Updated: 4/1/2019

Cytomegalovirus (CMV)

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Snapshot
  • A 40-year-old man with a past medical history of HIV presents to the clinic for follow-up. He reports that he has had difficulty swallowing, fevers and chills, nausea, vomiting, and abdominal pain. He reports that he has been compliant with his HIV medications. On physical exam, he has ulcers in his oropharynx. His laboratory tests reveal positive CMV-specific immunoglobulin G but negative heterophile antibodies. He is given an antiviral treatment and is admitted for an endoscopy workup and close monitoring. (CMV esophagitis)
Introduction
  • Classification
    • cytomegalovirus (CMV) or human herpesvirus-5 (HHV-5)
      • linear, double-stranded DNA virus
      • largest virus that causes human infections
      • transmission via body fluids or vertical transmission
  • Epidemiology
    • incidence
      • very common
    • risk factors
      • immunosuppression
      • men who have sex with other men
      • poor socioeconomic status
      • working in childcare
      • transplant recipients
        • prone to CMV pneumonia
  • Pathogenesis
    • CMV-caused diseases can either result from a primary infection or reactivation of a latent infection
    • replication of host cells (including epithelial cells, macrophages, and neurons) result in viremia and symptoms from primary infection
    • cellular immunity is crucial in clearing this virus
  • Associated conditions
    • congenital CMV infection
      • jaundice
      • hepatosplenomegaly
      • thrombocytic purpura and petechial rash
      • hearing loss
        • most common cause of non-hereditary congenital sensorineural deafness
      • seizures
      • microcephaly
      • ventriculomegaly
      • intracranial calcifications
  • Prognosis
    • often self-limited in immunocompetent patients
Presentation
  • Symptoms
    • immunocompetent patients
      • most cases are asymptomatic
      • if symptomatic, CMV infections often result in a mononucleosis syndrome with fevers, myalgias, arthralgias, and cough 
    • immunocompromised patients
      • esophagitis
      • colitis (most common)
      • encephalitis
      • hepatitis
      • pneumonia
      • retinitis
      • congenital CMV
      • hemolytic anemia
  • Physical exam
    • fever
    • cervical lymphadenopathy
    • hepatosplenomegaly
    • maculopapular rash
Studies
  • Labs
    • lymphocytosis with atypical lymphocytes
    • thrombocytopenia
    • transaminitis
    • negative heterophile antibody
    • CMV-specific immunoglobulin M (persists for 4-6 months) 
    • CMV-specific immunoglobulin G (2-3 weeks)
      • active infection
    • viral load 
      • does not distinguish active vs past infection
  • Histology
    • if warranted, may reveal CMV on immunohistochemistry
    • classic "owl's eye" appearance
  • Making the diagnosis
    • based on clinical presentation and laboratory studies
Differential
  • Epstein-Barr viral (EBV) mononucleosis
    • distinguishing factors
      • CMV mononucleosis often includes more myalgias, arthralgias, and cough than EBV infection
      • CMV infection also does not typically present with sore throat or lymphadenopathy
Treatment
  • Management approach
    • mainstay of treatment is supportive care
  • Conservative
    • supportive care
      • indication
        • all patients
      • modalities
        • hydration
  • Medical
    • antiviral medications
      • indications
        • immunocompromised patients
        • severe disease or organ damage
      • drugs
        • ganciclovir
        • valganciclovir
Complications
  • Thrombosis
  • Colitis
  • Permanent vision changes
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MC.75) A 35-year-old HIV+ man presents to the ophthalmologist complaining of worsening vision for the past two weeks, and seeing new flashes and floaters in his right eye. He reports no pain in his right eye nor is there any redness. On ophthalmoscopic exam, the following is observed (Figure A). Which of the following best describes the virus responsible for these findings? Review Topic

QID: 106726
FIGURES:
1

Linear (+)ssRNA, nonenveloped

9%

(18/194)

2

Linear (-)ssRNA, segmented, enveloped

10%

(19/194)

3

Partial circular, dsDNA virus, enveloped

11%

(22/194)

4

Linear dsDNA, enveloped

60%

(116/194)

5

Circular dsDNA, nonenveloped

8%

(15/194)

M1

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