Basic features of Pneumocystis
Pneumocystis is a yeast-like fungus.
- Previously classified as a protozoan
- Isolated in host alveolar spaces
- Cell wall consists of carbohydrates rich in:
- Asexual phase (binary fission)
- Sexual phase
- Trophic form:
- Thin walled
- Variable size
- Pseudohyphal structures
- Predominant form during active infection
- Cyst form (spore form):
- Contains 8 intracystic bodies
- Thick walled with an outer membrane
- Allows survival outside the lungs
- Releases trophic forms once matured
- Trophic form:
Clinically relevant species
P. jirovecii (formerly known as P. carinii) causes pneumocystis pneumonia (PCP).
Epidemiology and Pathogenesis
- Rare amongst immunocompetent individuals
- Incidence varies depending on patient risk factors, but is generally < 5% in immunocompromised patients:
- Closer to 6% in solid-organ transplant recipients
- < 1% in patients with hematologic malignancy or HIV
- Rate is declining in the United States due to prophylactic measures.
The reservoir for P. jirovecii is unknown, but immunocompetent humans may play a role.
P. jirovecii spreads through airborne transmission.
Host risk factors
Pneumocystis pneumonia occurs in immunocompromised individuals:
- HIV with CD4 count < 200 cells/μL (an AIDS-defining condition)
- Impaired cellular immunity
- Organ transplantation
- Immunosuppressive therapy
- Hematologic malignancies
- Major surface glycoprotein (MSG) or glycoprotein A:
- Main surface antigen
- MSG locus can undergo recombination to avoid host defenses.
- Binds to:
- Surfactant protein D (protein within lung collagen) of the host
- Macrophages of the host
- Biofilm formation provides a survival advantage.
- P. jirovecii is inhaled into the alveolar space → trophic form attaches to alveolar epithelium
- Both humoral and cell-mediated immunity are essential to host defense:
- CD4 lymphocytes are the principal regulator of the host response.
- Immunocompetent individuals can eradicate the organism or become colonized.
- In patients with impaired cell-mediated immunity:
- Patients cannot adequately clear the infection.
- Inflammation → alveolar damage → impaired gas exchange
Clinical Presentation and Diagnosis
Pneumocystis pneumonia can present in a nonspecific manner compared to other types of pneumonia.
Presentation may be subacute and evolve over the course of weeks:
- Chest pain
- Dry cough
- Respiratory failure
- Chest X-ray may show a variable presentation depending on severity:
- Normal in 10%–15%
- Bilateral, patchy opacities
- Subpleural blebs
- Chest CT generally shows diffuse ground glass opacities and may be compounded by:
- Alveolar airspace disease
- Reticular opacities
- Septal thickening in presence of ground glass opacities is referred to as “crazy paving.”
- Mediastinal lymphadenopathy (uncommon)
- Nodules may form cavities or “tree-in-bud” opacities.
- Thin-walled cysts (pneumatoceles) may progress to pneumothorax.
- Extrapulmonary inflammatory changes may also be seen on imaging of the:
- Demonstration of cysts or trophozoites in tissue or body fluids:
- Common modalities:
- Induced sputum
- Bronchoalveolar lavage (BAL)
- Transbronchial biopsy
- Video-assisted thoracoscopic surgery (VATS) biopsy (rarely used)
- Open lung biopsy (extremely rare)
- Common stains:
- Methenamine silver
- Toluidine Blue O
- Monoclonal antibody staining
- Common modalities:
- Immunofluorescence assays
- PCR of induced sputum or BAL fluid
- ↑ WBC (note: can be ↓ or normal in HIV infection when baseline WBC is low)
- ↑ LDH (reflects tissue damage, but is nonspecific)
- ↑ β-D-glucan (component of fungal cell wall, but is nonspecific)
- Arterial blood gas:
- PaO2 and alveolar-arterial oxygen gradient may be used to determine severity.
