Mononucleosis

Etiology

The cause of mononucleosis is the Epstein-Barr virus (EBV). EBV is a type of herpesvirus spread by contact, typically with salivary secretions. The duration of oral shedding is not entirely clear, but high levels of shedding can continue for a median of 6 months after illness onset. Transmission is generally person-to-person, but EBV is not considered a highly contagious disease. [3]

Besides EBV other causes include:

• CMV
• Adenovirus
• Hepatitis A
• HIV
• Toxoplasma
• Rubella

Epidemiology

It is estimated that up to 95% of adults in the world are eventually seropositive to EBV. Therefore, EBV is widely disseminated in all population groups. The traditional age group where peak incidence is noted, however, is in 15 to 24-year olds. Classically, the symptomatic infection is in adolescents, which is why laypersons may refer to the infection as the “kissing disease.” Mononucleosis is uncommon in adults:  approximately 2% of all pharyngeal disease in adults is attributable to this disease. Adults are generally not susceptible to clinical illness because of previous exposure. In the United States, clinically evident infection occurs at rates estimated at 30 times higher in whites than in blacks. One explanation for this disparity is that if acquired at a young (childhood) age, EBV is often subclinical. This would suggest earlier EBV exposures in blacks, and a higher frequency of asymptomatic infection as young children. [1][4]

After exposure, the EBV infects the epithelial cells of the salivary glands and the oropharynx. Lymphocytes residing in the tonsils get exposed to the virus and then enter the bloodstream. Lymphoid hyperplasia is common and may be seen as generalized lymphadenopathy, tonsillitis, and hepatosplenomegaly.

The infection of the B-lymphocytes results in the production of immunoglobulins (heterophile antibodies).

Pathophysiology

When EBV is introduced into the oropharynx, the virus begins the replication process. There is a predilection for infection of the B-cells of lymphoid tissue. Subsequently, the infection spreads through the lymphatic system. The body reacts by developing antibodies against the virus. In 90% or more of cases, heterophile antibodies are produced in response to the infection with EBV. EBV is a lifelong infection with periodic reactivation.  In poor immune response systems, there is a small risk of EBV-induced malignancy, such as Hodgkin lymphoma.[5][6]

History and Physical

Fever, sore throat, fatigue, and tender lymph nodes are classic findings on history-taking in infected individuals with mononucleosis. The incubation period for mononucleosis is long averaging 3-6 weeks and most patients do not recall the exposure.

The classical triad is fever, pharyngitis, and lymphadenopathy. Additional complaints include a headache, general malaise, and poor oral intake.  Unfortunately for some, fatigue can be persistent for months in select individuals. Lymphadenopathy is more common in the posterior cervical region. The pharyngitis is often heralded with tonsillar exudates. Petechial lesions on the palate occur infrequently. Also, splenomegaly is a key finding on physical in up to half of patients with active clinical mononucleosis. Identification is important in patients prone to future injury, e.g., active sports participants. Skin examination in some patients may infrequently reveal a nonspecific, generalized maculopapular rash. This is separate from the antibiotic-induced rash discussed below.

Evaluation

As always, initial evaluation should include airway assessment to determine that the airway is patent and there is no impending occlusion or compromise. In rare instances, abscess or edema can impede proper maintenance of the airway. Also, determination of hemodynamic stability is important to rule out concomitant splenic injury or rupture in the acute illness of mononucleosis. Laboratory evaluation most commonly will reveal lymphocytosis, with a lymphocyte differential often greater than 50%. Atypical lymphocytosis of greater than 10% can be seen on blood smear. A general leukocytosis and occasionally thrombocytopenia may also be appreciated. Imaging is generally not needed in the evaluation of mononucleosis. The monospot (or heterophile antibody) test for mononucleosis is the diagnostic test of choice and is nearly 100% specific for the disease. The sensitivity of this test is closer to 85%.  If the patient is early in the illness, the test may be falsely negative, and it should be repeated later during the course of the disease. If the diagnosis is unclear, the patient should also undergo evaluation for streptococcal infection by rapid antigen testing or throat culture.[7][8][9]

Treatment / Management

Treatment is generally supportive for mononucleosis. Antipyretics and anti-inflammatory medications help to treat fever, sore throat, and the general fatigue seen in this illness. Hydration, rest, and good nutritional intake should also be encouraged. Corticosteroids are not generally recommended in the routine treatment of mononucleosis because of concerns with immunosuppression; however, in cases of airway obstruction, corticosteroids (and possible otolaryngology consultation) are indicated along with appropriate airway management. In instances where antibiotics have been inappropriately administered in patients with mononucleosis, a generalized maculopapular rash may develop. Classically, this is after administration of amoxicillin but can be seen with other antibiotics as well. All athletes should avoid sports during the early course of the illness (approximately three weeks) because of the splenic enlargement was seen in approximately 50% of patients with mononucleosis and the associated risk of splenic rupture.[10][11]

Differential Diagnosis

Many other viral and some rickettsial illnesses have characteristics similar to EBV. The differential includes cytomegalovirus, human immunodeficiency virus (HIV), human herpesvirus type 6, hepatitis B, and tick-borne illnesses such as Lyme disease. Primary HIV may present with mucocutaneous ulcerations; furthermore, skin rash is frequently seen in primary HIV and is far less common in mononucleosis.

Prognosis

The majority of patients with EBV infection recover without sequelae and develop lifelong immunity to controlling the dormant virus. The acute phase of the illness resolves by the second week, but malaise symptoms may persist for months. In rare situations, malignancies have been linked with EBV infection, but additional study is needed to prove causation. Resumption of normal activity should be guided by the risk of splenic injury as well as other limitations that may be imposed by the fatigue that accompanies the illness.

Airway obstruction due to edema of the pharyngeal lymph nodes has also been reported. In addition, CNS complications include encephalitis, psychosis, cranial nerve palsies, peripheral neuritis, and Guillain barre syndrome.

Complications

• Upper airway obstruction from massive lymphadenopathy
• Splenic rupture
• Autoimmune hemolytic anemia
• Pancytopenia
• Hemolytic uremic syndrome
• Episcleritis, uveitis
• Erythema multiforme