0022-5347/91/1462-0417$03.00/0 THE JOURNAL OF UROLOGY Copyright© 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol. 146, 417-419, August 1991 Printed in U.S.A.
CYTOMEGALOVIRUS EPIDIDYMITIS FOLLOWING RENAL TRANSPLANTATION J. M. McCARTHY, M. G. McLOUGHLIN, C. R. SHACKLETON, E. C. CAMERON, C. K. YEUNG, E. C. JONES AND P. A. KEOWN From the Departments of Medicine, Surgery and Pathology, Vancouver General Hospital, University of British Columbia and British Columbia Transplant Society, Vancouver, British Columbia, Canada
ABSTRACT Cytomegalovirus infection is an important cause of morbidity and mortality in immunocompro mised individuals. The disease is usually systemic in expression although localized infection can occur, particularly in the lung, liver, retina and gastrointestinal tract. We report a case of cytomeg alovirus epididymitis with limited systemic manifestations occurring 2 months after renal trans plantation in a patient immunosuppressed with azathioprine, prednisone and cyclosporine. Diag nosis was confirmed by observation of typical cytopathic changes in epididymal cells. Clinical resolution occurred with epididymo-orchiectomy and 9-(1,3-dihydroxy-2-proproxymethyl)guanine therapy. To our knowledge this presentation has not been described previously in the transplant literature and it is extremely rare in other forms of inherited or acquired immune deficiency. KEY WORDS: cytomegaloviruses, epididymitis, kidney, transplantation
Cytomegalovirus disease of immunocompromised hosts, in cluding those therapeutically immunosuppressed after organ transplantation, causes extensive morbidity and mortality. The lung, liver, retina and intestinal tract have been the traditional sites affected. However, with the expanded use of increasingly potent immunosuppressive agents and with a rapidly growing population of individuals suffering from the acquired immu nodeficiency syndrome (AIDS), opportunistic infections are occurring at previously atypical sites. Awareness of this evolv ing pattern of cytomegalovirus disease is necessary to minimize morbidity and mortality in this susceptible population. We present a case of cytomegalovirus epididymitis in a patient immunosuppressed after renal transplantation to illus trate the unusual presentations of cytomegalovirus disease, and the possible diagnostic and therapeutic approaches available. CASE REPORT
A 61-year-old man received a cadaveric renal transplant in the left iliac fossa in November 1989. The donor and recipient were cytomegalovirus IgG seropositive. Immunosuppression was commenced with 15 mg./kg. Minnesota antilymphocyte globulin per day for 5 days, 1.5 mg./kg. azathioprine per day, 1 mg./kg. prednisone per day and 5 mg./kg. cyclosporine per day, the latter 2 agents being progressively tapered. Cytomegalovirus hyperimmune globulin and acyclovir were not administered prophylactically. The immediate postoperative period was com plicated by oral herpes, oral candidiasis and an Escherichia coli urinary tract infection that responded to acyclovir, nystatin and cephalexin, respectively. Satisfactory graft function was achieved and the patient was discharged from the hospital in December, well, fully ambulatory and with a serum creatinine of 132 µmol./1. He was rehospitalized 7 weeks after transplantation with a suspected left scrotal abscess. At hospitalization the blood pressure was 168/100 mm. Hg, heart rate 120 per minute and temperature 38.8C. There was no lymphadenopathy or icterus. Cardiovascular examination revealed a grade 2/6 systolic ejec tion murmur at the left sternal border. There were no abnormal respiratory findings and abdominal examination was unre markable. The transplanted kidney was nontender and the right iliac fossa incision was well healed. Genital examination revealed 2, 1.0 x 0.5 cm. ulcers in the perianal region. The Accepted for publication December 21, 1990.
