Infectious mononucleosis: causes, symptoms, diagnosis, and treatment

Infectious mononucleosis (IM), also known as glandular fever, is characterized by fever, pharyngalgia, swollen lymph nodes, splenomegaly, lymphocytosis, abnormal lymphocytes, and heterophilic antibody.


Infectious mononucleosis is caused by Epstein Barr (EB) virus, morphologically resembling herpes virus. It was originally found in Barkitt lymphoma cells and can only grow and replicate in lymphoma cells or lymphoidocytes in peripheral blood. Epstein-Barr virus selectively infects cells with surface expression of CD21, namely complement C3d receptor, and by binding to this receptor, Epstein-Barr virus can enter cells. Therefore, Epstein-Barr virus has a tropism for B lymphocytes and occasionally infects squamous epithelial cells. Primary EB virus infections are often asymptomatic, and can also be manifested in infectious mononucleosis. The disease is sporadic and occurs mostly in children and young adults, and may be transmitted through direct contacts or droplets. After the primary infection, the virus is latent in the resting B cells. Under certain conditions, when the resting B cell activation progresses into terminal differentiation or apoptosis, the virus replicates and proliferates, eventually resulting in the infected cell death. Latent infections are absent in epithelial cells, but persistent infection can shed viruses from epithelial cells. Viruses in throat infection are derived from regional differentiated B lymphocytes, and can be shed into saliva, resulting in human-to-human transmission.

Figure 1, Epstein Barr virus

In addition to infectious mononucleosis, EBV infection is also associated with nasopharyngeal carcinoma and various B lymphoproliferative diseases, including various B cell lymphomas.

Signs and Symptoms

The incubation period varies from several days to several weeks, relatively short in children, about 10 days. With slow onset, prodromal symptoms, such as headache, tireness, may be present. Most patients have moderate fever, sometimes high fever up to 39 - 39.5 °C, often lasting for 5 to 10 days, and lasting for 2 weeks or longer in server patients. Exudative angina in several days after onset is the most common symptom. Other presentations are diffuse membranous tonsillitis and some small bleeding points in the commissures of hard palate and soft palate, which are characteristic and usually occur 2 to 3 days after fever. Occasionally, white plaques on the palates or tonsils are present and are the lymphoid hyperplasia in the pharyngeal isthmus, and acataposis are present in the chief complaints. Patients are with lymphadenopathy in the early stage, often systemic, most common in cervical lymph nodes especially in the left posterior neck, followed by the axillae and groins, and most enlarged lymph nodes subside within few weeks after the fever drops, occasionally persisting for months, even years. About 50% of patients have moderate splenomegaly. The liver is also often involved, and its serum aminotransferase is increased, but jaundice is less common in clinical practices. Few patients may develop pneumonia and neurological symptoms.

Rashes occur 4 to 6 days after onset in about 1/3 of patients, mainly palpebral edema, maculae, or morbilliform eruptions, mainly in the trunk and upper limbs, merely scarlatiniform, herpetiform, erythema multiforme, or Gianott-Crosti-like eruptions, as well as cold urticaria and purpura. Rashes subside within few days. When with certain antibiotics such as ampicillin, the incidence of rash is as high as 90%. In other words, in 7 to 8 days after the application of these antibiotics, systemic morbilliform eruptions may occur, and occasionally thrombocytopenic purpura, meningoencephalitis, myocarditis, or autoimmune hemolytic anemia can occur. Administration of other antibiotics such as penicillin, tetracycline can also aggravate skin lesions occasionally.

The total count of peripheral blood leukocytes can be increased by (10 - 40) × 109/L, the absolute number of lymphocytes and monocytes is increased, and abnormal lymphocytes are present and are basophilic and contains foamy thick pulp and perforated nucleus. Abnormal lymphocytes can account for 10% of leukocytes. IgM and IgG antibodies to the anti-viral capsid antigen may appear in the serum shortly after infection. Patients are often with positive cryoagglutinin.


Extensive lymphoid hyperplasia and focal monocyte infiltration in the mononuclear phagocyte system and other organs can be seen.


On the basis of membranous exudative tonsillitis, systemic lymphadenopathy, abnormal lymphocyte count in peripheral blood > 10%, infectious mononucleosis can be considered.


There is currently no specific treatment, only symptomatic treatment. Glucocorticoids may be applied in patients with meningoencephalitis, myocarditis, autoimmune hemolytic anemia, or thrombocytopenic purpura. It is thought that chloroquine is effective in severe patients. Acyclovir has also been used to treat EBV infection.