General treatment strategies
- Address any respiratory distress with supplemental oxygen.
- Hemodynamic support in patients with shock physiology
- Manage etiology of immunosuppression.
- Trimethoprim-sulfamethoxazole (TMP-SMX) combination is the 1st line:
- For moderate disease: Oral route is preferred, consider adding corticosteroids.
- For severe disease: Use IV TMP-SMX plus corticosteroids.
- Alternative agents (prior reaction to TMP-SMX or glucose-6-phosphate-dehydrogenase (G6PD) deficiency):
- Trimethoprim plus dapsone
- Clindamycin plus primaquine
Prophylaxis varies depending on the etiology of the immunocompromised state:
- HIV patients with CD4 count < 200 cells/μL or presence of oropharyngeal candidiasis:
- TMP-SMX is the 1st line agent.
- Dapsone is an alternative.
- Stop prophylaxis therapy once CD4 count > 200 cells/μL.
- Patients on chronic steroids: Continue TMP-SMX until steroids are < 20 mg daily.
- Patients receiving chemotherapy or immunosuppressive agents temporarily: TMP-SMX until treatment is complete and the immune system has recovered.
- Transplant recipients:
- TMP-SMX should be given as long as high-dose immunosuppressive therapy is required.
- Lifelong therapy is typically required in lung transplant patients.
Complications and Prognosis
Complications of PCP include:
- ARDS: Address with invasive or noninvasive ventilation, and high-flow oxygenation (depending on severity).
- May contribute to pneumomediastinum and pneumothorax
- If possible, avoid high levels of positive pressure ventilation.
- Pneumothorax: may require chest tube placement or needle decompression (if tension physiology is present)
- Secondary infections:
- May be bacterial, fungal, or viral
- Supported by additional culture data
- Treat with appropriate antimicrobials.
Early recognition and initiation of therapy improves prognosis.
Factors negatively impacting outcomes:
- Old age
- Coexisting viral pneumonia
- ICU requirement
- Other infectious pneumonias: can be viral, bacterial, or fungal. Patients may present with fever, shortness of breath, cough, and malaise. A thorough history should address risk factors for COVID-19, influenza, tuberculosis, and Mycoplasma pneumonia. Diagnosis is based on history, exam, imaging, cultures, and viral testing. Treatment includes supportive care, supplemental oxygenation, and antimicrobials.
- Protein alveolar proteinosis: a rare disease characterized by abnormal intra-alveolar accumulation of surfactant-derived, lipoproteinaceous material. Protein alveolar proteinosis is classically associated with a pattern of crazy paving on CT scan. Diagnosis is based on BAL staining, and supported by granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies and clinical history. Treatment may involve whole-lung BAL and GM-CSF supplementation.
- Pneumonitis: inflammation of the lung tissue commonly related to a variety of exposures, including medication, aspiration, environmental, and/or radiation. Patients can present with an acute or chronic process with symptoms resembling an infectious process. Diagnosis is clinical and radiological. Infection should be ruled out. Treatment includes eliminating the offending agent, addressing the underlying cause, and corticosteroids or other immunosuppressive agents.
- Pulmonary hemorrhage: commonly related to an inflammatory process, which may include vasculitis, connective tissue disease, infection, medication, and coagulopathy. Pulmonary hemorrhage may present as a cough (with or without hemoptysis), fever, chills, and/or shortness of breath. Diagnosis is made with clinical history, imaging, and alveolar fluid analysis. Treatment includes supportive care, respiratory support with supplemental oxygenation, and addressing the underlying cause.
- Cryptogenic organizing pneumonia: an inflammatory and scarring form of idiopathic, interstitial pneumonia, which leads to obstruction of the small airways and alveoli. Patients may present with flu-like symptoms. Diagnosis is made radiologically after infection has been ruled out. Cryptogenic organizing pneumonia is considered idiopathic in etiology, and treatment generally consists of steroids.
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