Definition and Description
Pneumocystis is an opportunistic fungal pulmonary pathogen that is an important cause of pneumonia in the immunocompromised host. Although organisms within the Pneumocystis genus are morphologically very similar, they are genetically diverse and host-specific. P. jirovecii infects humans, whereas P. carinii—the original species described in 1909—infects rats. For clarity, only the genus designation Pneumocystis will be used in this chapter.
Developmental stages of the organism include the trophic form, the cyst, and the precyst (an intermediate stage). The life cycle of Pneumocystis probably involves sexual and asexual reproduction, although definitive proof awaits the development of a reliable culture system. Pneumocystis contains several different antigen groups, the most prominent of which are the 95- to 140-kDa major surface glycoprotein (MSG) and kexin (KEX1).
Serologic surveys have demonstrated that Pneumocystis has a worldwide distribution and that most healthy children have been exposed to the organism by 3–4 years of age. Airborne transmission of Pneumocystis has been documented in animal studies; person-to-person transmission has been suggested by hospital outbreaks of Pneumocystis pneumonia (PcP) and by molecular epidemiologic analysis of isolates. Data suggest that the cyst is the transmissible form.
Pathogenesis and Pathology
Studies over the past several years have shown that Pneumocystis commonly colonizes patients who are immunosuppressed or who have chronic obstructive pulmonary disease. This colonization elicits an inflammatory response and is associated with a decline in lung function.
The host factors that predispose to the development of PcP include defects in cellular and humoral immunity. The risk of PcP among HIV-infected patients rises markedly when circulating CD4+ T cell counts fall below 200/μL. Other persons at risk for PcP are patients receiving immunosuppressive agents (particularly glucocorticoids) for cancer and organ transplantation; those receiving biologic agents such as infliximab and etanercept for rheumatoid arthritis and inflammatory bowel disease; children with primary immunodeficiency diseases; and premature malnourished infants.
The principal host effector cells against Pneumocystis are alveolar macrophages, which ingest and kill the organism, releasing a variety of inflammatory mediators. Proliferating organisms remain extracellular within the alveolus, attaching tightly to type I cells. Alveolar damage results in increased alveolar-capillary permeability and surfactant abnormalities, including a fall in phospholipids and an increase in surfactant proteins A and D. The host inflammatory response to lung injury leads to increases in levels of interleukin 8 and in neutrophil counts in bronchoalveolar lavage (BAL) fluid. These changes correlate with disease severity.
On lung sections stained with hematoxylin and eosin, the alveoli are filled with a typical foamy, vacuolated exudate. Severe disease may include interstitial edema, fibrosis, and hyaline membrane formation. The host inflammatory changes usually consist of hypertrophy of alveolar type II cells, a typical reparative response, and a mild mononuclear cell interstitial infiltrate. Malnourished infants display an intense plasma cell infiltrate that gave the disease its early name: interstitial plasma cell pneumonia.
Patients with PcP develop dyspnea, fever, and nonproductive cough. HIV-infected patients are usually ill for several weeks and may have relatively subtle manifestations. Symptoms in non-HIV-infected patients are of shorter duration and often begin after the glucocorticoid dose has been tapered. A high index of suspicion and a thorough history are key factors in early detection.
Physical findings include tachypnea, tachycardia, and cyanosis, but lung auscultation reveals few abnormalities. Reduced arterial oxygen pressure (PaO2), increased alveolar-arterial oxygen gradient (PAO2 – PaO2), and respiratory alkalosis are evident. Diffusion capacity is reduced, and heightened uptake with nonspecific nuclear imaging techniques (gallium scan) may be noted. Elevated serum concentrations of lactate dehydrogenase, reflecting lung parenchymal damage, and β-d-glucan, a component of the fungal cell wall, have been reported; however, these elevations are not specific for PcP infection.
The classic findings on chest radiography consist of bilateral diffuse infiltrates beginning in the perihilar regions (Fig. 207-1A), but various atypical manifestations (nodular densities, cavitary lesions) have also been reported. Pneumothorax occurs, and its management is often difficult. Early in the course of PcP, the chest radiograph may be normal, although high-resolution CT of the lung may reveal ground-glass opacities at this stage (Fig. 207-1B).
A. Chest radiograph depicting diffuse infiltrates in an HIV-infected patient with PcP. B. High-resolution CT of the lung showing ground-glass opacification in an HIV-infected patient with PcP. (Courtesy of Dr. Cristopher Meyer, with permission.)
While Pneumocystis usually remains confined to the lungs, cases of disseminated infection have occurred in both HIV-infected and non-HIV-infected patients. Common sites of involvement include the lymph nodes, spleen, liver, and bone marrow.
Because of the nonspecific nature of the clinical picture, the diagnosis must be based on specific identification of the organism. A definitive diagnosis is made by histopathologic staining. Traditional cell wall stains such as methenamine silver selectively stain the wall of Pneumocystis cysts, while reagents such as Wright-Giemsa stain the nuclei of all developmental stages. Immunofluorescence with monoclonal antibodies is more sensitive and specific than histologic staining. DNA amplification by PCR may become part of routine diagnostics but may not distinguish colonization from infection.
The successful diagnosis of PcP depends on the collection of proper specimens. In general, the yield from different diagnostic procedures is higher for HIV-infected patients than for non-HIV-infected patients because of the higher organism burden in the former group. Sputum induction and oral washes have gained popularity as simple, noninvasive techniques; however, these procedures require trained and dedicated personnel. Fiberoptic bronchoscopy with BAL, which provides information about ...