eMedicine Specialties > Urology > Infections and Related Inflammatory Conditions

Cystitis, Nonbacterial

Author: Lynda A Frassetto, MD, Associate Clinical Professor, Department of Internal Medicine, University of California at San Francisco School of Medicine
Coauthor(s): Donna Y Deng, MD, Assistant Professor of Urology, Pelvic Reconstruction, Incontinence, and Neurourology, Department of Urology, University of California San Francisco School of Medicine
Contributor Information and Disclosures

Updated: Dec 12, 2008

Introduction

Nonbacterial cystitis is currently a catchall term that comprises various medical disorders, including nonbacterial infectious (viral, mycobacterial, chlamydial, fungal) and noninfectious (radiation, chemical, autoimmune, hypersensitivity) cystitis, as well as interstitial cystitis. This terminology has been recently updated to 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. The phrase interstitial cystitis is now reserved for cases that involve symptoms of PBS/IC and the classic cystoscopic and histologic findings.

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. If the diagnosis is interstitial cystitis (PBS/IC), treatment can be difficult and unrewarding. In recent years, recognition of the different possible causes of nonbacterial cystitis has allowed a more coherent approach to the diagnosis and treatment of this challenging entity.

Problem

Painful bladder syndrome/interstitial cystitis

No universal agreement about the definition of PBS/IC exists. In an effort to study this problem, a consensus panel at the National Institutes for Diabetes, Digestive, and Kidney Diseases (NIDDK) developed a list of inclusion criteria in 1987 to define persons with interstitial cystitis (PBS/IC), primarily to establish a standardized diagnostic parameter for research purposes.

The NIDDK criteria for interstitial cystitis require the exclusion of many other diagnoses, including infectious and malignant diseases and toxic exposures. The initial list required the presence of glomerulations or Hunner ulcers on cystoscopic examination and bladder pain or urgency. The presence of any one of the following excludes the diagnosis of interstitial cystitis for study purposes:

  • Bladder capacity greater than 350 mL on awake cystometry, using either gas or liquid as a filling medium
  • Absence of an intense urge to void with the bladder filled to 100 mL of gas or 150 mL of water during cystometry, using a fill rate of 30-100 mL/min
  • Demonstration of phasic involuntary bladder contractions on cystometry, using the fill rate of 30-100 mL/min
  • Duration of symptoms less than 9 months
  • Absence of nocturia
  • Symptoms relieved by antimicrobials, urinary antiseptics, anticholinergics, or antispasmodics (musculotropic relaxants)
  • Frequency of urination, while awake, less than 8 times per day
  • Diagnosis of bacterial cystitis or prostatitis within a 3-month period
  • Bladder or lower-ureteral calculi
  • Active genital herpes
  • Uterine, cervical, vaginal, or urethral cancer
  • Urethral diverticula
  • Cyclophosphamide or any type of chemical cystitis
  • Tuberculous cystitis
  • Radiation cystitis
  • Benign or malignant bladder tumors
  • Vaginitis
  • Age younger than 18 years

Many physicians who treat interstitial cystitis (PBS/IC) consider this list too rigid and exclusive. For example, not all experts consider cystoscopy to be a required diagnostic tool for interstitial cystitis in clinical practice. They argue that, once urine tests, such as cytology and cultures, have been used to screen for bladder cancer and infections, symptomatic patients who fail to respond well to simple medical therapies (eg, anticholinergic medications) should probably be treated for interstitial cystitis. Cystoscopy with hydrodistention requires general or spinal anesthesia because the characteristic glomerulations of interstitial cystitis are visible only after the bladder is hydrodistended (pressurized usually to 80-100 cm water pressure), which would be unacceptably painful without the anesthetic.

In a study by Denson and colleagues that compared the cystoscopic findings with histologic evidence of inflammation in patients suspected of having interstitial cystitis, 6 (9%) patients had no cystoscopic evidence of disease and 21 (30%) had no tissue inflammation. In this study, only one patient had a classic Hunner ulcer.1

Frequency

Infectious 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 Chlamydia 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.

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.2

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.3

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.4 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.5 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.

