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Lengthy Clinical Presentation

This case presentation details the ongoing clinical journey of a 33-year-old female patient experiencing symptoms of headache, nausea, fatigue, and facial pressure over several weeks. Initially diagnosed with recurrent sinusitis and treated with azithromycin, her condition showed no improvement. Subsequent evaluations revealed complications including superficial venous thrombophlebitis and NSAID-induced gastritis. Laboratory investigations prompted further analysis, leading to a review of cytomegalovirus (CMV) in immunocompetent patients, its epidemiology, pathology, and complications relevant to the presented case.

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Lengthy Clinical Presentation

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  1. Lengthy Clinical Presentation Ellen Mattes Barbouche, MD Primary Care Conference 10 March 2004

  2. No Funding for this Discussion

  3. Case – Initial Presentation Day 4 of illnessProvider #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, left-sided, anterior cervical adenopathy, otherwise unremarkable head, neck, chest exam

  4. 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

  5. Second clinic visit – Day 15Provider #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

  6. 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.

  7. Immediate Care/Emergency Department Visit – Day 23Provider #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

  8. Clinic Visit 3 – Day 29Provider #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

  9. 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

  10. Clinic visit 4, Day 31Provider #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

  11. Clinic visit #4, day 31 – cont’d • Diagnostic test performed

  12. Objectives: Review CMV in Immunocompetant Patient • Epidemiology • Pathology • Laboratory features • Clinical presentation and complications

  13. 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 life-threatening infection • AIDS: most common viral infection Mandell, 5th ed., 2000;1586-1596.

  14. 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

  15. 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.

  16. 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

  17. 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 80-90% EBV, 10-20% CMV • 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.

  18. CMV Complications • Hepatic • Frequent subclinical transaminitis • Rare granulomatous hepatitis • Gastrointestinal • Inflammatory colitis • Gastritis • Esophagitis • Ileitis Stam. J Clinical Gastroenterology. 1996;22:322.

  19. 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

  20. 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 • CAD risk correlates with CMV IgG titers High. Clinical Infectious Disease.1999:28(4)746-749. Sorlie. Archives Internal Medicine. 2000;160(13)2027-2032.

  21. 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

  22. CMV Prevention • Good hygeine • Child and health care workers • Immunocompromised population • Prophylaxis soon after transplant

  23. 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

  24. Case follow up • Gradual return to normal health and normal transaminases over 2.5 months • Repeat CMV IgM fell

  25. Conclusions • CMV may cause atypical mononucleosis syndrome • Diagnosis • Lymphocytosis with atypical lymphs • CMV IgM level

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