penis was uncircumcised, with a candidal infection beneath the prepuce and on the scrotum, which was erythematous and inflamed by the nearly constant dribbling of urine. A 4 x 4 cm. minimally tender mass was palpable in the left hemiscrotum. The testes and prostate were normal in size and character. The chest x-ray was normal and the white blood count was 6.1 X 109/1. (normal 4 to 11.0) with 98% granulocytes. Serum creati nine was 105 µmol./1. (normal 60 to 110), urea 7.4 mmol./1. (normal 1.8 to 8.2), alkaline phosphatase 109 U./1. (normal 45 to 125), AST 46 U./1. (normal 19 to 38) and lactic dehydro genase 249 U./1. (normal 90 to 210). The trough whole blood cyclosporine level was 217 µg./1. Ultrasound examination con firmed a left scrotal mass and showed compression of the left testicle. Blood cultures for aerobes and anaerobes were negative on 4 separate occasions within 10 days of hospitalization. A urine culture yielded 25 x 109 colonies per l. mixed organisms but all other cultures were negative. The scrotal swelling was believed to be consistent with clas sical epididymitis and 2 gm. intravenous ceftriaxone every 24 hours were given to cover likely pathogens. Despite antibiotic therapy, and persistently negative blood and urine cultures, the patient remained febrile and appeared ill. The perianal ulcers extended and new lesions typical of Herpes simplex virus appeared on the chin. These lesions were positive on culture for Herpes simplex virus and responded to oral acyclovir with out improvement in the testicular mass. Because of continuing clinical deterioration epididymo-orchiectomy was performed and antibiotics were discontinued. Microscopic examination of the resected epididymal tissues revealed typical cytomegalic cells containing large central basophilic intranuclear inclusions. Testicular tissues were uninvolved. Cytomegalovirus was iso lated from the urine. Intravenous 9-(1,3-dihydroxy-2-propoxy methyl)guanine (DHPG) therapy was instituted at 5 mg./kg. twice daily, and there was a steady improvement in clinical and laboratory parameters with resolution of the fever on day 4. Shortly thereafter, the white blood count decreased from 6.2 to 1.7 X 109/1. and the hemoglobin decreased from 88 to 61 gm.fl. despite withdrawal of azathioprine. Hepatic function deterio rated, with the lactic dehydrogenase level increasing from 188 to 280 U./1. and the GGT increasing to 94 U./1. (normal 10 to 50). DHPG therapy was uninterrupted by the leukopenia and was given for a total of 14 days. A month after discharge from the hospital the patient was completely asymptomatic. The white blood count was 6.6 x 109/1., hemoglobin 117 gm.fl.
417
418
MCCARTHY AND ASSOCIATES
(normal 145 to 175) and lactic dehydrogenase 239 U./1. DISCUSSION
The etiology of acute epididymitis is generally age dependent. In men younger than 35 years sexually transmitted organisms, such as Chlamydia trachomatis, Neisseria gonorrhea and Urea plasma urealyticum, are principally responsible, while in chil dren, older men and those with structural abnormalities E. coli and other more common urinary tract pathogens predominate. 1 Immunosuppressed individuals follow this pattern in most cases but are occasionally susceptible to more exotic agents, including Nocardia asteroides. 2 Cytomegalovirus, the largest member of the herpesvirus fam ily, is a ubiquitous, species specific, deoxyribonucleic acid (DNA) virus of clinical importance in immunosuppressed and nonimmunosuppressed populations. The virus is carried in blood, spermatic fluid, oral and genital secretions, urine and breast milk, and transmission occurs by genital, orpharyngeal and intravenous routes. Infection rates in North America range from 1% in neonates to approximately 60% in normal adults; rates in certain special populations, such as homosexual men and those in underdeveloped countries, approach 100%. 3 Cyto megalovirus infection frequently is subclinical in nonimmuno compromised populations although overt disease can result as manifested by the cytomegalovirus mononucleosis syndrome. 3• With the appearance of AIDS, and the expanded use of increasingly potent immunosuppressive agents in transplanta tion and autoimmune disease, cytomegalovirus disease is ap pearing with greater frequency and diversity of presentation. Cytomegalovirus causes greater morbidity and mortality than any other organism in therapeutically immunosuppressed pop ulations, and clinically detectable disease occurs in 2 to 60% of all renal transplant patients. 3• 5 The frequency and severity of disease are dependent on pre-transplant immunity, the degree of immunosuppression and the cytomegalovirus status of the graft donor. Reactivation of latent recipient virus and primary infection may occur. In transplant recipients cytomegalovirus disease commonly appears as pneumonitis, gastroenteritis or hepatitis but it can occur at other sites, 3• 5• 6 Retinitis, the most common manifestation of cytomegalovirus disease in AIDS patients, is uncommon in the transplant population for reasons that are not established. Cytomegalovirus epididymitis, to our knowledge, has not been reported previously in the transplant population and it is extremely rare in AIDS patients. 