Imaging 14:60-76 (2002)
© 2002 The British Institute of Radiology
Imaging of the thorax in AIDS
L J King, MRCP, FRCR and
S P G Padley, FRCP, FRCR
Department of Radiology, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
Correspondence: Dr S P G Padley
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Summary
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- Pulmonary manifestations of HIV disease are common.
- The pattern of disease has changed owing to a combination of factors. Plain radiography coupled with clinical assessment remains the starting point of investigation.
- CT is usually not required, except as a problem-solving tool.
- Whilst infection remains common, there are numerous non-infectious causes of acute chest symptoms.
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Introduction
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Since the start of the acquired immune deficiency syndrome (AIDS) epidemic in the 1980s, respiratory disease has been an important cause ofmorbidity and mortality, with the majority of human immunodeficiency virus (HIV) infected patients encountering a pulmonary complication during the course of their illness. Despite recent encouraging advances in the management of patients with AIDS, pulmonary manifestations of this disease remain common, accounting for approximately 30–40% of acute admissions to our institution. A variety of these thoracic disorders have been classified as AIDS-defining illnesses (Table 1
) and account for up to 50% of new AIDS presentations.
Changing patterns in the presentation and epidemiology of thoracic manifestations ofAIDS have been demonstrated in recent years, particularly since the introduction of combination anti-retroviral therapy and the use of prophylactic antibiotics. Thus, there has been a reduction in the number of patients presenting with the more traditional respiratory type pathogens and a simultaneous increase in morbidity due to less virulent organisms. For example, a reduction in the number of cases of Pneumocystis carinii pneumonia (PCP) has been paralleled by increased numbers of Mycobacterium avium complex(MAC) and cytomegalovirus (CMV) infection [1, 2].
There have also been changes in the population characteristics of patients with AIDS, and a greater proportion of new cases are now being reported in women and children as a result of heterosexual contact or intravenous drug abuse. A relative reduction in the proportion of new cases arising from homosexual or bisexual acquisition has also been noted.
Individual disease processes may manifest in a variety of different radiological appearances, and there is considerable overlap between the radiographic findings of the numerous infectious and neoplastic entities that are known to occur with increased frequency in AIDS patients. This degree of radiological variation creates considerable difficulty in the interpretation of chest radiographs and thoracic CT scans. Imaging findings should therefore be interpreted in conjuction with clinical information, including the nature of HIV acquisition, previous infectious or non-infectious complications, CD4+ count, current drug therapy, and acuteness of onset and severity of the illness. Furthermore, the results of important yet relatively simple tests, such as pulse oximetry and sputum microscopy, will also narrow the differential diagnosis.
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The role of thoracic imaging in AIDS
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Whilst imaging alone may be unable to provide a definitive diagnosis in each individual case, the radiologist does have a clear role in the assessment of thoracic disease in AIDS patients as follows:- confirming the presence of thoracic pathology in symptomatic AIDS patients;
- differential diagnosis;
- advising on and performing thoracic interventions such as biopsy or chest drainage;
- monitoring the response to therapy following diagnosis.
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The role of CT
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CT is superior to plain chest radiography in providing an accurate diagnosis. Several authors have expounded the utility of CT in the clinical management of AIDS patients with thoracic disease. Most of these studies, however, looked retrospectively at a series of patients in whom thediagnoses had already been established, with analysis mainly limited to radiological description. There have been a few important exceptions to this trend, most notably those series by Hartman et al [3] and Kang et al [4]. Hartman and colleagues assessed the accuracy of CT in the diagnosis of thoracic complications of AIDS by reviewing the CT images of 122 patients (102 with and 20 without disease). They found that a confident diagnosis could only be reached in 48% of the 122 patients, although when a confident radiological diagnosis was made, it was correct in 92% of cases [3]. A subsequent publication by the same authors comparing the diagnostic yield of CT with plain chest radiography found that the improvement in accuracy provided by CT was modest and concluded that "in the majority of cases the chest radiograph provides adequate information and CT is not warranted" [4].
