- Email: [email protected]
Abnormalities on ERCP in a case of human fascioliasis
0016-5107/84/3002-0080$02.00/0 GASTROINTESTINAL ENDOSCOPY Copyright © 1984 by the American Society for Gastrointestinal Endoscopy
Case Re po rts Abnormalities on ERCP in a case of human fascioliasis Stephen C. Hauser, MD Turner E. Bynum, MD
Human fascioliasis is well documented in many parts of the world,1-4 but clinically evident cases acquired in the United States are rare. 5 The acute and chronic phases of the disease have been well described,1,6,7 but the resemblance of the chronic phase on ERCP to sclerosing cholangitis has not been emphasized. We report a case of Fasciola hepatica acquired in the United States. The patient presented with a picture of biliary cirrhosis. ERCP suggested sclerosing cholangitis with intrahepatic cholelithiasis and an intrahepatic bile duct cyst, all of which had been initially interpreted as secondary to inflammatory bowel disease. CASE REPORT
The patient, a 42-year-old white woman, in 1964-65 suffered recurrent bloody diarrhea, diagnosed as ulcerative colitis, and was treated briefly with adrenal glucocorticosteroids and sulfasalazine. Her presumed colitis then remained in remission. In 1968 she developed frequent right upper quadrant pain with abnormal liver chemistry tests and "pancreatitis," for which she underwent cholecystectomy and intraoperative liver biopsy. There were no gallstones, and the pathology of the gallbladder showed "fibrosis of the gallbladder wall" accompanied by chronic inflammatory cells. The liver biopsy was interpreted as chronic active hepatitis for which she was treated with prednisone, in doses ranging from 15 to 60 mg/day, for the next 12 years. Attempts to taper and discontinue the prednisone were never accomplished because the patient complained of ensuing fatigue and malaise. In the 1970s, she had numerous admissions for hepatic encephalopathy, diffuse abdominal pain with intermittent jaundice and hyperamylasemia, and a T7 compression fracture. Recently, she had a normal barium edema and had been told that abdominal ultrasound showed a large intraabdominal cyst of unknown origin. The patient came for a second opinion concerning the chronic active hepatitis. On admission, she was a Cushingoid, ill appearing woman, complaining of her appearance, her weight, fatigue, and edema. She acknowledged intermittent jaundice, fever, nausea, vomiting, abdominal pain, and confusion. Her medications included prednisone (35 mg/day in divided doses), cimetidine, furosemide, potassium, prochlorperazine, lorazepam, and meperidine hydrochloride. On From the GQ1;troenterology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MQ1;sachusetts. Reprint requests: T. E. Bynum, MD, Brigham and Women's Hospital, 75 Francis Street, Boston, MQ1;sachusetts 02115.
80
physical examination she had Cushingoid facies with acneiform skin eruption, a buffalo hump, pigmented striae, and palmar erythema. Her blood pressure was 130/90, pulse rate 100 and regular, respiratory rate 20-30 at rest, and her temperature 99°F. Her chest was clear and the cardiovascular examination was unremarkable. She had 3+ pitting edema of her legs. Examination of the abdomen revealed a liver span of 13 cm with a prominent left lobe which was firm, blunt, nontender, and nonpulsatile. There was no splenomegaly. A proctosigmoidoscopy to 25 cm with a biopsy at 10 cm were both normal. The initial laboratory results were remarkable for a white blood cell count of 11,900 iron 27, platelets 300,000, normal prothrombin time and partial thromboplastin time, SGOT 47, SGPT 53, total bilirubin 1.0 alkaline phosphatase 425, and albumin 3.2. On ERCP (Fig. 1) the pancreatic duct and distal common bile duct were normal, the proximal common bile duct was moderately narrowed, and the intrahepatic radicles showed multiple areas of alternating narrowing and fusiform dilation. The right hepatic duct and its secondary radicles were abnormal with multiple filling defects consistent with calculi. The interpretation was sclerosing cholangitis. In addition, a faint diffuse contrast leakage was noted in the area of the left lobe ofthe liver, where there was thought to be a large cyst. An ultrasound examination confirmed the presence of a 8.5-cm cyst in the region of the left lobe of the liver, as well as multiple areas of increased echos in the liver (Fig. 2). Because of her 15-year history of ulcerative colitis, colonoscopy was performed. The colonoscope was inserted to the cecum, and there was no gross evidence of acute or chronic disease. On withdrawing the colonoscope, a sigmoid perforation was noted. The patient was surgically explored, and a diverting double barrel colostomy was fashioned; needle drainage of 750 ml of fluid from the cyst in the left lobe of the liver