Lymphadenitis caused by infection with the fungus Pneumocystis jiroveci.

Pneumocystis jiroveci (formerly P. carinii) infection of lymph nodes.

Although P. jiroveci organisms are ubiquitous in nature, normal persons of the general population become immune in early childhood, and infections in immunocompetent persons are extremely rare. By the middle of the twentieth century, Pneumocystis pneumonia (PCP) had not yet been recognized in North America (1). Cases of Pneumocystis infection were recorded in malnourished children in underdeveloped countries and in persons with congenital immunodeficiencies (2,3,4). The disease became more common with the increased use of immunosuppressive therapies in organ-transplant recipients and cancer patients, particularly those receiving intensive combination chemotherapy (5,6,7,8).

Since 1981, pneumocystosis has been recognized as the most common opportunistic infection associated with acquired immune deficiency syndrome (AIDS). At the peak of the epidemic of human immunodeficiency virus (HIV) infection, PCP developed in 60% to 85% of AIDS patients and was the most common cause of death (9,10,11,12). In the HAART era (ie, after the introduction of the highly active antiretroviral therapy) a marked reduction was noted in the opportunistic infections associated with AIDS, including PCP (13,14,15). However, in endemic areas of underdeveloped countries and in inner-city populations of some large cities, PCP is still the first indication of HIV infection (16,17).

Pneumocystis jiroveci, the agent of pneumocystosis, was previously considered a protozoan because of the presence of filopodia on its trophozoites. Subsequent studies, however, have shown that its ribosomal RNA has fungus-type sequences; consequently, it is a species of fungus (18). More recently, this microorganism underwent a further change of classification. DNA analysis demonstrated that Pneumocystis organisms in different mammals differ widely, leading to the renaming of the species infecting humans as P. jiroveci, whereas P. carinii remained to designate only those species derived from rats (19). Pneumocystis jiroveci has been detected in air and pond water, although in very low amounts. The spores survive long enough to infect a new host (19).

Pneumocystis organisms affect most mammalian species and can be found in hosts with no clinical or histologic evidence of disease. They may remain in latent or inactive states for long intervals. Activation and replication are stimulated and permitted by immunodeficiency. Pneumonia developed in 100% of experimental rats without P. carinii inoculation after 2 to 4 months of corticosteroid administration (1). In humans, P. jiroveci organisms are normally controlled and kept in latent cyst form by cellular immunity. Recent studies detected the presence of P. jiroveci DNA in the respiratory tract of immunocompetent adults, suggesting that the general population may be a reservoir and source of infection (20). When the number of CD4+ T cells is severely decreased, as in AIDS, sporozoites are released from the cysts, become trophozoites, increase in size, and mature into new cysts (1). Patients with CD4+ T cell counts of less than 200/mm³ are at highest risk for PCP (21).

In AIDS patients, Pneumocystis infection is with few exceptions limited to the lungs; it results in severe, acute, bilateral pneumonia, which is fatal if not treated (10,11,12). In HIV-infected infants and children, P. jiroveci is a major cause of pneumonia and death (22). Occasionally, the presentation is insidious, with the nonspecific symptoms developing slowly. In either case, the lesion is a foamy, granular, eosinophilic, intraalveolar fibrinous exudate containing numerous Pneumocystis organisms (23). With the introduction of anti-Pneumocystis drugs, particularly pentamidine, survival has increased; however, occasional cases of disseminated pneumocystosis have been reported (24,25,26,27,28,29,30). Although administering pentamidine as an aerosol rather than intravenously cleared the lungs of Pneumocystis organisms, it failed to prevent dissemination of the infection because the serum levels generated were insufficient to eradicate the organisms (31,32,33,34). In its rare disseminated form, pneumocystosis may involve bone marrow, lymph nodes, liver, spleen, heart, kidney, thyroid, adrenals, and other organs (23,24,25,26,27,28,29,30,31,32,33,34,35,36,37). Clinical symptoms and signs reflect the organs affected, and autopsies have confirmed widespread dissemination of the disease.