- Email: [email protected]
Ischemic necrosis of bile ducts complicating Schönlein–Henoch purpura
GASTROENTEROLOGY 1999;117:211–214
CASE REPORTS Ischemic Necrosis of Bile Ducts Complicating Scho ¨nlein–Henoch Purpura SHEILA VIOLA,* MARTINE MEYER,‡ MONIQUE FABRE,§ PATRICK TOUNIAN,\ ROLAND GODDON,¶ PIERRE DECHELOTTE,# JACQUES VALAYER,** MAX GRUNER,‡‡ and OLIVIER BERNARD* *He´patologie Pe´diatrique, **Chirurgie Pe´diatrique, and §Anatomie Pathologique, Ho ˆpital Bice ˆtre, Le Kremlin Bice ˆtre; ‡Pe´diatrie B and #Anatomie Pathologie, Hotel-Dieu, Clermont-Ferrand; \Gastroente´rologie et Nutrition Pe´diatrique and ‡‡Chirurgie Pe´diatrique, Ho ˆpital Armand-Trousseau, Paris; and ¶Pe´diatrie, Ho ˆpital de Montluc¸on, Montluc¸on, France
Gastrointestinal complications of Scho ¨nlein–Henoch purpura are frequent and sometimes severe. However, there seem to be no reports of liver involvement. A child is described in whom Scho ¨nlein–Henoch purpura was complicated by bile duct lesions, resulting in biliary cirrhosis and requiring liver transplantation. At surgical removal, the liver had lesions of bile ducts and of adjacent small blood vessels in the hilum, very similar to those complicating hepatic artery thrombosis after liver transplantation. These findings suggest that Scho ¨nlein–Henoch purpura can be complicated by vasculitis of the peribiliary vessels resulting in ischemic necrosis of the bile ducts. Scho ¨nlein–Henoch purpura can be added to the list of causes of ischemic cholangiopathies.
cho¨nlein–Henoch purpura is a form of vasculitis that mostly occurs during childhood and whose main targets are the skin, joints, gastrointestinal tract, and kidneys.1 The liver seems to be not involved, although a few cases of acute cholecystitis have been described.1,2 This case report describes a girl in whom severe Scho¨nlein– Henoch purpura was associated with bile duct lesions resulting in chronic cholestasis, biliary cirrhosis, and relapsing bacterial cholangitis that eventually required orthotopic liver transplantation. The histological lesions found in the native liver suggest that the origin of the biliary lesions was ischemic.
S
Case Report An 8-year-old girl had been well until she presented with fever, arthralgia, and a purpuric rash of the lower limbs clinically typical of Scho¨nlein–Henoch disease. A few days later, abdominal pain and severe bloody diarrhea required total parenteral nutrition for 6 weeks and steroid therapy. A week later, proteinuria was noted, and the child developed a nephrotic syndrome that was treated with additional steroid therapy for 2 months and cured with no apparent sequelae.
Four weeks after the beginning of the disease, the child again complained of abdominal pain. Liver ultrasonography showed several hypoechogenic round areas in segments III and VI with a hypodense and homogeneous appearance on computerized axial tomography scan. A diagnosis of intrahepatic hematomas was made. Liver function test results were normal. During the next 2 months, these hepatic lesions disappeared completely, but progressive dilatation of the bile ducts was noted on ultrasound images, associated with jaundice, pruritus, and high serum transaminase and ␥-glutamyltransferase activity (2 and 3 times above normal, respectively). Eight months after onset of the disease, transhepatic cholangiography showed stenosis of the left hepatic duct near the bifurcation, with no opacification of this duct (Figure 1). Cholecystectomy and wedge liver biopsy were performed; histological examination of the gallbladder showed signs of acute acalculous cholecystitis. Examination of the liver biopsy specimens showed portal fibrosis and ductular proliferation (Figure 2). Tests for hepatitis A, B, and C and antinuclear, antimitochondrial, and anti–smooth muscle antibodies were negative. One year after onset of the disease, repeat laparotomy was performed to treat the bile duct stenosis. A cystlike bile leak in the liver hilum was found, with necrosis of the right and left hepatic ducts. Hepatic portoenterostomy was performed; as a result, ultrasonography showed a transitory improvement in the signs of cholestasis and left bile duct dilatation. During the following 3 years, several attacks of bacterial cholangitis occurred. A needle liver biopsy, 39 months after the onset of Scho¨nlein–Henoch purpura, showed signs of patent biliary cirrhosis. The results of liver function tests were as follows: total serum bilirubin, 82 µmol/L; conjugated serum bilirubin, 63 µmol/L; alanine aminotransferase activity, 5 times above the upper limit of normal; serum alkaline phosphatase activity, 4 times above the upper limit of normal; and serum ␥-glutamylr 1999 by the American Gastroenterological Association 0016-5085/99/$10.00
