A 34-year-old man comes to the physician due to fever, myalgias, malaise, and progressive fatigue over a 2-week period. He has not experienced any sore throat. He recently received a blood transfusion while hospitalized for a bleeding duodenal ulcer. Physical examination shows mild splenomegaly. There is no lymphadenopathy and no jaundice. Lymphocytosis is identified in the peripheral blood with 30% atypical lymphocytes. The patient's serum fails to agglutinate horse erythrocytes. The agglutination test is repeated a week later and, again, no agglutination is noted. HIV testing is negative. Which of the following is the most likely cause of this patient's condition?

Question

A 34-year-old man comes to the physician due to fever, myalgias, malaise, and progressive fatigue over a 2-week period.  He has not experienced any sore throat.  He recently received a blood transfusion while hospitalized for a bleeding duodenal ulcer.  Physical examination shows mild splenomegaly.  There is no lymphadenopathy and no jaundice.  Lymphocytosis is identified in the peripheral blood with 30% atypical lymphocytes.  The patient's serum fails to agglutinate horse erythrocytes.  The agglutination test is repeated a week later and, again, no agglutination is noted.  HIV testing is negative.  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

Most cases of infectious mononucleosis (IM), caused by the Epstein-Barr virus (EBV), are associated with serum heterophile antibodies that agglutinate with erythrocytes from unrelated species (eg, horse erythrocytes in the Monospot test, sheep erythrocytes in the classic Paul-Bunnell test). The agglutination test may be negative at the beginning of the infection and can be repeated later for confirmation. Because the Monospot (horse erythrocyte agglutination) test was negative on 2 separate occasions in this patient with a mononucleosis-like syndrome (fever, fatigue, splenomegaly, atypical lymphocytosis), his symptoms are unlikely to be due to EBV; the lack of sore throat and lymphadenopathy is also atypical for classic EBV-associated IM (Choice C). In immunocompetent patients with a heterophile antibody-negative mononucleosis-like syndrome, the most likely diagnosis is cytomegalovirus (CMV) infection. Pharyngitis and lymphadenopathy are seen less commonly than with EBV. CMV can be acquired during the transfusion of leukocyte-laden blood products, as the virus infects leukocytes of granulocyte-macrophage lineage. Irradiation helps reduce this risk. Other causes of heterophile antibody-negative mononucleosis-like syndromes include human herpesvirus-6, HIV, and toxoplasmosis. (Choice A) Coxsackie A viruses cause aseptic meningitis and herpangina (fever, posterior pharyngeal gray vesicles/ulcers) in children. (Choice D) Acute hepatitis C (HCV) rarely causes symptoms. Transfusion-acquired HCV can cause chronic hepatitis, but highly sensitive blood donor screening tests have led to low transmission rates. Atypical lymphocytosis is less common with HCV than with EBV or CMV. (Choice E) JC virus causes progressive multifocal leukoencephalopathy (PML), a central nervous system viral infection seen in immunocompromised patients. Clinical manifestations include hemiparesis, visual field defects (eg, hemianopsia), and cognitive impairment. (Choice F) Parvovirus B19 causes erythema infectiosum, a childhood illness characterized by red, flushed cheeks ("slapped cheeks" appearance). The virus can also cause aplastic crises in patients with sickle cell anemia and hydrops fetalis in the fetus. Educational objective: The Monospot test is positive in most cases of Epstein-Barr virus-associated mononucleosis. In immunocompetent patients with a heterophile antibody-negative mononucleosis-like syndrome, the most likely diagnosis is cytomegalovirus infection.

A 34-Year-Old Man Comes to the Physician Due to Fever