Clinical Radiology (1992) 45, 73 78
Editorial Radiology in Malabsorption A diagnosis of malabsorption or the clinical suspicion of its presence are the indications for barium radiology in less than 5% of patients referred with small bowel related symptoms. Most of these patients are examined by small bowel enema (SBE), frequently supported by computed tomography (CT). CT is of unique importance in the study of the malignant complications, mostly of coeliac disease. It is of supplementary value in the further study of conditions which include Whipple's disease and secondary lymphangiectasia. The diagnosis of a malabsorption state should be the function of the clinician, not of the radiologist. The purpose of radiology is to accurately depict changes of the mucosal surface or of the bowel contour that may lead to the diagnosis of the cause of malabsorption and to demonstrate possible complications. Barium Examination for Diagnosis
SBE is recommended for the investigation of malabsorption since it can avoid or defer flocculation. Its further benefit is that it distends the bowel lumen, a more important feature in most small bowel investigations than the achievement of double contrast. Flocculated barium cannot adhere reliably to the gut mucosa and will fail to outline mucosal alterations accurately. Flocculation is of little value as a sign of a malabsorption state since it may occur in any hypersecretory state or even without apparent cause. The SBE - Technical Points
The standard SBE examination requires catheter placement into the distal duodenum or first loop of jejunum, preferably using a balloon-equipped catheter to reduce reflux into the stomach. A barium suspension, either undiluted Micropaque (Nicholas Corp., Slough) or Entero-H (E-Z-EM Comp., New York, USA) is injected through the catheter to a total amount of 180-220 ml. This is followed by the infusion of 1 2 litres of 0.5% methylcellulose solution, using a hand operated or peristaltic pump. Compression fluoroscopy and spot films are done during the single contrast phase, and the developing and established double contrast phases. An overview prone film is done at the end of the study. (For further detail see Herlinger and Maglinte, 1989a). In patients with malabsorption, especially if an excess of small bowel fluid has been shown on a preliminary plain film, it is necessary to inject more than the usual amount of barium through the catheter (e.g. 240 260 ml). The infusion of 0.5% methylcellulose should follow immediately. Early compression views of all bowel loops are taken in the lumen distended state, before double contrast has developed. Double contrast images may be recorded later, if flocculation has not already occurred. It may be important to include the distal duodenum in the SBE images. For this reason, the tip of the catheter should be left just short of the ligament of Treitz. A balloon catheter is desirable.
Interpretation of the SBE in Malabsorption
F r o m a radiological point of view, malabsorption states can be divided into two groups: l Those in which an almost specific SBE pattern can be recognized, though confirmation of a radiological diagnosis may still be required by means of clinical tests. Included in this group are bacterial overgrowth syndromes, adult coeliac disease, adult cystic fibrosis, Zollinger Ellison syndrome, short bowel syndrome. 2 Those in which the SBE appearances lack specificity and, therefore, the interpretation will depend heavily on an awareness of the patients's clinical background. It may then be possible to list likely diagnoses and suggest additional clinical and/or radiological investigations. Examples are Whipple's disease, lymphangiectasia, amyloidosis, abetalipoproteinaemia, mastocytosis.
BACTERIAL O V E R G R O W T H S Y N D R O M E S (BOS)
A normal bacterial flora primarily depends on an unimpeded through-flow of small bowel contents and also on the protective actions of gastric acid and of the intestinal immune system. Bacterial overgrowth is considered to be present when a culture of a jejunal aspirate yields at least 106 organisms per millilitre. Bile salts deconjugated by bacteria cause fat malabsorption by having become mucosal irritants and by being less efficient in the formation of miscelles. Light microscopy of biopsy specimens often demonstrates a patchy villous atrophy, a result of mucosal injury. Bacteria are also responsible for a reduction in the uptake of amino acids, carbohydrates and cobalamine. Bacterial overgrowth occurs more frequently in the elderly. Gastric acid hyposecretion may be responsible in some of the cases, prolonged small bowel transit almost amounting to stasis in others (Habanbi et al., 1990). Strictures, blind pouches, by-passed bowel loops and jejunal diverticulosis are among the structural alterations which may be associated with bacterial overgrowth. They are readily demonstrated by barium study. Jejunal Diverticulosis
In this acquired condition pouches of jejunal mucosa with elements of submucosa and some muscle fibres herniate through the mesenteric border at sites weakened by the entry of the vasa recta. These pseudodiverticula penetrate between the layers of the mesentery and may be hidden from view at laparotomy. They tend to congregate in a segment of jejunum, their size decreasing caudad. After resection, they have been known to reform in another segment. In the majority of cases, jejunal diverticulosis does not produce symptoms. In approximately 15% of cases, however, surgical intervention is indicated for complications which include bleeding, malabsorption (Fig. 1), diverticulitis or pseudo-obstruction. Diverticulosis can be
74
CLINICAL RADIOLOGY
Fig. I Jejunaldiverticulosisin a 65-year-oldman with malabsorption that responded to cyclicalantibiotic treatment. Small bowelenema film taken with patient erect to show barium/methylcellulosefluid levelsto identify the pseudodiverticula.
