RB - Aronson. I Mononucleosis. UpToDate, 2019

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Infectious mononucleosis
Authors: Mark D Aronson, MD, Paul G Auwaerter, MD, MBA, FIDSA
Section Editors: Martin S Hirsch, MD, Sheldon L Kaplan, MD
Deputy Editor: Sheila Bond, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2019. | This topic last updated: May 28, 2019.
INTRODUCTION
Infectious mononucleosis (IM) is characterized by a triad of fever, tonsillar pharyngitis, and

lymphadenopathy [1]. It was initially described as "Drusenfieber" or glandular fever in 1889, but
the term "infectious mononucleosis" was later used in 1920 to describe six college students with a
febrile illness characterized by absolute lymphocytosis and atypical mononuclear cells in the blood
[2,3]. The relationship between Epstein-Barr virus (EBV) and IM was established when a
laboratory worker was infected with EBV and developed IM and a newly positive heterophile test
[4].
Infectious mononucleosis in adults and adolescents will be reviewed here. A complete description
of EBV and other clinical manifestations of EBV infection (including malignancy) are discussed
separately. (See "Clinical manifestations and treatment of Epstein-Barr virus infection" and
"Virology of Epstein-Barr virus".)
EPIDEMIOLOGY
Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact
between susceptible persons and EBV shedders. The virus has not been recovered from
environmental sources, suggesting that humans are the major reservoir.
Antibodies to EBV have been demonstrated in all population groups, with worldwide distribution;
approximately 90 to 95 percent of adults are eventually EBV-seropositive. By age four, EBV
seroprevalence is close to 100 percent in developing countries and ranges from 25 to 50 percent
in lower socioeconomic groups in the United States [5]. Many attribute this finding to intense
personal contact and poor personal hygiene among children, which provide opportunities for early
acquisition and subsequent spread of EBV.
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EBV acquired during childhood years is often subclinical; less than 10 percent of children develop
clinical infection despite the high rates of exposure. The incidence of symptomatic infection begins
to rise in adolescent through adult years [6]. Large studies of infectious mononucleosis are now
decades old, but traditionally, the peak incidence of infection has been described in the 15- to 24-
year age range [7]. Some data derived in the United Kingdom suggest that infectious
mononucleosis (IM) cases may be occurring later in life with increasing severity, requiring
hospitalization [8]. IM is relatively uncommon in adults, accounting for less than two percent of
pharyngitis in adults [9]. The vast majority of adults are not susceptible to this infection because of
prior exposure.
The differences observed between infants and young adults with regard to symptomatic infection
may relate to the size of the viral inoculum at the time of infection or to the intensity of cellular
immune responses driven by EBV-infected B cells.
The incidence of clinical infection is approximately 30 times higher in whites than blacks in the
United States [10]. This may reflect both earlier exposures to EBV among the latter group and the
higher frequency of asymptomatic infection when acquired by young children. In addition, IM
occurs more frequently in same-sex twins and first-degree siblings, compared with second- and
third-degree relatives [11]. Thus, genetic factors may influence who develops clinical disease. In
one case series, GATA2 deficiency was associated with severe primary EBV requiring
hospitalization or hemophagocytic lymphohistiocytosis with lymphoma, suggesting that this
genetic deficiency may influence disease presentation in some cases [12].
TRANSMISSION
Person-to-person — Following infectious mononucleosis, virus may be shed in salivary

secretions at high levels for a prolonged period [13,14]. Oral shedding persists for a median
duration of approximately six months after the onset of illness [14], although it should be pointed
out that once infected with Epstein-Barr virus (EBV), virus may be intermittently shed in the
oropharynx for decades [13,15].
Although EBV primarily spreads via passage of saliva, it is not a particularly contagious disease.
In a classic study conducted among college students, susceptible roommates of patients with
either symptoms of infectious mononucleosis (IM) or asymptomatic viral shedding were no more
likely to seroconvert or develop clinical illness than other college students without evidence of
preexisting EBV infection [16]. The virus can persistently shed in the oropharynx of patients with
IM for up to 18 months following clinical recovery; this may explain in part why only a small
number of patients with IM recall previous contact with an infected individual [16,17]. Intrafamilial
spread among siblings has also been reported [18].

Breastfeeding — EBV has been isolated in breast milk from healthy nursing mothers [19].
However, in one study, there was no difference in EBV seropositivity between exclusively nursed
or bottle-fed infants, suggesting that breastfeeding is not an important route of transmission
[19,20].
Sexual transmission — EBV has also been isolated in both cervical epithelial cells and male
seminal fluid, suggesting that transmission may also occur sexually [21-23]. In an epidemiologic
study of more than 2000 university students in Scotland, questionnaires and serum samples were
analyzed to examine risk factors for EBV seropositivity [24]. Sexual activity before college
admission was significantly associated with an increased risk of EBV seropositivity. Furthermore,
the risk of a seropositive status increased with the number of sexual partners.
Despite the recovery of EBV in genital secretions, studies have been unable to discriminate with
certainty whether EBV was acquired through an oral or genital route. In one prospective study that
followed first-year university students who were EBV antibody negative, the time to infection in
individuals reporting deep kissing without coitus was similar to those who reported deep kissing
plus coitus [14]. Both groups had a significantly higher risk of acute EBV infection than subjects
reporting no kissing or coitus.
PATHOGENESIS
Contact of Epstein-Barr virus (EBV) with oropharyngeal epithelial cells allows replication of the
virus, release of EBV into the oropharyngeal secretions, and infection of B cells in the lymphoid-
rich areas of the oropharynx [25]. EBV-infected B cells are responsible for the dissemination of
infection throughout the lymphoreticular system. The incubation period prior to the development of
symptoms averages four to eight weeks.
A prospective study was performed in 20 subjects with serologically confirmed primary EBV
infection to assess viral kinetics in various compartments, including whole blood, peripheral blood
mononuclear cells, and oral wash fluid [26]. The median half-life of viral elimination from whole
blood in 19 subjects was three days; quantity in this compartment correlated with the severity of
symptoms. In contrast, virus persisted at an elevated level for 32 weeks in the oropharynx in
asymptomatic subjects, consistent with the theory that EBV is transmitted via saliva.
Primary EBV infection of B lymphocytes induces circulating antibodies directed against viral and
unrelated antigens found on sheep and horse red cells [27]. The latter antibodies, termed
heterophile antibodies, are a heterogeneous group of mostly IgM antibodies that do not cross-
react with EBV antigens [28,29]. Rarely, infected cells produce antineutrophil, antierythrocyte, and
antiplatelet antibodies, which are responsible for some of the less common clinical manifestations
associated with infectious mononucleosis (IM) (see below). An EBV-specific serologic response