7 The morbidity and mortality accompanying cytomegalovirus infec tion occur as a consequence of direct tissue infection and through the immunomodulating effects of the virus potentiat ing superinfection. During cytomegalovirus infection the ability to mount a leukocyte response to foreign antigen is diminished, T helper cell number and function are decreased, T suppressor count is increased and interferon production is decreased. 3• 8 Our patient suffered from 3 concurrent bacterial, fungal and viral infections, emphasizing this clustering effect. The differentiation between benign shedding of cytomeg alovirus and clinical disease is not always simple. Diagnosis in immunosuppressed individuals is best accomplished by isolat ing viral antigen, DNA or ribonucleic acid from human diploid fibroblast culture of cells or secretions from clinically affected sites, or by demonstrating typical cytopathic effect in infected cells. 3• 9 In our patient microscopic examination revealed dila tation and necrosis of the epididymal tubules, and acute and chronic inflammation in the surrounding stroma with fibroblast proliferation and numerous cytomegalovirus inclusions within stromal cells (figs. 1 and 2). Prevention or attenuation of cytomegalovirus disease has been attempted by matching cytomegalovirus status or organ donor and recipient, transfusing only cytomegalovirus negative blood, minimizing immunosuppression and using immunoglob ulin or acyclovir prophylaxis when other measures are not
FIG. 1. Transverse section reveals thickening, inflammation, ab scess formation and necrosis of epididymis (arrow) without involve ment of adjacent testis.
4
FIG. 2. Epididymis reveals cytomegalovirus infected cells (arrows) within inflamed stroma. Note cellular enlargement, large intranuclear inclusions with surrounding halo and granular cytoplasmic inclusions, H & E, reduced from X250.
practical or sufficient. Before the development of effective antiviral agents, cytomegalovirus infection required a decrease in or discontinuation of immunosuppressive therapy with fre quent graft loss. The present treatment of choice for serious cytomegalovirus disease is DHPG alone or in combination with hyperimmune anti-cytomegalovirus globulin, 10- 1 2 although other agents are under investigation in certain settings, 13 DHPG was chosen in this case because of our experience with this agent 14 and its reported efficacy in localized infection. Resolution of clinical symptoms was rapid although marked leukopenia, the most significant side effect of DHPG therapy, occurred with the white blood count reaching 1. 7 X 109 /1. Although recurrence in the contralateral epididymis is a pos sibility, maintenance therapy is of less importance once the diseased tissue is excised. In summary, immunocompromised patients are subject to atypical causes and presentations of disease that require ag gressive diagnostic measures and consideration of the unusual to prevent excessive morbidity and mortality. This case illus trates how such an awareness can lead to the accurate diagnosis and successful treatment of an unusual cytomegalovirus infec tion. REFERENCES
1. Melekos, M. D. and Asbach, H. W.: Epididymitis: aspects concern ing etiology and treatment. J. UroL, 138: 83, 1987. 2. Wheeler, J. S., Jr., Culkin, D. J., O'Connell, J. and Winters, G.: Nocardia epididymo-orchitis in an immunosuppressed patient. J. Urol., 136: 1314, 1986.
CYTOLfEGALOVIRDS EP!DiDYMlTIS FOLLOV,/II,JG RENAL TRAl�SPLANTATION 3. Aulitzky, W. E., Hengster, P., Tilg, H., Schulz, T., Die1·ich, !Vi. an_d Huber, C.: Cytomegalovirus infection. Wien. Klin. Wchnschr., 100: 33, 1988. 4. Kinney, J. S., Onorato, I. M., Stewart, J. A., Pass, R. F., Stagno, S., Cheeseman, S. H., Chin, J., Kumar, M. L., Yaeger, A. S., Herrmann, K. L., Hurwitz, E. S. and Schonberger, L. B.: Cyto megaloviral infection and disease. J. Infect. Dis., 151: 772, 1985. 5. Rubin, R. H., Tolkoff-Rubin, N. E., Oliver, D., Rota, T. R., Hamilton, J., Betts, R. F., Pass, R. F., Hillis, W., Szmuness, W., Farrell, M. L. and Hirsch, M.: Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal trans plantation. Transplantation, 40: 243, 1985. 6. Smiley, M. L., Wlodaver, C. G., Grossman, R. A., Barker, C. F., Perloff, L. J., Tustin, N. B., Starr, S. E., Plotkin, S. A. and Friedman, H. M.: The role of pretransplant immunity in protec tion from cytomegalovirus disease following renal transplanta tion. Transplantation, 40: 157, 1985. 7. Randazzo, R. F., Hulette, C. M., Gottlieb, M. S. and Rajfer, J.: Cytomegaloviral epididymitis in a patient with the acquired immune deficiency syndrome. J. Urol., 136: 1095, 1986. 8. Rook, A. H.: Interactions of cytomegalovirus with the human immune system. Rev. Infect. Dis., suppl. 3, 10: S460, 1988.
