- What does the chest radiograph show?
Both nodules and cavitation are seen, predominantly in upper lung fields.
- Describe the gross appearance of this lung representative of the disease process in your patient's lungs.
There is extensive granulomatous disease involving the lung parenchyma. Mainly upper lobe is involved. The larger tan-white granulomas have caseation with central necrosis and in some areas become almost confluent.
- Describe the microscopic appearance of the lungs. What is the probable diagnosis?
Granulomatous inflammation is present. The granulomas demonstrate central caseation and surrounding epithelioid macrophages. Some Langhans giant cells are seen. Also contributing to the inflammatory reaction are lymphocytes. The acid fast stain demonstrates many slender red rods consistent in morphology with Mycobacteria.
- What tests can be performed to diagnose this condition? What additional clinical findings might be present?
A tuberculin skin test is used mainly for screening patients
for possible tuberculosis. Sputum samples can be obtained for acid fast
smear and culture. This patient's acid fast smear was 3+ positive, and the
culture grew Mycobacterium tuberculosis that was sensitive to rifampin,
isoniazid, and ethambutol. A chest radiograph will show the extent of
pulmonary disease (in this case it was extensive, because of the
cavitation).
- Describe the additional gross pathologic patterns for this disease
process. What is the differential diagnosis?
Primary tuberculosis is often seen in children, and is often
subclinical. There is a subpleural granuloma and extensive hilar lymph node
granulomatous disease (the so-called Ghon complex, as seen in image 1.5).
In adults, when health status declines, the quiescent infection may
reactivate, or the patient may be reinfected, and then secondary
tuberculosis is seen. Secondary tuberculosis is what the patient in this
case had, because of the extensive upper lobe cavitary disease. When
resistance to infection is very poor, a miliary pattern of infection may be
seen, with numerous millet seed (1 to 3 mm) sized granulomas scattered
extensively throughout the lungs (image 1.6). The infection may also
disseminate to other organs.
- What standard pharmacologic therapies are available?
Several drugs are used in the treatment of tuberculosis. Foremost among these are rifampin, isoniazid, and pyrazinamide, with supplemental drugs ethambutol and streptomycin. The primary treatment protocol in most cases of tuberculosis in both adults and children consists of an initial 2-month course of isoniazid, rifampin, and pyrazinamide followed by a 4-month course of isoniazid and rifampin. Resistant organisms require more complex and prolonged treatment protocols. Most treatment failures stem from non-compliance. Since rifampin turns body fluids such as urine and saliva a red-orange color, it serves to check on patient compliance with therapy.
The most important adverse effects of isoniazid use are hepatotoxicity and peripheral neuropathy. Isoniazid-induced hepatitis is idiosyncratic and increases in incidence with age and with daily alcohol consumption, concomitant rifampin administration, and slow isoniazid acetylation. Persons at high risk on isoniazid therapy must have liver enzymes monitored. The peripheral neuropathy is ameliorated by use of supplemental dietary pyridoxine.
Treatment of non-tuberculous mycobacterial disease is different. One example is Mycobacterium avium-complex (MAC) seen in immunocompromised persons, such as those with AIDS. The most active drugs against MAC are the macrolides clarithromycin and azithromycin. Resistance as a consequence of a single point mutation in the gene coding for the large ribosomal subunit typically develops. Other drugs that show some effectiveness against MAC include ethambutol, ciprofloxacin, clofazimine, amikacin, rifampin, and rifabutin. The preferred regimen for treatment of disseminated infections is a combination of rifabutin, clarithromycin, and ethambutol.
