Diseases (2)
Diagnostic Testing (2)

Note:

EBV can be detected from formalin fixed paraffin-embedded tissue. However, PCR on fresh tissue can give faster results, and a quantitative viral load where clinically indicated.

Overview

The Epstein-Barr virus (EBV) is a member of the herpes virus family, and is responsible for many disorders including infectious mononucleosis, and other lymphoproliferative disorders. Herpes viruses are leading causes of viral infections worldwide, second only to the influenza and cold viruses. These viruses are important because they establish latency in B lymphocytes (a type of white blood cell or WBC), meaning they are never truly eliminated from the body and can pose a risk of reactivation under certain conditions. Reactivation of latent viruses is especially important in patients that have compromised or suppressed immune systems, such as immunodeficient patients (e.g., chemotherapy, HIV, organ transplant patients etc). In addition, two types of human cancers, Burkitt’s lymphoma and nasopharyngeal carcinoma, have been associated with EBV infection. There is no cure available for latent infections.

EBV infection is via exposure to oral secretions, usually by kissing, sharing food or utensils, or coughing. It can also be spread through blood transfusions and organ transplants. It does not survive outside the host and has not been recovered from any environmental sources. In the very young, EBV infections are generally asymptomatic. In adolescents the primary initial infection may be asymptomatic; however, the most common manifestation in this age group is infectious mononucleosis. In immunocompromised/ immunosuppressed patients, especially solid-organ transplant patients, there is a risk of developing a potentially fatal disorder called post-transplant lymphoproliferative disorder (PTLD). Although less common than in solid-organ recipients, EBV associated PTLD is also seen in bone marrow and blood stem cell transplant patients. In these populations, active EBV infection can result in high morbidity and mortality if left untreated.

Patients presenting with primary infection are generally diagnosed using serology testing. In normal, healthy individuals, once EBV has been identified as the causative agent, no further testing is required. Immunocompromised individuals, however, may not produce an appropriate serological response, and require testing using other methods. It is this population where EBV testing by molecular methods is beneficial. Also, once EBV has been identified in this population, either through primary infection or reactivation, it is important to know the amount of virus circulating in the patient in order to monitor disease progression and treatment outcome. Determining the amount of circulating virus is known as the “viral load.”

This assay detects the number of circulating EBV viral particles using polymerase chain reaction (PCR). This assay is not intended for diagnostic purposes in healthy individuals. Specimen types include serum, plasma, whole blood, and cerebral spinal fluid (CSF).

Clinical Utility
  • Diagnosis of an active EBV infection in transplant patients (solid-organ, bone marrow, blood stem cell)
  • Diagnosis of an active EBV infection in AIDS patients
  • Therapy treatment monitoring

Interpretation

Positive in:

  • Active EBV infection in transplant patients and AIDS patients
  • Infectious mononucleosis
  • Lymphoproliferative disease
  • Chronic fatigue syndrome
  • Burkitt’s lymphomas
  • Nasopharyngeal carcinoma

Negative in:

  • Past EBV infection
  • Uninfected individuals

Reference Ranges

Negative (Not detected)
 

 

Methodology

Polymerase Chain Reaction (PCR), Real-time PCR, PCR chip array technology, (qualitative or quantitative).

Specimen Collection

Serum (Red), Whole blood or Plasma EDTA (Lavander) or CSF

Stability:

  • Ambient: 48 hours
  • Refrigerated: 8 days
  • Frozen: Unacceptable

Additional Testing

EBV serology, CMV by PCR, HSV 1 and 2 by PCR, Herpes virus 8 (HHV8), Viral Culture.

