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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 50  |  Issue : 3  |  Page : 114-116

Cytomegalovirus infection in a kidney transplantation patient presented with skin lesion


1 Department of Urology, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi City, Taiwan
2 Department of Pharmacy, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi City, Taiwan
3 Department of Laboratory Medicine, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi City, Taiwan

Date of Submission21-Jul-2016
Date of Decision05-Sep-2016
Date of Acceptance24-Nov-2016
Date of Web Publication29-May-2017

Correspondence Address:
Yeong-Chin Jou
Department of Urology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, 539, Chung-Hhsiao Road, Chiayi City
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_38_17

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  Abstract 

Cytomegalovirus (CMV) infection commonly occurs after major organ transplantation. It mostly presents gastrointestinal tract symptoms in clinical manifestation. Dermatologic lesion as a main presenting feature for posttransplantation CMV is very rare. Here, we report a case of CMV infection predominated by skin ulcers in genitalia and perianal area in a 59-year-old female who received renal transplantation 3 months ago. She had initially been treated with both oral and topical antibiotics for suspicious bacterial or fungus infection without response. Subsequent serological study proved positive CMV infection. After treatment of ganciclovir and valganciclovir for 2 weeks, respectively, the skin ulcers healed gradually. This case report suggests that CMV-induced skin infection should be concerned in the diagnosis of poor healing skin ulcers in patients received organ transplantation.

Keywords: Cytomegalovirus infection, genitalia skin ulcer, renal transplantation


How to cite this article:
Chang SK, Jou YC, Tong SH, Lin YF, Kuo YL, Wu JF. Cytomegalovirus infection in a kidney transplantation patient presented with skin lesion. Formos J Surg 2017;50:114-6

How to cite this URL:
Chang SK, Jou YC, Tong SH, Lin YF, Kuo YL, Wu JF. Cytomegalovirus infection in a kidney transplantation patient presented with skin lesion. Formos J Surg [serial online] 2017 [cited 2019 May 26];50:114-6. Available from: http://www.e-fjs.org/text.asp?2017/50/3/114/207184


  Introduction Top


Cytomegalovirus (CMV) is a common source of viral infection after major organ transplant surgeries, and it affects more than 50% of recipients.[1],[2] The infection most commonly occurs a month after the surgery. CMV infection can be present in several forms, such as a primary infection, reinfection, or reactivation of latent disease and it makes up a large percentage of morbidity and mortality in renal transplant recipients (RTRs). Its clinical presentation ranges from asymptomatic infection to organ-specific involvement and can cause detrimental results to the allograft, reducing graft survival.[3] CMV infection most commonly presents itself as a viral syndrome, characterized by fever, fatigue, and cytopenia. Other well-documented manifestations including pneumonia, gastrointestinal disease, and liver dysfunction can be present as well. The most common site of tissue-invasive CMV infection is the gastrointestinal tract, presented with symptoms such as abdominal pain and diarrhea.[4] CMV seldom infects the skin; hence, diagnosis of cutaneous involvement is often delayed. Here, we report a case of a renal transplantation recipient who suffered skin ulcers over the genitalia without responding to antibiotics. CMV infection was proven by serological test with no other pathogen and the patient responded to anti-CMV treatment.


  Case Report Top


A 59-year-old female was admitted for a survey of several painful ulcers over perianal area and genitalia with white discharge for 2 months. She had previously been treated with topical anti-fungus ointment for presumed fungus infection in proctosurgery outpatient department with poor medical response. She had received cadaver kidney transplantation 3 months ago. Both of the donor and the patient were CMV-seropositive before transplantation. She was on triple immunosuppression therapy with cyclosporine, methylprednisolone, and mycophenolate mofetil (MMF) without induction immunosuppression. She had C4d-positive acute antibody-mediated rejection after 5 days of transplantation. It was treated with plasma exchange and methylprednisolone; then, the graft renal function restored to normal. On examination, there was no other significant finding, apart from the ulcers. There were multiple painful, flat, and variably sized maculopapular eruptions over perineal and anogenital regions surrounded by verrucous borders [Figure 1]. On admission, she received antibiotic for presumed bacterial infection. The ulcers did not heal and she became pyretic intermittently with consciousness disturbance even the broad-spectrum antibiotics were prescribed. The wound, blood, and urine culture revealed neither bacteria nor fungus growth. A presumptive diagnosis of opportunistic infection by virus was made. The serum of the recipient was positive for CMV IgG and negative for CMV IgM before operation. However, the serum of the recipient was tested positive for CMV IgM in this admission, and CMV infection was suspected. Oral ganciclovir 330 mg at 12-hour intervals was administered for 2 weeks. After discontinuation of oral ganciclovir, it was substituted by valganciclovir 900 mg b.i.d. for subsequent 2 weeks. The consciousness disturbance disappeared 2 days after antivirus treatment. She also became afebrile and the ulcers healed gradually without any sequel. The serological CMV IgM revealed negative status in the follow-up.
Figure 1: Exophytic maculopapular eruption developed ulceration (arrow) surrounded by verrucous plaque of the median aspect of the gluteus