was also done. The colonoscopic biopsies from the right and transverse colon were essentially normal. On cell block of the cyst fluid parasitic fragments were noted which, because of size and internal characteristics, were identified as belonging to the fluke family. At this point, further history revealed travel only to France, after 1968. She denied watercress ingestion or exposure to farm animals. Stool for ova and parasites was negative on three occasions. Peritoneal cultures from surgery grew Escherichia coli and Bacteroides {ragilis; she was treated with broad spectrum antibiotics and was discharged with a colostomy for later reanastomosis. Her serum was sent to the University of Puerto Rico where gel diffusion using a F. hepatica segment antigen and a positive F. hepatica serum control from France revealed that both reacted and linked with the patient's serum. A rabbit serum with two antibodies, one genus specific for F. hepatica, also reacted. Furthermore, a circumoval precipital test with Schistosoma mansoni eggs was negative. The patient was treated with bithionol, 1 g three times a day every other day for 15 dose days, and 3 months later her serum ~SrnillNnSTINALEND~CMY
Figure 1. Two views of the biliary tree as obtained by ERCP, showing irregularly narrowed intrahepatic ducts, alternating narrowing and fusiform dilation, and multiple intraductal filling defects. In A, just to the right of the common hepatic duct and proximal common bile duct (toward the patient's left), there is a faint blush of contrast material whic~ does not show well on this reproduction but could be identified as a large cyst on the original radiographs.
precipitating antibodies to F. hepatica and ELISHA antibody levels decreased to normal.
DISCUSSION
Figure 2. Abdominal ultrasound showing a large cyst in the left lobe of the liver. VOLUME 30, NO.2, 1984
Many of the details of this case from the time of cholecystectomy, unfortunately, are unavailable. Her acute right upper quadrant pains with pancreatitis may well have been acute fascioliasis, which is often accompanied by tender hepatomegaly and peripheral eosinophilia. Subsequently, as flukes mature and lay eggs, there is a latent clinical phase during which the flukes, or perhaps the high proline concentrations in the bile produced by the flukes even prior to bile duct invasion, cause hyperplasia and hypertrophy of the bile duct epithelium with enveloping periductal fibroSiS. 8- 1O This in time can cause secondary biliary cirrhosis and changes in the biliary tree which on ERCP resemble sclerosing cholangitis. In the chronic stage there may be neither eggs in the stool nor eosinophilia, and the diagnosis depends on recovering worms or worm fragments in cyst fluid, as in this case, or from the biliary tree. Laparoscopy may reveal abnormalities 81
suggesting fascioliasis,11 but needle liver biopsy specimens are usually nonspecific since they rarely include eggs. 12 Serology may be helpful but is not totally reliable. 2,13 In the acute phase, positive gallium scans, in cold areas by traditional liver scan, have been reported. 14 The current recommended treatment with bithionol is safe and effective. 15-18 There has been little reported experience with metronidazole. 19 Niclofolan may also be useful.20 F. hepatica may be overlooked in both acute and chronic cases. The ERCP in this patient initially misled us, as it was felt to be characteristic of idiopathic sclerosing cholangitis or that due to ulcerative colitis. 21 -22 A recent atlas discussing the ERCP in sclerosing cholangitis states that the findings "can hardly be confused with anything else."23 Our patient could have had idiopathic sclerosing cholangitis and coincidental fascioliasis, but since fascioliasis is known to cause severe abnormalities in the biliary tree, the most direct and economical explanation for her ERCP abnormalities, secondary biliary cirrhosis, and pancreatitis is that all were caused by F. hepatica. Somewhat similar but easily distinguished ERCP findings occur in Caroli's disease,24 echinococcosis,25 and ascariasis. 26 The clinical picture is not consistent with either cholangiocarcinoma or histiocytosis X. 27 Although rare in the United States fascioliasis belongs in the differential diagnosis for an ERCP appearance that is usually associated with sclerosing cholangitis. ACKNOWLEDGMENTS
The authors are most grateful to Dr. George Hillyer of the University of Puerto Rico for performing invaluable serologic determinations. REFERENCES 1. Malek E. Snail-transmitted parasitic diseases, vol 1. Boca Raton, FL: CRC Press, 1980:131. 2. Ashton WIG, Boardman PL, D'Sa CJ, Everall PH, Houghton AWJ. Human fascioliasis in Shropshire. Br MedJ 1970;3:500. 3. Hardman EW, Jones RLH, Davies AH. Fascioliasis-a large outbreak. Br Med J 1970;3:502.
