Young Woman With Sore Throat and Extreme Fatigue

A

n 18-year-old college studentpresents with a 4-day history ofincreasing throat pain, low-gradefever, and extreme exhaustion. Previously,she had been healthy and participatedactively in sports, includingmarathon running. Her appetiteand intake have been poor. No historyof cough, chest pain, shortness ofbreath, nausea, vomiting, diarrhea,or abdominal distention. She has noallergies, takes no medications, anddoes not smoke or drink alcohol.She is sexually active with a singlepartner.

Examination.

The patient appears ill. Pulse rate is 90 beats perminute and regular; temperature,37.9

^o

C (100.2

^o

F); respiration rate, 22breaths per minute; blood pressure,112/62 mm Hg. She is well hydrated.No scleral icterus. Throat is erythematous with normaltonsils; a petechial rash is noted on the hard palate.Posterior cervical, axillary, and inguinal lymph nodes arepalpable, nonmated, and nontender. Thyroid is not palpable.No rashes or ankle swelling. Liver is enlarged to3 fingers' breadth below the costal margin, and spleen istender and palpable 2 fingers' breadth below the costalmargin. The remainder of the examination is normal.

Laboratory studies.

White blood cell (WBC) count is18,500/μL, with 30% polymorphonuclear leukocytes, 60%lymphocytes (with 12% atypical lymphocytes), 6% monocytes,and 4% eosinophils. Hemoglobin level is 11.8 g/dL;erythrocyte sedimentation rate, 48 mm/h. The serum proteinlevel is 6.8 g/dL; albumin, 4.8 g/dL; total bilirubin,2.2 mg/dL; conjugated bilirubin, 1.6 mg/dL. The aspartateaminotransferase level is 182 U/L; alanine aminotransferase, 150 U/L; alkaline phosphatase, 126 U/L. Urinalysisresults are normal. A radiograph of the kidneys, ureters,and bladder is normal.

What abnormality does the peripheral smear show,and to which of the following disorders does theclinical picture point?

A.

Lymphocytic leukemia

B.

Monocytic leukemia

C.

Hodgkin lymphoma

D.

Infectious mononucleosis

E.

Cytomegalovirus hepatitis

OVERVIEW

Infectious mononucleosis is caused by EBV (humanherpesvirus 4). This highly common, acute febrile illnessoccurs worldwide. It is most common in persons betweenages 15 and 24 years; however, the infection can occur atany age. More than 50% of college students and 90% ofadults have been infected and have antibodies to the virus.EBV is spread by contact with oral secretions viakissing or contaminated objects. The virus is associatedwith Burkitt lymphoma, certain B-cell neoplasms in immunocompromisedpatients (such as those with HIV infection),and nasopharyngeal carcinoma.

CLINICAL FEATURES

Clinical illness usually begins after a 1- to 2-month incubationperiod. The onset is typically insidious and vague;patients experience several days of prodromal symptoms,including fatigue, malaise, myalgias, and anorexia.This is followed by the classic triad of pharyngitis,fever, and lymphadenopathy. The moderately severepharyngitis is associated with marked tonsillar hypertrophyand exudates. Palatal petechiae may also be seen. Alow-grade fever occurs in approximately 80% of patients.The posterior cervical lymph chain is typically involved,but enlargement of the submandibular, anterior cervical,axillary, and epitrochlear nodes may also be found.Splenomegaly occurs in 50% of cases; it is rarely massiveand resolves within 4 weeks of the onset of symptoms.Hepatomegaly, periorbital edema, and rashes mayalso be present. Up to 15% of patients with infectiousmononucleosis have a rash, which can be maculopapular,petechial, or urticarial. A pruritic, nonallergic, maculopapularrash develops in up to 90% of infected patientswho are given ampicillin.

LABORATORY FINDINGS

The total WBC count is elevated and ranges from10,000/μL to 20,000/μL. Lymphocytosis predominates;atypical lymphocytes account for at least 10% of total lymphocytes

(Figure).

Mild thrombocytopenia and neutropeniaare common but transient findings. Liver enzyme levels,particularly the transaminase levels, are mildly tomoderately elevated in up to 90% of infected patients.Detection of heterophil antibodies with the monospottest is the characteristic laboratory abnormality. These antibodiesare found in 90% of patients with acute infectiousmononucleosis, although the test may take up to 3 weeksto become positive. Therefore, repeated testing may be necessary--especially if the initial test is performed early.Several commercially available monospot tests, which aregenerally both sensitive and specific, can be used. Heterophilantibodies usually disappear by 3 months but maybe present for up to 1 year. False-positive monospot testresults are rare but can occur in patients with varicella, influenza,or lymphoma.EBV infection can also be detected by the presenceof specific antibodies. Routine virus-specific antibody detectionis not needed but may be helpful in patients withatypical cases of EBV infection or in young children, whoare often heterophil antibody-negative. Titers of IgM andIgG antibodies to EBV viral capsid antigen are elevated inmore than 90% of patients at the onset of disease. BecauseIgM antibody levels are elevated for only 2 to 3 months,they are most useful as a diagnostic indicator in patientswith acute infectious mononucleosis. In contrast, becauseelevated IgG antibody levels persist for life, they are betterused to assess previous EBV exposure.

COMPLICATIONS

The complications associated with acute EBV infectionare rare; most patients recover fully in 3 to 4 weeks.When complications do occur, however, they can be dramaticand even life-threatening.

• Neurologic complications include aseptic meningitis, encephalitis,Guillain-Barr syndrome, transverse myelitis, andBell palsy.
• Splenic rupture occurs in 0.1% to 0.2% of cases. It typicallyfollows mild trauma sustained during the second weekof illness and can be life-threatening.
• Pharyngeal edema can produce airway obstruction.
• Autoimmune hemolytic anemia occurs in about 2% of patients,usually during the first 2 weeks of illness.
• Other rare complications include hepatitis, myocarditis,and pericarditis.

TREATMENT

Therapy is mainly supportive. Advise patients to avoidcontact sports for at least 3 weeks, especially if splenomegalyis present, and to avoid alcohol for a minimum of 3months after liver function test results return to normal.Acetaminophen and NSAIDs can be used for fever.Pharyngitis can be treated with lozenges and saltwatergargles.The role of corticosteroids in uncomplicated caseshas been studied extensively--and their use is not advocated.However, in patients with impending airway obstruction,myocarditis, or hemolytic anemia, prednisone(40 to 60 mg/d with subsequent tapering over 1 to 2weeks) may be beneficial. Treatment with acyclovir hasbeen shown to limit viral shedding in the oropharynx buthas no significant clinical effect.

References:

FOR MORE INFORMATION:

• Auwaerter PG. Infectious mononucleosis in middle age. JAMA. 1999;281:454-459.
• Bailey RE. Diagnosis and treatment of infectious mononucleosis. Am FamPhysician. 1994;49:879-888.
• Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000;343:481-492.
• Cunha BA. EBV mononucleosis. Infect Dis Pract. 1994;18:8-14.
• Kaye KM, Kieff E. Epstein-Barr virus infection and infectious mononucleosis.In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. Philadelphia:WB Saunders Company; 1992:1646-1654.