212 VIOLA ET AL.
GASTROENTEROLOGY Vol. 117, No. 1
In the center of the liver, there was a dilated intrahepatic duct, with proliferation of the mucosa, infiltration by lymphocytes and plasmocytes, and ulcerations of the epithelium in these affected areas. Polymorphonuclear cells were also seen in the epithelium. Dilated bile ducts were located near areas of stenosis, and complete fibrotic occlusion of the lumina of these ducts was observed. At the periphery of the liver, no interlobular bile ducts were visible, and there was ductular proliferation and fibrosis, indicative of secondary biliary cirrhosis. Immunofluorescence studies showed no deposits of immunoglobulin (Ig) G, IgM, IgA, or complement on vessel walls.
Discussion
Figure 1. Transhepatic cholangiogram obtained 8 months after the onset of disease in a child with Scho¨nlein–Henoch purpura and cholestasis. Stenosis of the left primary hepatic duct and a bile leak near the bifurcation are visible.
transferase activity, 22 times above the upper limit of normal. Repeat transhepatic cholangiography showed almost complete stenosis of the left hepatic duct, with no visible right hepatic duct. An attempt at endoluminal dilatation of this stenosis was unsuccessful (Figure 3). Orthotopic liver transplantation was performed at age 12, 44 months after the onset of disease; 25 months later (September 1998), the child was in good clinical condition, was attending school, and was participating in sports normally. Liver function test results were normal, and creatinine clearance, according to the Schwartz formula, was 114 mL · min⫺1 · 1.73 m2. There was no proteinuria. The girl is currently being treated with tacrolimus and alternate-day prednisone. The native liver, removed 44 months after the onset of Scho¨nlein–Henoch purpura, weighed 1247 g. Examination of the liver revealed the presence of hypertrophic micronodular and macronodular cirrhosis (nodules 1–2 mm in diameter) with fibrous atrophy of the left lobe. Deeply bile-stained regenerative macronodules, which were partly surrounded by a fibrous rim and formed bulges on the cut surface, were present in segments I, III, IV, VI, and VIII. These macronodules were 6 mm in diameter. Around the nodules, hepatic cells had few copper granules after rhodamine stain. There were no Mallory bodies. In the liver hilum, the common hepatic duct was irregular in shape and dilated by fibrous thickening of its wall. Near this duct, we observed advanced vascular lesions consisting of concentric fibrous thickening of small vessel walls that reduced the diameter of the lumina, with subtotal occlusion by fibrosis (Figures 4 and 5). Iron stain of the vessels was negative.
