457
THE LANCET
Radiography in the Diagnosis of Acute Cholecystitis cholecystitis the trigger of the is obstruction cystic duct, by a gallstone or by the oedema due to a gallstone. The result is IN most attacks of acute
gallbladder distension,2 venous hypertensionvascular congestion,2subserosal oedema,2and sometimes small-arterial obliteration. 23 Inflammatory cells then infiltrate the gallbladder.45 In the pathogenesis of these changes the relative importance of bacterial contamination and the direct toxic effects of imprisoned bile-salts is still hotly debated.2 Acute cholecystitis is one of the major causes of emergency surgical admission in adults, and we know that early cholecystectomy can reduce the duration of hospital stay without increasing mortality or morbidity.6Clearly if the policy is to be early operation, correct diagnosis is very important. A surgeon who relies solely on clinical diagnosis will be wrong in at least 15% of cases.8 Fortunately there are several radiological techniques which will help him. The plain abdominal X-ray is of limited valuesince only 10-15% of gallstones are radio-opaque9 and other conditions which may be revealed, such as acute
emphysematous cholecystitis, are extremely
one should be taken. Oral chois often impossible- because of nausea lecystography and vomiting, but intravenous cholangiography (l.v.c.) can be very useful: a gallbladder which opacifies normally virtually rules out acute cholecystitis, whereas a well-opacified common bileduct with no filling of the gallbladder, even on delayed films, is almost pathognomonic of cystic-duct obstruction. 10 11 For I.V.C. most radiologists now use ioglycamide (’Biligram’) rather than the older and more toxic contrast agent iodipamide (’Biligrarare.
Nevertheless,
H. F., Northrap, U. D., Rosenblum, M., Abrahams, H. Am. J. Gastroent. 1968, 50, 476 2. Schein, C. Acute Cholecystitis. Evanston, Ill., 1972. 3. Gordon, K. P. D. Gut, 1967, 8, 565. 4. Robbins, S. L. Pathology. Philadelphia, 1967. 5. Moncada, R., Cardoso, M., Danley, R., Rodriguez, J., Kimura, K., Pickleman, J., Brandly, J. Am. J. Roentg. 1977, 129, 587. 6. McArthur, P., Cushieri, A., Sells, R. A., Shields, R. Br. J. Surg. 1975, 62, 850. 7. Van der Linden, W., Sunzel, H. Surgery Gynec. Obstet. 1970, 114, 1. 8. Essenhigh, D. M. Br. J. Surg. 1966, 53, 1032. 9. Cochrane, S., Shanks, S., Kerley, P. A Textbook of X-ray Diagnosis, vol. 4;
fin’).12 Drip-infusion cholangiography is preferable to bolus injection because toxic side-effects are less frequent and bile-duct opacification is better.14 15 i.v.c.s should never be done in a dehydrated patient"13 and success is unlikely if the serum-bilirubin is above 51 µmol/l (3 mg/dl). As CHEUNG and CHANG" lately emphasised, if neither the gallbladder nor the bile-duct is radiologically visible, the diagnosis may well be some acute intra-abdominal condition other than cholecystitis. A further trap for the unwary is that jaundiced patients excrete most of the i.v.c. dye through the kidneys16 rather than in the bile; the renal pelvis and upper ureter, faintly displayed, may be mistaken for bile-duct and gallbladder. Hepatobiliary scanning with technetium-99m pyridoxylidene glutamate is another diagnostic technique. Isotopic opacification of the gallbladder virtually excludes acute cholecystitis, 17—19 but disappointingly the technique has only a 71% positive predictive value.’8 Like i.v.c., isotope scanning is likely to fail in the presence of jaundice. Grey-scale ultrasonography has been employed to demonstrate gallstones,20 21 and in acute cholecystitis the diagnostic accuracy was 82%.17 This technique may have a particular place in the jaundiced patient, in whom LV.C. and hepatobiliary scanning methods are likely to be unsatisfactory. In 1970 GENEREUX and TCHANG,22 while performing an intravenous pyelogram, fortuitously noted opacification of the gallbladder wall in a case of hydrops of the gallbladder. From this observation stemmed the method knows. as infusion tomography. A solution of 150 ml 60% meglumine diatrizoate (’Urografin)’ mixed with 150 ml of 5% dextrose in water is given by rapid intravenous infusion. Linear tomograms of the anterior third of the right upper quadrant of the abdomen are then obtained. The test is positive when thickened gallbladder wall shows as an opacified ring. (Experimental work in dogs5 has revealed that the opacification is due to the uptake of contrast material by polymorphs in the inflamed tissue.) MONCADA et al.23 have reported the results of infusion tomography in 137 patients with suspected acute cholecystitis. Diagnostic accuracy was 96% in positive cases and 94% in histologically proven negative cases.23
1. Newman,
p. 546. London, 1969. 10. Eckleberg, M. E., Carlson, H. C., Mcllrath, D. C. Am. J. Roentg. 1970, 110, 235. 11. Cheung, L. Y., Chang, F. C. Archs Surg. 1978, 113, 568. 12. Bell, G. D., Fayadh, M., Smith, P. L. C., Frank, J., Kelsey Fry, I. Gut, 1975,
16,841.
