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Symptomatic herpes virus infections in postrenal transplant
Symptomatic Herpes Virus Infections in Postrenal Transplant R. Jha, G. Narayen, S. Sinha, K. Kadeer, and K.N. Prasad
V
IRAL infections in renal transplant (RT) patients are an important cause of morbidity and mortality. Among the herpes group of viruses, herpes simplex (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) have greatest impact.1 We studied the prevalence and impact of herpes virus infections in RT recipients at our center. MATERIALS AND METHODS Over a 10-year period (June 1990 to December 2000) 185 RT patients were performed with voluntary live donors. Follow-up ranged from 1 to 10 years. All subjects received triple drug immunosuppression (cyclosporine, prednisolone, azathioprine or mycophenolat mofetil), and 6 patients received additional basiliximab. The patients records were reviewed for symptomatic infection due to HSV, VZV, and/or CMV. Predisposing factors, time frame of occurrence, and outcomes of treatment were analyzed. The diagnosis was established by Tzanck smear inclusion bodies multinucleate giant cells (HSV), histopathology with immunohistochemistry (HSV, CMV), viral serology or polymerase chain reaction (PCR)-based viral assays (CMV) as well as clinical grounds (VZV). Statistical analysis was performed using chi-square tests.
RESULTS
Symptomatic viral infections due to the herpes virus group were observed in 36 RT recipients (19.4%). Infection due to HSV was seen in 17 patients (esophagitis 13, keratitis 1, anogenital ulcers 2, diffuse cutaneous blisters 1) all within the first 3 months. Esophagitis occurred exclusively in the first month. Varicella zoster virus infection was seen in 13 patients (herpes zoster 10, chicken pox 3) during the period of 1 to 36 months (mean 11.1 months). Symptomatic CMV disease was seen in 6 patients (pneumonia 2, gastrointestinal bleed 1, and fever with opportunistic infection in 3). All HSV and VZV patients received acyclovir therapy and improved, except for one with chickenpox who died. Two of the 6 patients with CMV disease received gancyclovir with improvement of fever and hepatitis, while 4 died of gastrointestinal bleed, pneumonia, or associated opportunistic infection. None of these infections were preceded by antirejection therapy. Cytomegalovirus was associated with renal dysfunction (creatinine ⬎ 2 mg%) in 3, basiliximab usage in 2, and coexisting immunomodulating hepatitis viral infection in 2 (one each of hepatitis B and C). 0041-1345/03/$–see front matter doi:10.1016/S0041-1345(02)03836-8 284
DISCUSSION
Viral infections, especially herpes viruses, are an important cause of morbidity and mortality.1 Such infections usually represent reactivation of latent viruses occurring within the first 6 months. The reported time-frame of contracting HSV by the first month and CMV disease between 1 to 6 months is in agreement with our observation.1 In our experience, VZV infections occurred at a later time than that previously reported1 even in developing countries.2 Risk-factor analysis failed to show any association of HSV and VZV with diabetes, renal dysfunction, leukopenia, age, or immunosuppression. However, 2 of 6 patients administered basiliximab developed CMV infections. Infection with HSV was noted in 9.1% of our patients, particularly during the first month. The HSV infection most often presents as esophagitis.3 Hence, dysphagia following RT requires endoscopic evaluation. Acyclovir prophylaxis reduces the incidence of these infections.4 In our patients, VZW was common. One of 13 patients died despite all receiving acyclovir. Adequate dosing is crucial since mortality has been linked to inadequate