Pneumocystis pneumonia (PCP), an opportunistic infection attacking the lungs, can be a harbinger of other diagnoses.
Case Presentation
A 39-year-old male with no past medical history presents to the ED via EMS for ongoing shortness of breath. Symptoms started about a month ago with associated night sweats and low-grade fevers. He lost about 37 pounds in the past year. Travel history includes a move from Mexico to the U.S. about 20 years ago. He works as a landscaper, is a chronic smoker, and is sexually active with a female and had one encounter with a male in the past couple years.
On exam, he is ill-appearing, febrile, tachycardic, tachypneic in the mid-30s saturating in the low 90s on 6L via nonrebreather. A bedside chest radiograph was obtained.
Discussion
Pneumocystis pneumonia (PCP), a leading cause of opportunistic infections in individuals with HIV and low CD4 cell counts, has seen a dramatic decline due to effective antiretroviral therapy (ART) and prophylaxis. However, it remains a significant concern, especially for those unaware of their HIV status or not receiving medical care. PCP—sometimes known as pneumocystis jirovecci pneumoniae or PJP—is caused by the fungus Pneumocystis jirovecii, primarily transmitted via the airborne route and existing almost exclusively within the alveoli of the lungs. The immune response to PCP involves CD4 T cells, which coordinate the host inflammatory response, and alveolar macrophages, which mediate organism clearance.
Diagnosis
Risk factors include advanced immunosuppression, low CD4 cell counts, oral thrush, recurrent bacterial pneumonia, and unintentional weight loss. Clinical manifestations of PCP typically include gradual onset of fever, cough, and dyspnea over days to weeks, with physical examination findings often showing fever and tachypnea. Common laboratory findings include low CD4 counts, poor oxygenation, abnormal diffusion capacity, and elevated lactate dehydrogenase (LDH).
Radiographic manifestations of PCP include diffuse interstitial or alveolar infiltrates on chest radiographs, and high-resolution computed tomography often shows bilateral patchy or nodular ground glass opacities.
PCP should be suspected in HIV patients with a CD4 count less than 200, especially those not receiving ART, who present with characteristic symptoms such as dyspnea, hypoxemia, and cough, along with diffuse interstitial or alveolar infiltrates on imaging. Empiric treatment is recommended in acutely ill patients with high clinical suspicion, as diagnostic testing can be delayed.
Diagnostic tests on respiratory specimens include PCR, DFA staining, and general fungal staining. A definitive diagnosis is ideal but may not always be possible. In such cases, a presumptive diagnosis based on clinical features, and the absence of alternative diagnoses, may be sufficient. Monitoring for co-infections and other diseases, such as tuberculosis, nontuberculous mycobacteria, various fungi, toxoplasmosis, cytomegalovirus, influenza, COVID-19, and Kaposi sarcoma, is crucial given their similar presentations in immunocompromised patients. Extrapulmonary PCP is rare but can occur in severely immunocompromised individuals, often involving the eye, ear, thyroid, spleen, and bone marrow, with diagnosis typically made via histological examination of affected tissues.
Treatment
The primary treatment for PCP involves antimicrobial therapy targeted at P. jirovecii, often supplemented with adjunctive corticosteroids. Initiating ART is also essential to restore immune function, and for patients already on ART, their regimen is continued during PCP treatment.
The treatment approach varies based on the severity of the disease, which is determined by the level of oxygenation and the alveolar-arterial oxygen gradient (A-a gradient).
- Mild disease (A-a O2 gradient <35 mmHg and/or PaO2 ≥70 mmHg), oral TMP-SMX is preferred. Alternative regimens include trimethoprim-dapsone, clindamycin-primaquine, or atovaquone, and corticosteroids are not required.
- Moderate disease (A-a O2 gradient ≥35 and <45 mmHg and/or PaO2 ≥60 and <70 mmHg) also warrants oral TMP-SMX, but requires adjunctive corticosteroids.
- Severe disease (A-a O2 gradient ≥45 mmHg and/or PaO2 <60 mmHg): intravenous TMP-SMX and corticosteroids are recommended.
The standard dose of TMP-SMX for PCP is 15 to 20 mg/kg/day, adjusted for severity and administered either orally or intravenously. Corticosteroids should be initiated for moderate to severe PCP to reduce mortality and respiratory failure. The recommended regimen is a tapered course of prednisone, starting with 40 mg twice daily for 5 days, then 40 mg daily for 5 days, and finally 20 mg daily for 11 days. Intravenous methylprednisolone can substitute for prednisone in severe disease.
Prognosis
Most patients with PCP improve with treatment, but some may develop progressive respiratory failure despite appropriate therapy. Prognosis is worse for patients with severe hypoxia at presentation, and mortality is high among those requiring intensive care or mechanical ventilation. Initiating ART improves outcomes, with early ART providing the best benefit.
Patients with treatment failure should be evaluated for a concurrent infection, as approximately 15% of patients with PCP have more than one opportunistic infection. This evaluation may involve more invasive testing such as bronchoalveolar lavage. For patients with severe respiratory failure, empiric therapy directed at one or more of these infections may be indicated while the results of diagnostic tests are pending. Some patients may be stable initially but worsen clinically two to three days after starting anti-Pneumocystis therapy due to increased inflammation in the lungs as the organisms are killed. Patients with respiratory failure should also be assessed for pneumothorax, as individuals with PCP are at risk for pneumothorax both spontaneously and in the setting of mechanical ventilation.
Prevention
After completing an initial 21-day course of treatment, patients should continue to receive antimicrobial therapy at a reduced dose to prevent recurrent infection (secondary prophylaxis). PCP prophylaxis is recommended for patients with a CD4 count of less than 200.
Case Conclusion
The patient was HIV+ with a CD4 count of 6. He was diagnosed with PCP via bronchoscopy. He was treated with TMP/SMX, steroids, and started on ART. He did well and was discharged for continued outpatient treatment of HIV and PCP.
References
UpToDate. UpToDate. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-infection-in-patients-with-hiv?search=pcp+pneumonia&topicRef=3704&source=see_link#H1154921003.