82
4. Facey RV, Marsden PD. Fascioliasis in man: an outbreak in Hampshire. Br Med J 1960;2:619. 5. Norton RA, Monroe L. Infection by Fasciola hepatica acquired in California. Gastroenterology 1961;41:46. 6. Seah SKK. Digenetic trematodes. Clin GastroenteroI1978;7:87. 7. Faust EC, Russell PF, Jung RC.Craig and Faust's Clinical parasitology, 8th ed. Philadelphia: Lea & Febiger, 1970:460. 8. Isseroff H, Sawma JT, Reino D. Fascioliasis-role of proline in bile duct hyperplasia. Science 1977;198:1157. 9. Campbell AJ, Sheers M, Moore RJ, Edwards SR, Montague E. Proline biosynthesis by Fasciola hepatica at different developmental stages in vivo and in vitro. Mol Biochem Parasitol1981; 3:91. 10. Foster JR. A study of the initiation of biliary hyperplasia in rats infected with Fasciola hepatica. Parasitology 1981; 83:253. 11. Moreto M, Barron, J. The laparoscopic diagnosis of the liver fascioliasis. Gastrointest Endosc 1980;26:147 12. Acosta-Ferreira W, Vercelli-Retta J, Falconi LM. Fasciola hepatica human infection-histopathological study of sixteen ,cases. Virchows Arch [Pathol Anat] 1979;383:319. 13. Hillyer GV, DeWeil NS. Serodiagnosis of experimental fascioliasis by immunoprecipitation tests. Int J Parasitol 1981;11:71. 14. Errasti CA, Gomez-Escolar lA, de Zarate PG, Angula JM. Scintigraphic evaluation of the liver in Fasciola hepatica with radiocolloid and 67Ga-citrate. Eur J Nucl Med 1981;6:57. 15. Anthony-Jones E, Kay JM, Milligan HP, Owens D. Massive infection with Fasciola hepatica in man. Am J Med 1977;63:836. 16. Donnelly B, Hederman W. Liver fluke in the common bile duct. Irish Med J 1977;70:507. 17. Dawes B. Some apparent effects of Bithionol on Fasciola hepatica. Nature 1966;209:424. 18. Ed: Drugs for parasitic infections. Med Lett Drugs Ther 1979;21:105. 19. Nik-Akhtar B, Tabibi V. Metronidazole in fascioliasis-report of four cases. J Trop Med Hyg 1977;80:179. 20. Eckhardt T, Heckers H. Treatment of human fascioliasis with Niclofolan. Gastroenterology 1981;81:795. 21. Longmire WP. When is cholangitis sclerosing? Am J Surg 1978;135:312. 22. Blackstone MV, Nemchausky BA. Cholangiographic abnormalities in ulcerative colitis associated pericholangitis which resemble sclerosing cholangitis. Am J Dig Dis 1978;23:579. 23. Stewart ET, Vennes JA, Greenan JE. Atlas ofERCP. St. Louis: CV Mosby, 1977:258. 24. Tulassay Z, Papp J, Szebeni A, Szucs J, Morvath T. Caroli's disease, diagnosed by ERCP and ultrasonography. Endoscopy 1978;10:211. 25. Cottone M, Amuse M, Cotton PB. Endoscopic retrograde cholangiography in hepatic hydatid disease. Br J Surg 1978;65:107. 26. Van Der Spuy S. Biliary ascariasis-endoscopic aspects. S. Afr Med J 1978;53:1030. 27. Leblanc A, Hadchouel M, Jehan P, Odievre M, Alagille D. Obstructive jaundice in children with histiocytosis X. Gastroenterology 1981;80:134.
