Radiology in AIDS

Abdominal manifestations

 

Abdominal manifestations of AIDS are numerous and include parenchymal, lymph node and primary gastrointestinal and urinary tract disorders. Abdominal symptoms are frequent and affect up to 90% of patients with AIDS or AIDS-related complex (ARC). Multiple infections are the rule in AIDS and may be associated with lymphoma and/or Kaposi's sarcoma (KS). Moreover, AIDS patients can also be affected by protozoan and bacterial infections, such as tuberculosis, related to sexual promiscuity and low socioeconomic status. Multiple sites of infections are involved in 64 % of patients. Clinical symptoms and physical findings alone rarely suggest a specific etiology. The role of imaging methods is to identify the target-organ as well as the extent of pathologic involvement, to suggest a specific diagnosis and to facilitate percutaneous needle biopsy for a precise diagnosis.

AIDS-related complex (ARC)

Patients with ARC generally present with weight loss, fever, malaise, diarrhoea, and generalized lymphadenopathy. Ultrasonography (US) and CT findings include mild splenomegaly and clusters of mesenteric and retroperitoneallymph nodes less than 1.5 cm in diameter. Percutaneous needle biopsy is warranted only when lymph nodes measure 2 cm or more in diameter, because such enlarged nodes are rarely the result of reactive hyperplasia but are generally the sign of infection or neoplastic disease.

Malignant lymphomas

An increased incidence of all lymphomas is observed in AIDS patients, especially non- Hodgkin's lymphoma (NHL) of the small noncleaved cell type, immunoblastic sarcoma and Hodgkin's disease of the high-grade mixed-cellularity type. Moreover, the Centre for Disease Control recognizes undifferentiated lymphomas as a criterion for AIDS. The majority of AIDS-related lymphomas (ARL) have aggressive histologic subtypes and are diagnose d at advanced stages, generally stage III or IV. They carry a poor prognosis, the median survival time for patients on chemotherapy being 5.5 months. AIDS patients with systemic NHL have an abnormally large number of Epstein-Barr virus-infected B cells. Symptoms at the time of presentation are often non-specific and include weight loss, fever, night sweats, diffuse abdominal pain and malaise. Only 4% of patients have demonstrable peripheral adenopathy. Moreover, 74-95% of AIDS patients have involvement of extranodal sites and the majority of patients have multiorgan involvement. Intrahepatic involvement is a striking feature of ARLs, when compared to non-immunocompromised patients. Its incidence is between 9% and 26%, compared with 4-6% in patients without AIDS. US and CT are equally valuable in diagnosing multiple small nodular areas of macroscopic involvement. The typical findings include hypoechoic nodules on US, and hypodense, homogeneous and well-defined nodules on CT (Fig. 10). However, the nodules can occasionally be hyperechoic with a target appearance on US, and peripheral enhancement on CT. Diffuse infiltration is less frequent and is associated with homogeneous he

Figure 10. AIDS-related lymphoma. Abdominal contrast-enhanced CT scan shows bilateral renal enlargement with low-density lymphomatous renal masses associated with two focal hepatic lesions (arrows).

patomegaly. Histologic subtyping of lymphoma is crucial for chemotherapy and can be obtained by percutaneous core liver biopsy.

Focal splenic involvement and bowel involvement are observed in 32% and 26%, respectively, of ARLs, as compared to 9% and 12% in other patient groups with similar histology. The incidence of renal lesions is also increased. Imaging findings of splenic and renal ARLs include solitary or multiple nodules, which are usually heterogeneous, hypoechoic on US and hypodense on CT scans (Fig. 10). Alimentary tract lymphoma in AIDS patients has a wide variety of radiographic appearances. In patients with gastric or small bowel lymphoma, thickened folds, multiple irregular masses and deep ulcerations can be noted on barium studies. Colonic involvement may present as polypoid lesions, circumferential, diffuse wall thickening and bowel intersusception, and can also present with perforation or obstruction. Compared to Kaposi's sarcoma, lymphomatous masses tend to be bulky and are more commonly associated with submucosal infiltration. Other sites of lymphomatous involvement are numerous and include the peritoneum, the pancreas and the adrenals.

The appearance of lymphadenopathy in ARLs is non-specific. Bulky abdominal lymphadenopathy is common in ARLs, although it is seldom the presenting feature. Moreover, central nodal groups are frequently involved without evidence of peripheral adenopathy. CT is the imaging modality of choice in determining the extent of involvement and for guiding percutaneous needle biopsy.