can also be documented, although this is necessary for less than 10 percent of heterophile
antibody-negative IM cases.
EBV-specific cytotoxic T-lymphocytes are considered essential in controlling acute and

reactivation infection. T cell activation leads to a T helper 1-type profile with production of
interleukin-2 and interferon-gamma cytokines [30]. The atypical lymphocytes that appear in the
peripheral blood of patients with acute IM between one and three weeks after the onset of
symptoms are primarily activated (HLA-DR+) CD8+ T-cells and also include CD16+ natural killer
(NK) cells (picture 1) [31-35].
Despite these immune responses, which control the initial lytic infection, EBV becomes a lifelong
infection as it establishes latency with periodic reactivation with oral shedding of EBV. On the other
hand, insufficient cellular immune responses may result in a poorly-controlled EBV infection and/or
generate an EBV-induced malignancy (see "Clinical manifestations and treatment of Epstein-Barr
virus infection", section on 'Malignancy'). Even with sufficient immune responses, some
epidemiological studies have linked IM to increased risks of other conditions, such as Hodgkin
lymphoma [36,37]. Other studies have linked acquisition of infection to increased risks for
autoimmune disorders, such as multiple sclerosis or systemic lupus erythematosus [38,39]. Such
associations will require significant additional study to prove causation as well as whether they
could be a result of direct viral or rather immunological consequences. Such concerns have
heightened interest in exploring potential preventative strategies, such as an EBV vaccine [40,41].
CLINICAL MANIFESTATIONS
Classic IM — Typical features of infectious mononucleosis (IM) include fever, pharyngitis,

adenopathy, fatigue, and atypical lymphocytosis (table 1) [42]. A review of over 500 patients found
that lymphadenopathy was present in all patients, fever in 98 percent, and pharyngitis in 85
percent [43,44]. The syndrome is often heralded by malaise, headache, and low-grade fever
before the development of these more specific signs [6,45].
Fatigue may be persistent and severe. In a prospective study of 150 patients, most initial
symptoms (eg, fever, sore throat) had resolved by one month, but fatigue resolved more slowly
and persisted in 13 percent of patients at six months [44]. Fatigue appears to be more common
with a more profound impact on studies and exercise abilities in young female university students
compared with male students [46].
Lymph node involvement in IM is typically symmetric and more commonly involves the posterior
cervical and posterior auricular nodes than the anterior chains. The posterior cervical nodes are
deep to the sternocleidomastoid muscles and must be carefully palpated. The nodes may be large
and moderately tender. Lymphadenopathy may also become more generalized, which
distinguishes IM from other causes of pharyngitis [9]. Lymphadenopathy peaks in the first week

and then gradually subsides over two to three weeks. A more detailed discussion of the evaluation
of peripheral lymphadenopathy is presented elsewhere. (See "Evaluation of peripheral
lymphadenopathy in adults".)
A history of sore throat is often accompanied by pharyngeal inflammation and tonsillar exudates,
which may appear white, gray-green, or even necrotic. Palatal petechiae with streaky
hemorrhages and blotchy red macules are occasionally present; this finding may also be seen in
patients with streptococcal pharyngitis. (See "Evaluation of acute pharyngitis in adults".)
Rare complications of IM include peritonsillar abscess or airway occlusion secondary to edema of

the soft palate and tonsils [47].
Clinical variants — There are a number of clinical variants of IM in which some but not all of the
classic findings are present:
● Many patients with acute EBV infection have relatively mild disease, and some present with
pharyngitis and tonsillitis in the absence of a full-blown IM syndrome [48]. Among 66 EBV-
seronegative university students who developed primary EBV infection, 77 percent had the
usual IM syndrome, 12 percent had atypical symptoms, and only 11 percent were
asymptomatic [14].
● Many patients present with fever and lymphadenopathy without pharyngitis, the so-called
"typhoidal form" of illness. Many of these patients are heterophile antibody-negative, and
should be termed "heterophile-negative IM." Other infectious causes of heterophile antibody-
negative IM include most importantly cytomegalovirus (CMV) [49] or acute HIV [50], with other
infections, such as toxoplasmosis [51], human herpesvirus type 6 (HHV-6) [52], and HHV-7
[53], possible. (See 'Differential diagnosis' below and 'Diagnosis' below.)
● Very young or older adults frequently do not develop the classic clinical syndrome (table 2)
[54]. In a study of patients ages 40 to 78, pharyngitis and myalgia were the most frequent
complaints, while cervical lymphadenopathy was less commonly noted on physical
examination [55]. Fever is common among older individuals and can last for several weeks
[54].
Other clinical manifestations
Splenomegaly and splenic rupture — Splenomegaly is seen in 50 to 60 percent of patients

with IM and usually begins to recede by the third week of the illness [56].
Splenic rupture is a rare, but potentially life-threatening complication of IM. It is estimated to occur
in one to two cases per thousand [57]; approximately 70 percent occur in males, usually under 30
years [58]. The typical manifestations are abdominal pain and/or a falling hematocrit [59]. When
splenic rupture occurs, it does so spontaneously in over one-half of patients. It typically occurs

about 14 days after symptom onset; however, it can range from four days to as far as eight weeks.
In some cases, it can be the presenting symptom [59].
The management of splenic rupture is similar to other forms of splenic injury. Nonoperative
treatment with intensive supportive care and splenic preservation is preferred, but some require
splenectomy [60]. Despite its life-threatening potential, fatality from IM-related splenic rupture is
rare.
Infarctions of the spleen have also been described as a rare consequence of IM. Of the 19
reported cases, abdominal pain is usually described, although in some cases, infarction can be an
incidental finding [61].
Rash — In patients with IM, a generalized maculopapular, urticarial, or petechial rash is

