A 32YearOld Man with Persistent Fever and Cough

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A 32-Year-Old Man with Persistent Fever and Cough
Eugene G. Martin, Ph.D. Associate Professor of
Pathology Laboratory Medicine

• A Powerpoint companion to LABORATORY MEDICINE
  CASEBOOK. An introduction to clinical
  reasoning
• Jana Raskova, MD Professor of Pathology
  Laboratory MedicineStephen Shea, MD
  Professor of Pathology Laboratory
  MedicineFrederick Skvara, MD Associate
  Professor of Pathology Laboratory MedicineNagy
  Mikhail, MD Assistant Professor of Pathology
  Laboratory MedicineUMDNJ-Robert Wood Johnson
  Medical SchoolPiscataway, NJ

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History and Presentation

• 32 year old male admitted to assess two week
  history of
• Persistent fever
• Unproductive Cough
• Immigrated from Taiwan 7 years earlier
• Lived in California and Michigan
• Physical Exam
• Alert
• Apprehensive
• Normally developed
• Temp. 103 oF
• HR 100 bpm normal sinus rhythm
• BP 110/52
• Exam unremarkable EXCEPT rales at both lung bases
• Chest X-ray exam bilateral, hilar
  lymphadenopathy

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Significance of Patient History

• Coccidiomycosis
• Common soil saprophyte found in Southern
  California
• Produces hilar lymphadenopathy

• How important is where he lived?
• Endemic to California
• Coccidiomycosis(San Joaquin Valley Fever)
• Endemic to Ohio River Valley
• Histoplasmosis
• What about Taiwan?
• http//www.cdc.gov/travel/eastasia.htm

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Differential Diagnosis

• Rule Outs
• PPD gt 5mm indurationTuberculosis
• ACE ? Sarcoidosis
• Fungal Serology Pulmonary Mycoses

• Possibilities
• Tuberculosis
• Sarcoidosis
• Pulmonary Mycoses
• Blastomyces
• Coccididoides
• Lymphoma
• Metastatic cancer

Angiotensin Converting Enzyme is ? in 50-80 of
patients with active sarcoidosis. In addition,
sarcoidosis usually demonstrates bilateral hilar
lymphadenopathy. Problem Test IS NOT highly
specific 5-20 of patients with hilar
lymphadenopathy demonstrate increased levels
Purified Protein Derivative (PPD) - reaction
indicates exposure toMycobacterium. NB
Immunosuppressed patients (e.g. HIV) maynot
react strongly or at all anergic. Newly
infected patients may also be negative as well
as patients with miliary TB. In warm, humid
climates exposure to non-pathogenic mycobacteria
may result in reactions
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HEMATOLOGY
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CHEMISTRY
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Albuminemia

• Explanations
• Distributional hypoalbuminemia
• Expansion of extracellular volume being reflected
  as ? albumin
• Nutritional deficiency hypoalbuminemia
• Significant weight loss can be associated with ?
  albumin
• Constitutional symptoms of TB and Lymphoma
  include
• Fever
• Night sweats and
• Weight loss
• 35 of patients with TB present with
  hypoalbuminemia and lymphopenia

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Other Tests
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Chest X-Ray
Normal
Patient

• Hilar Lymphadenopathy
• Is a common feature of
• Sarcoidosis
• TB
• Coccidiomycosis
• Histoplasmosis

http//www.vh.org/adult/provider/radiology/NormalR
adAnatomy/Images/Thoracic/PAChest1.html http//www
.indianchestsociety.org/radiography/radio_mediasti
nal_lymphadenopathy.asp
Interstitial Infiltrates Bilateral hilar
lymphadenopathy
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Lymphadenopathy

• Bilateral symmetric hilar and right paratracheal
  mediastinal adenopathy is the most common pattern
  of lymphadenopathy in sarcoidosis.
• Unilateral hilar lymphadenopathy is more common
  in TB, neoplasm and primary pulmonary fungal
  infection
• Frequently, the hila are prominent but not
  definitely abnormal. Even if the hila are
  enlarged, it may not be possible to determine if
  this is due to enlarged lymph nodes or enlarged
  pulmonary vessels.
• The lateral radiograph can often resolve
  uncertainties.
• http//www.meddean.luc.edu/lumen/MedEd/Radio/sarc/
  xrynodes.htm