Kaposi's sarcoma (KS)

KS is the most common malignancy in AIDS patients. For unknown reasons, its incidence is higher among homosexual men (44 %) than in other

Figure 11. Kaposi's sarcoma of the duodenum and proximal ileum. Note the presence of multiple, irregular filling defects associated with wall thickening.

patients with AIDS. The sites of involvement include the skin (93 %), lymph nodes (72 %), the gastro-intestinal tract (48 %) and both the liver and spleen (34%).
Nodal involvement is characterized by bulky mesenteric and retroperitoneal adenopathies with nodes more than 1.5 cm in diameter. On CT scans, they are typically homogeneous with no low-density areas (as in mycobacterial infection). However, KS cannot be distinguished from other neoplastic or infectious causes and pathologic confirmation is mandatory. It can be reliably obtained by fine needle aspiration biopsy. Involvement of the stomach and small bowel is common, while the colon is rarely affected. The lesions present as intraluminal filling defects on barium studies, of variable size and number (Fig. 11). Central umbilication is characteristic of KS, with a "target" appearance on air-contrast studies. Graded compression can help visualize a lesion hidden between folds; coalescent lesions may produce thickened folds visible on CT images. Focal hepatic lesions of KS are rarely encountered on US or CT; they include hepatic nodules and periportal infiltration with subsequent dilatation of the intrahepatic bile ducts. As KS can involve almost any abdominal organ, it can produce a variety of non-specific lesions which can be biopsied under CT guidance.

Opportunistic infections

Oesophagus
Candida is the most frequent cause of oesophagitis in AIDS and oesophageal candidiasis is diagnostic of AIDS in a patient with known HIV seropositivity. The main symptom is dysphagia. Double-contrast oesophagography has a higher sensitivity (85-90 %) in detecting esphageal candiadiasis than single-contrast studies. Candiadiasis can produce a diffusely ulcerated shaggy mucosa or more limited lesions such as focal plaques, subtle, longitudinally orientated filling defects and cobblestoning.

Cytomegalovirus (CMV) oesophagitis typically produces discretely marginated diamond-shaped ulcers with a peripheral lucency that represents a zone of edema against a background of normal mucosa. Furthermore, CMV often involves the distal half of the oesophagus with extension of the process in the stomach. Another unique feature of CMV is its propensity for causing giant oesophageal ulcers resulting from both infectious destruction of the mucosa and ischemic necrosis induced by CMV vasculitis. Herpex simplex virus is the third major aetiology of oesophageal infection in AIDS patients. It produces radiographic findings similar to those observed in CMV oesophagitis at both the early and advanced stages of disease.

Stomach
Most infectious gastric lesions are detected on barium studies, performed to evaluate the oesophagus or the small bowel in patients with ysphagia or diarrhoea. They rarely produce symptoms which suggest a diagnosis or focus investigations on the stomach. CMV is the main aetiological organism. It typically produces wall thickening of the OG junction and antrum, associated with gastroesophageal ulcerations which can lead to stricture formation and stenosis. Submucosal involvement can appear as "thumbprint" lesions, usually more regular and less discrete than the masses seen in KS. Gastric invasion by Mycobacterium tuberculosis with lesser omental abscess has also been described.

Small bowel
On upper gastrointestinal barium studies, abnormalities are often multifocal and affect the duodenum in 82 % of the cases, the jejunum in 64 % and the ileum in 46%. The main clinical manifestations of small bowel disease is diarrhoea. Mild diarrhoea is a frequent symptom in AIDS patients which can be related to infection, tumours or drug therapy. Some patients present with severe diarrhoea, accompanied by weight loss, dehydration, electrolyte imbalance and malabsorption. The most common cause of this serious syndrome is protozoan infection by cryptosporidia of Isospora belli. Radiographic findings include thickened folds in the proximal small bowel, fragmentation, spasm, and mild dilatation. More severe involvement produces mucosal atrophy with a subsequent "toothpaste" appearance. Differential diagnoses include giardiasis, strongyloidosis, acquired hypogammaglobulinemia, cystic fibrosis and mycobacterial infections. Several antimicrobial treatments have been attempted with limited success. Both Mycobacterium tuberculosis (MT) and Mycobacterium avium intracellulare (MAI) may be encountered in the small bowel. On barium studies, MAI infection is characterized by a pseudo- Whipple appearance and marked hypertrophy of the valvulae conniventes in the distal ileal loops. Associated mesenteric and retroperitoneal lymphadenopathy, splenomegaly and ascites are usually shown by CT.

CMV infection predominantly involves the distal ileum which has a narrowed appearance with discrete submucosal nodules and thickened folds. Ulceration, intestinal perforation or fistula are potential complications of the necrotizing vasculitis induced by CMV.