13. Ansell, G. Invest. Radiol. 1970, 5, 374. 14. Allen, W. M.C. Br. J. Radiol. 1969, 42, 347. 15. Bell, G. D., Frank, J., Fayadh, M., Smith, P. L. C.,
Kelsey Fry,
I. ibid.
1978,
51, 191. 16. Bell, G. D., Mullins, J., Doran, J., Oliver, J., McAllister, J., Monks, A., Richens, A. ibid. p. 251. 17. Mosley, J. G., Metrovelli, C., Gregory, A. Gut, 1977, 18, A985. 18. Hall, A. W., Wisbey, M. L., Hutchinson, F., Wood, R. A. B., Cuschieri, A. Br. J. Surg. 1978, 65, 361. 19. Stadalnik, R. C., Matalo, N. M., Jansholt, A., Krohn, K. A., De Narwo, G. L., Wolfman, E. F. Radiology, 1976, 121, 657. 20. Doust, B. D., Makland, N. F. ibid. 1974, 119, 643. 21. Bartram, R. J., Crow, H. C., Foote, S. R. New Engl. J. Med 1977, 296, 538. 22. Genereux, G. P., Tchang, S P. K.J. Can. Ass. Radiol. 1970, 21, 39. 23. Moncada, R., Cardoso, M., Danley, R., Rodriguez, J., Kimura, K., Pickleman,
J., Brandly, J. Am. J. Roentg. 1977, 129, 583.
458
Infusion
of the gallbladder is be safe, and, unlike i.v.c., should interfered with by jaundice.
tomography
seems to
Dermatitis
Herpetiformis—the
quick, not
be
Thin
Veneer? association between dermatitis herpetiformis (D.H.) and gluten-sensitive enteropathy (coeliac disease) is so strong that they are easily regarded as a single disease.12 Yet there are differences : patients with D.H. almost always have some jejunal abnormality and both gut and skin disease respond well to a gluten-free diet;but children with coeliac disease almost never get the skin sympTHE
toms.
Dermatitis
herpetiformis is an intensely itchy papulovesicular skin eruption which mainly affects
_
the extensor surfaces.4 It seldom starts before the late teens. The response to sulphones is excellent and until lately this was the criterion for diagnosis as well as the mainstay of treatment. Diagnosis is now facilitated by immunofluorescence, for in D.H. IgA is deposited at the dermal-papillary junction, both in affected and in unaffected skin. Some patients have granular, speckled deposits of IgA, usually associated with C3; others have IgA deposited alone in bandlike fashion.4 What is the pathological meaning of these IgA deposits? An attractive suggestion is that they represent immune-complex deposition-particularly since similar IgA and C3 deposition occurs in the jejunal lamina propria and basement membranes of children with coeliac disease immediately after challenge with gluten.5 Immune complexes have been detected in the sera of patients with D.H. and coeliac disease both in remission and in relapse,6-8 but the very tests used would only pick up IgG complexes or those activating complement by the classical pathway-not a characteristic of IgA. There was also little correlation with disease activity and immune-complex levels. Indeed one paper cites a 100% prevalence of immune complexes in D.H. and coeliac disease, whether patients are in remission or in relapse.8 With such conflicting information it is impossible to tell whether immune complexes are the cause or the result of the disease, but further characterisation of the complexes may shred light on these questions. It would be nice to know whether these patients do have cirScott, B. B., Lbsowsky, M. S. Lancet, 1975, ii, 956. Davies, M. G., Marks, R., Nuki, G. Q. Jl. Med. 1978, 186, 221. Fry, L., McMinn, R. M. H., Cowan, J. D., Hoffbrand, A. V. Lancet, 1968, i, 557. 4. Katz, S. I., Strober, M. D.J. invest. Dermat. 1978, 70, 63 5. Shiner, M., Ballard, J. Lancet, 1972, i, 1202. 6. Mowbray, J. F., Hoffbrand, A. V., Holborow, E. J., Seah, P. P., Fry, L. ibid. 1973, i, 400. 7. Doe, W. F., Booth, C. C., Brown, D. L. ibid. p. 402. 8. Mohammed, I., Holborow, E. J., Fry, L., Thompson, B., Hoffbrand, A. V., Steward, J. S. ibid. 1976, ii, 487. 1. 2. 3.