GASTROINTESTINAL ENDOSCOPY
Case Re po rts Abnormalities on ERCP in a case of human fascioliasis Stephen C. Hauser, MD Turner E. Bynum, MD
Human fascioliasis is well documented in many parts of the world,1-4 but clinically evident cases acquired in the United States are rare. 5 The acute and chronic phases of the disease have been well described,1,6,7 but the resemblance of the chronic phase on ERCP to sclerosing cholangitis has not been emphasized. We report a case of Fasciola hepatica acquired in the United States. The patient presented with a picture of biliary cirrhosis. ERCP suggested sclerosing cholangitis with intrahepatic cholelithiasis and an intrahepatic bile duct cyst, all of which had been initially interpreted as secondary to inflammatory bowel disease. CASE REPORT
The patient, a 42-year-old white woman, in 1964-65 suffered recurrent bloody diarrhea, diagnosed as ulcerative colitis, and was treated briefly with adrenal glucocorticosteroids and sulfasalazine. Her presumed colitis then remained in remission. In 1968 she developed frequent right upper quadrant pain with abnormal liver chemistry tests and "pancreatitis," for which she underwent cholecystectomy and intraoperative liver biopsy. There were no gallstones, and the pathology of the gallbladder showed "fibrosis of the gallbladder wall" accompanied by chronic inflammatory cells. The liver biopsy was interpreted as chronic active hepatitis for which she was treated with prednisone, in doses ranging from 15 to 60 mg/day, for the next 12 years. Attempts to taper and discontinue the prednisone were never accomplished because the patient complained of ensuing fatigue and malaise. In the 1970s, she had numerous admissions for hepatic encephalopathy, diffuse abdominal pain with intermittent jaundice and hyperamylasemia, and a T7 compression fracture. Recently, she had a normal barium edema and had been told that abdominal ultrasound showed a large intraabdominal cyst of unknown origin. The patient came for a second opinion concerning the chronic active hepatitis. On admission, she was a Cushingoid, ill appearing woman, complaining of her appearance, her weight, fatigue, and edema. She acknowledged intermittent jaundice, fever, nausea, vomiting, abdominal pain, and confusion. Her medications included prednisone (35 mg/day in divided doses), cimetidine, furosemide, potassium, prochlorperazine, lorazepam, and meperidine hydrochloride. On From the GQ1;troenterology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MQ1;sachusetts. Reprint requests: T. E. Bynum, MD, Brigham and Women's Hospital, 75 Francis Street, Boston, MQ1;sachusetts 02115.
80
physical examination she had Cushingoid facies with acneiform skin eruption, a buffalo hump, pigmented striae, and palmar erythema. Her blood pressure was 130/90, pulse rate 100 and regular, respiratory rate 20-30 at rest, and her temperature 99°F. Her chest was clear and the cardiovascular examination was unremarkable. She had 3+ pitting edema of her legs. Examination of the abdomen revealed a liver span of 13 cm with a prominent left lobe which was firm, blunt, nontender, and nonpulsatile. There was no splenomegaly. A proctosigmoidoscopy to 25 cm with a biopsy at 10 cm were both normal. The initial laboratory results were remarkable for a white blood cell count of 11,900 iron 27, platelets 300,000, normal prothrombin time and partial thromboplastin time, SGOT 47, SGPT 53, total bilirubin 1.0 alkaline phosphatase 425, and albumin 3.2. On ERCP (Fig. 1) the pancreatic duct and distal common bile duct were normal, the proximal common bile duct was moderately narrowed, and the intrahepatic radicles showed multiple areas of alternating narrowing and fusiform dilation. The right hepatic duct and its secondary radicles were abnormal with multiple filling defects consistent with calculi. The interpretation was sclerosing cholangitis. In addition, a faint diffuse contrast leakage was noted in the area of the left lobe ofthe liver, where there was thought to be a large cyst. An ultrasound examination confirmed the presence of a 8.5-cm cyst in the region of the left lobe of the liver, as well as multiple areas of increased echos in the liver (Fig. 2). Because of her 15-year history of ulcerative colitis, colonoscopy was performed. The colonoscope was inserted to the cecum, and there was no gross evidence of acute or chronic disease. On withdrawing the colonoscope, a sigmoid perforation was noted. The patient was surgically explored, and a diverting double barrel colostomy was fashioned; needle drainage of 750 ml of fluid from the cyst in the left lobe of the liver was also done. The colonoscopic biopsies from the right and transverse colon were essentially