WEEKLY TOP 7 – Top 7 clinical signs of EBV infectious mononucleosis

These days medical students are just flooded with a huge amount of information – different descriptions of diseases, fresher and fresher publications – available online. It is really difficult to pick the clinically relevant data, especially when you do not have those years of practice behind your back. In our blog series You will find short and straightforward lists of clinical signs, symptoms which are the most typical and pathognomonic in certain diseases.

The topic of this week is the famous “kissing disease” - the cause of unpleasant moments in teenage romances. Infectious mononucleosis was first described in 1920 but the link between the clinical syndrome and the EBV as a pathogen was discovered only in the late 1960s. Other pathogens such as CMV, Toxoplasma or hepatitis virus can also lead to infectious mononucleosis but today we discuss the most common form: EBV-mononucleosis.

1. Fever, fatigue

Why? EBV infects the oropharyngeal epithelium and the B-cells. The infection of B-cells results in humoral and cellular response to the virus, where T-cells play an important role. Cytokines produced by T-cells cause long-lasting fever and other general signs of infection, like fatigue and malaise.

2. Sore throat

Why? Since EBV penetrates the oropharyngeal epithelial cells, the clinical picture of mono also includes the symptoms of pharyngitis. The exudative form can be easily mistaken for streptococcal pharyngitis, especially  because both can appear with palatal petechiae. If the pharyngitis is accompanied by otherwise rare uvular edema, then we know: EBV stands in the background.

3. Tender and enlarged lymph nodes

Why? Through the infection of B-cells, EBV reaches every point of the immune system, including lymph nodes. Lymphadenopathy is typically symmetrical and affects the posterior cervical chain rather than the anterior. It may also become more generalized making it easier to distinguish EBV from other causes of pharyngitis.

4. Splenomegaly

Why? During the infection, increased antigen clearance is needed, leading to an increased number of reticuloendothelial cells in the spleen. EBV antigens also stimulate antibody production, which results in lymphoid hyperplasia.

5. Generalized rash

Why? The early maculopapular rash is a typical sign of many viral infections. It is caused by the immune antibodies produced by the host’s immune system. However, in the case of EBV, there is another type: Amoxicillin rash. The mechanism is not fully understood but EBV-infection and mistakenly prescribed beta-lactams together are essential for its development.

6. Hoagland-sign

Why? Also known as palpebral edema or more precisely - bilateral upper-lid edema. The background of this symptom has yet to be fully discovered. Inflammation in the lacrimal glands and lymphocytic infiltrate can be possible causes.  

7. Neurologic syndromes

Why? Reactions with the antibodies produced during EBV-infection can lead to several types of neurological pathologies, such as Guillan-Barré syndrome, facial and cranial nerve palsies or aseptic meningitis. The pathomechanism behind it is similar to autoimmune inflammations.


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Hoagland RJ. Infectious mononucleosis. Am J Med 1952; 13: 158-71.