Chirra, Annapoorna

English

eScholarship - University of California

UCLAProceedings of the UCLA Department of MedicineTitlePolyomavirus in Immunocompetent PatientsPermalinkhttps://escholarship.org/uc/item/7d82k7cgJournalProceedings of the UCLA Department of Medicine, 16(1)AuthorChirra, AnnapoornaPublication Date2012-02-28eScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaProceedings of UCLA Healthcare -VOLUME 16 (2012)-   CLINICAL VIGNETTE  Polyomavirus in Immunocompetent Patients  Annapoorna Chirra, M.D., DTMH      Case Report  A 59-year-old Asian female with a history of recently diagnosed type 2 diabetes presented with a four month history of lower abdominal pain  associated with urgency  and dysuria. She noted hourly nocturia with sleep disruption and urge incontinence.  She denied hematuria, fever, chills or flank pain or any history of recent urinary tract infections, back pain, constipation, or radiculopathy. She had already sought care with an urgent care physician and was told that she had a urinary tract infection and was prescribed a seven day course of ciprofloxacin. She noted no improvement with the antibiotics.  Past medical history was significant for hyper-tension, gout, and a remote history of endo-metrial cancer twenty years prior. Her medications included an ace inhibitor, metformin and allopurinol.  Surgical history was notable for TAH BSO. Family history was notable for diabetes and hypertension.   On physical examination she had a temperature of 98.6; blood pressure of 145/85 and heart rate of 75/minute.  She appeared in no acute distress. Notably on the exam was that she had mild pain in the suprapubic area. She had no masses, guarding or rebound. Pelvic exam and vaginal exam was significant for atrophy and anterior vaginal pain. No masses were noted.    Urinalysis was performed and was without leukocytes, protein or hematuria. Culture was negative. Post void residual was 75 cc.  Subsequent ultrasound of the pelvis, ovaries, bladder, kidneys and ureters was without abnormality.  Urine cytology on three specimens was notable for urothelial cell atypia and cells suggesting viral changes consistent with Polyomavirus.  Cystoscopy was performed. The uroepithelium was normal without evidence of      lesions, foreign body, tumors or granulomas. The trigone was slightly hyperemic but no specific lesions were noted.  The ureteral orifices were normal and patent with good ureteral reflux. The bladder capacity was normal.  Bladder irrigation was without evidence of malignant cells however had reactive and atypical uroethelial cells. Subsequent CT of the abdomen/pelvis and urogram was performed without any renal or bladder abnormality. The patient’s renal func-tion, electrolytes, white blood count, hemo-globin, and platelets were all normal. JC Poly-omavirus DNA was noted in urine.  JC Poly-omavirus was not detected in blood and BK Polyomavirus was not detected in either blood or urine.  HIV test was negative. CD counts were normal as was T cell function by lymphocyte mitogen and antigen proliferation assay.    Discussion  Polyomaviruses are nonenveloped viruses with a double stranded DNA. BK virus and JC Polyomavirus are two common Polyomaviruses  that infect humans. Primary infection with BK virus occurs early in childhood, while JC virus seroconversion occurs in adolescence1.  BK virus seroprevalence reaches 98% by 9 years of age, and JC virus  seroprevalence reaches 72% by 25 years of age2. The reason for the difference in the epidemiologic profiles of BK and JC infections is unknown but may be related to differences in the routes of transmission.  A fecal oral route of transmission is suspected in both3. Infection is cell specific in the host. Entry mechanism of Polyomaviruses into cells is only partially known. The pathogenesis of tissue damage in Polyomavirus infected tissues is unknown, but depends on immune status3.    Proceedings of UCLA Healthcare -VOLUME 16 (2012)- The primary infection with the Polyomaviruses are considered to be largely asymptomatic in the immunocompetent.  The BK virus has been implicated in short lived infections such as urinary tract infections and nephritic syndrome4. The virus remains in a latent state most often in the urogenital tract. Viruria occurs in reactivation of the BK virus and is implicated in renal transplant patients causing ureteric stenosis, transient allograft dysfunction, and irreversible graft failure due to tubulointerstitial nephritis5.  JC virus is largely considered an asymptomatic infection in adolescence and adulthood. Reactivation of the JC virus is the causative agent for Progressive Multifocal Leuko-encephalopathy in immunocompromised patients, most commonly in HIV patients.  Isolated JK virus and co-infection with BK virus has been associated with post transplant nephritis6. Notably, JC frequently is excreted in the urine of healthy individuals, and older individuals show a higher viral load7,8. Reactivation of JC virus has been suggested to occur more commonly in diabetes3.  The data to date suggest a possible relationship with Polyomaviruses and malignancy. It has been suggested that Polyomaviruses may serve as co-factors for malignancy9. Malignant transformation due to specific Polyomaviruses has been identified. The presumed causative agent for Merkel cell skin cancer has been linked to the Merkel cell Polyomavirus10.  