However, there is no agreement on its use due to the possibility of little benefit and the chance of side effects. Our evidence is current to August We did not identify any new trials for the update of this review. The previous publication of this review included seven trials with 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 doses used also varied. 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. The quality of the included trials was generally poor.
We cannot know the exact effect of using steroids for glandular fever. Infectious mononucleosis is also known as glandular fever, mono or the kissing disease. Pathophysiologically, infectious mononucleosis is considered to be a lymphoproliferative disorder that is caused by a virus.
EBV occurs worldwide Hellwig ; Luzuriaga Moreover, evidence of familial aggregation of infectious mononucleosis was found in a recent study Rostgaard While the infection in early childhood is often asymptomatic, adolescents or adults usually develop symptoms Hellwig ; Luzuriaga ; Maki Therefore, they generally do not develop symptomatic infectious mononucleosis when they are older. The overall incidence in the United States has been reported to be around cases per , persons per year Hellwig Symptomatic infectious mononucleosis infection has also been reported to be about 30 times higher in white people than in black people in the US Aronson ; Hellwig However, there are no predisposing differences in terms of gender.
There is no evidence that seasonal changes affect its incidence Hellwig ; Luzuriaga Young adults, for example, college students living in crowded surroundings, have the highest rates of infectious mononucleosis Aronson ; Hellwig ; Maki It is transmitted when there is contact with saliva e.
As a large proportion of the population is already seropositive for EBV precautions are not needed to prevent transmission, as it is not a particularly infectious disease Hellwig EBV infection results in a chronic, usually lifelong infection, as the virus resides in cells known as memory B cells, where it may later reactivate and spread through oropharyngeal secretions Hellwig ; Luzuriaga ; Souza Nevertheless, symptoms can last for weeks and occasionally months, leading to discomfort and affecting the educational and professional life aspects of the patients Candy Young children infected with EBV commonly have no or only mild symptoms, which may remain undiagnosed.
However, older children, teens and young adults commonly exhibit signs and symptoms. The disease begins with a prodromal period of symptoms such as headache, anorexia and fatigue for one to two weeks before the classical symptoms of the disease manifest Aronson ; Hellwig Some symptoms such as difficulty in breathing due to severe pharyngeal enlargement may require hospitalisation.
In recent decades, the number of patients with infectious mononucleosis who require hospitalisation, especially adolescents and young adults, has increased in England and the US, even though there is no evidence of changes in its virulence Tattevin Symptom relief and rest are commonly recommended treatments for infectious mononucleosis AAFP ; Brown ; Candy ; Cohen At that time, a number of reports based on single cases or small series of people noted the favourable effect that steroids had on acute symptoms, such as sore throat Bender ; Creditor ; Doran ; Fiese ; Frenkel ; Mandel ; Mason Steroids were also reported to be effective in treating complications or accompanying conditions, such as thrombocytopenia Doran , hepatitis Bender , pericarditis Bender , myocarditis Bender , and encephalitis Fiese More recently, steroid treatment has been combined with antivirals, such as acyclovir, with the aim of enhancing their effect Tynell The potential long duration of infectious mononucleosis and the age group most likely to be symptomatic is perhaps key in the prescription of steroids for symptom control.
As it can affect adolescents and young adults at a time in their school or academic careers when they are expected to be continually productive, there is often a distinct personal need to resume normal life as soon as possible.
In addition, it is a time in life where sports and social activities can be a major aspect of everyday life Candy However, because these effects are not exclusive to inflammation signalling and affect physiological signalling as well, one should bear in mind that using glucocorticoids in treatment often accompanied with adverse effects Rhen However, since the s, when formal trials of their effects began, the use of steroids for infectious mononucleosis has been considered controversial.
In particular:. In addition, the effectiveness of steroids for symptom control is unclear for some indications, including fever, sore throat and swollen lymph glands. Trial results for these symptoms are conflicting while for other indications enlarged liver and fatigue data are scant. There is also the cost of drug therapy to be considered, in particular if the steroids are used in combination with antiviral drugs Candy This is an update of a Cochrane review first published in Candy , updated in Candy , and updated again in Candy There are no universal criteria for the use of steroids in infectious mononucleosis.
They are generally used for severe complications, particularly compromised airways Auwaerter ; Ganzel ; McGowan ; Tsikoudas , but there are reports of practitioners treating all symptomatic patients with steroids Auwaerter ; Burton ; Straus ; Thompson Randomised controlled trials RCTs examining the effects of steroids in infectious mononucleosis.
Participants of any age with documented symptomatic infectious mononucleosis; that is, clinical and laboratory diagnoses. We included all healthcare settings. We noted the severity of symptoms. RCTs that evaluated the effects of a steroid therapy of any dosage, duration or route of administration. Overall improvement in health, measured by physical and psychological functional ability, time in hospital, time taken to return to normal activities, patient self report of health and relapse rates.
Side effects, mortality and adverse events, measured by subjective reports, clinical findings and laboratory parameters. The presence or absence of severe complications of glandular fever that is to say, respiratory obstruction, autoimmune cytopenias, severe cholestasis and chronic fatigue.
