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Case 049:
Sore throat and swollen glands in the neck.
Authors:
Isaac B Yang MB ChB
David C Chung MD FRCPC
Affiliation:
The Chinese University of Hong Kong
A 21 year old student presented to the University Health Clinic with complaints of
fever (oral temperature 38.7oC) despite taking antipyretics at home for 5 days. He
added that he has been feeling increasingly tired with loss of appetite. On further
questioning he gave a history of sore throat of recent onset, with increasing soreness
during swallowing. He lived with his parents and they were well.
On physical examination, his throat was found to be heavily congested. The tonsils
were enlarged and covered with exudate. Multiple lymph nodes were felt in the neck
bilaterally; these lymph nodes were generally small (1 cm in diameter) and mildly
tender. His chest was clear; heart sounds were normal; liver edge was felt 2 cm below
the right costal margin; the tip of the spleen was palpable.
1. What are the differential diagnoses?
o This patient has an exudative pharyngitis, which can be bacterial or viral in
origin: group A β hemolytic streptococci, diphtheria, gonorrhea, and
Epstein-Barr virus (EBV).
o His systemic signs are also consistent with EBV, CMV (cytomegalovirus),
acute HIV, human herpesvirus 6, toxoplasma, adenovirus, paramyxovirus, and
hepatitis (A, B, or C) infections. But, other than EBV infection, exudative
pharyngitis is not a usual feature in the rest. This patient’s youthful age is also
more consistent with EBV pharyngitis (infectious mononucleosis).
o Lymphadenopathy, hepatomegaly, and splenomegaly should also raise the
possibility of leukemia, lymphoma, and Hodgkin’s disease.
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2. What is infectious mononucleosis?
Infectious mononucleosis is a clinical syndrome characterized by the triad of fever
(may be as high as 40oC), pharyngitis, and lymphadenopathy. Other
manifestations include general malaise, headache, presence of atypical
lymphocytes and heterophil antibody in the blood, transient hepatic dysfunction
that is only mild in magnitude, and splenomegaly. Less frequent manifestations
are meningitis, encephalitis, Guillain-Barre syndrome, pericarditis, myocarditis,
hemolytic anemia, and thrombocytopenia. The causative agent is the EBV, a
herpesvirus.
EBV is one of the most common human viruses that is ubiquitous worldwide. As
many as 95% of adults reaching the age of 40 years have been infected with the
virus. Many children acquire the infection at an early age. Many of these early
infections are asymptomatic or are impossible to be distinguished from other
childhood illnesses. Although the immunity acquired following infection is life-long,
an infected individual is never rid of the EBV—the virus lies dormant and may
reappear in the saliva again without accompanying symptoms of reactivation.
Primary infection later on in life may still be asymptomatic, but 35 – 50% of
teenagers and young adults will develop full blown infectious mononucleosis. The
mode of human-to-human transmission is through direct contact with the saliva of
acutely infected individuals or individuals with reactivated disease:
ƒ
During the act of kissing—the reason why infectious mononucleosis is also
called the “kissing disease”.
ƒ
By sharing food using the same utensil.
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By inhaling infected droplets generated in a cough or sneeze.
The incubation period from exposure to overt disease is 3 – 4 weeks.
Spontaneous recovery is usually complete in 1 – 2 months; rarely the disease may
last as long as 4 months. If the infection lasts more than 4 months, the condition is
called chronic EBV infection. However, chronic active EBV infection is seldom
supported by laboratory tests. Patients in whom symptoms persist for more than 6
months should be investigated for other causes of debility.
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3. What laboratory investigations are helpful to establish the diagnosis?
This patient has an exudative pharyngitis of which infectious mononucleosis is the
most likely diagnosis, although bacterial pharyngitis (e.g. β hemolytic
streptococcal pharyngitis) should be ruled out. Had pharyngitis been absent, other
causes in the list of differential diagnoses should be considered in earnest. Tests
that should be performed to establish a diagnosis include:
o Throat culture to identify bacterial infection if present. A rapid antigen test that
can yield results in minutes for streptococcus pharyngitis is worthwhile.
o Complete blood count: The typical changes seen in infectious mononucleosis
are granulocytopenia initially that is followed by lymphocytic leukocytosis with
leukocyte count in the range of 12 – 25 X 109/L, lymphocytes accounting for
60 – 90% of the total count, and 10% or more of the lymphocytes being
atypical and larger than normal. The total leukocyte count typically returns to
normal range in 3 – 4 weeks.
o Heterophil antibody tests: Heterophil antibodies are human antibodies that can
agglutinate animal red blood cells. In infectious mononucleosis increasing titer
of heterophil antibodies can be detected during the first month of illness. The
titer declines thereafter but may still be detectable after 3 months. Sheep red
cells are used in the Paul-Brunnell and horse erythrocytes in the Monospot test.
