Imaging 14:8-23 (2002)
© 2002 The British Institute of Radiology
Imaging of HIV disease in children
A C Jeanes, MRCP, FRCR and
C M Owens, MRCP, FRCR
Department of Radiology, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK
 |
Summary
|
|---|
- Most HIV infection in children is acquired by vertical transmission from mother to child.
- Identification of HIV in pregnant women is key to transmission prevention.
- Clinical manifestations differ from the adult population.
- Pulmonary disease is the commonest manifestation of HIV infection in children and accounts for 50% of deaths.
- The commonest abdominal manifestation is chronic infection of the gastrointestinal tract.
- Neoplasia is greatly increased in the paediatric HIV population, non-Hodgkin's lymphoma being the commonest tumour.
- Modern management has greatly improved the outlook for Western children with HIV.
- 80% of HIV-infected children in the third world die before their third birthday.
|
Epidemiology
|
|---|
Introduction
Since the onset of the HIV/AIDS epidemic 15 years ago, the human immunodeficiency virus (HIV) has infected more than 47 million people worldwide, with 95% of deaths occurring in the developing world. The highest prevalence of HIV/AIDS is in sub-Saharan Africa, where in January 2000 the World Health Organisation estimated there to be 24.5 million infected adults and children [1]. By the end of 1999, the total number of children under 15 years of age estimated to be infected with HIV was 1.3 million, with 3.8 million deaths worldwide since the epidemic began [1]. Over 90% of these children live in the developing world, with less than 1% living within Europe and the USA. In April 2001, surveillance data from the British Paediatric Surveillance Unit (BPSU) and the Royal College of Obstetricians and Gynaecologists (RCOG) reported 813 children to be infected with HIV within the UK, with the majority being of African origin [2].
Vertical transmission of HIV
Vertical transmission from mother to child is the most common route of acquisition of HIV in children and may occur before, during or after delivery. Prevention of HIV infection in children ultimately requires prevention of infection in adults or alternatively interruption of vertical transmission from mother to child. In 1993 the European Collaborative Study estimated the vertical transmission rate in the UK to be approximately 20%, compared with 25–35% in Africa [3]. Factors known to increase the risk of vertical transmission include a low maternal CD4 count, p24 antigenaemia, prematurity, vaginal delivery and breast feeding [3, 4]. Avoiding breast feeding, as well as the introduction of anti-retroviral therapy (for infected pregnant women and their infants) and elective Caesarian section have since reduced the risk of vertical transmission to less than 2% in the UK [5, 6]. In contrast however, in sub-Saharan Africa the vertical transmission rate has not changed significantly over the last decade [1].
Seroprevalence in pregnancy
To monitor the prevalence of HIV within the UK, unlinked anonymous HIV serosurveys were introduced. These surveys utilize blood taken for rubella serology antenatally, infant dried blood spots (Guthrie tests) post-natally, and blood taken for grouping in women undergoing termination of pregnancy [7, 8]. In 1999 the HIV seroprevalence in pregnancy was estimated to be 1 in 400 in areas of inner city London, and 1 in 6000 outside London. Since 1999 the numbers have continued to increase, by approximately 10% per annum in London and 13% elsewhere [6]. As a consequence, the number of infants born to seropositive mothers in the UK is also increasing [6].
Prevention of transmission of HIV
Multicentre antenatal voluntary screening programmes for HIV were introduced in the early 1990s. In 1992 the Department of Health (DoH) recommended that antenatal screening of HIV should be offered to all women in high risk groups and within areas of high prevalence. Uptake of HIV testing was nevertheless low, and in 1997 over 70% of pregnant women with HIV remained undiagnosed at the time of delivery. In 1999 the DoH introduced national HIV testing targets recommending HIV testing to all pregnant women as an integral part of antenatal care. By June 2000, 73% of infected pregnant women in inner London were aware of their diagnosis before delivery [6, 7].
Diagnosis of HIV in children
In older children (over 18 months of age) and adolescents, diagnosis of HIV infection is made on the basis of the detection of HIV antibodies [3]. In the newborn and in infants under 18 months of age, confirmation of the diagnosis using this method is hampered by the presence of maternal antibodies to HIV, which may merely reflect maternal infection and transplacental passage of IgG into the fetal circulation. Isolation of HIV itself is therefore required in this age group. Polymerase chain reaction (PCR) for HIV-1 DNA and RNA in addition to HIV-1 RNA culture is the method of choice. Using these methods, HIV infection can now be established with certainty in virtually all infants by 6 months of age [9, 10]. The likely timing of transmission of HIV is also an important factor in confirming the diagnosis of HIV infection in these infants. Detection of the virus on two separate specimens, separated by time, is therefore required for a definitive diagnosis.
Diagnosis of AIDS in children
The diagnosis of acquired immune deficiency syndrome (AIDS) in children is based on the revised 1994 Communicating Diseases Centre (CDC) Classification of HIV and AIDS in children (Table 1
). Before 1994, the proportion of infected children developing AIDS within the first 6 months of life within the UK was 17.7%. By April 1999, as a result of surveillance data and the early introduction of Pneumocystis carinii pneumonia (PCP) prophylaxis, in addition to anti-retrovirals for infants born to infected mothers, the proportion of children developing AIDS within the first 6 months of life had fallen to 7.2% [5].
|
The chest
|
|---|
Pulmonary manifestations are the commonest initial manifestation of HIV infection in children and are the primary cause of death in 50% with AIDS [11]. The most common pulmonary disorders encountered are bacterial pneumonias, PCP and lymphocytic interstitial penumonitis (LIP) [11, 12]. Other infections include Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC), cytomegalovirus (CMV), respiratory syncytial virus (RSV), para influenza virus and fungal infections (Cryptococcus, Aspergillus spp.). The range of pulmonary complications broadly reflects the immunological status of the patient and will also be affected by the use of both anti-retrovirals and PCP prophylaxis.