It is well recognized, however, that chest radiographs can appear normal in patients with pulmonary disease such as PCP, and CT has been advocated as part of the diagnostic algorithm in such patients. Chest CT is not routinely performed in the assessment of an AIDS patient presenting with signs or symptoms of respiratory disease at our institution, but it does have an important role as follows:
- confirming suspected chest disease in the presence of a normal or near normal chest radiograph;
- clarification of abnormalities identified on plain chest radiographs, including the extent of disease and the pattern of parenchymal change;
- evaluation of mediastinal abnormalities identified on plain chest radiographs, particularly mediastinal lymph node enlargement;
- staging of malignant disease or re-staging post therapy;
- biopsy planning, including identification of representative lesions and the choice of biopsy technique;
- imaging guidance for draining of loculated pleural fluid collections and pneumothoraces.
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Radiographic pattern recognition
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Sider et al [5] have demonstrated the potential utility of radiographic pattern recognition in HIV patients. However, the radiological manifestations of thoracic disease in this population are often non-specific and must be interpreted in conjunction with the patient's clinical details. For example, Kaposi's sarcoma (KS) is unlikely to occur unless a patient has acquired AIDS through bisexual or homosexual contact, and is also unlikely with a CD4+ count greater than 200 x 106 cells l-1. In the absence of these factors, and whatever the radiological appearances, a suggested diagnosis of KS is unlikely to be correct. This principle holds true for a number of other AIDS-related chest diseases. Opportunistic chest infections for example, do not generally occur prior to a fall in the CD4+ count to less than 200 x 106 cells l-1, and a number of other disease processes tend to only be encountered as the CD4+ count falls below certain threshold levels (Table 2).
Within the constraints given above, imaging retains an important place in the management ofHIV patients with chest symptoms, both indisease process identification and specific diagnosis.
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Pneumocystis carinii pneumonia
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Prior to the introduction of antibiotic prophylaxis, PCP was the commonest respiratory tract infection to occur in the AIDS population. The impact of prophylactic preventative therapy has been to significantly reduce the likelihood of PCP following a fall in the CD4+ count to below 200 x 106 cells l-1 [6]. PCP prophylaxis has also been shown to increase life expectancy in this severely immunosuppressed group when combined with anti-viral therapy compared with patients receiving anti-viral therapy alone [6]. Whilst bacterial pneumonia has now superseded PCP as the commonest chest infection overall, PCP remains a significant problem that still occurs in the majority of patients at some time during their illness, and is still the most common opportunistic chest infection. PCP is slightly commoner in homosexuals than iv drug abusers, and is also more common in males and in the White population whatever the method of HIV acquisition [6, 7].
PCP becomes increasingly common as the CD4+ count falls below 200 x 106 cells l-1 but may still occur with cell counts above this level. Patients usually give a history of cough and fever developing over several days and are frequently hypoxic at presentation. The diagnosis is strongly suspected by the combination of a typical history and low CD4+ cell count, coupled with hypoxia on room air or early desaturation on exercise (reliable only if there has not been a previous episode of PCP). An induced sputum sample will usually provide a definitive diagnosis. If sufficient diagnostic doubt persists to prevent commencement of therapy, then bronchoscopy with bronchoalveolar lavage (BAL), and occasionally transbronchial biopsy, may be required.
The radiographic appearances of PCP demonstrate considerable variation. The chest radiograph is occasionally normal but most commonly demonstrates bilateral ground-glass or reticular infiltrates most marked in a perihilar distribution [8, 9] (Figure 1). On chest CT the acute infection classically results in a perihilar ground-glass infiltrate, often in a geographical distribution, with areas of affected lung interspersed by normal lung parenchyma [10–12]. A linear or reticular interstitial pattern is also frequently demonstrated, with thickening of the interlobular septae [10–12], which is often the feature that is slowest to resolve radiologically. A variety of less typical radiographic patterns have been described both on chest radiography and on CT, including focal areas of consolidation, mass lesions, multiple lung nodules, pleural fluid, pneumothorax, cavitation, lymph node enlargement and occasional nodal calcification [8–10, 13–16]. Development of a solitary pulmonary nodule due to PCP may be owing to a granulomatous response in less immunocompromised patients [10]. Whilst cavitation in an area of ground-glass change or pneumothorax are both suggestive of PCP, the other changes have a wide variety of possible causes, most notably bacterial pneumonias and typical or atypical mycobacterial infection. Patients receiving inhaled pentamidine prophylaxis often present with PCP that is isolated to or predominant in the upper lobes [9, 17].
