http://informahealthcare.com/rnf ISSN: 0886-022X (print), 1525-6049 (electronic) Ren Fail, 2014; 36(7): 1148–1150 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/0886022X.2014.926757
CASE REPORT
Cytomegalovirus-related hemorrhagic cystitis in an immunocompetent child Aysel Taktak1, Banu Acar1, Go¨kc¸e Gu¨r1, Tug˘rul Tiryaki2, Esra Karaku¸s3, F. S¸ emsa C¸aycı1, Nermin Uncu1, and Nilgu¨n C¸akar1 1
Ren Fail Downloaded from informahealthcare.com by Kainan University on 04/30/15 For personal use only.
Department of Pediatric Nephrology and Rheumatology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey, 2Department of Pediatric Surgery, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey, and 3 Department of Pathology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey Abstract
Keywords
Cytomegalovirus (CMV) infections are mostly seen in immunocompromised patients. However, unusual manifestations or complications of acquired CMV infections in immunocompetent patients are rarely reported. CMV-related hemorrhagic cystitis is extremely rare but should be considered even in immunocompetent patients. We present a case of a 3-year-old immunocompetent boy with intermittent, terminal gross hematuria lasting for 1 month. There was no history of genitourinary trauma or stone disease. Urine analysis revealed hematuria with eumorphic red blood cells and no proteinuria. Urine culture was negative. Ultrasonography showed increased bladder wall thickness and irregularity at inferior of bladder. Cystoscopy revealed hyperemia and edema. Histopathological examination was consistent with CMV infection, viral DNA by polymerase chain reaction in peripheral blood and urine were positive. Clinical, laboratory, and imaging features pointed towards hemorrhagic cystitis due to CMV. He was followed-up with no treatment. After 1 month, repeated investigations showed complete resolution of finding. This is a rare description of an immunocompetent child with CMV-induced cystitis.
Child, cytomegalovirus, hemorrhagic cystitis, immunocompetent
Introduction Hemorrhagic cystitis is an uncommon entity in children. It is mostly seen in immunocompromised patients due to cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy, acute leukemia and aplastic anemia.1 CMV is one of the predominant pathogens in these patients.2 CMV infections in immunocompetent patients are rarely reported. CMV-related hemorrhagic cystitis is extremely rare but should be considered even in immunocompetent patients. In this case report, we present an immunocompetent boy with CMV-related hemorrhagic cystitis, which has not been previously described.
Case report A previously healthy 3-year-old boy was admitted with intermittent gross hematuria and dysuria lasting for 1 month. It was primarily described at the terminal portion of
Address correspondence to Aysel Taktak, MD, Department of Pediatric Nephrology and Rheumatology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey. Tel: +90312 5969698; Fax: +90312 3472330; E-mail: aysel.taktak@ gmail.com
History Received 6 February 2014 Revised 8 April 2014 Accepted 11 May 2014 Published online 16 June 2014
micturition. Before admission he was treated with antibiotics despite negative urine cultures. He had no history of any infections, trauma or stone disease. His family history was also negative for hematuria and stone disease. Physical examination revealed a well-developed boy in good clinical condition, there was no pathological finding and his blood pressure was normal. The urine was macroscopically red-colored. Laboratory studies revealed hematuria, eumorphic red blood cell (RBC) count of 343 per highpower microscopic field and no proteinuria. Urine culture was negative. Spot urine calcium/creatinine ratio was normal (0.07). Blood tests revealed a white blood cell, count of 9200/mm3 with 60% lymphocytes. Serum creatinine was 0.2 mg/dL, blood urea nitrogen was 20 mg/dL, anti-nuclear antibodies were negative, and the level of complement (C) 3 and C4 were within normal levels. At ultrasonography, inferior bladder wall thickness was minimally increased (4 mm), and had an irregular section of 18 mm. Cystoscopy was performed for further investigation, which revealed hyperemia and edema at the inferior of the bladder wall. Histopathological examination showed minimal basal hyperplasia at the urinary epithelium. Epithelial lymphocytic infiltration, minimal karyorrhexis in the connective tissue was
DOI: 10.3109/0886022X.2014.926757
Cytomegalovirus-related hemorrhagic cystitis
1149
Discussion
Ren Fail Downloaded from informahealthcare.com by Kainan University on 04/30/15 For personal use only.
Figure 1. Epithelial lymphocytic infiltration at the urinary epithelium.