Imaging findings (both plain radiography and high resolution CT (HRCT)) are often non-specific and must be interpreted in association with clinical findings, CD4 count and viral load. Treatment is usually instituted on an empirical basis, although isolation of the organism is ideally required either by sputum analysis, nasopharyngeal aspirate (NPA), bronchiolo-alveolar lavage (BAL) or lung biopsy; the latter being less desirable owing to the high incidence of associated complications such as bronchopleural fistula and haemorrhage.
Bacterial pneumonias
Recurrent lower respiratory tract infections and bacterial pneumonias occur more frequently in children than adults with HIV/AIDS, with Streptococcus pneumoniae and Haemophilus influenzae being the most common infecting organisms [11–13]. Synchronous multi-organism infections, and infection with unusual organisms such as Salmonella sp., are also more common than in healthy aged-matched controls.
The chest radiograph usually demonstrates a focal or lobar pneumonia (Figure 1), with multilobar involvement and diffuse disease being much more common than in the normal childhood population [11]. Pleural effusions and empyemas are a frequent complication and, in contrast to adults, associated hilar or mediastinal lymphadenopathy is a common finding.
View larger version (131K):
[in this window]
[in a new window]
|
Figure 1. Staphylococcal pneumonia. Posteroanterior chest radiograph demonstrating right upper lobe consolidation. Staphylococcus aureus was isolated from blood cultures.
|
|
PCP
PCP is the most common opportunistic pulmonary infection in children with AIDS, occurring in as many as 50% of children. PCP is not infrequently the initial manifestation of HIV infection, often presenting in the early neonatal period at around 3–4 months of age.
Classical radiographic appearances include hyperinflation with diffuse bilateral interstitial or nodular infiltrates, which may be subtle initially, progressing to widespread alveolar shadowing (Figure 2). Focal or patchy infiltrates are a frequent finding, occurring in up to 50% of cases [14]. Other features include miliary or cavitatory nodules and cysts. Lymphadenopathy and pleural effusions are not a feature, and their presence suggests an alternative diagnosis [14, 15]. Cysts or pneumatocoeles occur in approximately one-third of children, with pneumothoraces and pneumomediastinum being frequent complications (Figure 3) [16]. The latter appear to be more common in children with AIDS than in those with PCP due to other causes of immunodeficiency and are thought to occur for two reasons: (1) alveolar pneumocysts evoke local connective tissue proliferation, resulting in "ball valve obstruction" with secondary obstructive emphysema and cyst/pneumatocoele rupture; (2) alternatively, increased numbers of activated macrophages result in excess elastase production, which alters the integrity of the alveolar membranes, predisposing them to rupture and the development of pneumomediastinum and pneumothorax [11, 16, 17].
View larger version (72K):
[in this window]
[in a new window]
|
Figure 2. Pneumocystis carinii pneumonia (PCP). (a) Anteroposterior (AP) chest radiograph in a 2-year-old child with vertically acquired HIV, demonstrating marked hyperinflation and bilateral, predominantly upper zoneconsolidation typical of PCP. (b) AP chest radiograph in a 6-month-old Nigerian child following an acute presentation with respiratory distress, demonstrating diffuse bilateral consolidation. Pneumocystis carinii was isolated from bronchio-alveolar lavage fluid.
|
|
View larger version (176K):
[in this window]
[in a new window]
|
Figure 3. Pneumocystis carinii pneumonia. Anteroposterior chest radiograph demonstrating predominantly upper lobe consolidation complicated by a left-sided tension pneumothorax and pneumomediastinum.
|
|
In those children where the chest radiograph remains normal or demonstrates only subtle interstitial change, HRCT can be extremely valuable in confirming the diagnosis. Although the majority of descriptions in the literature concern adults, HRCT findings appear to be identical in children [16, 17]. Findings include patchy or diffuse ground-glass opacity, consolidation, cyst or cavities, centrilobular opacities, nodules and interlobular septal thickening (Figure 4) [15, 18]. In the absence of pneumatocoeles, the majority of these findings are nevertheless rather non-specific and may also be seen with other infections, such as CMV.
View larger version (147K):
[in this window]
[in a new window]
|
Figure 4. Pneumocystis carinii pneumonia (PCP). (a)High resolution CT in a 9-month-old HIV-positive child, demonstrating patchy mosaic ground-glass opacity highly suggestive of PCP. Pneumocystis carinii was confirmed on bronchio-alveolar lavage.
|
|
In view of the variable imaging findings, demonstration of Pneumocystis carinii organisms or detection of Pneumocystis carinii DNA by PCR from NPA, expressed sputum or BAL fluid is ideally required for a definitive diagnosis.
LIP
LIP, also described as pulmonary lymphoid hyperplasia (PLH), is a lymphoroliferative disorder characterized by a diffuse interstitial infiltrate of polyclonal lymphocytes and plasma cells in addition to pulmonary lymphoid hyperplasia [19]. LIP is part of the diffuse infiltrative lymphocytosis syndrome (DILS), where there is infiltration of CD8 T-lymphocytes into the lungs, parotid glands, gastrointestinal tract and skin, and only occurs in those expressing the HLA DR5 alleles [12]. The cause is unknown, however it is thought to represent a direct "hyperimmune" lung response to the presence of either HIV or Epstein-Barr virus (EBV) and appears to be associated with a slower rate of disease progression [13, 20]. LIP is rare in adults with HIV although it occurs in approximately one-third of infected children.
Typical radiographic features are of an interstitial reticulonodular infiltrate, which may progress to patchy air space consolidation [16]. Lymphadenopathy is common and often becomes more prominent during episodes of superimposed infection (Figure 5) [11, 12]. Chronic LIP often results in patchy fibrosis with secondary traction bronchiectasis [12]. Regression of reticulonodular change may be seen, and either occurs as a consequence of the introduction of triple therapy and/or corticosteroids, or alternatively may indicate immunological deterioration and progression of HIV disease [12].
View larger version (147K):
[in this window]
[in a new window]
|
Figure 5. Lymphocytic interstitial pneumonitis (LIP). Posteroanterior chest radiograph in a 2-year-old child, demonstrating hilar lymphadenopathy and multiple parenchymal nodules typical of LIP.
|
|
HRCT features of LIP include poorly defined centrilobular nodules, diffuse ground-glass opacity, interlobular septal thickening and thickening of the bronchovascular interstitium [19, 21, 22]. In our experience, the manifestations of LIP on HRCT in children with HIV differ from those reported in the adult (non-HIV) literature, in particular cystic air spaces and transformation to malignant lymphoma are rare.