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Figure 1. Adult male HIV patient with Pneumocystis carinii pneumonia. The chest radiograph shows typical bilateral ground-glass shadowing, cystic change in the right upper lobe and a left pneumothorax.
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Pulmonary infection with Pneumocystis carinii is complicated by the development of pulmonary cysts or pneumatocoeles in around 10–38% of cases [8, 10, 18–21]. These air-filled cysts are typically thin walled, with smooth inner and outer margins, although thicker walled lesions may also be demonstrated. The cysts may be regular or irregular in shape, do not contain fluid or other material [18] and may be predominantly apical or subpleural in location, or distributed throughout the lung parenchyma [18–21] (Figure 2). Theexact aetiology of these lesions is unclear, although a variety of mechanisms have been suggested, including "check valve" obstruction of small airways, pulmonary infarction and production of proteases or elastases [18, 21]. Pneumothorax and pneumomediastinum are also widely recognized as further complications that may arise in patients with post-PCP lung cysts [8–10, 18–21] and can be difficult to resolve by tube thoracostomy drainage owing to persistent air leaks [19, 21].
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Figure 2. 33-year-old male with AIDS and Pneumocystis carinii pneumonia. High resolution CT demonstrates bilateral ground-glass opacity, lung consolidation, multiple thin-walled cysts and several thickened interlobular septae.
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At our institution there is relatively little use of high resolution CT (HRCT) in the diagnosis of suspected PCP. However, CT may be valuable inthe assessment of atypical cases and in the management of complications such as pneumothoraces. Other workers have proposed that CT, and especially HRCT, has a role in the avoidance of other more invasive diagnostic procedures since it has been shown to be reliable in detecting parenchymal change when the diagnosis is suspected but the chest radiograph is normal orequivocal [12]. Several other studies have supported the ability of HRCT to confidently diagnose PCP based on typical radiological features [3, 4].
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Bacterial pneumonia
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Although the major immune deficiency in AIDS patients relates to T-cell function, B-cell function and antibody production are also affected, thus increasing susceptibility to pyogenic organisms. Bacterial pneumonias tend to occur throughout the course of HIV illness, becoming increasingly common with a falling CD4+ count. Since they often occur at relatively high CD4+ counts, bacterial infections tend to be the first pneumonic processes to occur prior to the onset of full blown AIDS.
Recurrent pyogenic bacterial pneumonia is now the most common clinically apparent parenchymal lung infection in the HIV population, both before and after the onset of AIDS [22], and is included in the Centres for Diseases Control list of AIDS-defining illnesses. The incidence of bacterial pneumonia is approximately five times greater than in an otherwise similar but HIV-negative population [22]. Furthermore, the incidence of pneumococcal disease, including pneumonia, is 10 times greater, and the development of pneumococcal septicaemia is 100 times greater than in the general population [23]. Widespread use of anti-PCP prophylaxis and the changing demographics of the HIV-positive population have both contributed to this increased incidence of bacterial pneumonia, which is particularly common in iv drug users [24].
The clinical presentation of pneumonia is generally the same as in the HIV-negative population and it usually follows a similar clinical course, although the tendency to rapid progression, cavitation, parapneumonic effusion and empyema formation are greater than in the general population (Figures 3 and 4).
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Figure 3. 39-year-old male AIDS patient with a community-acquired pneumonia complicated by an empyema. Contrast enhanced CT demonstrates pulmonary consolidation (straight arrow) and a loculated left-sided pleural fluid collection (curved arrows).
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Figure 4. Adult male HIV-positive patient with a community-acquired staphylococcal pneumonia. The chest radiograph shows a right upper lobe pulmonary consolidation with central cavitation.
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The organisms encountered mirror those seen in the general population, although less common organisms are identified with relatively greater frequency. The bulk of community-acquired pneumonias are due to Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus viridans and Staphylococcus aureus [16, 24–26]. Opportunistic bacterial infections may be encountered in the later stages on immunosuppression, including Rochalimaea sp. and Rhodococcus equi, which usually causes a cavitatory pneumonia often with associated mediastinal lymphadenopathy [27].