culating IgA complexes and whether these particucomplexes contain gluten and activate complement via the alternative pathway. Even so, the question why IgA complexes should deposit differentially in the intestinal mucosa in childhood coeliacs and in the skin of D.H. patients is still to be
lar
answered. The finding of antireticulin antibodies in the sera of patients with D.H. is similarly controversial.9 10 One suggestion is that the antireticulin antibodies which are bound to skin cross-react with gluten and trap circulating gluten-antigen antibody complexes in dermal papillx. There are conflicting statements on whether antireticulin antibodies may be absorbed out of sera by gluten.9 10 Also, when antireticulin antibodies have been characterised, they tend to be IgG class9 and if these were deposited in the skin, the characteristic IgA immunoflourescent pattern would be different, unless the IgG antibodies were masked by subsequent deposition of circulating IgA complexes. This is highly unlikely, since the deposited IgA is very hard to elute from the tissues, suggesting a very strong
bond.4 Evidence from jejunal tissue-culture studies in both coeliac disease and D.H. suggests that gluten is not directly cytopathic to epithelial cells of the gastrointestinal tract. 11 Although tissue obtained from patients with active disease shows inhibition of brush-border enzyme increase when gluten is added to the culture medium, no such inhibition is obtained when tissue from a patient on prolonged gluten-free diet is cultured with gluten. This implies that gluten activates an endogenous damaging mechanism which, after a time, allows tissue from patients with gluten-sensitive enteropathy to react to gluten in vitro. There is some evidence that gluten activates the alternative pathway of complement independently, 12 but this does not provide the answer to why some individuals are susceptible and others not. A local mucosal immune deficiency is possible. Mucosal IgA synthesis is increased strikingly after gluten challenge in coeliacs and some of the local antibody produced has anti-gluten specificity." Antibody-dependent cytotoxicity of epithelial cells by lymphocytes has been suggested as a possible damaging mechanism, 14 but this is a function of IgG rather than IgA antibody. There is strong association with both HLA B8s and DW316 in coeliac disease and dermatitis herpe9. Seah, P. P., Fry, L., Hoffbrand, A. V., Holborow, E. J. ibid. 1971, i, 834. 10. Wright, R. Int. Archs Allergy, 1973, 45, 216. 11. Falchuk, Z. M., Gebhard, R. L., Sessoms, C., Strober, W. J. clin. Invest
1974, 53, 487. Massey, A., Capner, P. M., Mowbray, J. F. Immunology, 1977, 33, 339. Falchuk, Z. M., Strober, W. Gut, 1974, 15, 947. Ezeoki, A., Ferguson, A., Fakhri, O., Hekkens, W. T. J. M., Hobbs, J. R. Cœliac Disease: Proceedings of 2nd International Cœliac Symposium (edited by W. T. J. M. Hekkens and A. S. Pena); p. 176, 1974. 15. Katz, S. I., Falchuk, Z. M., Dahl, M. V., Rogentine, G. N., Strober, W. J. clin. Invest. 1972, 51, 2977. 12. 13. 14.
