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Herpes Zoster Workup

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 16, 2016
 

Approach Considerations

Diagnosis of herpes zoster is based primarily on the history and physical findings—specifically, the characteristic location and appearance of the skin eruption in association with localized pain. Systemic manifestations are uncommon and usually are confined to patients in whom the immune system has been compromised by other disease processes or chemotherapy.

In most patients, confirming the diagnosis via laboratory testing usually has no utility, because most tests are time consuming, lack specificity, or are unavailable outside of research facilities. In select patient populations, however, the presentation of herpes zoster can be atypical and may require additional testing. This is particularly true in immunocompromised patients.

Zoster has been considered a harbinger of other occult disease (eg, malignancies in older patients). Both zoster and malignancy are common in elderly individuals; therefore, most experts currently consider the association to be purely coincidental. There also appears not to be and increased incidence of malignancy in children with herpes zoster. Approximately 3% of pediatric zoster cases occur in children with malignancies. Accordingly, a malignancy workup is not indicated in an otherwise healthy child who has herpes zoster.

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Laboratory Studies

Although varicella-zoster virus (VZV) can be cultured, its growth rate is usually too slow for culturing to make a timely contribution to diagnosis.

One of the least expensive and simplest laboratory diagnostic methods for VZV and other herpesviruses is the Tzanck smear. The Tzanck smear is performed by obtaining a scraping from the base of a fresh vesicular lesion after it has been unroofed, spreading and drying the collected material on a glass slide, staining the result with Giemsa, and examining the material with a microscope for the characteristic presence of multinucleated giant cells.

The Tzanck smear confirms that the lesion is herpetic but cannot differentiate between VZV and other herpesviruses. Further, this test has a limited sensitivity compared with other diagnostic methods, such as polymerase chain reaction (PCR) assay. Therefore, a negative result does not rule out a herpes virus infection and should not preclude empiric treatment in patients.[66]

When acute diagnostic confirmation is desired, modern tests, such as direct fluorescent antibody (DFA) testing or PCR (if available), are preferred to the Tzanck smear. DFA testing of vesicular fluid or a corneal lesion can yield the VZV antigen. Both DFA and PCR have far greater sensitivity and specificity than the Tzanck smear and allow differentiation between herpes simplex virus (HSV) and VZV infections.

PCR assay of vesicular fluid or a corneal scraping can yield the VZV nucleic acid. Detection of VZV DNA in plasma can facilitate the early recognition of VZV infection in immunocompromised hosts.[67] [#WorkupSkinBiopsyFindings]In cases of zoster sine herpete, DNA analysis by means of PCR appears more useful than the standard assays, especially for early diagnosis.

Herpes zoster is seen approximately 7 times more frequently in patients with HIV infection; therefore, when clinically indicated, an HIV test should be ordered.

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Other Studies

No imaging tests are indicated in typical cases of cutaneous herpes zoster infection. Magnetic resonance imaging (MRI) may be used in cases of myelopathy or encephalopathy as a means of excluding other etiologies.

A small percentage of patients, particularly those with cranial nerve (CN) involvement, may develop headache and neck stiffness, necessitating a lumbar puncture to exclude meningitis. Because the inflammatory response involves the leptomeninges, cerebrospinal fluid (CSF) may show increased protein and a pleocytosis.

Because the diagnosis of herpes zoster can almost always be made on clinical grounds, skin biopsy is seldom necessary; as a rule, it is reserved for cases that are difficult to diagnose (eg, atypical lesions).

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Histologic Findings

On rare occasions when skin biopsy is necessary, histologic findings are similar to those of herpes simplex and varicella. Ballooning degeneration and acantholysis of keratinocytes result in an intraepidermal vesicle. Multinucleated giant cells with accentuation of nuclear material at the periphery of nuclei are characteristic.[68] Underlying leukocytoclastic vasculitis often is a prominent finding and helps differentiate zoster from other herpetic infections.

Lymphocytes may be found in the lower part of the epidermis, accompanied by a combination of spongiosis and vacuolar alteration. The papillary dermis is often edematous. Extravasated erythrocytes in variable numbers are a common finding. A brisk lymphocytic infiltrate is present in the upper dermis.

Some of these lymphocytes may have large and polygonal nuclei. They are dense, perivascular, and sparse interstitial, superficial, and deep collections, sometimes assuming a patchy, lichenoid pattern. The lymphocytes may be prominent in and around adnexal structures, often peppering follicles, sebaceous glands, and eccrine glands.

Neutrophils and nuclear dust are occasionally seen; eosinophils are rare.

Conventional microscopy is routinely used to confirm infection by herpesviruses, though on occasion, PCR assay may then be used to demonstrate herpesvirus-specific DNA.

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Contributor Information and Disclosures
Author

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Joseph S Eastern, MD Clinical Assistant Professor, Department of Internal Medicine, Section of Dermatology, University of Medicine and Dentistry of New Jersey; Clinical Assistant Professor, Seton Hall University School of Graduate Medical Education

Joseph S Eastern, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, International Society for Dermatologic Surgery, Medical Society of New Jersey

Disclosure: Nothing to disclose.

