Pneumocystis Jiroveci (Carinii) Pneumonia Imaging 

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Pneumocystis jiroveci pneumonia (also known as Pneumocystis pneumonia, or PCP; formerly P carinii pneumonia) is caused by the ubiquitous unicellular eukaryote, P jiroveci. This organism is a rare cause of infection in the general population, but it is a frequent cause of morbidity and mortality in persons who are immunocompromised, especially patients with acquired immunodeficiency syndrome (AIDS). ^{[1, 2, 3, 4]}  PCP is classified as a fungal pneumonia but does not respond to antifungal therapy. The incidence of PCP has decreased as a result of  and highly active antiretroviral therapy (HAART).(See the images below.)

Patients who do not have AIDS but are immunocompromised and at risk for P jiroveci pneumonia include individuals with hematologic malignancies ^[4] ; organ transplant recipients ^{[5, 6]} ; and those receiving long-term steroid or cytotoxic therapy, including patients with systemic vasculitis or other autoimmune deficiency. Other patients with immune deficiency disorders who are at particular risk for PCP include those with thymic dysplasia, those with severe combined immunodeficiency, and those with hypogammaglobulinemia. Severe malnutrition may predispose patients to PCP.

A subset of patients present with atypical clinical and radiographic features termed chronic PCP. These patients have a prolonged clinical course over months or years, with persistent stable symptoms and radiographic abnormalities corresponding to pathologic findings of interstitial fibrosis, traction bronchiectasis, and honeycombing.

Chest radiographs should be included in the initial evaluation for PCP. Frequently, these are the only images required. High-resolution computed tomography (HRCT) scanning and, occasionally, gallium-67 (⁶⁷Ga) scanning are useful in symptomatic patients in whom chest radiograph findings are normal or equivocal. ^{[7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]}

The hallmark finding of PCP on HRCT scans is diffuse ground-glass opacity (GGO), which reflects the accumulation of intra-alveolar fibrin, debris, and organisms. ^{[17, 18]} The term ground-glass refers to parenchymal opacification, which does not obscure the underlying pulmonary architecture. This usually occurs in a bilateral, symmetrical, predominantly perihilar distribution and may be geographic or mosaic in appearance, with areas of normal lung adjacent to areas of affected lung.

A study of 32 patients with AIDS-related PCP showed a a central distribution of ground-glass opacity with relative peripheral sparing in 41% of patients, a mosaic pattern in 29%, and a diffuse distribution in 24%. ^[17]

Chest radiography retains a key role in the diagnosis of pneumonia in the immune compromised. ^[15] Chest radiography retains its position as the prime modality in the diagnosis and exclusion of pneumonia, follow-up imaging to check for resolution, and to evaluate potential complications. CT scanning is more sensitive and, with certain infections, more specific. MRI provides an option for monitoring progress, although it cannot yet replace chest radiography or CT scanning as the initial diagnostic procedure. ^[13]

In a study of 105 non-AIDS PCP immunocompromised patients, chest radiographic findings wre divided into 3 stages: early stage (normal or nearly normal chest radiograph), mid-stage (bilateral pulmonary infiltrates), and late stage (bilateral pulmonary consolidations). Chest HRCT findings were also divided into 3 stages: early stage (bilateral diffuse ground-glass opacity [GGO]), mid-stage (bilateral diffuse GGO and patchy consolidations), and late stage (bilateral diffuse consolidations). ^[15]

Chest radiograph findings may be normal in 10-39% of patients with PCP. With CT and ⁶⁷Ga scanning, the appearance of PCP is nonspecific.

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In patients with Pneumocystis jiroveci pneumonia (PCP), chest radiographs classically demonstrate bilateral, diffuse, often perihilar, fine, reticular interstitial opacification, which may appear somewhat granular. This opacification progresses to air-space consolidation over 3-4 days. This appearance may be followed by coarse reticulation as the infection resolves. (See the images below.) ^{[20, 21, 22, 19]}

Chest radiograph findings may be normal in 10-39% of patients, or radiographic changes may lag behind the clinical symptoms.

Trends are changing in the radiographic manifestations of PCP; features that previously were considered to be unusual are seen with increasing frequency. ^[20]

Atypical radiographic patterns are reported to occur in 5% of patients and include cystic lung disease, spontaneous pneumothorax, and isolated lobar or focal consolidation, particularly with an upper-lobe predominance.

Pulmonary nodules, which may be cavitated, have been described, but they are rare in PCP. The nodules have been shown histologically to represent granulomas, and these are usually encountered early in the course of HIV infection, when the patient is still capable of mounting a granulomatous response.

