https://doi.org/10.5812/numonthly.1844

Rare Presentations of Cytomegalovirus Infection in Renal Allograft Recipients

authors:

avatar Mohammadreza Ardalan 1 , 2 , *

Department of Nephrology, Tabriz University of Medical Sciences, Tabriz, IR Iran
Mario Negri Institute of Pharmacological Research, Bergamo, Italy
Nephro-Urology Monthly: Vol.4, issue 2; 431-436
published online: March 1, 2012
article type: Review Article
received: July 7, 2011
revised: July 19, 2011
accepted: July 27, 2011

how to cite: Ardalan M. Rare Presentations of Cytomegalovirus Infection in Renal Allograft Recipients. Nephro-Urol Mon. 2012;4(2): 431-436. https://doi.org/10.5812/numonthly.1844.

Abstract

Cytomegalovirus is the most common viral infection after kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. Most symptomatic infections manifest as fever and cytopenia. The gastrointestinal tract is the most common site of tissue-invasive infection, often presenting as diarrhea or gastrointestinal bleeding. Gastrointestinal obstruction, perforation, thrombosis of large gastrointestinal veins, splenic artery thrombosis, and pancreatitis are rare gastrointestinal presentations of cytomegalovirus infection. Renal-allograft ureteral stricture and skin involvement are other rare presentations of cytomegalovirus infection. hemophagocytic syndrome, thrombotic microangiopathy, adrenal insufficiency, and renal allograft artery stenosis are other rare symptoms of cytomegalovirus infection.

1. Introduction

Cytomegalovirus (CMV) is the most common viral infection contracted after kidney transplantation, and its clinical presentation ranges from asymptomatic infection to organ-specific involvement (1). Most symptomatic infections manifest as fever, fatigue, and cytopenia. The gastrointestinal tract is the most common site of tissue-invasive CMV infection, with abdominal pain and diarrhea as the most prominent symptoms. In severe cases, gastrointestinal hemorrhage and perforation occur. CMV infection can involve the liver, lungs, heart, pancreas, and kidneys. Chorioretinitis, which is a common manifestation in HIV-infected patients, is very rare in sol-id-organ recipients (1-3). Through its ability to modulate the immune system, CMV infection increases the risk of other opportunistic infections, including human herpes viruses (HHV-6 and HHV-7), Epstein-Barr virus, nocardia, mycobacteria, and fungi such as Aspergillus and candida (1, 4, 5). Patients with CMV infection are more likely to experience acute and chronic rejection. The greatest CMV-induced damage tends to occur within the transplanted organ itself; that is, bronchitis obliterant and pneumonitis in lung-transplant recipients, hepatitis in liver-transplant recipients, and transplant vasculopathy in heart-transplant recipients. CMV is also considered a risk for the development of malignancy and posttransplant diabetes (1-3). Active CMV infection can be confirmed by specific antibody assays, detection of inclusion bodies within the infected cells, antigen staining by immunohistochemical methods, detection of viremia by polymerase chain reaction (PCR), and CMV-DNA in peripheral blood leukocytes (1, 3, 6).

2. Vascular Involvement

CMV-induced vasculopathy and thrombosis have been reported in both immune-compromised and immune-competent individuals. Endothelium is a latency site for the CMV virus. Thrombosis of the jugular, cerebral, retinal, and upper-extremities veins have been reported as a complication of CMV infection in HIV-infected patients (7). Some cases of arterial and venous thrombosis have been repoted among immune-competent individuals (8-10). CMV infection plays an important role in atherosclerosis of the coronary arteries after heart transplantation and in restenosis after angioplasty (8, 9). CMV infection especially affects the gastrointestinal microvasculature and manifests as colonic ulceration, bleeding, and perforation. Enlarging of the colonic vein and splenic venous and arterial thrombosis have been associated with CMV infection (10). CMV infection induces endothelial inflammation, increasing leukocyte and platelet adhesion and endothelial expression of Vwf, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1 (11, 12)). The plasma levels of factor VIII, fibrinogen, protein S, platelet-derived growth factor, and transforming growth factor–B are higher in patients with active cytomegalovirus infection (13). The presence of antiphospholipid antibodies increases the risk of CMV-induced vascular damage. Extensive splenic infarct has been reported after CMV infection in a patient with heterozygous mutation of factor V leiden (14). one of the gene products of CMV, IE84, inhibits P53-mediated apoptosis and enhances vascular smooth-muscle-cell proliferation (15). It has been shown that CMV is a cause of aortic inflammation in mice infected with CMV (16). In a case study of induced CMV, acute transplant renal artery stenosis was resolved after ganciclovir therapy without any need for angioplasty (17). CMV infection has been suggested in the pathogenesis of polyarteritis nodosa (PAN), systemic necrotizing vasculitis, and Kawasaki disease (16, 18, 19). It has been reported that carotid artery intima thickening disappears after appropriate therapy for acute CMV infection (20).

