Steroids for short-term symptom control in infectious mononucleosis (glandular fever)

Review question

We reviewed evidence about the effect of steroids on symptom control in people with glandular fever (infectious mononucleosis) when compared to placebo or different medications.

Background

Glandular fever is caused by a virus. It spreads in saliva through kissing, coughing and sneezing. Symptoms vary in terms of how severe they are and for how long they persist. While young adults commonly suffer from severe symptoms, some people may have mild symptoms or none. Common symptoms include fever, sore throat, swollen lymph nodes and feeling tired.These symptoms usually last for two to three weeks, but can last for months. Symptom relief and rest are common treatments. Doctors commonly use prednisone, a steroid, to reduce the symptoms of sore throat or enlarged tonsils. However, there is no agreement on its use due to the possibility of little benefit and the chance of side effects.

Study characteristics

Our evidence is current to August 2015. We did not identify any new trials for the update of this review. The previous publication of this review included seven trials with 362 participants. Four trials compared the effect of a steroid to a placebo, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral.

The length of treatment varied between a single dose and a 12-day course. The doses used also varied. The length of follow-up varied from short periods (i.e. days or weeks) to longer periods (i.e. six months and 12 months).

Key results

Steroid treatment relieved sore throat in the short term (at 12 hours). The researchers noticed a benefit at two to four days when steroids were used in combination with an antiviral medication, but these findings are limited since researchers assessed them in one or two trials only. The findings on the effect of steroids alone or when used with an antiviral medication for other symptoms were less clear. We are unsure about adverse effects from using steroids. With the exception of two trials, most studies did not set out a prior plan to evaluate the occurrence of side effects, or other adverse events. None of the trials explored adverse effects in the longer term (over years).

Quality of the evidence

The quality of the included trials was generally poor. We cannot know the exact effect of using steroids for glandular fever.

Authors' conclusions: 

There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications.

Read the full abstract...
Background: 

Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the Epstein-Barr virus (EBV), a ubiquitous herpes virus that is found in all human societies and cultures. Epidemiological studies show that over 95% of adults worldwide have been infected with EBV. Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. It is transmitted through close contact with an EBV shedder, contact with infected saliva or, less commonly, through sexual contact, blood transfusions or by sharing utensils; however, transmission actually occurs less than 10% of the time. Precautions are not needed to prevent transmission because of the high percentage of seropositivity for EBV. Infectious mononucleosis is self-limiting and typically lasts for two to three weeks. Nevertheless, symptoms can last for weeks and occasionally months.

Symptoms include fever, lymphadenopathy, pharyngitis, hepatosplenomegaly and fatigue. Symptom relief and rest are commonly recommended treatments. Steroids have been used for their anti-inflammatory effects, but there are no universal criteria for their use.

Objectives: 

The objectives of the review were to determine the efficacy and safety of steroid therapy versus placebo, usual care or different drug therapies for symptom control in infectious mononucleosis.

Search strategy: 

For this 2015 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (January 1966 to August 2015) and EMBASE (January 1974 to August 2015). We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. We combined the MEDLINE search with the Cochrane search strategy for identifying randomised controlled trials (RCTs). We adapted the search terms when searching EMBASE.

Selection criteria: 

RCTs comparing the effectiveness of steroids with placebo, usual care, or other interventions for symptom control for people with documented infectious mononucleosis.

Data collection and analysis: 

We used the standard methodological procedures expected by Cochrane.

Main results: 

For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis.

Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under-reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear.

Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained.

In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite.

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