Etiology

1. 90% of cases of infectious mononucleosis are caused by the Epstein-Barr virus. Acute reactivation of EBV disease has never been reported 
2. Other causes include CMV, Toxoplasmosis, Adenoviruses, Hepatitis A, and HIV

1. EBV infects approximately 95% of the world's population. 
2. Transmitted by oral secretions and possibly by sexual contacts. 
3. The virus may be shed for months after the acute infection. 
4. In younger children, the infection is often indistinguishable from other viral illnesses.
5. Adolescents and adults usually manifest common triad of fatigue, sore throat, and swollen glands.
6. Incubation period 30-50 days.

1. Young children are often asymptomatic
2. Older children have malaise, fever, fatigue, sore throat, abdominal pain (often LUQ), headache, and muscle pains
3. Physical examination findings
1. Increased size of anterior and posterior cervical nodes that are not tender, increase size of lymph nodes all over body, hepatomegaly (30%), and splenomegaly (50%)
2. Exudative pharyngitis with enlarged tonsilar tissue and palatal petechiae
3. Eyelid swelling
4. Nasal congestion, noisy breathing, mouth breathing, and very bad breath
5. May have MP rash (15%) and great majority will have rash 7-10 days after Amoxicillin exposure.
6. Often present with sore throat indistinguishable from Streptococcal infection and will have positive throat culture (5-25%) THis mnay represent colonization.  The child does not respond to Penicillin with worsening of symptoms and returns to office for follow -up and Mono test is positive.

1. Usually a clinical diagnosis based on history, age, symptoms, and physical examination.  Most other viral illnesses are resolved in 7 days
   
2. Laboratory
1. Lymphocytosis (>50% lymphocytes), atypical lymphocytes, mild decrease of platelets, increase of liver enzymes
2. Serologic Test
1. presence of heterophile antibodies, not EBV specific Ab,  that will react with horse erythrocytes. Heterophile Ab is an IgM and found much more frequently in older children. If initially negative, may turn positive in 3-4 weeks. This is the basis for most "slide' tests available commercially. Test is 85% sensitive and 97% specific. Test will stay positive for many months and therefore may not indicate active disease. 
2. EBV antibodies. Usually done to confirm diagnosis or in clinical situations where the slide test is negative and IM suspected.
1. IgM to viral capsid antigen (VCA) which turns positive a the time of presentation of symptoms in 2nd or third week and disappears in 4- 8 weeks
2. IgG to VCA. Positive in 2-4 week and stays positive for life
3. EBV nuclear antigen.  (EBNA) Arises after 6 weeks and coincides with recovery phase
   

1. Airway obstruction secondary to lymphoid tissue proliferation
2. Splenic rupture occurs in 0.1% of cases and often without significant trauma.
3. Aseptic meningitis, Guillain Barre, ataxia, aplastic and hemolytic anemia, ITP
4. Hemophagocytic lymphohistiocytosis (HLH)
   
5. Prolonged fatigue and malaise.

1. Bedrest as necessary. There is no evidence that bedrest will hasten recovery. Patient can return to activities. including school and job, when feeling well and able to participate
2. No contact sports or activities that can cause rupture of spleen until it is not palpable
3. Steroids- rarely needed but may use if airway obstruction, hemolytic anemia, and ITP
4. Acyclovir- no benefit has been shown in use in uncomplicated IM
5. Reassurance and symptomatic treatment. Don't restrict child if it is not necessary. Longer insist on restrictions, the longer to recover. Mononucleosis often occurs when teenagers have important activities and let them participate if they feel up to it. 

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2. John P and Ray CG. Infectious Mononucleosis. Pediatrics in Review. 1998; 19:276-279.
3. Cohen J. Epstein-Barr Virus Infections. New England Journal of Medicine Vol 343 No. 7 August 17, 2000
4. Roy M. et al. Dexamethasone for the Treatment of Sore Throat in Childrn With Suspected Infectious Mononucleosis. Archives of Pediatric and Adolescent Medicine. March 2004
5. Thorley-Lawson DA, Gross A. Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med. 2004 Mar 25; 350(13)"1328-37. Review
6. Junker A. Epstein-Barr Virus.  Pediatrics in Review.  March 2005
7. Luzuriaga K, Sullivan J.  Infectious Mononucleosis.  NEJM 362;21 May 27, 2010