Infection with the varicella-zoster virus, the etiologic agent of chickenpox and herpes zoster, is more serious in immunosuppressed renal transplant recipients than it is in the general population. Chickenpox is a rare infection in adult renal transplant recipients; however, it is significant owing to the severity of its clinical features and its associated high mortality rate. To date, there are no reported outbreaks of primary varicella-zoster virus infection in adult renal transplant recipients. Here, we report 3 patients with chickenpox who presented to our center between May 2006 and June 2006.

Key words : Varicella-zoster virus, Herpes, Kidney, Epidemiology, Organ graft

Infection with primary varicella-zoster virus (VZV), the etiologic agent of chickenpox and herpes zoster, is an uncommon infectious complication after organ transplant [1-3]. There have been some reports of sporadic primary VZV infection in adult renal transplant recipients [4-8]. Primary VZV infection in adult renal transplant recipients is associated with a poor outcome. In this article, we report an outbreak of 3 cases of chickenpox in adult renal transplant recipients that took place between May 2006 and June 2006 in Khuzestan, a province in southwest Iran. There are 823 renal transplant recipients in this area, all of whom have access to medical care through only 1 tertiary care center. From 1990 until this report, there were no reports of chickenpox in renal transplant recipients living in this area. To our knowledge, this is the first report in the English literature of a chickenpox outbreak in adult renal transplant recipients.

Case 1
A 37-year-old man had undergone a living-unrelated renal transplant in 2005. His immunosuppression regimen consisted of cyclosporine (225 mg qd), mycophenolate mofetil (1500 mg qd), and prednisolone (10 mg qd). In May 2006, he was admitted to our hospital with severe abdominal pain. On physical examination, there was mild epigastric tenderness and no rebound tenderness. Results of a complete blood count and biochemical assays were within the normal range. His serum creatinine level was 167.96 µmol/L (1.9 mg/dL), his serum amylase and lipase levels were within the normal ranges, and results of his liver function tests were normal. The results of an abdominal ultrasonography and a computed tomography scan were normal.

Three days after being admitted to the hospital, a papuloerythematous rash appeared on the patient’s chest and face, which progressed to a vesiculopustular rash. His abdominal pain subsequently stopped. The diagnosis of chickenpox infection was established according to typical skin lesions. He was treated with intravenous acyclovir (10 mg/kg q 12 h) for 10 days and discharged home without complications 15 days after admission.

Case 2
A 44-year-old man had undergone a living-unrelated renal transplant in 1997 owing to hypertensive nephropathy. His immunosuppression regimen consisted of prednisone (7.5 mg qd), mycophenolate mofetil (1 g bid), and cyclosporine (200 mg qd). In June 2006, he was admitted to our hospital with low back pain of 2 days’ duration. He complained of persistent, severe low back pain that was not due to an inflammatory condition or a predominantly mechanical condition. No radiculopathy was present; however, the patient did experience muscle weakness and malaise. Results of the patient’s physical examination were unremarkable. The results of his imaging studies (ie, lumbosacral radiograph and lumbosacral magnetic resonance imaging scan) were significant for mild degenerative changes in the lumbar spine. His serum creatinine level was 212.16 µmol/L (2.4 mg/dL), and mild normocytic anemia was present (hemoglobin level was 112 g/L). The patient’s white blood cell count was within the normal range, and the results of his liver function tests were normal. Two days after admission, he became febrile and developed a widespread papulovesicular rash characteristic of chickenpox. The diagnosis of chickenpox infection was established according to typical skin lesions. He was treated immediately with intravenous acyclovir (10 mg/kg q 12 h) for 10 days. Three days after the initiation of treatment with acyclovir, the patient’s low back pain subsided. Fifteen days after admission, the patient was discharged home without complications.

