Pneumonia diagnosis

Diagnosis of Pneumocystis pneumonia

Pneumocystis pneumonia is a life-threatening infection caused by the fungal organism Pneumocystis jiroveci. Initially observed in premature and malnourished infants, Pneumocystis Pneumonia is today one of the most common opportunistic infections in adults infected with the human immunodeficiency virus (HIV).

As nonspecific symptoms often hamper prompt diagnosis, one of the most important diagnostic tools for Pneumocystis pneumonia is a high level of clinical suspicion. Clinicians should always consider this diagnosis in patients with HIV infection who complain of shortness of breath, non-productive cough, and / or fever. Microbiological and molecular methods are then employed as a step towards a final diagnosis.

Pneumocystis pneumonia (PCP): Part I

Microbiological and molecular methods

Like Pneumocystis jiroveci does not lend itself to conventional culture methods, the gold standard for the diagnosis of Pneumocystis pneumonia has traditionally been the microscopic demonstration of the organism in respiratory samples. Visualization of this fungal pathogen, however, is highly dependent on the experience and skill of the observer.

Cysts can be effectively stained with toluidine blue, methenamine silver, or calcium flour white. In contrast, trophic forms, which are more abundant during the development of pneumonia, are usually detected with the Diff-Quik and Wright-Giemsa staining procedures. Today, monoclonal antibodies are also used due to their improved sensitivity and specificity in diagnosis from sputum samples.

The expansion of molecular techniques – notably polymerase chain reaction (PCR) testing – has provided a more reliable approach in the clinical diagnosis of this disease. In research studies on respiratory samples from adult patients, PCR has shown similar specificity and increased sensitivity compared to standard microscopy.

Additionally, real-time PCR can help quantify the burden of organisms, which can further help differentiate whether Pneumocystis jiroveci colonizes or infects the host. This type of PCR can even be performed on formalin fixed samples of bronchoalveolar lavage fluid that are embedded in paraffin, with sensitivities approaching 83%.

Radiological presentation

On a thoracic film, Pneumocystis pneumonia usually presents with bilateral or scattered opacities in frosted glass. Some less common patterns have also been reported, such as lung nodules, lobar infiltrates, and pneumatoceles. Chest x-rays may also appear normal in at least one-third of cases.

When high-resolution computed tomography is used, diffuse ground-glass opacities with uneven distribution are often observed, suggesting the accumulation of debris, intra-alveolar fibrin, and responsible microorganisms. A predilection for the upper parts of the lungs has also been described as a characteristic sign.

Serum markers

Although the serum β-D-glucan (which is part of the cell wall of Pneumocystis and other fungi) is not specific to Pneumocystis infections, its measurement has been used as a useful tool in the diagnosis of Pneumocystis pneumonia, or at least in the detection of the disease.

However, it should be noted that false positive results can occur due to certain factors such as:

  • bacteremia
  • hemodialysis
  • some antimicrobial drugs
  • administration of immunoglobulins

In addition, the cut-off value for the diagnosis of Pneumocystis pneumonia has yet to be determined.

Krebs von den Lungen-6 (abbreviated KL-6) is another marker expressed on pneumocytes and bronchial epithelial cells. It acts as a sensitive indicator of different types of interstitial lung disease. Therefore in case of Pneumocystis pneumonia, this marker is elevated following injury and subsequent regeneration of alveolar epithelial cells.

Likewise, serum lactate dehydrogenase (LDH) may indicate damage to lung tissue, but its diagnostic importance is less than that of β-D-glucan. In short, all these biomarkers are promising, but their diagnostic performance must be further developed in order to know their predictive values ​​in patients at risk. These results should be combined with the microbiological evaluation.

Further reading