Infectious mononucleosis is a common viral infection known to cause pharyngitis and fever. It is primarily an infection of teenagers and young adults caused by the Epstein Barr virus.
Presentation
The majority of patients with infectious mononucleosis have mild symptoms. However a few will complain of the following features:
- Once EBV is acquired it does not immediately cause any symptoms. The virus has to multiply and reach a certain threshold before it results in symptoms. The incubation period for EBV is about 4-6 weeks.
- Prodrome of general malaise, fatigue and headache may start 3-4 days prior to the actual sore throat and fever. The majority of symptomatic patients will complain of a prolonged history of fatigue and malaise.
- The fever in infectious mononucleosis is low grade but continuous. The sore throat is often the second complaint and may vary from moderate to severe. Complaints of muscle and joint pain is also rare, which is different from other viral infections like influenza where the muscle pain is moderate.
- Patients with infectious mononucleosis may also complain of a dry cough, lack of appetite and vague chest pain.
- The rare patient with CNS involvement may complain of a headache, visual disturbances and dizziness. The CNS features of infectious mononucleosis usually occur late.
- The physical exam in a patient with infectious mononucleosis depends on when the patient presents. Patients presenting early in the course of the infection may have a fever, skin rash, redden throat and localized cervical adenopathy.
- Those patients presenting late may present with splenomegaly, palatal petechiae, jaundice and abdominal pain if there is splenic rupture/enlargement. If the spleen is enlarged, the patient may complain of tenderness to palpation.
- Skin discoloration and icterus is sometime seen in patients with hepatosplenomegaly, and is slightly more common in elderly individuals.
- Examination of the oral cavity usually will shows a redden pharynx with signs of an inflammatory process. The pharyngitis may be exudative and often confused with group A streptococcal infection. The tonsils are usually enlarged and the upper airway passageway may appear narrowed. Petechiae on the soft palate are also common.
- Rarely some patients with infectious mononucleosis may present with generalized macular papular rash that is non pruritic and seen on the face and trunk. This rash is faint and often disappears within several days.
- Other rare observation may include bilateral periorbital edema, conjunctivitis or eyelid edema.
- The oral cavity should not be repeatedly examined or manipulated as it may irritate the swollen tonsil and result in sudden airway distress. This patient is best monitored in an intensive care setting and an intubation set and a tracheostomy set should be available at the bedside.
Workup
The diagnosis of infectious mononucleosis may be suspected on clinical presentation, but confirmation requires some type of laboratory study. Over the years several tests have been developed to identify antibodies to EBV in serum [6] [7].
The test most commonly performed is the latex agglutination assay which identifies heterophile antibodies (Monospot test). These antibodies often peak 14 to 40 days after an infection and may be detectable in blood for 12 months, albeit at low levels. It is important to be aware that the Monospot test may be negative when performed right after the infection but the test does start to become positive over the next several weeks. There are some patients who will have a negative Monospot test and yet manifest symptoms of mononucleosis, these individuals should be considered as having heterophile-negative infectious mononucleosis after further examination. It is also important to note that falsely positive Monospot tests may occur in people with rubella, toxoplasmosis and certain malignancies like lymphoma and leukemia.
Other blood work
Patients with suspected infectious mononucleosis may require other blood tests that are not specific for mononucleosis but can help eliminate other causes. Blood work often done includes:
- Complete blood count (CBC) and white cell count. Leukocytosis is a common feature of infectious mononucleosis and absence of this should suggest an alternative diagnosis. Lymphocytosis and thrombocytopenia alone are not confirmative for infectious mononucleosis because such a finding can be seen with many other noninfectious causes (malignancies) and viral infections. Anemia is not a common presentation of infectious mononucleosis and hence, if present, should suggest an alternate diagnosis.
- Erythrocyte sedimentation rate (ESR) is often elevated in patients with infectious mononucleosis but is usually within normal limits in patients with group A streptococcal pharyngitis. However, ESR alone is a very nonspecific finding as it may be elevated in many other disorders, besides infections.
- Blood smear may reveal lymphocytosis.
- Liver function tests may reveal increase in serum transaminases, but such elevations can also be seen in patient with viral hepatitis.
- Throat culture is rarely done in patients with infectious mononucleosis as the yield for group A streptococci is very low. Even presence of group A streptococci from the throat is not diagnostic because of colonization.
Other studies
- Patients with neurological symptoms may have CNS involvement and some type of imaging study is recommended. A CT scan or an MRI should be performed to rule out other causes.
- Patients who present with neurological signs and symptoms with infectious mononucleosis should also undergo a lumbar puncture. The fluid obtained should be sent for culture, biochemistry and serological studies.
- If the patient has seizures or any seizure like activity, an EEG may help rule out other causes of encephalitis.
- In the rare patient in whom the diagnosis is not clear, a lymph node biopsy may be required. Because aspiration of a lymph node has very low yield a small open biopsy is required. Enough tissue must be obtained to rule out a lymphoma. If infectious mononucleosis is the cause, the history will reveal predominantly lymphocytic infiltration in the peripheral regions of the lymph node.
Treatment
The majority of patients with infectious mononucleosis are managed as outpatients. The few patients who are ill looking and have enlarged tonsils, should be admitted for observation. There is a potential for airway compromise and hence, these patients should be admitted for close monitoring of the respiratory status for a period of 24 to 48 hours. If tonsillar enlargement is moderate to severe, an ENT consult should be made. In addition, anesthesia must also be notified about such an admission, in case there is a need for emergent intubation. At the bedside, an emergency tracheostomy must be available. All healthcare workers should be told to avoid oral cavity examination to prevent irritation of the tonsils that can potentially aggravate the respiratory distress. Admitted patients should have an intravenous line and oxygen if the saturation is below 94% at room air. If wheezing is present, bronchodilator therapy may be required. The decision to administer steroids rests on the severity. Some physicians do administer a short course of IV steroids to decrease the inflammation.
