Pneumocystis pneumonia (PCP) is an opportunistic infectious disease caused by Pneumocystis species, a genus of single-celled fungi found in the respiratory tracts of mammals and humans. Previously referred to as Pneumocystis carinii, genomic sequencing in the 1980s revealed its classification as a fungus. In 2002, it was renamed Pneumocystis jiroveci, the species specific to humans.
Etiology and Pathogenesis
Pneumocystis exists in three structural forms: trophozoites, cysts, and intracystic spores. It can parasitize various animals, including mice, dogs, cats, rabbits, sheep, pigs, horses, and monkeys, as well as healthy humans. It is widely distributed in the environment, such as in soil and water. Different strains of Pneumocystis exhibit host specificity, and Pneumocystis jiroveci is the species that infects humans. Its cysts are thin-walled, round, and measure 5-8 μm in diameter. PCP is the most common and severe opportunistic infection in immunocompromised patients.
PCP is transmitted through airborne routes or by reactivation of latent Pneumocystis within the body. The organism proliferates in the lungs, gradually filling the alveolar spaces and causing vacuolization and desquamation of alveolar epithelial cells. Pulmonary interstitial congestion and edema occur, with widening of the alveolar septa. Lymphocytes, macrophages, and plasma cells infiltrate the interstitial tissue, and neutrophils and eosinophils may also be present.
Clinical Manifestations
The incubation period of PCP is generally around two weeks, but it may extend to approximately four weeks in AIDS patients. The disease shows no gender or seasonal preference. Clinical manifestations vary widely depending on the individual and the stage of the disease.
Epidemic PCP
This PCP primarily affects premature infants and malnourished children aged 2-6 months, often spreading within infant care facilities. The onset is typically insidious, with slow progression. Early symptoms include irritability, reduced appetite, diarrhea, low-grade fever, and weight loss. Gradually, dry cough, dyspnea, nasal flaring, and cyanosis develop, with progressive respiratory distress. Splenomegaly may occasionally occur. The disease course lasts 3-8 weeks, and without timely treatment, patients may die from respiratory failure, with a mortality rate of 20%-50%.
Sporadic PCP
This PCP is more common in immunocompromised individuals but can occasionally occur in healthy individuals. In patients undergoing chemotherapy or organ transplantation, PCP progresses rapidly, while in AIDS patients, the progression is slower. Early symptoms include anorexia and weight loss, followed by dry cough, fever, cyanosis, and dyspnea. Respiratory distress develops quickly, and without timely diagnosis and treatment, the mortality rate can reach 70%-100%. A notable feature of PCP is the dissociation between symptoms and physical findings: severe symptoms may occur with minimal physical signs. Recurrence is not uncommon, particularly in AIDS patients.
Laboratory and Other Examinations
Blood Tests
Peripheral blood white cell counts may be elevated or decreased, with eosinophilia and reduced absolute lymphocyte counts. Arterial blood gas analysis shows hypoxemia and respiratory alkalosis. Lactate dehydrogenase (LDH) levels are significantly elevated. The (1→3)-β-D-glucan (G-test) may also be elevated.
Pulmonary Function Tests
Tidal volume, total lung capacity, and diffusion capacity are reduced.
Imaging
Early chest X-rays typically show diffuse alveolar and interstitial infiltrates, appearing as bilateral perihilar diffuse exudates with a reticular or small nodular pattern. Progression leads to butterfly opacities in the perihilar regions, with pulmonary consolidation and air bronchograms.
Pathogen Detection
Pathogen identification can be performed using sputum or induced sputum samples. Bronchoscopic brushing, lung biopsy, bronchoalveolar lavage, percutaneous lung puncture, or open lung biopsy specimens can be stained to observe cyst walls and spores.
Molecular Diagnosis
Nucleic acid testing for Pneumocystis jiroveci is also helpful for diagnosis.
Diagnosis
The diagnosis of PCP is based on clinical presentation, imaging findings, and laboratory results, with confirmation through pathogen detection or nucleic acid testing.
Treatment
In addition to symptomatic and underlying disease management, pathogen-directed therapy is the mainstay of treatment. The first-line therapy is trimethoprim-sulfamethoxazole (TMP-SMZ) at a dose of TMP 15-20 mg/kg/day or SMZ 75-100 mg/kg/day, divided into 3-4 doses, administered orally or via intravenous infusion for 2-3 weeks. If TMP-SMZ is ineffective or not tolerated, alternative treatments include:
- Dapsone
- Clindamycin + Primaquine
- Trimethoprim + Dapsone
- Atovaquone
Echinocandin antifungal agents, such as caspofungin, have also shown good efficacy against PCP.
Glucocorticoids can suppress the inflammatory response in PCP and reduce mortality in HIV-associated PCP. However, there is no clear evidence supporting their use in non-HIV-associated PCP. For patients with a partial pressure of arterial oxygen (PaO2) ≤ 70 mmHg, early administration of prednisone is recommended as follows:
- 40 mg twice daily for 5 days,
- 40 mg once daily for 5 days,
- 20 mg once daily for 10 days, followed by discontinuation.
Preventive treatment may be considered for high-risk populations.