3. Urologic Complications

In two early reports, CMV infection was proposed as a cause of renal allograft ureteral stricture (21, 22). later reports confirmed this idea. A review of reported cases showed that induction therapy with antilymphocyte globulin and antirejection therapy with antilymphocyte globulin and intravenous methylprednisolone are the most prominent risk factors in the development of CMV-induced urologic complications. Symptoms often begin around 4 to 5 weeks after an intensive immunosuppressive therapy. Patients do not show major symptoms of viremia and often present with low-grade fever, supra-pubic pain, and rising serum creatinine. In one report, CMV cystitis began 10 days after antirejection therapy (23). Ultrasounds are useful for diagnosing ureteral stricture. Serologic tests often show an active CMV infection. Ureteral stricture is often severe and found in the upper or middle ureter or in the ureteropelvic junction. At the time of this writing, all CMV studies using histologic examinations have shown extensive inflammation, ureteral necrosis, and intranuclear inclusion bodies in endothelial and vascular smooth muscle cells. All patients in previous studies were treated with surgical resection and reanastomosis (Table 1; (24-27)).

Table 1

Ureteral Stenosis in CMV Infection

Age/SexCMVR a/D aInductionRejectionSigns/Time bDiagnosis/Treatment
42/F a+/+ATG a /5d-Suprapubic pain, hydronephrosis /1 moPP65 antigenemia & histology c/resection & re-anastomosis (24)
50/M a+/-ATG a /5d-Fever, suprapubic pain, leukopenia, hydronephrosis /25 dHistology /resection & re-anastomosis (24)
45/MIgG+/IgG-Basiliximab41 d, MTP aAllograft dysfunction & hydronephrosis/ 65 dHistology/resection & re-anastomosis (25)
31/F-/+, (No prophylaxy)-2 wk, MTPHydronephrosis & oliguria/2 moHistology/resection & re-anastomosis (26)
26/F+/--8 d, MTPSuprapubic pain & cystitis /18 d Hydronephrosis /45 dHistology/ resection & re-anastomosis (23)
62/F+/--8 d, MTPFever, suprapubic pain, hydronephrosis/ 6 wkHistology/resection & re-anastomosis
35/M+/--10 d, MTPFever, suprapubic pain HydronephrosisHistology/resection & re-anastomosis (23)
56/M+/--15 d, MTPAllograft dysfunction & hydronephrosis /8 wkHistology/resection & re-anastomosis (23)
62/M+/- -10 d, MTPLower extremity edema, Periallograft urine CollectionHistology/resection & re-anastomosis (27)

aAbbreviations: ATG, antithymocyte globuline; CMV, cytomegalovirus; D, donor; F, female; M, male; MTP, methyl prednisolone; R, recipient.

bTime; time of occurrence of the complication after transplantation.

cHistology; specific pathologic changes including CMV inclusion bodies and owl’s eye lesion found in a histological study of involved organs and detection of CMV antigens by immuno-histochemical staining.

4. Gastrointestinal Complications

Symptomatic CMV disease of the gastrointestinal tract occurs in about 5–10% of renal-transplant recipients. Gastrointestinal involvement can be localized or extensive. Ulcers of the esophagus, stomach, small intestine, and colon also manifest as dysphagia, abdominal pain, diarrhea, bleeding, or perforation. hepatitis can occur, especially after a liver transplant. CMV vasculitis can affect the gastrointestinal tract significantly, causing colonic ulceration, bleeding, and perforation. Colonic complications are usually severe and vascular in origin. A study using a pathologic examination revealed ulcerations and necrosis with scattered CMV inclusions (28). Duodenal vasculitis, intermittent small-bowel obstruction, acute pancreatitis, bloody ascites, colonic obstruction, and painful hemorrhoids have been reported as rare gastrointestinal presentations of CMV infection (28-36). Rare gastrointestinal presentations of CMV infection in kidney-transplant recipients are shown in Table 2.