Fig. 2 Systemicsclerosis with malabsorption. Grossly dilatated loop of jejunum with somewhat crowded, stretched folds, the pathognomonic 'hide-bound' bowel sign.
a marker for disordered motility with underlying structural abnormalities of the smooth muscle or the myenteric plexus. Stasis within the diverticula and/or in relation to an associated motility disorder is held responsible for the infrequently complicating malabsorption. Demonstration of the diverticula with barium does not usually present a problem though a SBE, especially with the patient erect, will show these more reliably and could do so in 2-2.3% of adults over 40 years old (Maglinte et al., 1986).
missed. Atypical presentations such as anaemia, neuropathy or bone pain seem to occur with increased frequency, especially in older patients. Yet, a firm diagnosis needs to be made before placing the patient on a life-long diet of considerable difficulty. Should clinical suspicion of coeliac disease be sufficiently strong, a jejunal mucosal biopsy demonstrating subtotal villous atrophy and crypt hyperplasia followed by a positive clinical response to few weeks of gluten elimination will provide this definitive diagnosis. A barium study is then unnecessary. Jejunal suction biopsies, however, are now only rarely done, certainly in the USA. Biopsy by endoscopy is preferred since additional, visual gastroduodenal information can be obtained. Yet, duodenal biopsies for the diagnosis of coeliac disease are not often carried out unless sound clinical indications exist for the so often elusive coeliac disease. Moreover, the changes produced by coeliac disease may be atypical in the second part of the duodenum, the usual site for endoscopic biopsy. A recent editorial called for a reliable and non-invasive screening test to select patients for duodenal biopsy. Barium radiography of the small bowel, it stated, should be discarded as a screening test (Shanahan and Weinstein, 1988). Though requiring intubation, thus being mildly invasive, the small bowel enema is capable of positively identifying coeliac disease in about 75% of patients and ruling it out in 60% of controls (Herlinger and Maglinte, 1989b). The demonstration of fewer than four folds per inch of distended proximal jejunum would be diagnostic of untreated coeliac disease (Fig. 3). This diagnosis would be further supported by finding an increased number of, usually, thickened folds in the ileum. Thus, it has become by no means rare for the SBE to supplement an uncertain biopsy diagnosis of coeliac disease or to make such a diagnosis in the absence of prior clinical evidence.
PROGRESSIVE SYSTEMIC SCLEROSIS Deposition of collagen in the small bowel wall has been reported in over 40% of patients with systemic sclerosis. Yet, malabsorption is an infrequent feature of the disease. When present, it is usually due to stasis-related bacterial overgrowth and to the deposition of collagen around vessels in the mucosa/submucosa. The smooth muscle is predominantly involved. Systemic sclerosis is the most frequent cause of pseudo-obstruction. The 'hide-bound' bowel sign, lumen dilatation with normally spaced or even crowded folds (Fig. 2), is a pathognomonic radiological sign and can be shown in over 60% of patients (Horowitz and Meyers, 1973). Sacculations are a less frequent finding.
A D U L T C O E L I A C DISEASE In coeliac disease genetic factors influence environmental agents to bring about an immune system-mediated tissue damage (Shanahan and Weinstein, 1988). The diagnosis of coeliac disease is far too often delayed or
RADIOLOGY IN MALABSORPTION
75
Fig. 3 Adult patient with radiological features ofcoeliac disease. In the distended proximal jejunum folds are widely separated, with only two folds crossed by lines representing a distance of 25 mm.
The value of the small bowel enema in coeliac disease has been extended by a recent paper which reported the return of normal numbers of jejunal folds after successful therapy and a persistence of fold separation in refractory coeliac disease (Mike et al., 1990). Complications of coeliac disease influence survival. Analysis of a large group of patients with coeliac disease from a defined population area has shown that deaths from malignant disease were three times more frequent than in the general population (Logan et al., 1989). This study also confirmed the greatly increased risk of lymphoma and the slightly increased risk of carcinoma of the oesophagus and, to an even lesser extent, of carcinoma of the small bowel including the duodenum. The small bowel enema can depict the often subtle changes which indicate the presence of lymphoma, usually of T cell type and the more obvious but often atypical changes of B cell nonHodgkin's lymphoma (Fig. 4). Other radiologically demonstrable complications of coeliac disease include hyposplenism, mesenteric lymph node enlargement, ulcerative jejuno-ileitis, carcinoma of the oesophagus, carcinoma of the small bowel and the rare cavitation of mesenteric nodes. Z O L L I N G E R - E L L I S O N S Y N D R O M E (ZE) Gastrin-secreting tumours are mostly of pancreatic origin, but may also occur in the duodenum and rarely at other sites. They may be part of the type 1 multiple endocrine neoplasia (MEN) syndrome. High levels of gastrin cause excessive secretion of gastric acid which cannot be neutralized in the duodenum and which inactivates pancreatic enzymes and precipitates bile salts. Diarrhoea is, therefore, a frequent feature, often associated with steatorrhoea. The clinical diagnosis of ZE can be difficult at times. Some 25o/,, of ZE patients have no peptic ulcer at diagnosis and two thirds have only a single, apparently simple, peptic ulcer. Gastric acid hypersecretion need not
Fig. 4 An 81-year-old m a n with prolonged diarrhoea and weight loss, not responding to a gluten-free diet. A small bowel enema confirmed the diagnosis of coeliac disease and demonstrated three short, ulcerated segments with annular constricting involvement. The most proximal segment is illustrated here. Resection and histology showed diffuse large cell non-Hodgkin's lymphoma of B cell origin.