MTB
The incidence of MTB in adults has dramatically increased as a result of the AIDS epidemic and, in parallel, the frequency of MTB in children with HIV is also increasing [19, 23]. MTB infection may occur at any stage of HIV disease although it is not uncommonly the presenting manifestation [11, 12, 24]. In children, MTB disease usually occurs as a result of primary infection and it is usually acquired from an infected adult [13, 23]. In contrast to adults, only disseminated or extrapulmonary MTB disease is classified as an AIDS indicator disease in children [1, 25].
Imaging findings usually reflect the degree of immune impairment, with the likelihood of atypical presentations and disseminated disease increasing with progressive immunodeficiency. Radiological features are similar to those in immunocompetent controls, although pulmonary cavitation appears to be uncommon [24, 26]. Typical features include lobar consolidation, segmental or lobar atelectasis, pleural effusions and lymphadenopathy (Figure 6). Lymphadenopathy is usually large in volume, with the paratracheal and hilar regions being the most common sites [11, 19, 24, 27]. In contrast to adults, miliary disease is uncommon in children. Radiological findings include diffuse reticulonodular infiltrates and lymphadenopathy, which may be indistinguishable from LIP. Although this is uncommon, the chest radiograph may remain normal and has been reported to occur in as many as 15% of adults with confirmed sputum positive MTB infection [19, 28].
View larger version (138K):
[in this window]
[in a new window]
|
Figure 6. Mycobacterium tuberculosis. Anteroposterior chest radiograph in an 18-month-oldHIV-positive child, demonstrating right upper lobe consolidation typical of primary tuberculosis.
|
|
Contrast enhanced CT (CECT) and HRCT increase diagnostic accuracy compared with the chest radiograph and are of particular value in the confirmation of mediastinal and miliary disease.
CECT has an important role in the detection of mediastinal lymphadenopathy, which may be undetectable or underestimated on the chest radiograph. Nodes are typically of low density on CT and demonstrate prominent peripheral enhancement following intravenous (iv) contrast medium. These appearances are strongly suggestive of MTB infection, although are not pathognomic, and may also occur with fungal infections, such as cryptococcus, and with lymphoma [11, 27].
HRCT is valuable in the detection of parenchymal infiltrates, endobronchial disease, cavitation and miliary disease. Typical HRCT features of miliary tuberculosis (TB) are of a reticulonodular infiltrate (Figure 7). The nodules are classically uniform in size, measure 1–3 mm, and are peribronchovascular and random in distribution; associated interlobular septal thickening is common [19]. There is nevertheless considerable overlap in imaging appearances between miliary TB and a number of other conditions, the most important in children being LIP.
View larger version (109K):
[in this window]
[in a new window]
|
Figure 7. Miliary tuberculosis. High resolution CT demonstrating multiple widespread centrilobular nodules.
|
|
Confirmation of the diagnosis of MTB can be extremely difficult, particularly in children with AIDS. First, impaired T-cell function commonly leads to a negative tuberculin skin test despite active pulmonary TB [28, 29]. Second, sputum analysis is often unreliable, with positive smear tests occurring in less than 50% of patients and as few as 20% having a positive BAL [30]. Third, although in recent years DNA probes and PCR for MTB have improved the accuracy of diagnosis, these techniques are not sufficiently specific, thus culture of the organism, which usually takes several weeks, is ultimately required to confirm the diagnosis [28].
Non-tuberculous mycobacterial infections
Non-tuberculous mycobacterial (NTMB) organisms are ubiquitous in the environment although they are potential pathogens, the major risk factor for infection being immunodeficiency. Several species have been isolated; the commonest to cause infection in children with AIDS are Mycobacterium avium and Mycobacterium intracellulare (MAI), collectively known as Mycobacterium avium complex (MAC). Mycobacterium kansasii infection has also been reported, although it occurs much less commonly. Pulmonary NTMB infection usually occurs secondary to disseminated MAC infection from the gastrointestinal tract. Primary pulmonary NTMB infection is rare and usually occurs in patients with advanced HIV disease [24].
Radiographic features are similar in adults and children, and are indistinguishable from MTB infection. Findings include hilar or mediastinal lymphadenopathy, pulmonary infiltrates, atelectasis and cavitatory nodules [31, 32].
Viral infections
The clinical manifestations of viral superinfection in children with HIV are dependent upon the degree of immunodeficiency at the time of infection. Infection may occur as a result of a primary infection or reactivation of latent virus. Viruses commonly implicated include RSV, influenza and para influenza virus, CMV, measles and, less frequently, Varicella-Zoster virus (VZV).
Radiographic features are usually non-specific and include diffuse interstitial infiltrates, nodules and consolidation (Figure 8). Bacterial superinfection is common, and isolation of the virus in secretions or washings is required.
View larger version (120K):
[in this window]
[in a new window]
|
Figure 8. Cytomegalovirus (CMV) pneumonitis complicated by Adult Respiratory Distress Syndrome. Anteroposterior chest radiograph demonstrating hilar and mediastinal lymphadenopathy, with bilateral widespread air space consolidation. CMV was isolated from nasopharyngeal aspirate.
|
|
VZV
Primary VZV infection results in chicken pox, with subsequent reactivation causing shingles. VZV infection in children with HIV usually results in a more protracted illness than healthy controls, with approximately 50% suffering from chronic or recurrent infection [33]. With increasing immunological impairment, the risk of complications such as varicella pneumonia or encephalitis increases. The mortality rate in children with AIDS is 15% [34].
The chest radiograph typically shows bilateral diffuse reticulonodular infiltrates. The nodules are typically variable in size, ranging from 3 mm to 10 mm, and often coalesce resulting in focal areas of consolidation (Figure 9). Superimposed bacterial infection is also common.
