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Chicken pox in adult renal transplant patients: A report of two cases with review of literature
Indian Journal of Transplantation 2012 January–March Volume 6, Number 1; pp. 27–29
Case Report
Chicken pox in adult renal transplant patients: A report of two cases with review of literature Jai Prakash1, Surendra Singh Rathore2, Tauhidul Alam Choudhury2, Takhellambam Brojen Singh2 1
Professor, 2Senior Resident, Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi – 221005, Uttar Pradesh, India.
INTRODUCTION Varicella–zoster virus (VZV) infection is uncommon in renal transplant recipients with incidence ranged between 1% and 11%, but it is more serious in transplant patients than in general population.1,2 In adults, reactivation in the form of herpes-zoster is more common than primary infection because of ubiquitous occurrence of infection in childhood. Chicken pox, because of primary or re-infection, is very rare in adults and it could be associated with substantially high morbidity and mortality. We report two cases of post transplant chicken pox in adult patients.
CASE HISTORY Case 1 A 23-year-old male had undergone live-related renal transplant in March 1996 because of chronic pyelonephritis. The donor was his mother. Donor and recipient were ABO-compatible and pre-transplant human leukocyte antigen (HLA) matching showed two mismatches, one each at HLA-A and HLA-DR loci. He was on triple immunosuppressive regimen: Cyclosporine, azathioprine and steroids. His graft function was good with serum creatinine in the range of 0.8–1.3 mg/dL and no episode of acute rejection was noted. Six-year post transplant, he presented with high grade fever of 1 day duration with generalized vesiculopustular rash which started from scalp and involved trunk and back. Laboratory investigations including hemoglobin, total leukocyte count, liver and renal function tests, and chest radiograph were unremarkable. Clinical picture was suggestive of chicken pox. He was started on intravenous (IV)
acyclovir (10 mg/kg ter die sumendum [TDS]) for 14-days and immunosuppression was decreased. He recovered fully.
Case 2 A 28-year-old male patient received ABO-compatible renal allograft from his mother in June 2000 due to focal segmental glomerulosclerosis (FSGS). He received second live-related, ABO-compatible graft in June 2004 because of failure in previous graft. Pre-transplant HLA screening showed one mismatch at HLA-A locus. After transplant, his serum creatinine remained in the range of 0.7–1.3 mg/dL without occurrence of any acute rejection episode. He was on triple drug immunosuppression in the form of tacrolimus, azathioprine and steroids. In 2011, 7 years after his second transplant, he presented with severe retrosternal chest pain and dyspnea at rest of 2 days duration. On examination, his blood pressure was 134/86 mmHg, pulse was 98/min and respiratory rate was 34/min. Chest auscultation demonstrated crackles in right basal area. Chest radiograph showed bilateral lower zone infiltrates, more on right side. His serum creatinine was raised to 2.15 mg/dL. Serum glutamicoxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), serum lipase values were 1153 IU/L, 412 IU/L, and 373 IU/L, respectively, suggestive of acute hepatitis and pancreatitis. Cardiac enzymes and two-dimensional echo were normal. Arterial blood gas (ABG) analysis showed hypoxemic respiratory failure. Patient was prescribed IV antibiotics and supportive treatment. However, on 2nd day of admission, he developed typical vesiculopustular rash which started from face and spread to trunk, genitals, back and upper thigh region (Figure 1). Diagnosis of chicken pox with visceral dissemination was made on clinical ground. Patient was treated with IV acyclovir therapy (5 mg/kg TDS)
Correspondence: Dr. Surendra Singh Rathore, email: [email protected] doi: 10.1016/S2212-0017(12)60078-1
ISSN:2212-0017 Copyright © 2012. Indian Society of Organ Transplantation. All rights reserved.