be excessive. In many ZE patients gastric acid levels do not exceed 15 mEq/litre, a level also found in some 10% of duodenal ulcer patients without ZE and in other conditions. The secretin provocation test may be required to confirm a diagnosis Of ZE. Barium radiology can provide the first indication of ZE. In the stomach there may be the features of a high acid output, namely hyperrugosity, fluid increase, accentuated and irregular areae gastricae, and erosions. Peptic oesophagitis is a frequent accompaniment. Typical changes occur in the duodenum. Folds are thick and stiffened (Fig. 5a). They may present a nodular surface pattern, occasionally with erosions (Matsui et al., 1989). In the proximal jejunum, folds may be slightly thickened, and there may be increase of fluid (Fig. 5b). Peptic ulceration may be multiple, at times involving unusual sites, like the postbulbar duodenum and the jejunum. Surgical restoration of eugastrinaemia can be effected in 20-40% of cases and may be preferred to life-long acid output suppression (Frucht et al., 1991). Radiological demonstration of an underlying gastrinoma and the exclusion of liver metastases should precede surgical intervention. CYSTIC F I B R O S I S IN A D U L T S Cystic fibrosis (CF) is increasingly a disease of young adults. Over one third of the more than 15 000 patients
76
CLINICAL RADIOLOGY
listed in the registry of the North American Cystic Fibrosis Foundation are now older than 21 years. Though usually diagnosed by a positive sweat test during childhood, a minority of patients may escape diagnosis until early adult life (Hodson, 1989). Adult patients with CF may look quite well, their height and weight usually within the lower limits of normal. Though pancreatic insufficiency is found in 95% of these patients, symptoms can be few. It is in this patient group that a radiological diagnosis of CF m a y be made before it has been suspected clinically. Barium radiology shows typical alterations of the duodenum in 84% of the patients (Rogers et al., 1979). Beyond the bulb, the duodenum is persistently narrowed with thickened folds and a frequently sacculated appearance of the outer border (Fig. 6a). N o ulcers are seen. Duodenal p H has been shown to be low, especially in the post-prandial period (Robinson et al., 1990), and this m a y contribute to the radiographic appearances and to a malabsorption of fat. The jejunum may be of normal appearance. In the ileum, normal folds are replaced by irregular lacelike, hazy filling defects with an almost haustral outline of the lumen (Fig. 6b). An irregular linear pattern also characterizes the right colon (Fig. 6c). These changes are considered to be caused by inspissated mucus. SHORT BOWEL SYNDROME
(a)
The minimum length of residual small intestine needed for the eventual restoration of oral nutritional autonomy was found to be 150 cm if colectomy had been done also, and 50-70 cm with the colon left in situ (Gouttebel et al., 1989). In this process of adaptation, the small bowel remnant alters to carry out digestive and absorptive functions previously performed by its totality. Over a period of about l year, the residual bowel lengthens, thickens and dilatates and develops an increased mucosal cell mass. Total parenteral nutrition (TPN) is essential if severe malnutrition is to be avoided in the interim. Yet, T P N tends to cause bowel atrophy and retards adaptation. Early addition of an elemental diet is essential. Directly related to the amount of small bowel loss is a degree of gastric hypersecretion which can be massive soon after resection (Williams et al., 1985). This outflow of acid not only interferes with digestive processes but may also lead to ulceration and to the breakdown of sutures. Though acid output will lessen with time, gastrin levels tend to remain elevated. Diagnostic radiology can be used to demonstrate: 1 2 3 4
the approximate length of residual bowel, its integrity or any residual pathology, complications due to the high acid output, the features of intestinal adaptation, e.g. thickened folds and increased lumen diameter.
WHIPPLE'S DISEASE
(b) Fig. 5 - Patient with Zollinger Ellison syndrome. Diarrhoea but no peptic ulceration. (a) Gross, somewhat nodular fold thickening in the duodenum. (b) Slight thickening of jejunal folds with moderate fluid increase. (Courtesy of Seth N. Click, MD, Philadelphia, USA.)
This rare, formerly fatal disease can be cured if diagnosed in time. It is a multisystem disease with a varied clinical presentation. A diagnosis may not be made for a long time. Barium radiology, though not demonstrating specific changes, may allow the radiologist to include Whipple's disease in the differential diagnosis and recommend duodenal or jejunal biopsy.
77
RADIOLOGY IN MALABSORPTION
(a)
(c) Fig. 6 A 28-year-old male patient with steatorrhoea. Cystic fibrosis had not been suspected clinically. (a) The second part of the duodenum is narrowed above, and coarse folds are present. (b) The distal ileum shows grossly thickened folds with an unsharp reticular surface pattern. (c) A similar though coarser reticular pattern is seen in the ascending colon. A radiological diagnosis of cystic fibrosis was made and later confirmed by the sweat test.