View larger version (139K):
[in this window]
[in a new window]
|
Figure 9. Varicella-Zoster virus pneumonia. Anteroposterior chest radiograph demonstrating widespread nodules, which have become confluent at the right lung base.
|
|
Miscellaneous conditions
Bronchiectasis
Bronchiectasis is defined pathologically as a permanent abnormal dilatation of the bronchial tree and is common in both adults and children with HIV/AIDS [35]. It is thought to occur as a consequence of either recurrent or chronic infection or, in children, secondary to chronic LIP.
HRCT is the imaging modality of choice in children and adults both for confirmation of the diagnosis of bronchiectasis and for assessment of disease extent.
Cardiovascular manifestations
Cardiac disease is common both in children and adults with HIV. Manifestations include dilated cardiomyopathy, myocarditis, pericardial effusions, arrhythmias and myocardial infarction [11, 36–38]. Dilated cardiomyopathy is the most frequent finding in children and, although several mechanisms have been postulated, the aetiology remains unclear [37, 38]. Suggested causes include direct infection by HIV itself, opportunistic infections, malnutrition, drug cardiotoxicity and selenium deficiency. Zidovudine therapy has been reported to cause cardiomyopathy in adults, although its effect in children remains controversial [39].
The chest radiograph may show cardiomegaly or pulmonary oedema, although it is insensitive for the diagnosis or exclusion of cardiac disease. Echocardiography is the investigation of choice, with approximately 60% of children showing some degree of myocardial dysfunction [37].
|
Abdominal manifestations
|
|---|
The most common abdominal manifestations of HIV infection in children are recurrent or chronic infections of the gastrointestinal tract. Oral manifestations are frequently the first indicator of HIV infection and include angular cheilitis, gingivitis, mucositis, pharyngitis and oesophagitis. Pathogens include Candida, herpes simplex virus (HSV) and CMV. Gastroenteritis and diarrhoea are common and may be chronic, severe and debilitating, resulting in malabsorption and malnutrition. Pathogens include enteric bacteria such as Salmonella sp, Campylobacter, viruses such as CMV and opportunistic organisms such as cryptosporidium and MAI [11, 12]. Generalized lymphadenopathy and hepatosplenomeagly are also common and may be secondary to HIV infection, DILS, neoplasia or superinfection with opportunistic organisms such as CMV, Pneumocystis carinii, MAI and hepatitis B or C virus. Complications such as pneumatosis coli and toxic megacolon may occur secondary to infective colitis [12]. Intussusception is a frequent complication, particularly in those with bowel wall thickening or mesenteric adenopathy secondary to lymphoma, DILS, or MAI or MTB infection.
The radiological findings of many of these conditions are non-specific, however some specific imaging characteristics have been reported and will be described below.
Candidiasis
Candida is a normal gut commensal, which can colonize and cause infection in both the immunocompetent and immunodeficient host. Oral candidiasis is the presenting manifestation of HIV in approximately 10% of children [33]. Invasive candidiasis (oesophagitis, candida enteritis or pneumonia) is classified as an indicator disease for AIDS in children [1].
Classical radiological features of oesophageal candidiasis on barium examination are of either a "cobblestone" appearance, due to diffuse ulceration, or, less commonly, focal discrete ulcerations. HSV and CMV infection can cause similar imaging appearances. Anti-fungal treatment is usually commenced on an empirical basis, and endoscopy and microbiological confirmation are usually reserved for those not responding to therapy.
CMV
CMV infection is the commonest cause of infective enteritis and causes a small vessel vasculitis resulting in ischaemic necrosis and ulceration [12, 40]. It predominantly affects the terminal ileum and caecum, although the stomach and small bowel may also be affected. Complications include gastric outlet obstruction, intussusception, pneumatosis intestinalis and toxic megacolon, which may be complicated by perforation (Figure 10).
View larger version (129K):
[in this window]
[in a new window]
|
Figure 10. Cytomegalovirus (CMV) colitis. Plain abdominal radiograph demonstrates abdominal distension and marked subserosal (arrows) and intramural gas due to CMV colitis. Pneumatosis intestinalis can also occur with other viral and bacterial infections such as rota virus, cryptosporidium and Clostridium difficile.
|
|
Contrast examination may demonstrate thickening of mucosal folds and luminal narrowing secondary to wall thickening and strictures. Although these features are rather non-specific and may be seen with other enteric infections, the presence of focal ulceration of the terminal ileum or caecum strongly suggests the diagnosis of CMV enteritis.
PCP
Disseminated PCP (usually following treatment and healing) may result in scattered punctate calcifications within the liver, spleen and other abdominal organs [11].
MAI
MAI infection usually occurs with advanced HIV disease and is usually disseminated at the time of presentation. MAI is classified as an AIDS indicator disease both in adults and children with HIV [1]. Symptoms are commonly non-specific and include fever, weight loss, anaemia, abdominal pain and diarrhoea.
Common features include hepatosplenomegaly, lymphadenopathy and bowel wall or peritoneal thickening. Lymphadenopathy is usually large in volume, with the mesentery and retroperitoneum being the commonest sites. Up to one-third also demonstrate mediastinal adenopathy [31]. Nodes are characteristically echo-poor on ultrasound and low density on CT, demonstrating marked peripheral enhancement following iv contrast medium (Figure 11). Occasionally, superinfection of large necrotic nodal masses may be complicated by abscess and fistula formation. Although these features are considered characteristic of disseminated MAI [11, 12, 31], identical appearances may also occur with MTB and fungal infections such as Cryptococcus, and culture of the organism from blood, tissue, faeces or bone marrow is therefore required for confirmation of the diagnosis.
View larger version (71K):
[in this window]
[in a new window]
|
Figure 11. Mycobacterium avium intracellulare (MAI). (a) Ultrasound of the abdomen in a 12-year-old girl with AIDSdemonstrates bulky echo-poor mesenteric adenopathy. (b) Contrast enhanced CT abdomen of the same child, demonstrating characteristic low density ring enhancing lymphadenopathy (arrow). MAI was cultured from stools.
|
|
DILS
DILS is rare in adults, occurring in only 4% of patients compared with 30% of children [12]. Clinically there is parotid gland enlargement in addition to varying degrees of lymphadenopathy and organomegaly. Associated LIP is common. Both children and adults with DILS appear to demonstrate a slower rate of disease progression, presumably secondary to improved immune surveillance [12].