drug doses.5 In contrast to the uncommon life-threatening chickenpox syndrome,6 localized skin involvement, which has been reported in 20% to 30% of patients, is benign.1 Prevention of chickenpox by vaccination has been shown to be effective and economical in pediatric RT, with a durable response.7 A similar strategy for antibody-negative adults should be strongly considered.5 Cytomegalovirus infection was observed in at least twothirds of these patients,1,8 although clinical disease was seen less often (10% to 20%). Data from other Indian transplant centers suggest a hypeendemicity of seropositivity.9 A negative CMV PCR in blood excludes clinical disease, but a positive report is insufficient to start treatment.10 Quantitative PCR, which strongly predicts clinical disease, is recommended.9 Four of 6 patients died of CMV due to gancylovir being prohibitively expensive. Gancyclovir is effective both for prophylaxis and treatment, although additional IV immunoglobulin might be needed for patients who get intensive immunosuppression.11 From Departments of Nephrology and Urology, Medwin Hospital, Hyderabad, India. Address reprint requests to Dr Ratan Jha, Consultant Nephrologist, Medwin Hospitals, Hyderabad, Andhra Pradesh, India 500001. © 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 35, 284 –285 (2003)
HERPES VIRUS INFECTIONS
We conclude that herpes viral infection is an important cause of morbidity and mortality. Delayed VZV is common in developing countries. Our experience on symptomatic infections with the herpes virus group was lower than that reported in the Western literature, possibly due to less intense immunosuppression in a live donor program. The lack of sensitive diagnostic tools in the initial years of our program as well as the retrospective nature of this analysis might have influenced the data. REFERENCES 1. Rubin RH: Kidney Int 44:221, 1993 2. John GT, Date A, Mathew CM, et al: Transplantation 61:970, 1996
285 3. Alexander JA, Brouillette DE, Chien MC, et al: Dig Dis Sci 33:1121, 1988 4. Birkeland SA, Anderson HK, Gahm-Hansen B: Scand J Infect Dis 30:221, 1998 5. Bradley JR, Wreghitt TG, Evans DB: Nephrol Dial Transplant 1:242, 1987 6. Parnham AP, Flexman JP, Saker BM, et al: Clin Transplant 9:115, 1995 7. Olson AD, Shope TC, Flynn JT: Pediatr Transplant 5:44, 2001 8. Sia IG, Paya CV: Surg Clin North Am 78:95, 1998 9. Rao M, Finny GJ, Abraham P, et al: Nephron 84:367, 2000 10. Benedette E, Mihalor M, Asolati M, et al: Clin Transplant 12:391, 1998 11. Isenberg AZ, Shan GK, Singh TP, et al: Clin Transplant 14:193, 2000
V
IRAL infections in renal transplant (RT) patients are an important cause of morbidity and mortality. Among the herpes group of viruses, herpes simplex (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) have greatest impact.1 We studied the prevalence and impact of herpes virus infections in RT recipients at our center. MATERIALS AND METHODS Over a 10-year period (June 1990 to December 2000) 185 RT patients were performed with voluntary live donors. Follow-up ranged from 1 to 10 years. All subjects received triple drug immunosuppression (cyclosporine, prednisolone, azathioprine or mycophenolat mofetil), and 6 patients received additional basiliximab. The patients records were reviewed for symptomatic infection due to HSV, VZV, and/or CMV. Predisposing factors, time frame of occurrence, and outcomes of treatment were analyzed. The diagnosis was established by Tzanck smear inclusion bodies multinucleate giant cells (HSV), histopathology with immunohistochemistry (HSV, CMV), viral serology or polymerase chain reaction (PCR)-based viral assays (CMV) as well as clinical grounds (VZV). Statistical analysis was performed using chi-square tests.