THE LANCET
Radiography in the Diagnosis of Acute Cholecystitis cholecystitis the trigger of the is obstruction cystic duct, by a gallstone or by the oedema due to a gallstone. The result is IN most attacks of acute
gallbladder distension,2 venous hypertensionvascular congestion,2subserosal oedema,2and sometimes small-arterial obliteration. 23 Inflammatory cells then infiltrate the gallbladder.45 In the pathogenesis of these changes the relative importance of bacterial contamination and the direct toxic effects of imprisoned bile-salts is still hotly debated.2 Acute cholecystitis is one of the major causes of emergency surgical admission in adults, and we know that early cholecystectomy can reduce the duration of hospital stay without increasing mortality or morbidity.6Clearly if the policy is to be early operation, correct diagnosis is very important. A surgeon who relies solely on clinical diagnosis will be wrong in at least 15% of cases.8 Fortunately there are several radiological techniques which will help him. The plain abdominal X-ray is of limited valuesince only 10-15% of gallstones are radio-opaque9 and other conditions which may be revealed, such as acute
emphysematous cholecystitis, are extremely
one should be taken. Oral chois often impossible- because of nausea lecystography and vomiting, but intravenous cholangiography (l.v.c.) can be very useful: a gallbladder which opacifies normally virtually rules out acute cholecystitis, whereas a well-opacified common bileduct with no filling of the gallbladder, even on delayed films, is almost pathognomonic of cystic-duct obstruction. 10 11 For I.V.C. most radiologists now use ioglycamide (’Biligram’) rather than the older and more toxic contrast agent iodipamide (’Biligrarare.
Nevertheless,
H. F., Northrap, U. D., Rosenblum, M., Abrahams, H. Am. J. Gastroent. 1968, 50, 476 2. Schein, C. Acute Cholecystitis. Evanston, Ill., 1972. 3. Gordon, K. P. D. Gut, 1967, 8, 565. 4. Robbins, S. L. Pathology. Philadelphia, 1967. 5. Moncada, R., Cardoso, M., Danley, R., Rodriguez, J., Kimura, K., Pickleman, J., Brandly, J. Am. J. Roentg. 1977, 129, 587. 6. McArthur, P., Cushieri, A., Sells, R. A., Shields, R. Br. J. Surg. 1975, 62, 850. 7. Van der Linden, W., Sunzel, H. Surgery Gynec. Obstet. 1970, 114, 1. 8. Essenhigh, D. M. Br. J. Surg. 1966, 53, 1032. 9. Cochrane, S., Shanks, S., Kerley, P. A Textbook of X-ray Diagnosis, vol. 4;
fin’).12 Drip-infusion cholangiography is preferable to bolus injection because toxic side-effects are less frequent and bile-duct opacification is better.14 15 i.v.c.s should never be done in a dehydrated patient"13 and success is unlikely if the serum-bilirubin is above 51 µmol/l (3 mg/dl). As CHEUNG and CHANG" lately emphasised, if neither the gallbladder nor the bile-duct is radiologically visible, the diagnosis may well be some acute intra-abdominal condition other than cholecystitis. A further trap for the unwary is that jaundiced patients excrete most of the i.v.c. dye through the kidneys16 rather than in the bile; the renal pelvis and upper ureter, faintly displayed, may be mistaken for bile-duct and gallbladder. Hepatobiliary scanning with technetium-99m pyridoxylidene glutamate is another diagnostic technique. Isotopic opacification of the gallbladder virtually excludes acute cholecystitis, 17—19 but disappointingly the technique has only a 71% positive predictive value.’8 Like i.v.c., isotope scanning is likely to fail in the presence of jaundice. Grey-scale ultrasonography has been employed to demonstrate gallstones,20 21 and in acute cholecystitis the diagnostic accuracy was 82%.17 This technique may have a particular place in the jaundiced patient, in whom LV.C. and hepatobiliary scanning methods are likely to be unsatisfactory. In 1970 GENEREUX and TCHANG,22 while performing an intravenous pyelogram, fortuitously noted opacification of the gallbladder wall in a case of hydrops of the gallbladder. From this observation stemmed the method knows. as infusion tomography. A solution of 150 ml 60% meglumine diatrizoate (’Urografin)’ mixed with 150 ml of 5% dextrose in water is given by rapid intravenous infusion. Linear tomograms of the anterior third of the right upper quadrant of the abdomen are then obtained. The test is positive when thickened gallbladder wall shows as an opacified ring. (Experimental work in dogs5 has revealed that the opacification is due to the uptake of contrast material by polymorphs in the inflamed tissue.) MONCADA et al.23 have reported the results of infusion tomography in 137 patients with suspected acute cholecystitis. Diagnostic accuracy was 96% in positive cases and 94% in histologically proven negative cases.23
1. Newman,
p. 546. London, 1969. 10. Eckleberg, M. E., Carlson, H. C., Mcllrath, D. C. Am. J. Roentg. 1970, 110, 235. 11. Cheung, L. Y., Chang, F. C. Archs Surg. 1978, 113, 568. 12. Bell, G. D., Fayadh, M., Smith, P. L. C., Frank, J., Kelsey Fry, I. Gut, 1975,
16,841.
