Infectious mononucleosis

Infectious mononucleosis is a childhood infection caused by Epstein-Barr virus. Initial symptoms are fever, fatigue, headache, pharyngitis, lymphadenopathy, and splenomegaly. The virus is transmitted by saliva from asymptomatic adults to infants and between adolescents and young adults by kissing.

1,500,000 (US); 30,000,000 (Global)
Epstein-Barr virus (EBV) infections;
4-6 weeks; [CCDM]
Fever, fatigue, headache, pharyngitis, lymphadenopathy, and splenomegaly; [CCDM]
Standard; "The isolation of patients with IM is unnecessary." [Harrison ID, p. 756]
Among infected young adults, jaundice occurs in 4%, abnormal liver function tests in 95%, and splenomegaly in 50%. [CCDM, p. 196-7] A transient thrombocytopenia is common, and a self-limited hemolytic anemia may occur. [Merck Manual, p. 1626] Some patients with mononucleosis have a mild conjunctivitis. Uveitis and Parinaud's oculoglandular conjunctivitis have also been associated with EBV infection. [Guerrant, p. 995] Uncommon findings are hemolytic anemia, cytopenia, pneumonitis, carditis, seizures, palsies, Guillain-Barre, and encephalitis; [ABX Guide] EBV is one of the rare causes of parotitis. [Cohen, p. 1637] Uncommon symptoms are abdominal discomfort (9%), cough (5%), and arthralgias (2%). [PPID, p. 1877t]

Laboratory findings include a lymphocytosis of 50% or higher, 10% or more atypical lymphocytes, abnormal liver function tests, and positive serology for Epstein-Barr antibodies (VCA and EBNA). [CCDM, p. 197] Leukocytosis (10-18K) and lymphocytosis are common. Usually 10-30% or more of lymphocytes are atypical. [ABX Guide] 90-95% of adults have EBV antibodies. About 50% of children in the US and UK have EBV seroconversion before the age of 5. [PPID, p. 1875] Common urinary findings are proteinuria and hematuria. [PPID, p. 1878-9] Children less than 5 years of age and the elderly usually do not develop heterophile antibodies. [Harrisons, p. 549]

Various rashes develop in 10% of cases, and a diffuse maculopapular rash may be triggered by ampicillin or amoxicillin therapy. The rash may involve the palms/soles. [ID, p. 60, 1535-9] "Earlier studies reported that most pts treated with penicillin derivatives develop a macular rash; these rashes do not represent a true penicillin allergy, nor do they occur more frequently in pts exposed to penicillin derivatives rather than other drugs." [Harrisons, p. 548] About 10% of patients have a rash that may be macular, petechial, urticarial, or erythema multiforme-like; it is usually located on the trunk and arms and is present on days 4-6 of the illness. [Cohen, p. 79]

The virus is transmitted by saliva from asymptomatic adults to infants and between adolescents and young adults by kissing. [Harrison ID, p. 752] About 50% of children have been infected and seroconverted by the age of 5. Infection by transfusion has been reported. [Merck Manual, p. 1625-6]

Complications of mononucleosis include CNS infection, transverse myelitis, neuritis, cranial nerve palsies, splenic rupture, myocarditis, pericarditis, kidney dysfunction, and pneumonia. [ID, p. 60, 1535-9] Neurological complications include Guillain-Barre syndrome, optic neuritis, mononeuritis multiplex, and transverse myelitis. {PPID, p. 1878t] Oral hairy leukoplakia, presumed to be caused by EBV, is an early manifestation of HIV infection in adults. [Harrison ID, p. 754, 836] Patients with deficient cellular immunity may develop fever, lymphadenopathy, and GI symptoms. "EBV-associated malignancies include Burkitt's lymphoma (~90% of cases in Africa and ~15% of cases in the U.S.), anaplastic nasopharyngeal carcinoma in southern China, gastric cancer (with ~9% of these tumors positive for EBV), Hodgkin's disease (especially the mixed-cellularity type), and CNS lymphoma (especially HIV-related)." [Harrisons, p. 549) "In almost all humans, strong CD4+ and CD8+ T cell immune responses to the antigenic EBV latent-infection nuclear proteins prevent uncontrolled B cell lymphoproliferation. However, when humans are severely immunosuppressed by transplantation-associated medication, HIV infection, or genetic immunodeficiencies, EBV-induced B cell malignancies can emerge." [Harrison ID, p. 721] Epstein-Barr infections are associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and possibly other malignancies (Hodgkin's disease and non-Hodgkin's lymphomas). [CCDM, p. 199-202]

Other causes of the "mono syndrome" include cytomegalovirus, Toxoplasma gondii, hepatitis B, rubella, HIV, and adverse drug reactions. [Merck Manual, p. 1626] Other causes of atypical lymphocytes (usually less than 10% of the WBCs) are acute infections (cytomegalovirus, toxoplasmosis, HIV, rubella, mumps, other herpesviruses, and rickettsiae) and drug hypersensitivity reactions. [ID, p. 1535-9]
Monospot (heterophile): false - common 1st 10-14 days; + in 90% by 3rd wk; Viral capsid-specific IgM disappears after several weeks. [5MCC-2020-] Early primary EBV infection = + anti-VCA titer & - anti-EBVA titer; [CCDM, p. 197]
  • >arthralgia
  • >fatigue, weakness
  • >fever
  • >myalgia
  • E pharyngitis
  • E stomatitis
  • G abdominal pain
  • G hepatomegaly
  • G jaundice
  • G liver function test, abnormal
  • G nausea, vomiting
  • H anemia
  • H hemolysis
  • H leukocytosis
  • H leukopenia
  • H lymphadenopathy
  • H splenomegaly
  • H thrombocytopenia
  • N headache
  • N seizure
  • N stiff neck
  • O conjunctivitis, acute
  • O oculoglandular syndrome
  • R cough
  • S lymphadenitis, acute
  • S papules or plaques
  • S petechiae and ecchymoses
  • S rash (exanthem)
  • S rash on palms
  • S urticaria
  • U hematuria
  • X hilar lymphadenopathy
  • X pleural effusions
  • *cancer
  • *cranial neuropathy
  • *encephalitis
  • *erythema nodosum
  • *glomerulonephritis
  • *hepatitis
  • *meningitis
  • *myelitis
  • *myocarditis
  • *paralysis
  • *parotitis
  • *pericarditis
  • *peripheral neuropathy
  • *pneumonia
  • *pneumonitis
  • *rhabdomyolysis
  • *uveitis




Needle (Includes Drug Abuse), Scalpel or Transfusion, Skin or Mucous Membranes (Includes Conjunctiva)
  • AIDS patients
  • Cancer patients
  • Have a blood transfusion
1. (US) EBV pharyngitis: 5 cases/1000 person-years; In rich countries, 1/2 of IM cases occur in early childhood and 1/2 of cases occur in late adolescence; In poor countries, most cases occur in early childhood; 90-95% of adults have serological evidence of previous infection; [Gorbach, p. 216] Calculate: 5 x 300,000 = 1.5 million cases;
2. (Global) 20 X US cases/yr;