mostly in the jejunum. Mucosal folds may be thickened and there is usually fluid increase. The enlarged lymph nodes, often containing lipid material, can be shown by CT and by ultrasound (Davis and Patel, 1990). OTHER CONDITIONS
(b) The small intestine and mesenteric or retroperitoneal lymph nodes may be involved together with joint capsules, heart valves, the central nervous system and other sites. Whipple's bacilli are found in profusion. In the lamina propria and its extension into villi, the bacilli and/ or PAS-positive material are seen within macrophages that are present in sufficient numbers to produce villous distension. This feature forms the basis of the more specific changes shown by the SBE. A fine, 1-2 m m nodular pattern of patchy distribution is demonstrated,
A similar pattern of fine nodules may be demonstrated by the SBE in other conditions. In lymphangiectasia, villi may be distended by engorged lacteals and mucosal folds are thickened. Mesenteric node enlargement may also be seen in the secondary form of the disease. In amyloidosis affecting the small bowel, amyloid may be deposited in the lamina propria, causing distension of villi and a fine, 1-3 m m nodular pattern (Tada et al., 1991). Larger nodules can also be seen. Macroglobulinaemia only rarely involves the small bowel or presents with malabsorption; villous enlargement may then be caused by the extracellular deposition of macroglobulin and by dilatated lacteals. An enteritis caused by Mycobacterium aviurn intracellulare (MAI) is mostly Found in A I D S patients, and often shows a fine nodular pattern of the small intestinal mucosa. It has been referred to as 'pseudo-Whipple', a term to be avoided. Compared with Whipple's disease there are differences in the degree of cell-mediated immune deficiency and differences in clinical presentation. The slim, gram-positive Whipple's bacillus does not resemble the shorter, stouter acid-fast mycobacterium (Gillings et al., 1987). Nodular lymphoid hyperplasia, enlarged lymph follicles that bulge into the overlying epithelial layer, is mostly asymptomatic. In adults there may be a relationship to viral infection, rarely
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CLINICAL RADIOLOGY
Fig. 7 Small bowel enema demonstrating a pattern of villi at the upper limits of normal thickness. Filling defects measuring up to 1 mm can be seen en.face or in profile at the edge of normal mucosal folds.
to a systemic immune deficiency, very occasionally to a lymphoproliferative process. Barium studies show 2-4 mm nodules, uniformly distributed over normal mucosa, often with umbilications. N o r m a l villi c a n b e s h o w n b y t h e S B E ; t h e d i a m e t e r o f i n d i v i d u a l filling d e f e c t s p r o d u c e d b y t h e m o c c a s i o n a l l y r e a c h e s 1 r a m , a l m o s t t h e size o f t h e villi in W h i p p l e ' s d i s e a s e (Fig. 7).
REFERENCES
Davis, SJ & Patel, A (1990). Case report: distinctive echogenic lymphadcnopathy in Whipple's disease. Clinical Radiology, 42, 60-62. Frucht, H, Maton, PN & Jensen, RT (1991). Use of omeprazole in patients with Zollinger-Ellison syndrome. Digestive Diseases and Sciences, 36, 394 404.
Gillings,_ JS, Uhrmacher, C, West, R & Shikc, M. (1987). Disseminated mycobacterium avium intracellulareinfection in acquired immunodeficiency syndrome mimicking Whipple's disease. Gastroenterology, 92, 1127 1132. Gouttebel, MC, Saint Aubert, B, Colette, C, Astre, C, Monnier, LH & Joyeux, H (1989), Intestinal adaptation in patients with short bowel syndrome; measurement by calcium absorption. Digestive Diseases and Sciences, 34, 709 715. Habanbi, NY, Montgomery, RD, Asquith, P & Lee, GS (1990). Significant of small bowel bacterial overgrowth in the elderly. Gut, 31, A1194. Herlinger, H & Maglinte, DDT (1989a). The small bowel enema with methylcellulose. In: Clinical Radiology of the Small Intestine. pp. 119-137. WB Saunders, Philadelphia. Herlinger, H & Maglinte, DDT (1989b). Malabsorption and immune deficiencies. In: Clinical Radiology of the Small Intestine. pp. 354 361. WB Saunders, Philadelphia. Hodson, ME (1989). Editorial. Managing adults with cystic fibrosis. Chest medicine's success story. British Journal of" Medicine, 298, 471 472. Horowitz, AL & Meyers, MA (1973). The "hide-bound" small bowel of scleroderma: characteristic mucosal fold pattern. American Journal of Roentgenology, 119, 332 334. Logan, RF, Rifkind, EA, Turner, ID & Ferguson, A (1989). Mortality in celiac disease. Gastroenterology, 97, 265 271. Maglinte, DDT, Chernish, SM, De Weese, R, Kelvin, FM & Brunelle, RL (1986). Acquired jejunoileal diverticular disease. Subject Review. Radiology, 158, 577 580. Matsui, T, lida M, Fujishima, M, Fuchigami, T & Yao, T (1989). Linear erosions on Kerkring's folds may be diagnostic of Zollinger-Ellison syndrome. Journal of Clinical Gastroenterology, 11, 278 281. Mike, N, Udeshi U, Asquith, P & Ferrando, J (1990). Small bowel enema in non-responsive coeliac disease. Gut, 31, 883 885. Robinson, PJ, Smith, AL & Sly, PD (1990). Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Digestive Diseases and Sciences, 33, 1299 1304. Rogers, LF, Armstrong, JD, Ferrucci, JT, Jr, Poznanski, AK, Resnick, DL & Stanley, RJ (1979). Special report. Radiology, 133, 813-814. Shanahan, F & Weinstein, WM (1988). Editorial. Extending the scope in celiac disease. New England Journal of Medicine, 319, 782-783. Tada, S, Iida, M, Matsui, T, Fuchigami, T, Iwashita, A, Yao, T et al. (1991). Amyloidosis of the small intestine: findings on doublecontrast radiographs. American Journal of Roentgenology, 156, 741 744. Williams, NS, Evans, P & King, RFGJ (1985). Gastric acid secretion and gastrin production in the short bowel syndrome. Gut, 26, 914 919. H. HERLINGER
Emeritus Professor o f Radiology Hospital o f the University o f Pennsylvania 3400 Spruce Street Philadelphia PA 19104-4283 USA