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  Discussion Top


The CMV virus belongs to the herpesviridae family of DNA viruses. Infection of the virus is usually latent and asymptomatic in healthy individuals. However, CMV infection in children or adults with compromised immune system may be more frequent and severe. The risk and progression of disease both depend on the use of antiviral prophylaxis, net state of immunosuppression, and the viral exposure load.[5],[6],[7] CMV infections in transplant patients usually present in three patterns: (1) primary infection occurs in seronegative recipient from seropositive donor, (2) reactivation of latent virus occurs in seropositive donor after transplant, and (3) superinfection occurs when seropositive recipient receives allograft from a seropositive donor.[1] The predominant defense against CMV is the MHC restricted cytotoxic T-cell, with increasing evidence of contribution from CD4+ T-cells and humoral immunity. Using anti-thymocyte globulin and OKT3 as induction immunosuppression is linked to an increased risk of CMV infection secondary to the “cytokine storm” which is associated with reactivation of the elevated tumor necrosis factor-α-induced latent CMV in the early stages of RTRs wound bed repair.[8] Then CMV antigenemia develops. Maintenance therapy, with cyclosporine, tacrolimus, and prednisolone, suppresses cytotoxic cells in a dose-dependent effect, enhancing viral replication previously stimulated by other factors. Moreover, CMV virus itself has immunosuppressive activity and has the ability to activate the host cell's cellular production of chemokines, pro-inflammatory cytokines, and growth factors.

It has been postulated that the dermis is a relatively hostile environment to CMV with cutaneous disease only occurring in the significantly immunocompromised patient. There are two possible explanations for CMV skin ulcers: the latent virus resides in the gastrointestinal tract and infects the perineum skin through fecal shedding when it is reactivated, or the local latent virus is reactivated in the endothelial cells during endothelial colonization on the path to hematogenous dissemination.[9] There has been growing evidence suggesting that CMV may target long-lived cells such as the CD34+ hematopoietic cells which give rise to monocyte-derived macrophages and dendritic cells.[3] During the wound healing process, the CD34+ bone marrow progenitors differentiate macrophages and endothelial progenitor cells in the lesion. Then, granulation with macrophage infiltrates and hypervascularity develops. It is likely that latent CMV is reactivated in the skin ulcer on the path to hematogenous dissemination.[3]

The classic clinical presentations of CMV are fever, visceral disease (e.g., colitis, esophagitis or hepatitis), laboratory evidence of bone marrow suppression and pneumonitis, and cytopenia which includes leukopenia, thrombocytopenia, and petechiae. Cutaneous involvement remains a rare manifestation of CMV infection in RTRs. Cutaneous involvement usually presents as generalized maculopapular eruptions, plaques, petechiae, indurated hyperpigmented nodules, and vesiculobullous lesions, and can be easily mistaken for herpetic infections.[10] CMV with cutaneous disease rarely occurs and only be noted in the significantly immunocompromised patient. As such, we commonly associate skin infection with disseminated disease such as pneumonitis, reflecting the overall degree of immunosuppression in these patients.