Figure 2. Immune fluorescent microscopy showed significant positivity of cytomegalovirus (CMV) antigen.
also found. Immune fluorescent microscopy showed significant positivity of cytomegalovirus (CMV) antigen (Figures 1 and 2). CMV specific serology and detection of viral DNA by polymerase chain reaction (PCR) in peripheral blood and urine was performed, according to histopathological examination results. The blood and urine PCR was positive (1081 copies/mL). After definition of the infection, the patient was detected for concomitant symptoms of CMV infection. The complete blood count and liver function tests were normal, HIV, adeno virus and Epstein-Barr virus serology were negative, neurological and ophthalmological examinations showed no pathological finding. Immunodeficiency syndromes were excluded with immunological studies (serum IgG, IgA, IgM, lymphocyte subpopulations CD3, CD4, CD8, CD56 + 16 counts were normal. HIV serology was negative). At the follow-up period he was evaluated regularly and no treatment was given. Hematuria resolved within 1 month. CMV PCR in urine and blood sample was performed 1 month later, blood CMV PCR was negative but urine sample was positive. The patient has been followed for 1 year and no relapse of cystitis was observed.
CMV is a common cause of morbidity and mortality in patients receiving immunosuppression. Moreover, CMV is the most common viral infection following kidney transplantations and has been recognized as a major factor for graft loss and increased incidence of acute rejection. Hepatitis, gastritis, pneumonia, colitis are more common than CMV-related cystitis in immunocompromised patients.2 CMV-related hemorrhagic cystitis mostly seen in immunocompromised patients due to cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy, acute leukemia and aplastic anemia.1,2 However unusual manifestations or complications of acquired CMV infections in immunocompetent patients are rarely reported. Most common manifestations involve gastrointestinal, hepatic, hematologic and respiratory systems.3–7 Most immunocompetent patients are presented with a mononucleosis-like syndrome with fever, fatigue, pharyngitis, cervical adenopathy and elevation in liver enzymes.8 In our patient, surprisingly a diagnosis of histopathologically proven CMV cystitis was made. Extensive immunological screening revealed no signs of immunodeficiency. The indications for ganciclovir treatment in CMV infections are usually limited to immunocompromised patients, human immunodeficiency virus and congenital CMV infections. In addition to immunocompromised patients, ganciclovir treatment is suggested in certain severe CMV infections in immunocompetent children.2 CMV-induced cystitis in an immunocompetent child has not been previously described in the literature. Therefore, there is not enough data concerning the benefits and side effects of ganciclovir for immunocompromised patients. According to our patient’s clinical and laboratory finding, anti-viral treatment was not indicated. He was followed-up with no treatment and after 1 month, repeated investigations showed complete resolution of finding and he remained asymptomatic. A diagnosis of CMV-related cystitis should be considered in immunocompetent patients presenting with unexplained hematuria. An evaluation with cystoscopy and biopsy of bladder is indicated in such cases. Patients with proved CMV infection should be evaluated for immunodeficiency however urgent anti-viral treatment is not indicated in immunocompetent patients.
Declaration of interest The authors declare no conflicts of interests. The authors alone are responsible for the content and writing of this article.
References 1. Paduch DA. Viral lower urinary tract infections. Curr Urol Rep. 2007;8:324–335. 2. Riachy E, Krauel L, Rich BS, et al. Risk factors and predictors of severity score and complications in pediatric hemorrhagic cystitis. J Urol. 2014;191:186–192. 3. Justo D, Finn T, Atzmony L, et al. Thrombosis associated with acute cytomegalovirus infection: a meta-analysis. Eur J Int Med. 2011;22:195–199. 4. Grilli E, Galati V, Bordi L, et al. Cytomegalovirus pneumonia in immunocompetent host: case report and literature review. J Clin Virol. 2012;55:356–359.
1150
A. Taktak et al.
Ren Fail Downloaded from informahealthcare.com by Kainan University on 04/30/15 For personal use only.
5. Tezer H, Sec¸meer G, Kara A, et al. Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children. Turk J Pediatr. 2008;50:228–234. 6. Hoshina T, Kusuhara K, Saito M, et al. Cytomegalovirusassociated protein-losing enteropathy resulting from lymphangiectasia in an immunocompetent child. Jpn J Infect Dis. 2009;62: 236–238.
Ren Fail, 2014; 36(7): 1148–1150
7. Canan O, Ozc¸ay F, Bilezikc¸i B. Me´ne´trier’s disease and severe gastric ulcers associated with cytomegalovirus infection in an immunocompetent child: a case report. Turk J Pediatr. 2008;50: 291–295. 8. Hadaya K, Kaiser L, Rubbia-Brandt L. Ganciclovir for severe cytomegalovirus primary infection in an immunocompetent child. Eur J Clin Microbiol Infect Dis. 2004;23:218–220.