occasionally seen, while erythema nodosum is rare [54]. It was once thought that the
maculopapular rash usually occurred following the administration of ampicillin or amoxicillin;
however, it has also been described occasionally with a variety of other antibiotics, including
azithromycin [62], levofloxacin [63], piperacillin/tazobactam [64], and cephalexin (picture 2) [65], or
with no antibiotic exposure at all.
The mechanism responsible for this rash is not well understood, but it may represent a transient
virus-mediated immune alteration, resulting in the development of a reversible, delayed-type
hypersensitivity reaction to the antibiotic [66]. Thus, a rash arising in the setting of penicillin
derivative use during IM may not predict a true drug allergy, and many patients subsequently
tolerate amoxicillin or ampicillin without an adverse reaction.
Although the incidence of rash associated with beta-lactams initially was reported to be as high as
70 to 90 percent [51], more recent studies have suggested the rate of this rash may be much
lower [66-69]. As an example, in a retrospective study of children <18 years of age in which
serology was used to diagnose IM, the reported rate of amoxicillin-related rash was 32.9 percent
compared with 23.1 percent among untreated patients [67]. One report suggested that there was
no association [68]. In this prospective observational study of 184 patients with IM, in which 103
patients were exposed to at least one penicillin derivative, there were equivalent rates of rash in
both those treated with a penicillin derivative and those who did not receive any drug [68].
Neurologic syndromes — Neurologic syndromes include Guillain-Barré syndrome, facial and

other cranial nerve palsies [70-72], meningoencephalitis [73], aseptic meningitis, transverse
myelitis, peripheral neuritis, optic neuritis, and encephalomyelitis [74]. These manifestations tend
to occur two to four weeks or more after the initial symptom onset. There may also be an
association between a clinical presentation of IM and the subsequent development of multiple
sclerosis [75,76].
Other — EBV can affect virtually any organ system and has been associated with such diverse
disease manifestations as hepatitis or cholestasis [77,78], pneumonia, pleural effusions [79],
myocarditis, pancreatitis and acalculous cholecystitis [80], mesenteric adenitis, myositis, acute
renal failure [81], glomerulonephritis, gastric pseudolymphoma [82], and genital ulceration [83].
Jaundice and hepatomegaly are less common, although ascites [77,79] and fatal cases of
hepatitis have been described [78].
EBV infection during pregnancy — There is little evidence of a teratogenic risk to the fetus in
women who develop infection during pregnancy [84]. Transplacental transmission of EBV appears
to be rare [85].
LABORATORY ABNORMALITIES
Hematologic abnormalities — The most common laboratory finding in association with infectious
mononucleosis (IM) is lymphocytosis, defined as an absolute count >4500/microL or, on peripheral
smear, a differential count >50 percent. The smear may also identify significant atypical
lymphocytosis, defined as more than 10 percent of total lymphocytes. The majority of reactive
lymphocytes in patients with IM are CD8+ cytotoxic T cells. In one study, the severity of illness
correlated with the magnitude of CD8+ lymphocytosis (as well as with blood Epstein-Barr viral
(EBV) load) [14]. (See 'Hematologic findings' below and 'Detection of EBV virus' below.)
The total white blood cell count in patients with IM averages 12,000 to 18,000/microL, although it
may be much higher. Some patients have a mild relative and absolute neutropenia and
thrombocytopenia. These are generally benign findings that are self-limited.
Unusual hematologic manifestations include hemolytic anemia, thrombocytopenia, aplastic

anemia, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, and disseminated
intravascular coagulation. Some of these complications result from EBV-induced production of
antibodies directed against red blood cells, white blood cells, and platelets [54]. The hemolytic
anemia is typically associated with an anti-I cold agglutinin [86]. (See "Cold agglutinin disease",
section on 'Pathogenesis'.)
Primary EBV infection is also a well-described trigger for hemophagocytic lymphohistiocytosis

(HLH), a rare disorder characterized by cytopenias, liver function abnormalities, coagulopathies,
high serum ferritin levels, and other signs and symptoms of marked systemic inflammation. (See
"Clinical manifestations and treatment of Epstein-Barr virus infection" and "Clinical features and
diagnosis of hemophagocytic lymphohistiocytosis".)
Liver function tests — Elevated aminotransferases are seen in the vast majority of patients, but
are self-limited. Abnormal liver function tests in a patient with pharyngitis strongly suggest the
diagnostic possibility of IM.
DIFFERENTIAL DIAGNOSIS
Patients with fever, pharyngitis, and lymphadenopathy may have infection due to group A
streptococcus, Arcanobacterium haemolyticum, cytomegalovirus (CMV), acute HIV, or, rarely,
Toxoplasma gondii [49-51,87]. Streptococcal infection is not usually accompanied by significant
fatigue or splenomegaly on examination. Pharyngitis associated with CMV tends to be extremely
mild, if present at all, but may cause liver function test elevations, as does acute Epstein-Barr virus
(EBV).
Differentiating between infectious mononucleosis (IM) caused by EBV and a similar syndrome due
to CMV or HIV infection is often not possible clinically. Diagnostic testing is particularly important if
the patient is pregnant since CMV, HIV, and toxoplasma infections can have significant adverse
effects on pregnancy outcomes. (See 'EBV-negative mononucleosis' below and "Cytomegalovirus
infection in pregnancy" and "Overview of TORCH infections", section on 'Clinical features of
TORCH infections'.)
A mononucleosis syndrome with atypical lymphocytosis can also be induced by several drugs,
particularly anticonvulsants such as phenytoin, carbamazepine, and antibiotics, such as isoniazid
or minocycline [88-90]. Patients with lymphadenopathy and splenomegaly may also have
lymphoma.
DIAGNOSIS
General approach — Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) should be

