Pneumocystis Pneumonia
Allen P. Burke, M.D.
Background
Pneumocystis organisms were first described in rats and guinea pigs in the early 20th century as protozoa related to trypanosomes (reviewed by Catherinot et al.1). Pneumocystis was recognized as a fungus relatively recently, based on rRNA sequencing.2 In the 1950s, the first human infections were identified in malnourished and premature infants and rarely in adults.3,4 Later, pneumocystis pneumonia (PCP) was a recognized pathogen in immunocompromised children5,6 and then in adults with HIV disease. The routine use of highly active antiretroviral therapy (HAART) has seen a decline in its incidence,7 and the primary clinical setting of PCP is no longer AIDS, but immunosuppression secondary to chemotherapy for hematologic malignancies.8
Pneumocystis has its own class, order, and family under the phylum Ascomycota. The organism was known as Pneumocystis carinii for many years, named after one of the first discoverers of the organism in animals. Although the human species was recommended to be called “jiroveci” (after one of the first discoverers of human infection) as long ago as 1976,9 only in 2001 was it decided to use the designation carinii specifically for one of the animal species of the fungus.10 The current accepted designation for the human pathogen is “jirovecii” (with two terminal “Is”).1
Pneumocystis jirovecii is a normal bronchial inhabitant in infants and children, with serologic conversion common at an early age.1 Although species of pneumocystis are found in diverse reservoirs, including in bats, swine, hens, as well as rats and guinea pigs, no animal reservoir for P. jirovecii has been found.1,11 Most studies have shown 0% to 20% colonization rate in healthy adults, although there is a wide range of sampling and methodology for detection of the organism. Using sensitive polymerase chain reaction (PCR) techniques and tissue concentration methods, the organism has been identified in nearly two-thirds of traumatic and natural deaths in adult lungs.12 There is an increased incidence of bronchial colonization in chronic lung disease, smoking, HIV, steroid use, and children.1
Clinical Settings of Pneumocystis Pneumonia
Before AIDS and the widespread use of immunosuppressive drugs, PCP was a rare disease, reported in only 10 patients per year in the United States, mostly children with immunodeficiency or acute leukemia (Table 42.1).5
Although the largest numbers of PCPs were seen in the early years of the AIDS epidemic, the rate of PCP in HIV-infected adults has dropped to 0.3 per 100 person-years in developed countries. This figure represents a more than 10-fold decrease compared to era of HIV therapies before the availability of HAART.15 Despite the decline in incidence since the beginning of the AIDS epidemic, P. jirovecii pneumonia remains the most common cause of respiratory failure in HIV patients even in the HAART era, for which the mortality rate remains around 10%.16,17,18 In this group of patients, CD4 as biomarker works well, with a cutoff of 200 cells per µL of blood, or 15% of T cells, a reliable indication for treatment prophylaxis.
Primary immunodeficiency syndromes predispose to PCP, usually those affecting T cells.6 Most patients are infants under 1 year of age, and two-thirds suffer from severe combined immunodeficiency.5 The incidence of pneumocystis ranges between one-fourth and one-half of patients prior to bone marrow transplant, depending on whether the infant is on pneumocystis prophylaxis.6,19,20 PCP is rare in pure B-cell disorders and agammaglobulinemia.21
The rate of PCP complicating hematologic and solid malignancies is fairly low, in the range of 1% to 2%. Immunosuppression by steroids especially predisposes to pneumocystis infection, although a large number of drugs have been implicated.
Prior to routine prophylaxis, PCP was relatively common in solid organ transplants, occurring in up to 50% of heart transplant recipients and 10% of kidney and liver transplants. Currently, the rate is closer to 1%, affecting patients who did not receive prophylaxis or who discontinued trimethoprim-sulfamethoxazole.22 The rate is slightly higher in patients with allogeneic stem cell transplant, and similarly occurs in patients who are no longer on prophylaxis, typically with low CD4 counts or with recurrent malignancy.23
Autoimmune connective tissues have a low rate of pneumocystis infection complicating immunosuppression, generally <0.5%. Virtually any condition treated with steroids may predispose to PCP including steatohepatitis.24
Clinical and Radiologic Findings
PCP is in the differential diagnosis of an immunocompromised patient with bilateral pulmonary infiltrates, typically with fever and cough. The major clinical diagnostic considerations include other infections, interstitial pneumonia (usually diffuse alveolar damage or organizing pneumonia), drug toxicity, and malignancy (Table 42.2). Serologic screening for 1,3-beta-D-glucan may be useful in diagnosing invasive fungal infection, but is not specific for pneumocystis.28
TABLE 42.1 Clinical Settings of Pneumocystis Pneumonia | ||||||||||||||||||
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On chest radiograph, PCP usually presents with bilateral, diffuse, reticular, or granular opacities. Up to one-fourth of patients have predominantly nodular densities.29 Chest radiograph may be normal. Chest computed tomography typically shows ground-glass opacities predominating in perihilar regions of lungs.30 Atypical patterns are more common currently with treatment and prophylaxis and include predominantly upper lobe disease, pneumothorax, and cyst formation (Fig. 42.1). Cyst formation, which may lead to pneumothorax, may reverse with treatment.31 Other atypical findings include large nodules or areas of consolidation that may cavitate with thick walls. Lymphadenopathy and effusions are infrequent.30
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