What is the classic triad of Infectious Mononucleosis?

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Elsevier ClinicalKey Derived Clinical Overview

Infectious mononucleosis (IM) is a symptomatic infection most commonly caused by Epstein-Barr virus (EBV) and characterized by a classic triad of fever, tonsillar pharyngitis, and lymphadenopathy (predominantly cervical).Fatigue is also a very common finding. IM was first coined in 1920 to describe a syndrome characterized as an acute infectious process accompanied by atypical large peripheral blood lymphocytes.

• Following an incubation period of 4 to 7 wk, there are two common presentations.1-3The first presentation represents the prodromal period with gradual onset of fever, chills, malaise, and anorexia for several days. This is followed by the second presentation of the classic triad of pharyngitis, fever, and lymphadenopathy. These patients often report the worst sore throat of their life. Pharyngitis (Fig. E1) is typically the most severe symptom and is characterized by white tonsillar exudates that may spread to the tongue. Up to half of patients may have palatal petechiae. • Lymphadenopathy (nonnecrotic) can be diffuse, but most commonly occurs in both the anterior and posterior triangles of the neck. • Splenomegaly may be palpable, most commonly during the second week of illness. Most patients have some degree of splenomegaly on ultrasound assessment. Hepatomegaly with some degree of hepatitis is also common. In 75% of cases there is some increase in alanine aminotransferase (ALT). • Rash (Fig. E2) is uncommon but will occur in nearly all patients who receive ampicillin or amoxicillin due to a transient penicillin hypersensitivity. • IM is usually a self-limited illness (2 to 4 wk), but symptoms of malaise and fatigue may last months before resolving. • At times, IM can present as fever and adenopathy without pharyngitis. • Although acute complications may be severe, they are uncommon and tend to resolve completely. Reported complications include cholestatic liver disease, chronic hepatitis, or even liver failure; hemolytic anemia; splenic rupture; or airway compromise., • Splenic rupture is rare, with an incidence rate <1%, but it is the most feared.It should be suspected in anyone with confirmed or suspected IM who presents with acute abdominal or chest pain. Most cases occur in the first 3 wk of symptoms.

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Schooley, Robert T., Allen, Upton D. (2024). In Goldman-Cecil Medicine (pp. 2253). DOI: 10.1016/B978-0-323-93038-3.00348-8

Most cases of acute EBV infection are clinically silent. The syndrome of infectious mononucleosis consists of the clinical triad of fever, sore throat (Chapter 397),and lymphadenopathy, in association with an atypical lymphocytosis(Fig. 348-1) and the transient appearance of heterophile antibodies. The incubation period between exposure and the onset of symptoms is generally 30 to 50 days. The onset of symptoms may be abrupt, or it may be heralded by a several-day nonspecific prodrome of malaise and low-grade fever. Although the classic syndrome includes fever, sore throat, and adenopathy, the findings may be dominated by only one or any combination of these symptoms. Other common clinical manifestations include headache, malaise, and anorexia. On physical examination, patients are usually febrile. Pharyngeal erythema, tonsillar enlargement (seeFig. 397-4inChapter 397), and cervical adenopathy are generally present. Mild periorbital edema may also be observed. Abdominal findings may include splenomegaly or hepatomegaly, or both. Splenomegaly can be demonstrated by ultrasonographic examination in virtually all patients with infectious mononucleosis, although palpable splenomegaly is present in only about 20% of patients. Splenic enlargement is usually maximal inthe second or third week of illness and might not be detectable at the initial presentation. Adenopathy may be observed in noncervical regions, but it is usually much less prominent than in cervical regions. More serious primary infections can occur in individuals over age 30 years. Approximately 5% of patients will exhibit a rash that may be macular, scarlatiniform, or urticarial in nature. Ampicillin or its derivatives evoke a pruritic maculopapular eruption in 15 to 30% of patients with acute EBV infection in recent series, compared with a reported 80 to 100% in earlier reports. Patients with an ampicillin-induced rash during acute EBV infection generally tolerate the drug and other penicillin products when administered later in life.

Terminology Epstein-Barr virus (human herpesvirus 4) is a gammaherpesvirus infecting more than 90% of the human population worldwide Most commonly recognized presentation of acute infection is syndrome of infectious mononucleosis, characterized by classic triad of fever, lymphadenopathy, and tonsillar pharyngitis After primary infection, virus establishes lifelong latency in infected B cells, which may lead to development of various epithelial or lymphoid cancers, especially in patients with primary or acquired immune system abnormalities; it is also associated with oral hairy leukoplakia, an opportunistic condition in patients with AIDS

Synopsis Epstein-Barr virus (human herpesvirus 4) is a gammaherpesvirus infecting more than 90% of the human population worldwide Children infected at young age may be asymptomatic or may have mild symptoms indistinguishable from those of other viral illnesses In adolescents and young adults, may begin insidiously with prodrome of fatigue, malaise, and myalgia that can persist for 1 to 2 weeks before onset of other symptoms or may present with more abrupt onset Classic triad of signs and symptoms includes fever, lymphadenopathy, and tonsillar pharyngitis Transmission of Epstein-Barr virus occurs predominantly through exposure to infected saliva; however, virus may be transmitted by sexual contact, blood transfusion, organ transplant, or hematopoietic cell transplant Diagnosis is based mostly on clinical presentation; CBC with differential, heterophile antibody testing can support clinical diagnosis Epstein-Barr virus–specific antibody tests may also be used to confirm diagnosis in young children or in patients in whom this infection is suspected despite negative heterophile antibody test results Treatment is supportive to manage symptoms and prevent complications. It includes adequate hydration; NSAIDs or acetaminophen to manage pain and fever; and throat sprays, lozenges, or gargles with 2% lidocaine to manage pharyngeal pain Short course of corticosteroids is appropriate in cases of severe tonsillar enlargement impinging on airway, severe thrombocytopenia, or hemolytic anemia Antivirals are not generally recommended Approximately 20% of patients experience early complications most commonly affecting hematologic, nervous, gastrointestinal/hepatic, and/or respiratory systems