28
Indian Journal of Transplantation 2012 January–March; Vol. 6, No. 1
Figure 1 Photograph shows extensive vesiculopustular rash with crusting and hemorrhagic transformation around genitals, an upper thigh area, in post transplant chicken pox patient. Similar lesions were noted over trunk, back, and face.
but his condition deteriorated, and 2 days later, he developed features of encephalopathy, disseminated intravascular coagulopathy (DIC), and multiple organ failure. He died of multiple organ failure which was attributed to chicken pox with visceral dissemination.
DISCUSSION Chicken pox is considered as common benign, self limiting infectious disease of pediatric population. More than 90% of adults are seropositive for VZV indicating exposure in childhood.3 In children, it presents as generalized papulovesicular eruption which starts from scalp or face and spreads in centripetal fashion. The most characteristic feature of varicella rash is the simultaneous presence of lesions at all stages of development—papules, vesicles, erosions, and crusts. Following primary infection, virus remains latent in dorsal root ganglia. However, viral reactivation can occur, either at the time of depressed immunity or spontaneously. This reactivation form is known as herpes-zoster (shingles), which is characterized by painful vesicular eruption in single dermatomal distribution. Both types of diseases which are thought to be benign could be cause of significant morbidity and mortality in immunocompromised transplant recipients. Reported incidence of VZV infection following renal transplant varies from 1% to 11%.1,2,4 It is uncommon during immediate post transplant period. The onset of VZV infection was reported with median duration of 6.6 months after renal transplant.1
Prakash et al.
Majority of such patients present with features of herpeszoster and presentation as chicken pox is rare. Most cases of post transplant chicken pox have been reported in pediatric patients.5 In adult renal transplant recipients, occurrence as chicken pox is an extremely rare event.6 In immunocompromised patients, herpes-zoster may present in disseminated form and may be confused with chicken pox or other viral infections. However, chicken pox can be differentiated from zoster on the basis of previous history of disease, presence of typical rash which start from face or scalp and spread in centripetal fashion, absence of characteristic pain associated with shingles, and negative VZV serology. Both of our patients neither had history of childhood occurrence of chicken pox nor received vaccination prior to transplantation. Although, VZV serology was not available, clinical ground was sufficient to label it as chicken pox. Visceral dissemination in chicken pox may cause multiple organ dysfunctions such as pneumonitis, encephalitis, hepatitis, pancreatitis, glomerulonephritis, and disseminated intravascular coagulation, in up to 33% cases and has very high case fatality rate.7–9 Also, it may have atypical presentation like pain abdomen, and systemic features and rash appear late in disease course which may cause delay in diagnosis.6 Our patient (case 2) had systemic features of visceral involvement with atypical presentation. He succumbed to illness despite treatment, while second patient (case 1) had milder form of disease and responded well to antiviral therapy. Limited data are available regarding epidemiology of VZV, risk factors and prognosis in transplant patients. Increasing age at transplant and use of induction therapy are only established risk factors.1,2 Earlier mycophenolate mofetil (MMF) was thought to be with increased risk of VZV infection but recent studies did not find any correlation.1,2,10 Antiviral prophylaxis in the form of acyclovir and/ or valganciclovir has been found to be protective for VZV infection during prophylaxis period.2 Since, delay in treatment could prove fatal, all cases should be treated aggressively with IV acyclovir. Varicella–zoster virus immunoglobulin can prevent infection following exposure only when administered early, however it has no role in established cases.8 Live attenuated vaccine is available for active immunization. It is recommended to determine VZV serology status prior to transplant and to provide vaccination to those with seronegative status.11
SUMMARY In summary, we reported two extremely rare cases of post transplant chicken pox in adults. In immunocompromised
Post transplant chicken pox
patients, it may have visceral involvement before appearance of typical rash which may cause delay in diagnosis. Hence, high index of suspicion is required for early detection.
REFERENCES 1.
2.
3.
4.