Scho¨nlein–Henoch purpura was clinically evident in this child, and the digestive and renal involvement are consistent with this diagnosis. Other causes of acute liver or biliary damage associated with systemic manifestations such as viral hepatitis, systemic lupus erythematosus, or autoimmune cholangitis were extremely unlikely on clinical grounds or were excluded by appropriate tests. Liver or bile duct involvement is extremely rare in children with Scho¨nlein–Henoch disease, and only 3 cases of cholecystitis have been reported.1,2 In these 3 cases, abdominal pain of the upper right quadrant led to ultrasonographic findings consistent with cholecystitis. In 1 patient, abnormal liver function test results were mentioned but no investigation of the biliary tree was reported. The pathophysiological mechanism of these cases of cholecystitis is obscure, and no biopsy specimens were obtained. We suggest that, in our patient, the intrahepatic and extrahepatic bile duct lesions resulted from vascular damage, mostly arteriolar, caused by Scho¨nlein–Henoch purpura vasculitis. Biliary ischemia secondary to the lesions of small arteries seen in the native liver would explain the necrosis of the extrahepatic bile ducts leading to the biliary leak seen at surgery, the stenosis of the left hepatic duct seen on the cholangiograms, and the fibrous bile duct lesions seen in the native liver. The absence of IgA and complement deposits on the damaged arterial and arteriolar walls close to the damaged bile ducts does not mean that no such deposits were formed, because they are always present in the early stages of Scho¨nlein– Henoch glomerulopathy, but they may decrease or disappear with time.3 In our patient, the histopathologic examination was performed 44 months after the onset of the disease, an interval that may explain the examination’s negative results. The biliary lesions were indeed very similar to those complicating thrombosis of the hepatic artery after liver transplantation.4 Furthermore, lesions of the peribiliary blood vessels resulting in bile
July 1999
Figure 2. A liver biopsy specimen at age 9, 8 months after the onset of Scho¨nlein–Henoch purpura, shows portal and septal fibrosis and ductular proliferation suggestive of biliary disease (trichrome stain; original magnification 63⫻).
duct ischemia have been reported after hepatic artery fluxoridine injection,5 hepatic arterial chemoembolization,6 bile duct irradiation,7 and paroxysmal nocturnal hemoglobinuria.8 In rats, hepatic artery thrombosis may eventually result in biliary cirrhosis9; nonarterialized liver grafts display bile duct damage after 3 days, cellular infiltration and ductular proliferation after 4 weeks, and fibrosis after 6 months. In our patient, severe stenosis of the left hepatic duct was seen 3 months after the onset of disease. The liver first had portal fibrosis and ductular proliferation and then patent signs of biliary cirrhosis.
Figure 3. Repeat transhepatic cholangiogram obtained 35 months after the onset of Scho¨nlein–Henoch purpura. The left hepatic duct is almost completely stenosed.
¨ NLEIN–HENOCH PURPURA 213 BILIARY CIRRHOSIS AND SCHO
Figure 4. Native liver removed during transplantation. In the left parahilar region, bile ducts are irregular, dilated, and surrounded by fibrosis (B). Some ducts have been destroyed and replaced by scars. A network of arteries of various sizes can be seen, with fibromuscular hyperplasia (A). Portal phlebosclerosis is visible in the center of the field (V). Nerve hyperplasia is present with fibrosis (N) (H&E stain; original magnification 4⫻).
Liver transplantation was indicated in this patient because of the refractory bacterial cholangitis and the signs of biliary cirrhosis. In patients with severe Scho¨nlein–Henoch nephropathy, the original disease may relapse in the transplanted kidney.10–12 Its recurrence may be observed for up to 5 years after transplantation, despite an interval of 1 year between the last bout of purpura and the time of transplantation. The risk of relapse seems to be associated with a shorter duration of the original disease.12 In our patient, Scho¨nlein–Henoch purpura lasted less than 6 months, the interval between purpura and liver transplantation was 44 months, and 2 years after transplantation there were no biochemical or ultrasonographic signs of relapse in the transplanted liver.
Figure 5. Native liver removed during transplantation. In the hilum, there are vascular lesions with concentric fibrous thickening of small vessel walls reducing the diameter of the arterial lumina and subtotal occlusion with fibrosis (elastic-orcein stain; original magnification 12.5⫻).
214 VIOLA ET AL.
In conclusion, this patient’s history suggests that vasculitis of the peribiliary vessels may occur during Scho¨nlein–Henoch purpura, resulting in ischemic necrosis and stenosis of bile ducts and, ultimately, obstructive biliary cirrhosis. Therefore, Scho¨nlein–Henoch purpura may be added to the list of possible causes of ischemic cholangiopathies.
