Is It Mono or a Different Kind of Sore Throat?

Pharmacy Times, December 2019, Volume 85, Issue 12

Mononucleosis can pose challenges for diangosis, as its presentation is similar to that of other bacterial and viral pharyngitis infection.

Sore throat is one of the top 10 complaints in primary care1 and retail health.2 Most often sore throats are caused by viral infections,3 and 40% of these are caused specifically by adenovirus and rhinovirus.4 Other viral causes are coronavirus, coxsackievirus, cytomegalovirus, Epstein-Barr, herpes simplex, HIV, influenza, and parainfluenza.5 The Epstein-Barr virus (EBV), which causes infectious mononucleosis (IM), is extremely prevalent. It is estimated that more than 95% of the world’s adult population has been infected with the virus, but only some patients will become symptomatic with initial infection.6 The development of symptomatic IM correlates strongly with age.7 In infants and young children, IM is typically asymptomatic or may have nonspecific symptoms.7 Adolescents and adults are more likely to show classic IM symptoms,7 but not all who become infected will have symptoms.7 It is estimated that 30% to 77% of adolescents and adults will develop symptoms of IM.7 However, clinical presentation of IM can be very similar to that of other bacterial and viral pharyngitis infections, posing a challenge in diagnosis of IM.

EBV-associated IM is also known as glandular fever, kissing disease, mono, mononucleosis, and Pfeiffer syndrome.7


Typical IM symptoms in adolescents and adults are fever, lymphadenopathy, and pharyngitis.7 Fatigue and malaise, which can persist for weeks and even months,6 are also very common, occurring in about 47% of adults and about 24% of children.6,7 Abdominal pain/nausea/vomiting occurs in about 17% to 18% of both adults and children, headaches occur in about 38% of adults, and a rash can be present in about 8% of adults and 17% of children.7 Less common symptoms include palatal petechiae and periorbital edema.6

The physical symptoms of IM are similar to those of many other bacterial and viral infections. The pharyngitis could be exudative or nonexudative, may have petechiae on the soft palate, and may look like streptococcus pharyngitis.8 The fever typically ranges from a temperature of 100°F to 102°F but can get as high as 106°F.8 This fever usually lasts 1 to 2 weeks but may last up to 5 weeks.8 Another common finding upon physical exam can be splenomegaly, which occurs in about 52% of all cases.8 Other symptoms that patients may experience are hepatomegaly (12% of patients), jaundice (9% of patients), and myalgias (28% of patients).8

Risk factors for IM include age greater than 20 years, residence in or a visit to a developing nation, poor sanitation, the sharing of saliva, and time spent in a day care center.7


A few tests can confirm an IM diagnosis.

These include:

  • Complete blood count. This test can support diagnosis. In up to 90% of patients, atypical lymphocytosis greater than 10% can be found, and in about 70% of patients, lymphocytosis greater than 50% will be present and is highest during the second and third week.8
  • EBV-specific serologies (panel of 4 antibodies). This can provide a definitive diagnosis when heterophile antibody testing is negative.7 It has a high sensitivity and specificity and is more sensitive than the heterophile antibody test.8
  • Heterophile antibody testing (Mono-Latex or Monospot).7 This test is common and can be used during the first few weeks of IM, but the sensitivity will vary depending on the patient’s age, how far along the patient is in their illness, and the type of test used.7 This is often the test of choice, but it can produce false negatives early in the illness. False negatives are also common in infants and children younger than 4 years.9
  • Real-time polymerase chain reaction. This test has a 95% sensitivity and a 97% specificity for primary EBV infection but can be expensive and is not widely used.8


IM is rarely fatal, but it can potentially lead to other complications. In about 25% to 50% of patients, mild hematologic conditions can occur, including aplastic and hemolytic anemia, disseminated intravascular coagulation, hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, and thrombocytopenia.6 Less commonly, neurologic complications can arise. In about 1% to 5% of patients, conditions such as aseptic meningitis, cerebellitis, facial nerve palsy, Guillain-Barré syndrome, meningoencephalitis, optic neuritis, peripheral neuritis, and transverse myelitis may occur.6 Splenic rupture, a life-threatening condition, can occur in about 0.5% to 1.0% of cases, and airway obstruction can occur in about 1.0% of patients, as a result of lymphoid hyperplasia and mucosal edema.6


The mainstay of treatment for IM is prevention of potential complications and transmission to others as well as supportive care. Patients can take acetaminophen and ibuprofen for aches, fever, and sore throats and should drink plenty of water. Clinicians should monitor the patient for splenomegaly to prevent splenic rupture. Patients should avoid contact sports and strenuous activities for at least 3 to 4 weeks or even up to 8 weeks, depending on individual circumstances.9 Clinicians must confirm that the patient’s spleen has returned to normal size before returning to playing sports. This can be done with an abdominal ultrasound, and serial ultrasounds may be needed for persistent splenomegaly.9

Sara Hunt, MSN, RN, PHN, FNP-C, is a licensed and board-certified family nurse practitioner, a public health nurse, an adjunct assistant professor of health policy, and a doctor of nursing practice student at the University of California, San Francisco. She was the spring 2015 health policy fellow at the American Association of Nurse Practitioners’ Government Affairs Office in Washington, DC.


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  • Mehrotra A, Wang MC, Lave JR, Adams JL, McGlynn EA. Retail clinics, primary care physicians, and emergency departments: a comparison of patients’ visits. Health Aff (Millwood). 2008;27(5):1272-1282.doi: 10.1377/hlthaff.27.5.1272.
  • Patel C, Green BD, Batt JM, et al. Antibiotic prescribing for tonsillopharyngitis in a general practice setting: can the use of Modified Centor Criteria reduce antibiotic prescribing? Aust J Gen Pract. 2019;48(6):395-401. doi: 10.31128/AJGP-08-18-4685.
  • Renner B, Mueller CA, Shephard A. Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat). Inflamm Res. 2012;61(10):1041-1052. doi: 10.1007/s00011-012-0540-9.
  • Anjos LM, Marcondes MB, Lima MF, Mondelli AL, Okoshi MP. Streptococcal acute pharyngitis. Rev Soc Bras Med Trop. 2014;47(4):409-413. doi: 10.1590/0037-8682-0265-2013.
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  • Epstein-Barr virus-associated infectious mononucleosis. Dynamed website. Updated July 30, 2019. Accessed October 10, 2019.
  • Infectious mononucleosis. Epocrates website. Updated October 31, 2019. Accessed November 17, 2019.
  • Aronson MD, Auwaerter PG. Infectious mononucleosis. UptoDate website. Accessed November 20, 2019.