Editors

TeaNieminen

Mononucleosis

An infection usually caused by EBV (HHV-4); transmission generally requires mucosal contact ("kissing disease")
The most common symptoms are fever, sore throat and enlarged lymph nodes in the neck area.
The treatment is symptomatic.
In adults, the acute illness often manifests with severe symptoms, and the symptoms are relatively long lasting (several weeks).
The duration of required sick leave is often longer than that required in many other respiratory tract infections.
Serious complications are possible but rare.

The incubation period is estimated to be 30-50 days.
In many countries practically all people will contract EBV at some time in their lives.
In western countries, about half of the population will be infected at the age of 1 to 5 years. Another incidence peak is in the 15-24-year age group.
Those infected remain virus carriers and excrete the virus in their saliva from time to time, which promotes the spread of the infection in the population.

In children, the infection is often asymptomatic or only produces mild symptoms.
In young adults, the infection usually (in 70-80%) leads to clinical mononucleosis.
In individuals over 30 years of age, the infection is rare but they have a greater risk of complications.
Common symptoms include high fever, a nasal voice, tonsillitis and enlarged lymph nodes (around the mandibular angles, under the chin).
About one in ten patients develop a rash with erythematous macules.
- Administration of amoxicillin in a fresh EBV infection approximately doubles the proportion of patients who develop a rash; picture 1.
- The skin reaction does not indicate an allergy that would prevent the use of amoxicillin in the future.
The spleen appears enlarged in ultrasonography in nearly all patients but only some have an enlarged spleen that can be felt by palpation (video Mononucleosis and Splenomegaly).
Hepatomegaly and jaundice occur in less than 10% of patients.
Spontaneous recovery is usually seen within a couple of weeks. In rare cases, fever may persist for as long as 4-6 weeks.
A small proportion of patients suffer from chronic fatigue that may last up to several months and resembles chronic fatigue syndrome Fatigue, but the condition does not usually fulfil the criteria of this syndrome with regard to severity, duration and prognosis of symptoms.
Even though the EBV may cross the placenta, any adverse health effects on the foetus or the newborn are extremely rare.

Sometimes the symptoms are so severe as to require hospitalization.
The risk of spleen rupture is highest within 3 weeks from falling ill.
The risk of airway obstruction due to enlarged palatine tonsils is less than 1%.
The incidence of neurological disorders (meningitis, polyradiculitis, mental disturbances) is 1-5%.
Severe symptoms may also include hepatitis or pancreatitis.
Autoimmune haemolytic anaemia (AIHA) or thrombocytopenia may cause bleeding.
Concomitant streptococcal infection or peritonsillar abscess may make pharyngeal symptoms more severe.

EBV causes 80-90% of cases of mononucleosis.
- Cytomegalovirus (CMV) may cause a similar clinical disease.
- The possibility of first symptoms of HIV infection should also be kept in mind.
- The patient may be found to have a concomitant streptococcal throat infection (20-30%). In many cases, however, they are asymptomatic carriers.

Blood count
- A typical finding is an increase in mononuclear cells (over 50% of white blood cells are lymphocytes).
- Up to 30% of all lymphocytes in peripheral blood are atypical.
- Thrombocytopenia and granulocytopenia are fairly common.
- Sometimes the blood count erroneously raises the suspicion of a malignant haematological disease.
The rapid test that detects heterophilic antibodies is quite specific but it only identifies about 90% of mononucleosis cases in adults, 75% in older children and only 30% in children below 2 years of age.
A positive rapid test together with a typical clinical picture provides a quite reliable diagnosis in young adults.
- If the rapid test is negative but definite confirmation of the diagnosis is important (for differential diagnostic reasons, for example) EBV antibodies should be tested for.
- IgM antibodies are nearly always found at the beginning of the disease already.
- Specific antibodies may also be used as a diagnostic test in the initial phase.
Other laboratory tests are needed only for differential diagnosis.
- CRP may be low.
- ALT is elevated in 80% of patients (by as much as several hundred IU/ml).
- Throat culture
Mononucleosis causes polyclonal activation of B cells which may give false positive results for IgM class antibodies (e.g. for mycoplasma or borrelia).

Treatment is mostly symptomatic, i.e. rest, fluid administration, pain medication and use of NSAIDs for fever.
The patient should be warned to avoid physical exercise and especially hobbies that predispose the patient to injuries (risk of spleen rupture) for a period of 4 weeks if the spleen is enlarged ( i.e. the spleen can be felt on palpation or is longer than 10-12 cm in ultrasonography).
Antiviral medication (aciclovir, valaciclovir) is not recommended.
Swelling that compromises eating or breathing should be treated in hospital, often with glucocorticoids.

De Paor M, O'Brien K, Fahey T et al. Antiviral agents for infectious mononucleosis (glandular fever). Cochrane Database Syst Rev 2016;12(12):CD011487. [PubMed]
Ebell MH, Call M, Shinholser J et al. Does This Patient Have Infectious Mononucleosis?: The Rational Clinical Examination Systematic Review. JAMA 2016;315(14):1502-9. [PubMed]
Rezk E, Nofal YH, Hamzeh A et al. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev 2015;2015(11):CD004402. [PubMed]
Lennon P, Crotty M, Fenton JE. Infectious mononucleosis. BMJ 2015;350():h1825. [PubMed]