Case 3
A 34-year-old man had received a living-unrelated renal transplant in 1998 for end-stage renal disease due to focal segmental glomerulosclerosis. His immunosuppression regimen consisted of cyclosporine (150 mg qd), mycophenolate mofetil (2 g qd), and prednisolone (10 mg qd). In June 2006, the patient had traveled to another city and then had returned home 1 day prior to admission to our hospital. At that time, he experienced the sudden onset of severe, generalized abdominal pain. He was admitted to our hospital with acute abdominal pain and intractable nausea and vomiting. On physical examination, his abdomen was soft but not tender to palpation. His abdominal pain did not subside with analgesic treatment including high dosages of opioids. Results of standard laboratory tests were unremarkable as were the results of his imaging studies (ie, abdominal and pelvic computed tomography scan and Doppler sonography of the mesenteric arteries). Pancreatitis and mesenteric ischemia were ruled out. A papulovesicular rash appeared on his face and trunk after 48 hours and subsequently became generalized. The diagnosis of chickenpox infection was established according to typical skin lesions. Intravenous acyclovir (10 mg/kg q 8 h) was administered for 7 days and then changed to oral acyclovir for 3 days. After 2 days of acyclovir therapy, the patient’s refractory abdominal pain disappeared, and he stated that he felt well. No additional complications occurred, and the patient was discharged home 13 days after admission.

Discussion

Owing to severe and prolonged immunosuppression during the posttransplant period, renal transplant recipients are at high risk for severe disseminated varicella-zoster infection, the etiology of chickenpox [1-3]. There are some reports of sporadic primary varicella-zoster infections in adult renal transplant recipients [4-8]. To the best of our knowledge, however, this is the first report in the English literature of an outbreak of chickenpox in adult renal transplant recipients.

Khuzestan, a region in southwest Iran, has a large population (the province had an estimated population of 4 277 000 inhabitants). An outbreak of any contagious disease in the general population could be transmitted to renal transplant recipients. In Khuzestan, during the summer of 2006, there was a prevalence of varicella-zoster infection. The renal transplant patients reported here had not taken precautions to avoid contact with the infection. However, on admission, all of them denied contact with an infected patient.

In some reports, chickenpox in adult renal transplant recipients is in the disseminated form, and numerous organ systems are involved resulting in death [1-2]. The chickenpox in our patients presented initially as dull, disabling pain. Atypical skin lesions presented after 3 to 5 days . The severity of the pain decreased after manifestation of the lesions and disappeared 3 to 4 days later. No internal organs were involved. The infection did not affect the renal functioning of any of the patients in this report.

In all patients, we discontinued cyclosporine, continued prednisolone at its prior dosage, and prescribed mycophenolate mofetil at half of its prior dosage. Acyclovir effectively treats VZV infections in immunocompromised patients. All of the patients reported here were treated successfully with intravenous acyclovir.

Prior to transplant, the patients reported here were seronegative for VZV; they all received renal transplant without immunization against VZV, as is our policy. Immunization against VZV remains controversial, and there are, at present, no guidelines for using varicella vaccine either before or during end-stage renal failure. Regarding active immunization, because seronegative patients tend to develop a much more severe disease, and VZV vaccine is effective, the authors of an increasing number of reports have recommended vaccination before transplant [8-9]. Varicella vaccination prior to renal transplant should reduce morbidity in sero-negative recipients and provide considerable cost savings [10]. A vaccination program in sero-negative recipients should be included as part of the pretransplant workup. Timely administration of this vaccine may protect posttransplant patients from early and severe VZV infection [11].

Conclusions

Renal transplant recipients with chickenpox might present with atypical symptoms such as acute abdomen and low back pain. Delayed diagnosis owing to atypical presentations could be life threatening. Renal transplant recipients should avoid contact with actively VZV-infected individuals. In some situations, such as an outbreak of chickenpox in the general population, renal transplant recipients (especially seronegative patients without a history of VZV vaccination with suspicious symptoms) should be worked up for chickenpox. Early diagnosis and aggressive treatment with intravenous acyclovir could be life saving. All renal transplant recipients should be screened for VZV immunization prior to transplant irrespective of previous history of VZV infection. The live VZV vaccine preferably should be administered in sero-negative recipients several months prior to transplant.

References:

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