Recently, 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 100,000.6

Etiology

Infectious etiologies

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 infections, such as BK viremia (associated with hemorrhagic cystitis after bone marrow transplant7,8 ) and adenoviral infections.9 Herpes and chlamydial nonbacterial cystitis is sexually transmitted, while other types, such as fungal cystitis, occur mainly in immunocompromised hosts.10,11 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.12

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.13

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.14 Low-dose methotrexate, used to treat rheumatoid arthritis, has also been reported to cause hemorrhagic cystitis.15

Painful bladder syndrome/interstitial cystitis

The etiology of PBS/IC is unknown. Although first described as a pathologic condition in 1887, it was not recognized as a disorder until the mid 1970s. Before then, patients with PBS/IC were often labeled hysterical females because physicians could find no organic cause and because most cases involved women. Currently, PBS/IC is not believed to be a disease but rather 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.

In a study of 231 patients with PBS/IC and 41 healthy subjects, Parsons and associates demonstrated that infusing 50 mL water into the bladders of both healthy subjects and those with interstitial cystitis produced no reaction.17 Infusing 50 mL of a 0.4 M KCl solution triggered symptoms in 75% of subjects with interstitial cystitis, but only 4% of healthy subjects experienced symptoms (P <.01).

However, in a 1999 study by Chambers et al in 39 consecutive patients treated in urology clinic for evaluation of symptoms consistent with interstitial cystitis, the potassium leak test demonstrated a sensitivity of only 69.5% and a specificity of 50%.18 These authors concluded that the test is not a useful diagnostic tool because physicians would not be able to diagnose the disease using the test in half of the cases and endoscopic diagnosis according to the stricter NIDDK criteria was more useful. This issue remains unresolved. In the authors' practice, the potassium leak test is at least occasionally useful in helping direct therapy in selected patients.

In the potassium leak test, the subjects are blinded to which solution contains the potassium; the result is positive if the subject rates the pain after potassium solution infusion at 2 or more points higher (on a scale of 1-5) than after sterile water instillation. Instillations are performed via Foley catheters.

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.19

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.20

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.

Pathophysiology

Infectious cystitis

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. Adenovirus and BK polyoma 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.

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,2 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.13

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.

Presentation

Infectious etiologies

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.11

Clinical features of fungal infections can range from asymptomatic urinary tract colonization (the most common finding), to cystitis, pyelonephritis, or even sepsis with fungemia.21 In rare cases, candidal infections also can cause pneumaturia.22

Infection with chlamydial organisms may or may not produce symptoms but may have an associated mucopurulent cervical or urethral discharge.

Infections with tuberculosis often have 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.23 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.24 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.25

Eosinophilic cystitis often causes frequency, hematuria, dysuria, and suprapubic pain.13

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.4

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.26 However, as many as half the patients reported spontaneous remission of symptoms lasting an average of 8 months (range, 1-80 mo).

No clear genetic component for interstitial cystitis has been described, but 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.27 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.

Diagnosis of interstitial cystitis

The strict NIDDK standard for the diagnosis of interstitial cystitis requires exclusion of many other diagnoses, including bladder infections; bladder or gynecologic tumors or cancer; kidney or bladder stones; vaginitis; endometriosis; sexually transmitted diseases; tuberculous, radiation, or chemical cystitis; and prostatitis. This standard was intended for research purposes and is generally considered too strict and rigorous for routine clinical practice.

Clinical diagnosis of interstitial cystitis

There is no single correct way to diagnose interstitial cystitis. Many specialists begin the patient evaluation with an extensive history to understand which organ systems are involved, followed by a physical examination directed toward the involved organ systems. Abdominal, genital, and rectal examinations may help localize specific areas of pathology. Basic urinary laboratory tests are also performed.

Important inclusion criteria on history include the following:

  • Pelvic or bladder pain
  • Urinary frequency while awake more than 8 times per day
  • Nocturia
  • Duration of symptoms longer than 9 months

Important exclusion criteria by history include the following:

  • Frequency, urgency, or mild incontinence without suprapubic pain that is easily controlled with anticholinergics
  • Prior radiation therapy
  • Prior administration of chemicals such as cyclophosphamide
  • Diagnosis of tuberculosis or other active infection

Important exclusion criteria by physical examination include the following:

  • Active genital herpes
  • Vaginal discharge
  • Mass lesions
  • Prostatic tenderness
  • Urethral discharge

Clinical pearls in the diagnosis of interstitial cystitis include the following:

