Mononucleosis infectious B27.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 09.05.2023

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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. EBV target cells include the naso- and oropharyngeal epihtelia and the B lymphocytes, which carry the CD-21 antigen as EBV receptor.

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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 form (most frequent), especially in infancy.
  2. glandular form (50% of cases): generalized lymphadenopathy (>50%), splenomegaly, tonsillitis
  3. exanthematic form (3-15% of cases): tonsillitis, exanthema and petechial enanthema).
    • acute tonsillitis, pharyngitis, high fever with significant feeling of illness, 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 a lymphoproliferative disease of B lymphocytes.

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Leukocytosis 10,000-40,000/μl, numerous atypical monocytoid cells. Frequent elevation of transaminases up to 10,000 U/l).

Wolf quotient: lymphocyte count/leukocyte count: a quotient >0.35 indicates infectious mononucleosis.

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

Fresh infection:

  • Paul-Bunnel reaction (heterophilic IgM-AK agglutinating mutton erythrocytes) is positive, in children only in 40-50% of cases. However, 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

Common streptococcal angina

Multiforme drug exanthema

Acute HIV infection (HIV serology)

Plaut-Vincenti angina


Syphilitic exanthema

Infections with HHV-6 and HHV-7 viruses


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

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  • Granulocytopenia, thrombocytopenia.
  • Rarely, an infection-associated hemophagic syndrome (IHS) with pancytopenia. Possibly bleeding as a result of increased hemophagocytosis.
  • Splenic rupture (rare: increased risk in high performance athletes who prematurely return to weight bearing training (Shephard RJ 2017).
  • Meningoencephalitis
  • Myocarditis
  • Possibly post-infectious fatigue(fatigue syndrome) (this can last for several months)
  • Chronic active EBV infection with persistent viral replication: especially in children, fever, weight loss, lymphadenopathy, hepatosplenomegaly, possibly.hemolytic anemia.
  • Oral hairy leukoplakia: in coincident HIV infection.
  • EBV infections in immunodeficient patients (see:Immunodeficiencies primary (defects of intrinsic immunity) due to uncontrolled proliferation of EBV-infected , immortalized B lymphocytes result in lymphoproliferative disorders of B lymphocytes.
  • Patients with infectious mononucleosis in anamnee, have a 3-fold increased risk of Hodgkin's disease.

  • EBV-associated Burkitt's lymphoma, which is endemic in Equtorial Africa. EBV plays a co-factor role in this lymphoma.

  • EBV-associated nasopharyngeal carcinoma, which is endemic in southern China and Alaska.

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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: 09.05.2023