Gourishankar S, McDermid JC, Jhangri GS, Preiksaitis JK. Herpes zoster infection following solid organ transplantation: incidence, risk factors and outcomes in the current immunosuppressive era. Am J Transplant 2004;4:108–15. Arness T, Pedersen R, Dierkhising R, Kremers W, Patel R. Varicella zoster virus-associated disease in adult kidney transplant recipients: incidence and risk-factor analysis. Transplant Infect Dis 2008;10:260–8. Jenkins FJ, Rowe DT, Rinaldo CR. Herpesvirus infections in organ transplant recipients. Clin Diagn Lab Immunol 2003; 10:1–7. Rodriguez-Moreno A, Sanchez-Fructuoso AI, Calvo N, et al. Varicella infection in adult renal allograft recipients: experience at one center. Transplant Proc 2006;38:2416–8.
Case Report
5.
29
Lynfield R, Herrin JT, Rubin RH. Varicella in pediatric renal transplant recipients. Pediatrics 1992;90:216–20. 6. Ishikawa N, Tanabe K, Shimmura H, Tokumoto T, Toma H. Primary varicella virus in adult renal transplant recipients: case reports. Transplant Proc 2000;32:1952–3. 7. Smith SR, Butterly DW, Alexander BD, Greenberg A. Viral infections after renal transplantation. Am J Kidney Dis 2001; 37:659–76. 8. Fehr T, Bossart W, Wahl C, Binswanger U. Disseminated varicella infection in adult renal allograft recipients: four cases and a review of the literature. Transplantation 2002;73: 608–11. 9. Sato A, Amada N, Kikuchi H, Fukumori T, Haga I, Takahashi Y. Pneumonia due to varicella-zoster virus reinfection in a renal transplant recipient. Transplant Proc 2009;41:3959–61. 10. Lauzurica R, Bayés B, Frías C, et al. Disseminated varicella infection in adult renal allograft recipients: role of mycophenolate mofetil. Transplant Proc 2003;35:1758–9. 11. Kitai IC, King S, Gafni A. An economic evaluation of varicella vaccine for pediatric liver and kidney transplant recipients. Clin Infect Dis 1993;17:441–7.
Case Report
Chicken pox in adult renal transplant patients: A report of two cases with review of literature Jai Prakash1, Surendra Singh Rathore2, Tauhidul Alam Choudhury2, Takhellambam Brojen Singh2 1
Professor, 2Senior Resident, Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi – 221005, Uttar Pradesh, India.
INTRODUCTION Varicella–zoster virus (VZV) infection is uncommon in renal transplant recipients with incidence ranged between 1% and 11%, but it is more serious in transplant patients than in general population.1,2 In adults, reactivation in the form of herpes-zoster is more common than primary infection because of ubiquitous occurrence of infection in childhood. Chicken pox, because of primary or re-infection, is very rare in adults and it could be associated with substantially high morbidity and mortality. We report two cases of post transplant chicken pox in adult patients.
CASE HISTORY Case 1 A 23-year-old male had undergone live-related renal transplant in March 1996 because of chronic pyelonephritis. The donor was his mother. Donor and recipient were ABO-compatible and pre-transplant human leukocyte antigen (HLA) matching showed two mismatches, one each at HLA-A and HLA-DR loci. He was on triple immunosuppressive regimen: Cyclosporine, azathioprine and steroids. His graft function was good with serum creatinine in the range of 0.8–1.3 mg/dL and no episode of acute rejection was noted. Six-year post transplant, he presented with high grade fever of 1 day duration with generalized vesiculopustular rash which started from scalp and involved trunk and back. Laboratory investigations including hemoglobin, total leukocyte count, liver and renal function tests, and chest radiograph were unremarkable. Clinical picture was suggestive of chicken pox. He was started on intravenous (IV)
acyclovir (10 mg/kg ter die sumendum [TDS]) for 14-days and immunosuppression was decreased. He recovered fully.