CPT
87798$ 35.09
87799$ 42.84

ICD10
A83Mosquito-borne viral encephalitis
A84Tick-borne viral encephalitis
A85Other viral encephalitis, not elsewhere classified
A85.0Enteroviral encephalitis
A85.1Adenoviral encephalitis
A85.2Arthropod-borne viral encephalitis, unspecified
A85.8Other specified viral encephalitis
A86Unspecified viral encephalitis
B00.4Herpesviral encephalitis
C77Secondary and unspecified malignant neoplasm of lymph nodes
C83Non-follicular lymphoma
C83.7Burkitt lymphoma
C83.70Burkitt lymphoma, unspecified site
C83.79Burkitt lymphoma, extranodal and solid organ sites
C85.88Other specified types of non-Hodgkin lymphoma, lymph nodes of multiple sites
C85.90Non-Hodgkin lymphoma, unspecified, unspecified site

Additional ICD10
A17.82Tuberculous meningoencephalitis
A32.1Listerial meningitis and meningoencephalitis
A32.12Listerial meningoencephalitis
A39.81Meningococcal encephalitis
A42.82Actinomycotic encephalitis
A50.42Late congenital syphilitic encephalitis
A52.14Late syphilitic encephalitis
A81.1Subacute sclerosing panencephalitis
A83.0Japanese encephalitis
A83.1Western equine encephalitis
A83.2Eastern equine encephalitis
A83.3St Louis encephalitis
A83.4Australian encephalitis
A83.5California encephalitis
A83.6Rocio virus disease
A83.8Other mosquito-borne viral encephalitis
A83.9Mosquito-borne viral encephalitis, unspecified
A85.0Enteroviral encephalitis
A85.1Adenoviral encephalitis
A85.2Arthropod-borne viral encephalitis, unspecified
A85.8Other specified viral encephalitis
C77.0Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck
C77.1Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes
C77.2Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes
C77.3Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes
C77.4Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes
C77.5Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes
C77.8Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions
C77.9Secondary and unspecified malignant neoplasm of lymph node, unspecified
C83.0Small cell B-cell lymphoma
C83.00Small cell B-cell lymphoma, unspecified site
C83.01Small cell B-cell lymphoma, lymph nodes of head, face, and neck
C83.02Small cell B-cell lymphoma, intrathoracic lymph nodes
C83.03Small cell B-cell lymphoma, intra-abdominal lymph nodes
C83.04Small cell B-cell lymphoma, lymph nodes of axilla and upper limb
C83.05Small cell B-cell lymphoma, lymph nodes of inguinal region and lower limb
C83.06Small cell B-cell lymphoma, intrapelvic lymph nodes
C83.07Small cell B-cell lymphoma, spleen
C83.08Small cell B-cell lymphoma, lymph nodes of multiple sites
C83.09Small cell B-cell lymphoma, extranodal and solid organ sites
C83.1Mantle cell lymphoma
C83.10Mantle cell lymphoma, unspecified site
C83.11Mantle cell lymphoma, lymph nodes of head, face, and neck
C83.12Mantle cell lymphoma, intrathoracic lymph nodes
C83.13Mantle cell lymphoma, intra-abdominal lymph nodes
C83.14Mantle cell lymphoma, lymph nodes of axilla and upper limb
C83.15Mantle cell lymphoma, lymph nodes of inguinal region and lower limb
C83.16Mantle cell lymphoma, intrapelvic lymph nodes
C83.17Mantle cell lymphoma, spleen
C83.18Mantle cell lymphoma, lymph nodes of multiple sites
C83.19Mantle cell lymphoma, extranodal and solid organ sites
C83.3Diffuse large B-cell lymphoma
C83.30Diffuse large B-cell lymphoma, unspecified site
C83.31Diffuse large B-cell lymphoma, lymph nodes of head, face, and neck
C83.32Diffuse large B-cell lymphoma, intrathoracic lymph nodes
C83.33Diffuse large B-cell lymphoma, intra-abdominal lymph nodes
C83.34Diffuse large B-cell lymphoma, lymph nodes of axilla and upper limb
C83.35Diffuse large B-cell lymphoma, lymph nodes of inguinal region and lower limb