normal. On cell block of the cyst fluid parasitic fragments were noted which, because of size and internal characteristics, were identified as belonging to the fluke family. At this point, further history revealed travel only to France, after 1968. She denied watercress ingestion or exposure to farm animals. Stool for ova and parasites was negative on three occasions. Peritoneal cultures from surgery grew Escherichia coli and Bacteroides {ragilis; she was treated with broad spectrum antibiotics and was discharged with a colostomy for later reanastomosis. Her serum was sent to the University of Puerto Rico where gel diffusion using a F. hepatica segment antigen and a positive F. hepatica serum control from France revealed that both reacted and linked with the patient's serum. A rabbit serum with two antibodies, one genus specific for F. hepatica, also reacted. Furthermore, a circumoval precipital test with Schistosoma mansoni eggs was negative. The patient was treated with bithionol, 1 g three times a day every other day for 15 dose days, and 3 months later her serum ~SrnillNnSTINALEND~CMY
Figure 1. Two views of the biliary tree as obtained by ERCP, showing irregularly narrowed intrahepatic ducts, alternating narrowing and fusiform dilation, and multiple intraductal filling defects. In A, just to the right of the common hepatic duct and proximal common bile duct (toward the patient's left), there is a faint blush of contrast material whic~ does not show well on this reproduction but could be identified as a large cyst on the original radiographs.
precipitating antibodies to F. hepatica and ELISHA antibody levels decreased to normal.
DISCUSSION
Figure 2. Abdominal ultrasound showing a large cyst in the left lobe of the liver. VOLUME 30, NO.2, 1984
Many of the details of this case from the time of cholecystectomy, unfortunately, are unavailable. Her acute right upper quadrant pains with pancreatitis may well have been acute fascioliasis, which is often accompanied by tender hepatomegaly and peripheral eosinophilia. Subsequently, as flukes mature and lay eggs, there is a latent clinical phase during which the flukes, or perhaps the high proline concentrations in the bile produced by the flukes even prior to bile duct invasion, cause hyperplasia and hypertrophy of the bile duct epithelium with enveloping periductal fibroSiS. 8- 1O This in time can cause secondary biliary cirrhosis and changes in the biliary tree which on ERCP resemble sclerosing cholangitis. In the chronic stage there may be neither eggs in the stool nor eosinophilia, and the diagnosis depends on recovering worms or worm fragments in cyst fluid, as in this case, or from the biliary tree. Laparoscopy may reveal abnormalities 81
suggesting fascioliasis,11 but needle liver biopsy specimens are usually nonspecific since they rarely include eggs. 12 Serology may be helpful but is not totally reliable. 2,13 In the acute phase, positive gallium scans, in cold areas by traditional liver scan, have been reported. 14 The current recommended treatment with bithionol is safe and effective. 15-18 There has been little reported experience with metronidazole. 19 Niclofolan may also be useful.20 F. hepatica may be overlooked in both acute and chronic cases. The ERCP in this patient initially misled us, as it was felt to be characteristic of idiopathic sclerosing cholangitis or that due to ulcerative colitis. 21 -22 A recent atlas discussing the ERCP in sclerosing cholangitis states that the findings "can hardly be confused with anything else."23 Our patient could have had idiopathic sclerosing cholangitis and coincidental fascioliasis, but since fascioliasis is known to cause severe abnormalities in the biliary tree, the most direct and economical explanation for her ERCP abnormalities, secondary biliary cirrhosis, and pancreatitis is that all were caused by F. hepatica. Somewhat similar but easily distinguished ERCP findings occur in Caroli's disease,24 echinococcosis,25 and ascariasis. 26 The clinical picture is not consistent with either cholangiocarcinoma or histiocytosis X. 27 Although rare in the United States fascioliasis belongs in the differential diagnosis for an ERCP appearance that is usually associated with sclerosing cholangitis. ACKNOWLEDGMENTS
The authors are most grateful to Dr. George Hillyer of the University of Puerto Rico for performing invaluable serologic determinations. REFERENCES 1. Malek E. Snail-transmitted parasitic diseases, vol 1. Boca Raton, FL: CRC Press, 1980:131. 2. Ashton WIG, Boardman PL, D'Sa CJ, Everall PH, Houghton AWJ. Human fascioliasis in Shropshire. Br MedJ 1970;3:500. 3. Hardman EW, Jones RLH, Davies AH. Fascioliasis-a large outbreak. Br Med J 1970;3:502.