Lobar or segmental consolidation are the usual radiographic findings [14], although an increased frequency of interstitial infiltrates has been reported [27–29]. Differentiation from opportunistic infection, including Mycobacterium tuberculosis and PCP, is often not possible from the chest radiograph when the appearances are atypical [28, 29]. CT may occasionally be useful in patients with a bacterial pneumonia, especially when the appearances are atypical. Cavitation and pleural complications are also better delineated on CT than on plain radiographs, but in the majority of cases CT is not required.
Bacterial chest infections in the HIV infected population are not always pneumonic in nature anda number of recent studies have highlighted theimportant morbidity associated with bronchitis, bronchiolitis and bronchiectasis [24, 30–33]. In these cases the chest radiograph often demonstrates an apparent interstitial infiltrate or multiple small nodules [34], although HRCT allows the truebronchocentric nature of the disease process tobe appreciated. HRCT may also demonstrate airway abnormalities in the face of a normal chest radiograph [24]. Typical changes consist of branching centrilobular nodules due to plugging of the respiratory and terminal bronchioles (tree in bud appearance), or larger branching opacities when subsegmental bronchial impaction is present. Airway obstruction may also manifest itself as mosaic attenuation, particularly on expiratory images, which can be helpful in differentiating airway disease from ground-glass change due to a parenchymal infiltrate [24]. Bronchiectasis in the segmental and subsegmental airways is increasingly recognized (Figure 5) and may give rise to chronic symptomatic lung disease, with acute exacerbations and chronic sputum production [35].
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Figure 5. 36-year-old male HIV-positive patient with recurrent bronchitis. Thin section CT demonstrates extensive segmental and subsegmental bronchiectasis(straight arrows) with diffuse air trapping and several centrilobular nodules due to plugging of small airways (curved arrow).
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Mycobacterium tuberculosis
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The incidence of tuberculosis (TB) is several hundred times greater in the AIDS population than in the general population [36]. It is most frequently encountered in iv drug abusers,although rates of infection are probably related to the prevalence of TB in the local community rather than the means of HIV acquisition [36]. TB tends to become increasingly common towards the later stages of immunosuppression but, as with bacterial pneumonia, it may occur at relatively high CD4+ counts. Since the inclusion of TB as an AIDS-defining illness in 1993, it has accounted for 7% of AIDS-defining diagnoses [37].
Both the clinical and radiological features of TB are dependent on the degree of immunosuppression. At higher CD4+ counts the appearances resemble re-activation TB in the general population. At lower CD4+ counts the features are more typical of primary infection, with lymph node enlargement, pleural disease and a tendency to haematological and bronchopulmonary dissemination. As patients become more immunosuppressed, so they may become anergic to skin testing. Diagnosis is usually obtained by microscopy, culture or polymerase chain reaction testing of expectorated or induced sputum. The importance of making a timely diagnosis has been recently demonstrated by Kramer et al [38], who reported increased mortality when a diagnosis ofTB was delayed due to failure of the usual diagnostic tests. Response to treatment is dependent on the organisms sensitivity to anti-tuberculous chemotherapy, with increasingly higher rates of drug resistance being reported.
Radiological appearances, as mentioned above, may be typical of primary or reactivation TB, butatypical patterns occur particularly in the advanced stages of immune suppression. A number of series have highlighted differences in the radiological appearances of TB between the HIV infected and general populations, including lobar consolidation at unusual sites, florid lymph node enlargement, bronchopulmonary patterns and miliary spread [16, 39–41]. An important minority of patients may have normal chest radiographs despite active TB, and this is increasingly common at low CD4+ counts [39, 41]. Cavitation also tends to become less common at lower CD4+ counts.
On chest CT the commonly reported findings include consolidation, cavitation, solitary or multiple nodules, pleural effusions, nodal enlargement with necrosis, and centrilobular branching nodules or "tree in bud" due to plugging of small airways [24, 39] (Figure 6). Enlarged lymph nodes may show a typical pattern of peripheral nodal enhancement and central low attenuation on contrast enhanced CT (Figure 7), a finding that is felt to be sufficiently specific to allow empirical therapy to be commenced if the diagnosis of TBhas not otherwise been established [24]. Lymphadenopathy may also become more pronounced following the introduction of anti-viral therapy owing to a partial reversal of the previous immunological anergy.