Editorial Radiology in Malabsorption A diagnosis of malabsorption or the clinical suspicion of its presence are the indications for barium radiology in less than 5% of patients referred with small bowel related symptoms. Most of these patients are examined by small bowel enema (SBE), frequently supported by computed tomography (CT). CT is of unique importance in the study of the malignant complications, mostly of coeliac disease. It is of supplementary value in the further study of conditions which include Whipple's disease and secondary lymphangiectasia. The diagnosis of a malabsorption state should be the function of the clinician, not of the radiologist. The purpose of radiology is to accurately depict changes of the mucosal surface or of the bowel contour that may lead to the diagnosis of the cause of malabsorption and to demonstrate possible complications. Barium Examination for Diagnosis
SBE is recommended for the investigation of malabsorption since it can avoid or defer flocculation. Its further benefit is that it distends the bowel lumen, a more important feature in most small bowel investigations than the achievement of double contrast. Flocculated barium cannot adhere reliably to the gut mucosa and will fail to outline mucosal alterations accurately. Flocculation is of little value as a sign of a malabsorption state since it may occur in any hypersecretory state or even without apparent cause. The SBE - Technical Points
The standard SBE examination requires catheter placement into the distal duodenum or first loop of jejunum, preferably using a balloon-equipped catheter to reduce reflux into the stomach. A barium suspension, either undiluted Micropaque (Nicholas Corp., Slough) or Entero-H (E-Z-EM Comp., New York, USA) is injected through the catheter to a total amount of 180-220 ml. This is followed by the infusion of 1 2 litres of 0.5% methylcellulose solution, using a hand operated or peristaltic pump. Compression fluoroscopy and spot films are done during the single contrast phase, and the developing and established double contrast phases. An overview prone film is done at the end of the study. (For further detail see Herlinger and Maglinte, 1989a). In patients with malabsorption, especially if an excess of small bowel fluid has been shown on a preliminary plain film, it is necessary to inject more than the usual amount of barium through the catheter (e.g. 240 260 ml). The infusion of 0.5% methylcellulose should follow immediately. Early compression views of all bowel loops are taken in the lumen distended state, before double contrast has developed. Double contrast images may be recorded later, if flocculation has not already occurred. It may be important to include the distal duodenum in the SBE images. For this reason, the tip of the catheter should be left just short of the ligament of Treitz. A balloon catheter is desirable.
Interpretation of the SBE in Malabsorption
F r o m a radiological point of view, malabsorption states can be divided into two groups: l Those in which an almost specific SBE pattern can be recognized, though confirmation of a radiological diagnosis may still be required by means of clinical tests. Included in this group are bacterial overgrowth syndromes, adult coeliac disease, adult cystic fibrosis, Zollinger Ellison syndrome, short bowel syndrome. 2 Those in which the SBE appearances lack specificity and, therefore, the interpretation will depend heavily on an awareness of the patients's clinical background. It may then be possible to list likely diagnoses and suggest additional clinical and/or radiological investigations. Examples are Whipple's disease, lymphangiectasia, amyloidosis, abetalipoproteinaemia, mastocytosis.
BACTERIAL O V E R G R O W T H S Y N D R O M E S (BOS)
A normal bacterial flora primarily depends on an unimpeded through-flow of small bowel contents and also on the protective actions of gastric acid and of the intestinal immune system. Bacterial overgrowth is considered to be present when a culture of a jejunal aspirate yields at least 106 organisms per millilitre. Bile salts deconjugated by bacteria cause fat malabsorption by having become mucosal irritants and by being less efficient in the formation of miscelles. Light microscopy of biopsy specimens often demonstrates a patchy villous atrophy, a result of mucosal injury. Bacteria are also responsible for a reduction in the uptake of amino acids, carbohydrates and cobalamine. Bacterial overgrowth occurs more frequently in the elderly. Gastric acid hyposecretion may be responsible in some of the cases, prolonged small bowel transit almost amounting to stasis in others (Habanbi et al., 1990). Strictures, blind pouches, by-passed bowel loops and jejunal diverticulosis are among the structural alterations which may be associated with bacterial overgrowth. They are readily demonstrated by barium study. Jejunal Diverticulosis
In this acquired condition pouches of jejunal mucosa with elements of submucosa and some muscle fibres herniate through the mesenteric border at sites weakened by the entry of the vasa recta. These pseudodiverticula penetrate between the layers of the mesentery and may be hidden from view at laparotomy. They tend to congregate in a segment of jejunum, their size decreasing caudad. After resection, they have been known to reform in another segment. In the majority of cases, jejunal diverticulosis does not produce symptoms. In approximately 15% of cases, however, surgical intervention is indicated for complications which include bleeding, malabsorption (Fig. 1), diverticulitis or pseudo-obstruction. Diverticulosis can be
74
CLINICAL RADIOLOGY
Fig. I Jejunaldiverticulosisin a 65-year-oldman with malabsorption that responded to cyclicalantibiotic treatment. Small bowelenema film taken with patient erect to show barium/methylcellulosefluid levelsto identify the pseudodiverticula.
