All About Infectious Mononucleosis (The Epstain Barr Viral Infection)

Infectious mononucleosis is an acute infectious disease that is caused by the Epstein-Barr virus is characterized by the fever, tonsillitis, increase of lymphatic nodes, hepato- and splenomegaly, by presence of atypical mononuclear cells in a peripheral blood and heterophyl antibodies.

Etiology: an EBV, belong to Herpes viruses, type IV

Epidemiology:

Source of infection are patients with symptomatic and asymptomatic forms, EBV-carriers

Mechanism of transmission is droplet, rarer is contact. The virus is transmitted primarily through saliva during speaking, breathing, coughing, especially during kisses, hand-to-hand contacts.

The transmission of EBV through blood product transfusions has been well documented.

Susceptibility - any age, disease is low contagious, more frequent up to 15 years, in boys

Pathogenesis:

Inoculation of the virus into upper respiratory tract mucous membranes.

Diffusion by lymph to the lymph nodes, spleen, liver.

Lymphoprolipherative syndrome.

Bacterial complications.

Persistence of the virus (even 16 months or more).

 

Clinical criteria

Incubation period is 10-15 days (may be longer-2 month).

Beginning is acute from fever, intoxication (headache, myalgia, arthralgias, malaise).

Fever usually febrile from 3 days till 3 weeks

Tonsilopharyngitis, which may be exudative (follicular, lacunar) in case of secondary bacterial infection (photo), lymphoid follicles hyperplasia (on the back pharyngeal wall).

Adenoiditis, posterior rhinitis (appearance of the patient is typical – breathing with open mouth, absence of nasal discharge, usually snore is present).

Generalized lymphadenopathy with previous enlargement of cervical and occipital lymph nodes (photo).

Hepatosplenomegaly is the sign of lymphoproliferative syndrome (photo).

Maculopapular rashes (photo), wich may confluence with erythema development (photo), sometimes hemorrhagic elements with later skin pigmentation (photo) may occur as a sign of hypersensitivity in case of amoxicillin, ampicillin treatment (in 70-80%).  In the young childhood patient in 25% of cases “spontaneous” rashes can develop.

Other signs: hepatitis (jaundice form of infectious mononucleosis);

toxic myocarditis

diarrhea.

Tonsilopharyngitis

Tonsilopharyngitis

Generalized lymphadenopathy with previous enlargement of cervical lymph nodes

Generalized lymphadenopathy with previous enlargement of cervical lymph nodes

 

Hepatosplenomegaly

Maculopapular rashes

Maculopapular rashes wich confluence

Maculopapular rashes wich confluence

Toxic erythema (next day)

Pigmentation in few days

Classification     

         Form:         - typical                                           

                            - atypical:   - effaced (mild)              

                                               - asymptomatic (subclinical) mild

                                               - visceral - severe (heart, kidneys, adrenal glands, CNS damage)

         Severity (for typical forms):     - mild

                                               - moderate

                                               - severe

         Duration    -    smooth (uncomplicated)

complicated

prolonged

Infectious mononucleosis Severity Criteria

Sign	Mild	Moderate	Severe
Toxic syndrome	absent, mild	Moderate	Expressed
Body t°	Up to 38 °С	38,5-39 °С	More than 40 °С
Lymph nodes damage	mild, cervical predominantly	marked, cervical especially, visible	conglomerates, neck disfiguration, neck subcutaneous tissue swelling
Nasal breathing	Some labored	Labored, "snoring" in sleep	Absent, snoring, opened mouth, puffy face
Throat damage	Catarrhal tonsillitis	tonsils hyperplasia  1st-2nd degree, considerable exudates	tonsils hyperplasia  3rd degree, large membranous exudates
Hepato-  splenomegaly(outcome from the rib arch)	Up to 2-3 сm	3-4 сm	4-5 сm and more,jaundice
Atypical mononuclear cells number	Up to 30 %	20-50 %	More than 50 %
Cough	Rare	Often	Often
Rashes	Rare	Often	Hemorrhagic in 1/3, nasal bleeding
Dyspepsia	Rare	Present abdominal pain, vomiting	abdominal pain, several vomiting
Heart changes “toxic-infectious heart”	Not typical	Rare	Often

Peculiarities of infectious mononucleosis in infants:

often catarrhal syndrome is present (cough, sneezing, corryza);

expressed polyadenia, snore, edematous face from the first day of the disease;

early development of bacterial tonsillitis (on the third day);

rashes are more often;

dyspepsia;

in the peripheral blood – neutrophyllosis with left shift;

favorable duration.

Complications, which may occur (rare):  

Respiratory tract – pneumonia, airway obstructions.

Neurological – seizures, meningitis, encephalitis, peripheral facial nerve paralysis, Gillian – Barrette syndrome. 

Hematological – thrombocytopenia, hemolytic anemia.

Infectious – recurrent tonsilopharyngitis.

Renal – glomerulonephritis.

Genital – orchitis.

Spleen rupture (is lethal).

 

Laboratory findings

Blood analyses: leucocytosis, even 15-30,000/mm3, lymphocytosis, monocytosis, appearing of atypical mononuclear cells (virocytes) more than 10%, ESR enlarges to 20-30mm/hour.

Heterophil agglutination test (is positive in 25-95% of preschool children, 53-94 young school children, and nearly 100% of older children).

Immune-enzyme method – VCA Ig M, EA Ig M presence in the blood.