RESULTS
Symptomatic viral infections due to the herpes virus group were observed in 36 RT recipients (19.4%). Infection due to HSV was seen in 17 patients (esophagitis 13, keratitis 1, anogenital ulcers 2, diffuse cutaneous blisters 1) all within the first 3 months. Esophagitis occurred exclusively in the first month. Varicella zoster virus infection was seen in 13 patients (herpes zoster 10, chicken pox 3) during the period of 1 to 36 months (mean 11.1 months). Symptomatic CMV disease was seen in 6 patients (pneumonia 2, gastrointestinal bleed 1, and fever with opportunistic infection in 3). All HSV and VZV patients received acyclovir therapy and improved, except for one with chickenpox who died. Two of the 6 patients with CMV disease received gancyclovir with improvement of fever and hepatitis, while 4 died of gastrointestinal bleed, pneumonia, or associated opportunistic infection. None of these infections were preceded by antirejection therapy. Cytomegalovirus was associated with renal dysfunction (creatinine ⬎ 2 mg%) in 3, basiliximab usage in 2, and coexisting immunomodulating hepatitis viral infection in 2 (one each of hepatitis B and C). 0041-1345/03/$–see front matter doi:10.1016/S0041-1345(02)03836-8 284
DISCUSSION
Viral infections, especially herpes viruses, are an important cause of morbidity and mortality.1 Such infections usually represent reactivation of latent viruses occurring within the first 6 months. The reported time-frame of contracting HSV by the first month and CMV disease between 1 to 6 months is in agreement with our observation.1 In our experience, VZV infections occurred at a later time than that previously reported1 even in developing countries.2 Risk-factor analysis failed to show any association of HSV and VZV with diabetes, renal dysfunction, leukopenia, age, or immunosuppression. However, 2 of 6 patients administered basiliximab developed CMV infections. Infection with HSV was noted in 9.1% of our patients, particularly during the first month. The HSV infection most often presents as esophagitis.3 Hence, dysphagia following RT requires endoscopic evaluation. Acyclovir prophylaxis reduces the incidence of these infections.4 In our patients, VZW was common. One of 13 patients died despite all receiving acyclovir. Adequate dosing is crucial since mortality has been linked to inadequate drug doses.5 In contrast to the uncommon life-threatening chickenpox syndrome,6 localized skin involvement, which has been reported in 20% to 30% of patients, is benign.1 Prevention of chickenpox by vaccination has been shown to be effective and economical in pediatric RT, with a durable response.7 A similar strategy for antibody-negative adults should be strongly considered.5 Cytomegalovirus infection was observed in at least twothirds of these patients,1,8 although clinical disease was seen less often (10% to 20%). Data from other Indian transplant centers suggest a hypeendemicity of seropositivity.9 A negative CMV PCR in blood excludes clinical disease, but a positive report is insufficient to start treatment.10 Quantitative PCR, which strongly predicts clinical disease, is recommended.9 Four of 6 patients died of CMV due to gancylovir being prohibitively expensive. Gancyclovir is effective both for prophylaxis and treatment, although additional IV immunoglobulin might be needed for patients who get intensive immunosuppression.11 From Departments of Nephrology and Urology, Medwin Hospital, Hyderabad, India. Address reprint requests to Dr Ratan Jha, Consultant Nephrologist, Medwin Hospitals, Hyderabad, Andhra Pradesh, India 500001. © 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 35, 284 –285 (2003)
HERPES VIRUS INFECTIONS
We conclude that herpes viral infection is an important cause of morbidity and mortality. Delayed VZV is common in developing countries. Our experience on symptomatic infections with the herpes virus group was lower than that reported in the Western literature, possibly due to less intense immunosuppression in a live donor program. The lack of sensitive diagnostic tools in the initial years of our program as well as the retrospective nature of this analysis might have influenced the data. REFERENCES 1. Rubin RH: Kidney Int 44:221, 1993 2. John GT, Date A, Mathew CM, et al: Transplantation 61:970, 1996
285 3. Alexander JA, Brouillette DE, Chien MC, et al: Dig Dis Sci 33:1121, 1988 4. Birkeland SA, Anderson HK, Gahm-Hansen B: Scand J Infect Dis 30:221, 1998 5. Bradley JR, Wreghitt TG, Evans DB: Nephrol Dial Transplant 1:242, 1987 6. Parnham AP, Flexman JP, Saker BM, et al: Clin Transplant 9:115, 1995 7. Olson AD, Shope TC, Flynn JT: Pediatr Transplant 5:44, 2001 8. Sia IG, Paya CV: Surg Clin North Am 78:95, 1998 9. Rao M, Finny GJ, Abraham P, et al: Nephron 84:367, 2000 10. Benedette E, Mihalor M, Asolati M, et al: Clin Transplant 12:391, 1998 11. Isenberg AZ, Shan GK, Singh TP, et al: Clin Transplant 14:193, 2000