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Figure 6. 39-year-old AIDS patient with endobronchial spread of pulmonary tuberculosis diagnosed on sputum culture. Thin section CT demonstrates multiple thick-walled cavities (straight arrow) and a "tree in bud" appearance due to plugging of small airways (curved arrow).
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Figure 7. 18-year-old male with HIV and primaryMycobacterium tuberculosis infection. Contrast enhanced CT demonstrated multiple, enlarged and centrally necrotic mediastinal lymph nodes (arrow). Minor, right upper lobe pulmonary consolidation was also demonstrated on the lung windows (not shown).
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Atypical mycobacteria
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Thoracic infection with MAC usually occurs as part of a disseminated infection acquired via thegastrointestinal tract in patients with CD4+ counts below 50 x 106 cells l-1. Although rare as an initial diagnosis in patients presenting with AIDS, MAC affects up to 35% of patients during the course of their illness [1, 2]. Imaging findings are varied and include interstitial or alveolar infiltrates, hilar lymphadenopathy and rarely cavitation [42]. The radiological appearances are similar to Mycobacterium tuberculosis (Figure 8), although pleural effusions or a normal chest radiograph are more common than in TB [42]. Miliary disease is particularly uncommon with MAC and nodal disease is usually less florid than in TB at the same stage of immunosuppression. Endobronchial disease is also reported with MAC infection, giving rise to a tree in bud appearance on thin section CT [34]. Diagnosis is usually made by isolating atypical mycobacteria from blood cultures or bone marrow aspirates.
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Figure 8. 33-year-old male with Mycobacterium avium complex infection diagnosed on blood cultures. Chest CT demonstrates multiple, well defined, soft tissue nodules throughout both lungs.
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Bacillary angiomatosis
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Bacillary angiomatosis is due to infection with the bacillus Bartonella henselae, which occurs almost exclusively in AIDS patients and results inlocalized areas of vascular proliferation at a number of anatomical sites including the airways and lung parenchyma. Radiological appearances vary, with solitary or multiple pulmonary nodules of varying size ranging from 1 mm to several centimetres in diameter having been reported [43, 44]. Associated mediastinal lymphadenopathy is a common finding and intense enhancement of both the nodules and intrathoracic nodes is reported on contrast enhanced CT, which probably reflects the marked vascularity of these lesions [43, 44].
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Fungal infections
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Fungal infections are encountered in AIDS patients but are uncommon in comparison with other infective disorders. This may be because the host defence mechanisms to fungal pathogens rely more on phagocytic cells than on T-cell-mediated mechanisms. The relative frequency of different varieties of fungal pathogens is largely dependent on the endemic rate in the local population.
Cryptococcus neoformans
Cryptococcus is the commonest pulmonary fungal pathogen in the AIDS population, accounting for up to 15% of pneumonic episodes in some series from North America [45]. Although meningitis is the commonest manifestation of cryptococcal infection, the lung is thought to be the portal of entry. Infection may be asymptomatic, but a clinically apparent pneumonia occurs in approximately 30% of patients. In common with other fungal infections, Cryptococcus tends to occur at low CD4+ counts of less than 100 x 106 cells l-1.
The diagnosis may be established by the combination of a positive cryptococcal antigen test together with isolation of the organism by microscopy or culture from expectorated or induced sputum, bronchial washings, transbronchial biopsy or percutaneous needle biopsy.
The classical appearances of focal nodule formation, with or without cavitation, are relatively rare inthe HIV infected population. The commonest radiological features in HIV patients include reticular or reticulonodular interstitial infiltrates, alveolar consolidation, ground-glass change, miliary nodules, lymphadenopathy and small pleural effusions [45–47] (Figure 9). With this wide variation in appearance, cryptococcal pneumonia shouldbe considered in the differential diagnosis ofPCP, TB and pyogenic bacterial infections [46].
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Figure 9. 36-year-old male AIDS patient with pulmonary cryptococcal infection. Thin section CT demonstrates diffuse ground-glass shadowing, pulmonary nodules (curved arrow) and an area of mass-like consolidation in the left upper lobe (straight arrows). Cryptococcus neoformans was isolated from the sputum and the lesions resolved on anti-fungal therapy.
