CME INDIA Case Presentation by Dr. Pratik Savaj, MD (ID Specialist) and Dr. Anil Italiya (MD medicine), Surat.

CME INDIA Case Study

How Presented?

• 21-year male, admitted with high grade fever, abdominal pain and headache of 5 days

Routine investigation suggested viral like illness

  • CBC – Normal with lymphocytosis of 60%, LFT – Normal, USG – terminal ileitis, blood culture – no growth.
  • Started with ceftriaxone and azithromycin.

It is day 7 of antibiotics but fever is persistent

  • Daily high grade with severe myalgia. Relatives are anxious now. Repeat blood investigation suggested.
  • CBC – Again normal with lymphocytosis.
A Case with High Grade Fever, Abdominal Pain and Headache
  • Now LFT alteration started.
  • Bilirubin- 4 (D-3.8), SGPT-172.
  • Brucella IgM and IgG Elisa – normal.
  • Repeat blood culture – no growth.
  • HIV, HBsAg, HCV – negative.
  • ANA – negative.

Story on the day 14 of fever

  • Daily high grade.

What could be D/D

  • Lymphoma.
  • Koch’s.
  • Deep seated infective focus.
  • Cytomegalovirus, human immunodeficiency virus (HIV), human herpesvirus type 6, hepatitis B, and tick-borne illnesses such as Lyme disease should be kept in mind.

On examination

  • Multiple cervical lymph nodes found.
  • CECT Chest and Abdomen – multiple abdominal nodes, non-necrotic.

Now diagnosis is clear?

  • Young patient.
  • PUO.
  • Lymphocytosis.
  • Multiple lymph node enlargements.

Probable diagnosis – Infectious mononucleosis

  • EBV IgM was asked which came positive.
A Case with High Grade Fever, Abdominal Pain and Headache

Interpretation of Viral capsid antigen (VCA)

  • Anti-VCA IgM and anti-VCA IgG antibodies directed against EBV viral capsid antigen are present at the onset of infection.
  • Anti-VCA IgM appears early.
  • It usually disappears within 4 to 6 weeks.
  • Anti-VCA IgG appears in the acute phase of the infection and peaks at 2 to 4 weeks and will remain for life.
  • Anti-VCA IgM is highly suggestive of acute EBV infection, other herpes viruses (e.g., cytomegalovirus) can induce IgM antibodies to cell lines that express EBV antigens.

EBV Nuclear antigen (EBNA) –

  • It is expressed only when the virus begins to establish latency.
  • It begins to appear 6 – 12 weeks after the onset of initial symptoms and persists throughout life.
  • Its presence early in the disease course of an illness excludes acute EBV infection. 

Early antigen (EA)

  • Anti-EA IgG appears during the acute phase and falls to undetectable levels after 3 to 6 months.
  • The presence of anti-EA IgG anti-D antibodies is consistent with recent infection, but their absence does not exclude acute illness. 

The monospot (or heterophile antibody) test for mononucleosis is the diagnostic test of choice

  • It is nearly 100% specific for the disease.
  • The sensitivity of this test is closer to 85%. 
  • If the patient is early in the illness, the test may be falsely negative, and it should be repeated later during the course of the disease.

Treatment suggested:

  • Only paracetamol and supportive care 😊
  • Patient became afebrile by day 18 😊

CME INDIA Discussion

Dr. Keyur Acharya, Intensivist, UK:

  • Need biopsy of lymph node.
  • Tissue diagnosis whenever possible!
  • Who knows? Could even be Kikuchi.

CME INDIA Learning Points

  • Infectious mononucleosis, a clinical syndrome seen in children and adolescents.
  • It is caused by Epstein-Barr virus (EBV), is characterized by the triad of fever, lymphadenopathy and pharyngitis.
  • It is usually transmitted through oral pharyngeal secretions.
  • EBV is a herpes virus that replicates primarily in lymphocytes but may also do so in epithelial cells of pharynx and parotid duct.
  • The infection is spread primarily by saliva.
  • Incubation period: four to eight weeks.