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Resolving uncertainties

• Hilar lymphadenopathy seen as a "donut" of soft
  tissue density surrounding the "doughnut hole"
  which is the end on left upper lobe bronchus
• Infrahilar soft tissue density that is much too
  large to be a normal pulmonary vein.
• Credit http//www.meddean.luc.edu/lumen/MedEd/Rad
  io/sarc/latcxr.htm

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Sputum Acid-fast Stain
Patient

• Dark-staining cocci and rods
• Slender, pink, acid-fast positive, slightly
  curved rods consistent with Mycobacteria
• Positive acid-fast stains are PRESUMPTIVE
  evidence of active TB, although non-pathogenic
  mycobacteria and Nocardia species can give
  positive results

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Other Test Results
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TB Treatments

• Treatment
• Isoniazid (INH) - dose - adult 300 mg pediatric
  10-15 mg/kg qd
• Rifampin (RIF) dose - adult 600 mg pediatric
  10-20 mg/kg qd
• Pyrazinamide (PZA), dose - adult 20-35 mg/kg)
  pediatric 20-40 m/kg qd
• Rifapentine (RFP)
• Streptomycin (SM) IM, dose - 20-40 mg/kg ped
  20-40 mg/kg
• Ethambutol (EMB) - dose 15-25 mg/kg, a week

• Initial therapy of uncomplicated pulmonary TB
  (including cavitary disease) should include four
  drugs unless
• the likelihood of drug resistance is very low
  i.e., the rate of isoniazid (INH) resistance in
  the community is less than 4
• the patient has not received prior therapy for
  TB, has not been exposed to any contacts with
  drug-resistant TB, and
• is not from an area where drug-resistant TB is
  prevalent.
• INH (5 mg/kg maximum, 300 mg PO qd), RIF (10
  mg/kg maximum, 600 mg PO qd),pyrazinamide (PZA,
  15-30 mg/kg PO qd), and either ethambutol (EMB,
  15 mg/kg PO qd) or streptomycin (15 mg/kg
  maximum, 1.5 g IM qd) should be administered
  initially.
• Pyridoxine (vitamin B6 ), 25-50 mg PO qd, should
  be given to those who are prone to neuropathy
  (diabetics, alcoholics, patients with dietary
  deficiencies) and considered in all patients.

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CHEMISTRY DAY 11
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Post-treatment Laboratories

• Obtain liver screen before beginning therapy
• Uric acid levels are affected by pryazinaminde
• http//www.ci.nyc.ny.us/html/doh/html/tb/cpp7.html
  

• Renal function and hearing may be affected if
  patient is treated with aminoglycosides or
  capreomycin

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TB Granuloma Lung

• Edge of granuloma visible on right
• Demonstrates
• Epithelioid cells
• Fibroblasts
• Langerhans giant cells
• Wall Hyaline fibrosis
• Granular, caseous necrosis on the right side of
  the image
• Lower image demonstrates intense lymphocytic
  inflammatory infilrate

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Lung biopsy -

• Note the presence of slender acid-fast positive,
  slightly curved and beaded bacilli, suggestive of
  Mycobacteria

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X-Ray Miliary TB

• Miliary TB occurs when a TB-infected lymph node
  erodes a vessel wall and tubercle bacilli are
  spread through the blood stream to other parts of
  the body and the rest of the lung
• Diffuse miliary pattern is associated with
  appearance of "millet seeds".

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Lung Gross in TB
Granuloma andCaseation necrosis
Reactivation granulomas

• Hilar and pleural lymph nodes

When infection with TB first occurs, the
organisms are inhaled and proliferate in alveoli
at the periphery of the lung just beneath the
pleura. Called a Ghon focus.
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Histopathology Lung TB
Low Power Granulomas
High Power Langerhans