Case 2 A 28-year-old male patient received ABO-compatible renal allograft from his mother in June 2000 due to focal segmental glomerulosclerosis (FSGS). He received second live-related, ABO-compatible graft in June 2004 because of failure in previous graft. Pre-transplant HLA screening showed one mismatch at HLA-A locus. After transplant, his serum creatinine remained in the range of 0.7–1.3 mg/dL without occurrence of any acute rejection episode. He was on triple drug immunosuppression in the form of tacrolimus, azathioprine and steroids. In 2011, 7 years after his second transplant, he presented with severe retrosternal chest pain and dyspnea at rest of 2 days duration. On examination, his blood pressure was 134/86 mmHg, pulse was 98/min and respiratory rate was 34/min. Chest auscultation demonstrated crackles in right basal area. Chest radiograph showed bilateral lower zone infiltrates, more on right side. His serum creatinine was raised to 2.15 mg/dL. Serum glutamicoxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), serum lipase values were 1153 IU/L, 412 IU/L, and 373 IU/L, respectively, suggestive of acute hepatitis and pancreatitis. Cardiac enzymes and two-dimensional echo were normal. Arterial blood gas (ABG) analysis showed hypoxemic respiratory failure. Patient was prescribed IV antibiotics and supportive treatment. However, on 2nd day of admission, he developed typical vesiculopustular rash which started from face and spread to trunk, genitals, back and upper thigh region (Figure 1). Diagnosis of chicken pox with visceral dissemination was made on clinical ground. Patient was treated with IV acyclovir therapy (5 mg/kg TDS)
Correspondence: Dr. Surendra Singh Rathore, email: [email protected] doi: 10.1016/S2212-0017(12)60078-1
ISSN:2212-0017 Copyright © 2012. Indian Society of Organ Transplantation. All rights reserved.
28
Indian Journal of Transplantation 2012 January–March; Vol. 6, No. 1
Figure 1 Photograph shows extensive vesiculopustular rash with crusting and hemorrhagic transformation around genitals, an upper thigh area, in post transplant chicken pox patient. Similar lesions were noted over trunk, back, and face.
but his condition deteriorated, and 2 days later, he developed features of encephalopathy, disseminated intravascular coagulopathy (DIC), and multiple organ failure. He died of multiple organ failure which was attributed to chicken pox with visceral dissemination.
DISCUSSION Chicken pox is considered as common benign, self limiting infectious disease of pediatric population. More than 90% of adults are seropositive for VZV indicating exposure in childhood.3 In children, it presents as generalized papulovesicular eruption which starts from scalp or face and spreads in centripetal fashion. The most characteristic feature of varicella rash is the simultaneous presence of lesions at all stages of development—papules, vesicles, erosions, and crusts. Following primary infection, virus remains latent in dorsal root ganglia. However, viral reactivation can occur, either at the time of depressed immunity or spontaneously. This reactivation form is known as herpes-zoster (shingles), which is characterized by painful vesicular eruption in single dermatomal distribution. Both types of diseases which are thought to be benign could be cause of significant morbidity and mortality in immunocompromised transplant recipients. Reported incidence of VZV infection following renal transplant varies from 1% to 11%.1,2,4 It is uncommon during immediate post transplant period. The onset of VZV infection was reported with median duration of 6.6 months after renal transplant.1
Prakash et al.