suspected when an adolescent or young adult complains of sore throat, fever, and malaise and
also has lymphadenopathy and pharyngitis on physical examination [9,91]. The presence of
palatal petechiae, splenomegaly, and posterior cervical adenopathy are highly suggestive of IM,
while the absence of cervical lymphadenopathy and fatigue make the diagnosis less likely [92,93].
(See 'Clinical manifestations' above.)
The presence of a lymphocytosis and increased circulating atypical lymphocytes supports the
diagnosis of EBV infection. However, the diagnosis should be confirmed with a heterophile
antibody test or through EBV-specific antibodies. Although there is no specific antiviral therapy to
treat IM, confirmatory testing is helpful to inform patients with IM of certain risks, such as splenic
rupture and airway obstruction, as well as why fatigue may take some time to remit. A detailed
discussion of serologic testing is found below. (See 'Heterophile antibodies' below and 'EBV-
specific antibodies' below.)
Patients with fever, lymphadenopathy, and pharyngitis should also have a diagnostic evaluation for
streptococcal infection by culture or antigen testing. (See "Evaluation of acute pharyngitis in
adults".)
Hematologic findings — The most common laboratory finding in association with IM is

lymphocytosis, defined as an absolute count >4500/microL or, on peripheral smear, a differential
count >50 percent. The smear may also identify significant atypical lymphocytosis, defined as
more than 10 percent of total lymphocytes (picture 1). In a review of 156 heterophile-positive
patients, a lymphocytosis ≥50 percent was seen in two-thirds, and an atypical lymphocytosis of
≥10 percent was present in 75 percent of patients [94]. The specificity of these two findings,
compared to a heterophile-negative control group with similar manifestations, was 85 and 92
percent, respectively.
Atypical lymphocytes may also be found in patients with toxoplasmosis, rubella, roseola, viral
hepatitis, mumps, CMV, acute HIV infection, and some drug reactions [54]. On the other hand,
older individuals may have less prominent absolute lymphocytosis and fewer atypical lymphocytes
[95].
When an automated differential from a hematology analyzer flags a specimen as possibly

containing atypical lymphocytes, the smear should be reviewed manually since blasts, and other
abnormalities cannot be reliably distinguished from atypical lymphocytes in these systems [94].
(See "Automated hematology instrumentation", section on 'Leukocyte counting errors'.)
Heterophile antibodies — Reactive heterophile antibodies in a patient with a compatible

syndrome are diagnostic of EBV infection [1]. Further testing for specific antibodies to EBV is not
necessary for patients with a reactive heterophile antibody. Although EBV-specific antibodies can
also be used to make the diagnosis (see 'EBV-specific antibodies' below), the results of the
heterophile test typically return more quickly. Thus, the heterophile test is the diagnostic test of
choice in many clinical settings.
Heterophile antibodies react to antigens from phylogenetically unrelated species. For example,
they agglutinate sheep red blood cells (the classic Paul-Bunnell test), horse red blood cells (used
in the "Monospot" test), and ox and goat erythrocytes. The Monospot is a latex agglutination assay
using horse erythrocytes as the substrate [96,97]. Other rapid diagnostic tests use ELISA
(enzyme-linked immunosorbent assay) techniques. The sensitivity and specificity of the rapid kits
approach 85 and 100 percent, respectively [98].
Although they are highly specific in the appropriate clinical setting, heterophile antibodies can be
somewhat insensitive. As examples:
● Early infection – The false-negative rates are highest during the beginning of clinical
symptoms (25 percent in the first week; 5 to 10 percent in the second week, 5 percent in the
third week) [92]. In patients with a compatible syndrome and negative heterophile antibodies,
the test can be repeated if the patient is early in his/her clinical illness. Alternatively (or in
addition), EBV-specific antibodies can be ordered. (See 'EBV-specific antibodies' below and
'EBV-negative mononucleosis' below.)
● Young children – Heterophile antibody tests are often negative in infants and children less
than four years of age; thus, EBV-specific serologies are generally favored for diagnosing
acute EBV infection in young children [99-103]. (See 'EBV-specific antibodies' below.)
In one series that described 32 children younger than four years of age who were diagnosed
with IM by EBV serology (positive IgG-viral capsid antigen [VCA], and negative antibodies to
EBV nuclear antigen [EBNA]), the heterophile antibody test was only positive in 27 percent of
children ages 10 to 24 months and 76 percent of those aged 24 to 48 months [100]. Despite
the relative reduction in associated antibody production, young infants (defined as 20 to 35
months of age in one study) can mount an EBV-specific cytotoxic T lymphocyte response
during the acute, lytic-phase of EBV infection, and the latent proteins recognized are identical
to those recognized by young adults [104].
Rare false-positive heterophile tests have been reported in patients with leukemia, lymphoma,
pancreatic cancer, systemic lupus erythematosus, HIV infection, and rubella [105]. In addition,
heterophile antibodies can persist at low levels for up to one year after IM.
EBV-specific antibodies — As noted above, the measurement of EBV-specific antibodies is