Classically the parotid glands demonstrate multiple lymphoepithelial cysts, which appear as multiple hypoechoic or anechoic nodules on ultrasound, with or without parotid calcification. Similar appearances may also be seen within the spleen (Figure 12).
View larger version (123K):
[in this window]
[in a new window]
|
Figure 12. Diffuse infiltrative lymphocytosis syndrome (DILS). High resolution ultrasound of the right parotid gland demonstrates multiple hypoechoic lymphoepithelial cysts.
|
|
|
Neoplasia in paediatric AIDS
|
|---|
The incidence of malignancy in children with HIV in the UK is increased compared with the general paediatric population. The risk of developing a malignancy is reported to be approximately 2500 times greater than that expected in age-matched healthy controls (under 5 years of age) [32]. HIV-related malignancies are reported to occur in those with advanced HIV disease. However, a recent report by Caselli et al [41] has shown that up to 40% of children do not have overt immunodeficiency.
Non-Hodgkin's lymphoma is the most common tumour and is classified as an AIDS indicator disease [1]. Kaposi's sarcoma and immunoblastic sarcoma are also AIDS indicator diseases, although they are rare in children. Other common childhood soft tissue sarcomas such as rhabdomyosarcoma are not classified as indicator diseases [32].
Non-Hodgkin's lymphoma
Non-Hodgkin's lymphoma (NHL) is usually of B-cell origin and is almost invariably associated with infection or reactivation of EBV [41]. The clinical and radiological features of AIDS-related lymphoma (ARL) in children are similar to those encountered in adults, although B symptoms are less common in children [42]. The distribution of disease differs from that in the immunocompetent population, with a high incidence of extranodal disease occurring at unusual sites [41, 42]. The abdomen is the most common disease site in children, with other sites including the central nervous system, lung and bone marrow.
Diffuse infiltration of the liver, spleen or kidneys usually results in global enlargement, and as a consequence imaging features are non-specific. Focal parenchymal hepatic and splenic lesions are, however, a frequent manifestation of NHL both in adults and children with AIDS and may be large and confluent or small and widely scattered. These lesions are typically echo-poor on ultrasound (Figure 13) and hypodense on CT, enhancing poorly following contrast medium [43]. Necrosis and cystic change are common features, and may be easier to appreciate on ultrasound than on CT. The presence of focal parenchymal masses is reported to be specific for ARL by some authors; however, in our experience focal lesions may be present in both infection and malignancy and are a non-specific finding [12]. Direct involvement of the gastrointestinal tract occurs in approximately 50% of cases of ARL, with the small bowel and stomach being the most common disease sites [43]. Typical features include diffuse or focal bowel wall thickening, and eccentric nodular masses. Intraperitoneal and omental involvement may manifest as nodules or diffuse thickening with imaging appearances identical to those seen in diffuse carcinomatosis (Figure 14) [44].
View larger version (109K):
[in this window]
[in a new window]
|
Figure 13. Non-Hodgkins B-cell lymphoma. High resolution ultrasound of the spleen in a child with AIDS-related lymphoma, demonstrating a focal hypoechoic splenic lesion.
|
|
View larger version (91K):
[in this window]
[in a new window]
|
Figure 14. Abdominal Burkitt's lymphoma. (a) CT abdomen following intravenous contrast medium, demonstrating ascites, peritoneal and mesenteric infiltration, and dilatation of the common bile duct secondary to infiltration of the porta hepatis (arrow). (b) Ultrasound of the abdomen of the same child using a high resolution linear array transducer demonstrates echo-poor peritoneal nodules and extensive mesenteric infiltration (arrow).
|
|
Kaposi's sarcoma
Kaposi's sarcoma is associated with human herpes virus-8 (HHV-8) infection and, although rare in paediatric HIV in Europe, it is the commonest neoplasm in adult homosexual HIV-positive men, with a reported incidence of 15% [13, 41].
Radiological features include focal or diffuse hepatic and splenic involvement in addition to large volume retroperitoneal lymphadenopathy and focal gastrointestinal infiltration [41].
|
Renal manifestations of HIV and AIDS
|
|---|
Renal abnormalities in children with AIDS are common and include HIV nephropathy, recurrent urinary tract infection and, less commonly, renal malignancy [11, 45].
HIV nephropathy
HIV nephropathy (HIVN) is the most common renal manifestation of AIDS in children. The cause is uncertain; however, infection, particularly the direct effects of HIV itself, immune complex deposition and the deposition of viral proteins have all been implicated [45]. Pathologically there is microscopic dilatation of collecting tubules containing hyaline casts in addition to focal segmental glomerular sclerosis [11]. HIVN usually progresses to end-stage renal disease, although the rate of progression is reported to be slower in children than in adults.
Classical ultrasound appearances are of bilateral enlarged echogenic kidneys. An increased frequency of simple renal cysts has also been reported in children with HIVN compared with aged-matched controls, although the cause for this is uncertain [45].
Infectious complications
Recurrent urinary tract infections may affect as many as 50% of children with AIDS, with an increased frequency of unusual and opportunistic infections such as Cryptococcus neoformans, MTB, Pneumocystis carinii and, rarely, Candida and Aspergillus sp.
Ultrasound is the imaging modality of choice, although appearances are usually normal or non-specific despite documented infection. Renal candidiasis, although more commonly seen in children with primary immunodeficiency or premature neonates, has also been reported in children with HIV [44]. Ultrasound features are characteristic and include focal echo-poor or echogenic masses within the renal collecting system or parenchyma, with associated with hydronephrosis secondary to urinary tract obstruction.
|
Central nervous system manifestations of HIV in children
|
|---|
The spectrum of neurological manifestations differs from those in adults with AIDS and includes HIV encephalopathy, neurobehavioural disturbances, basal ganglia calcific vasculopathy, cerebrovascular complications secondary to acquired protein S/C inhibitors and arterial ectasia, opportunistic infections and lymphoma [46]. Central nervous system (CNS) complications occur more frequently in children with AIDS than adults, although in contrast to adults, opportunistic infections are rare [46].