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH Adjunct Professor of Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Infectious Diseases, International Society of Travel Medicine, Medical Mycological Society of the Americas, Armed Forces Infectious Diseases Society, International Society for Human and Animal Mycology, American College of Physicians, American Society for Microbiology, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

James E Moon, MD, FACP, FIDSA Associate Director, Malaria Vaccine Branch, Military Malaria Research Program, Walter Reed Army Institute of Research; Assistant Professor, Department of Medicine, Uniformed Services University of the Health Sciences

James E Moon, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Tropical Medicine and Hygiene, Armed Forces Infectious Diseases Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Wayne E Anderson, DO Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Law, Medicine & Ethics, California Medical Association, and San Francisco Medical Society

Disclosure: Teva Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Insys Honoraria Speaking and teaching; DepoMed Honoraria Speaking and teaching

Jeffrey Glenn Bowman, MD, MS Consulting Staff, Highfield MRI

Disclosure: Nothing to disclose.

Kevin P Connelly, DO Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center

Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Maria M Diaz, MD Staff Physician, Department of Emergency Medicine, Memorial Hospital

Maria M Diaz, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Andrea N Driano, MD Consulting Staff, Department of Emergency Medicine, Children's Hospital and Medical Center, Seattle WA

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

C Stephen Foster, MD, FACS, FACR, FAAO Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

C Stephen Foster, MD, FACS, FACR, FAAO is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Association of Immunologists, American College of Rheumatology, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, American Uveitis Society, Association for Research in Vision and Ophthalmology, Massachusetts Medical Society, Royal Society of Medicine, and Sigma Xi

Disclosure: Nothing to disclose.

Kilbourn Gordon III, MD, FACEP Urgent Care Physician

Kilbourn Gordon III, MD, FACEP is a member of the following medical societies: American Academy of Ophthalmology and Wilderness Medical Society

Disclosure: Nothing to disclose.

Robin R Hemphill, MD, MPH Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University School of Medicine

Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Ryan I Huffman, MD, Staff Physician, Department of Ophthalmology, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Associate Professor of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Cynthia Haeshin Moon, MD Staff Physician, Department of Emergency Medicine, SUNY Downstate Medical Center/Kings County Hospital Center

Disclosure: Nothing to disclose.

Barbara L Roque, MD Full Partner, Ophthalmic Consultants Philippines Co; Service Chief, Pediatric Ophthalmology and Strabismus, Department of Ophthalmology, Asian Hospital and Medical Center; Active Staff, International Eye Institute, St Luke's Medical Center Global City; Visiting Ophthalmologist, AMC Eye Center, Alabang Medical Center

Barbara L Roque, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Society of Cataract and Refractive Surgery, Philippine Academy of Ophthalmology, Philippine Society of Cataract and Refractive Surgery, and Philippine Society of Pediatric Ophthalmology

Disclosure: Nothing to disclose.

Manolette R Roque, MD, MBA General Manager, Full Partner, Ophthalmic Consultants Philippines Co.; President and CEO, Chief Refractive Surgeon, EYE REPUBLIC Ophthalmology Clinic; Section Chief, Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center; Section Chief, Ocular Immunology and Uveitis, International Eye Institute, St Luke's Medical Center Global City; Senior Eye Surgeon, The LASIK Surgery Clinic; Director, AMC Eye Center, Alabang Medical Center; President, Philippine Ocular Inflammation Society

Manolette R Roque, MD, MBA is a member of the following medical societies: American Academy of Ophthalmic Executives, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, American Society of Ophthalmic Administrators, American Uveitis Society, International Ocular Inflammation Society, Philippine Medical Association, Philippine Ocular Inflammation Society, and Philippine Society of Cataract and Refractive Surgery

Disclosure: Nothing to disclose.

Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Mark A Silverberg, MD, MMB, FACEP Assistant Professor, Associate Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate Medical Center

Mark A Silverberg, MD, MMB, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Florian P Thomas, MD, MA, PhD, Drmed Director, Regional MS Center of Excellence, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, St Louis University School of Medicine

Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, and Sigma Xi

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Head of Infectious Disease Fellowship Program, Orlando Regional Medical Center

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, University of Tennessee College of Medicine

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University Medical Center

Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Typical zoster in the vicinity of right popliteal fossa in a vertebral nerve L4 distribution.
Suspected zoster of the hand.
Herpes zoster, unilateral, on trunk.
Herpes zoster on lateral part of abdomen.
Maculopapular rash due to herpes zoster in child with history of leukemia. Image courtesy of Centers for Disease Control and Prevention (CDC).
Herpes zoster in ophthalmic (V1) distribution of trigeminal nerve. Note unilateral distribution of rash and how V1 distribution may extend to tip of nose. Though at risk for keratitis with zoster in this distribution, patient had normal ocular examination. Patient consented to picture distribution for educational use; written permission on file. Image courtesy of JS Huff.
Herpes zoster on neck.
 
 
 
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