B Candy and M Hotopf ran the previous update search in March For details of earlier searches see Appendix 1. For this update, three review authors AH, MFA, YN independently evaluated citation titles and abstracts identified from the electronic databases using the inclusion criteria.
We obtained and assessed the full text of all potentially relevant studies. We resolved differences over study selection by discussion. For the initial version of this review, study selection was performed by two review authors who independently evaluated citation titles and abstracts identified from the electronic databases using the inclusion criteria Candy Differences over study selection were resolved by discussion. Again, we planned to discuss any disagreement, to document decisions and, if necessary, to contact the trial authors for clarification.
We planned to extract data presented only in graphs and figures whenever possible, but we would only include the data if two review authors independently had the same result. The review authors for the initial version of this review extracted data from included studies using a standardised form.
They captured:. For dichotomous data, they extracted the number of participants who experienced the outcome in each group and the total number in each group. For continuous data, they extracted the number of participants, the mean value and standard deviation for the outcome in each group. We planned that the review authors would independently assess the quality of included trials according to criteria described in the Cochrane Handbook for Systematic Reviews of Interventions Higgins We planned to assess the quality of included trials using the Cochrane Collaboration's 'Risk of bias' tool.
The instrument assesses six domains:. We planned to assess each domain according to whether the criteria for that domain were met i. We planned to measure treatment effect on symptoms by using either dichotomous data or an ordinal rating scale.
We planned to assess effects measures for ordinal data as continuous data. We planned to generate the mean difference MD for ordinal data if the data were provided as a mean and standard deviation.
When the standard deviation SD for continuous outcomes was missing, we planned to contact the trial authors. When we undertook such imputation, we planned to perform sensitivity analyses to assess its impact on combined analyses.
Missing studies can result from an inadequate search for data or from publication bias in that papers with negative findings are less likely to be published. How we planned to deal with this is detailed in the Assessment of reporting biases and Search methods for identification of studies sections.
We planned to report attrition rates, per trial, in the 'Risk of bias' tables. We did not plan to undertake any imputation for missing participant data.
We planned to assess the included studies for clinical homogeneity. For this update, we planned to assess the potential for publication bias in funnel plot analysis when we had sufficient and appropriate trial data to combine. We planned to present the findings by outcome from within these groups. For this update, we planned to assess statistical heterogeneity between trials using the Chi 2 test and I 2 statistic we considered a Chi 2 P value of less than 0.
We planned to undertake subgroup analyses to investigate its possible sources when substantial heterogeneity was identified. We planned to perform sensitivity analysis on the outcome results following the guidance in the Cochrane Handbook for Systematic Reviews of Interventions Higgins However, the sensitivity analysis could not be performed because there was only one study in every outcome reported.
For this update, we found no new trials that met the inclusion or exclusion criteria. In our update we obtained a total of search results from the electronic searches. We found all of these citations to be irrelevant and none of them were eligible for inclusion. In the previous update, the authors obtained a total of 36 search results from the electronic searches. None of these citations were eligible for inclusion. For the initial version of this review, the authors obtained a total of abstracts and citations from earlier electronic searches.
From the screening of titles and abstracts, they found 16 studies to be potentially relevant. On retrieval of the full text nine studies were not RCTs. We included no additional studies in this update. See Characteristics of included studies table.
In the other three trials, the sample participants were hospitalised Bolden ; Prout ; Tynell One trial did not report the healthcare location Simon All trials were undertaken by researchers either located at universities or in hospitals. In one trial, two of the authors were from a drug company GlaxoSmithKline Simon Diagnosis of infectious mononucleosis was based on various laboratory parameters, clinical expression and symptoms.
The laboratory tests used included the monospot test Collins ; Roy , the heterophil test Bolden ; Klein ; Prout , the reversal of the ratio between lymphocytes and polymorphonuclear cells in the blood smear Prout , EBV titre Bolden ; Collins ; Roy ; Simon , and white blood cell and differential count Bolden ; Collins ; Klein It should be noted that the earlier studies identified were undertaken before the highly specific EBV titre test was available.
The average time from onset of symptoms to initiation of trial treatment was not reported in most trials. In one trial participants were excluded if they had been ill for more than seven days Tynell Time from study baseline assessment to initiation of trial treatment was reported in three trials; one treatment was given immediately Roy , and in two the average was around three days Klein ; Prout Age in three trials ranged from adolescents aged from 14 or 18 years to young adults up to 30 years of age Collins ; Prout ; Tynell Two trials did not report the participants' ages.
However, they were likely to be mostly young adults, as the participants were recruited from student university health services Bolden ; Klein Two trials explored the effects in younger samples, aged two to 18 years Simon , and eight to 18 years Roy Three trials did not report the gender of the participants. In the trials that reported gender, there were consistently more males than females. Two trials explored the effects of steroids in conjunction with an antiviral: these were acyclovir Tynell , and valacyclovir Simon The steroids evaluated were prednisone Bolden ; Collins , prednisolone Simon ; Tynell , paramethasone Klein ; Prout , and dexamethasone Roy The duration of treatment varied.