13. Ansell, G. Invest. Radiol. 1970, 5, 374. 14. Allen, W. M.C. Br. J. Radiol. 1969, 42, 347. 15. Bell, G. D., Frank, J., Fayadh, M., Smith, P. L. C.,
Kelsey Fry,
I. ibid.
1978,
51, 191. 16. Bell, G. D., Mullins, J., Doran, J., Oliver, J., McAllister, J., Monks, A., Richens, A. ibid. p. 251. 17. Mosley, J. G., Metrovelli, C., Gregory, A. Gut, 1977, 18, A985. 18. Hall, A. W., Wisbey, M. L., Hutchinson, F., Wood, R. A. B., Cuschieri, A. Br. J. Surg. 1978, 65, 361. 19. Stadalnik, R. C., Matalo, N. M., Jansholt, A., Krohn, K. A., De Narwo, G. L., Wolfman, E. F. Radiology, 1976, 121, 657. 20. Doust, B. D., Makland, N. F. ibid. 1974, 119, 643. 21. Bartram, R. J., Crow, H. C., Foote, S. R. New Engl. J. Med 1977, 296, 538. 22. Genereux, G. P., Tchang, S P. K.J. Can. Ass. Radiol. 1970, 21, 39. 23. Moncada, R., Cardoso, M., Danley, R., Rodriguez, J., Kimura, K., Pickleman,
J., Brandly, J. Am. J. Roentg. 1977, 129, 583.
458
Infusion
of the gallbladder is be safe, and, unlike i.v.c., should interfered with by jaundice.
tomography
seems to
Dermatitis
Herpetiformis—the
quick, not
be
Thin
Veneer? association between dermatitis herpetiformis (D.H.) and gluten-sensitive enteropathy (coeliac disease) is so strong that they are easily regarded as a single disease.12 Yet there are differences : patients with D.H. almost always have some jejunal abnormality and both gut and skin disease respond well to a gluten-free diet;but children with coeliac disease almost never get the skin sympTHE
toms.
Dermatitis
herpetiformis is an intensely itchy papulovesicular skin eruption which mainly affects
_
the extensor surfaces.4 It seldom starts before the late teens. The response to sulphones is excellent and until lately this was the criterion for diagnosis as well as the mainstay of treatment. Diagnosis is now facilitated by immunofluorescence, for in D.H. IgA is deposited at the dermal-papillary junction, both in affected and in unaffected skin. Some patients have granular, speckled deposits of IgA, usually associated with C3; others have IgA deposited alone in bandlike fashion.4 What is the pathological meaning of these IgA deposits? An attractive suggestion is that they represent immune-complex deposition-particularly since similar IgA and C3 deposition occurs in the jejunal lamina propria and basement membranes of children with coeliac disease immediately after challenge with gluten.5 Immune complexes have been detected in the sera of patients with D.H. and coeliac disease both in remission and in relapse,6-8 but the very tests used would only pick up IgG complexes or those activating complement by the classical pathway-not a characteristic of IgA. There was also little correlation with disease activity and immune-complex levels. Indeed one paper cites a 100% prevalence of immune complexes in D.H. and coeliac disease, whether patients are in remission or in relapse.8 With such conflicting information it is impossible to tell whether immune complexes are the cause or the result of the disease, but further characterisation of the complexes may shred light on these questions. It would be nice to know whether these patients do have cirScott, B. B., Lbsowsky, M. S. Lancet, 1975, ii, 956. Davies, M. G., Marks, R., Nuki, G. Q. Jl. Med. 1978, 186, 221. Fry, L., McMinn, R. M. H., Cowan, J. D., Hoffbrand, A. V. Lancet, 1968, i, 557. 4. Katz, S. I., Strober, M. D.J. invest. Dermat. 1978, 70, 63 5. Shiner, M., Ballard, J. Lancet, 1972, i, 1202. 6. Mowbray, J. F., Hoffbrand, A. V., Holborow, E. J., Seah, P. P., Fry, L. ibid. 1973, i, 400. 7. Doe, W. F., Booth, C. C., Brown, D. L. ibid. p. 402. 8. Mohammed, I., Holborow, E. J., Fry, L., Thompson, B., Hoffbrand, A. V., Steward, J. S. ibid. 1976, ii, 487. 1. 2. 3.