419
9. Drew, W. L.: Diagnosis of cytomegaiovirus infection. Rev. Infect. Dis., suppl. 3, 10: 8468, 1988. 10. Collaborative DHPG Treatment Study Group: Treatment of seri ous cytomegalovirus infections with 9-(1,3-dihydroxy-2-propox ymethyi)guanine in patients with AIDS and other immunodefi ciencies. New Engl. J. Med., 314: 801, 1986. 11. Verheyden, J. P.: Evolution of therapy for cytomegalovirus infec tion. Rev. Infect. Dis., suppl. 3, 10: 8477, 1988. 12. LeHoang, P., Girard, B., Robinet, M., Marcel, P., Zazoun, L., Matheron, S., Rozenbaum, W., Katlama, C., Marer, I., Lernestedt, J. 0., Saraux, H., Pouliquen, Y., Gentilins, M. and Rousselie, F.: Foscarnet in the treatment of cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmol ogy, 96: 865, 1989. 13. Jacobson, M. A. and Mills, J.: Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical find ings, diagnosis, and treatment. Ann. Intern. Med., 108: 585, 1988. 14. Jones, C., Damji, K., Landsberg, D. and Keown, P.: Efficacy of ganciclovir in renal transplant (RTx) patients with CMV disease. Proc. Roy. Coll. Phys. Surg., Toronto, Canada, p. B133, abstract 815, 1990.
Vol. 146, 417-419, August 1991 Printed in U.S.A.
CYTOMEGALOVIRUS EPIDIDYMITIS FOLLOWING RENAL TRANSPLANTATION J. M. McCARTHY, M. G. McLOUGHLIN, C. R. SHACKLETON, E. C. CAMERON, C. K. YEUNG, E. C. JONES AND P. A. KEOWN From the Departments of Medicine, Surgery and Pathology, Vancouver General Hospital, University of British Columbia and British Columbia Transplant Society, Vancouver, British Columbia, Canada
ABSTRACT Cytomegalovirus infection is an important cause of morbidity and mortality in immunocompro mised individuals. The disease is usually systemic in expression although localized infection can occur, particularly in the lung, liver, retina and gastrointestinal tract. We report a case of cytomeg alovirus epididymitis with limited systemic manifestations occurring 2 months after renal trans plantation in a patient immunosuppressed with azathioprine, prednisone and cyclosporine. Diag nosis was confirmed by observation of typical cytopathic changes in epididymal cells. Clinical resolution occurred with epididymo-orchiectomy and 9-(1,3-dihydroxy-2-proproxymethyl)guanine therapy. To our knowledge this presentation has not been described previously in the transplant literature and it is extremely rare in other forms of inherited or acquired immune deficiency. KEY WORDS: cytomegaloviruses, epididymitis, kidney, transplantation
Cytomegalovirus disease of immunocompromised hosts, in cluding those therapeutically immunosuppressed after organ transplantation, causes extensive morbidity and mortality. The lung, liver, retina and intestinal tract have been the traditional sites affected. However, with the expanded use of increasingly potent immunosuppressive agents and with a rapidly growing population of individuals suffering from the acquired immu nodeficiency syndrome (AIDS), opportunistic infections are occurring at previously atypical sites. Awareness of this evolv ing pattern of cytomegalovirus disease is necessary to minimize morbidity and mortality in this susceptible population. We present a case of cytomegalovirus epididymitis in a patient immunosuppressed after renal transplantation to illus trate the unusual presentations of cytomegalovirus disease, and the possible diagnostic and therapeutic approaches available. CASE REPORT
