CASE REPORTS Herpes Simplex Virus Encephalitis in a Renal Transplant Patient: Diagnosis by Polymerase Chain Reaction Detection of HSV DNA Ernest0 G6mez, MD, Santiago Melbn, MD, Sixto Aguado, MD, Jo& Emilio SBnchez, MD, Carmen Portal, MD, Ana Fernandez, MD, Ana Martinez, MD, Maria Luisa Sbchez, MD, and Jaime Alvarez, MD 0 A case of herpes simplex virus (HSV) encephalitis with disseminated primary HSV infection in a renal transplant patient is described. The diagnosis of the disease was achieved by nested polymerase chain reaction (PC%)-DNA in cerebrospinal fluid (CSF). Other diagnostic measures (immunoglobulin [lg] M and virological cultures both in blood and CSF) were negative. Blood IgG gave a false-positive signal. Although ganciclovir is not the drug of choice, its concomitant administration in our patient as a prophylactic measure against CMV infection may have decreased the usual severity normally expected in this kind of primary HSV infection. The subsequent increase in ganciclovir dose to full therapeutic range, which was implemented before the diagnosis was achieved, led to the disappearance of symptoms. The detection of PCR-DNA in CSF will probably become the diagnostic method of choice. One of its great advantages, in addition to its diagnostic reliability, is that it may obviate the performance of many cerebral biopsies. 0 7997 by the National Kidney Foundation, Inc. INDEX WORDS: Herpes simplex; encephalitis; PCR; renal transplant. H ERPES simplex virus (HSV) encephalitis is an uncommon disease in immunocom- promised patients.’ The diagnosis used to be made by culture of the virus in brain tissue, be- cause other methods were unreliable. Thus, viral culture in cerebrospinal fluid (CSF) was achieved in only 4% of patients2 Furthermore, because the production of antibodies is delayed in these immunosuppressed patients, any treatment based on its detection in CSF may begin too late to be effective.3 Recent reports have shown that isolation of the viral genome by polymerase chain reaction (PCR) in CSF allows a rapid diagnosis of the disease.4‘6 These findings have now been con- firmed by further studies that compare the detec- tion of PCR in CSF with viral cultures of brain tissue obtained by biopsy or necropsy.7 The high sensitivity and specificity of PCR tests has led to this technique being the diagnostic method of choice. We describe a case of disseminated disease with primary HSV encephalitis diagnosed using HSV-DNA detection in CSF by nested PCR. Di- agnostic and therapeutic problems are also dis- cussed. CASE REPORT A 36-year-old white man who began hemodialysis in De- cember 1976 because of end-stage renal failure of unknown origin received a first cadaveric renal transplant in March 1979. In June 1982, the patient underwent further hemodialy- sis because of chronic rejection. The serological status of both donor and recipient regarding HSV was unknown. In November 1987 a second cadaveric renal transplant was implanted. Pretransplantation serology showed that the patient was cytomegalovirus (CMV) immunoglobulin (Ig) G positive, varicella zoster virus (VZV) IgG positive, and Ep- stein-Barr virus (EBV) IgG positive, but HSV 1 and HSV 2 IgG negative. This second graft lasted until June 1988, when the patient once again underwent hemodialysis because of chronic rejection. In March 1993, a new serology was ob- tained, showing identical results. On April 6, 1995, the patient received a third cadaveric kidney graft. At this moment, the patient had received a total of 51 blood transfusions. However, pretransplantation serology remained unchanged with respect to the last determi- nation. Pretransplantation anti-hepatitis C virus (HCV) anti- bodies were positive, whereas tests for hepatitis B and human immunodeficiency virus (HIV) were negative. The donor was a 21-year-old woman who died of cranial trauma. Premortem viral serology showed serum IgG positiv- ity against HSV. Serological (IgG) tests for CMV, VZV, and EBV were all positive, and hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV tests were all negative. The immunosuppressive protocol included monoclonal OKT3 antibodies, low-dose prednisone, azathioprine, and cyclosporine. Ganciclovir was included prophylactically against CMV, following the protocol previously described.8 From the Nephrology and Microbiology Services, Hospital Central de Asturias, Oviedo, Spain. Received July 15, 1996; accepted in revised form March 11, 1997. Address reprint requests to Ernest0 Gdmez, MD, Nephrol- ogy Service, Hospital Central de Asturias, c/ Celestino Vil- lamil s/n, 33006 Oviedo, Spain. 0 1997 by the National Kidney Foundation, Inc. 0272-6386/97/3003-0015$3.00/O American Journal of Kidney Diseases, Vol 30, No 3 (September), 1997: pp 423-427 423