CASE REPORT
Cytomegalovirus-related hemorrhagic cystitis in an immunocompetent child Aysel Taktak1, Banu Acar1, Go¨kc¸e Gu¨r1, Tug˘rul Tiryaki2, Esra Karaku¸s3, F. S¸ emsa C¸aycı1, Nermin Uncu1, and Nilgu¨n C¸akar1 1
Ren Fail Downloaded from informahealthcare.com by Kainan University on 04/30/15 For personal use only.
Department of Pediatric Nephrology and Rheumatology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey, 2Department of Pediatric Surgery, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey, and 3 Department of Pathology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey Abstract
Keywords
Cytomegalovirus (CMV) infections are mostly seen in immunocompromised patients. However, unusual manifestations or complications of acquired CMV infections in immunocompetent patients are rarely reported. CMV-related hemorrhagic cystitis is extremely rare but should be considered even in immunocompetent patients. We present a case of a 3-year-old immunocompetent boy with intermittent, terminal gross hematuria lasting for 1 month. There was no history of genitourinary trauma or stone disease. Urine analysis revealed hematuria with eumorphic red blood cells and no proteinuria. Urine culture was negative. Ultrasonography showed increased bladder wall thickness and irregularity at inferior of bladder. Cystoscopy revealed hyperemia and edema. Histopathological examination was consistent with CMV infection, viral DNA by polymerase chain reaction in peripheral blood and urine were positive. Clinical, laboratory, and imaging features pointed towards hemorrhagic cystitis due to CMV. He was followed-up with no treatment. After 1 month, repeated investigations showed complete resolution of finding. This is a rare description of an immunocompetent child with CMV-induced cystitis.
Child, cytomegalovirus, hemorrhagic cystitis, immunocompetent
Introduction Hemorrhagic cystitis is an uncommon entity in children. It is mostly seen in immunocompromised patients due to cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy, acute leukemia and aplastic anemia.1 CMV is one of the predominant pathogens in these patients.2 CMV infections in immunocompetent patients are rarely reported. CMV-related hemorrhagic cystitis is extremely rare but should be considered even in immunocompetent patients. In this case report, we present an immunocompetent boy with CMV-related hemorrhagic cystitis, which has not been previously described.
Case report A previously healthy 3-year-old boy was admitted with intermittent gross hematuria and dysuria lasting for 1 month. It was primarily described at the terminal portion of
Address correspondence to Aysel Taktak, MD, Department of Pediatric Nephrology and Rheumatology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey. Tel: +90312 5969698; Fax: +90312 3472330; E-mail: aysel.taktak@ gmail.com
History Received 6 February 2014 Revised 8 April 2014 Accepted 11 May 2014 Published online 16 June 2014
micturition. Before admission he was treated with antibiotics despite negative urine cultures. He had no history of any infections, trauma or stone disease. His family history was also negative for hematuria and stone disease. Physical examination revealed a well-developed boy in good clinical condition, there was no pathological finding and his blood pressure was normal. The urine was macroscopically red-colored. Laboratory studies revealed hematuria, eumorphic red blood cell (RBC) count of 343 per highpower microscopic field and no proteinuria. Urine culture was negative. Spot urine calcium/creatinine ratio was normal (0.07). Blood tests revealed a white blood cell, count of 9200/mm3 with 60% lymphocytes. Serum creatinine was 0.2 mg/dL, blood urea nitrogen was 20 mg/dL, anti-nuclear antibodies were negative, and the level of complement (C) 3 and C4 were within normal levels. At ultrasonography, inferior bladder wall thickness was minimally increased (4 mm), and had an irregular section of 18 mm. Cystoscopy was performed for further investigation, which revealed hyperemia and edema at the inferior of the bladder wall. Histopathological examination showed minimal basal hyperplasia at the urinary epithelium. Epithelial lymphocytic infiltration, minimal karyorrhexis in the connective tissue was
DOI: 10.3109/0886022X.2014.926757
Cytomegalovirus-related hemorrhagic cystitis
1149
Discussion
Ren Fail Downloaded from informahealthcare.com by Kainan University on 04/30/15 For personal use only.
Figure 1. Epithelial lymphocytic infiltration at the urinary epithelium.
