Although 15- to 24-year-olds account for the greatest incidence of infectious mononucleosis (IM), antibodies to the Epstein-Barr virus, the causative organism, may be present in 95% of the population. Learn to distinguish between IM and other illnesses with similar presentations—and to watch for the potentially severe complications of IM.
Infectious mononucleosis (IM), commonly known as kissing disease, is a viral syndrome resulting from an acute infection with Epstein-Barr virus (EBV). Mononucleosis typically occurs between early childhood and early adulthood and is ordinarily self-limiting as the patient develops EBV-specific immunity; in some cases, however, IM can lead to severe complications.1-4
Worldwide, the EBV may be present in 95% of adults between 35 and 40.2,5,6 In patients previously infected during early adulthood, the EBV remains dormant in the B-lymphocytes, and those affected may continue to carry asymptomatic infection lifelong.1,7
EPIDEMIOLOGY
IM antibodies may be present in 90% to 95% of the population; however, epidemiologic data regarding infection vary among age-groups and by geographic location.2,4 IM occurring in patients between ages 1 and 5 years is very limited in industrialized countries and within higher socioeconomic groups; in these settings, infection onset occurs primarily in the second decade of life. EBV is rarely found in patients younger than 1 year, possibly because of serologic protection from maternal antibodies.6
Early childhood infection with EBV is predominantly found in the developing countries and in lower socioeconomic groups. EBV infection in young children usually presents with nonspecific symptoms. Wherever improvements in hygiene have been made during recent years, EBV infection in early childhood has become increasingly rare.5,8
Susceptibility to EBV becomes more pronounced during adolescence and early adulthood; in the United States, the incidence of IM is 500 cases per 100,000 persons per year, with persons between ages 15 and 24 accounting for the greatest incidence.5 Among college freshmen who are initially seronegative for EBV (estimates range from 30% to 70%), between 10% and 20% will become infected with the virus; of these, 30% to 50% will develop IM. IM is not seasonal or cyclical and has no sexual predisposition.5,8,9
PATHOPHYSIOLOGY
EBV, a gamma herpes virus, is spread via intimate contact from persons recently infected with EBV infection to other susceptible humans.5 EBV is typically transmitted through oropharyngeal secretions, mainly saliva. After its transmission, the EBV enters epithelial B-lymphocytes, which contain receptors for EBV. Infected B-lymphocytes target the salivary glands, the lymphoid cells, and the oropharynx, causing pharyngitis and other early manifestations of IM. After infection, the host immune response is an activation of T cells against infected B cells, producing larger, atypical lymphocytes called Downey cells.10
The infected B cells then enter the blood stream, carrying the virus throughout the body to the spleen, liver, and peripheral lymph nodes. The spread of these infected lymphocytes elicits a significant cellular immunologic response to the viral infection. This immunologic response is largely responsible for the clinical presentation of IM in the lymph nodes, spleen, and possibly the liver.10
Once acute infection occurs, antibodies are produced against both EBV and unrelated viral species. Recent-onset infection produces heterophile antibodies, the presence of which is helpful in the diagnosis of IM. Specific antibodies to the EBV also develop, including immunoglobulin G (IgG) and IgM; these and others can be useful for serologic identification of EBV. Once an individual is acutely infected with EBV, he or she becomes a lifelong carrier of the virus.10
The incubation period of the EBV is between 30 and 50 days,5,10 making it difficult to pinpoint an exact date of exposure. Transmission of the virus to others may be possible for three months or longer; even after symptoms are resolved, the virus is shed in the saliva for months. Additionally, the EBV has been found in semen and cervical secretions, indicating the possibility of sexual transmission.5,9,10,11
CLINICAL MANIFESTATIONS
Patients with IM usually seek medical treatment for worsening sore throat and increasing fever. The clinical presentation of IM can vary, depending on time between symptom onset and that of presentation.4 However, the triad of most common clinical symptoms, which ordinarily resolve in one to three weeks, are sore throat, fever, and lymphadenopathy.5,10 During the one- or two-week-long prodromal period, patients may also have nonspecific symptoms of malaise, fatigue, and myalgia. About half of patients report headache.10,12
Triad of Common Symptoms
Pharyngitis, the most prominent physical finding, can be severe. It presents in the initial weeks of illness, with pharyngeal exudates present in about half of cases.10,13 The pharyngeal exudates in IM may be difficult to distinguish from those associated with streptococcal pharyngitis. With inflammation of the lymphoid tissue, tonsillitis develops; tonsillar ulceration has been reported in 20% of patients with IM.13 “Kissing tonsils,” with enlargement of the tonsillar pillars causing the tonsils to touch, can lead to airway compromise.14 In addition to pharyngitis and tonsillitis, oral palatal petechiae may develop.5,8,10
Low-grade fever, rarely exceeding 102°F, usually lasts for one to two weeks but may persist for as long as five weeks.11
Cervical lymphadenopathy usually presents with symmetrically enlarged, firm, mobile and tender anterior and posterior lymph nodes, as well as the submandibular lymph nodes; however, clinicians should be aware that more generalized adenopathy may be present, affecting the axillary and inguinal nodes.2,10,11 Lymphadenopathy usually resolves within one to two weeks.
Additional Manifestations of IM
Skin rashes have been reported in 3% to 15% of patients with IM,5 although results from a recent retrospective study suggest that one-third of patients with IM who are initially treated with amoxicillin experience rash.15 This maculopapular, pruritic, copper-colored or tan and brown rash usually begins about 5 to 10 days after antibiotic therapy is initiated. The rash, which is not considered an allergic reaction, usually resolves once the antibiotic is discontinued.10,12,16
Hepatosplenomegaly, particularly splenomegaly, is common—although this is usually a late finding in patients with IM, developing during the second to third week of illness.11,12,16 Abdominal pain is typically absent. However, when patients complain of severe left upper quadrant abdominal pain, splenic ultrasound should be considered to assess for splenic enlargement or possible rupture.8
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