culating IgA complexes and whether these particucomplexes contain gluten and activate complement via the alternative pathway. Even so, the question why IgA complexes should deposit differentially in the intestinal mucosa in childhood coeliacs and in the skin of D.H. patients is still to be
lar
answered. The finding of antireticulin antibodies in the sera of patients with D.H. is similarly controversial.9 10 One suggestion is that the antireticulin antibodies which are bound to skin cross-react with gluten and trap circulating gluten-antigen antibody complexes in dermal papillx. There are conflicting statements on whether antireticulin antibodies may be absorbed out of sera by gluten.9 10 Also, when antireticulin antibodies have been characterised, they tend to be IgG class9 and if these were deposited in the skin, the characteristic IgA immunoflourescent pattern would be different, unless the IgG antibodies were masked by subsequent deposition of circulating IgA complexes. This is highly unlikely, since the deposited IgA is very hard to elute from the tissues, suggesting a very strong
bond.4 Evidence from jejunal tissue-culture studies in both coeliac disease and D.H. suggests that gluten is not directly cytopathic to epithelial cells of the gastrointestinal tract. 11 Although tissue obtained from patients with active disease shows inhibition of brush-border enzyme increase when gluten is added to the culture medium, no such inhibition is obtained when tissue from a patient on prolonged gluten-free diet is cultured with gluten. This implies that gluten activates an endogenous damaging mechanism which, after a time, allows tissue from patients with gluten-sensitive enteropathy to react to gluten in vitro. There is some evidence that gluten activates the alternative pathway of complement independently, 12 but this does not provide the answer to why some individuals are susceptible and others not. A local mucosal immune deficiency is possible. Mucosal IgA synthesis is increased strikingly after gluten challenge in coeliacs and some of the local antibody produced has anti-gluten specificity." Antibody-dependent cytotoxicity of epithelial cells by lymphocytes has been suggested as a possible damaging mechanism, 14 but this is a function of IgG rather than IgA antibody. There is strong association with both HLA B8s and DW316 in coeliac disease and dermatitis herpe9. Seah, P. P., Fry, L., Hoffbrand, A. V., Holborow, E. J. ibid. 1971, i, 834. 10. Wright, R. Int. Archs Allergy, 1973, 45, 216. 11. Falchuk, Z. M., Gebhard, R. L., Sessoms, C., Strober, W. J. clin. Invest
1974, 53, 487. Massey, A., Capner, P. M., Mowbray, J. F. Immunology, 1977, 33, 339. Falchuk, Z. M., Strober, W. Gut, 1974, 15, 947. Ezeoki, A., Ferguson, A., Fakhri, O., Hekkens, W. T. J. M., Hobbs, J. R. Cœliac Disease: Proceedings of 2nd International Cœliac Symposium (edited by W. T. J. M. Hekkens and A. S. Pena); p. 176, 1974. 15. Katz, S. I., Falchuk, Z. M., Dahl, M. V., Rogentine, G. N., Strober, W. J. clin. Invest. 1972, 51, 2977. 12. 13. 14.