82
4. Facey RV, Marsden PD. Fascioliasis in man: an outbreak in Hampshire. Br Med J 1960;2:619. 5. Norton RA, Monroe L. Infection by Fasciola hepatica acquired in California. Gastroenterology 1961;41:46. 6. Seah SKK. Digenetic trematodes. Clin GastroenteroI1978;7:87. 7. Faust EC, Russell PF, Jung RC.Craig and Faust's Clinical parasitology, 8th ed. Philadelphia: Lea & Febiger, 1970:460. 8. Isseroff H, Sawma JT, Reino D. Fascioliasis-role of proline in bile duct hyperplasia. Science 1977;198:1157. 9. Campbell AJ, Sheers M, Moore RJ, Edwards SR, Montague E. Proline biosynthesis by Fasciola hepatica at different developmental stages in vivo and in vitro. Mol Biochem Parasitol1981; 3:91. 10. Foster JR. A study of the initiation of biliary hyperplasia in rats infected with Fasciola hepatica. Parasitology 1981; 83:253. 11. Moreto M, Barron, J. The laparoscopic diagnosis of the liver fascioliasis. Gastrointest Endosc 1980;26:147 12. Acosta-Ferreira W, Vercelli-Retta J, Falconi LM. Fasciola hepatica human infection-histopathological study of sixteen ,cases. Virchows Arch [Pathol Anat] 1979;383:319. 13. Hillyer GV, DeWeil NS. Serodiagnosis of experimental fascioliasis by immunoprecipitation tests. Int J Parasitol 1981;11:71. 14. Errasti CA, Gomez-Escolar lA, de Zarate PG, Angula JM. Scintigraphic evaluation of the liver in Fasciola hepatica with radiocolloid and 67Ga-citrate. Eur J Nucl Med 1981;6:57. 15. Anthony-Jones E, Kay JM, Milligan HP, Owens D. Massive infection with Fasciola hepatica in man. Am J Med 1977;63:836. 16. Donnelly B, Hederman W. Liver fluke in the common bile duct. Irish Med J 1977;70:507. 17. Dawes B. Some apparent effects of Bithionol on Fasciola hepatica. Nature 1966;209:424. 18. Ed: Drugs for parasitic infections. Med Lett Drugs Ther 1979;21:105. 19. Nik-Akhtar B, Tabibi V. Metronidazole in fascioliasis-report of four cases. J Trop Med Hyg 1977;80:179. 20. Eckhardt T, Heckers H. Treatment of human fascioliasis with Niclofolan. Gastroenterology 1981;81:795. 21. Longmire WP. When is cholangitis sclerosing? Am J Surg 1978;135:312. 22. Blackstone MV, Nemchausky BA. Cholangiographic abnormalities in ulcerative colitis associated pericholangitis which resemble sclerosing cholangitis. Am J Dig Dis 1978;23:579. 23. Stewart ET, Vennes JA, Greenan JE. Atlas ofERCP. St. Louis: CV Mosby, 1977:258. 24. Tulassay Z, Papp J, Szebeni A, Szucs J, Morvath T. Caroli's disease, diagnosed by ERCP and ultrasonography. Endoscopy 1978;10:211. 25. Cottone M, Amuse M, Cotton PB. Endoscopic retrograde cholangiography in hepatic hydatid disease. Br J Surg 1978;65:107. 26. Van Der Spuy S. Biliary ascariasis-endoscopic aspects. S. Afr Med J 1978;53:1030. 27. Leblanc A, Hadchouel M, Jehan P, Odievre M, Alagille D. Obstructive jaundice in children with histiocytosis X. Gastroenterology 1981;80:134.
GASTROINTESTINAL ENDOSCOPY