Laboratory Testing
Evaluation of Specific Cases in Practice
Case 1
A previously well two-year-old returns to your office with a six day history of fever. When you saw him on the second day of his illness he had an erythematous pharynx and enlarged cervical nodes with a temperature of 101.8ºF. Today his temperature is 102ºF and he presents with no change in his cervical nodes and axillary and inguinal nodes are mobile, rubbery, slightly tender, and 1½ cm in diameter. Upon abdominal exam his liver is 1cm below the costal margin and his spleen is palpable 2cm below the costal margin. He looks tired but not toxic. His mother says he is taking liquids well but not eating much. You order a Mono Spot test which comes back negative that afternoon. A CBC, which you review yourself with the lab technician, shows 18,000 WBC, 35% neutrophils, 51% lymphocytes, 5% monocytes, 11% atypical lymphocytes, and a ferritin less than 65 mmol/Lyes. What should you tell the mother about the likelihood that her child’s illness is mono?EBV virus, the etiologic agent in mononucleosis, is a common cause of prolonged fever in two year olds. Generalized adenopathy, pharyngitis, and an enlarged spleen are typical symptoms. Atypical lymphocytes are also typical. The Mono Spot test is known to have a sensitivity of less than 50% in 2 year olds. Mono is a likely diagnosis in this child. EBV specific serology can confirm the diagnosis but samples will go to an outside lab and probably will not be back before the patient improves clinically. Most pediatricians would order these tests for confirmation and reassure the parent that mono is the most likely diagnosis.
Case 2
A 16 year old child presents in April with a five day history of fever of 102º F and exudative pharyngitis. He has prominent cervical adenopathy. You do a mono spot which is positive. Both rapid strep and confirmatory culture done at an outside hospital are negative. What will you tell the patient about his diagnosis?Since the mono spot test is a sensitive and specific test in adolescents, the mono spot combined with typical symptoms, as in this case, makes the diagnosis of mono very likely.
Case 3
Purified protein derivative (PPD) is prepared by precipitation of protein components from culture filtrate of M. tuberculosis. The precipitation removes some of the large carbohydrate antigens. PPD is more specific for the detection of TB infection than is old tuberculin. A person infected with M. tuberculosis will react to an intradermal injection of tuberculin with delayed type hypersensitivity (DTH) response mediated by T lymphocytes. Cellular infiltration by T cells in combination with other recruited inflammatory cells results in maximal induration at 48 to 72 hours after inoculation with intradermal antigen. The ATS/CDC guidelines vary the definition of a ‘positive PPD’ depending on the patients’ situation:Guidelines for determining a positive tuberculin skin test reaction | ||
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Induration >5 mm | Induration >10 mm | Induration >15 mm |
HIV-positive persons | Recent arrivals (<5 yr.) from high-prevalence countries | Persons with no risk factors for TB |
Recent contacts of TB case | Injection drug users | |
Fibrotic changes on chest radiograph consistent with old TB | Residents and employees* of high-risk congregate settings: prisons and jails nursing homes and other health care facilities, residential facilities for AIDS patients, and homeless shelters | |
Patients with organ transplants and other immunosuppressed patients (receiving the equivalent of >15 mg/d prednisone) | Mycobacteriology laboratory personnel | |
Persons with clinical conditions that make them high-risk:
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Children less than four years of age or infants, children, and adolescents exposed to adults in high-risk categories |
In the case of tuberculosis, we are faced with a situation where both false negatives and false positives can have dire consequences. False negatives can lead to untreated TB with progression of the disease and a spreading to others. False positives can lead to the prescription of INH for latent tuberculosis infection, requiring daily medication for 6-9 months with the possibility of significant side effects. To maximize benefit and minimize harm, the cut off for interpreting a test as positive is varied by risk group. With people in the high risk group, the prior likelihood of the disease is high and defining 5 mm as positive will capture most people with the disease and not lead to a large number of false positives. In low risk groups, positive is defined as 15 mm. In low risk populations there is a low prior likelihood of the disease and so a large number of people with reactions of 5-15 mm do not have the disease. We would not want to treat people without disease with INH for 6 months. The cut off of 15 mm improves specificity.