usually unnecessary since the vast majority of patients are heterophile positive. (See 'Heterophile
antibodies' above.)
However, testing for EBV-specific antibodies may be warranted in patients with suspected IM who
have a negative heterophile test [106]. Specific EBV testing should also be pursued in those with
more prolonged illness or in those who do not fit classic diagnostic criteria. In some countries,
EBV-specific antibodies are used routinely for the diagnosis of IM instead of heterophile antibody
assays. IgM and IgG antibodies directed against viral capsid antigen have high sensitivity and
specificity for the diagnosis of IM (97 and 94 percent, respectively) [107].
Viral capsid antigen — IgM and IgG antibodies directed against the Epstein-Barr viral capsid
antigen (VCA) are usually present at the onset of clinical illness because of the long viral
incubation period. IgM levels wane approximately three months later; thus, they are a reliable
marker of acute infection in a clinically appropriate picture. IgG VCA antibodies persist for life and
are a marker of EBV infection.
Results of viral capsid antigen testing need to be interpreted within the appropriate clinical context.
Although the presence of IgM VCA antibodies is highly suggestive of acute EBV infection, other
herpesviruses (eg, CMV) can induce IgM antibodies to cell lines that express EBV antigens. In
addition, during illnesses associated with intense immune activation, serologic EBV reactivation
with detectable EBV IgM VCA antibodies has been described in the absence of clinical IM [108].
A number of other antibodies are expressed in individuals exposed to EBV, a few of which may
also be used for diagnostic purposes. (See "Virology of Epstein-Barr virus".)
Nuclear antigen — IgG antibodies to EBV nuclear antigen (EBNA; a protein expressed only
when the virus begins to establish latency) begin to appear 6 to 12 weeks after the onset of
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symptoms and persist throughout life; their presence early in the course of an illness effectively
excludes acute EBV infection.
Thus, while the presence of IgM VCA antibodies suggests the likely presence of acute EBV
infection, the diagnosis is almost certain in the presence of IgM VCA and the absence of IgG
EBNA antibodies.
Early antigen — IgG antibodies to early antigen (EA) are present at the onset of clinical illness.
There are two subsets of EA IgG: anti-D and anti-R. The presence of anti-D antibodies is
consistent with recent infection since titers disappear after recovery, but their absence does not
exclude acute illness because the antibodies are not expressed in a significant number of patients.
Anti-R antibodies are only occasionally present in IM.
Serum IgA antibody — In a study of 15 individuals with primary EBV infection, serum IgA
antibodies against early lytic antigens were detected using flow cytometry [109]. Furthermore,
levels of IgA antibodies rapidly declined one month after onset of acute illness, while IgM
antibodies continued to be produced.
The role that serum IgA antibodies will have in the diagnosis of IM is unclear pending further study.
Detection of EBV virus — EBV DNA quantification can be accomplished through polymerase
chain reaction (PCR) assays on blood or plasma [110,111]. Viral genomes can be detected in the
blood in 40 to 70 percent of patients at symptom onset (depending upon which assay is used),
and this increases to 90 percent about two weeks after onset [112].
One study evaluated the clinical utility of detecting EBV viremia with real-time PCR in children with
primary EBV infection compared with controls [113]. Twenty-one (75 percent) of the patients in the
primary EBV infection group, one (4 percent) of the EBV-seronegative patients and none of the
EBV-seropositive patients had detectable EBV DNA. Within the primary infection group, those with
detectable virus were more likely to have lymphadenopathy, higher atypical lymphocytes counts,
and higher aminotransferases than those without detectable virus. In a study of university students
with acute EBV infection, the severity of illness correlated with blood EBV load [14]. However, this
quantitative assessment of EBV viral load is not recommended for immunocompetent patients with
suspected EBV infection since it offers no therapeutic guidance.
The use of PCR in the management of transplant recipients who develop lymphoproliferative
disorders related to EBV infection is discussed elsewhere. (See "Epidemiology, clinical
manifestations, and diagnosis of post-transplant lymphoproliferative disorders", section on
'Measurement of EBV viral load'.)
Summary — Patients with suspected IM based upon the history and physical examination should
have a white blood cell count with differential and a heterophile test.

If the heterophile test is positive, no further testing is necessary if the clinical scenario is
compatible with typical IM. If the heterophile test is negative, but there is still a strong clinical
suspicion of EBV infection, the Monospot test can be repeated since testing can be negative early
in clinical illness.
If the clinical syndrome is prolonged, or if the patient does not have a classic EBV syndrome, IgM
and IgG VCA and EBNA antibodies should be measured. The presence of IgG EBNA within four
weeks of symptom onset excludes acute primary EBV infection as an explanation and therefore
should prompt consideration of EBV-negative causes of mononucleosis.
EBV-NEGATIVE MONONUCLEOSIS
Approximately 10 percent of mononucleosis-type cases are not caused by Epstein-Barr virus

(EBV) [114]. Other agents that produce a similar clinical syndrome include cytomegalovirus (CMV)
[49], HIV [50], Toxoplasma [115], human herpesvirus type 6 (HHV-6) [52], hepatitis B [116], and
possibly HHV-7 [53].
Primary HIV infection — Primary HIV infection causes a febrile illness resembling mononucleosis
[50]. The most common findings are fever, sore throat, myalgias, and lymphadenopathy (table 3)
[117]. (See "Acute and early HIV infection: Pathogenesis and epidemiology".) The following
features may help to distinguish primary HIV infection from IM:
● Mucocutaneous ulceration is unusual in IM; its presence should heighten the suspicion for
acute HIV infection.
● Rash is less common in IM (unless antibiotics have been administered), but is seen frequently
in the setting of primary HIV infection within 48 to 72 hours after the onset of fever.
The heterophile test is typically negative during acute HIV infection [118]; false positive heterophile
tests have been rarely reported [119,120]. Atypical lymphocytes also may be present in acute HIV
infection, although the overall incidence of atypical lymphocytosis is lower in HIV infection and the
percentage of atypical cells is usually lower than that seen with EBV.
Patients who present with a heterophile-negative mononucleosis-like syndrome should have

quantitative plasma HIV RNA and HIV antibody testing to rule out primary HIV infection since early
diagnosis is important for patient management and to decrease the risk of transmission to others.
(See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on
'Diagnosis'.)
Cytomegalovirus — CMV causes a syndrome that is similar but often milder than EBV-
associated IM (table 4) [121,122]. The illness is characterized primarily by prolonged fever, less
prominent lymphadenopathy, and absent or mild pharyngitis. Hepatitis is nearly universal. The
hematologic picture resembles that of EBV infection. The disease is self-limited, and the great
majority of patients recover with no sequelae. The diagnosis can be supported by the identification
of IgM antibodies to CMV. (See "Overview of diagnostic tests for cytomegalovirus infection".)
Toxoplasma gondii — Toxoplasma causes a syndrome characterized predominantly by fever and

lymphadenopathy [115]. It rarely causes pharyngitis or abnormal liver function tests, and is not
associated with the characteristic hematologic abnormalities seen with CMV and EBV infections.
Human herpesvirus — Symptomatic primary infection with HHV-6 or HHV-7 is uncommon in

adults. However, a mononucleosis-like syndrome of varying severity with prolonged
lymphadenopathy has been described in association with HHV-6 seroconversion in adults. (See
"Clinical manifestations, diagnosis, and treatment of human herpesvirus 6 infection in adults",
section on 'Immunocompetent hosts'.)
CHRONIC ACTIVE EBV INFECTION
Chronic active Epstein-Barr virus (CAEBV) infection is a rare, life-threatening lymphoproliferative

disorder that may involve B lymphocytes, T lymphocytes, or natural killer (NK) cells. The
syndrome is characterized by a persistent infectious mononucleosis (IM)-like syndrome with
fevers, pancytopenia, elevated liver function tests, and EBV viremia [123]. A more detailed
discussion of chronic active EBV infections is presented elsewhere. (See "Clinical manifestations
and treatment of Epstein-Barr virus infection", section on 'Chronic active EBV infection'.)
TREATMENT
Primary Epstein-Barr virus (EBV) infections rarely require more than supportive therapy.
Symptomatic treatment — The mainstay of treatment for individuals with infectious

