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infectious mononucleosis

Symtomatic primary infection with Epstein-Barr virus (EBV). Etiology: 1) Epstein-Barr virus (EBV) a) transmission 1] generally occurs through infected saliva, probably requiring repeated & prolonged contact with infected oral secretions, yet few patients can identify a known contact 2] rarely blood transfusions or bone-marrow transplant 3] viral excretion occurs for months 4] asymptomatic carrier state is common 2) infrequent causes < 10% a) cytomegalovirus (CMV) b) human immunodeficiency virus (HIV) c) Toxoplasma gondii d) human Herpes virus type 6 Epidemiology: 1) endemic in children in developing countries 2) most common in adolescence & young adulthood in developed nation with adequate sanitation 3) most common viral cause of fever of unknown origin [8] 4) EBV transmitted by kissing [2] Genetics: - vulnerability to infectious mononucleosis has a genetic basis [4] Clinical manifestations: 1) incubation period is 3-7 weeks 2) acute phase lasts 1-2 weeks with recovery in 6-8 weeks 3) wide spectrum of disease from asymptomatic to fulminant infection leading to death in immunocompromised individuals 4) overt illness most common in adolescents & young adults 5) prodrome of malaise, fatigue & persistent low-grade headache 6) severe non-exudative pharyngitis is the most prominent feature [6] - exudative [8] 7) flu-like symptoms of fever/chills, myalgias, arthralgias, nausea, abdominal discomfort, cough 8) petechiae on the palate 9) stiff neck 10) lymphadenopathy - posterior cervical & axillary lymphadenopathy - generalized lymphadenopathy [9] 11) splenomegaly 12) hepatomegaly 13) rash [8] * images [5] Laboratory: 1) complete blood count (CBC) with differential a) absolute lymphocytosis (> 50%) b) atypical lymphocytes (> 10%) 2) liver function tests (LFTs) may be elevated 2-3 fold 3) direct antiglobulin test (DAT, Coombs' test) 4) heterophile antibody test (Monospot test) - specific but not sensitive - may be negative during first week of infection [4] - children are less likely than adults to develop heterophile antibodies [8] 3) serology, if heterophile antibody negative a) heterophile antibody - indicates acute infection with EBV b) IgM anti EBV viral capsid antigen (anti-VCA IgM) - indicates acute infection with EBV c) IgG anti EBV viral capsid antigen (anti-VCA IgG) - indicates acute or past infection with EBV d) IgA anti EBV viral capsid antigen (anti-VCA IgA) - useful for evaluation of nasopharyngeal carcinoma e) EBV early antigen Ab (anti-EA IgG) - indicates acute infection with EBV f) EBV nuclear antigen Ab (anti-EBNA IgG) - indicates past infection with EBV 4) Epstein-Barr virus DNA Radiology: - assessment of spleen size before returning to contact sports Differential diagnosis: 1) bacterial infection a) exudative pharyngitis with group A beta hemolytic streptococci b) Mycoplasma 2) viral infection a) cytomegalovirus b) respiratory viruses 1] influenza 2] parainfluenza 3] adenovirus c) viral hepatitis d) rubella e) mumps f) acute retroviral syndrome (HIV1 infection) g) herpesvirus type 6 3) toxoplasmosis 4) drug reaction 5) hematologic malignancy Complications: 1) bacterial pharyngitis 2) splenic rupture 3) upper airway obstruction 4) pneumonitis 5) hematologic a) hemolytic anemia b) thrombocytopenia c) neutropenia 6) neurologic a) seizures b) meningoencephalitis c) Bell's palsy d) Guillain-Barre syndrome e) psychosis f) Reye's syndrome 7) cardiac a) myocarditis b) pericarditis 8) glomerulonephritis 9) jaundice, hepatitis [6] 10) neoplasms a) Burkitt's lymphoma b) nasopharyngeal carcinoma c) B-cell lymphoma Management: 1) uncomplicated acute infectious mononucleosis generally requires only supportive therapy a) warm salt water or anesthetic gargle for pharyngitis b) acetaminophen for fever or malaise 2) antibiotic treatment of concomitant group A beta hemolytic streptococcus a) penicillin or erythromycin for 10 days b) avoid ampicillin or amoxicillin because they frequently produce a morbilliform rash in patients with infectious mononucleosis [3] c) rash is not an allergic reaction & patients can safely susequently use ampicillin or amoxicillin without recurrence of rash [6] 3) prednisone 40-80 mg QD with 5-14 day taper a) may shorten duration of fever b) can reduce obstructive tonsillar enlargement c) may improve cardiac, neurologic & hematologic complications 4) antiviral agents in fulminant infections in immunocompromised hosts a) acyclovir b) ganciclovir c) zidovudine d) foscarnet 4) rest with limited activity to prevent splenic rupture 5) gradual return to activity with degree of splenomegaly as a monitor (see radiology) 6) isolation unnecessary: EBV shedding continues after acute illness Comparative biology: - nanoparticle vaccine prevents EBV infection in mice & nonhuman primates

Related

Epstein-Barr virus (EBV); human herpesvirus 4 (HHV4) heterophile antibody

General

Herpes virus infection

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 872-73
  2. Balfour HH Jr et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis 2013 Jan 1; 207:80 PMID: 23100562
  3. Chovel-Sella A et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics 2013 May 1; 131:e1424 PMID: 23589810
  4. Rostgaard K et al. A genetic basis for infectious mononucleosis: Evidence from a family study of hospitalized cases in Denmark. Clin Infect Dis 2014 Jun 15; 58:1684. PMID: 24696238 http://cid.oxfordjournals.org/content/58/12/1684 - Balfour HH. Genetics and infectious mononucleosis. Clin Infect Dis 2014 Jun 15; 58:1690. PMID: 24696239 http://cid.oxfordjournals.org/content/58/12/1690
  5. Brady MP (images) Cutaneous and Mucosal Manifestations of Viral Diseases. Medscape. March 2017 http://reference.medscape.com/features/slideshow/viral-skin
  6. Medical Knowledge Self Assessment Program (MKSAP) 18, 19 American College of Physicians, Philadelphia 2018, 2021 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  7. Jenson HB. Epstein-Barr virus. Pediatr Rev 2011 Sep; 32:375 PMID: 2188566
  8. NEJM Knowledge+ - NEJM Knowledge+ Question of the Week. Aug 20, 2019 https://knowledgeplus.nejm.org/question-of-week/4127/
  9. Sinert RH Fast Five Quiz: Pharyngitis (Sore Throat). Medscape. December 14, 2022 https://reference.medscape.com/viewarticle/984986