Differentials
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
Signs and symptoms are similar so it may be difficult to differentiate between the conditions clinically.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
It is not possible to differentiate COVID-19 from other causes of pneumonia on chest imaging.
Bacterial pneumonia
SIGNS / SYMPTOMS
Onset of symptoms is more rapid and acute than Pneumocystis pneumonia.
Patients with bacterial pneumonia often have focal lung findings, purulent sputum, and chest pain.
INVESTIGATIONS
Chest x-ray typically shows an alveolar pattern in a focal segment or lobar distribution.
Bacterial pneumonia can occur with any CD4 cell count.
Blood and sputum cultures may help determine aetiology.
Aetiological agent is most often Streptococcus pneumoniae.
Bronchoalveolar lavage, sputum, or tissue biopsy is negative for Pneumocystis jirovecii.
Coccidioidomycosis
SIGNS / SYMPTOMS
Patients typically have travel history to areas of California, Arizona, New Mexico, south-western Texas, or southern parts of Utah and Nevada.
Usually present with an influenza-like syndrome, chest pain, and dyspnoea.
There may be skin findings of erythema nodosum or erythema multiforme.
INVESTIGATIONS
Coccidioidomycosis can be diagnosed with serological testing, skin testing, culture positivity from appropriate samples, or histopathology that shows typical characteristic spherules in tissue samples.[94]
Chest x-ray may show interstitial pneumonia similar to Pneumocystis pneumonia but may have single or multiple nodules, thin-walled cavities, or hilar or mediastinal lymphadenopathy.[94]
Cytomegalovirus (CMV)
SIGNS / SYMPTOMS
The presentation can be similar. CMV pneumonitis is usually associated with a non-productive cough and minimal findings on lung examination.[95]
CMV pneumonitis is more common in HIV-negative patients than in those with HIV.
INVESTIGATIONS
CMV pneumonitis is typically associated with CMV viraemia. Tests for diagnosis include: viral culture, serology, pp65 antigenaemia test, histopathology, and nucleic acid amplification and detection systems, most commonly polymerase chain reaction.
Tissue biopsy with CMV-positive histology may suggest invasive disease.[95]
Histoplasmosis
SIGNS / SYMPTOMS
Similar to Pneumocystis pneumonia (PCP), patients may present with several weeks of fever and malaise but there may also be weight loss.
Examination findings include hepatomegaly, splenomegaly and generalised lymphadenopathy. In some disseminated cases, patients can present with septicaemia, hypotension, disseminated intravascular coagulation, acute respiratory distress syndrome, liver failure, or renal failure.
Unlike PCP, which rarely has extrapulmonary involvement, histoplasmosis may present with skin manifestations, neurological involvement, gastrointestinal involvement, and adrenal insufficiency.[96]
INVESTIGATIONS
Culturing the organism from an appropriate source is diagnostic but can take up to 4 weeks.
Serological testing is limited in immunocompromised patients, who may not make antibodies. Antigen detection from appropriate samples can be a rapid and sensitive diagnostic test; however, false positives can occur with Blastomycosis, Paracoccidioidomycosis, and Penicillium marneffei infections.
Fungal staining is rapid but is not a sensitive test.[96]
Kaposi's sarcoma lung involvement
SIGNS / SYMPTOMS
Symptoms can include dyspnoea, fatigue, wheezing, and haemoptysis.
May be associated with large pleural effusions.[97]
Often associated with skin lesions.
INVESTIGATIONS
High-resolution computed tomography of the chest may show nodules >1 cm in a bronchovascular distribution.
Bronchoscopy shows typical pigmented lesions in the airways.
Histopathology shows atypical spindle cells and vasoformative areas.
Biopsy for Kaposi's sarcoma may be associated with an increased risk of bleeding and is generally not necessary.
Lymphocytic interstitial pneumonitis
SIGNS / SYMPTOMS
Symptoms include progressive dyspnoea, non-productive cough, and fevers.
More common in HIV-positive children than adults.
INVESTIGATIONS
High-resolution computed tomography shows an interstitial pattern.
Can occur with any CD4 cell count.
Diagnosis may require an open lung biopsy, in which case tissue is negative for Pneumocystis jirovecii.
Mycobacterium avium complex (MAC)
SIGNS / SYMPTOMS
Pulmonary MAC is uncommon in HIV-positive subjects and more often presents with extrapulmonary manifestations.
INVESTIGATIONS
High-resolution computed tomography may show a bronchiolitis pattern.
CD4 cell count is often low as <100 cells/microlitre.
Blood or sputum culture is positive for Mycobacterium avium intracellulare.
Bronchoalveolar lavage, sputum, or tissue biopsy is negative for histochemical staining of Pneumocystis jirovecii.
Non-infectious interstitial lung disease
SIGNS / SYMPTOMS
Typical symptoms are dyspnoea and fatigue.
Fever is atypical.
Onset is indolent over months to years.
INVESTIGATIONS
High-resolution computed tomography findings may be helpful and show fibrosis and a peripheral distribution of abnormalities. These findings would be atypical for Pneumocystis pneumonia.
May require open lung biopsy to provide a tissue diagnosis.
Penicilliosis
SIGNS / SYMPTOMS
Caused by Penicillium marneffei. Once considered rare, its occurrence has increased as a result of AIDS. It is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of South-east Asia.