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The diagnostic accuracy of CT for cryptococcal infection has not been specifically studied, although the ability of CT to correctly identify fungal pneumonia was assessed by Hartman et al [3] in a series of 122 patients, 11 of whom had fungal infections. Using the CT findings from previously published series as a guide, they found that a diagnosis of fungal infection was correctly included in the top three choices in 86%, and was the correct first choice diagnosis in 41% of patients.
Aspergillus fumigatus
Infection with Aspergillus is being increasingly encountered as patients with profound immunosuppression are surviving for longer in the latter stages of HIV infection [48–51]. A number of forms of infection have been described, usually in series based on chest radiographic appearances. Intissue invasive pulmonary aspergillosis, the commonest radiographic findings are thick-walled cavities with or without an intracavitary mass [48]. In keeping with other groups of immunocompromised patients, these appearances are pathologically due to haemorrhagic infarction as a result of angioinvasion [48]. Less common findings include non-cavitating nodules and lung consolidation.
Three other patterns of disease due to Aspergillus infection have also been described in the HIV infected population, two of which affect the airways. The first is necrotizing tracheobronchial aspergillosis [49], resulting in nodular thickening of the tracheal and bronchial walls owing to plaque-like lesions of Aspergillus. The second involves the more distal airways and causes bronchial obstruction due to plugs of endoluminal fungus, akin to allergic bronchopulmonary aspergillosis. These patients may be severely unwell, and radiographically may have bilateral lower lobe atelectasis and consolidation [50]. The final pattern of disease is mycetoma formation and, in keeping with the non-HIV population, these most frequently occur in a pre-existing cavity due to previous PCP or TB [24].
Histoplasma capsulatum
Histoplasmosis is relatively uncommon in the AIDS population except in patients who originate from or live in an endemic area. Pulmonary disease may occur alone, or more commonly in association with disseminated disease, usually at profound levels of immunosuppression. In a series of 18 patients born in endemic areas but living elsewhere, the pulmonary component of disseminated histoplasmosis infection included bilateral nodular or interstitial shadowing on chest radiographs [52]. In this series, and also in the study by Conces et al [53], the nodules were usually less than 3–5 mm in diameter. Other reported findings include lung consolidation, small pleural effusions and hilar or mediastinal lymphadenopathy [52, 53]. A normal chest radiograph is not uncommon with disseminated histoplasmosis, even in patients who have proven pulmonary involvement [52, 53]. Since the radiological appearances are non-specific, the diagnosis requires isolation of the organism from the lungs or elsewhere. Sputum analysis has been found to be unreliable and examination of bronchial aspirates is often necessary for diagnosis [54]. In keeping with other opportunistic infections, CT is particularly useful in the patient who has symptoms but in whom the chest radiograph is normal.
Nocardia asteroides
Nocardiosis is well described in immunocompromised patients, particularly after organ transplantation, and has been documented in AIDS patients, usually when the CD4+ count is low [55]. A study by Kramer and Uttamchandani [56] of 21 HIV-positive patients with pulmonary nocardia found the radiological appearances to be variable. Lobar or multilobar consolidation was the commonest appearance, seen in 52% of patients. Solitary pulmonary masses were identified in 24% of cases, reticulonodular infiltrates in 33% and pleural effusions in 33%. Cavitation was also a common feature, which was identified within masses or areas of consolidation in 62% of cases. Typical radiological appearances may raise the possibility of nocardia, but the diagnosis depends on demonstration of the organism on sputum culture, lavage or biopsy.
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Viral infections
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Cytomegalovirus
CMV is the most common viral pathogen to cause morbidity and mortality in patients with AIDS [57, 58]. Although commonly recovered from the lungs of AIDS patients at autopsy and isolated from bronchial washings or biopsy samples, the presence of CMV does not necessarily indicate clinical infection. Proven cases of clinically relevant pneumonitis have been notably limited. Diagnosis of CMV pneumonitis requires identification of the typical CMV inclusion bodies, but these may be present in the absence of symptoms. When there are symptoms of respiratory infection and CMV inclusion bodies are detected in the absence of other pathogens, then anti-CMV treatment can prove valuable forrelief of symptoms and may be life-saving. Waxman et al [59] described a series of patients admitted with pneumonia who underwent thorough investigation and in whom CMV was the only lung isolate. These patients had very low CD4+ counts (averaging 29 x 106 cells l-1) and presented with hypoxia, increased respiratory rates and interstitial infiltrates. In this series of nine patients, five were treated with anti-viral therapy and recovered. Three were untreated and died of respiratory failure, with CMV pneumonitis confirmed at post-mortem. Some recent studies report an increase in the prevalence of CMV pneumonitis, which appears to result from the increased use of steroid therapy in AIDS patients, longer survival of severely immunocompromised patients and increased use of PCP prophylaxis [58, 60]. Patients with pneumonitis are all severely immunocompromised, having CD4+ counts below 100 x 106 cells l-1, and in one series of 21 patients below 50 x 106 cells l-1 [61]. In this series, CMV pneumonitis was rarely found in isolation, frequently being in combination with extrathoracic CMV infection or KS.