References 1. Amemoto K, Nagita A, Aoki S, Azumagawa K, Hirano K, Mino M. Ultrasonographic gallbladder wall thickening in children with Henoch–Scho¨nlein purpura. J Pediatr Gastroenterol Nutr 1994;19: 126–128. 2. De La Pena A, Yuste JR, Beloqui O, Prieto J. Acalculous cholecystitis in Scho¨nlein–Henoch purpura. A propos of a case. Rev Med Univ Navarra 1995;39:126–129. 3. Habib R, Niaudet P, Levy M. Scho¨nlein–Henoch purpura nephritis and Ig A nephropathy. In: Tisher CC, and Brenner BM, eds. Renal pathology: with clinical and functional correlations. 2d ed. Philadelphia: Lippincott, 1994:472–510. 4. Sanchez-Urdazpal L, Gores GJ, Ward EM, Maus TP, Buckel EG, Steers JL, Wiesner RH, Krom RAF. Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation. Hepatology 1993;17:605–609. 5. Ludwig J, Kim CH, Wiesner RH, Krom RA. Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy? Hepatology 1989;9:215–218. 6. Richardet JP, Lons T, Sibony M, Chowy A, Ajavon Y, Coderc E, Grimbert S, Hecht Y, Beaugrand M. Cholangite scle´rosante
GASTROENTEROLOGY Vol. 117, No. 1
7.
8.
9.
10. 11.
12.
secondaire et chimio-embolisation lipiodole´e. Gastrenterol Clin Biol 1994;18:168–171. Cherqui D, Palazzo L, Piedbois P, Charlotte F, Duvoux C, Duron JJ, Fagniez PL, Valla D. Common bile duct stricture as a late complication of upper abdominal radiotherapy. J Hepatol 1994;20: 693–697. Huong D, Valla D, Franco D, Wechsler B, De Gramont A, Auperin A, Godeau P. Cholangitis associated with paroxysmal nocturnal hemoglobinuria: another instance of ischemic cholangiopathy? Gastroenterology 1995;109:1338–1343. Zhao D, Zimmermann A, Kuznetsova LV, Wheatley AM. Regression of bile duct damage and bile duct proliferation in the nonrearterialized transplanted rat liver is associated with spontaneous graft rearterialization. Hepatology 1995;21:1353–1360. Weinreich T, Binswanger U. Does the primary disease recur in kidney transplantation? Ther Umsch 1995;52:566–71. Kessler M, Hiesse C, Hestin D, Mayeux D, Boudenider K, Charpentier B. Recurrence of immunoglobulin A nephropathy after renal transplantation in the cyclosporine era. Am J Kidney Dis 1996;28:99–104. Meulders Q, Pirson Y, Cosyns JP, Squifflet JP, Van-Ypersele, De-Strihou C. Course of Henoch–Scho¨nlein nephritis after renal transplantation. Report on ten patients and review of the literature. Transplantation 1994;58:1179–1186.
Received April 2, 1998. Accepted March 23, 1999. Address requests for reprints to: Sheila Viola, M.D., Service de Gastroente ´rologie et Nutrition Pe ´diatrique, Ho ˆpital Armand-Trousseau, 26 Avenue du Dr Arnold Netter, 75 571 Paris Cedex 12, France. The authors thank M. Dreyfus for revision of the manuscript.
CASE REPORTS Ischemic Necrosis of Bile Ducts Complicating Scho ¨nlein–Henoch Purpura SHEILA VIOLA,* MARTINE MEYER,‡ MONIQUE FABRE,§ PATRICK TOUNIAN,\ ROLAND GODDON,¶ PIERRE DECHELOTTE,# JACQUES VALAYER,** MAX GRUNER,‡‡ and OLIVIER BERNARD* *He´patologie Pe´diatrique, **Chirurgie Pe´diatrique, and §Anatomie Pathologique, Ho ˆpital Bice ˆtre, Le Kremlin Bice ˆtre; ‡Pe´diatrie B and #Anatomie Pathologie, Hotel-Dieu, Clermont-Ferrand; \Gastroente´rologie et Nutrition Pe´diatrique and ‡‡Chirurgie Pe´diatrique, Ho ˆpital Armand-Trousseau, Paris; and ¶Pe´diatrie, Ho ˆpital de Montluc¸on, Montluc¸on, France
Gastrointestinal complications of Scho ¨nlein–Henoch purpura are frequent and sometimes severe. However, there seem to be no reports of liver involvement. A child is described in whom Scho ¨nlein–Henoch purpura was complicated by bile duct lesions, resulting in biliary cirrhosis and requiring liver transplantation. At surgical removal, the liver had lesions of bile ducts and of adjacent small blood vessels in the hilum, very similar to those complicating hepatic artery thrombosis after liver transplantation. These findings suggest that Scho ¨nlein–Henoch purpura can be complicated by vasculitis of the peribiliary vessels resulting in ischemic necrosis of the bile ducts. Scho ¨nlein–Henoch purpura can be added to the list of causes of ischemic cholangiopathies.