Table 2

Rare Gastrointestinal Manifestations of CMV Infection

Age, ySexRecipientDonorTimebType of transplantationInduction or antirejectionmedicationSignsDiagnosisTreatment
37F a++30 dkidneyAnti-CD52Abdominal pain, bloody peritoneal fluid, leukopeniaPeritoneal fluid RT-PCR c, CMV-pp65 dPeritoneal-catheter removal, medical therapy (34)
41F--6 mo-ATG aAbdominal pain, PancreatitisRT-PCRMedical therapy (36)
46F++2 mokidneyBasiliximabFever, abdominal pain, duodenal vasculitisRT-PCRHistology e, medical therapy (33)
50M a++8 wkKidney, LiverATGAbdominal pain, duodenal vasculitis, obstructionRT-PCRHistology, surgical resection (35)
58F++6 mokidney-Fever, leukopenia, thrombocytopenia, painful hemorrhoidCMV-PP65 AgHistology (32)
44M?-2 moKidneyOKT3 FAbdominal pain, diarrhea, leukopenia, large colonic veins thrombosisHistologyTotal colectomy (30)
62M++4 yheart-Abdominal pain, hematochezia, colonic stenosisHistologySurgical resection (31)

aAbbreviation: ATG, antithymocyte globuline; F, female; M,male

bTime at which the complication presents after transplantation.

cRT-PCR, detection of CMV-DNA in plasma or other bodily fluid by real-time polymerase chain reaction.

dCMV-pp65, detection of CMV-PP65 antigen.

eHistology, that pathologic changes including CMV inclusion bodies have been found in involved tissues.

FOKT3 is an anti Tcell murine monoclonal anibody.

5. Cytomegalovirus Skin Involvement

Skin involvement is extremely rare in CMV infections. It should be considered when multiple anogenital, axillary, scrotal, and penile ulcers appear in an immune-compromised individual and are not responding to conventional antibiotic therapy (37). Painful ulceration of the tongue was reported as one manifestation of CMV infection in two renal-transplant patients. A combination of multiple anogenital ulcerations and generalized maculopapular rashes has been reported as a rare symptom of CMV infection (38). In one study, CMV vasculitis was the cause of perineal lesion in patients with partial response to anti hSV therapy. Perineal nerves are a potential site of CMV reactivation (39). Most cytopathic changes occur in the dermis, particularly within the vascular endothelium. CMV has been considered in the pathogenesis of immune-based cutaneous lesions such as cutaneous vasculitis and scleroderma (40).

The dermis is a relatively inhospitable site for CMV replication in that skin involvement occurs only in severely immune-compromised individuals (41). A skin biopsy can identify the disease before cultural or serologic conurbation. Early diagnosis and specific treatment can reduce the mortality rate for this potentially fatal condition (Table 3).

Table 3

Coetaneous Manifestation of CMV Infection

Age/SexTime bPresentationDiagnosis/Treatment
56/M a4 moMacula-papular skin lesions colonic ulcerHistology c/medical therapy (37)
31/M-Multiple penile ulcersHistology/medical therapy (38)
62/F a3 moMultiple perineal ulcerHistology/medical therapy (41)
62/F3 moPainful tongue ulcer, diffuse petechial Lesion on face. Diarrhea, low feverHistology, CMV-PP65 d RT-PCR e, ulcer swabbing medical therapy (41)
39/F7 yperi-anal ulcerHistology/surgical resection, medical therapy
34/M6 moFever, tongue ulcer, pinnal nodule, non productive cough, neutropeniaHistology (pinnal nodule) /medical therapy (41)
52/M2.5 moFever, vesicular ulcer on axilla, scrotum and penisHistology, RT-PCR/medical therapy

aAbbreviations: F, female; M, male

bTime, time of presentation after transplantation

cHistology, specific pathologic changes including CMV inclusion bodies, owl,s eye lesion, and detection of CMV antigens by immuno-histochemical staining

dCMV-pp65, detection of CMV-PP65 antigen

eRT-PCR, detection of CMV-DNA in plasma or other bodily fluid by real-time polymerase chain reaction

