Transcript CMV Mononucleosis - Department of Medicine

Lengthy Clinical Presentation
Ellen Mattes Barbouche, MD
Primary Care Conference
10 March 2004
No Funding for this Discussion
Case – Initial Presentation
Day 4 of illness
Provider #1
• 33 year old female with 3 days of headache,
nausea, fatigue, facial pressure
• History of migraine with aura, mononucleosis as
teenager
• Topical pimecrolimus for atopic dermatitis
• Penicillin allergy, no alcohol or tobacco
• Married researcher at UW Primate Center
• FH: mother hypothyroidism
• PE: Afebrile, injected posterior oropharynx, leftsided, anterior cervical adenopathy, otherwise
unremarkable head, neck, chest exam
Initial presentation – cont’d
• Laboratory: Negative urine pregnancy
• Diagnosis: Probable recurrent sinusitis
• Treatment: Azithromycin 500 mg day 1,
then 250 mg daily, days 2-5
Second clinic visit – Day 15
Provider #1
• No improvement with azithromycin
• Continued daily (AM) headaches, some relief
with ibuprofen
• PM “indigestion”
• Sore throat, post-nasal drainage, myalgias,
fatigue
• PE: T 99.4, pale and fatigued, left tonsillar and
anterior cervical adenopathy, otherwise normal
head, neck, chest, and neurologic exams
Clinic visit 2, day 15 – cont’d
• Laboratory: Normal CBC with 40%
lymphocytes and normal free T4 and TSH
• Impression: Possible viral illness
• Recommendation: Discontinue ibuprofen.
Acetominophen if necessary, rest, and
hydrate well. Call if symptoms continue.
Immediate Care/Emergency
Department Visit – Day 23
Provider #3
• 3 days of left leg pain after days off work to
recuperate from illness
• 3 cm linear erythema and pain to palpation left
lower extremity
• Diagnosis: Superficial venous thrombophlebitis
• Treatment: Elevate for 48 hours with moist heat
QID, ibuprofen 400 mg TID or aspirin 325 mg
QID with ranitidine 150 mg BID
• Follow up with primary MD if symptoms persist
over 2 days
Clinic Visit 3 – Day 29
Provider #5
• Continued headache, facial pain, and low-grade
fever
• Recurrent epigastric discomfort after ibuprofen
for leg pain
• Immediate care visit discontinued ibuprofen,
encouraged ranitidine, which helped
• PE: Afebrile. Posterior oropharyngeal erythema,
no adenopathy, otherwise normal head and
chest exam
Clinic visit 3, day 29 – cont’d
• Laboratory: Normal CBC, although 64%
lymphocytes, normal sinus films, ESR 21,
ALT 256, AST 145, CRP 2, Lyme EIA 0.02
• Impression: Prolonged illness with
NSAID-induced gastritis
• Follow up with primary MD
Clinic visit 4, Day 31
Provider #6, Primary MD
• Myalgias, fatigue, low-grade fevers persist
• Headaches decreased
• Post-prandial right upper quadrant abdominal
discomfort for one week
• No jaundice, but “dark urine”
• No acetominophen
• PE: Afebrile, weight stable for 6 months, normal
funduscopic exam, no icterus, small superior,
anterior adenopathy, no hepatosplenomegaly,
normal neuro, heart, lung, skin exams
Clinic visit #4, day 31 – cont’d
• Diagnostic test performed
Objectives: Review CMV in
Immunocompetant Patient
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Epidemiology
Pathology
Laboratory features
Clinical presentation and complications
CMV spectrum of disease
• Asymptomatic to mononucleosis
syndrome in normal host
• Congenital CMV syndrome frequently fatal
• Potential for much more severe disease in
immunocompromised
• BMT: CMV pneumonia most common lifethreatening infection
• AIDS: most common viral infection
Mandell, 5th ed., 2000;1586-1596.
Epidemiology
• Common, but socioeconomically
determined
– Developing countries near 100% during
childhood
– US population
• Lower socioeconomics approach 90% CMV IgG by
age 40
• Upper socioeconomics near 50% by adulthood
• Transmitted by body fluid contact
CMV pathology
• Largest herpes virus to infect humans
• CMV glycoproteins complex with HLA-1
molecules
– Prevents recognition and destruction by CD8
lymphocytes
• Nuclear inclusion cells (cytomegaly)
• Allows latent infection
• Most antivirals target CMV DNA
polymerase
Beersma. J Immunology. 1993;151:4455-4464.
Laboratory Diagnosis of CMV
• Detection of nuclear inclusion-cells in urine
sediment,saliva, blood, biopsy specimens
• Immunocompetant: IgM CMV (SLC $30)
– Specificity increased by removing IgG and
rheumatoid factor prior to testing
– Remains elevated < 4 months
• Immunocompromised: CMV DNA probe
CMV Mononucleosis
• Classic triad of infectious mononucleosis:
FEVER, LYMPHADENOPATHY, LYMPHOCYTOSIS
• Hematologic hallmark of infectious mononucleosis:
>50% lymphocytes, of these >10% atypical
• Of infectious mononucleosis cases, approximately 8090% EBV, 10-20% CMV
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CMV usually heterophile agglutinin negative
CMV usually more systemic – fever, adenopathy
CMV more likely older young adults (20-35)
EBV more likely sore throat, exudative tonsils
Klemola. J Infectious Disease. 1970;121: 608-614.
CMV Complications
• Hepatic
– Frequent subclinical transaminitis
– Rare granulomatous hepatitis
• Gastrointestinal
– Inflammatory colitis
– Gastritis Stam. J Clinical Gastroenterology. 1996;22:322.
– Esophagitis
– Ileitis
CMV Complications, cont’d
• Neurologic
– Meningitis
– Encephalitis
– Guillain-Barre syndrome
• CMV and campylobacter most frequently identified
• Younger patients
• Increased sensory deficits, more frequent
respiratory insufficiency and cranial nerve
impairment
• Slower recovery
CMV Complications, cont’d
• Cardiovascular
– Pericarditis
– Myocarditis
– Atherosclerosis
• Mechanism: infected vascular endothelium
increased proliferation smooth muscle cells which
increase oxygenated scavengers and decrease
LDL uptake High. Clinical Infectious Disease.1999:28(4)746-749.
• CAD risk correlates with CMV IgG titers
Sorlie. Archives Internal Medicine. 2000;160(13)2027-2032.
CMV Complications
• Pulmonary
– Pneumonitis
• Ocular
– Retinitis
• Hematologic
– Anemia: hemolytic – cold agglutinins
– Thrombocytopenia – if infected megakaryocytes
• Rheumatologic
– Frequent arthralgias, RARE arthritis
– 25-35% develop positive rhematoid factor
CMV Prevention
• Good hygeine
• Child and health care workers
• Immunocompromised population
– Prophylaxis soon after transplant
CMV during pregnancy
• Primary infection in 1-3% of U.S. pregnant
women
• Most mothers asymptomatic, few mononucleosis
• 2/3 infants not infected, of the remaining third,
only 10-15% symptomatic at birth
• Effected fetus may develop hepatosplenomegaly
to death
• 80-90% of infected infants will develop
complications within 2 years: hearing loss,
visual impairment, mental retardation
cdc.gov/ncidod/diseases/cmv.htm
Case follow up
• Gradual return to normal health and
normal transaminases over 2.5 months
• Repeat CMV IgM fell
Conclusions
• CMV may cause atypical mononucleosis
syndrome
• Diagnosis
– Lymphocytosis with atypical lymphs
– CMV IgM level