Fig. 2 Systemicsclerosis with malabsorption. Grossly dilatated loop of jejunum with somewhat crowded, stretched folds, the pathognomonic 'hide-bound' bowel sign.
a marker for disordered motility with underlying structural abnormalities of the smooth muscle or the myenteric plexus. Stasis within the diverticula and/or in relation to an associated motility disorder is held responsible for the infrequently complicating malabsorption. Demonstration of the diverticula with barium does not usually present a problem though a SBE, especially with the patient erect, will show these more reliably and could do so in 2-2.3% of adults over 40 years old (Maglinte et al., 1986).
missed. Atypical presentations such as anaemia, neuropathy or bone pain seem to occur with increased frequency, especially in older patients. Yet, a firm diagnosis needs to be made before placing the patient on a life-long diet of considerable difficulty. Should clinical suspicion of coeliac disease be sufficiently strong, a jejunal mucosal biopsy demonstrating subtotal villous atrophy and crypt hyperplasia followed by a positive clinical response to few weeks of gluten elimination will provide this definitive diagnosis. A barium study is then unnecessary. Jejunal suction biopsies, however, are now only rarely done, certainly in the USA. Biopsy by endoscopy is preferred since additional, visual gastroduodenal information can be obtained. Yet, duodenal biopsies for the diagnosis of coeliac disease are not often carried out unless sound clinical indications exist for the so often elusive coeliac disease. Moreover, the changes produced by coeliac disease may be atypical in the second part of the duodenum, the usual site for endoscopic biopsy. A recent editorial called for a reliable and non-invasive screening test to select patients for duodenal biopsy. Barium radiography of the small bowel, it stated, should be discarded as a screening test (Shanahan and Weinstein, 1988). Though requiring intubation, thus being mildly invasive, the small bowel enema is capable of positively identifying coeliac disease in about 75% of patients and ruling it out in 60% of controls (Herlinger and Maglinte, 1989b). The demonstration of fewer than four folds per inch of distended proximal jejunum would be diagnostic of untreated coeliac disease (Fig. 3). This diagnosis would be further supported by finding an increased number of, usually, thickened folds in the ileum. Thus, it has become by no means rare for the SBE to supplement an uncertain biopsy diagnosis of coeliac disease or to make such a diagnosis in the absence of prior clinical evidence.
PROGRESSIVE SYSTEMIC SCLEROSIS Deposition of collagen in the small bowel wall has been reported in over 40% of patients with systemic sclerosis. Yet, malabsorption is an infrequent feature of the disease. When present, it is usually due to stasis-related bacterial overgrowth and to the deposition of collagen around vessels in the mucosa/submucosa. The smooth muscle is predominantly involved. Systemic sclerosis is the most frequent cause of pseudo-obstruction. The 'hide-bound' bowel sign, lumen dilatation with normally spaced or even crowded folds (Fig. 2), is a pathognomonic radiological sign and can be shown in over 60% of patients (Horowitz and Meyers, 1973). Sacculations are a less frequent finding.
A D U L T C O E L I A C DISEASE In coeliac disease genetic factors influence environmental agents to bring about an immune system-mediated tissue damage (Shanahan and Weinstein, 1988). The diagnosis of coeliac disease is far too often delayed or
RADIOLOGY IN MALABSORPTION
75
Fig. 3 Adult patient with radiological features ofcoeliac disease. In the distended proximal jejunum folds are widely separated, with only two folds crossed by lines representing a distance of 25 mm.
The value of the small bowel enema in coeliac disease has been extended by a recent paper which reported the return of normal numbers of jejunal folds after successful therapy and a persistence of fold separation in refractory coeliac disease (Mike et al., 1990). Complications of coeliac disease influence survival. Analysis of a large group of patients with coeliac disease from a defined population area has shown that deaths from malignant disease were three times more frequent than in the general population (Logan et al., 1989). This study also confirmed the greatly increased risk of lymphoma and the slightly increased risk of carcinoma of the oesophagus and, to an even lesser extent, of carcinoma of the small bowel including the duodenum. The small bowel enema can depict the often subtle changes which indicate the presence of lymphoma, usually of T cell type and the more obvious but often atypical changes of B cell nonHodgkin's lymphoma (Fig. 4). Other radiologically demonstrable complications of coeliac disease include hyposplenism, mesenteric lymph node enlargement, ulcerative jejuno-ileitis, carcinoma of the oesophagus, carcinoma of the small bowel and the rare cavitation of mesenteric nodes. Z O L L I N G E R - E L L I S O N S Y N D R O M E (ZE) Gastrin-secreting tumours are mostly of pancreatic origin, but may also occur in the duodenum and rarely at other sites. They may be part of the type 1 multiple endocrine neoplasia (MEN) syndrome. High levels of gastrin cause excessive secretion of gastric acid which cannot be neutralized in the duodenum and which inactivates pancreatic enzymes and precipitates bile salts. Diarrhoea is, therefore, a frequent feature, often associated with steatorrhoea. The clinical diagnosis of ZE can be difficult at times. Some 25o/,, of ZE patients have no peptic ulcer at diagnosis and two thirds have only a single, apparently simple, peptic ulcer. Gastric acid hypersecretion need not
Fig. 4 An 81-year-old m a n with prolonged diarrhoea and weight loss, not responding to a gluten-free diet. A small bowel enema confirmed the diagnosis of coeliac disease and demonstrated three short, ulcerated segments with annular constricting involvement. The most proximal segment is illustrated here. Resection and histology showed diffuse large cell non-Hodgkin's lymphoma of B cell origin.
