| disease | Pneumocystis Carinii Pneumonia |
| alias | PCP, Pneumocystis Carinii Pneumonia, Interstitial Plasma Cell Pneumonia |
Pneumocystis carinii pneumonia (PCP), also known as Pneumocystis pneumonia or interstitial plasma cell pneumonia, is a rare form of pneumonia that primarily occurs in immunocompromised children.
bubble_chart Pathogen
The pathogen is Pneumocystis carinii, which exists in both trophozoite and cyst forms, primarily residing in the lungs. It was previously classified as a protozoan, but recent studies based on its ultrastructure and phylogenetic analysis of ribosomal RNA suggest that Pneumocystis belongs to the fungal kingdom. In 1951, Vanek first reported the presence of Pneumocystis carinii in cases of interstitial plasma cell pneumonia among {|###|}premature labor{|###|} infants. Over the past few decades, the widespread use of immunosuppressants and chemotherapy for {|###|}tumor diseases{|###|} has led to an increased incidence of this condition. Particularly in the last decade, with the emergence of Acquired Immune Deficiency Syndrome (AIDS), Pneumocystis pneumonia (PCP) has garnered significant attention. According to data from the U.S. CDC, from 1981 to 1990, 1,200 pediatric AIDS cases were reported, with PCP being the most common and severe opportunistic infection, occurring in 39% of cases, while in adult AIDS patients, the rate could be as high as 80%. Pneumocystis {|###|}cysticercosis{|###|} primarily affects five groups of patients: ① {|###|}premature labor{|###|} infants and newborns; ② children with congenital or secondary immunodeficiency; ③ patients with malignancies such as leukemia or lymph {|###|}tumor diseases{|###|}; ④ children undergoing immunosuppressive therapy after organ transplantation; and ⑤ children with AIDS. As early as the 1950s, a few cases of PCP were identified in Beijing. In the mid-1980s, Beijing Children's Hospital reported 16 cases of PCP occurring in leukemia patients during the {|###|}stage of remission{|###|}. Animal models and clinical observations have demonstrated a strong correlation between PCP and impaired T-lymphocyte immune function. Currently, international guidelines suggest that a CD4
(helper T-cell) count of ≤200/mm3 significantly increases the risk of PCP, though this standard does not apply to children, especially those under one year of age.bubble_chart Pathological Changes
The lungs show extensive and severe involvement visible to the naked eye, with a texture and color resembling the liver. The alveoli and bronchioles are filled with foamy material, a mixture of necrotic parasites and immunoglobulins. The alveolar septa are infiltrated by plasma cells and lymphocytes, causing thickening of the septa to 5–20 times the normal thickness, occupying three-quarters of the total lung volume. Initially, cysts are located within the cytoplasm of macrophages in the alveolar septa. Subsequently, alveolar cells containing cysts detach and enter the alveolar space, or the sporozoites within the cysts proliferate and mature, leading to cyst wall rupture and the release of sporozoites as free trophozoites into the alveolar space. The alveolar exudate contains plasma cells, lymphocytes, and histiocytes.
bubble_chart Clinical Manifestations
1. Symptoms and signs can be divided into two types: ① Infantile type: Mainly occurs in infants aged 1 to 6 months, belonging to interstitial plasma cell pneumonia. The onset is slow, with main symptoms including poor feeding, dysphoria, cough, increased respiratory rate, and cyanosis, while fever is not prominent. Few rales are heard during auscultation, and respiratory distress gradually worsens within 1–2 weeks. The disproportion between the scarcity of lung signs and the severity of respiratory distress symptoms is one of the characteristics of this disease. The course lasts 4–6 weeks, and without treatment, about 25–50% of affected children die. ② Childhood type: Mainly occurs in children with compromised immune function due to various causes. The onset is acute, differing from the infantile type in that almost all patients have fever. Additionally, common symptoms include rapid breathing, cough, cyanosis, retractions, nasal flaring, and diarrhea. The disease progresses rapidly, and most cases are fatal without treatment.
bubble_chart Auxiliary Examination
The white blood cell count is normal or slightly elevated, with approximately half of the cases showing lymphocytopenia and grade I eosinophilia. Blood gas analysis reveals significant hypoxemia and an increased alveolar-arterial oxygen gradient. Pulmonary function tests demonstrate progressive deterioration.
The diagnosis relies on observing clusters of foamy eosinophilic material in the alveoli containing protozoa in tracheal aspirates or lung biopsy tissue sections stained with methenamine silver nitrate, which reveals dark brown, round, or oval cysts measuring 6–8 μm in diameter, located extracellularly. In recent years, hypertonic saline nebulization has been used to improve pathogen detection rates. Additionally, bronchial alveolar lavage and bronchial lung biopsies have shown a cyst detection rate of up to 90%. Staining methods for cysts include Toluidine blue, methenamine silver, Gömöri-Grocott, Gram-Wright, Giemsa, and immunofluorescence antibody staining. Recently, ELISA has been employed to detect Pneumocystis IgG antibodies, latex particle agglutination tests for cyst antigens, and molecular biology techniques such as PCR for rapid early diagnosis.
For etiological treatment, pentamidine isothionate was previously commonly used at a dose of 100–150 mg/(m2·d) or 4–5 mg/(kg·d), administered intramuscularly for 10–14 days. It could also be inhaled as an aerosol. Early application of this drug could cure at least 60% of affected children, but approximately half of them might experience severe side effects such as local sterile abscesses, rashes, hypotension, nausea, vomiting, vertigo, hypoglycemia, hypocalcemia, megaloblastic anemia, thrombocytopenia, neutropenia, and liver or kidney function impairment. Currently, the first-line drugs are trimethoprim (TMP) at 20 mg/(kg·d) combined with sulfamethoxazole (SMZ) at 100 mg/(kg·d), divided into two doses and taken for two weeks. The efficacy is comparable to pentamidine, but the side effects are far less common, mainly manifesting as skin allergies and gastrointestinal reactions. Some also advocate using SMZCo at 100 mg/(kg·d) for two weeks, then reducing to half the dose for another two weeks, followed by a quarter of the dose for two months, achieving an efficacy rate of 75%. This drug can also serve as a chemoprophylactic agent to prevent the disease in high-risk children receiving immunosuppressive therapy, with a dose of TMP 5 mg/(kg·d) and SMZ 25 mg/(kg·d), both divided into two oral doses or taken continuously for three days per week with four days off, for six months.
Supportive therapy includes intramuscular injection of gamma globulin or placental globulin to enhance immunity. Oxygen therapy may be administered if necessary. If the disease occurs during the use of adrenal corticosteroids, the dose should be reduced or discontinued. To prevent cross-infection in high-risk children, recent recommendations advocate respiratory isolation until the treatment is completed.
Poor prognosis. Foreign reports indicate a mortality rate of 10-50%, averaging around 40%. However, recent studies suggest that with timely and aggressive treatment, the cure rate can reach as high as 70%.
This disease needs to be differentiated from bacterial pneumonia, viral pneumonia, fungal pneumonia, ARDS, and lymphocytic interstitial pneumonia (LIP). Among these, LIP is particularly difficult to distinguish from this disease, as both are prone to occur in children with AIDS. However, LIP is mostly chronic, characterized mainly by cough and dry rales, accompanied by generalized lymph node enlargement and salivary gland enlargement. EBV-DNA can be detected in lung biopsy specimens1, whereas PCP cannot be detected.