The typical clinical features

  • Fever.
  • Pharyngitis, Lymphadenopathy.
  • Malaise.
  • In older patients are less likely to have sore throat and lymphadenopathy and more likely to have hepatomegaly and jaundice.

Diagnostic criteria

An atypical lymphocytosis of at least 20 percent or atypical lymphocytosis of at least 10 percent plus lymphocytosis of at least 50 percent in peripheral blood in the presence of fever, pharyngitis and lymphadenopathy and confirmed by a positive serology.

Atypical lymphocytes

  • These resemble as monocytes or immature cells and are highly pleomorphic.
  • They are classified as Downey cells type 1, 2 & 3. Type 1, which are small, have indented or lobulated nuclei with clumped chromatin and scanty cytoplasm, Type 2 which have a round to oval nucleus, moderately clumped chromatin, absent or indistinct nucleoli and abundant grey-blue cytoplasm and Type 3 which are larger with round to oval nuclei having moderately dispersed chromatin, one or more prominent nucleoli and is moderately abundant cytoplasm which stains deeply basophilic.

What about the original serologic Paul-Bunnell test?

  • It is for detection of heterophile antibodies by tube agglutination of sheep or horse red blood cells.
  • It is now replaced by convenient slide latex agglutination or solid-phase immunoassay.
  • Although relatively specific, they are less sensitive in the first week of illness and in patients younger than 12 years.

More specific and sensitive tests are VCA-IgG and VCA-IgM (VCA-Viral Capsid Antigen)

The mainstay of treatment

  • Good supportive care, including adequate hydration.
  • NSAIDS or acetaminophen for fever and myalgias, throat lozenges or sprays, or gargling with a lidocaine solution to relieve pharyngeal discomfort.
  • Corticosteroids are recommended only in patients with haemolytic anaemia, thrombocytopenia, aplastic anaemia, thrombotic thrombocytopenic purpura, haemolytic uremic syndrome and DIC.
  • Neurologic complications seen in 1-5% of cases include Guillain-Barre syndrome, facial paralysis, meningoencephalitis, aseptic meningitis, peripheral neuritis, cyberelites and optic neuritis.
  • Potentially fatal complications include splenic rupture and air way obstruction caused by lymphoid hyperplasia and mucosal edema.
  • Approximately 40% of children 4 years of age or younger do not develop heterophile antibodies following a primary EBV infection. If the heterophile is the only test ordered, the diagnosis will be missed or false.

CME INDIA Tail Piece

A Case with High Grade Fever, Abdominal Pain and Headache

Bulletin of the Johns Hopkins Hospital (1920) 31:410–417 says:

  • The earliest clinical descriptions of infectious mononucleosis are found in writings of the 1880s, principally the report of Pfeiffer, who referred to the disease as “glandular fever.”
  • The serum from three additional cases of infectious mononucleosis also had high titers, whereas other diseases including lymphocytic leukemia did not.
  • During the next 30 years, much was learned about the clinical spectrum of infectious mononucleosis, its complications, and its management. As was the case with the recognition that a high titer of the heterophile antibody was associated with infectious mononucleosis, a serendipitous event led to the discovery of the etiologic agent.
  • The heterophile antibody test remained the gold standard, confirming diagnostic test in clinical practice for over 40 years, and the procedure was made more rapid and efficient by the substituting horse or bovine red cells, and using red cell membranes or more purified heterophile antigen available in the form of laboratory kits such as the mono spot test.


  1. Gonzalez Saldana et al: Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children. BMC Research Notes 2012, 5:361
  2. Luzuriaga K, Sullivan JL: Infectious Infectious Mononucleosis. New Eng J Med 2010, 362:1993-2000.
  3. Henry H Balfour, Jr, Samantha K Dunmire, and Kristin AHogquist Clin Transl Immunology. 2015 Feb; 4(2): e33 Published online 2015 Feb 27. doi: 10.1038/cti.2015.1
  4. Sprunt TPV, Evans FA. Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis). Bulletin of the Johns Hopkins Hospital. Baltimore, 1920. 31:410-417.

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