JC virus role in uroethelial cancers is controversial at this time. One recent small study did not support an involvement of Polyomavirus in transitional bladder cell cancer in immunocompetent individuals11. Shen CH, Wu JD, et al have found a significant association with JK virus and uroethelial cells in a Taiwanese cohort12. BK virus infection after transplantation is known to cause graft failure, but the association with malignancies has been controversial based on a recent study13.    Reactivation of BK and JC viruses with asymptomatic viruria occurs in 10-50% of hematopoietic stem cell and bone marrow transplant recipients and in 30% of renal transplant recipients14. Pathological transfor-mation due to the JC virus is presently being studied in patients using anti-tumor necrosis alpha inhibitors. Although Infliximab treatment did not directly affect JC reactivation in one study, further investigation on host factors regulated by it will be important in understanding the mechanisms that may affect viral persistence with Infliximab or immuno-suppression overall15.  To date it is unclear if the patient had a reactivation of the JK virus causing symptoms or chronic viruria unrelated to her symptoms. One could postulate that she had reactivation related to her diabetes. This patient underwent extensive evaluation based on her chronic and progressive urinary symptoms and abnormal urinary cytology. This is appropriate based on current studies which have demonstrated it is difficult to distinguish benign Polyomavirus infected cells from their malignant counterparts by cytology16.  Additionally, the risk factors for atypia have not been clearly identified and will require further study.   Clinicians should remember that asymptomatic Polyomavirus viruria is common in immunocompetent patients.  In certain circum-stances patients may demonstrate symptoms related to the Polyomavirus.  Additionally, clinicians should be aware that abnormal urine cytology demonstrating Polyomavirus should lead to further evaluation as urine cytology can be misleading. Increased surveillance may be recommended pending further study.   REFERENCES   1. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971 Jun 19;1(7712):1253-7. PubMed PMID: 4104714. 2. Stolt A, Sasnauskas K, Koskela P, Lehtinen M, Dillner J. Seroepidemiology of the human polyomaviruses. J Gen Virol. 2003 Jun;84(Pt 6):1499-504. PubMed PMID:12771419. 3. Erard V, Limaye AP, Boeckh M. Human Polyomavirus.   In: Long S, editor. Principles and Practice of Pediatric Infectious Diseases Revised Reprint. 3rd ed. Maryland Heights;Elsevier Publishing;2009.p. 1058-1062.  4. Saitoh K, Sugae N, Koike N, Akiyama Y, Iwamura Y, Kimura H. Diagnosis of childhood BK virus cystitis by electron microscopy and PCR. J Clin Pathol. 1993 Aug;46(8):773-5. PubMed PMID: 8408709; PubMed Central PMCID: PMC501471. 5. Nickeleit V, Hirsch HH, Binet IF, Gudat F, Prince O, Dalquen P, Thiel G, Mihatsch MJ. Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. J Am Soc Nephrol. 1999 May;10(5):1080-9. PubMed PMID: 10232695. 6. Kazory A, Ducloux D, Chalopin JM, Angonin R, Fontanière B, Moret H. The first case of JC virus   Proceedings of UCLA Healthcare -VOLUME 16 (2012)-   allograft nephropathy. Transplantation. 2003 Dec 15;76(11):1653-5. PubMed PMID: 14702550. 7. Kitamura T, Aso Y, Kuniyoshi N, Hara K, Yogo Y. High incidence of urinary JC virus excretion in nonimmunosuppressed older patients. J Infect Dis. 1990 Jun;161(6):1128-33. PubMed PMID: 2161040.  8. Agostini HT, Ryschkewitsch CF, Stoner GL. Genotype profile of human polyomavirus JC excreted in urine of immunocompetent individuals. J Clin Microbiol. 1996 Jan;34(1):159-64. PubMed PMID: 8748293; PubMed Central PMCID: PMC228750. 9. Harris KF, Chang E, Christensen JB, Imperiale MJ. BK virus as a potential co-factor in human cancer. Dev Biol Stand. 1998;94:81-91. Review. PubMed PMID: 9776229. 10. Schrama D, Ugurel S, Becker JC. Merkel cell carcinoma: recent insights and new treatment options. Curr Opin Oncol. 2012 Mar;24(2):141-9. Review. PubMed PMID: 22234254. 11. Polesel J, Gheit T, Talamini R, Shahzad N, Lenardon O, Sylla B, La Vecchia C, Serraino D, Tommasino M, Franceschi S. Urinary human polyomavirus and papillomavirus infection and bladder cancer risk. Br J Cancer. 2012 Jan 3;106(1):222-6. doi: 10.1038/bjc.2011.519. Epub 2011 Nov 24. PubMed PMID: 22116302; PubMed Central PMCID: PMC3251864. 12. Shen CH, Wu JD, Hsu CD, Jou YC, Lin CT, Wang M, Wu SF, Chan MW, Chiang MK, Fang CY, Chang D. The high incidence of JC virus infection in urothelial carcinoma tissue in Taiwan. J Med Virol. 2011 Dec;83(12):2191-9. doi:10.1002/jmv.22240. PubMed PMID: 22012728. 13. Wang HH, Liu KL, Chu SH, Tian YC, Lai PC, Chiang YJ. BK virus infection in association with posttransplant urothelial carcinoma. Transplant Proc. 2009 Jan-Feb;41(1):165-6. PubMed PMID: 19249504. 14. Storch G. Polyomavirus In:Kliegman R, Standton B, editors. Nelson Textbook of Pediatrics.19th ed. Maryland Heights; Elsevier Publishing;2011.p 1157 15. Giannecchini S, Clausi V, Vultaggio A, Macera L, Maggi F, Martelli F, Azzi A, Maggi E, Matucci A. Assessment of the risk of polyomavirus JC reactivation in patients with immune-mediated diseases during long-term treatment with infliximab. J Neurovirol. 2012 Feb;18(1):55-61. Epub 2012 Jan 27. PubMed PMID: 22281875. 16. Loghavi S, Bose S. Polyomavirus infection and urothelial carcinoma. Diagn Cytopathol. 2011 Jul;39(7):531-5. doi: 10.1002/dc.21490. Epub 2010 Oct 1. PubMed PMID: 20891007.     Submitted on February 28, 2012 

Polyomavirus in Immunocompetent Patients

https://escholarship.org/content/qt7d82k7cg/qt7d82k7cg.pdf

Polyomavirus in Immunocompetent Patients

Abstract

Similar works

Full text

Available Versions

eScholarship - University of California