Nonbacterial and Noninfectious Cystitis Workup
- Author: Lynda A Frassetto, MD; Chief Editor: Edward David Kim, MD, FACS more...
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.
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.
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.
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. 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.
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.
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. 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.
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.
Pezzone MA, Liang R, Fraser MO. A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology. 2005 Jun. 128(7):1953-64. [Medline].
Perez CA, Lee HK, Georgiou A, Lockett MA. Technical factors affecting morbidity in definitive irradiation for localized carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 1994 Mar 1. 28(4):811-9. [Medline].
Teegavarapu PS, Sahai A, Chandra A, Dasgupta P, Khan MS. Eosinophilic cystitis and its management. Int J Clin Pract. 2005 Mar. 59(3):356-60. [Medline].
Sharma BN, Li R, Bernhoff E, et al. Fluoroquinolones inhibit human polyomavirus BK (BKV) replication in primary human kidney cells. Antiviral Res. 2011 Oct. 92(1):115-23. [Medline].
Boeckh M, Erard V, Zerr D, Englund J. Emerging viral infections after hematopoietic cell transplantation. Pediatr Transplant. 2005 Dec. 9 Suppl 7:48-54. [Medline].
Fioriti D, Degener AM, Mischitelli M, Videtta M, Arancio A, Sica S, et al. BKV infection and hemorrhagic cystitis after allogeneic bone marrow transplant. Int J Immunopathol Pharmacol. 2005 Apr-Jun. 18(2):309-16. [Medline].
Carrigan DR. Adenovirus infections in immunocompromised patients. Am J Med. 1997 Mar 17. 102(3A):71-4. [Medline].
Bavastrelli M, Midulla M, Rossi D, Salzano M, Calzolari E, Midulla C, et al. Sexually active adolescents and young adults: a high-risk group for Chlamydia trachomatis infection. J Travel Med. 1998 Jun. 5(2):57-60. [Medline].
Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000 Mar 23. 342(12):844-50. [Medline].
Pierciaccante A, Pompeo ME, Fabi F, Venditti M. Successful treatment of Corynebacterium urealyticum encrusted cystitis: a case report and literature review. Infez Med. 2007 Mar. 15(1):56-8. [Medline].
Martin-Suarez I, D'Cruz D, Mansoor M, Fernandes AP, Khamashta MA, Hughes GR. Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann Rheum Dis. 1997 Aug. 56(8):481-7. [Medline]. [Full Text].
Kawabe Y, Eguchi K, Tsuboi M, Kita M, Tsukada T, Takashima H, et al. [Untoward effects of low dose methotrexate therapy in rheumatoid arthritis]. Ryumachi. 1996 Jun. 36(3):514-21. [Medline].
Chu PS, Ma WK, Wong SC, Chu RW, Cheng CH, Wong S, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome?. BJU Int. 2008 Dec. 102(11):1616-22. [Medline].
Kauffman CA. Diagnosis and management of fungal urinary tract infection. Infect Dis Clin North Am. 2014 Mar. 28(1):61-74. [Medline].
Barsoum RS. Schistosomiasis and the kidney. Semin Nephrol. 2003 Jan. 23(1):34-41. [Medline].
Haarala M, Alanen A, Hietarinta M, Kiilholma P. Lower urinary tract symptoms in patients with Sjögren's syndrome and systemic lupus erythematosus. Int Urogynecol J Pelvic Floor Dysfunct. 2000. 11(2):84-6. [Medline].
Mnif A, Loussaief H, Ben Hassine L, Chebil M, Ayed M. [Aspects of evolving urogenital tuberculosis. 60 cases]. Ann Urol (Paris). 1998. 32(5):283-9. [Medline].
Beard CJ, Lamb C, Buswell L, Schneider L, Propert KJ, Gladstone D, et al. Radiation-associated morbidity in patients undergoing small-field external beam irradiation for prostate cancer. Int J Radiat Oncol Biol Phys. 1998 May 1. 41(2):257-62. [Medline].