The radiological appearances of CMV pneumonitis are varied and non-specific. They include alveolar, interstitial and nodular infiltrates on the chest radiograph, which are most typically perihilar and extend into the lower zones. Usually these appearances are attributed to PCP. The CT appearances of CMV pneumonitis have also been reported and include ground-glass attenuation, dense consolidation, bronchial wall thickening or bronchiectasis, interstitial reticulation without air-space disease and discrete pulmonary nodules or masses [61].
Herpes simplex
Herpes simplex virus (HSV) is rare as a cause ofpneumonia in the HIV infected population, and when encountered it is usually associated with profound immunosuppression. Pulmonary HSV infection is much less common than CMV and manifests as either a focal necrotizing tracheobronchitis or a diffuse interstitial pneumonitis [62]. The few case reports of HSV pneumonia have been in association with other pathogens, especially Pneumocystis carinii [63, 64].
Respiratory syncitial virus and varicella zoster are also occasional causes of pneumonitis [65]. Ebstein-Barr virus has been implicated in the pathogenesis of lymphocytic interstitial pneumonia, which is discussed elsewhere, and HIV itself may infect pulmonary macrophages [66].
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Parasitic infections
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Strongyloides stercoralis is a rare infection in the HIV infected population and may occur many years after travel to an endemic area. There are scant case reports [67, 68] documenting pulmonary infiltrates in patients with disseminated infection. Isolation of the organism from lung has been reported, with rapid improvement in symptoms following institution of anti-helminthic drug therapy. The radiological appearances are non-specific.
Toxoplasma gondii is an obligate intracellular parasite and is a rare cause of lung disease in the HIV infected population. Pomeroy and Filice [69] reported shortness of breath, cough, fever and rales in association with hepatosplenomegaly in immunocompromised patients. Goodman and Schnapp [70] reported nodular infiltrates or reticulonodular infiltrates similar to PCP in a series of patients with pulmonary toxoplasmosis. The radiological features are therefore non-specific and the diagnosis is most frequently made from bronchial washings.
Cryptosporidium and Microsporidium are both protozoans that most commonly affect the gastrointestinal tract in the HIV infected population and only rarely cause lung disease [71, 72]. The imaging appearances are non-specific, with pulmonary infiltrates and pleural effusions both described. Diagnosis is usually made by analysis of fluid obtained from BAL.
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Lymphocytic interstitial pneumonitis
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Lymphocytic interstitial pneumonitis (LIP) is a reactive pulmonary lymphoproliferative disorder occurring more commonly in immunocompromised patients, including those with AIDS. It is characterized by a polyclonal proliferation of lymphocytes with varying admixtures of plasma cells and other elements, which diffusely infiltrate the pulmonary lymphatics [73–75]. In the paediatric population, LIP is an AIDS-defining disease but the association with AIDS in the adult population is controversial, as LIP also occurs in non-HIV-infected adults.
Typical appearances on chest radiography are reticular or reticulonodular shadowing in the lower zones, ground-glass shadowing, consolidation or a nodular infiltrate [76]. Typical CT features include bilateral ground-glass shadowing, poorly defined centrilobular nodules and small subpleural or peribronchovascular nodules[77–80] (Figure 10). Other reported findings include septal thickening, thickened bronchovascular bundles, air space consolidation, large nodules, lung cysts, honeycombing, bronchiectasis, pleural thickening and lymphadenopathy in 25–68% of cases [76–81]. Lung cysts are typically located deep within the lung parenchyma and may be due to partial bronchiolar obstruction by a peribronchiolar lymphocytic infiltrate [81].