mononucleosis (IM) is supportive care. Acetaminophen or nonsteroidal anti-inflammatory drugs
are recommended for the treatment of fever, throat discomfort, and malaise. Provision of adequate
fluids and nutrition is also important. It is prudent to get adequate rest, although complete bed rest
is unnecessary.
The use of corticosteroids in the treatment of EBV-induced IM has been controversial. In a

multicenter, placebo-controlled study of 94 patients with acute IM, the combination of acyclovir and
prednisolone reduced oropharyngeal shedding of the virus but did not affect the duration of
symptoms or lead to an earlier return to school or work [124]. A subsequent meta-analysis of
seven studies found insufficient evidence to recommend steroid treatment for symptom relief;
furthermore, two studies reported severe complications in patients assigned to the corticosteroid
arm compared to placebo [125]. We do not recommend corticosteroid therapy for routine cases of
IM since it is generally a self-limited illness and there are theoretical concerns about
immunosuppression during clinical illness with a virus that has been causally linked to a variety of
malignancies. However, corticosteroids may be considered in the management of patients with

some EBV-associated complications.
Complications including airway obstruction — Corticosteroids, as well as emergent

consultation with an otolaryngologist, are warranted in individuals with impending airway
obstruction (manifested clinically by difficulty breathing or dyspnea in the recumbent position).
Data on dosing and duration of corticosteroid therapy is scant. One case series described children
with impending airway closure who were treated successfully with high-dose corticosteroids (eg,
dexamethasone 0.25 mg/kg every six hours) but no information was given on duration of
treatment [126]. Once clinical improvement has been achieved, tapering the corticosteroid dose
slowly (eg, over 7 to 14 days) is likely prudent.
Corticosteroid therapy may also be considered in those with severe overwhelming life-threatening
infection (eg, fulminant liver failure) or other complications such as severe hemolytic or aplastic
anemia. Data supporting the benefit of corticosteroids in these settings are less robust than what
is found for the treatment of IM-related airway obstruction.
Despite lack of evidence, one retrospective study of 206 patients with IM treated at a single
tertiary medical center found that 45 percent received corticosteroids mainly for constitutional
symptoms; only 8 percent of patients were treated based on traditional criteria [127].
A more detailed discussion of complications associated with acute EBV infection is found in a
separate topic review.
Antiviral treatment — Acyclovir is a nucleoside analog that inhibits permissive EBV infection
through inhibition of EBV DNA polymerase but has no effect on latent infection or ability to cure
the infection (see "Acyclovir: An overview"). Specific therapy of acute EBV infections with
intravenous and oral formulations of acyclovir has been studied [124,128]. Short-term suppression
of oral viral shedding can be demonstrated, but significant clinical benefit has not been shown.
A meta-analysis of five randomized controlled trials of acyclovir in the treatment of acute IM,
including two trials of intravenous therapy in patients with severe disease, also failed to show a
clinical benefit compared to placebo [129]. These results are not surprising since ongoing viral
replication plays a less significant role in the symptomatic phase of EBV-induced IM than the host
immune responses.
RETURN TO SPORTS
Since infectious mononucleosis (IM) mostly affects teenagers and young adults, many of whom
participate in competitive sports and other forms of exercise, a common question is when to
recommend resumption of athletic activities. More than 50 percent of patients with IM develop
splenic enlargement within the first two weeks of symptoms; as a result, the central issue is

avoiding activities that may precipitate splenic rupture, while a secondary consideration relates to
resumption of training in an athlete complaining of fatigue.
Avoiding splenic rupture — All athletes should refrain from sport activities during early illness.
As recuperation occurs, clinicians should keep in mind that spontaneous or traumatic splenic
rupture in the setting of IM appears to be most likely within 2 to 21 days after the onset of clinical
symptoms [130]. Descriptions of splenic rupture after the fourth week are rare [60,131].
Recommendations to resume sports are somewhat arbitrary given the lack of prospective data.
Several authors recommend potential resumption of all sport activities, except for strenuous
contact sports, no earlier than 21 days after illness onset [132,133]. Others advocate a more
universal four-week time frame regardless of activity level [134].
A conservative synthesis of retrospective studies yields the following suggestions [135]:
● For athletes planning to resume non-contact sports, training can be gradually restarted
starting three weeks from symptom onset. This recommendation assumes that participants
avoid any activities capable of causing chest or abdominal trauma.
● For strenuous contact sports (including football, gymnastics, rugby, hockey, lacrosse,
wrestling, diving, and basketball) or activities associated with increased intraabdominal
pressure (such as weightlifting) that may carry a higher risk of splenic injury, we recommend
waiting for a minimum of four weeks after illness onset.
Ways in which to document that the spleen has returned to normal size vary from practitioner to
practitioner. Splenic palpation or percussion is generally unreliable in athletes with firm abdominal
musculature, although experienced examiners can trust a positive finding of enlargement [136].
The safest option may be obtaining an ultrasound examination to document resolution of
splenomegaly [137,138]. However, the use of imaging studies before a return to sports remains a
debated issue due to a lack of clinical outcomes data and the cost of ultrasound [139].
Some patients with IM appear to have splenic enlargement that persists on serial ultrasound
studies. This may be due to the occasional long-term splenomegaly seen after IM or to "normal"
splenomegaly that may be observed in 3 to 7 percent of healthy young adults, especially taller
individuals [140,141]. Since seven weeks is among the latest descriptions of IM-related splenic
rupture, clinical judgment must dictate when to allow an athlete with splenomegaly that persists
beyond seven to eight weeks to resume strenuous sports [131]. Routine ultrasonography is not
needed in most patients; the decision to obtain imaging should be influenced by whether the
patient is returning to contact sports [142].
Fatigue — A common sense approach to the resumption of training suggests that clinicians wait
for the resolution of objective symptoms as well as an improvement in the athlete's sense of well-
being. For the first few days, athletes should train at reduced levels compared to their premorbid