cho¨nlein–Henoch purpura is a form of vasculitis that mostly occurs during childhood and whose main targets are the skin, joints, gastrointestinal tract, and kidneys.1 The liver seems to be not involved, although a few cases of acute cholecystitis have been described.1,2 This case report describes a girl in whom severe Scho¨nlein– Henoch purpura was associated with bile duct lesions resulting in chronic cholestasis, biliary cirrhosis, and relapsing bacterial cholangitis that eventually required orthotopic liver transplantation. The histological lesions found in the native liver suggest that the origin of the biliary lesions was ischemic.
S
Case Report An 8-year-old girl had been well until she presented with fever, arthralgia, and a purpuric rash of the lower limbs clinically typical of Scho¨nlein–Henoch disease. A few days later, abdominal pain and severe bloody diarrhea required total parenteral nutrition for 6 weeks and steroid therapy. A week later, proteinuria was noted, and the child developed a nephrotic syndrome that was treated with additional steroid therapy for 2 months and cured with no apparent sequelae.
Four weeks after the beginning of the disease, the child again complained of abdominal pain. Liver ultrasonography showed several hypoechogenic round areas in segments III and VI with a hypodense and homogeneous appearance on computerized axial tomography scan. A diagnosis of intrahepatic hematomas was made. Liver function test results were normal. During the next 2 months, these hepatic lesions disappeared completely, but progressive dilatation of the bile ducts was noted on ultrasound images, associated with jaundice, pruritus, and high serum transaminase and ␥-glutamyltransferase activity (2 and 3 times above normal, respectively). Eight months after onset of the disease, transhepatic cholangiography showed stenosis of the left hepatic duct near the bifurcation, with no opacification of this duct (Figure 1). Cholecystectomy and wedge liver biopsy were performed; histological examination of the gallbladder showed signs of acute acalculous cholecystitis. Examination of the liver biopsy specimens showed portal fibrosis and ductular proliferation (Figure 2). Tests for hepatitis A, B, and C and antinuclear, antimitochondrial, and anti–smooth muscle antibodies were negative. One year after onset of the disease, repeat laparotomy was performed to treat the bile duct stenosis. A cystlike bile leak in the liver hilum was found, with necrosis of the right and left hepatic ducts. Hepatic portoenterostomy was performed; as a result, ultrasonography showed a transitory improvement in the signs of cholestasis and left bile duct dilatation. During the following 3 years, several attacks of bacterial cholangitis occurred. A needle liver biopsy, 39 months after the onset of Scho¨nlein–Henoch purpura, showed signs of patent biliary cirrhosis. The results of liver function tests were as follows: total serum bilirubin, 82 µmol/L; conjugated serum bilirubin, 63 µmol/L; alanine aminotransferase activity, 5 times above the upper limit of normal; serum alkaline phosphatase activity, 4 times above the upper limit of normal; and serum ␥-glutamylr 1999 by the American Gastroenterological Association 0016-5085/99/$10.00
212 VIOLA ET AL.
GASTROENTEROLOGY Vol. 117, No. 1
In the center of the liver, there was a dilated intrahepatic duct, with proliferation of the mucosa, infiltration by lymphocytes and plasmocytes, and ulcerations of the epithelium in these affected areas. Polymorphonuclear cells were also seen in the epithelium. Dilated bile ducts were located near areas of stenosis, and complete fibrotic occlusion of the lumina of these ducts was observed. At the periphery of the liver, no interlobular bile ducts were visible, and there was ductular proliferation and fibrosis, indicative of secondary biliary cirrhosis. Immunofluorescence studies showed no deposits of immunoglobulin (Ig) G, IgM, IgA, or complement on vessel walls.
