Pulmonary Pneumocystis jirovecii infection

Pneumocystis pneumonia (PCP)Pulmonary pneumocystis jirovecii infection, also referred to as Pneumocystis jirovecii pneumonia (PJP)and previously termed Pneumocystis pneumonia (PCP),, is an atypical pulmonary infection and the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS).

Terminology

Classically, PCP"PCP" was the acronym for Pneumocystis carinii pneumonia, but the causative organism was reclassified as Pneumocystis jirovecii. Strictly speaking, Pneumocystis carinii refers to a species found in rats, while Pneumocystis jirovecii refers to the human isolate. However, physicians have been slow to adopt the updated terminology, and there continues to be widespread use of the term PCP; a post-hoc justification for its use is it stands for pneumocystis pneumonia.

Epidemiology

Pneumocystis pneumonia is virtually never present in immunocompetent individuals. It is one of the most common causes of life-threatening pulmonary infections in HIV positive patients. It occurs twice as frequently in homosexual males versus IVDAs. It typically occurs at CD4 counts below 200 cells/mm^3,8.

It is seen particularly in patients with AIDS; therefore, the demographics closely match those of the AIDS population. Typically, non-AIDS patients are severely immunosuppressed due to other causes, such as haematological malignancy or in bone marrow transplant recipients.

Clinical presentation

Presentation is usually non-specific and insidious, the most common symptoms being dyspnoea and/or non-productive cough. In patients who are profoundly immunocompromised, onset may be more dramatic and resemble other pulmonary infections ^7,9.

The diagnosis can often be confirmed with bronchoalveolar lavage which has a sensitivity of 85-90% ⁸. It is one of the most common causes of life-threatening pulmonary infections in HIV positive patients.

Pathology

Pneumocystis jirovecii is an atypical yeast-like fungus of the genus Pneumocystis ¹⁰ that was previously thought to be a protozoan.

Histology of infected lung demonstrates intra-alveolar eosinophilic masses with a foamy appearance, due to small cysts within which the Pneumocystis jirovecii organism is found ⁹. 

Culturing Pneumocystis jirovecii can be very difficult. Diagnostic confirmation requires identification of organisms in sputum or bronchoalveolar lavage fluid. Monoclonal antibodies for detecting Pneumocystis jirovecii are available and have a sensitivity greater than 90% for detecting Pneumocystis jirovecii in induced sputum from HIV-infected patients ¹⁰.

Radiographic features

Plain radiograph

Although up to 90% of chest radiographs in patients with PCP are abnormal, appearances are often non-specific. Between 10-15% of patients with PCP have normal chest radiographs and close to 30% have non-specific or inconclusive findings ^2-4,6,7.

Features which are highly suggestive of PCP in patients with CD4 counts below 200/mm³  include ⁵:

• small pneumatoceles
• subpleural blebs
• fine reticular interstitial changes
• predominantly perihilar in distribution

Pleural effusions are normally not a feature, seen in less than 5% of cases ⁹.

CT

High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs ³.

Features include ^2,3,7:

• ground-glass pattern
  • considered a principal finding
  • predominantly involving perihilar or mid zones
    • there may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolised medication
    • if they are, then the poorly ventilated upper zones are prone to infection ⁹, whereas, in those who are not, the lower zones are more frequently involved
    • there may be relative preservation of previously irradiated areas
    • may show some peripheral sparing in a considerable number of patients (~40%) ¹⁰
• reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are superimposed on one another
• pneumatoceles
  • varying shape, size, and wall thickness
  • are seen in up to 30% of cases ⁷
• pleural effusions are rare ^2,3
• lymphadenopathy is uncommon (10%)

Especially in patients treated prophylactically, features are more frequently atypical including ⁷:

• consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
• nodules (granulomas)
  • may cavitate
  • small nodules and tree-in-bud opacities are uncommon in patients with AIDS and PCP and usually indicate the presence of infectious bronchiolitis from other organisms
• lymphadenopathy
• pleural effusions are also more frequently encountered in this group of patients

A cystic form of PCP is also recognised, again more frequently in patients receiving aerosolised prophylaxis. In this pattern, features include ⁷:

• thin walled cysts: in most cases these are pneumatoceles
• upper lobes
• may be bilateral
• increased risk of pneumothorax

Nuclear medicine

Gallium⁶⁷ lung scintigraphy is highly sensitive for PCP, and a normal gallium scan renders the diagnosis of PCP very unlikely. The gallium scan in patients with PCP demonstrates diffuse pulmonary uptake, which may be heterogeneous or homogeneous.

Despite this, the specificity of the gallium scan is low; hence, it is most useful in patients in whom bronchoalveolar lavage may be less diagnostic (e.g. in suspected relapse).

Treatment and prognosis

Most patients with acute infection are treated with trimethoprim-sulfamethoxazole (co-trimoxazole or TMP-SMZ), combined with corticosteroids in patients with moderate to severe infections ⁸. The same agent may be used as prophylaxis. A number of alternative agents may also be employed, both for acute treatment and prophylaxis, although these are beyond the scope of this article.

Overall, with prompt treatment, survival is good (50-95%), although relapses are common ⁹.

Differential diagnosis

The differential diagnosis on HRCT is strongly influenced by knowledge of HIV status and CD4 count. In these patients the differential includes:

• viral pneumonitis: similar, but cysts are absent
  • CMV pneumonitis
• mycobacterium tuberculosis: when upper zone cysts are prominent
• angioinvasive aspergillosis
• immune reconstitution inflammatory syndrome (IRIS): patients receiving HAART

Other conditions to be considered, which also occur in non-AIDS patients, include:

• for prominent cysts consider
  • pulmonary Langerhans cell histiocytosis (LCH)
  • lymphangioleiomyomatosis (LAM)
  • honeycomb lung
  • bronchiectasis: due to various causes
• for a reticulonodular pattern consider
  • sarcoidosis
  • granulomatosis with polyangiitis
  • pneumoconioses
  • hypersensitivity pneumonitis
  • Kaposi sarcoma
  • see: differential of a reticulonodular pattern

See also

• pulmonary manifestations of HIV/AIDS
• pulmonary fungal infection