Typically, patients have a travel history to endemic areas of South-east Asia and the southern part of China.
Can present with skin lesions, subcutaneous nodules, haemoptysis, anaemia, lymphadenopathy, and hepatomegaly.
INVESTIGATIONS
Similar to Pneumocystis pneumonia, radiography may show cavitary lung lesions.
Diagnosis is by identification of the fungus in a clinical specimen.
Bronchoalveolar lavage, sputum, or tissue biopsy is negative for Pneumocystis jirovecii.
Pulmonary tuberculosis
SIGNS / SYMPTOMS
Presentation can vary widely depending on the level of immunocompetency.
May co-exist with Pneumocystis pneumonia in HIV-positive patients.
Symptoms can be present for weeks to months.
INVESTIGATIONS
Acid-fast bacillus staining and culture of respiratory or other specimens, if positive, is definitive for tuberculosis.
Bronchoalveolar lavage, sputum, or tissue biopsy is negative for Pneumocystis jirovecii.
Legionella
SIGNS / SYMPTOMS
Legionnaires disease may also be characterised by a fever with non-productive cough and few pulmonary symptoms.
Infected patients may also have diarrhoea, bradycardia, and abdominal pain.
INVESTIGATIONS
Legionella pneumophila is the most common clinical type. Serology is diagnostic with acute IgG, IgM, or IgA titres. Aspartate aminotransferase and alanine aminotransferase may be elevated.
Cryptococcus
SIGNS / SYMPTOMS
Causes pulmonary, neurological, and disseminated disease and pedunculated skin lesions.
Central nervous system manifestations are more suggestive of cryptococcosis than Pneumocystis pneumonia.
INVESTIGATIONS
Peripheral and cerebrospinal fluid cryptococcal serology are sensitive and specific tests.
Bronchoalveolar lavage, sputum, or tissue biopsy is negative for Pneumocystis jirovecii.
Blastomycosis
SIGNS / SYMPTOMS
Blastomyces dermatitidis is endemic to North America and is a fungal organism present in soil.
There may be a history of contact with infected dogs or cats.
Presents with systemic symptoms of fever and with pneumonia.
Skin lesions are widespread, ulcerated with typical pustules around the margin.
INVESTIGATIONS
Characteristic broad-based, budding fungal organisms in sputum or tissues by cytology or histology.
Bronchoalveolar lavage, sputum, or tissue biopsy is negative for Pneumocystis jirovecii.
Sarcoidosis
SIGNS / SYMPTOMS
May present with similar symptoms to Pneumocystis pneumonia but also with systemic involvement, including skin nodules.
INVESTIGATIONS
Bilateral hilar lymphadenopathy on chest x-ray.
Lung biopsy demonstrates granulomatous tissue.
Mycoplasma pneumoniae
SIGNS / SYMPTOMS
Respiratory infection occurs mainly in children and young adults and is often seen in close community settings, such as boarding schools, colleges, and military bases.
There is a relative increase in incidence in the late summer or autumn and epidemics often occur at 3- to 5-year intervals.
INVESTIGATIONS
Microbiology and culture of Mycoplasma pneumoniae from either nasopharyngeal aspirate or sputum or throat swabs. Not widely available.
Rise in serum titre of Mycoplasma-specific Ig on convalescent serum. The amount of titre change is dependent on the commercial assay used.
Pulmonary embolus
SIGNS / SYMPTOMS
History of deep-vein thrombosis may be present.
Symptoms include chest pain and dyspnoea.
Syncope may be present.
Signs include tachypnoea (respiratory rate >16 breaths per minute), fever >37.8°C (100.0°F), and increased heart rate (>100 bpm).
INVESTIGATIONS
Definitive diagnostic modalities of exclusion/confirmation include D-dimer, multi-detector computed tomography of chest, ventilation-perfusion scan, and pulmonary angiography.
Viral pneumonia
SIGNS / SYMPTOMS
Symptoms and signs may be similar to Pneumocystis pneumonia.
Lack of effectiveness of antibiotics.
INVESTIGATIONS
Positive nasopharyngeal viral cultures.
Relative lymphocytosis in WBC.
Influenza
SIGNS / SYMPTOMS
Symptoms and signs may be similar to Pneumocystis pneumonia.
Lack of effectiveness of antibiotics.
INVESTIGATIONS
Viral serology or culture may be positive for influenza.
Acute respiratory distress syndrome (ARDS)
SIGNS / SYMPTOMS
History of aspiration, inhalation injury, acute pancreatitis, trauma, burns, pulmonary contusion, transfusion-related lung injury, cardiopulmonary bypass, fat embolism, disseminated intravascular coagulation, and drug overdose.
On physical examination, patients with ARDS have acute hypoxic respiratory failure requiring high levels of oxygen and/or PEEP to maintain oxygen saturation >90%.
Lung examination may reveal basilar or diffuse rales.
ARDS may also complicate Pneumocystis pneumonia and both conditions may co-exist.
INVESTIGATIONS
Blood, sputum, and urine cultures and lipase tests are done to test for underlying infection and pancreatitis.
Bronchoalveolar lavage (BAL) or tracheal aspirate is recommended in patients with ARDS due to suspected pneumonia and those without a defined predisposing condition. BAL can be tested for the presence of Pneumocystis jirovecii.
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