Mononucleosis infectious B27.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

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

History
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Filatov, 1887; Pfeiffer, 1889

Definition
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Infectious disease caused worldwide by the Epstein-Barr virus(HHV-4; see below herpes viruses, human, see below EBV virus infections), a DNA virus of the herpes family The virus is transmitted by droplet infection or saliva contact (kissing disease). The infection usually does not spread in small children.

In later life the infectious disease appears under 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 obligatory with the administration of aminopenicillins (ampicillin, amoxycillin).

Occurrence/Epidemiology
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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).

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

Manifestation
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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. exanthematic form (3-15% of cases): tonsillitis, exanthema and petechial enanthema)
    • Acute tonsillitis, pharyngitis, high fever with considerable feeling of illness, cervical lymphadenopathy, blood count changes.
    • Day 4-6 of the clinically manifest disease: generalized, trunk and extremity stressed, often itchy, dense maculo-papular (morbilliform) or erythema-multiforme-like exanthema; not rarely accompanying enanthema with raspberry tongue. Often clearly palpable enlargement of the liver and spleen.
    • Rare is the occurrence of erythema nodosum.
  4. hepatic form (5% of cases): hepatitis, possibly with appearance of icterus

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

Laboratory
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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
  • Streptococcus angina
  • Drug exanthema
  • Syphilitic exanthema
  • Infections with HHV-6 and HHV-7 viruses
  • Toxoplasmosis
  • With lymphadenopathy and leukocytosis, a myeloproliferative disease must also be considered

Complication(s)
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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)

Meningoencephalitis

Myocarditis

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.

Therapy
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  • Symptomatic therapy after hospitalization with bed rest, fever reduction by calf compresses and/or paracetamol (e.g. Ben-u-ron) 3 times/day 500 mg p.o.
  • For itching external Tannolact Lotio, Lotio alba, also with addition of 3-5% Polidocanol R200 or if necessary treatment with antihistamines such as Desloratadine (e.g. Aerius) 1-2 Tbl./day or Levocetirizine (e.g. Xusal) 1-2 Tbl./day.
  • If the oral mucosa is affected, antiphlogistic and astringent mouthwash (e.g. Kamillosan, R255 ).
  • In severe cases, sonographic controls of liver and spleen

Remember! No application of aminopenicillins (e.g. ampicillin, amoxycillin, bacampicillin) in case of mononucleosis! If aminopenicillins are taken in the acute phase(the non-exanthematic forms), maculopapular exanthema occurs in >1/3 of cases! S.u. Drug reaction, undesirable. Furthermore, periorbital facial edema (30%) and petechiae on the palate occur.

Literature
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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

Disclaimer

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

Authors

Last updated on: 29.10.2020