From the Guidelines
Epstein-Barr virus (EBV) can present atypically beyond the classic symptoms of infectious mononucleosis, including neurological, hematologic, hepatic, cardiac, respiratory, and dermatologic manifestations, as well as associations with certain malignancies and chronic active EBV infection. These atypical presentations are important to recognize because they may delay diagnosis, as they don't fit the classic infectious mononucleosis pattern. The virus's ability to infect B lymphocytes and establish latency contributes to this wide spectrum of clinical manifestations 1.
Atypical Presentations
Some of the atypical presentations of EBV infection include:
- Neurological manifestations such as Guillain-Barré syndrome, facial nerve palsy, aseptic meningitis, encephalitis, and transverse myelitis
- Hematologic complications including hemolytic anemia, thrombocytopenia, and hemophagocytic lymphohistiocytosis
- Hepatic involvement causing hepatitis with jaundice and elevated liver enzymes that may mimic other forms of viral hepatitis
- Cardiac involvement presenting as myocarditis or pericarditis
- Respiratory complications including interstitial pneumonitis and upper airway obstruction due to tonsillar hypertrophy
- Dermatologic manifestations beyond the typical rash, such as erythema multiforme, urticaria, and petechiae
Chronic Active EBV Infection
Chronic active EBV infection can develop, characterized by persistent symptoms, recurrent fever, lymphadenopathy, and hepatosplenomegaly lasting more than six months 1. This condition is often associated with a poor prognosis and may be linked to certain EBV-associated T-cell lymphomas.
Diagnostic Guidelines
Proposed diagnostic guidelines for chronic active EBV infection include:
- Persistent or recurrent IM-like symptoms
- Unusual pattern of anti-EBV antibodies with raised anti-VCA and anti-EA, and/or detection of increased EBV genomes in affected tissues, including the peripheral blood
- Chronic illness which cannot be explained by other known disease processes at diagnosis 1.
Laboratory Tests
Recommended specific laboratory tests for diagnosing chronic active EBV infection include:
- Detection of EBV DNA, RNA, related antigens, and clonality in affected tissue, including the peripheral blood
- Histopathological and molecular evaluation, including general histopathology, immunohistological staining, chromosomal analysis, and rearrangement studies
- Immunological studies, including generalized immunological studies, marker analysis of peripheral blood, and cytokine analysis 1.
Importance of Recognition
Recognizing these atypical presentations of EBV infection is crucial for timely diagnosis and appropriate management, as they may not fit the classic infectious mononucleosis pattern. The ability of EBV to infect B lymphocytes and establish latency contributes to this wide spectrum of clinical manifestations, making it essential to consider EBV in the differential diagnosis of various clinical presentations 1.
From the Research
Atypical Presentations of Epstein-Barr Virus (EBV) Infection
- EBV infection can present with atypical manifestations, including neurological complications such as encephalitis, which can be fatal in immunocompetent individuals 2, 3.
- Atypical serological profiles can make it difficult to interpret EBV infection results, with isolated VCA-IgG positivity being the most frequent pattern detected 4.
- Multisystem involvement is common in atypical EBV presentations, including pneumonia, hepatic, hematologic-oncologic, and autoimmune diseases 5.
- Acute acalculous cholecystitis is an atypical clinical presentation of primary EBV infection, with few cases reported in the literature 6.
- Other atypical presentations of EBV infection include:
- Fulminant EBV encephalitis with acute fulminant cerebral edema (AFCE) 2.
- EBV-associated acute disseminated encephalomyelitis (ADEM) 3.
- Atypical serologic profiles, including isolated EBNA-1 IgG positivity and all three markers positive 4.
- Severe and atypical manifestations, including anemia, thrombocytopenia, and leukopenia 5.
Diagnostic Challenges
- Normal or non-specific CT and MRI scans do not exclude encephalitis diagnosis if clinical presentation fulfills the diagnostic criteria 2.
- Early recognition and consideration of infectious etiologies, including EBV, are essential for timely intervention and optimal patient outcomes 3.
- Clinical diagnosis and serologic follow-up are important for the interpretation of atypical profiles 4.
- Comprehensive evaluation and awareness in clinical diagnosis are necessary to identify atypical manifestations of EBV infection 5.