cystitis, but symptoms can often be controlled with anti-inflammatory agents or corticosteroids.
Eosinophilic cystitis often recurs despite resection of the lesion and anti-inflammatory treatments, so long-term follow-up is required.[12]
Interstitial cystitis
Interstitial cystitis is probably the most difficult disease to treat. The symptoms of many patients can be ameliorated, although not completely eradicated, with medical treatment and a combined modality therapy program.
Relief of symptoms in the highly selected subset of patients who undergo surgery has been reported to be 60-90% for supra-trigonal cystectomy and more variable for total cystectomy. Some patients have continued pain despite total cystourethrectomy, emphasizing the poorly understood nature of the disease.
Many controversies exist in nonbacterial cystitis, including possible etiologic agents, methods of diagnosis, and treatment, especially for noninfectious causes.
The National Institutes of Health (NIH) has sponsored research on the topic of nonbacterial cystitis, and several organizations are devoted to helping patients with nonbacterial cystitis (particularly interstitial cystitis) and promoting research.
Advances in understanding the pathophysiology of complex pain syndromes have demonstrated growth of bridging neurons in the dorsal horns of the spinal cord between the type C pain fibers and the type A pain fibers, indicating perception of pain started by stimulus that is usually nonpainful. Another example of neural cross-talk in rats is an experiment that demonstrated increased muscle spasm in the bladder with colonic irritation and in the colon with bladder irritation, perhaps helping to explain the concomitant occurrences of irritable bowel syndrome, pelvic pain syndrome, and interstitial cystitis.
Other anti-inflammatory agents are also under investigation, such as IPD-1151T, an immunoregulatory agent that suppresses T cell–mediated cytokines responsible for IgE production and eosinophilia, as well as IL-4 and IL-5.
Some kinds of infectious, recurrent, nonbacterial cystitis are being treated with transfer factor (TF) specific for the kind of infection (Candida, herpes). De Vinci and associates demonstrated a marked decrease in the number of recurrences (P < 0.001) in females treated with TF for this disorder.[39]
More information about interstitial cystitis and support information for patients can be obtained from the following associations:
Interstitial Cystitis Association
51 Monroe St. Suite 1402
Rockville, MD 20580
Telephone toll-free: 1-800-help ICA
Email: ICAmail@ichelp.com
WWW.ichelp.org
American Foundation for Urologic Disease, Inc.
300 West Pratt St. Suite 401
Baltimore, MD 21201
Telephone toll-free: 1-800-242-2383
The following is a Web site about interstitial cystitis: HealthlinkUSA
Patient materials and links (a urologic opinion of interstitial cystitis) can be found at the following:
Cystitis Support Group - United Kingdom
Interstitial Cystitis Network
The Interstitial Cystitis Network is a large archive of information on the Web for interstitial cystitis, including patient materials, a research library, and physician referrals.
The NIH maintains a patient information site for Interstitial Cystitis.
Urology Channel is another good source of general health information about urological subjects with a nice review of interstitial cystitis.
Lynda A Frassetto, MD, Clinical Professor, Department of Internal Medicine, University of California at San Francisco School of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Benjamin N Breyer, MD, Clinical Instructor, Department of Urology, University of California, San Francisco Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Erik T Goluboff, MD, Professor, Department of Urology, College of Physicians and Surgeons, Columbia University; Director of Urology, Allen Pavilion, New York Presbyterian Hospital
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
J Stuart Wolf Jr, MD, FACS, The David A Bloom Professor of Urology, Director, Division of Endourology and Stone Disease, Department of Urology, University of Michigan Medical School
Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching
Held PJ, Hanno PA, Wein AJ, et al. Epidemiology of interstitial cystitis. In: Hanno PM, et al, eds. Interstitial Cystitis. London: Springer-Verlag; 1990:29-30.
La Rock DR, Sant GR. Intravesical therapies for interstitial cystitis. In: Sant GR, ed. Interstitial Cystitis. Philadelphia, Pa: Lippincott-Raven; 1997:247-54.
Shanberg AM, Malloy T. Use of lasers in interstitial cystitis. In: Sant GR, ed. Interstitial Cystitis. Philadelphia, Pa: Lippincott-Raven; 1997:215-17.
Gross pathology, bladder with candidal infection and hemorrhage.
Infiltration of yeast in the bladder wall.
Schistosomiasis of the ureter.
Gross anatomy of the female pelvis.
Gross anatomy of the bladder.
Female perineal anatomy. The urogenital diaphragm and levator ani muscles have been removed, revealing the internal pudendal nerves and vessels, the rectum, and the posterior vaginal wall.
Gross anatomy of the female pelvis.
Gross anatomy of the bladder.
Female perineal anatomy. The urogenital diaphragm and levator ani muscles have been removed, revealing the internal pudendal nerves and vessels, the rectum, and the posterior vaginal wall.
Schistosomiasis of the ureter.
Gross pathology, bladder with candidal infection and hemorrhage.
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