Page 138 - AIDSBK23C

Page 138

distress syndrome (ARDS). P jiroveci (carinii) pneumonia can be a presumptive clinical
diagnosis to define AIDS using the following suggested guidelines:[392]

* A history of dyspnea on exertion or nonproductive cough with onset in the previous three
months; AND
* Chest roentgenogram evidence of diffuse bilateral interstitial infiltrates or gallium scan
evidence of diffuse bilateral pulmonary disease; AND
* Arterial blood gas analysis showing an arterial pO2 of less than 70 mm Hg or a low
respiratory diffusing capacity (less than 80% of predicted values or an increase in the
alveolar-arterial oxygen tension gradient; AND
* No evidence of a bacterial pneumonia

The chest radiograph can appear normal in up to 10% of cases. High resolution CT
imaging typically shows ground glass attenuation, often with a geographic or mosaic distribution
pattern, in 90% of cases. As the inflammatory infiltrates begin to organize, there can be foci of
consoliation and septal thickening. Variably sized multiple and bilateral cysts can be found in up
to a third of cases and may remain up to 3 years following resolution of the infection. The cysts
may be complicated by pneumothorax, which can be refractory to chest tube drainage. Atypical
findings on chest radiograph in up to 10% of cases can include isolated focal or asymmetrical
dense consolidation and adenopathy. Rare findings include pleural effusions, as well as
parenchymal nodules from granulomatous inflammation. When present, such nodules may be
miliary, or larger in size, and may undergo cavitation and calcification.[606,607]
Use of aerosolized pentamidine for prophylaxis against PCP may lead to the appearance
of localized upper lobe disease because this drug is preferentially deposited in middle and lower
lobes.[602] In children, PCP may manifest radiographically as a rapidly progressive increase in
air space opacity with air bronchograms.[608]
Therapies can include trimethoprim-sulfamethoxazole (oral or parenteral), pentamidine
isethionate (parenteral or in aerosolized form), prednisone, trimethoprim-dapsone, dapsone,
trimetrexate, pyrimethamine-sulfadoxine, or clindamycin-primaquine. Prednisone may be added
as an adjunctive agent to lessen hypoxemia.[208,307] Trimethoprim-sulfamethoxazole (TMP-
SMZ), if tolerated, is the first choice for either prophylaxis or therapy in both adults and
children. If TMP-SMZ cannot be tolerated, then alternative therapy for prophylaxis may consist
of dapsone, a combination of dapsone with pyrimethamine and leucovorin, or aerosolized
pentamidine. Regimens containing dapsone and pyrimethamine are also effective prophylaxis
against toxoplasmosis. Prophylactic therapy to prevent PCP is also recommended in
pregnancy.[208] Resistance to TMP-SMZ and dapsone may result from mutations in the DHPS
gene encoding for an enzyme that is inhibited by these drugs.[397]
Drug allergy or toxicity may develop in over half of treated patients and these reactions
may also interfere with concomitant zidovudine therapy. Adverse reactions with trimethoprim-
sulfamethoxazole occur in half of patients and include fever, skin rash (rarely Stevens-Johnson
syndrome), nausea, vomiting, nephritis, leukopenia, hepatitis with elevated liver enzymes, and
bone marrow suppression. Adverse reactions with pentamidine may include nausea, vomiting,
rash, hypotension, serum glucose alterations, pancreatitis, hepatotoxicity, nephrotoxicity, and
leukopenia. Aerosolized pentamidine, which is preferentially deposited in middle and lower
lobes, is often accompanied by bronchoconstriction that must be alleviated with concomitant use
of an inhaled beta-adrenergic agent. Dapsone may cause rash, nausea, and hemolysis.