6. CMV and Malignancy

A possible relationship between CMV infection and cancer has been suggested in several studies. In addition to epidemiologic evidence, the detection of CMV-DNA, mRNA, or antigens in tumor tissues in some studies suggests a possible role of CMV infection in the pathogenesis of several human malignancies (42-45). human CMV nucleic acids and proteins have been discovered in a high percentage of low- and high-grade malignant gliomas (45). CMV is found within the breast epithelial cells, which suggests that it may play a role in the neoplastic process (46). US28 is a costimulatory chemokine receptor encoded by CMV. Transgenic coexpression of the US28 ligand, CCl2, which is an inflammatory chemokine, increases intestinal endothelial cell proliferation and the development of intestinal neoplasia (47).

7. Miscellaneous Presentations

Hemophagocytic syndrome, also referred to as macrophage activation syndrome, is a rare, systemic proliferation of benign monocyte–macrophage lineage (48-50). hemophagocytic syndrome has been reported as a rare complication of CMV infection in renal-transplant recipients. Patients often present with fever, splenomegaly anemia, pancytopenia, and elevated aminotransferase levels. Bone marrow examination often discloses extensive hemophagocytosis (48, 49, 51, 52).

After kidney transplantation, thrombotic microangiopathy (TMA) can reoccur. CMV infection can be a trigger for TMA in kidney-transplant recipients, and TMA can occur shortly after a transplant or even years later (53-55). A case of bilateral CMV retinitis presented as a floater was reported in a case study of a woman with systemic lupus erythematous who was undergoing hemodialysis. the condition improved after Ganciclovir therapy (56). In another case study, acute unilateral sensorineural hearing loss was reported as a sign of CMV infection 8 months after simultaneous pancreas and kidney transplant. The recipient was CMV-antibody negative and the donor was CMV-antibody positive, and CMV developed 2 months after completing 6 months of Valganciclovir prophylactic therapy. Hearing loss improved 5 weeks after intravenous ganciclovir therapy (57). Concomitant CMV pneumonitis and subacute thyroiditis were reported in a case study of a recipient of a bone-marrow transplant. The condition successfully responded to treatment with ganciclovir and prednisolone (58). CMV-induced adrenal insufficiency is a known condition in HIV-infected patients and has also been reported in one renal-transplant recipient, whose condition improved after increasing his corticosteroid dosage (59).

Cytomegalovirus is a common viral infection after kidney transplantation. Familiarity with unusual manifestations of CMV infection can help the clinician to better care and manage treatment for renal-transplant recipients.

Acknowledgements

References

  • 1.

    Eid AJ, Razonable RR. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs. 2010;70(8):965-81. [PubMed ID: 20481654]. https://doi.org/10.2165/10898540-000000000-00000.

  • 2.

    Fishman J, Ramos E. Pereira B, Sayegh M, Blake P, editors. Infection in Renal Transplant Recipients in Chronic Kidney Disease, Dialysis and Transplantation. 2nd ed. Philadelphia: Saunders; 2005. https://doi.org/10.1016/B978-1-4160-0158-4.50041-0.

  • 3.

    Fishman JA, Emery V, Freeman R, Pascual M, Rostaing L, Schlitt HJ, et al. Cytomegalovirus in transplantation - challenging the status quo. Clin Transplant. 2007;21(2):149-58. [PubMed ID: 17425738]. https://doi.org/10.1111/j.1399-0012.2006.00618.x.

  • 4.

    Ardalan M, Ghaffari A, Ghabili K, Shoja MM. lepromatous leprosy in a kidney transplant recipient: a case report. Exp Clin Transplant. 2011;9(3):203-6. [PubMed ID: 21649570].

  • 5.

    Ardalan MR, Shoja MM, Ghabili K. Concomitant pulmonary tuberculosis and tuberculous appendicitis in a recipient of a renal transplant: a case report. J Med Case Reports. 2011;5(1):191. [PubMed ID: 21599877]. https://doi.org/10.1186/1752-1947-5-191.

