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Nonbacterial and Noninfectious Cystitis Workup

  • Author: Lynda A Frassetto, MD; Chief Editor: Edward David Kim, MD, FACS  more...
Updated: Apr 28, 2015

Approach Considerations

Infectious etiologies


Viral infections are often difficult to diagnose, and viral culture results can be falsely negative. Some viruses can be detected by polymerase chain reaction (PCR) assay or by detection of antibodies to the virus. Also, Chlamydia can 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 assay. Of all of these tests, PCR assay is probably the most reliable.[21]


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 10mm develops at the injection site within 48-72 hours. 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 carbolfuchsin 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 assay. In a study by Moussa et al, the sensitivity of acid-fast bacilli (AFB) staining was 52% versus 96% for PCR assay, when compared with cultures.[22]

Intravenous urography remains the primary imaging modality for mycobacterial cystitis, although ultrasonography, computed tomography (CT) scanning, or magnetic resonance imaging (MRI) may also be used. However, all imaging findings may be normal in early disease. For more information, see the Medscape Reference article Imaging of Tuberculosis in the Genitourinary Tract.

Other infections

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.[23] Some fungi, such as Candida species, grow on many media, while others, such as Blastomyces dermatitidis, require specialized culture techniques. Deoxyribonucleic acid (DNA) probes for detection of numerous fungal infections by PCR assay are also available.[24]

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 assays 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 urinary tract infections 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. Cystoscopy with biopsy is the criterion standard for diagnosing eosinophilic cystitis.[3] Some patients may also have peripheral eosinophilia.

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.

Serologic tests likely to be positive in patients with systemic lupus erythematosus (SLE) include low C3, anti–double stranded (ds) DNA, anti-Smith (Sm), and antiribonucleoprotein (anti-RNP) antibodies. In patients with SLE and bladder involvement, abdominal CT scanning may demonstrate thickening of the bladder wall, hydronephrosis, ascites, and bowel-wall thickening.[25]

Biopsy of other affected organs may show vasculitis. Tests likely to have positive results in patients with Sj ö gren 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.

Contributor Information and Disclosures

Lynda A Frassetto, MD Clinical Professor, Department of Internal Medicine, University of California, San Francisco, School of Medicine

Lynda A Frassetto, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.


Benjamin Newell Breyer, MD, MS Assistant Professor, Trauma and Reconstruction, Department of Urology, University of California, San Francisco, School of Medicine

Benjamin Newell Breyer, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

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, Tennessee Medical Association, Sexual Medicine Society of North America, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Repros.


Erik T Goluboff, MD Professor, Department of Urology, College of Physicians and Surgeons, Columbia University College of Physicians and Surgeons; 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.

Stephen W Leslie, MD, FACS Founder and Medical Director, Lorain Kidney Stone Research Center; Associate Professor of Surgery at Creighton University School of Medicine, Chief of Urology at Creighton University Medical Center

Stephen W Leslie, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, National Kidney Foundation, and Ohio State Medical Association

Disclosure: Nothing to disclose.

Grannum R Sant, MD Residency Program Director, Charles M Whitney Professor and Chairman, Department of Urology, Tufts University School of Medicine

Grannum R Sant, MD is a member of the following medical societies: American Urological Association, International Association for the Study of Pain, Massachusetts Medical Society, Society for Basic Urologic Research, and Society of University Urologists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Gross pathology of the bladder with candidal infection and hemorrhage.
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.
Infiltration of yeast in the bladder wall.
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