  • A bladder capacity of more than 350 mL in a person who is awake excludes interstitial cystitis as the diagnosis. (Under general anesthesia, bladder capacity can be higher, even in interstitial cystitis.)
  • Interstitial cystitis is almost always associated with pain (other than possibly due to spasm).
  • Although interstitial cystitis may be associated with significant frequency and urgency, it almost never causes urge incontinence.
  • Interstitial cystitis is usually uncontrolled with a single anticholinergic medication (eg, tolterodine [Detrol], oxybutynin [Ditropan]). On the other hand, if a condition is adequately managed this way, it is very unlikely ever to be diagnosed as interstitial cystitis unless it progresses.
  • Urethritis and urethral syndrome may be relatively mild forms of interstitial cystitis.
  • In men, what appears to be nonbacterial prostatitis or chronic pelvic pain syndrome may actually be interstitial cystitis in some cases, especially in cases resistant to standard therapy.
  • The goal of diagnostic testing in interstitial cystitis is not to actually establish the diagnosis as much as it is to exclude other explanations and etiologies.
  • Interstitial cystitis is not a curable disorder, and no purely evidence-based treatment strategy is currently available. Therapy decisions must be individualized based on patient preference, expected compliance, and trial and error.
  • Combining the available treatment modalities of behavioral techniques (dietary modifications and biofeedback), oral drug therapy (eg, pentosan polysulfate [Elmiron], amitriptyline [Elavil], hydroxyzine [Atarax], various anticholinergics), hydrodistention under anesthesia, and intravesical instillations with heparin or dimethyl sulfoxide (DMSO) would seem to offer the most potential for palliation of symptoms.

Relevant Anatomy

Images 1-3 demonstrate the anatomy of the female pelvis and bladder and the muscles of the pelvic floor that may be involved in nonbacterial cystitis.

Contraindications

Also see the Treatment section for indications and contraindications for surgery for specific problems.

Surgery is rarely indicated for nonbacterial cystitis caused by infectious diseases. Tuberculous cystitis is one possible exception, but only when medical treatment has failed.

Radiation cystitis may cause bleeding that is massive enough to require surgery, but this is also unusual. Most bleeding episodes stop without treatment or with a combination of bladder irrigation and blood transfusion support.

For interstitial cystitis, surgery is considered the treatment of last resort. Less than 10% of patients are considered candidates for surgical treatment, and then only if multiple medical therapies have failed. Patients with poorly localized or diffuse pelvic pain may not be cured even by removal of the affected organs, emphasizing the poorly understood neurologic and psychiatric components of interstitial cystitis.

More on Cystitis, Nonbacterial

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References
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References

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Further Reading

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Keywords

nonbacterial cystitis, interstitial cystitis, IC, noninfectious cystitis, urgency-frequency syndrome, chemical cystitis, radiation cystitis, autoimmune cystitis, viral cystitis, mycobacterial cystitis, chlamydial cystitis, fungal cystitis, hypersensitivity cystitis, nonbacterial infectious cystitis, potassium leak test, chronic pelvic pain syndrome, painful bladder syndrome, PBS, infectious cystitis, tuberculous cystitis, eosinophilic cystitis

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Contributor Information and Disclosures

Author

Lynda A Frassetto, MD, Associate Clinical Professor, Department of Internal Medicine, University of California at San Francisco School of Medicine
Lynda A Frassetto, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology
Disclosure: Nothing to disclose.

Coauthor(s)

Donna Y Deng, MD, Assistant Professor of Urology, Pelvic Reconstruction, Incontinence, and Neurourology, Department of Urology, University of California San Francisco School of Medicine
Donna Y Deng, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, California Medical Association, International Continence Society, Société Internationale d'Urologie (International Society of Urology), and Society of Women in Urology
Disclosure: Nothing to disclose.

Medical Editor

Erik T Goluboff, MD, Professor, Department of Urology, College of Physicians and Surgeons, Columbia University; Director of Urology, Allen Pavilion, New York Presbyterian Hospital
Erik T Goluboff, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Urological Association, Medical Society of the State of New York, New York Academy of Medicine, Phi Beta Kappa, and Society for Basic Urologic Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

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
Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association
Disclosure: Lilly Consulting fee Consulting; Astellas Consulting fee Speaking and teaching; Indevus Consulting fee Speaking and teaching

 
 
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