  • 6.

    lashini H, Goodarzi z, Hosseini M, Saberfar E. Development of PCR assay for early detection of CMV infection in renal transplant recipients. Nephro-Urol Mon. 2011;3(2):106-8.

  • 7.

    Sullivan PS, Dworkin MS, Jones Jl, Hooper WC. Epidemiology of thrombosis in hIV-infected individuals. The Adult/Adolescent Spectrum of hIV Disease Project. AIDS. 2000;14(3):321-4. [PubMed ID: 10716509]. https://doi.org/10.1097/00002030-200002180-00015.

  • 8.

    Abgueguen P, Delbos V, Chennebault JM, Payan C, Pichard E. Vascular thrombosis and acute cytomegalovirus infection in immunocompetent patients: report of 2 cases and literature review. Clin Infect Dis. 2003;36(11):E134-9. [PubMed ID: 12766855]. https://doi.org/10.1086/374664.

  • 9.

    Pastacaldi S, Teixeira R, Montalto P, Rolles K, Burroughs AK. Hepatic artery thrombosis after orthotopic liver transplantation: a review of nonsurgical causes. Liver Transpl. 2001;7(2):75-81. [PubMed ID: 11172388]. https://doi.org/10.1053/jlts.2001.22040.

  • 10.

    Ofotokun I, Carlson C, Gitlin SD, Elta G, Singleton TP, Markovitz DM. Acute cytomegalovirus infection complicated by vascular thrombosis: a case report. Clin Infect Dis. 2001;32(6):983-6. [PubMed ID: 11247723]. https://doi.org/10.1086/319353.

  • 11.

    Rahbar A, Soderberg-Naucler C. Human cytomegalovirus infection of endothelial cells triggers platelet adhesion and aggregation. J Virol. 2005;79(4):2211-20. [PubMed ID: 15681423]. https://doi.org/10.1128/JVI.79.4.2211-2220.2005.

  • 12.

    Ghielmetti M, Millard Al, Haeberli L, Bossart W, Seebach JD, Schneider MK, et al. Human CMV infection of porcine endothelial cells increases adhesion receptor expression and human leukocyte recruitment. Transplantation. 2009;87(12):1792-800. [PubMed ID: 19543055]. https://doi.org/10.1097/TP.0b013e3181a75a41.

  • 13.

    Alcami J, Barzu T, Michelson S. Induction of an endothelial cell growth factor by human cytomegalovirus infection of fibroblasts. J Gen Virol. 1991;72(Pt 11):2765-70. [PubMed ID: 1658202]. https://doi.org/10.1099/0022-1317-72-11-2765.

  • 14.

    Atzmony L, Saar N, Chundadze T, Arbel Y, Justo D, Mashav N. Cytomegalovirus-associated splenic infarcts in a female patient with Factor V leiden mutation: a case report. J Med Case Reports. 2008;2:385. [PubMed ID: 19087249]. https://doi.org/10.1186/1752-1947-2-385.

  • 15.

    Jeejeebhoy FM, Zaltzman JS. Thrombotic microangiopathy in association with cytomegalovirus infection in a renal transplant patient: a new treatment strategy. Transplantation. 1998;65(12):1645-8. https://doi.org/10.1097/00007890-199806270-00018.

  • 16.

    Meyer MF, Hellmich B, Kotterba S, Schatz H. Cytomegalovirus infection in systemic necrotizing vasculitis: causative agent or opportunistic infection? Rheumatol Int. 2000;20(1):35-8. [PubMed ID: 11149660]. https://doi.org/10.1007/s002960000063.

  • 17.

    Ardalan MR, Shoja MM, Tubbs RS, Ghabili K. Transplant renal artery stenosis associated with acute cytomegalovirus infection: resolution following ganciclovir administration. Ren Fail. 2009;31(10):982-4. [PubMed ID: 20030536]. https://doi.org/10.3109/08860220903288526.

  • 18.

    Fernandes SR, Bertolo MB, Rossi Cl, Samara AM, Bonon SH, DuranteDurante P, et al. Polyarteritis nodosa and cytomegalovirus: diagnosis by polymerase chain reaction. Clin Rheumatol. 1999;18(6):501-3. [PubMed ID: 10638780]. https://doi.org/10.1007/s100670050148.

