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Lengthy Clinical Presentation

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

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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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