be excessive. In many ZE patients gastric acid levels do not exceed 15 mEq/litre, a level also found in some 10% of duodenal ulcer patients without ZE and in other conditions. The secretin provocation test may be required to confirm a diagnosis Of ZE. Barium radiology can provide the first indication of ZE. In the stomach there may be the features of a high acid output, namely hyperrugosity, fluid increase, accentuated and irregular areae gastricae, and erosions. Peptic oesophagitis is a frequent accompaniment. Typical changes occur in the duodenum. Folds are thick and stiffened (Fig. 5a). They may present a nodular surface pattern, occasionally with erosions (Matsui et al., 1989). In the proximal jejunum, folds may be slightly thickened, and there may be increase of fluid (Fig. 5b). Peptic ulceration may be multiple, at times involving unusual sites, like the postbulbar duodenum and the jejunum. Surgical restoration of eugastrinaemia can be effected in 20-40% of cases and may be preferred to life-long acid output suppression (Frucht et al., 1991). Radiological demonstration of an underlying gastrinoma and the exclusion of liver metastases should precede surgical intervention. CYSTIC F I B R O S I S IN A D U L T S Cystic fibrosis (CF) is increasingly a disease of young adults. Over one third of the more than 15 000 patients
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CLINICAL RADIOLOGY
listed in the registry of the North American Cystic Fibrosis Foundation are now older than 21 years. Though usually diagnosed by a positive sweat test during childhood, a minority of patients may escape diagnosis until early adult life (Hodson, 1989). Adult patients with CF may look quite well, their height and weight usually within the lower limits of normal. Though pancreatic insufficiency is found in 95% of these patients, symptoms can be few. It is in this patient group that a radiological diagnosis of CF m a y be made before it has been suspected clinically. Barium radiology shows typical alterations of the duodenum in 84% of the patients (Rogers et al., 1979). Beyond the bulb, the duodenum is persistently narrowed with thickened folds and a frequently sacculated appearance of the outer border (Fig. 6a). N o ulcers are seen. Duodenal p H has been shown to be low, especially in the post-prandial period (Robinson et al., 1990), and this m a y contribute to the radiographic appearances and to a malabsorption of fat. The jejunum may be of normal appearance. In the ileum, normal folds are replaced by irregular lacelike, hazy filling defects with an almost haustral outline of the lumen (Fig. 6b). An irregular linear pattern also characterizes the right colon (Fig. 6c). These changes are considered to be caused by inspissated mucus. SHORT BOWEL SYNDROME
(a)
The minimum length of residual small intestine needed for the eventual restoration of oral nutritional autonomy was found to be 150 cm if colectomy had been done also, and 50-70 cm with the colon left in situ (Gouttebel et al., 1989). In this process of adaptation, the small bowel remnant alters to carry out digestive and absorptive functions previously performed by its totality. Over a period of about l year, the residual bowel lengthens, thickens and dilatates and develops an increased mucosal cell mass. Total parenteral nutrition (TPN) is essential if severe malnutrition is to be avoided in the interim. Yet, T P N tends to cause bowel atrophy and retards adaptation. Early addition of an elemental diet is essential. Directly related to the amount of small bowel loss is a degree of gastric hypersecretion which can be massive soon after resection (Williams et al., 1985). This outflow of acid not only interferes with digestive processes but may also lead to ulceration and to the breakdown of sutures. Though acid output will lessen with time, gastrin levels tend to remain elevated. Diagnostic radiology can be used to demonstrate: 1 2 3 4
the approximate length of residual bowel, its integrity or any residual pathology, complications due to the high acid output, the features of intestinal adaptation, e.g. thickened folds and increased lumen diameter.
WHIPPLE'S DISEASE
(b) Fig. 5 - Patient with Zollinger Ellison syndrome. Diarrhoea but no peptic ulceration. (a) Gross, somewhat nodular fold thickening in the duodenum. (b) Slight thickening of jejunal folds with moderate fluid increase. (Courtesy of Seth N. Click, MD, Philadelphia, USA.)
This rare, formerly fatal disease can be cured if diagnosed in time. It is a multisystem disease with a varied clinical presentation. A diagnosis may not be made for a long time. Barium radiology, though not demonstrating specific changes, may allow the radiologist to include Whipple's disease in the differential diagnosis and recommend duodenal or jejunal biopsy.
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RADIOLOGY IN MALABSORPTION
(a)
(c) Fig. 6 A 28-year-old male patient with steatorrhoea. Cystic fibrosis had not been suspected clinically. (a) The second part of the duodenum is narrowed above, and coarse folds are present. (b) The distal ileum shows grossly thickened folds with an unsharp reticular surface pattern. (c) A similar though coarser reticular pattern is seen in the ascending colon. A radiological diagnosis of cystic fibrosis was made and later confirmed by the sweat test.