Majority of such patients present with features of herpeszoster and presentation as chicken pox is rare. Most cases of post transplant chicken pox have been reported in pediatric patients.5 In adult renal transplant recipients, occurrence as chicken pox is an extremely rare event.6 In immunocompromised patients, herpes-zoster may present in disseminated form and may be confused with chicken pox or other viral infections. However, chicken pox can be differentiated from zoster on the basis of previous history of disease, presence of typical rash which start from face or scalp and spread in centripetal fashion, absence of characteristic pain associated with shingles, and negative VZV serology. Both of our patients neither had history of childhood occurrence of chicken pox nor received vaccination prior to transplantation. Although, VZV serology was not available, clinical ground was sufficient to label it as chicken pox. Visceral dissemination in chicken pox may cause multiple organ dysfunctions such as pneumonitis, encephalitis, hepatitis, pancreatitis, glomerulonephritis, and disseminated intravascular coagulation, in up to 33% cases and has very high case fatality rate.7–9 Also, it may have atypical presentation like pain abdomen, and systemic features and rash appear late in disease course which may cause delay in diagnosis.6 Our patient (case 2) had systemic features of visceral involvement with atypical presentation. He succumbed to illness despite treatment, while second patient (case 1) had milder form of disease and responded well to antiviral therapy. Limited data are available regarding epidemiology of VZV, risk factors and prognosis in transplant patients. Increasing age at transplant and use of induction therapy are only established risk factors.1,2 Earlier mycophenolate mofetil (MMF) was thought to be with increased risk of VZV infection but recent studies did not find any correlation.1,2,10 Antiviral prophylaxis in the form of acyclovir and/ or valganciclovir has been found to be protective for VZV infection during prophylaxis period.2 Since, delay in treatment could prove fatal, all cases should be treated aggressively with IV acyclovir. Varicella–zoster virus immunoglobulin can prevent infection following exposure only when administered early, however it has no role in established cases.8 Live attenuated vaccine is available for active immunization. It is recommended to determine VZV serology status prior to transplant and to provide vaccination to those with seronegative status.11
SUMMARY In summary, we reported two extremely rare cases of post transplant chicken pox in adults. In immunocompromised
Post transplant chicken pox
patients, it may have visceral involvement before appearance of typical rash which may cause delay in diagnosis. Hence, high index of suspicion is required for early detection.
REFERENCES 1.
2.
3.
4.
Gourishankar S, McDermid JC, Jhangri GS, Preiksaitis JK. Herpes zoster infection following solid organ transplantation: incidence, risk factors and outcomes in the current immunosuppressive era. Am J Transplant 2004;4:108–15. Arness T, Pedersen R, Dierkhising R, Kremers W, Patel R. Varicella zoster virus-associated disease in adult kidney transplant recipients: incidence and risk-factor analysis. Transplant Infect Dis 2008;10:260–8. Jenkins FJ, Rowe DT, Rinaldo CR. Herpesvirus infections in organ transplant recipients. Clin Diagn Lab Immunol 2003; 10:1–7. Rodriguez-Moreno A, Sanchez-Fructuoso AI, Calvo N, et al. Varicella infection in adult renal allograft recipients: experience at one center. Transplant Proc 2006;38:2416–8.
Case Report
5.
29
Lynfield R, Herrin JT, Rubin RH. Varicella in pediatric renal transplant recipients. Pediatrics 1992;90:216–20. 6. Ishikawa N, Tanabe K, Shimmura H, Tokumoto T, Toma H. Primary varicella virus in adult renal transplant recipients: case reports. Transplant Proc 2000;32:1952–3. 7. Smith SR, Butterly DW, Alexander BD, Greenberg A. Viral infections after renal transplantation. Am J Kidney Dis 2001; 37:659–76. 8. Fehr T, Bossart W, Wahl C, Binswanger U. Disseminated varicella infection in adult renal allograft recipients: four cases and a review of the literature. Transplantation 2002;73: 608–11. 9. Sato A, Amada N, Kikuchi H, Fukumori T, Haga I, Takahashi Y. Pneumonia due to varicella-zoster virus reinfection in a renal transplant recipient. Transplant Proc 2009;41:3959–61. 10. Lauzurica R, Bayés B, Frías C, et al. Disseminated varicella infection in adult renal allograft recipients: role of mycophenolate mofetil. Transplant Proc 2003;35:1758–9. 11. Kitai IC, King S, Gafni A. An economic evaluation of varicella vaccine for pediatric liver and kidney transplant recipients. Clin Infect Dis 1993;17:441–7.