Question of the week # 262

262) A 17 year old male is admitted with fever and severe pain while swallowing for the past 1 week. He denies any rash or joint pains. His girlfriend had similar symptoms 1 month ago that resolved spontaneously. He was started on azithromycin by his primary doctor as outpatient however, the symptoms have not subsided. On examination, temperature is 102F. Throat examination reveals diffuse pharyngeal erythema and swelling of the tonsils with exudates. There are no mucosal ulcerations. Abdominal examination reveals moderate splenomegaly. Laboratory investigations reveal WBC count 12000/µl with 60% Lymphocytes, Hemoglobin 14gm% and Platelet count 120k/µl. Peripheral smear shows atypical lymphocytes comprising 30% of lymphocyte population. Liver panel reveal mild elevation of transaminases with AST 80U/L and ALT 96U/L. Total bilirubin is 0.6gm%. A heterophile antibody test is negative on two occasions. Ebstein Barr Virus serology including EBV viral capsid antigen (VCA) – IgM and IgG as well as EBV nuclear antigen antibody (EBNA-IgG) has been ordered. Which of the following combinations are most consistent with this patient’s presentation?

A)     VCA IgG  negative, VCA IgM negative, EBNA-IgG positive

B)      VCA IgG  positive, VCA IgM negative, EBNA-IgG positive

C)      VCA IgG  negative, VCA IgM negative, EBNA-IgG negative

D)     VCA IgG  positive, VCA IgM positive, EBNA-IgG positive

E)      VCA IgG  positive, VCA IgM positive, EBNA-IgG negative

9 Responses

  1. E think require more explanation regarding answer.

  2. E

  3. Answer E. Recognize heterophile –ve IM and understand the interpretation of EBV serology.
    Choice E is consistent with acute EBV infection and confirms the diagnosis of Infectious mononucleosis.
    This patient’s clinical picture is consistent with acute Infectious Mononucleosis. Heterophile antibody can be negative in some cases of IM. In such cases, Heterophile antibody tests needs to be repeated. If the repeat test is also negative but clinical suspicion of IM is high, EBV serology must be obtained. This includes antibodies (IgM and IgG) to Viral Capsid antigen (VCA) and antibody to EBV nuclear Antigen (EBNA-IgG). EBNA –IgG takes about 6 weeks to show up in the blood after acute infection. Hence, presence of EBNA excludes acute infection. So, choices A, B and D are incorrect. Choice B is consistent with Past EBV infection. Choice C is consistent with seronegativity and excludes EBV infection. In such cases, other differential diagnoses that can closely mimic Infectious mononucleosis must be ruled out. These include Primary HIV infection, CMV infection, Toxoplasma and HHV-7

  4. sir this is my doubt, we know that, IgM is marker of acute infection & IgG is marker of chronic infection. so, when this is acute infection—how can IgG for viral vapsid of EBV be +ve here ?

    • Hi venkat, VCA IgM is seen at symptom onset and VCA IgG starts getting detected soon after symptom onset. So, both VCA – IgG and IgM are detected in acute phase. Hence, you should rely on EBNA which does not appear until late in order to accurately interpret the stage of EBV infection . INCUBATION ( BEFORE SYMPTOM ONSET) is the time when only VCA-IGM is detected but VCA-IGG is not. Once symptoms start, both are detected

  5. C is also a correct answer if this is CMV mononucleosis – this question is technically wrong since it has two possible correct answers i.e C and E.

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