HIV encephalopathy
HIV is both lymphotropic and neurotropic and has been isolated from both the cerebrospinal fluid and brain parenchyma of adults and children with HIV encephalopathy (HIVE). Direct invasion of the CNS by HIV is thought to result in apoptosis and myelin damage [11]. HIVE is the commonest CNS manifestation of HIV infection in children, with between 50% and 90% having clinical or radiological evidence of encephalopathy at some stage. Approximately 10% of children with HIVE present within their first year of life [39, 47].
HIVE is an AIDS indicator disease and is both a clinical and radiological diagnosis. Two main patterns are described in children: a "static" encephalopathy manifesting as non-progressive developmental delay; and a "progressive" encephalopathy with associated microcephaly, pyramidal tract signs and spasticity [39, 47].
Radiological findings include cerebral atrophy and white matter disease, which may be associated with basal ganglia or white matter calcification [46, 47]. Cerebral atrophy may be demonstrated either on CT or MRI, and three patterns are described. First, there may be ventriculomegaly, which is out of proportion to the degree of cortical atrophy; second, there may be generalized atrophy (Figure 15); and third, there may be features of a necrotizing encephalopathy with an associated cardiomyopathy [11, 46, 47]. White matter lesions are typically seen within the periventricular white matter and centrum semi-ovale. They are usually underestimated on CT and are best demonstrated on MRI, as low signal on T1 weighted sequences and high signal on T2 weighted sequences (Figure 16) [46]. In contrast to adults, basal ganglia calcification is common in children with HIVE, occurring in up to 33% of children [46, 47]. Classical CT appearances are of bilateral symmetrical calcification involving the globus pallidus, putamen, thalamus and grey/white matter (Figure 17). Basal ganglia calcification is reported to be rare under 10 months of age [46, 47], although in our experience, cranial ultrasound may detect basal ganglia calcification prior to visualization on CT as early 3 months of age (Figure 18).
View larger version (137K):
[in this window]
[in a new window]
|
Figure 15. HIV encephalopathy. (a) Axial non-contrast CT of the head in a 5-month-old boy demonstrates typical appearances of HIV atrophy with ventricular enlargement and prominence of the cortical sulci.
|
|
View larger version (127K):
[in this window]
[in a new window]
|
Figure 16. HIV encephalopathy. (a) Axial T2 weighted spin echo MRI demonstrating mild cortical atrophy with high signal within the periventricular white matter.
|
|
View larger version (124K):
[in this window]
[in a new window]
|
Figure 17. Axial non-contrast CT of the head in a 10-year-old girl, demonstrating a right frontal infarct and basal ganglia calcification. Thrombophilia screen demonstrated protein S deficiency.
|
|
View larger version (154K):
[in this window]
[in a new window]
|
Figure 18. Sagittal ultrasound of the head in a 3-month-old child with HIV, demonstrating typical linear appearances of early basal ganglia calcification within lenticulostriate vessels (arrows).
|
|
CNS infection
Congenital TORCH infections (toxoplasmosis, rubella, CMV and herpes simplex) have identical imaging appearances to those in infants without HIV infection [46]. Opportunistic infections such as toxoplasmosis, CMV and progressive multifocal leukoencephalopathy (PML) are all AIDS indicator diseases (Figure 19). All are rare in children, except CMV, which is still common in endemic areas such as sub-Saharan Africa. Imaging appearances are similar to adults with AIDS.
View larger version (103K):
[in this window]
[in a new window]
|
Figure 19. Cerebral toxoplasmosis. (a) T1 weighted and (b) T2 weighted spin echo MRI demonstrates two focal periventicular basal ganglia lesions, which are of intermediate signal on T1 weighting and demonstrate marked perilesional high signal compatible with oedema on T2 weighting.
|
|
Intracranial neoplasms
Intracranial neoplasms are rare in children with HIV/AIDS [12]. NHL is the commonest, occurring in approximately 4% of children with AIDS. Histologically, CNS lymphoma is usually of B-cell origin and is frequently associated with EBV infection [41].
Classical CT and MRI appearances are of solitary or multiple homogeneous mass lesions within the periventricular white matter, basal ganglia, or at the grey/white matter interface, which enhance homogeneously following iv contrast medium. Lesions are typically isodense or hyperdense relative to brain on CT, and hypointense on T1 weighted sequences and isointense or hyperintense on T2 weighted sequences [48]. In children and adults with AIDS, imaging appearances are often atypical owing to necrosis or haemorrhage (Figure 20). In addition, ring enhancement following iv contrast medium is common and may lead to diagnostic difficulties, particularly in differentiating lymphoma from intracerebral toxoplasmosis [48].
View larger version (127K):
[in this window]
[in a new window]
|
Figure 20. Central nervous system B-cell non-Hodgkin's lymphoma (NHL). T2 weighted spin echo MRI of the brain in a 7-year-old girl, demonstrating a large solitary right frontal mixed signal mass lesion with local mass effect. Biopsy confirmed B-cell NHL.
|
|
Recently, fluorodeoxyglucose positron emission spectroscopy (FDG-PET) and proton magnetic resonance (1H-MR) spectroscopy have both been used in the evaluation and quantification of early HIVE in children, in addition to differentiating focal CNS lesions, in particular lymphoma, from infections such as toxoplasmosis and PML. Both techniques have been shown to be more sensitive and specific than MRI alone [49, 50].
|
Musculoskeletal manifestations
|
|---|
Musculoskeletal manifestations usually occur in those with advanced HIV infection and may be the initial manifestation [11, 12]. Septic arthritis, osteomyelitis and skin sepsis are the most frequent manifestations in children, and isolation of unusual or opportunistic organisms is common (Figures 21 and 22). Bacillary angiomatosis is a rare infectious manifestation of HIV infection and although it has been documented in adults with HIV there have only been anecdotal reports in children.