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Figure 10. 25-year-old female HIV patient with lymphocytic interstitial pneumonitis (LIP). The chest radiograph demonstrates typical changes of LIP with a bilateral nodular infiltrate predominantly distributed in the mid and lower zones. The diagnosis was established by exclusion of infective organisms and demonstration of typical features on transbronchial biopsy.
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Follicular bronchiolitis
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Follicular bronchiolitis is a benign polyclonal hyperplasia of bronchus associated lymphoid tissue that is linked with collagen vascular disorders, hypersensitivity reactions and immunodeficiency states including AIDS [82–85]. It is characterized histologically by the presence of hyperplastic lymphoid follicles with reactive germinal centres and a minor alveolar interstitial inflammatory component distributed along the bronchioles and to a lesser extent the bronchi [82, 83, 86].
On CT, the characteristic findings are centrilobular or perilobular nodules and areas ofground-glass opacity [87]. Less common CT findings include bronchial wall thickening, bronchial dilatation, emphysema, architectural distortion, interlobular septal thickening and peribronchovascular air space consolidation [87]. These appearances are similar to a variety of other diseases that affect the centrilobular bronchioles, pulmonary arteries and lymphatics, including sarcoidosis and respiratory bronchiolitis. In the context of AIDS, the appearances are also similar to the histologically related condition LIP.
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Kaposi's sarcoma
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KS is the most common AIDS-associated malignancy in Western countries and Africa. However, the incidence now appears to be falling in response to the widespread use of anti-herpes virus drugs and combination anti-retroviral therapy [88, 89]. A virus from the herpes family has been identified as the causal agent for KS and is referred to as Kaposi's sarcoma associated herpes virus (KSHV) or human herpes virus-8 [90–92]. Almost all cases of KS have been documented in either homosexual or bisexual men and their partners.
Pulmonary KS occurs in 18–47% of patients with known cutaneous KS [93, 94] and can affect the lung parenchyma, pleura or tracheobronchial tree. Bilateral perihilar pulmonary infiltrates are seen in the majority of patients, which extend into the pulmonary parenchyma along the bronchovascular bundles (Figure 11). Associated findings include thickening of the interlobular septae and nodularity of the fissures. The commonest reported CT features are ill defined parenchymal nodules, which may be surrounded by a small area of ground-glass shadowing. Pleural effusions, pericardial effusions and mediastinallymphadenopathy are also described [95]. Chest wall disease involving the sternum, ribs, thoracic spine and subcutaneous tissues has been reported in 53% of patients with thoracic KS [96].
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Figure 11. Pulmonary Kaposi's sarcoma in a 39-year-old male AIDS patient. Thin section chest CTshows multiple, bilateral lung masses and ground-glass opacity plus bilateral pleural effusions.
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Lymphoma
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Lymphoma occurs with increased frequency in AIDS patients, probably as a consequence of B-lymphocyte proliferation due to long-term stimulation by HIV and Epstein-Barr virus infection [97, 98]. Thoracic involvement maybe part of a widespread systemic disorder involving multiple organ systems or can arise as a primary tumour within the thorax, in some cases originating within mucosa associated lymphoid tissue (MALT) [99, 100]. AIDS-related lymphomas are typically high grade, B-cell, non-Hodgkin's lymphoma (NHL). NHL is thesecond most common AIDS-associated malignancy, occuring in 3–6% of AIDS patients as the first AIDS-defining illness and in up to 10% of AIDS patients at some time in their illness [101]. Unlike KS, there has not been a substantial reduction in the number of cases following the introduction of anti-retroviral therapy [88]. The reported incidence of thoracic involvement in AIDS-related lymphoma (ARL) varies from around 5% to 20% in most clinical series [102–106] but may be more common. Eisner et al [107] have reported thoracic involvement atautopsy in 71% of patients with ARL, which compared with an incidence of only 5.8% in theirclinical series. Although NHL is a frequent AIDS-defining illness, it is usually a late manifestation ofHIV disease with relatively low CD4+ cell counts in the range 100–200 x 106 cells l-1, and pulmonary involvement tends to occur in the advanced stages of immunosuppression [103, 107, 108].
Hodgkin's lymphoma is also reported in AIDS patients but is
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