Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jiroveci parasitizing the lungs, mostly in immunocompromised patients, such as, such as HIV-infected individuals, tissue and organ transplant recipients, and patients undergoing radiotherapy and chemotherapy for malignant tumors.
Etiology and pathogenesis
Pneumocystis has three structural forms, namely trophozoite, cyst, and sporozoite (intracystic body). Pneumocystis can parasitize various animals, such as mice, dogs, cats, rabbits, sheep, pigs, horses, and monkeys, and can also parasitize healthy humans. It is widely distributed in nature, such as soil and water. Different strains have host specificity. Pneumocystis jiroveci is a pathogen that infects humans specifically, with a thin-walled, round, 5 - 8μm cyst. PCP is the most common and most serious opportunistic infection in immunocompromised patients.
The infection route of PCP is airborne transmission and activation of latent Pneumocystis in the human body. The fungus reproduces in the lungs and gradually fills the entire alveolar cavity, causing vacuolation and shedding of alveolar epithelial cells. The pulmonary interstitium is congested and edematous, and the alveolar septa are widened. Lymphocytes, macrophages, and plasma cells infiltrate the interstitium, and neutrophils and eosinophils can also be seen.
Clinical manifestations
The incubation period of PCP is generally 2 weeks, while the incubation period in AIDS patients is about 4 weeks. There is no gender or seasonal difference in the onset. The clinical manifestations of PCP vary greatly in different individuals and different courses of the disease.
Epidemic or classic PCP is mainly seen in premature infants and malnourished infants, mostly aged 2 - 6 months, and can be prevalent in infant care institutions. The disease presents with insidious onset and slow progression. The clinical manifestations include sleep refusal, apositia, diarrhea, low-grade fever, and emaciation in the early stage; followed by dry cough, tachypnea, progressive aggravation, dyspnea, nasal flaring, and cyanosis. Sometimes splenomegaly may occur. The course of the disease generally lasts for 3 - 8 weeks. If not treated promptly, patients may die of respiratory failure, and the mortality is 20% - 50%.
Sporadic or modern PCP is more common in immunocompromised patients and occasionally in healthy individuals. PCP progresses rapidly in patients with chemotherapy or organ transplantation, but slowly in AIDS patients. The symptoms include anorexia, emaciation in the early stage; followed by dry cough, fever, cyanosis, dyspnea, and respiratory distress. If not treated properly, the mortality is 70% - 100%. PCP patients often present separated symptoms and signs; that is, although the symptoms are severe, the signs are often absent. Relapses are present in few patients, particularly in AIDS patients.
Laboratory and auxiliary examinations
The leukocyte count in the peripheral blood is generally elevated, but declined in some patients, eosinophils are increased, and the absolute value of lymphocytes are decreased. Arterial blood gas shows hypoxemia and respiratory alkalosis. Lactate dehydrogenase is significantly increased. Serum 1,3-β-D-glucan (BDG) may be increased. The tidal volume, total lung volume, and diffusion capacity are reduced.
Chest x-ray shows that the typical early changes are diffuse alveolar and interstitial infiltrative opacities, manifested by diffuse exudation around the bilateral hilar area, with reticular and nodular opacities, followed by butterfly opacities at the bilateral hilar area, revealing pulmonary consolidation and bronchial inflation signs.
Etiological examination can use sputum or induced sputum specimens. Specimens from bronchial brushing, lung biopsy, alveolar lavage, percutaneous lung puncture, or open lung biopsy can be stained and used to observe cyst walls and sporozoites.
Diagnosis
Since Pneumocystis cannot be easily cultured in the laboratory, microscopic examination of pathogens in respiratory specimens has always been the gold standard for diagnose of PCP. Nucleic acid testing is also helpful for the diagnosis of this disease.
Treatment
In addition to symptomatic treatment and treatment of underlying diseases, pathogen-oriented treatment is the main strategy. Trimethoprim-sulfamethoxazole (TMP-SMZ) is preferred, and the dosing regimen is TMP 15 - 20 mg/(kg.d) or SMZ 75 - 100 mg/(kg.d) orally or intravenously in 3 - 4 divided doses for 2 - 3 weeks. If there is resistance or intolerance to TMP-SMZ, dapsone, clindamycin plus primaquine, trimethoprim plus dapsone, and atovaquone can also be chosen. Echinocandin antifungal drugs such as caspofungin also have a good effect against PCP. In addition, glucocorticoids can inhibit the inflammatory response of PCP and reduce the mortality in patients with concurrent HIV and PCP, but there is no clear evidence-based medical evidence in non-HIV patients with PCP. In patients with PaO2 ≤ 70 mmHg, the treatment plan is prednisone orally 40mg twice a day for 5 days, followed by 40 mg once a day for 5 days, followed by 20 mg once a day for 10 days. Clinically, prophylactic treatment can be used for high-risk populations.