  • 19.

    Usta Guc B, Cengiz N, Yildirim SV, Uslu Y. Cytomegalovirus infection in a patient with atypical Kawasaki disease. Rheumatol Int. 2008;28(4):387-9. [PubMed ID: 17717671]. https://doi.org/10.1007/s00296-007-0440-4.

  • 20.

    Hirabayashi Y, Ishii T, Kodera T, Fujii H, Munakata Y, Sasaki T. Acute cytomegalovirus infection and transient carotid intimalmedial thickening in a young, otherwise healthy woman. J Clin Microbiol. 2003;41(8):3978-80. [PubMed ID: 12904434]. https://doi.org/10.1128/JCM.41.8.3978-3980.2003.

  • 21.

    Lowell JA, Stratta RJ, Morton JJ, Kolbeck PC, Taylor RJ. Invasive cytomegalovirus infection in a renal transplant ureter after combined pancreas-kidney transplantation: an unusual cause of renal allograft dysfunction. J Urol. 1994;152(5 Pt 1):1546-8. [PubMed ID: 7933197].

  • 22.

    Bisteni A. [Editorial: Early electrocardiographic changes in disease]. Arch Inst Cardiol Mex. 1976;46(2):119-20. [PubMed ID: 938153].

  • 23.

    Thomas MC, Russ GR, Mathew Th, Rao Mohan M, Cooper J, Walker RJ. Four cases of CMV ureteritis: emergence of a new pattern of disease? Clin Transplant. 2001;15(5):354-8. [PubMed ID: 11678963]. https://doi.org/10.1034/j.1399-0012.2001.150509.x.

  • 24.

    Ducloux D, Bresson-Vautrin C, Chalopin JM. Is cytomegalovirus a cause of ureteral stricture in renal transplant recipients? Transpl Int. 1997;10(3):238-40. [PubMed ID: 9163867]. https://doi.org/10.1111/j.1432-2277.1997.tb00693.x.

  • 25.

    Leikis MJ, Denford AJ, Pidgeon GB, Hatfield PJ. Post-renal transplant obstruction caused by cytomegalovirus ureteritis. Nephrol Dial Transplant. 2000;15(12):2063-4. [PubMed ID: 11096159]. https://doi.org/10.1093/ndt/15.12.2063-a.

  • 26.

    Vongwiwatana A, Vareesangthip K, Vasuvattakul S, Prommol S, Nualyong C, Parichatikanond P, et al. Ureteritis due to cytomegalovirus infection in renal transplant recipient: a case report. Transplant Proc. 2000;32(7):1927. https://doi.org/10.1016/S0041-1345(00)01496-2.

  • 27.

    Vaessen C, Kamar N, Mehrenberger M, Mazerolles C, Mengelle C, Rischmann P, et al. Severe cytomegalovirus ureteritis in a renal allograft recipient with negative CMV monitoring. Nephrol Dial Transplant. 2005;20(1):227-30. [PubMed ID: 15632357]. https://doi.org/10.1093/ndt/gfh531.

  • 28.

    Shrestha BM, Parton D, Gray A, Shephard D, Griffith D, Westmoreland D, et al. Cytomegalovirus involving gastrointestinal tract in renal transplant recipients. Clin Transplant. 1996;10(2):170-5. [PubMed ID: 8664513].

  • 29.

    Chang HR, Lian JD, Chan CH, Wong LC. Cytomegalovirus ischemic colitis of a diabetic renal transplant recipient. Clin Transplant. 2004;18(1):100-4. https://doi.org/10.1046/j.0902-0063.2003.00108.x.

  • 30.

    Muldoon J, O'Riordan K, Rao S, Abecassis M. Ischemic colitis secondary to venous thrombosis. A rare presentation of cytomegalovirus vasculitis following renal transplantation. Transplantation. 1996;61(11):1651-3. [PubMed ID: 8669113]. https://doi.org/10.1097/00007890-199606150-00018.

  • 31.

    Crespo MG, Arnal FM, Gomez M, Monserrat L, Suarez F, Rodriguez JA, et al. Cytomegalovirus colitis mimicking a colonic neoplasm or ischemic colitis 4 years after heart transplantation. Transplantation. 1998;66(11):1562-5. [PubMed ID: 9869101]. https://doi.org/10.1097/00007890-199812150-00023.