Levenback C, Eifel PJ, Burke TW, Morris M, Gershenson DM. Hemorrhagic cystitis following radiotherapy for stage Ib cancer of the cervix. Gynecol Oncol. 1994 Nov. 55(2):206-10. [Medline].
Wagenlehner FM, van Till JW, Magri V, Perletti G, Houbiers JG, Weidner W, et al. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) symptom evaluation in multinational cohorts of patients with chronic prostatitis/chronic pelvic pain syndrome. Eur Urol. 2013 May. 63(5):953-9. [Medline].
Shurbaji MS, Dumler JS, Gage WR, Pettis GL, Gupta PK, Kuhadja FP. Immunohistochemical detection of chlamydial antigens in association with cystitis. Am J Clin Pathol. 1990 Mar. 93(3):363-6. [Medline].
Moussa OM, Eraky I, El-Far MA, Osman HG, Ghoneim MA. Rapid diagnosis of genitourinary tuberculosis by polymerase chain reaction and non-radioactive DNA hybridization. J Urol. 2000 Aug. 164(2):584-8. [Medline].
Etienne M, Caron F. [Management of fungal urinary tract infections]. Presse Med. 2007 Dec. 36(12 Pt 3):1899-906. [Medline].
Min JK, Byun JY, Lee SH, Hong YS, Park SH, Cho CS, et al. Urinary bladder involvement in patients with systemic lupus erythematosus: with review of the literature. Korean J Intern Med. 2000 Jan. 15(1):42-50. [Medline].
De Vinci C, Pizza G, Cuzzocrea D, Menniti D, Aiello E, Maver P, et al. Use of transfer factor for the treatment of recurrent non-bacterial female cystitis (NBRC): a preliminary report. Biotherapy. 1996. 9(1-3):133-8. [Medline].
Egli A, Binggeli S, Bodaghi S, Dumoulin A, Funk GA, Khanna N, et al. Cytomegalovirus and polyomavirus BK posttransplant. Nephrol Dial Transplant. 2007 Sep. 22 Suppl 8:viii72-viii82. [Medline].
Xu HG, Fang JP, Huang SL, Zhou DH, Chen C, Huang K, et al. [Risk factors and treatment of hemorrhagic cystitis in children after hematopoietic stem cell transplantation]. Zhonghua Er Ke Za Zhi. 2006 Feb. 44(2):126-30. [Medline].
Mott KE, Dixon H, Osei-Tutu E, England EC, Davis A. Effect of praziquantel on hematuria and proteinuria in urinary schistosomiasis. Am J Trop Med Hyg. 1985 Nov. 34(6):1119-26. [Medline].
Sommariva ML, Sandri SD, Ceriani V. Efficacy of sodium hyaluronate in the management of chemical and radiation cystitis. Minerva Urol Nefrol. 2010 Jun. 62(2):145-50. [Medline].
Allen S, Kilian C, Phelps J, et al. The use of hyperbaric oxygen for treating delayed radiation injuries in gynecologic malignancies: a review of literature and report of radiation injury incidence. Support Care Cancer. 2012 Jan 14. [Medline].
Del Pizzo JJ, Chew BH, Jacobs SC, Sklar GN. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: long-term followup. J Urol. 1998 Sep. 160(3 Pt 1):731-3. [Medline].
Chong KT, Hampson NB, Corman JM. Early hyperbaric oxygen therapy improves outcome for radiation-induced hemorrhagic cystitis. Urology. 2005 Apr. 65(4):649-53. [Medline].
Srisupundit S, Kraiphibul P, Sangruchi S, Linasmita V, Chingskol K, Veerasarn V. The efficacy of chemically-stabilized chlorite-matrix (TCDO) in the management of late postradiation cystitis. J Med Assoc Thai. 1999 Aug. 82(8):798-802. [Medline].
Ballen KK, Becker P, Levebvre K, Emmons R, Lee K, Levy W, et al. Safety and cost of hyperhydration for the prevention of hemorrhagic cystitis in bone marrow transplant recipients. Oncology. 1999 Nov. 57(4):287-92. [Medline].