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Infectious diseases Board Review Manual Statement of Editorial Purpose The Hospital Physician Infectious Diseases Board Review Manual is a study guide for fellows and practicing physicians preparing for board exam inations in infectious diseases. Each manual reviews a topic essential to current practice in the subspecialty of infectious diseases. The Hospital Physician® Infectious Diseases Board Review Manuals are published by Turner White Communications, Inc., an independent medical publisher dedicated to serving the information and education needs of clinical trainees and practicing physicians. PUBLISHING STAFF PRESIDENT, Group PUBLISHER Bruce M. White Senior EDITOR Robert Litchkofski executive vice president Viral Infections in the Immunocompromised . Patient: Herpesviruses Series Editor: Varsha Moudgal, MD Infectious Diseases Fellowship Program Director, St. Joseph Mercy Hospital, Ann Arbor, MI; and Assistant Professor of Medicine, Wayne State University School of Medicine, Detroit, MI Contributor: Gregory M. Anstead, MD, PhD Associate Professor of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX; Director, Immunosuppression and Infectious Diseases Clinics, South Texas Veterans Health Care System, San Antonio, TX Barbara T. White executive director of operations Jean M. Gaul Table of Contents Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Factors Associated with Specific Infections. . . . . . . . . . . . . . . . 4 NOTE FROM THE PUBLISHER: This publication has been developed with out involvement of or review by the Amer ican Board of Internal Medicine. The Herpesviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Copyright 2012 by Turner White Communications Inc., Wayne, PA. All rights reserved. www.hpboardreview.com Infectious Diseases Volume 13, Part 3 Infectious Diseases Board Review Manual Viral Infections in the Immunocompromised Patient: Herpesviruses Gregory M. Anstead, MD, PhD INTRODUCTION Immunocompromised patients are at risk for infection from a variety of opportunistic viral pathogens and may also suffer more severe manifestations from common community-acquired viruses. For the purposes of this review, immunocompromised patients include recipients of solid organ transplants (SOT), bone marrow transplants (BMT), and hematopoietic stem cell transplants (HSCT); those on immunomodulator therapy; and patients with HIV infection. In part 1 of this 2-part review on viral infections in immunocompromised patients, infections due to viruses of the family Herpesviridae will be addressed; these viruses include human herpesviruses 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesviruses-6 and -8 (HHV-6, HHV-8). The second part of the review will focus on infections due to other major viral pathogens: parvovirus B19, the respiratory viruses, the JC and BK viruses, lymphocytic choriomeningitis virus, rabies virus, and West Nile virus (WNV). These reviews will not cover infection with the human papillomavirus and the hepatitis viruses A, B, C, D, and E. The broad range of pathogens and the potential for rapid progression of disease mandates a prompt diagnostic approach in the immunosuppressed patient with suspected viral infection. General diagnostic techniques for viral infections include biopsy with histopathologic/cytologic exam as well as viral culture, polymerase chain reaction (PCR), and antigen detection performed on tissue and/or body fluids, depending on the specific virus. Also, in the case of suspected disease due to a specific pathogen, empiric treatment may be necessary, pending a definitive diagnosis. For infections in transplant patients for which a specific antiviral medication is not available, the patient may benefit from modification of the immunosuppressive regimen.1 Hospital Physician Board Review Manual Factors Associated with Specific Infections Immunosuppressive Regimens The susceptibility of a transplant patient to infection depends on his or her particular immunosuppressive regimen. Cytotoxic agents such as cyclophosphamide and azathioprine are associated with high risk for CMV reactivation.2 Corticosteroids have broadly immunosuppressive effects, but the introduction of calcineurin inhibitors, such as cyclosporine and tacrolimus, has allowed a dose reduction of corticosteroids, with fewer infectious disease complications.3 No differences in overall infection rate have been observed among patients receiving cyclosporine or tacrolimus4; however, tacrolimus is suspected to increase the risk of BK virus nephropathy as compared to cyclosporine.5 Mycophenolate mofetil (MMF) is a selective inhibitor of purine biosynthesis, preventing the proliferation of T and B cells; it has largely replaced azathioprine in transplant immunosuppressive regimens.5 However, MMF use is associated with a higher risk of CMV infection.4 Tacrolimus and MMF have been associated with an increased risk for parvovirus B19 infection.6 Polyclonal antilymphocyte serums and antithymocyte globulins (lymphocyte-depleting antibodies) are used in transplant induction regimens and to treat rejection. However, these agents cause increased risk of CMV disease and post-transplant lymphoproliferative disease due to EBV.7,8 It has been suggested that when these agents are used to treat rejection, anti-CMV prophylaxis is appropriate.9 Recently, non–lymphocyte depleting monoclonal antibodies, such as daclizumab and basiliximab, directed specifically against activated T-cells have been employed as immunosuppressants; these agents pose less risk for CMV reactivation than the lymphocyte-depleting antibodies.8 www.hpboardreview.com