  • 32.

    Khosravi M, Nobakht A, Nikokar AR. Cytomegalovirus disease with atypical presentation in a renal transplant patient: case report. Exp Clin Transplant. 2006;4(1):458-61. [PubMed ID: 16827643].

  • 33.

    Toussaint N, Goodman D, Langham R, Gock H, Hill P. Haemorrhagic Campylobacter jejuni and CMV colitis in a renal transplant recipient. Nephrol Dial Transplant. 2005;20(4):823-6. [PubMed ID: 15772269]. https://doi.org/10.1093/ndt/gfh687.

  • 34.

    Meier M, Hiss M, Hafer C, Buth W, Radermacher J, Haller H, et al. Cytomegalovirus peritonitis after renal transplantation under induction therapy with alemtuzumab in a young woman previously treated with peritoneal dialysis. Nephrol Dial Transplant. 2005;20(8):1771. [PubMed ID: 15928098]. https://doi.org/10.1093/ndt/gfh921.

  • 35.

    Alhyraba M, Grim SA, Benedetti E, Clark NM. Unusual presentation of cytomegalovirus enteritis after liver and kidney transplantation. Transpl Infect Dis. 2007;9(4):343-6. [PubMed ID: 17850246]. https://doi.org/10.1111/j.1399-3062.2007.00276.x.

  • 36.

    Schwartz J, Woods B, Shihab F. A Case of Native Cytomegalovirus Pancreatitis Following Deceased-Donor Renal Transplantation. Open Transpl J. 2009;3:1-3. https://doi.org/10.2174/1874418400903010001.

  • 37.

    Trimarchi H, Casas G, Jordan R, Martinez J, Schropp J, Freixas EA, et al. Cytomegalovirus maculopapular eruption in a kidney transplant patient. Transpl Infect Dis. 2001;3(1):47-50. https://doi.org/10.1034/j.1399-3062.2001.003001047.x.

  • 38.

    Choi YL, Kim JA, Jang KT, Kim DS, Kim WS, Lee JH, et al. Characteristics of cutaneous cytomegalovirus infection in non-acquired immune deficiency syndrome, immunocompromised patients. Br J Dermatol. 2006;155(5):977-82. [PubMed ID: 17034528]. https://doi.org/10.1111/j.1365-2133.2006.07456.x.

  • 39.

    Ramdial PK, Dlova NC, Sydney C. Cytomegalovirus neuritis in perineal ulcers. J Cutan Pathol. 2002;29(7):439-44. [PubMed ID: 12139640]. https://doi.org/10.1034/j.1600-0560.2002.290709.x.

  • 40.

    Magro CM, Crowson AN, Ferri C. Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change. Hum Pathol. 2007;38(1):42-9. [PubMed ID: 17084440]. https://doi.org/10.1016/j.humpath.2006.06.002.

  • 41.

    Kaisar Mo, Kirwan RM, Strutton GM, Hawley CM, Mudge DW, Campbell SB, et al. Cutaneous manifestations of cytomegalovirus disease in renal transplant recipients: a case series. Transpl Infect Dis. 2008;10(3):209-13. [PubMed ID: 17850247]. https://doi.org/10.1111/j.1399-3062.2007.00273.x.

  • 42.

    Prasad N, Jain M, Gupta A, Sharma R, Agarwal V. An unusual case of CMV cutaneous ulcers in a renal transplant recipient and review of literature. NDT Plus. 2010;3(4):379-82. https://doi.org/10.1093/ndtplus/sfq082.

  • 43.

    Harkins L, Volk AL, Samanta M, Mikolaenko I, Britt WJ, Bland KI, et al. Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet. 2002;360(9345):1557-63. https://doi.org/10.1016/S0140-6736(02)11524-8.

  • 44.

    Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS. high prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol. 2003;170(3):998-1002. [PubMed ID: 12913758]. https://doi.org/10.1097/01.ju.0000080263.46164.97.

  • 45.

    Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62(12):3347-50. [PubMed ID: 12067971].

  • 46.