Miliary nodularity, bronchiectasis, endobronchial lesions, and mediastinal lymphadenopathy (18%), which may show calcification, have been reported. ^[23]

Pleural effusions and hilar lymphadenopathy are uncommon. Indeed, the presence of an effusion should prompt the search for a different pathogen.

Cysts are visible on chest radiographs in 10% of patients, although these entities are appreciated far more commonly on HRCT scans (33%). Findings of cysts or pneumatoceles are not infrequent in patients with PCP.

Cysts may occur in the acute or postinfective period and range in number, size, shape, and distribution. They are are commonly multiple, with a predilection for the upper lobes, and may be related to an ongoing or previous PCP infection.

The etiology of the cysts is unclear, but several hypotheses have been proposed, including the release of elastase from alveolar macrophages, which causes tissue necrosis and cavitation; vascular invasion with subsequent infarction; and cavitation obstruction of small airways, leading to a ball-valve effect.

Radiologic-pathologic correlation has shown persistent infection in some of the cyst walls.

Spontaneous pneumothorax may be a feature of PCP infection, with a reported incidence of approximately 6%, rising to approximately 35% in patients with cysts. Development of a spontaneous pneumothorax has important implications for treatment and prognosis of patients because this condition tends to be refractory to conventional tube drainage, frequently requiring pleurodesis or surgical intervention. In addition, spontaneous pneumothorax is associated with a significantly higher mortality rate, particularly in patients on ventilation. Pneumothoraces are frequently bilateral.

Chest radiograph findings usually resolve within 2-4 weeks with successful treatment. This resolution may be accelerated by the use of steroids. Occasionally, radiographic findings remain abnormal, and the images demonstrate reticular opacities, interstitial fibrosis, or focal scarring and/or nodularity.

Despite the presence of overlapping radiographic features in PCP, chest radiograph findings are often of diagnostic value. Usually, chest radiography is the only imaging required, and the overall accuracy for the diagnosis of PCP is approximately 75%.

Chest radiograph findings may be normal in 5-30% of patients with PCP. The literature reports a false-negative rate for the diagnosis of PCP by using chest radiography of 35-40%. Adult respiratory distress syndrome, pulmonary edema, other opportunistic lung infections, lymphoma, and Kaposi sarcoma may mimic PCP.

HRCT scanning is more sensitive than chest radiography for the detection and exclusion of Pneumocystis jiroveci pneumonia (PCP), and the results may be positive when chest radiograph findings are normal. ^{[11, 15, 17, 18]}

The hallmark finding of PCP on HRCT scans is ground-glass attenuation, which is present in more than 90% of patients and represents an exudative alveolitis. The term ground-glass refers to parenchymal opacification, which does not obscure the underlying pulmonary architecture. This usually occurs in a bilateral, symmetrical, predominantly perihilar distribution and may be geographic or mosaic in appearance (56%), with areas of normal lung adjacent to areas of affected lung. (See the images below.)

Thickening of interlobular septa (due to edema) and foci of consolidation may be associated. Septal thickening in the subacute stage is usually more extensive and represents organizing inflammatory infiltrate.

In the proper clinical setting, the presence of ground-glass attenuation on HRCT scans in patients with AIDS is virtually diagnostic of PCP, with a diagnostic accuracy of approximately 94%. Normal HRCT findings virtually exclude the possibility of PCP.

Ground-glass attenuation is highly suggestive of PCP, but cytomegalovirus (CMV), ^[16] pneumonitis, and lymphoid interstitial pneumonia can (albeit infrequently) give rise to a similar appearance. However, CMV pneumonitis is rare in patients with CD4 counts of greater than 50 cells/mm³.

Although PCP can give rise to parenchymal nodules, this feature is more common in CMV infection; thus, the combination of ground-glass attenuation and nodularity is more likely to be secondary to CMV infection.

Motion artifacts and low lung volumes due to reduced inspiratory effort may occasionally give rise to a spurious ground-glass appearance.

Ground-glass opacification can also be seen in conditions such as pulmonary edema, pulmonary hemorrhage, drug toxicity, other infections, and hypersensitivity pneumonitis. Clinical correlation usually allows the exclusion of most of these differential diagnoses.

Hilar lymphadenopathy may occur in patients with tuberculosis, Mycobacterium avium-intracellulare (MAI or MAC) infection, fungal infection, Kaposi sarcoma, and AIDS-related lymphoma, but this condition is rare in patients with PCP.

Ultrasonography may be useful in the evaluation of systemic Pneumocystis carinii infection (hepatic/splenic and renal microabscesses), but this imaging modality is of no value in assessing pulmonary disease.

Ga citrate is useful in the investigation of fevers of unknown origin (FUO), because it is taken up by areas of inflammation, infection, and tumor.⁶⁷ Ga also accumulates in Pneumocystis jiroveci pneumonia (PCP) infection and can detect PCP in asymptomatic patients with AIDS in the absence of abnormal plain radiographic findings.