In four trials the tapered schedules were for more than five days. One trial involved one dose Roy , and another used a schedule that was adjusted to the individual participant's responsiveness to treatment Prout Dosages varied from a starting dose of 5 mg prednisone or equivalent to to 25 mg prednisone or equivalent to. The dexamethasone trial used a dose of 0. Six trials used oral treatments. In one trial intravenous treatment was used if participants had difficulty swallowing Tynell The seventh trial did not specify how the treatment was administered Simon Three trials reported additional treatments provided to all participants Bolden ; Klein ; Roy Another provided a penicillin course, aspirin and throat gargles to all participants Klein The effectiveness of steroids was evaluated on a range of symptoms and outcomes.
The most evaluated outcome was sore throat Collins ; Klein ; Prout ; Roy ; Tynell Other outcomes that were reported by more than one trial were duration of fever Bolden ; Prout ; Roy , fatigue Collins ; Simon , duration of absence from work because of sickness Collins ; Tynell , psychological morbidity Bolden ; Collins , and the rate of return to normal activities Collins ; Roy One trial set out a priori to evaluate adverse effects or complications relating to steroids Collins Adverse effects occurring were reported in one trial Roy There were no additional excluded studies in this update.
The previous publication of this review excluded nine studies, all of which were not RCTs. See Characteristics of excluded studies table. The risk of bias of the previously included studies is summarised in Figure 1 , and Figure 2. Three trials did not adequately describe the sequence generation for randomisation Bolden ; Simon ; Tynell Four trials provided adequate details on allocation concealment Collins ; Klein ; Roy ; Simon There is no clear evidence of any other potential risk of bias in the included studies.
The initial version of this review included seven trials; the most recent trial was published in Across the seven trials there was little overlap in steroid treatment schedules, diagnostic criteria or outcomes assessed and some data were inadequately reported.
In other words, the trials were heterogeneous in their outcome assessment and how this was reported, therefore we did not combine the results of the trials. Five trials assessed the effectiveness of a steroid as a monotherapy Bolden ; Collins ; Klein ; Prout ; Roy Three trials reported assessments relating to overall improvement; none fully reported the data Bolden ; Collins ; Prout In two trials there was no significant difference in psychological morbidity between the steroid group and the comparison group Bolden ; Collins One trial reported a reduced hospital stay in the steroid group three days versus six days in the comparison group Prout In three of four assessments there was no significant difference found between those in the intervention group and the comparison group.
In one trial more participants in the steroid group than the control group had returned to normal activities at one week odds ratio OR 5. The other trial found at one week that the rates were not significantly different between the steroid and placebo group OR 2. One of the trials also explored sickness absence from school Collins Comparison 1 Steroid versus placebo, Outcome 1 Return to normal activities at 1 week.
Comparison 1 Steroid versus placebo, Outcome 2 Return to normal activities at 4 weeks. Comparison 1 Steroid versus placebo, Outcome 3 Return to normal activities at 1 week. One trial reported that one participant in the comparison group and one in the active treatment group relapsed Bolden In another trial, four participants in the active drug group relapsed after treatment Prout Two trials assessed duration of fever Bolden ; Prout In two assessments out of four, steroids reduced fever.
In the other trial, for fever duration between those in the active group compared to the comparison group, the results were different between the two research centres Four trials evaluated the effectiveness of steroids in the treatment of sore throat Collins ; Klein ; Prout ; Roy We did not combine the findings from the trials because of heterogeneity in outcome assessment and in dose schedules.
Comparison 1 Steroid versus placebo, Outcome 5 Relief of sore throat at 12 hours: 1 dose. One trial assessed other symptoms Collins At one and four weeks there was no significant difference in improvement in fatigue OR 0. There were also no statistically significant differences between those in the actively treated group and those in the control group at one and four weeks following treatment in: anorexia OR 0.
None of the trials planned a priori to assess adverse events. One trial reported possible complications relating to the steroid treatment, with one participant developing an acute onset of diabetes mellitus with acidosis. Another participant who initially improved developed a peritonsillar cellulitis, requiring hospitalisation and active treatment Collins One trial set out a priori to explore whether steroids decrease or increase the incidence of complications of infectious mononucleosis, although it did not report evidence either way in the results Prout In one trial, four ambulant participants were admitted to hospital: three were in the control group Roy She later developed respiratory distress and was found to have a pleural effusion and empyema and was admitted to a paediatric intensive care unit for two weeks.
The mechanism of the disease remains debated but recent publications suggest a primary role of Epstein-Barr Virus EBV. The genetic locus of steroid sensitive nephrotic syndrome was also identified as influencing antibodies directed against EBNA1. EBV is able to establish, latent benign infection in memory B cells that display phenotypes similar to antigen-selected memory B cells. 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.
Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. 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. 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.
We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. RCTs comparing the effectiveness of steroids with placebo, usual care , or other interventions for symptom control for people with documented infectious mononucleosis. For this update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 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. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours eight-day course odds ratio OR
0コメント