View larger version (89K):
[in this window]
[in a new window]
|
Figure 21. Soft tissue Mycobacterium avium intracellulare infection. Axial T2 weighted spin echo MRI of both thighs demonstrates focal areas of increased signal within the subcutaneous fat of the left buttock and right anterior leg, with high signal tracking along the fascial planes of sartorius (arrow).
|
|
View larger version (76K):
[in this window]
[in a new window]
|
Figure 22. Septic arthritis. (a) Radiograph of the left shoulder in a 14-year-old HIV-positive boy demonstrates marked soft tissue swelling inferomedial to the glenoid. (b) High resolution ultrasound in the same child demonstrates a large complex collection within the infraglenoid bursa. Multiple granulomata were isolated from synovial biopsies, and empirical anti-tuberculous chemotherapy was commenced. Neither Mycobacterium tuberculosis or non-tuberculous mycobacterium were identified on microscopy or culture.
|
|
|
Conclusions
|
|---|
The natural history of vertically acquired HIV in children has not as yet been fully evaluated and the long-term prognosis remains unknown. Current estimates are that approximately 20% of vertically infected children will develop AIDS in infancy, 10% will die and 40% will develop AIDS by 5 years [9]. After infancy it is estimated that approximately 5% of children per year progress to AIDS. The current median survival is reported to be approximately 9–10 years although, owing to the introduction of triple combination therapy in addition to PCP prophylaxis, the rate of disease progression of HIV in Europe and North America appears to be slowing and some children may survive into early adulthood. Whether this increased longevity results in a higher or lower prevalence of HIV-related cancers remains to be elucidated [41].
In the Western world, with earlier diagnosis in infancy and the use of more potent anti-retroviral agents, survival is likely to improve further in the future. This starkly contrasts with the dismal status in Africa, where the mortality for children with vertically acquired HIV remains high, with 80% dying within their first 3 years of life.
|
References
|
|---|
-
UNAIDS. Report on the global HIV/AIDS epidemic. World Health Organisation, Communicable Disease Surveillance and Response. Joint United Nations Programme on HIV/AIDS, June 2000.
-
Tookey PA, Masters J. National study of HIV in pregnancy, Newsletter 47. Royal College of Obstetricians and Gynaecologists, June 2001:1–4.
-
HIV in pregnancy and early childhood. Drug Ther Bull 1999;37:65–7.[Abstract/Free Full Text]
-
Newell ML, Peckham C. Vertical transmission of HIV infection. Acta Paediatrica Suppl 1994;400:43–5.[Medline]
-
Duong T, Ades AE, Gibb DM, Tookey PA, Masters J. Vertical transmission rates for HIV in the British Isles: estimates based on surveillance data. BMJ 1999;319:1227–9.[Abstract/Free Full Text]
-
Tookey PA, Cliffe S. Antenatal HIV testing—making a difference. Plenary session VII RCPH, York 2001. Arch Dis Child 2001;84(Suppl.):A1–A9.
-
Prevalence of HIV in the UK. Summary report from the Unlinked Anonymous Surveys Steering Group. Department of Health 1999. Institute of Child Health, PHLS Communicable Disease Surveillance Centre. The Scottish Centre for Infection and Environmental Health.
-
Nicoll A, Gill ON, Peckham CS, Ades AE, Parry J, Mortimer P, et al. The public health applications of unlinked anonymous seroprevalence monitoring for HIV in the United Kingdom. Int J Epidemiol 2000;29:1–10.[Abstract/Free Full Text]
-
Gibb D. Guidelines for management of children with HIV infection (3rd edn). Feb 1998:1–7.
-
Nielson K, Bryson YJ. Diagnosis of HIV infection in children. Pediatr Clin North Am 2000;47:39–63.[Medline]
-
Haller JO, Cohen HL. Paediatric HIV infection: an imaging update. Pediatric Radiology 1994;24:224–30.[Medline]
-
Owens CM, Allan R, Thomas K, Evans J, Stevens J. The radiological spectrum of vertically-acquired HIV infection. Br J Radiol 1996;69:777–82.[Abstract]
-
Mcloud TC, Naidich DP. Thoracic disease in the immunocompromised patient. Radiol Clin North Am 1992;30:525–54.[Medline]
-
Sivit CJ, Miller CR, Rakusan TA, Ellaurie M, Kushner DC. Spectrum of chest radiographic abnormalities in children with AIDS and pneumocystis carinii pneumonia. Pediatr Radiol 1995;25:389–92.[Medline]
-
Webb WR, Muller NL, Naidich DP. Disease characterised primarily by parenchymal opacification. In: High resolution CT of the Lung (3rd edn). Philadelphia, PA: Lippincott-Williams & Wilkins, 2001:355–420.
-
Ambrosino MM, Roche KJ, Genieser NB, Kaul A, Lawrence RM. Application of thin section low dose chest CT (TSCT) in the management of paediatric AIDS. Paediatr Radiol 1995;25:393–400.[Medline]
-
Evlogias NE, Leonidas JC, Rooney J, Valderama E. Severe cystic pulmonary disease associated with chronic Pneumocystis carinii infection in a child with AIDS. Pediatr Radiol 1994;24:606–8.[Medline]
-
Gruden JF, Huang L, Turner J, Webb WR, Merrifield C, Stansell JD, et al. High resolution CT in the evaluation of clinically suspected pneumocystis carinii pneumonia in AIDS patients with normal, equivocal or non specific radiographic findings. AJR 1997;169:967–75.[Abstract/Free Full Text]
-
Webb WR, Muller NL, Naidich DP. Disease characterised primarily by nodular or reticulonodular opacities. In: High resolution CT of the lung (3rd edn). Philadelphia, PA: Lippincott-Williams & Wilkins, 2001:259–353.