    Harkins LE, Matlaf LA, Soroceanu L, Klemm K, Britt WJ, Wang W, et al. Detection of human cytomegalovirus in normal and neoplastic breast epithelium. Herpesviridae. 2010;1(1):8. [PubMed ID: 21429243]. https://doi.org/10.1186/2042-4280-1-8.

  • 47.

    Bongers G, Maussang D, Muniz LR, Noriega VM, Fraile-Ramos A, Barker N, et al. The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice. J Clin Invest. 2010;120(11):3969-78. [PubMed ID: 20978345]. https://doi.org/10.1172/JCI42563.

  • 48.

    Ponticelli C, Alberighi OD. Haemophagocytic syndrome--a life-threatening complication of renal transplantation. Nephrol Dial Transplant. 2009;24(9):2623-7. [PubMed ID: 19525363]. https://doi.org/10.1093/ndt/gfp282.

  • 49.

    Ardalan MR, Shoja MM, Tubbs RS, Esmaili H, Keyvani H. Postrenal transplant hemophagocytic lymphohistiocytosis and thrombotic microangiopathy associated with parvovirus b19 infection. Am J Transplant. 2008;8(6):1340-4. [PubMed ID: 18522549]. https://doi.org/10.1111/j.1600-6143.2008.02244.x.

  • 50.

    Karras A, Thervet E, Legendre C. Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004;77(2):238-43. [PubMed ID: 14742988]. https://doi.org/10.1097/01.TP.0000107285.86939.37.

  • 51.

    Hot A, Madoux MH, Viard JP, Coppere B, Ninet J. Successful treatment of cytomegalovirus-associated hemophagocytic syndrome by intravenous immunoglobulins. Am J Hematol. 2008;83(2):159-62. [PubMed ID: 17849465]. https://doi.org/10.1002/ajh.21008.

  • 52.

    Gurkan A, Yakupoglu U, Yavuz A, Dikici H, Yakupoglu YK, Tuncer M, et al. Hemophagocytic syndrome in kidney transplant recipients: report of four cases from a single center. Acta Haematol. 2006;116(2):108-13. [PubMed ID: 16914905]. https://doi.org/10.1159/000093640.

  • 53.

    De Keyzer K, Van Laecke S, Peeters P, Vanholder R. De novo thrombotic microangiopathy induced by cytomegalovirus infection leading to renal allograft loss. Am J Nephrol. 2010;32(5):491-6. [PubMed ID: 20975262]. https://doi.org/10.1159/000321328.

  • 54.

    Ardalan MR, Shoja MM, Tubbs RS, Etemadi J, Esmaili H, Khosroshahi HT. Thrombotic microangiopathy in the early post-renal transplant period. Ren Fail. 2008;30(2):199-203. [PubMed ID: 18300121]. https://doi.org/10.1080/08860220701810547.

  • 55.

    Ardalan MR. Review of thrombotic microangiopathy (TMA), and post-renal transplant TMA. Saudi J Kidney Dis Transpl. 2006;17(2):235-44. [PubMed ID: 16903637].

  • 56.

    Shahnaz S, Choksi MT, Tan IJ. Bilateral cytomegalovirus retinitis in a patient with systemic lupus erythematosus and end-stage renal disease. Mayo Clin Proc. 2003;78(11):1412-5. [PubMed ID: 14601702]. https://doi.org/10.4065/78.11.1412.

  • 57.

    Lipshutz GS, Dow AC, Pham PC, Pham PT. CMV otitis: a rare presentation in an adult transplant recipient. Transplantation. 2008;85(12):1870-71. [PubMed ID: 18580487]. https://doi.org/10.1097/TP.0b013e31817b0264.

  • 58.

    Kawano C, Muroi K, Akioka T, Izumi T, Kodera Y, Ozawa K. Cytomegalovirus pneumonitis, activated prothrombin time prolongation and subacute thyroiditis after unrelated allogeneic bone marrow transplantation. Bone Marrow Transplant. 2000;26(12):1347-9. [PubMed ID: 11223977]. https://doi.org/10.1038/sj.bmt.1702711.

  • 59.

    Ardalan M, Shoja MM. Cytomegalovirus-induced adrenal insufficiency in a renal transplant recipient. Transplant Proc. 2009;41(7):2915-6. [PubMed ID: 19765472]. https://doi.org/10.1016/j.transproceed.2009.07.024.