Steroids Should Not Be Used Routinely for Uncomplicated Mononucleosis
Steroids are not recommended for routine treatment of infectious mononucleosis and should be reserved only for life-threatening complications such as impending airway obstruction, severe pharyngeal edema causing respiratory compromise, or autoimmune hematologic complications. 1, 2
Evidence Against Routine Steroid Use
Lack of Efficacy for Symptom Control
A Cochrane systematic review of 7 randomized controlled trials (362 participants) found insufficient evidence for steroid efficacy in symptom control for infectious mononucleosis 3
Only 2 of 10 health improvement assessments showed any benefit, with transient sore throat relief at 12 hours that was not maintained beyond that timepoint 3
No sustained benefit was demonstrated for fever, lymphadenopathy, pharyngitis, or fatigue—the primary symptoms patients experience 3
A retrospective study of 206 patients found no significant differences in disease complications, hospital admission rates, or length of hospital stay between steroid-treated and non-steroid-treated groups 4
Documented Serious Complications
Prolonged steroid use in uncomplicated mononucleosis has been associated with severe infectious complications, including polymicrobial bacteremia leading to septic shock, pulmonary septic emboli, sinus thrombosis, empyema, and orbital cellulitis 5
Adverse events documented in trials include respiratory distress and acute onset of diabetes, though causality is uncertain 3
The Cochrane review specifically noted a lack of research on side effects and long-term complications, raising safety concerns 3
When Steroids May Be Appropriate
Specific Life-Threatening Indications Only
Impending airway obstruction from severe tonsillar hypertrophy causing respiratory compromise 1, 2
Severe pharyngeal edema threatening airway patency 1
Autoimmune hematologic complications (such as severe thrombocytopenia or hemolytic anemia) 2
These indications represent only approximately 8% of mononucleosis cases 4
Recommended Management Approach
Standard Supportive Care
Adequate hydration, analgesics, antipyretics, and rest are the mainstays of treatment 1
Activity should be guided by the patient's energy level rather than enforced bed rest 1
Withdrawal from contact or collision sports for at least 4 weeks after symptom onset to prevent splenic rupture 1
What Not to Do
Do not prescribe corticosteroids for routine symptom control including sore throat, fever, or lymphadenopathy 1, 3, 2
Do not use acyclovir or antihistamines routinely 1
Avoid immunosuppressive therapies during the active viral phase, as they may prolong viral shedding 6
Clinical Reality vs. Evidence
Despite clear evidence against routine use, steroids continue to be prescribed in approximately 45% of mononucleosis cases, with 92% of steroid use occurring outside traditional indications 4. This practice pattern persists without supporting evidence and carries potential serious risks 5, 4.
The bottom line: symptomatic treatment with hydration, analgesics, and rest is sufficient for uncomplicated mononucleosis, with steroids reserved exclusively for the rare patient with life-threatening airway compromise or severe autoimmune complications. 1, 3, 2