A 61-year-old man received a cadaveric renal transplant in the left iliac fossa in November 1989. The donor and recipient were cytomegalovirus IgG seropositive. Immunosuppression was commenced with 15 mg./kg. Minnesota antilymphocyte globulin per day for 5 days, 1.5 mg./kg. azathioprine per day, 1 mg./kg. prednisone per day and 5 mg./kg. cyclosporine per day, the latter 2 agents being progressively tapered. Cytomegalovirus hyperimmune globulin and acyclovir were not administered prophylactically. The immediate postoperative period was com plicated by oral herpes, oral candidiasis and an Escherichia coli urinary tract infection that responded to acyclovir, nystatin and cephalexin, respectively. Satisfactory graft function was achieved and the patient was discharged from the hospital in December, well, fully ambulatory and with a serum creatinine of 132 µmol./1. He was rehospitalized 7 weeks after transplantation with a suspected left scrotal abscess. At hospitalization the blood pressure was 168/100 mm. Hg, heart rate 120 per minute and temperature 38.8C. There was no lymphadenopathy or icterus. Cardiovascular examination revealed a grade 2/6 systolic ejec tion murmur at the left sternal border. There were no abnormal respiratory findings and abdominal examination was unre markable. The transplanted kidney was nontender and the right iliac fossa incision was well healed. Genital examination revealed 2, 1.0 x 0.5 cm. ulcers in the perianal region. The Accepted for publication December 21, 1990.
penis was uncircumcised, with a candidal infection beneath the prepuce and on the scrotum, which was erythematous and inflamed by the nearly constant dribbling of urine. A 4 x 4 cm. minimally tender mass was palpable in the left hemiscrotum. The testes and prostate were normal in size and character. The chest x-ray was normal and the white blood count was 6.1 X 109/1. (normal 4 to 11.0) with 98% granulocytes. Serum creati nine was 105 µmol./1. (normal 60 to 110), urea 7.4 mmol./1. (normal 1.8 to 8.2), alkaline phosphatase 109 U./1. (normal 45 to 125), AST 46 U./1. (normal 19 to 38) and lactic dehydro genase 249 U./1. (normal 90 to 210). The trough whole blood cyclosporine level was 217 µg./1. Ultrasound examination con firmed a left scrotal mass and showed compression of the left testicle. Blood cultures for aerobes and anaerobes were negative on 4 separate occasions within 10 days of hospitalization. A urine culture yielded 25 x 109 colonies per l. mixed organisms but all other cultures were negative. The scrotal swelling was believed to be consistent with clas sical epididymitis and 2 gm. intravenous ceftriaxone every 24 hours were given to cover likely pathogens. Despite antibiotic therapy, and persistently negative blood and urine cultures, the patient remained febrile and appeared ill. The perianal ulcers extended and new lesions typical of Herpes simplex virus appeared on the chin. These lesions were positive on culture for Herpes simplex virus and responded to oral acyclovir with out improvement in the testicular mass. Because of continuing clinical deterioration epididymo-orchiectomy was performed and antibiotics were discontinued. Microscopic examination of the resected epididymal tissues revealed typical cytomegalic cells containing large central basophilic intranuclear inclusions. Testicular tissues were uninvolved. Cytomegalovirus was iso lated from the urine. Intravenous 9-(1,3-dihydroxy-2-propoxy methyl)guanine (DHPG) therapy was instituted at 5 mg./kg. twice daily, and there was a steady improvement in clinical and laboratory parameters with resolution of the fever on day 4. Shortly thereafter, the white blood count decreased from 6.2 to 1.7 X 109/1. and the hemoglobin decreased from 88 to 61 gm.fl. despite withdrawal of azathioprine. Hepatic function deterio rated, with the lactic dehydrogenase level increasing from 188 to 280 U./1. and the GGT increasing to 94 U./1. (normal 10 to 50). DHPG therapy was uninterrupted by the leukopenia and was given for a total of 14 days. A month after discharge from the hospital the patient was completely asymptomatic. The white blood count was 6.6 x 109/1., hemoglobin 117 gm.fl.
