How Mononucleosis Is Diagnosed

The diagnosis of infectious mononucleosis (mono) is usually made based on the symptoms, findings in a physical examination, and blood tests. Mono is usually caused by the Epstein-Barr virus (EBV) or similar viruses, but strep throat and some other conditions can cause similar signs and symptoms. While the Centers for Disease Control (CDC) no longer recommends the ​monospot test, many guidelines still encourage using this test to help identify the cause of mono.

Self-Checks

You probably won't immediately recognize that you or your child has mono because the early symptoms are like those of a cold, the flu, or strep throat. It is important not to rely on self-diagnosis for mono because the symptoms are similar to those of illnesses that need a different course of treatment.

The symptoms most likely to send you to the healthcare provider are swollen lymph nodes in the neck, extreme fatigue, sore throat, fever, and body aches that have lasted for longer than 10 days.

The symptoms can be mild in babies and younger children.

You should note the timeline of your symptoms, including when you or your child first started feeling sick, which symptoms developed, and how long they have lasted. This can help your healthcare provider make a diagnosis if you go in for a medical evaluation.

You should see your healthcare provider immediately if you develop any of the serious symptoms of mono.

These include:

• A high fever
• Severe or persistent abdominal pain
• Severely swollen throat or tonsils
• Difficulty breathing or swallowing
• Limb weakness
• A severe headache

These could be due to mono, but could also be caused by other conditions and complications.

Labs and Tests

During your medical evaluation, your healthcare provider will consider your symptoms and your age since people infected with EBV are more likely to develop mono during the teenage or young adult years. During your physical evaluation, your provider will look in the back of your throat for petechiae (red spots), feel your neck and other areas where you may have swollen lymph nodes, and listen to your lungs.

Your healthcare provider will usually order a complete blood count (CBC) and an antibody test. If you have a sore throat, it is likely that a rapid strep test will be performed. If you are pregnant, more extensive antibody testing may be done to rule out problems that could affect your pregnancy.

CBC

If you have mono, your CBC will typically show an elevated white blood count (WBC) with more lymphocytes than usual, which is known as lymphocytosis. Lymphocytes are a part of your body's immune system and it is natural for them to be elevated during certain types of infections. These lymphocytes will have an atypical appearance when examined with a microscope.

You will also have fewer of the other predominant type of white cells, neutrophils, and you may have a lower than usual platelet count.

Antibody Testing

Your blood may be analyzed in a laboratory for antibodies, although this test isn't required for a diagnosis of infectious mononucleosis. Antibodies are produced by your immune system to fight infections.

The monospot (heterophile antibody test) is an older test that is commonly used to make the mono diagnosis. A positive monospot test accompanied by the symptoms of mono helps in the diagnosis of infectious mononucleosis. However, the CDC says the monospot test is no longer recommended because it produces too many inaccurate results.

False results include:

• Monospot tests can be false-negative about 10% to 30% of the time, particularly in the early stages of the illness. 
• You stand an approximately 25% chance of getting a false-negative test result if you are tested within the first week of symptom onset. 
• You can have a false negative test if you waited too long to see a healthcare provider because the antibodies rapidly decrease after you've been infected for more than four weeks.
• If you have mono from a different virus than EBV, such as cytomegalovirus (CMV), the monospot won't detect it.
• A monospot test can be falsely positive with hepatitis, leukemia, lymphoma, rubella, systemic lupus erythematosus, and toxoplasmosis.

More extensive antibody tests may be done if the illness symptoms aren't typical for mononucleosis or you have been ill for more than four weeks. You may be tested for cytomegalovirus or Toxoplasma antibodies. 

More specific tests for EBV include:

• Viral capsid antigen (VCA)
• Early antigen (EA)
• EBV nuclear antigen (EBNA) tests

Mononucleosis Doctor Discussion Guide

Get our printable guide for your next doctor's appointment to help you ask the right questions.

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Differential Diagnosis

Your healthcare provider will consider your symptoms and other tests to distinguish between EBV mono and other conditions. Illness with CMV and Toxoplasma gondii may be designated as infectious mononucleosis or called a mono-like illness. As with EBV mono, only supportive treatment is recommended. However, these illnesses can complicate pregnancy, so further tests to identify the cause of the illness are recommended for moms-to-be.

Similar conditions your doctor may consider include:

• A sore throat, fever, and swollen glands seen in mono can appear like the symptoms of strep throat. A rapid strep test or throat culture can help distinguish these. Strep throat usually improves quickly to antibiotics, which have no effect on mono.
• Influenza can also mimic some of the symptoms of mono but usually doesn't produce swollen neck glands. Influenza will usually get better in less than two weeks.
• Mono-like symptoms can be seen in infections other than Epstein-Barr virus. Other pathogens (infectious organisms) that can produce these symptoms include CMV, adenovirus, human immunodeficiency virus (HIV), rubella, hepatitis A, human herpesvirus-6, and the parasite Toxoplasma gondii.