Thanks to Dr. Michael Chung for presenting today’s case about a young transgender woman with a history of untreated HIV who presented with gradual onset fever, cough, and acute hypoxic respiratory failure with a high A-a gradient, found to have PJP pneumonia on induced sputum. A special thanks to Dr. Kirsch for attending morning report and giving us stellar clinical pearls.

The differential for pulmonary symptoms in an HIV patient is broad, including typical viral, bacterial, and fungal etiologies with the addition of PJP, TB, MAC, toxo (other parasites including strongyloides, microsporidium, and crypto), lymphoma, Kaposi’s sarcoma, and immune reconstitution syndrome (if ART has been recently started).

Epidemiology:

Basics: HIV and severely immunocompromised

PJP is the most common AIDS-defining opportunistic infection in the US. It affects severely immunocompromised patients including HIV with CD4<200, hematologic malignancies, transplant patients, chronic steroids, and severe malnutrition. Risk factors that should raise your clinical suspicion for PJP are history of previous PJP or recurrent bacterial pneumonia, high viral loads, unintentional weight loss, or presence of oral thrush.

Clinical Presentation:

Basics: 3 weeks of nonproductive cough, dyspnea, and constitutional symptoms, now with hypoxic respiratory failure

HIV patients with PJP typically present with gradual worsening of symptoms over days to weeks (average 3 weeks): nonproductive cough (95%), fever (80-100%), and dyspnea (95%). Chills, chest pain, and unintentional weight loss are also commonly present. Physical exam usually reveals tachypnea and desaturations, but lung exam can be clear in 50% of patients.

Lab Evaluation:

Basics: LDH and B-D Glucan are sensitive, but nonspecific indicators of PJP that can help you decide to treat empirically if confirming the diagnosis in a timely manner is impractical. 

LDH is nonspecific, but very sensitive (elevated in >90% of HIV patients with PJP). LDH has been proposed as a prognostic marker in PJP pneumonia as those who do not survive PJP despite treatment were observed to have higher initial LDH levels than those who did survive. LDH can also be trended throughout treatment to evaluate response and prognosis. B-D-glucan, a component of fungal cell walls, is also nonspecific, but is elevated in PJP pneumonia. Due to the high mortality of untreated PJP pneumonia in HIV patients, these lab tests can raise your clinical suspicion for the disease and help you decide to treat empirically in the absence of confirmed diagnosis.

It is necessary to get an ABG in all patients with suspected PJP pneumonia to calculate the Alveolar-arterial oxygen gradient. This indicates severity of disease and will be useful in deciding on whether to give steroids with your antibiotics.

A-a gradient at sea level on room air= [150- PaCO2/0.8] – PaO2. Normal is <10 but increases with age.

Imaging: 

Basics: PJP can cause almost any presentation on CXR/CT but diffuse bilateral infiltrates is most common. CXR is not sensitive so get a CT if clinical suspicion is high. 

25% of chest XRs of HIV patients with PJP are normal. The most common manifestations is diffuse bilateral infiltrates, but PJP can present in almost any way. CT scan is 100% sensitive for PJP in HIV patients.

Diagnosis:

Basics: Don’t delay treatment for diagnosis. Induced sputum first, then BAL if negative. 

If clinical suspicion is high, diagnosis should not delay treatment. Treat empirically in these cases. Diagnosis can be made with sputum induction (variable sensitivity 50s%-90% depending on patient characteristics, sputum characteristics, and skill of RT/lab/pathologist). If negative, proceed to bronchoscopy with BAL (sensitivity up to 90%). If clinical suspicion is extremely high, but these tests are negative, lung biopsy with PCR can be done, but is very rarely indicated and very invasive. Usually it is only done when lung biopsy is needed to diagnose other pathology concurrently. Silver stain with cysts or trophozoites is the typical method of detection for board exams.

At SCVMC, induced sputum to diagnose PJP requires a pulmonology consult due to the specialized nature of the induction procedure and patient selection and possibility of bronchoscopy.

Treatment:

Basics: Treat with Bactrim. Use adjunctive steroids if significant hypoxia. Things will get worse before they get better. 

Treat with Bactrim 15-20mg/kg PO or IV (equal bioavailability) x 21 days. If sulfa allergy, desensitize in the MICU and treat. If SJS or TEN with sulfa drugs, consider alternative regimens (clinda + primaquine, trimethoprim + dapsone, atovaquone, pentamidine). Always check for G6PD deficiency before starting primaquine or dapsone. Keep in mind that pentamidine is rarely used due to severe side effects: hypotension, hypoglycemia, nephrotoxicity, pancreatitis. It is often necessary to monitor these patients in the ICU for treatment due to the propensity of respiratory failure to initially worsen with treatment before getting better.

Give adjunctive steroids if PaO2 <= 70 or A-a gradient >= 35 or hypoxemia on pulse ox. Steroids have been shown to decrease mortality in these patients without an increase in other opportunistic infections.

 

Key Points:

• HIV (CD4<200) and severely immunocompromised get PJP
• Presents with 3 weeks of nonproductive cough, dyspnea, and constitutional symptoms, now with hypoxic respiratory failure
• LDH and B-D Glucan are sensitive, but nonspecific indicators of PJP that can help you decide to treat empirically if confirming the diagnosis in a timely manner is impractica
• PJP can cause almost any presentation on CXR/CT but diffuse bilateral infiltrates is most common. CXR is not sensitive so get a CT if clinical suspicion is high. 
• Don’t delay treatment for diagnosis. Induced sputum first, then BAL if negative. 
• Treat with Bactrim. Use adjunctive steroids if significant hypoxia. Things will get worse before they get better.