Table of contents

Infectious mononucleosis

What's new

Updated 2023 AMSSM guidelines for the diagnosis and management of infectious mononucleosis.



IM, also known as mono or "kissing disease", is an acute infection characterized by fever, lymphadenopathy, and pharyngitis.
IM is most frequently caused by the EBV transmitted through infected saliva during kissing.
The incidence of IM in the US is estimated at 500 cases per 100,000 population per year, with the peak incidence between ages 15-24 years. However, over 90% of adults globally are EBV seropositive.
Disease course
Young children are often asymptomatic, and symptoms frequently occur in adolescents and young adults. Clinical manifestations include pharyngitis, bilateral cervical lymphadenopathy, fever, generalized muscle aches, hepatosplenomegaly, maculopapular rash, jaundice, arthritis, conjunctivitis, and edema. Complications include hematological complications (hemolytic anemia, thrombocytopenia, aplastic anemia, TTP, HUS, and DIC), neurologic complications (Guillain-Barre syndrome, facial paralysis, meningoencephalitis, aseptic meningitis, transversal myelitis, peripheral neuritis, cerebellitis, and optical neuritis), splenic rupture, airway obstruction, pneumonia, hemophagocytic lymphohistiocytosis (prolonged fever, lymphadenopathy, hepatosplenomegaly, exanthem, hepatic dysfunction, and cytopenia).
Prognosis and risk of recurrence
Most patients achieve complete resolution within weeks, and mortality rates are low (5.3%). EBV remains dormant post-recovery, but symptomatic reactivation is rare.


Key sources

The following summarized guidelines for the evaluation and management of infectious mononucleosis are prepared by our editorial team based on guidelines from the American Medical Society for Sports Medicine (AMSSM 2023) and the American Academy of Family Physicians (AAFP 2004). ...
Show more

Screening and diagnosis

Diagnosis: as per AAFP 2004 guidelines, suspect IM in 10-30 years old patients presenting with sore throat and significant fatigue, palatal petechiae, posterior cervical or auricular lymphadenopathy, marked axillary lymphadenopathy, or inguinal lymphadenopathy.
Create free account

Classification and risk stratification

Risk of splenic rupture
As per N/A 2014 guidelines:
Recognize that splenic rupture is a rare complication of IM with an incidence of < 0.5%.
Recognize that most splenic ruptures occur in the first 2 days of illness and are exceedingly rare after 28 days from the onset of IM.

More topics in this section

  • Risk of chronic fatigue

Diagnostic investigations

Clinical assessment: as per AMSSM 2023 guidelines, recognize that clinical manifestations of IM can be nonspecific and physical examination techniques have poor sensitivity and specificity in identifying relative splenic enlargement, and inter-rater reliability for physical examination is also poor.

More topics in this section

  • Laboratory tests

  • Splenic imaging

Medical management

Supportive care: as per AMSSM 2023 guidelines, offer supportive care for the treatment of uncomplicated IM.

More topics in this section

  • Corticosteroids

  • Antiviral therapy

  • Antihistamines

Nonpharmacologic interventions

Exercise restriction: as per N/A 2014 guidelines, advise athletes with IM to refrain from sports activity until afebrile, asymptomatic, and well-hydrated.

Follow-up and surveillance

Return to sport: as per AMSSM 2023 guidelines, consider advising a trial of supervised, nonimpact, low-intensity activity 2 weeks from the onset of symptoms in afebrile athletes with an adequate energy level and improving clinical examination findings. Consider delaying return to sport in the presence of ongoing clinical signs/symptoms, lack of athlete readiness, and/or IM-associated complications.
Show 2 more