PCR (measuring of EBV nucleinic acid in the blood, saliva, lymphatic tissues).

atypical mononuclear cells

Diagnosis example:

Infectious mononucleosis, typical form, moderate severity, complicated by the bilateral  bronchopneumonia  

Differential diagnosis should be performed with ‘mononucleosis like’ syndrome caused of AIDS. Another disease, which has similar features: diphtheria, adenoviral infection, acute leukemia, lymphogranulomathosis, viral hepatitis etc.

Sign	Pseudotuberculosis	Scarlet fever	Infectious mononucleosis	Typhoid fever	Enterovirus infection	Viral hepatitis
Beginning	Acute	Acute	Acute	Acute	Acute	Acute, subacute
Initial signs	Toxic,  dyspeptic and different other signs	Sore throat, toxic	Lymphoproliferative, toxic	Toxic	Catarrhal, toxic	Catarrhal,dyspeptic, arthralgic, asthenic
Rashes	Pin-point, maculous-papulous, erythema	Pin-point, sand paper	maculous-papulous, erythema	Single roseols	Small maculous	Rare (in case of B hepatitis)
Catarrhal sign	Typical	Absent	Absent	Rare	Typical	In the initial period
Changes in the throat	Hyperemia of the back pharyngeal wall	Tonsillitis	Tonsillitis Hyperemia of the back pharyngeal wall, posterior rhinitis	Hyperemia of the palatal arch, back pharyngeal wall	Herpangina	Absent
Joints’ damage	Arthritis, arthralgias	Not typical	Absent	Absent	Absent	Arthralgias in the initial period
Abdominal pain	Around the navel	Absent	Absent	In the right inguinal region	Around the navel	In the right hypochondria
Dyspeptic syndrome	Typical	Rare	Absent	Constipation, rare - diarrhea	Typical	More intensive in prodromal period
Hepatitis	May be	Absent	May be	Absent	Absent	Typical
Lymphoproliferative	May be	Regional lymphadenitis	Typical	Hepato- and splenomegaly	Absent	Hepato-, rare - splenomegaly
Tongue	Coated, strawberry from the 4th-5th day	Coated, strawberry from the 4th-5th day	Coated	Coated with grey, teeth excavation on its’ borders	Coated	Coated
Damage of the nervous system	May be	Not typical	Not typical	Delirium, sopor	May be serous meningitis, encephalitis (rare)	Hepatic encephalopathy in severe case

Differential diagnostic of tonsillitis different etiology

Signs	Diphtheria of the pharynx	Scarlatina	Infectious mononucleosis	Streptococcus (staphylococcus) tonsillitis
Beginning	acute	acute	acute	acute
Leading symptoms	fibrinous inflammation in a throat, toxic syndrome	tonsillitis,exanthema from1-2 day, Filatov’s sign,  toxic syndrome	Lymphoproliferative syndrome, tonsillitis is not obvious (secondary)	Tonsillitis (follicle,lacunar, necrotizing, toxic syndrome
Throat changes	Cyanotic hyperemia, edema	Bright "blazing" hyperemia marked off from the hard palate	Absent or bright hyperemia	Bright hyperemia
Character of tonsilar exudates	Grey-white, or yellow membranes, can spread outside the tonsils, are dense, hardly removed, mucus membranes bleeds under them, after the removal arise up again, are not separated	purulent in follicles or in lacunas, keep only on the tonsils, is easily taken off, mucus membranes does not bleed, are separated	purulent in follicles or in lacunas, white-yellowish, keep only on the tonsils, is easily taken off, mucus membranes does not bleed, are separated	purulent in follicles or in lacunas, white-yellowish, keep only on the tonsils, is easily taken off, mucus membranes does not bleed, are separated
Lymphadenitis	Regional	Regional	General	Regional
Hepatosplenomegaly	Absent	Absent	Typical	Absent
Rashes	Absent	Pin-point, red	Maculous-papulous may be erythema in 70-80% of patients, who take semisynthetic penicillins	Absent
Toxic sign	Proportional to the surface of the inflammatory process (mild, moderate or severe	Severe in the first days	Prolong with gradual development (moderate or severe)	moderate or severe in the first days
Subcutaneous fat edema	Typical for toxic forms	Absent	Upon the regional lymph nodes in severe cases	Absent
Changes on the tongue	Coated	Coated, strawberry from the 4-5th day	Coated	Coated

 

Treatment

Reduction of activity and bed rest.

special diet (diet N 5),

Exclude heavy fats (like pork), spices, fried foods, "fast food"”; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt.

Foods boiled, steamed and baked are recommended; food taking 5 times daily

Control of fever and myalgia (when the temperature is more than 38.5-39˚C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases – when the temperature is up to 38˚C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours. Aspirin is contraindicated for children before 12 years.

Antihistamines (in average doses) – pipolphen, suprastin, claritin, cetirizin.

Corticosteroids - in severe cases 1-2 mg/kg/day prednisone for 3-5 days.

In case of secondary bacterial complications macrolides (erythromycin 30-50 mg/kg/day, azythromycin 10 mg/kg/day, clarythromycin) or cefalosporins (cefalexin 50 mg/kg/day, cefuroxim 50 mg/kg/day, cephasolin 100 mg/kg/day), Ampicillin and other semisynthetic penicillins are contraindicated!

The administration of oral acyclovir does not significantly alter the course of clinical illness from placebo.

 

Prophylaxis: is nonspecific, includes disinfecting;

Isolation of the patient, hospitalization of children younger 1 year, in case of severe forms.

A quarantine is not imposed.

Key words and phrases: infectious mononucleosis, EBV-infection, lymphoprolipherative syndrome, atypical mononuclear cells, heterophyl  agglutination test, and “mononucleosis” syndrome.