False-positive result is found in only a small number of patients. Therefore a
typical clinical picture of infectious mononucleosis together with a positive
heterophil antibody test is diagnostic of the disease. False-negative result is
present in as many as 15% of patients but mainly in young children.
o Serologic tests: When the clinical manifestations are typical and yet the
heterophil antibody test result is repeatedly negative, serologic tests of
antibodies against viral markers may be necessary to differentiate infectious
mononucleosis from other look-alike illnesses (see differential diagnoses listed
previously). The optimal combination consists of checking IgM and IgG
antibodies against viral capsid antigen, IgM antibody against the early antigen,
and antibody against the viral nuclear antigen.
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4. What is the treatment for infectious mononucleosis?
The disease is self-limiting; treatment is largely supportive:
o Advise patient to have plenty of fluid.
o Rest is important and malaise can persist for months after the acute phase of
the illness, so much so that investigation of the chronic fatigue syndrome may
have to be considered in some patients
o Prescribe acetaminophen for fever, sore throat, and headache. More potent
NSAID analgesic drugs may be required but care should be exercised in
patients with thrombocytopenia because of their anti-platelet effect.
o Warm water or throat lozenge can soothe the pain of sore throat.
o A 5 day course of steroid treatment is sometimes prescribed for swollen tonsils
but this should be reserved for patients in whom the swollen tonsils threaten
airway obstruction. A longer course of steroid therapy is also prescribed to
treat complications of autoimmune hemolytic anemia and thrombocytopenia.
o Acyclovir and it derivatives have activities against EBV in vitro and decreases
viral shedding in vivo, but these drugs do not alter the clinical course of
infectious mononucleosis and are not approved for treating EVB infection.
o Hepatitis is transient and mild and requires only symptomatic treatment.
o Although it is a rare complication, an enlarged spleen is at risk of rupture;
patient should be advised against vigorous exercise and contact sports until
involution is observed.
o Antibiotic therapy is not indicated for the treatment of infectious mononucleosis
in itself but is indicated in concurrent β hemolytic streptococcal pharyngitis. A
10 day course of penicillin or erythromycin should be prescribed but ampicillin
and amoxicillin should be avoided because of the frequent association with
skin rash wrongly attributed to allergic reaction.
5. What preventive measures should be exercised in EBV infection?
A large number of individuals are already infected by EBV, many of them in their
childhood and are immune to a repeat infection. These previously infected
individuals remain as asymptomatic carriers of the virus as described previously
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and are the main source of new infections. Therefore no special precautions or
isolation procedures are necessary in the handling of patients with infectious
mononucleosis.
6. Are there any long term complications of EBV infection?
EBV infection has been linked to the development of nasopharyngeal carcinoma
and Burkitt’s lymphoma of the jaw. The former is prevalent among natives of
southern China; the latter among children in equatorial Africa. It is also associated
with a subtype of Hodgkin’s disease. But an overwhelming majority of patients
recover from infectious mononucleosis without serious or long term complications.
Further readings
http://www.cdc.gov/ncidod/diseases/ebv/htm. Epstein-Barr virus and infectious
mononucleosis. Naional Center for Infectious Diseases, Centers for Disease Control
and Prevention, USA; 2006.
Moran A, Shandera WX. Chapter 32 – Infectious diseases: Viral & Rickettsial. In
Tierney LM Jr et al (editors): Current Medical Diagnosis & Treatment, 45th edition.
McGraw-Hill; 2006.
Kieff ED. Chapter – Infectious mononucleosis: Epstein-Barr virus infection. In
Goldman: Cecil Textbook of Medicine, 22nd edition. Saunders; 2004.