Established CMV disease is primarily treated with antiviral agent ganciclovir IV. This antiviral agent induces remission of CMV disease in RTRs. However, there have been rare cases where the CMV strain is ganciclovir-resistant. Ganciclovir-resistant strains are usually sensitive to foscarnet, which is otherwise avoided due of nephrotoxicity. With the small number of published cases, there are no published data specifically addressing the type and duration of antiviral treatment used in cutaneous CMV disease in the immunocompromised hosts. In general, uncontrolled studies have suggested 2–3 weeks of ganciclovir treatment for organ involvement in CMV disease.[11]

In our case, both recipient and donor were CMV-seropositive and we suspect the appearance of the CMV disease was due to either reactivation or superinfection of CMV in this patient. The pp65 antigenemia assay and quantitation of CMV DNA by the PCR are effective tests utilized in the diagnosis of CMV infection. However, due to resource limitation of our laboratory facility, we could only demonstrate the presumptive opportunistic infection by the positive change in status of CMV IgM antibodies and rule out bacterial infection due to previous poor response to broad-spectrum antibiotics as well as the negative bacterial culture results. Our patient was on triple immunosuppressive therapy (cyclosporine-MMF-prednisolone) after renal transplantation. By inhibition of the de novo purine synthesis, MMF can affect both T- and B-cells. As cited in a recent meta-analysis, MMF is linked to an increased risk of CMV disease though it has not been proven whether this is an independent effect or related to overall immunosuppression.[12] Patients with cutaneous CMV infection generally warrant poor prognosis as the reported mortality is 85%.[1] With the appropriate antiviral therapy and reduction in immunosuppression, our patient with cutaneous manifestations responded well and recovered.

The CMV skin infection is extremely rare and can present as the first sign of high-mortality systemic CMV infection. This case report reminds us that CMV skin ulcer should be put into consideration in the differential diagnosis of nonhealing ulcer in RTRs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her image and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Prasad N, Jain M, Gupta A, Sharma RK, Agarwal V. An unusual case of CMV cutaneous ulcers in a renal transplant recipient and review of literature. NDT Plus 2010;3:379-82.  Back to cited text no. 1
    
2.
Shaver MJ, Bonsib SM, Abul-Ezz S, Barri YM. Renal allograft dysfunction associated with cytomegalovirus infection. Am J Kidney Dis 1999;34:942-6.  Back to cited text no. 2
    
3.
Moscarelli L, Zanazzi M, Rosso G, Farsetti S, Caroti L, Annunziata F, et al. Can skin be the first site of CMV involvement preceding a systematic infection in a renal transplant recipient? NDT Plus 2011;4:53-5.  Back to cited text no. 3
    
4.
Ardalan M. Rare presentations of cytomegalovirus infection in renal allograft recipients. Nephrourol Mon 2012;4:431-6.  Back to cited text no. 4
    
5.
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;10:209-13.  Back to cited text no. 5
    
6.
Emery VC. Investigation of CMV disease in immunocompromised patients. J Clin Pathol 2001;54:84-8.  Back to cited text no. 6
    
7.
Drago F, Aragone MG, Lugani C, Rebora A. Cytomegalovirus infection in normal and immunocompromised humans. A review. Dermatology 2000;200:189-95.  Back to cited text no. 7
    
8.
Fietze E, Prösch S, Reinke P, Stein J, Döcke WD, Staffa G, et al. Cytomegalovirus infection in transplant recipients. The role of tumor necrosis factor. Transplantation 1994;58:675-80.  Back to cited text no. 8
    
9.
Horn TD, Hood AF. Clinically occult cytomegalovirus present in skin biopsy specimens in immunosuppressed hosts. J Am Acad Dermatol 1989;21(4 Pt 1):781-4.  Back to cited text no. 9
    
10.
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;155:977-82.  Back to cited text no. 10
    
11.
Snydman DR. Ganciclovir therapy for cytomegalovirus disease associated with renal transplants. Rev Infect Dis 1988;10 Suppl 3:S554-62.  Back to cited text no. 11
    
12.
Song AT, Abdala E, Bonazzi PR, Bacchella T, Machado MC. Does mycophenolate mofetil increase the risk of cytomegalovirus infection in solid organ transplant recipients? A mini-review. Braz J Infect Dis 2006;10:132-8.  Back to cited text no. 12
    


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This article has been cited by
1 Ciclosporin/methylprednisolone/mycophenolate
Reactions Weekly. 2017; 1674(1): 91
[Pubmed] | [DOI]



 

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