The most common pattern of radionuclide uptake seen in patients with PCP is diffuse pulmonary uptake. ^{[7, 8, 22, 9]} A negative heart with diffuse pulmonary uptake in a patient with AIDS is indicative of PCP. However, uptake varies in patients treated with aerosolized pentamidine and is observed only in areas of the lungs where the drug fails to reach. Patchier uptake is seen with recurrent PCP; however, gallium scanning is expensive, is poorly tolerated by patients, and requires delayed scans at 48 hours. In practice, this study is little used.

Indium-111 (¹¹¹In) – labeled autologous leukocytes accumulate in PCP, but the overall performance in immunosuppressed patients is poor compared with ⁶⁷Ga studies.

The clearance of technetium-99m (^99mTc) diethylenetriamine pentaacetic acid (DTPA) aerosol across the alveolar-capillary membrane is accelerated in patients with PCP. The shortened half-life for clearance of radionuclide activity has been shown to be more sensitive than in ⁶⁷Ga imaging. After effective therapy, the shortened clearance times rapidly return to normal. ^[24]

Tc-99m-labeled nonspecific polyclonal human immunoglobulin (HIG) has been used in the evaluation of patients with AIDS. ^{[8, 25]} The sensitivity varies from 0-100% in PCP. Similar to ⁶⁷Ga scanning, ^99mTc-labeled nonspecific polyclonal HIG appears more sensitive than chest radiography. The pattern of activity is usually diffuse, but focal uptake has been described.

An Fab fragment of an antibody labeled with ^99mTc has been used to image the infection in patients with AIDS; this fragment recognizes PCP. In a small series, a sensitivity of 85.7% and a specificity of 86.7% were achieved. ^[26]

Ga-67 scans are extremely sensitive for PCP, with reported sensitivities of 87-100%; however, the specificity of ⁶⁷Ga imaging may vary considerably and reportedly ranges from 20-100%. This variation partly depends on the nuclear medicine department’s clinical practice and referral patterns. The specificity can be increased when diffuse pulmonary uptake of greater intensity than the liver is included in the diagnostic criteria. The discordance between pulmonary ⁶⁷Ga uptake and negative chest radiographic findings in patients with AIDS can be used to increase the specificity in detecting PCP.

The overall performance with the uptake of radiolabeled leukocytes is poor in PCP, and this technique should be reserved for imaging suggesting bacterial pneumonia and infections at other sites in patients with AIDS and patients who are immunosuppressed but do not have AIDS.

Tc-99m DTPA aerosol clearance times provide a simple and noninvasive technique for follow-up imaging in patients receiving treatment for PCP. Although abnormalities in the clearance of ^99mTc DTPA aerosol have been reported with other pulmonary infections in patients with AIDS, a clearance time greater than 4.5% per minute has been shown to be specific for PCP in patients with AIDS.

The sensitivity and specificity of ^99mTc–labeled HIG are too variable to warrant use of this technique in patients with AIDS-related PCP. Further large-scale studies are required to justify its use.

Ga-67 also accumulates in lymphoma and other malignant processes that are associated with AIDS.

Accelerated clearance of  ^99mTc DTPA aerosol is not specific in patients with PCP, and this process has been reported with other pneumonitides that are associated with AIDS.

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Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR Chief Medical Officer, Silk Road Medical

Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR is a member of the following medical societies: British Medical Association, Cardiovascular and Interventional Radiological Society of Europe, British Society of Interventional Radiology, International Society for Vascular Surgery, Royal College of Physicians, Royal College of Radiologists, British Society of Endovascular Therapy, Scottish Radiological Society, Vascular Society of Great Britain and Ireland

Disclosure: Received salary from Silk Road Medical for employment.

Carolyn M Allen, MBChB, MRCP, FRCR Consultant Radiologist, Clinical Director, Department of Clinical Radiology, North Manchester General Hospital, UK

Carolyn M Allen, MBChB, MRCP, FRCR is a member of the following medical societies: Society of Thoracic Radiology

Disclosure: Nothing to disclose.

Klaus L Irion, MD, PhD Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK

Klaus L Irion, MD, PhD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Nothing to disclose.

Satinder P Singh, MD, FCCP Professor of Radiology and Medicine, Chief of Cardiopulmonary Radiology, Director of Cardiac CT, Director of Combined Cardiopulmonary and Abdominal Radiology, Department of Radiology, University of Alabama at Birmingham School of Medicine

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Dr Hari Panigrahi to the development and writing of this article.

Pneumocystis Jiroveci (Carinii) Pneumonia Imaging 

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