C83.36Diffuse large B-cell lymphoma, intrapelvic lymph nodes
C83.37Diffuse large B-cell lymphoma, spleen
C83.38Diffuse large B-cell lymphoma, lymph nodes of multiple sites
C83.39Diffuse large B-cell lymphoma, extranodal and solid organ sites
C83.5Lymphoblastic (diffuse) lymphoma
C83.50Lymphoblastic (diffuse) lymphoma, unspecified site
C83.51Lymphoblastic (diffuse) lymphoma, lymph nodes of head, face, and neck
C83.52Lymphoblastic (diffuse) lymphoma, intrathoracic lymph nodes
C83.53Lymphoblastic (diffuse) lymphoma, intra-abdominal lymph nodes
C83.54Lymphoblastic (diffuse) lymphoma, lymph nodes of axilla and upper limb
C83.55Lymphoblastic (diffuse) lymphoma, lymph nodes of inguinal region and lower limb
C83.56Lymphoblastic (diffuse) lymphoma, intrapelvic lymph nodes
C83.57Lymphoblastic (diffuse) lymphoma, spleen
C83.58Lymphoblastic (diffuse) lymphoma, lymph nodes of multiple sites
C83.59Lymphoblastic (diffuse) lymphoma, extranodal and solid organ sites
C83.7Burkitt lymphoma
C83.70Burkitt lymphoma, unspecified site
C83.71Burkitt lymphoma, lymph nodes of head, face, and neck
C83.72Burkitt lymphoma, intrathoracic lymph nodes
C83.73Burkitt lymphoma, intra-abdominal lymph nodes
C83.74Burkitt lymphoma, lymph nodes of axilla and upper limb
C83.75Burkitt lymphoma, lymph nodes of inguinal region and lower limb
C83.76Burkitt lymphoma, intrapelvic lymph nodes
C83.77Burkitt lymphoma, spleen
C83.78Burkitt lymphoma, lymph nodes of multiple sites
C83.79Burkitt lymphoma, extranodal and solid organ sites
C83.8Other non-follicular lymphoma
C83.80Other non-follicular lymphoma, unspecified site
C83.81Other non-follicular lymphoma, lymph nodes of head, face, and neck
C83.82Other non-follicular lymphoma, intrathoracic lymph nodes
C83.83Other non-follicular lymphoma, intra-abdominal lymph nodes
C83.84Other non-follicular lymphoma, lymph nodes of axilla and upper limb
C83.85Other non-follicular lymphoma, lymph nodes of inguinal region and lower limb
C83.86Other non-follicular lymphoma, intrapelvic lymph nodes
C83.87Other non-follicular lymphoma, spleen
C83.88Other non-follicular lymphoma, lymph nodes of multiple sites
C83.89Other non-follicular lymphoma, extranodal and solid organ sites
C83.9Non-follicular (diffuse) lymphoma, unspecified
C83.90Non-follicular (diffuse) lymphoma, unspecified, unspecified site
C83.91Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of head, face, and neck
C83.92Non-follicular (diffuse) lymphoma, unspecified, intrathoracic lymph nodes
C83.93Non-follicular (diffuse) lymphoma, unspecified, intra-abdominal lymph nodes
C83.94Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of axilla and upper limb
C83.95Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of inguinal region and lower limb
C83.96Non-follicular (diffuse) lymphoma, unspecified, intrapelvic lymph nodes
C83.97Non-follicular (diffuse) lymphoma, unspecified, spleen
C83.98Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of multiple sites
C83.99Non-follicular (diffuse) lymphoma, unspecified, extranodal and solid organ sites

References
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  • Am Fam Physician. 2004;70:1279.[PMID:15508538]
  • Annu Rev Pathol. 2006;1:375-404. [PMID:18039120]
  • Lancet Infect Dis. 2003 Mar;3(3):131-40. [PMID:12614729]
  • Am J Med. 2007 Oct;120(10):911.e1-8. [PMID:17904463]
  • In Vivo. 2007 Sep-Oct;21(5):707-13. [PMID:18019402]
  • Clin Otolaryngol Allied Sci. 2001 Feb;26(1):3-8. [PMID:11298158]
  • Stevens, Christine Dorresteyn. Clinical Immunology & Serology A Laboratory Perspective 3rd edition. Philadelphia: F.A. Davis Company. 2010.
  • EBV early antigen (EA) ELISA II package insert. Wampole laboratories ref. 425000CE 06/2005