417
418
MCCARTHY AND ASSOCIATES
(normal 145 to 175) and lactic dehydrogenase 239 U./1. DISCUSSION
The etiology of acute epididymitis is generally age dependent. In men younger than 35 years sexually transmitted organisms, such as Chlamydia trachomatis, Neisseria gonorrhea and Urea plasma urealyticum, are principally responsible, while in chil dren, older men and those with structural abnormalities E. coli and other more common urinary tract pathogens predominate. 1 Immunosuppressed individuals follow this pattern in most cases but are occasionally susceptible to more exotic agents, including Nocardia asteroides. 2 Cytomegalovirus, the largest member of the herpesvirus fam ily, is a ubiquitous, species specific, deoxyribonucleic acid (DNA) virus of clinical importance in immunosuppressed and nonimmunosuppressed populations. The virus is carried in blood, spermatic fluid, oral and genital secretions, urine and breast milk, and transmission occurs by genital, orpharyngeal and intravenous routes. Infection rates in North America range from 1% in neonates to approximately 60% in normal adults; rates in certain special populations, such as homosexual men and those in underdeveloped countries, approach 100%. 3 Cyto megalovirus infection frequently is subclinical in nonimmuno compromised populations although overt disease can result as manifested by the cytomegalovirus mononucleosis syndrome. 3• With the appearance of AIDS, and the expanded use of increasingly potent immunosuppressive agents in transplanta tion and autoimmune disease, cytomegalovirus disease is ap pearing with greater frequency and diversity of presentation. Cytomegalovirus causes greater morbidity and mortality than any other organism in therapeutically immunosuppressed pop ulations, and clinically detectable disease occurs in 2 to 60% of all renal transplant patients. 3• 5 The frequency and severity of disease are dependent on pre-transplant immunity, the degree of immunosuppression and the cytomegalovirus status of the graft donor. Reactivation of latent recipient virus and primary infection may occur. In transplant recipients cytomegalovirus disease commonly appears as pneumonitis, gastroenteritis or hepatitis but it can occur at other sites, 3• 5• 6 Retinitis, the most common manifestation of cytomegalovirus disease in AIDS patients, is uncommon in the transplant population for reasons that are not established. Cytomegalovirus epididymitis, to our knowledge, has not been reported previously in the transplant population and it is extremely rare in AIDS patients. 7 The morbidity and mortality accompanying cytomegalovirus infec tion occur as a consequence of direct tissue infection and through the immunomodulating effects of the virus potentiat ing superinfection. During cytomegalovirus infection the ability to mount a leukocyte response to foreign antigen is diminished, T helper cell number and function are decreased, T suppressor count is increased and interferon production is decreased. 3• 8 Our patient suffered from 3 concurrent bacterial, fungal and viral infections, emphasizing this clustering effect. The differentiation between benign shedding of cytomeg alovirus and clinical disease is not always simple. Diagnosis in immunosuppressed individuals is best accomplished by isolat ing viral antigen, DNA or ribonucleic acid from human diploid fibroblast culture of cells or secretions from clinically affected sites, or by demonstrating typical cytopathic effect in infected cells. 3• 9 In our patient microscopic examination revealed dila tation and necrosis of the epididymal tubules, and acute and chronic inflammation in the surrounding stroma with fibroblast proliferation and numerous cytomegalovirus inclusions within stromal cells (figs. 1 and 2). Prevention or attenuation of cytomegalovirus disease has been attempted by matching cytomegalovirus status or organ donor and recipient, transfusing only cytomegalovirus negative blood, minimizing immunosuppression and using immunoglob ulin or acyclovir prophylaxis when other measures are not
FIG. 1. Transverse section reveals thickening, inflammation, ab scess formation and necrosis of epididymis (arrow) without involve ment of adjacent testis.