state, increasing activities gradually as tolerated [143]. Competitive athletes may not attain pre-
illness levels of fitness for three or more months. The physician should be especially careful when
giving recommendations to athletes who may be unduly pressured by themselves or others to
resume strenuous activity too soon.
PROGNOSIS
Most individuals with primary Epstein-Barr virus (EBV) infection recover uneventfully and develop
durable immunity. Most acute symptoms generally resolve in one to two weeks, although fatigue
and poor functional status can persist for months [144-146]. Approximately 10 percent of
individuals have persistent fatigue six months after symptom onset [145-147]. This rate declines
over subsequent years, and most individuals recover completely over time. Some studies suggest
the initial severity of illness correlates with the development of persistent fatigue [145-147]. Other
studies have found that female gender [46,148] and premorbid mood disorders [148] are
associated with an increased likelihood of developing persistent fatigue.
The reason why some patients do not return to prior health is unclear, but some studies show
abnormalities in mitochondrial function, as well as message levels for a variety of regulatory
molecules [149-151].
EBV has been associated with a variety of malignancies, particularly lymphoma. Many of these
infections are subclinical, but Hodgkin lymphoma has been associated with a history of infectious
mononucleosis. (See "Hodgkin lymphoma: Epidemiology and risk factors", section on 'Epstein-
Barr virus' and "Clinical manifestations and treatment of Epstein-Barr virus infection", section on
'Malignancy'.)
PREVENTION
At present, there is no commercially available vaccine to prevent Epstein-Barr virus (EBV)

infection. Glycoprotein 350, a viral antigen expressed on the EBV capsid, enables entry of the
virus into B cells and is targeted by the immune system during natural infection [152]. One phase
two placebo-controlled trial evaluated a recombinant gp350 vaccine in 181 volunteers and found
that although the number of cases of infectious mononucleosis was decreased in the vaccine
group, gp350 did not prevent asymptomatic infection [41].
Return to school or work — Since EBV may be shed intermittently for months to years in people
who have acquired infection, and the source of infection is rarely known in the patient who
develops infectious mononucleosis, there are no restrictions regarding recently ill IM patients for
returning to school or the workplace. The decision to return to full activities should be guided by
the level of fatigue and other constitutional symptoms.

INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Mononucleosis (The Basics)")
● Beyond the Basics topic (See "Patient education: Infectious mononucleosis (mono) in adults
and adolescents (Beyond the Basics)".)
SUMMARY AND RECOMMENDATIONS
● Infectious mononucleosis (IM) is an acute illness due to Epstein-Barr virus (EBV) infection,
which occurs mainly in adolescents and young adults. (See 'Epidemiology' above.)
● IM is classically characterized by fever, pharyngitis, fatigue, and lymphadenopathy. Other

findings can include splenomegaly and palatal petechiae. Cervical lymphadenopathy tends to
involve the posterior chain of lymph nodes. (See 'Clinical manifestations' above.)
● Rare complications include splenic rupture and airway obstruction.
● A generalized maculopapular, urticarial, or petechial rash is occasionally seen. Rash may be

more common following the administration of ampicillin or amoxicillin.
● Common laboratory findings include an absolute or relative lymphocytosis, an increased

proportion of atypical lymphocytes, and elevated aminotransferases. (See 'Laboratory
abnormalities' above.)
● Patients with suspected IM, based upon the history and physical examination, should have a
white blood cell count with differential and a heterophile test (eg, the "Monospot" test). In
addition, patients should also have a diagnostic evaluation for streptococcal infection by
culture or antigen testing. (See 'Diagnosis' above.)

● In a patient with a compatible syndrome and a negative heterophile antibody, the Monospot
test can be repeated since this test can be negative during the first week of clinical illness.
Alternatively (or in addition), EBV-specific antibodies (IgM and IgG antibodies directed against
viral capsid antigen [VCA], IgG antibodies to nuclear antigen and early antigen) can be
obtained. EBV-specific antibodies can be particularly helpful if the patient has a repeatedly
negative Monospot. (See 'Diagnosis' above and 'EBV-specific antibodies' above.)
● The presence of IgG antibodies to EBV nuclear antigen (EBNA), or the absence of IgG and
IgM antibodies to VCA, excludes acute primary EBV infection and should prompt
consideration of alternative etiologies of a mononucleosis-like illness, such as
cytomegalovirus (CMV), primary HIV infection, and toxoplasmosis. The most important
diagnosis to exclude is primary HIV infection; this can be accomplished with both quantitative
HIV RNA and HIV antibody testing. The evaluation for CMV takes on great importance in the
pregnant female. (See 'EBV-negative mononucleosis' above.)
● We recommend NOT administering acyclovir for IM (Grade 1B). Primary EBV infections
rarely require more than supportive therapy. (See 'Treatment' above.)
● In individuals with impending airway obstruction, we suggest corticosteroids, as well as

emergent consultation with an otolaryngologist (Grade 2B). (See 'Treatment' above.)
● For athletes planning to resume non-contact sports, training can be gradually restarted three
weeks from symptom onset. For strenuous contact sports or activities associated with
increased intraabdominal pressure, we suggest waiting for a minimum of four weeks after
illness onset (Grade 2C). (See 'Return to sports' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 8318 Version 34.0

GRAPHICS
Atypical lymphocytes in infectious mononucleosis
Peripheral smear from a patient with infectious mononucleosis shows three

atypical lymphocytes with generous cytoplasm.
Courtesy of Carola von Kapff, SH (ASCP).
Graphic 55986 Version 2.0

Clinical manifestations of infectious mononucleosis
Symptoms and signs Frequency, percent
Symptoms
Malaise and fatigue 90 to 100
Sweats 80 to 95
Sore throat, dysphagia 80 to 85
Anorexia 50 to 80
Nausea 50 to 70
Headache 40 to 70
Chills 40 to 60
Cough 30 to 50
Myalgia 12 to 30
Ocular muscle pain 10 to 20
Chest pain 5 to 20
Arthralgia 5 to 10
Photophobia 5 to 10
Signs
Adenopathy 100
Fever 80 to 95
Pharyngitis 65 to 85
Splenomegaly 50 to 60
Bradycardia 35 to 50
Periorbital edema 25 to 40
Palatal enanthem 25 to 35
Liver and spleen tenderness 15 to 30
Hepatomegaly 15 to 25
Rhinitis 10 to 25
Jaundice 5 to 10
Skin rash 3 to 6
Pneumonitis <3
Modified from Chervenik PA. Dis Mon 1974; 1:29.