mostly in the jejunum. Mucosal folds may be thickened and there is usually fluid increase. The enlarged lymph nodes, often containing lipid material, can be shown by CT and by ultrasound (Davis and Patel, 1990). OTHER CONDITIONS
(b) The small intestine and mesenteric or retroperitoneal lymph nodes may be involved together with joint capsules, heart valves, the central nervous system and other sites. Whipple's bacilli are found in profusion. In the lamina propria and its extension into villi, the bacilli and/ or PAS-positive material are seen within macrophages that are present in sufficient numbers to produce villous distension. This feature forms the basis of the more specific changes shown by the SBE. A fine, 1-2 m m nodular pattern of patchy distribution is demonstrated,
A similar pattern of fine nodules may be demonstrated by the SBE in other conditions. In lymphangiectasia, villi may be distended by engorged lacteals and mucosal folds are thickened. Mesenteric node enlargement may also be seen in the secondary form of the disease. In amyloidosis affecting the small bowel, amyloid may be deposited in the lamina propria, causing distension of villi and a fine, 1-3 m m nodular pattern (Tada et al., 1991). Larger nodules can also be seen. Macroglobulinaemia only rarely involves the small bowel or presents with malabsorption; villous enlargement may then be caused by the extracellular deposition of macroglobulin and by dilatated lacteals. An enteritis caused by Mycobacterium aviurn intracellulare (MAI) is mostly Found in A I D S patients, and often shows a fine nodular pattern of the small intestinal mucosa. It has been referred to as 'pseudo-Whipple', a term to be avoided. Compared with Whipple's disease there are differences in the degree of cell-mediated immune deficiency and differences in clinical presentation. The slim, gram-positive Whipple's bacillus does not resemble the shorter, stouter acid-fast mycobacterium (Gillings et al., 1987). Nodular lymphoid hyperplasia, enlarged lymph follicles that bulge into the overlying epithelial layer, is mostly asymptomatic. In adults there may be a relationship to viral infection, rarely
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CLINICAL RADIOLOGY
Fig. 7 Small bowel enema demonstrating a pattern of villi at the upper limits of normal thickness. Filling defects measuring up to 1 mm can be seen en.face or in profile at the edge of normal mucosal folds.
to a systemic immune deficiency, very occasionally to a lymphoproliferative process. Barium studies show 2-4 mm nodules, uniformly distributed over normal mucosa, often with umbilications. N o r m a l villi c a n b e s h o w n b y t h e S B E ; t h e d i a m e t e r o f i n d i v i d u a l filling d e f e c t s p r o d u c e d b y t h e m o c c a s i o n a l l y r e a c h e s 1 r a m , a l m o s t t h e size o f t h e villi in W h i p p l e ' s d i s e a s e (Fig. 7).
REFERENCES
Davis, SJ & Patel, A (1990). Case report: distinctive echogenic lymphadcnopathy in Whipple's disease. Clinical Radiology, 42, 60-62. Frucht, H, Maton, PN & Jensen, RT (1991). Use of omeprazole in patients with Zollinger-Ellison syndrome. Digestive Diseases and Sciences, 36, 394 404.
Gillings,_ JS, Uhrmacher, C, West, R & Shikc, M. (1987). Disseminated mycobacterium avium intracellulareinfection in acquired immunodeficiency syndrome mimicking Whipple's disease. Gastroenterology, 92, 1127 1132. Gouttebel, MC, Saint Aubert, B, Colette, C, Astre, C, Monnier, LH & Joyeux, H (1989), Intestinal adaptation in patients with short bowel syndrome; measurement by calcium absorption. Digestive Diseases and Sciences, 34, 709 715. Habanbi, NY, Montgomery, RD, Asquith, P & Lee, GS (1990). Significant of small bowel bacterial overgrowth in the elderly. Gut, 31, A1194. Herlinger, H & Maglinte, DDT (1989a). The small bowel enema with methylcellulose. In: Clinical Radiology of the Small Intestine. pp. 119-137. WB Saunders, Philadelphia. Herlinger, H & Maglinte, DDT (1989b). Malabsorption and immune deficiencies. In: Clinical Radiology of the Small Intestine. pp. 354 361. WB Saunders, Philadelphia. Hodson, ME (1989). Editorial. Managing adults with cystic fibrosis. Chest medicine's success story. British Journal of" Medicine, 298, 471 472. Horowitz, AL & Meyers, MA (1973). The "hide-bound" small bowel of scleroderma: characteristic mucosal fold pattern. American Journal of Roentgenology, 119, 332 334. Logan, RF, Rifkind, EA, Turner, ID & Ferguson, A (1989). Mortality in celiac disease. Gastroenterology, 97, 265 271. Maglinte, DDT, Chernish, SM, De Weese, R, Kelvin, FM & Brunelle, RL (1986). Acquired jejunoileal diverticular disease. Subject Review. Radiology, 158, 577 580. Matsui, T, lida M, Fujishima, M, Fuchigami, T & Yao, T (1989). Linear erosions on Kerkring's folds may be diagnostic of Zollinger-Ellison syndrome. Journal of Clinical Gastroenterology, 11, 278 281. Mike, N, Udeshi U, Asquith, P & Ferrando, J (1990). Small bowel enema in non-responsive coeliac disease. Gut, 31, 883 885. Robinson, PJ, Smith, AL & Sly, PD (1990). Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Digestive Diseases and Sciences, 33, 1299 1304. Rogers, LF, Armstrong, JD, Ferrucci, JT, Jr, Poznanski, AK, Resnick, DL & Stanley, RJ (1979). Special report. Radiology, 133, 813-814. Shanahan, F & Weinstein, WM (1988). Editorial. Extending the scope in celiac disease. New England Journal of Medicine, 319, 782-783. Tada, S, Iida, M, Matsui, T, Fuchigami, T, Iwashita, A, Yao, T et al. (1991). Amyloidosis of the small intestine: findings on doublecontrast radiographs. American Journal of Roentgenology, 156, 741 744. Williams, NS, Evans, P & King, RFGJ (1985). Gastric acid secretion and gastrin production in the short bowel syndrome. Gut, 26, 914 919. H. HERLINGER
Emeritus Professor o f Radiology Hospital o f the University o f Pennsylvania 3400 Spruce Street Philadelphia PA 19104-4283 USA