4
FIG. 2. Epididymis reveals cytomegalovirus infected cells (arrows) within inflamed stroma. Note cellular enlargement, large intranuclear inclusions with surrounding halo and granular cytoplasmic inclusions, H & E, reduced from X250.
practical or sufficient. Before the development of effective antiviral agents, cytomegalovirus infection required a decrease in or discontinuation of immunosuppressive therapy with fre quent graft loss. The present treatment of choice for serious cytomegalovirus disease is DHPG alone or in combination with hyperimmune anti-cytomegalovirus globulin, 10- 1 2 although other agents are under investigation in certain settings, 13 DHPG was chosen in this case because of our experience with this agent 14 and its reported efficacy in localized infection. Resolution of clinical symptoms was rapid although marked leukopenia, the most significant side effect of DHPG therapy, occurred with the white blood count reaching 1. 7 X 109 /1. Although recurrence in the contralateral epididymis is a pos sibility, maintenance therapy is of less importance once the diseased tissue is excised. In summary, immunocompromised patients are subject to atypical causes and presentations of disease that require ag gressive diagnostic measures and consideration of the unusual to prevent excessive morbidity and mortality. This case illus trates how such an awareness can lead to the accurate diagnosis and successful treatment of an unusual cytomegalovirus infec tion. REFERENCES
1. Melekos, M. D. and Asbach, H. W.: Epididymitis: aspects concern ing etiology and treatment. J. UroL, 138: 83, 1987. 2. Wheeler, J. S., Jr., Culkin, D. J., O'Connell, J. and Winters, G.: Nocardia epididymo-orchitis in an immunosuppressed patient. J. Urol., 136: 1314, 1986.
CYTOLfEGALOVIRDS EP!DiDYMlTIS FOLLOV,/II,JG RENAL TRAl�SPLANTATION 3. Aulitzky, W. E., Hengster, P., Tilg, H., Schulz, T., Die1·ich, !Vi. an_d Huber, C.: Cytomegalovirus infection. Wien. Klin. Wchnschr., 100: 33, 1988. 4. Kinney, J. S., Onorato, I. M., Stewart, J. A., Pass, R. F., Stagno, S., Cheeseman, S. H., Chin, J., Kumar, M. L., Yaeger, A. S., Herrmann, K. L., Hurwitz, E. S. and Schonberger, L. B.: Cyto megaloviral infection and disease. J. Infect. Dis., 151: 772, 1985. 5. Rubin, R. H., Tolkoff-Rubin, N. E., Oliver, D., Rota, T. R., Hamilton, J., Betts, R. F., Pass, R. F., Hillis, W., Szmuness, W., Farrell, M. L. and Hirsch, M.: Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal trans plantation. Transplantation, 40: 243, 1985. 6. Smiley, M. L., Wlodaver, C. G., Grossman, R. A., Barker, C. F., Perloff, L. J., Tustin, N. B., Starr, S. E., Plotkin, S. A. and Friedman, H. M.: The role of pretransplant immunity in protec tion from cytomegalovirus disease following renal transplanta tion. Transplantation, 40: 157, 1985. 7. Randazzo, R. F., Hulette, C. M., Gottlieb, M. S. and Rajfer, J.: Cytomegaloviral epididymitis in a patient with the acquired immune deficiency syndrome. J. Urol., 136: 1095, 1986. 8. Rook, A. H.: Interactions of cytomegalovirus with the human immune system. Rev. Infect. Dis., suppl. 3, 10: S460, 1988.
419
9. Drew, W. L.: Diagnosis of cytomegaiovirus infection. Rev. Infect. Dis., suppl. 3, 10: 8468, 1988. 10. Collaborative DHPG Treatment Study Group: Treatment of seri ous cytomegalovirus infections with 9-(1,3-dihydroxy-2-propox ymethyi)guanine in patients with AIDS and other immunodefi ciencies. New Engl. J. Med., 314: 801, 1986. 11. Verheyden, J. P.: Evolution of therapy for cytomegalovirus infec tion. Rev. Infect. Dis., suppl. 3, 10: 8477, 1988. 12. LeHoang, P., Girard, B., Robinet, M., Marcel, P., Zazoun, L., Matheron, S., Rozenbaum, W., Katlama, C., Marer, I., Lernestedt, J. 0., Saraux, H., Pouliquen, Y., Gentilins, M. and Rousselie, F.: Foscarnet in the treatment of cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmol ogy, 96: 865, 1989. 13. Jacobson, M. A. and Mills, J.: Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical find ings, diagnosis, and treatment. Ann. Intern. Med., 108: 585, 1988. 14. Jones, C., Damji, K., Landsberg, D. and Keown, P.: Efficacy of ganciclovir in renal transplant (RTx) patients with CMV disease. Proc. Roy. Coll. Phys. Surg., Toronto, Canada, p. B133, abstract 815, 1990.