Clinical features of infectious mononeucleosis in younger and older age groups
Patients, percent
≤35 years ≥40 years
Lymphadenopathy 94 47
Pharyngitis 84 43
Fever 75 95
Splenomegaly 52 33
Hepatomegaly 12 42
Rash 10 12
Jaundice 9 27
Data in patients ≤35 years from Schooley, RT. In: Mandell, GL, Bennett, JE, Dolin, R (eds), Mandell, Douglas and
Bennett's Principles and Practice of Infectious Disease, 4th ed, Churchill Livingstone, Inc, New York 1995, p.1364. Data in
patients ≥40 years from Axelrod, P, Finestone, AJ. Am Fam Physician 1990; 42:1599.

Rash in infectious mononucleosis
A generalized, erythematous, maculopapular eruption may be seen in patients

with infectious mononucleosis after the administration of amoxicillin
or ampicillin.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders
CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.
http://www.lww.com

Frequency of common symptoms in acute HIV infection
Symptom No. patients Percent
Fever 200 96
Adenopathy 154 74
Pharyngitis 146 70
Rash 146 70
Myalgia/arthralgia 112 54
Diarrhea 67 32
Headache 66 32
Nausea/vomiting 56 27
Neuropathy 13 6
Encephalopathy 12 6
Adapted from Niu, MT, Stein, DS, Schnittman, SM, J Infect Dis 1993; 168:1490.

Symptoms and signs in nine patients with spontaneous cytomegalovirus

mononucleosis
Number of patients
Symptoms
Malaise 9
Fever 8
Chills 6
Myalgia 6
Sore throat 5
Headache 4
Anorexia 3
Abdominal pain 2
Signs
Pharyngeal erythema 5
Lymphadenopathy 5
Rash* 5
Splenomegaly 3
Hepatomegaly 0
Exudative pharyngitis 0
* Includes one patient whose rash was associated with ampicillin therapy.
Modified from Jordan, MC, Rousseau, W, Stewart, JA, et al. Spontaneous cytomegalovirus mononucleosis. Clinical and
laboratory observations in nine cases. Ann Intern Med 1973; 79:153.

Contributor Disclosures
Mark D Aronson, MD Nothing to disclose Paul G Auwaerter, MD, MBA, FIDSA Nothing to disclose Martin
S Hirsch, MD Nothing to disclose Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: Pfizer
[Streptococcus pneumoniae (PCV13, linezolid)]; Merck [Staphylococcus aureus (Tedizolid)]; MeMed
Diagnostics [Bacterial and viral infections]. Consultant/Advisory Board: Pfizer [Staphylococcus aureus]. Other
Financial Interest: Pfizer [Speaker on PCV13, linezolid]; Medscape [Video discussion on bacterial meningitis];
Elsevier [Co-editor (Feigin and Cherry Textbook of Pediatric Infectious Diseases)]. Sheila Bond, MD Nothing
to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.
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23/01/2020 Infectious mononucleosis - UpToDate

Official reprint from UpToDate®

Infectious mononucleosis (IM) is characterized by a triad of fever, tonsillar pharyngitis, and

Person-to-person — Following infectious mononucleosis, virus may be shed in salivary

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EBV-specific cytotoxic T-lymphocytes are considered essential in controlling acute and

Classic IM — Typical features of infectious mononucleosis (IM) include fever, pharyngitis,

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Rare complications of IM include peritonsillar abscess or airway occlusion secondary to edema of

Other clinical manifestations

Splenomegaly and splenic rupture — Splenomegaly is seen in 50 to 60 percent of patients

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Rash — In patients with IM, a generalized maculopapular, urticarial, or petechial rash is

Neurologic syndromes — Neurologic syndromes include Guillain-Barré syndrome, facial and

Unusual hematologic manifestations include hemolytic anemia, thrombocytopenia, aplastic

Primary EBV infection is also a well-described trigger for hemophagocytic lymphohistiocytosis

General approach — Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) should be

Hematologic findings — The most common laboratory finding in association with IM is

When an automated differential from a hematology analyzer flags a specimen as possibly

Heterophile antibodies — Reactive heterophile antibodies in a patient with a compatible

EBV-specific antibodies — As noted above, the measurement of EBV-specific antibodies is

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Approximately 10 percent of mononucleosis-type cases are not caused by Epstein-Barr virus

Patients who present with a heterophile-negative mononucleosis-like syndrome should have

Toxoplasma gondii — Toxoplasma causes a syndrome characterized predominantly by fever and

Human herpesvirus — Symptomatic primary infection with HHV-6 or HHV-7 is uncommon in

CHRONIC ACTIVE EBV INFECTION

Chronic active Epstein-Barr virus (CAEBV) infection is a rare, life-threatening lymphoproliferative

Symptomatic treatment — The mainstay of treatment for individuals with infectious

The use of corticosteroids in the treatment of EBV-induced IM has been controversial. In a

malignancies. However, corticosteroids may be considered in the management of patients with

Complications including airway obstruction — Corticosteroids, as well as emergent

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A conservative synthesis of retrospective studies yields the following suggestions [135]:

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At present, there is no commercially available vaccine to prevent Epstein-Barr virus (EBV)

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INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: Mononucleosis (The Basics)")

SUMMARY AND RECOMMENDATIONS

● IM is classically characterized by fever, pharyngitis, fatigue, and lymphadenopathy. Other

● Rare complications include splenic rupture and airway obstruction.

● A generalized maculopapular, urticarial, or petechial rash is occasionally seen. Rash may be

● Common laboratory findings include an absolute or relative lymphocytosis, an increased

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● In individuals with impending airway obstruction, we suggest corticosteroids, as well as

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4. Henle G, Henle W, Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to

11. Rostgaard K, Wohlfahrt J, Hjalgrim H. A genetic basis for infectious mononucleosis:

25. Anagnostopoulos I, Hummel M, Kreschel C, Stein H. Morphology, immunophenotype, and

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33. Johnsen HE, Madsen M, Kristensen T, Kissmeyer-Nielsen F. Lymphocyte subpopulations in

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