Figure 2. Immune fluorescent microscopy showed significant positivity of cytomegalovirus (CMV) antigen.
also found. Immune fluorescent microscopy showed significant positivity of cytomegalovirus (CMV) antigen (Figures 1 and 2). CMV specific serology and detection of viral DNA by polymerase chain reaction (PCR) in peripheral blood and urine was performed, according to histopathological examination results. The blood and urine PCR was positive (1081 copies/mL). After definition of the infection, the patient was detected for concomitant symptoms of CMV infection. The complete blood count and liver function tests were normal, HIV, adeno virus and Epstein-Barr virus serology were negative, neurological and ophthalmological examinations showed no pathological finding. Immunodeficiency syndromes were excluded with immunological studies (serum IgG, IgA, IgM, lymphocyte subpopulations CD3, CD4, CD8, CD56 + 16 counts were normal. HIV serology was negative). At the follow-up period he was evaluated regularly and no treatment was given. Hematuria resolved within 1 month. CMV PCR in urine and blood sample was performed 1 month later, blood CMV PCR was negative but urine sample was positive. The patient has been followed for 1 year and no relapse of cystitis was observed.
CMV is a common cause of morbidity and mortality in patients receiving immunosuppression. Moreover, CMV is the most common viral infection following kidney transplantations and has been recognized as a major factor for graft loss and increased incidence of acute rejection. Hepatitis, gastritis, pneumonia, colitis are more common than CMV-related cystitis in immunocompromised patients.2 CMV-related hemorrhagic cystitis mostly seen in immunocompromised patients due to cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy, acute leukemia and aplastic anemia.1,2 However unusual manifestations or complications of acquired CMV infections in immunocompetent patients are rarely reported. Most common manifestations involve gastrointestinal, hepatic, hematologic and respiratory systems.3–7 Most immunocompetent patients are presented with a mononucleosis-like syndrome with fever, fatigue, pharyngitis, cervical adenopathy and elevation in liver enzymes.8 In our patient, surprisingly a diagnosis of histopathologically proven CMV cystitis was made. Extensive immunological screening revealed no signs of immunodeficiency. The indications for ganciclovir treatment in CMV infections are usually limited to immunocompromised patients, human immunodeficiency virus and congenital CMV infections. In addition to immunocompromised patients, ganciclovir treatment is suggested in certain severe CMV infections in immunocompetent children.2 CMV-induced cystitis in an immunocompetent child has not been previously described in the literature. Therefore, there is not enough data concerning the benefits and side effects of ganciclovir for immunocompromised patients. According to our patient’s clinical and laboratory finding, anti-viral treatment was not indicated. He was followed-up with no treatment and after 1 month, repeated investigations showed complete resolution of finding and he remained asymptomatic. A diagnosis of CMV-related cystitis should be considered in immunocompetent patients presenting with unexplained hematuria. An evaluation with cystoscopy and biopsy of bladder is indicated in such cases. Patients with proved CMV infection should be evaluated for immunodeficiency however urgent anti-viral treatment is not indicated in immunocompetent patients.
Declaration of interest The authors declare no conflicts of interests. The authors alone are responsible for the content and writing of this article.
References 1. Paduch DA. Viral lower urinary tract infections. Curr Urol Rep. 2007;8:324–335. 2. Riachy E, Krauel L, Rich BS, et al. Risk factors and predictors of severity score and complications in pediatric hemorrhagic cystitis. J Urol. 2014;191:186–192. 3. Justo D, Finn T, Atzmony L, et al. Thrombosis associated with acute cytomegalovirus infection: a meta-analysis. Eur J Int Med. 2011;22:195–199. 4. Grilli E, Galati V, Bordi L, et al. Cytomegalovirus pneumonia in immunocompetent host: case report and literature review. J Clin Virol. 2012;55:356–359.
1150
A. Taktak et al.
Ren Fail Downloaded from informahealthcare.com by Kainan University on 04/30/15 For personal use only.
5. Tezer H, Sec¸meer G, Kara A, et al. Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children. Turk J Pediatr. 2008;50:228–234. 6. Hoshina T, Kusuhara K, Saito M, et al. Cytomegalovirusassociated protein-losing enteropathy resulting from lymphangiectasia in an immunocompetent child. Jpn J Infect Dis. 2009;62: 236–238.
Ren Fail, 2014; 36(7): 1148–1150
7. Canan O, Ozc¸ay F, Bilezikc¸i B. Me´ne´trier’s disease and severe gastric ulcers associated with cytomegalovirus infection in an immunocompetent child: a case report. Turk J Pediatr. 2008;50: 291–295. 8. Hadaya K, Kaiser L, Rubbia-Brandt L. Ganciclovir for severe cytomegalovirus primary infection in an immunocompetent child. Eur J Clin Microbiol Infect Dis. 2004;23:218–220.
