Bonus online case: Acute CMV infection

A patient with four weeks of fevers diagnosed with cytomegalovirus (CMV) infection.


The patient

A 45-year-old man presented with four weeks of fevers, myalgias, and malaise despite frequent acetaminophen and ibuprofen use. One week before his symptoms developed, he had an uncomplicated root canal procedure. The patient did not report any localizing symptoms, recent travel, sick contacts, or pets. On presentation to the hospital, vital signs included a temperature of 101.4 °F and normal pulse, blood pressure, respirations, and oxygen saturation. His physical examination was notable for rigors, with a normal cardiac, respiratory, abdominal, and musculoskeletal exam, and the absence of rash or lymphadenopathy. Initial infectious workup with blood cultures, urine studies, and chest X-ray was unrevealing.

The patient's erythrocyte sedimentation rate was 16 mm/h (reference range, 0 to 15 mm/h) and his C-reactive protein level was 35.0 mg/L (reference range, ≤7.4 mg/L). Additional negative tests included respiratory viral nasopharyngeal swab, urine legionella, serum HIV antibody, tuberculosis, Lyme antibodies, antinuclear antibody, antineutrophil cytoplasmic antibody, and rheumatoid factor. A facial X-ray did not show any sinus abscess. Transthoracic echocardiogram did not show any cardiac valvular vegetations. A CT of the chest, abdomen, and pelvis showed moderate hepatic steatosis and nonspecific peri-hepatic lymph nodes that were interpreted as reactive. Liver enzymes were mildly elevated with an aspartate aminotransferase level of 84 U/L (reference range, 15 to 41 U/L), an alanine aminotransferase level of 126 U/L (reference range, 14 to 54 U/L), and an alkaline phosphatase level of 165 U/L (reference range, 38 to 126 U/L). Viral hepatitides (A, B, and C) were negative, as were serologies for Epstein-Barr virus (EBV), varicella zoster virus, and herpes simplex virus. Cytomegalovirus (CMV) IgM antibody level was greater than 240 U/mL (reference range, ≤29.9 U/mL), along with a positive CMV IgG antibody. The patient was discharged with outpatient follow up, and two weeks later his fevers and symptoms had resolved.

The diagnosis

This patient was diagnosed with acute CMV infection. CMV is a member of the Herpesviridae viral family. Human exposure is highly common in the general population and is estimated to be present in at least 40% of adults worldwide. Risk factors for exposure include older age (it's nearly ubiquitous in those older than age 80 years), female gender, socioeconomic disadvantage, and immunosuppression. The virus, like other types of herpes viruses, stays latent after initial infection and can reactivate later in life. As such, CMV can present a primary infection, secondary re-infection from a separate strain, or reactivation of latent CMV infection. Infection syndromes range from the asymptomatic or subclinical infection to multiorgan involvement. Symptomatic CMV infection is uncommon in those with normal immune systems, but when there are symptoms, fevers and malaise are typical and can be present for weeks. Lymphadenopathy and/or a generalized maculopapular or morbilliform rash are commonly noted on physical examination, and transaminitis and/or atypical lymphocytes can be seen on laboratory testing. CMV infection mimics EBV infection in a “mononucleosis-like” syndrome; however, the splenomegaly and pharyngitis often present in EBV infection are not typical for CMV.

Organ involvement in CMV infection is rare but may include colitis, pneumonia, encephalitis, Guillain-Barré syndrome, pericarditis, and myocarditis. Diagnosis is most commonly made via serologic detection of CMV IgM and IgG antibodies, and quantitative polymerase chain reaction (PCR) testing is also widely available. Quantitative PCRs have a general viral load detection range of 50 to several million IU/mL. The sensitivity of these PCRs is low and specificity is high, and differences among assays have prevented establishment of a standard cutoff value for diagnosis of active disease. Qualitative PCR has extremely high sensitivity and specificity for CMV DNA but cannot differentiate latent from active disease and thus has no role in the diagnosis of active CMV infection. In patients in whom organ-specific involvement is a concern, tissue diagnosis is the gold standard.

The treatment for acute CMV infection in immunocompetent hosts is supportive care, as the disease is typically self-limited in this population. There is no evidence to support antiviral therapy, although it is often considered on a case-by-case basis for those with critical illness or severe organ-specific involvement. For immunocompromised hosts, treatment and surveillance for acute CMV infection vary depending on the underlying immunodeficiency, severity of illness, and viral load.

Pearls

  • Immunocompetent hosts with CMV are typically asymptomatic, but when symptomatic typically present with a “mononucleosis-like” syndrome of fevers, malaise, lymphadenopathy, and hepatitis.
  • Although symptoms of CMV infection may last weeks, they are typically self-limited and require supportive care; for severe disease and organ-specific involvement, antiviral therapy is often utilized but without robust data to support its use.

Other cases in this issue