Colon
Colitis may be due to opportunistic infections, as well as to the common pathogens which are frequently encountered in homosexual men. The "gay bowel syndrome" includes traumatic and infectious lesions of the rectum and colon by pathogens such as amoebae, gonococci, salmonellae, shigellae and Campylobacter. In 90% of homosexual men, CT shows an infiltration of the perirectal fat and thickening of the rectal wall. Although several colitides are unique to immunocompromised patients, only CMV colitis produces distinctive radiographic findings. They include diffuse mucosal granularity, aphthous ulcers and caecal spasm with terminal ileal fold effacement. The presence on CT of a "target sign" due to submucosal oedema as well as right-sided and ileal involvement, are suggestive of CMV colitis. In advanced stages, CMV colitis may present with toxic megacolon, perforation, deep ulceration and submucosal

a	Figure 12. Hepatic abscess. a) Contrast-enhanced CT scan shows small hepatic abscesses (arrows) with a hypodense and nodular appearance. Liver biopsy was positive for MAI. b) In another patient, contrast-enhanced CT scan shows ill-defined area of low-density in the right hepatic lobe (arrow). Liver biopsy revealed Candida albicans.
b

hemorrhage. Plain films occasionally show pneumatosis coli.

Liver. AIDS-related cholangitis
The most frequent pathogens involved in hepatic abscess formation are MAI, CMV, Cryptococcus, Candida and Histoplasma capsulatum. Imaging findings include multiple focal lesions on US with a hypodense appearance on CT (Fig. 12 a). However, granuloma formation is frequently impaired in AIDS and disseminated hepatic infections can present as ill-defined lesions (Fig. 12 b) which can be difficult to detect with US and CT and to differentiate from diffuse or focal steatosis. In these patients, liver biopsy with culture almost always establishes the correct diagnosis.

Abnormalities of the biliary tract in AIDS patients include acalculous cholecystitis, papillary stenosis and cholangitis. The proposed pathogenic mechanisms are infection of the biliary tree by CMV or cryptosporidia, and less probably, direct infiltration of the bile duct mucosa by HIV or biliary inflammation due to the immune deficiency. Patients

Figure 13. Adenopathy from Mycobacterium tuberculosis infection.CT scan demonstrates bulky retroperitoneal, coeliac and periportal nodes with central low density areas.

present with right upper quadrant pain, jaundice, fever or abnormal liver function tests. US or CT can demonstrate segmental or diffuse dilatation, irregularity, and narrowing of the intra- or extra-hepatic bile ducts. Wall thickening of the bile ducts and gallbladder is frequently associated with enhancement of the wall of the bile ducts on CT. Periportal hyperechogenicity due to fatty infiltration of the liver has been observed in addition to cholangitis. Non-invasive imaging with US and CT may suggest AIDS-related cholangitis. However, direct cholangiography or ERCP may be useful to document the presence of subtle cholangitis. The only effective treatment is endoscopic sphincterotomy which can be performed in patients with isolated ampullary stenosis in order to obtain relief of the right upper quadrant pain.

Lymph nodes
Abdominal opportunistic infections produce clinical and radiographic patterns that can be indistinguishable from AIDS-related Kaposi's sarcoma, lymphoma or even lymphadenopathy syndrome. MAI produces a systemic infection and is more common than MT. Culture is necessary to differentiate them. They typically involve the mesenteric and retroperitoneal lymph nodes and produce bulky nodal masses. On CT images, the presence of focal parenchymal lesions and low-attenuation lymph nodes suggest MT (Fig. 13), whereas marked hepatic and splenic enlargement, diffuse jejunal wall thickening and solid lymphadenopathy suggest MAI. Low-attenuation lymph nodes in MT probably represent areas of necrosis or caseation. Definitive diagnosis requires culture of the nodal tissue which can be obtained by percutaneous biopsy.

Genito-urinary tract
The incidence of urinary tract infection has been reported to be as high as 50% in AIDS patients. Pyelonephritis is frequently complicated by intrarenal or perinephric abscesses. CT in these patients shows swollen kidneys with perirenal fascia thickening and focal areas of low density, with a peripheral enhancement representing renal abscesses. MT and aspergilloma can present as multiple masses, with a hyperechoic appearance on ultrasonography. Hydronephrosis can be caused by an obstruction due to fungus balls. Intrarenal areas of increased echogenicity have been reported in patients with Pneumocystis carinii disease, MAI and histoplasmosis. These changes can be associated with extrarenal infections and with AIDS-related nephropathy which is characterized by increased echogenicity. Multiple pathologic processes have been proposed to explain this increased echogenicity, including glomerulopathy, acute tubular necrosis, interstitial nephritis, nephrocalcinosis, tubular dilatation and atrophy.

Diagnosis and role of imaging

Radiologists have a key role in evaluating abdominal disorders in AIDS patients. In patients with dysphagia, diarrhoea, or colitis, barium studies can identify the site of involvement of the GI tract, suggest a diagnosis and guide the site of endoscopic search and site of biopsies. Ultrasonography is the initial screening method in patients with abdominal pain and jaundice. It can reveal cholangitis, focal parenchymal lesions and enlarged lymph nodes. However, CT remains the imaging modality of choice for the diagnosis, staging and follow-up of abdominal neoplasms including lymphoma and Kaposi' sarcoma.

 

Marie-France Bellin, Philippe Grenier and Nadine Martin- Duverneuil