Mononucleosis infectious B27.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 20.01.2022

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EBV infection; Epstein-Barr virus infection; glandular fever; Glandular fever; infectious mononucleosis; Infectious Mononucleosis; Monocyteangina; mononucleosis infectiosa; Pfeiffer glandular fever; Pfeiffer's disease

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Filatov, 1887; Pfeiffer, 1889

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Infectious disease occurring worldwide caused by the Epstein-Barr virus(HHV-4; see below Herpes viruses, human, see below EBV virus infections), a virus with a DNA genome of the genus Lymphokryptovirus, from the family Herpesviridae. The virus is transmitted by droplet infection or saliva contact (kissing disease). The infection is usually inapparent in infancy.

Later in life, the infectious disease presents with the typical picture of "Pfeiffer's glandular fever" with necrotizing angina, lymphadenopathy, hepatosplenomegaly, atypical monocytosis and exanthema (3-15% of cases). The maculo-papular exanthema occurs almost obligatorily with the administration of aminopenicillins (ampicillin, amoxycillin).

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Like all herpes viruses, HHV 4 is ubiquitously distributed and infects humans persistently. It is excreted in saliva and is also transmitted. The main mode of transmission is droplet infection, which is why the mononucleosis occurring with the primary infection has also been given the name "kissing disease".

In industrialized countries, the infection reaches about 40% by the age of 15, and then rises steeply with puberty to 80-90% in adulthood. In the developing countries, due to the lower hygiene standards, the infestation is practically 100 % already among the under 3-year-olds. Iatrogenic transmission in transplants has been reported. Especially HHV-4-seronegative recipients are at risk (Schnitzler P et al. 2019).

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Transmission by droplet infection, saliva, sexual contact ("kissing-disease") or physical contact.

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Mainly occurring in teenagers or young adults, preferably in spring. In 90% of infants mostly inapparent course.

Clinical features
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The incubation period is 4-50 days.

The clinical picture is characterized by the triad:

  • febrile (usually >39 °C) angina tonsillaris.
  • generalized lymphadenopathy.
  • Blood count with virocytes (leukocytosis: 10,000 - 40,000 cells/l; lymphocytosis >50% with atypical lymphocytes).

The clinical course can be divided into 4 variants:

  1. inapparent course (most frequent)
  2. glandular form (50% of cases): generalized lymphadenopathy (>50%), splenomegaly, tonsillitis
  3. exanthematous form (3-15% of cases): tonsillitis, exanthema and petechial enanthema).
    • acute tonsillitis, pharyngitis, high fever with significant malaise, cervical lymphadenopathy, blood count changes.
    • Day 4-6 of the clinically manifest disease: generalized, trunk- and extremity-focused, often pruritic, dense maculo-papular (morbilliform) or erythema-multiforme-like exanthema; not infrequently accompanying enanthema with raspberry tongue. Often clearly palpable liver and spleen enlargement.
    • Rare is the occurrence of erythema nodosum.
  4. Hepatic form (5% of cases): hepatitis, possibly with appearance of jaundice.

EBV in immunocompromised patients: uncontrolled proliferation of EBV-infected , immortalized B lymphocytes leads to lymphoproliferative disease of B lymphocytes.

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Leukocytosis 10.000-40.000/μl, numerous atypical monocytoid cells. Frequent increase of transaminases up to 10.000 U/l)

Serological AK detection (see detailed explanation for EBV virus infections):

Fresh infection:

  • Paul-Bunnel reaction (heterophilic IgM-AK, which agglutinates mutton erythrocytes) is positive, in children only in 40-50% of cases AK are not EBV-specific!
  • Anti-VCA(viral capsid antigen) IgG- + IgM - antibodies against Epstein-Barr virus, fourfold increase in titer at intervals of 10-14 days.
  • Detection of Epstein-Barr-Virus DNA via PCR.

Past infection:

  • Detection of IgG type anti-VCA

Differential diagnosis
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Cytomegalovirus infection

Streptococcal angina

Drug exanthema

Syphilitic exanthema

Infections with HHV-6 and HHV-7 viruses


In case of lymphadenopathy and leukocytosis, myeloproliferative disease must also be considered.

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Granulocytopenia, thrombocytopenia

Rare is an infectious haemophagic syndrome (IHS) with pancytopenia. Possible bleeding due to increased hemophagocytosis

Rupture of the spleen (rare: increased risk for top athletes, who start prematurely with stressful training sessions (Shephard RJ 2017)



Possible post-infectious fatigue (this can last for several months)

Chronically active EBV infection with persistent viral replication: especially in children, fever, weight loss, lymphadenopathy, hepatosplenomegaly, possibly hemolytic anemia.

Oral hair leukoplakia: in coincidental HIV infection.

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  • Symptomatic therapy according to clinic with bed rest, fever reduction by calf compresses and/or paracetamol (e.g. Ben-u-ron) 3 times/day 500 mg p.o..
  • In case of itching, external Tannolact Lotio, Lotio alba, also with addition of 3-5% Polidocanol R200 or, if necessary, treatment with antihistamines such as Desloratadin (e.g. Aerius) 1-2 tbl./day or Levocetirizin (e.g. Xusal) 1-2 tbl./day.
  • If the oral mucosa is affected, use an antiphlogistic and astringent mouth rinse (e.g. Kamillosan, R255 ).
  • In severe cases sonographic control of liver and spleen.

Reminder. Do not use aminopenicillins (e.g. ampicillin, amoxycillin, bacampicillin) in mononucleosis! When aminopenicillins are taken in the acute phase(of the non-exanthematous forms), maculopapular exanthema occurs in >1/3 of cases! See adverse drug reaction below. Furthermore, periorbital facial oedema (30%) and petechiae on the palate occur.

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  1. Balfour HH Jr et al (2015) Infectious mononucleosis. Clin TranslImmunology 4:e33
  2. Berger C et al (2001) Dynamics of Epstein-Barr virus DNA levels in serum during EBV-associated disease. J Med Virol 64: 505-512
  3. Chen J et al (2003) Just another simple case of infectious mononucleosis? Lancet 361: 1182
  4. Chovel-Sella A et al (2013) Incidence of rash after amoxicillin treatment in children with infectious mononucleosis.pediatrics 131:e1424-1427
  5. Filatov N (1887) Lektsii ob ostrikh infeksionnîkh boleznyakh u dietei. Vol. 1 u.2, A. Lang, Moscow
  6. Ikediobi NI, Tyring SK (2002) Cutaneous manifestations of Epstein-Barr virus infection. Dermatol Clin 20: 283-289
  7. Lennon P et al.(2015) Infectious mononucleosis. BMJ 350:h1825
  8. McArthtur JR et al (2002) Infectious mononucleosis, peripheral blood. Hematology morphology forum. Hematology 7: 201-202
  9. Pfeiffer E (1889) glandular fever. Yearbook for Pediatrics and Physical Education (Vienna) 29: 257-264
  10. Rosenberg ES et al (1999) Acute HIV infection among patients tested for mononucleosis. N Engl J Med 340: 969
  11. Shephard RJ (2017) Exercise and the Athlete With Infectious Mononucleosis.
    Clin J Sport Med 27:168-178.
  12. Schnitzler P et al (2019) Virology. In: Hof H et al (Ed.) Medical Microbiology Thieme Verlag S 256-260


Please ask your physician for a reliable diagnosis. This website is only meant as a reference.


Last updated on: 20.01.2022