Nonbacterial and Noninfectious Cystitis Workup

Updated: Jul 29, 2021
  • Author: Lynda A Frassetto, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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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. [29]

While immunocompetent individuals also periodically shed BKV in urine, detection of urinary viral loads of 106 to 107 copies/ml and BK viremia of >104 copies/ml is associated with a higher risk of HC in transplant recipients. [6]  


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. 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 a polymerase chain reaction (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. [30]

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 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. [31] 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. [32]

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. [5] 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. [33]

Biopsy of other 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.