Surgery is required when patients present with rupture of the spleen. The diagnosis is often made with a CT scan. Attempts to salvage the spleen are often undertaken but if preservation is not possible, a splenectomy is performed.
Patients who are stable and have no airway compromise can resume a regular diet. In general, patients with infectious mononucleosis are told to refrain from physical activity for at least 3 to 4 weeks to ensure that splenic rupture does not occur. Those patients admitted for observation are only discharged when the tonsillar swelling has subsided and the patient is able to tolerate a diet. Following discharge patients need to be monitored to ensure that there is resolution of the symptoms. Patients should be warned that prolonged fatigue may occur [8] [9].
Prognosis
For the majority of patients with infectious mononucleosis, the prognosis is excellent.
- Both central nervous system (CNS) involvement and airway obstruction are rare events and only anecdotal case reports exist. When managed appropriately these individuals have an excellent prognosis.
- Those patients who have an enlarged spleen have a risk of rupture and should avoid all physical activity until the gland size returns to normal. Splenic rupture has been reported in the literature but is not a common complication. Even if spleen rupture occurs, the prognosis is good if the patient is able to get to an emergency room and undergo surgery. All patients who have the spleen removed are at risk for the postsplenectomy sepsis. These patients need to be monitored closely.
- Patients with neurological signs also fully recover. However, a few patients with infectious mononucleosis may develop prolonged fatigue that may last a few months or even years.
- Death following infectious mononucleosis is very rare and even when it occurs is due to comorbidity like a malignancy.
- In patients who are immunocompromised, liver infection with EBV can lead to necrosis and death.
- There are also reports suggesting that patients who undergo solid organ transplants may be at risk for developing a lymphoproliferative disorder induced by EBV. Other EBV associated malignancies reported in the literature include nasopharyngeal cancer, Burkitt lymphoma and leiomyosarcoma which may occur in immunocompromised individuals.
Etiology
The cause of infectious mononucleosis is acquisition of EBV from an infected individual. Individuals with infectious mononucleosis develop oral and nasal secretions that persist for many months after the symptoms have subsided. These secretions tend to have a high concentration of the virus. Individuals at highest risk for acquiring infectious mononucleosis are those who have immunosuppression from malignancies, chemotherapeutic agents, human immunodeficiency virus (HIV) infection or congenitally acquired immune deficiency syndromes. Children who develop Burkitt lymphoma which is also caused by EBV, are also at risk for development of infectious mononucleosis.
Epidemiology
Infectious mononucleosis is a global viral infection that is known to occur in people of all ages but is most common in teenagers and adolescents. Studies show that seroconversion is quite common before the age of five, but not all individuals develop clinical disease. However, teenagers and young adults who seroconvert often develop infectious mononucleosis.
The viral infection occurs in all races and in both genders. Because the infection is mild in many cases, most people do not come to medical attention. Hence exact numbers of people with infectious mononucleosis remains unknown, but the numbers are high.
Pathophysiology
EBV is acquired after a person comes into contact with body secretions from an infected individual. Patients with infectious mononucleosis often develop profuse oral and nasal secretions with a high concentration of the virus. The virus is also known to be shed from the epithelial lining of the cervix, which suggests that it may be contracted during unprotected sex. There are also reports of EBV present in donated blood from patients with infectious mononucleosis, thus suggesting that it can be acquired via a blood transfusion [4].
Once EBV enters the systemic circulation, it has an affinity for the reticular endothelial system such as the lymph nodes, liver and spleen. Here the virus induces an immune response with proliferation of B and T lymphocytes [5]. It is this cellular response that governs the clinical expression of symptoms after EBV infection. If the cellular response is intense, the virus will be killed and only a mild infection is seen. In immunocompromised people the virus is freely able to divide and hence produces a marked systemic response. The fever seen in infectious mononucleosis is due to the release of various cytokines that occurs as a result of lymphocytes attacking the EBV. The pharyngitis occurs because of infiltration and proliferation of the infected B lymphocytes in the lymphatic tissue in the pharynx.
Prevention
The only way to prevent infectious mononucleosis is to avoid close contact with people who are already infected. This means avoiding contact with all body fluids, especially oral and nasal secretions since they harbor high concentrations of the virus. Washing hands frequently is also recommended. One needs to avoid using all personal care items from an infected person. Patients with infectious mononucleosis should avoid physical activity for 3 to 4 weeks to prevent splenic rupture.
Summary
Infectious mononucleosis is a common viral infection known to cause fever, pharyngitis and localized adenopathy. The disorder is caused by the Epstein Barr virus (EBV), which is acquired after contact with an infected individual. Blood work usually reveals presence of lymphocytosis and the diagnosis is confirmed with the Monospot test. The infection is common globally and often presents in teenagers and young adolescents. In the majority of cases, infectious mononucleosis presents with mild symptoms that are often mistaken for the common cold or streptococcal pharyngitis. The symptoms in children are mild whereas the symptoms in adults tend to be quite pronounced [1] [2] [3].
Patient Information
Infectious mononucleosis is a viral infection of the throat that presents with fever and swelling of the lymph nodes. While the infection is mild in most people, it can sometimes cause breathing difficulties, which requires admission to the hospital. Some patients may require a tube down the throat for a few days so that they can breathe. The virus can also cause enlargement of the spleen, which in some cases ruptures [10]. This often requires emergent surgery. Overall, the outcome of most patients with infectious mononucleosis is excellent. A few patients may develop prolonged fatigue for a few months or even years.
References
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