-
Heitzmann ER. Pulmonary neoplastic and lymphoproliferative disease in AIDS: a review. Radiology 1990;177:347.[Abstract]
-
Gibson M, Hansell DM. Lymphocytic disorders of the chest: pathology and imaging. Clin Radiol 1998;53:469–80.[Medline]
-
Fishback N, Koss M. Update in lymphoid interstitial pneumonitis. Curr Opin Pulm Med 1996;2:429–33.[Medline]
-
Donald PR. Childhood tuberculosis. Curr Opin Pulm Med 2000;6:187–92.[Medline]
-
Rigsby MO, Curtis AM. Pulmonary disease from nontuberculous mycobacteria in patients with human immunodeficiency virus. Chest 1994;106:913–9.[Free Full Text]
-
Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults, Centres for Disease Control, 1993 MMWR Morb Mortal Wkly Rep. 1992;41:1–11.
-
Leung AN, Braunes MW, Gamsu G, Mlika-Cabanne N, Ben Romdhane H, Carette MF, et al. Pulmonary tuberculosis: comparison of CT findings in HIV-seropositive and HIV-seronegative patients. Radiology 1996;198:687–91.[Abstract]
-
Kim WS, Moon WK, Kim IO, Lee HJ, Im JG, Yeon KM, et al. Pulmonary tuberculosis in children: evaluation with CT. AJR 1997;168:1005–9.[Abstract/Free Full Text]
-
Goodman PC. Tuberculosis and AIDS. Radiol Clin North Am 1995;33:707–15.[Medline]
-
Snider DE, Rieder HL, Combs D, Bloch AB, Hayden CH, Smith MHD. Tuberculosis in children. Pediatr Infect Dis J 1988;7:271–8.[Medline]
-
Fitzgerald JM, Grzybowski S, Allen EA. The impact of human immunodeficiency virus infection on tuberculosis and its control. Chest 1991;100:191–200.[Free Full Text]
-
Pursner M, Haller JO, Berdon WE. Imaging features of mycobacterium avium-intracellulare complex (MAC) in children with AIDS. Pediatr Radiol 2000;30:426–9.[Medline]
-
Evans AJ, Crisp AJ, Hubbard RB, Colville A, Evans SA, Johnston IDA. Pulmonary mycobacterium kansasii infection: comparison of radiological appearances with pulmonary tuberculosis. Thorax 1996;51:1243–7.[Abstract]
-
Ambrosino MM, Genieser NB, Krasinski K, Greco MA, Borkowsky W. Opportunistic infections and tumours in immunocompromised children. Radiol Clin North Am 1992;30:591.
-
Jura E, Chadwick E, Josephs S. Varicella zoster virus infection in children infected with HIV. Paediatr Infect Dis J 1989;8:586–90.[Medline]
-
Thurlbeck WM, Churg AM. Bronchiectasis. In: Pathology of the lung (2nd edn). New York: Thieme, 1995:804–11.
-
Barbaro G, Di Lorenzo G, Grisorio B, Barbarini G. Incidence of dilated cardiomyopathy and detection of HIV in myocardial cells of HIV-positive patients. Gruppo Italiano per Lo Studio Cardiologico dei Pazienti Affetti da AIDS. N Engl J Med 1998;339:1093–9.[Abstract/Free Full Text]
-
Rerkpattanapipat P, Wongpraparut N, Jacobs LE, Kotler MN. Cardiac manifestations of acquired immunodeficiency syndrome. Arch Intern Med 2000;160:602–8.[Abstract/Free Full Text]
-
Lipshultz SE, Orav EJ, Sanders SP, Hale AR, McIntosh K, Colan SD. Cardiac structure and function in children with human immunodeficiency virus infection treated with zidovudine. N Engl J Med 1996;327:1260–5.[Abstract]
-
Tardieu M, Le Chenadec J, Persoz A, Meyer L, Blanche S, Mayaux MJ. HIV-1-related encephalopathy in infants compared with children and adults. French Pediatric HIV Infection Study and the SEROCO Group. Neurology 2000;54:1089–95.[Abstract/Free Full Text]
-
Jeffrey RB. Abdominal imaging in the immunocompromised patient. Radiol Clin North Am 1992;30:549–50.
-
Caselli D, Klersy C, De Martino M, Gabiano C, Galli L, Tovo PA, et al. Human imunodeficiency virus-related cancer in children: incidence and treatment outcome—report of the Italian Register. J Clin Oncol 2000;18:3854–61.[Abstract/Free Full Text]
-
Siskin GP, Haller JO, Miller S, Sundaram R. AIDS-related lymphoma: radiologic features in paediatric patients. Radiology 1995;196:63–6.[Abstract]
-
Dodd GD III, Greenler DP, Confer SR. Thoracic and abdominal manifestation of lymphoma occurring in the immunocompromised patient. Radiol Clin North Am 1992;30:597–610.[Medline]
-
Zinn HL, Haller JO. Renal manifestations of AIDS in children. Paediatr Radiol 1999;29:558–61.[Medline]
-
Zinn HL, Rosberger ST, Haller JO, Schlesinger AE. Simple renal cysts in children with AIDS. Pediatr Radiol 1997;27:827–8.[Medline]
-
Davenport C, Dillon WP, Sze G. Neuroradiology of the immunosuppressed state. Radiol Clin North Am 1992;30:611–37.[Medline]
-
Angelini L, Zibordi F, Triulzi F, Cinque P, Giudici B, Pinzani R, et al. Age dependant neurologic manifestations of HIV infection in children. Neurol Sci 2000;21:135–42.[Medline]
-
Lee SH, Rao KCVG, Zimmerman RA. Primary tumours in adults. In: Cranial MRI and CT (3rd edn). McGraw-Hill, 1992:295–380.
-
Safriel YI, Haller JO, Lefton DR, Obedian R. Imaging of the brain in the HIV-positive child. Pediatr Radiol 2000;30:725–32.[Medline]
-
Lu D, Pavlakis SG, Frank Y, Bakshi S, Pahwa S, Gould RJ, et al. Proton MR spectroscopy of the basal ganglia in healthy children and children with AIDS. Radiology 1996;199:423–8.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
Answers to multiple-choice questionnaire: Imaging in AIDS/HIV [from Imaging 14(1)]
Imaging,
June 1, 2002;
14(3):
246 - 249.
[Full Text]
[PDF]
|
|
|
Top
Summary
Epidemiology