Discussion
Figure 1. Transhepatic cholangiogram obtained 8 months after the onset of disease in a child with Scho¨nlein–Henoch purpura and cholestasis. Stenosis of the left primary hepatic duct and a bile leak near the bifurcation are visible.
transferase activity, 22 times above the upper limit of normal. Repeat transhepatic cholangiography showed almost complete stenosis of the left hepatic duct, with no visible right hepatic duct. An attempt at endoluminal dilatation of this stenosis was unsuccessful (Figure 3). Orthotopic liver transplantation was performed at age 12, 44 months after the onset of disease; 25 months later (September 1998), the child was in good clinical condition, was attending school, and was participating in sports normally. Liver function test results were normal, and creatinine clearance, according to the Schwartz formula, was 114 mL · min⫺1 · 1.73 m2. There was no proteinuria. The girl is currently being treated with tacrolimus and alternate-day prednisone. The native liver, removed 44 months after the onset of Scho¨nlein–Henoch purpura, weighed 1247 g. Examination of the liver revealed the presence of hypertrophic micronodular and macronodular cirrhosis (nodules 1–2 mm in diameter) with fibrous atrophy of the left lobe. Deeply bile-stained regenerative macronodules, which were partly surrounded by a fibrous rim and formed bulges on the cut surface, were present in segments I, III, IV, VI, and VIII. These macronodules were 6 mm in diameter. Around the nodules, hepatic cells had few copper granules after rhodamine stain. There were no Mallory bodies. In the liver hilum, the common hepatic duct was irregular in shape and dilated by fibrous thickening of its wall. Near this duct, we observed advanced vascular lesions consisting of concentric fibrous thickening of small vessel walls that reduced the diameter of the lumina, with subtotal occlusion by fibrosis (Figures 4 and 5). Iron stain of the vessels was negative.
Scho¨nlein–Henoch purpura was clinically evident in this child, and the digestive and renal involvement are consistent with this diagnosis. Other causes of acute liver or biliary damage associated with systemic manifestations such as viral hepatitis, systemic lupus erythematosus, or autoimmune cholangitis were extremely unlikely on clinical grounds or were excluded by appropriate tests. Liver or bile duct involvement is extremely rare in children with Scho¨nlein–Henoch disease, and only 3 cases of cholecystitis have been reported.1,2 In these 3 cases, abdominal pain of the upper right quadrant led to ultrasonographic findings consistent with cholecystitis. In 1 patient, abnormal liver function test results were mentioned but no investigation of the biliary tree was reported. The pathophysiological mechanism of these cases of cholecystitis is obscure, and no biopsy specimens were obtained. We suggest that, in our patient, the intrahepatic and extrahepatic bile duct lesions resulted from vascular damage, mostly arteriolar, caused by Scho¨nlein–Henoch purpura vasculitis. Biliary ischemia secondary to the lesions of small arteries seen in the native liver would explain the necrosis of the extrahepatic bile ducts leading to the biliary leak seen at surgery, the stenosis of the left hepatic duct seen on the cholangiograms, and the fibrous bile duct lesions seen in the native liver. The absence of IgA and complement deposits on the damaged arterial and arteriolar walls close to the damaged bile ducts does not mean that no such deposits were formed, because they are always present in the early stages of Scho¨nlein– Henoch glomerulopathy, but they may decrease or disappear with time.3 In our patient, the histopathologic examination was performed 44 months after the onset of the disease, an interval that may explain the examination’s negative results. The biliary lesions were indeed very similar to those complicating thrombosis of the hepatic artery after liver transplantation.4 Furthermore, lesions of the peribiliary blood vessels resulting in bile
July 1999
Figure 2. A liver biopsy specimen at age 9, 8 months after the onset of Scho¨nlein–Henoch purpura, shows portal and septal fibrosis and ductular proliferation suggestive of biliary disease (trichrome stain; original magnification 63⫻).
duct ischemia have been reported after hepatic artery fluxoridine injection,5 hepatic arterial chemoembolization,6 bile duct irradiation,7 and paroxysmal nocturnal hemoglobinuria.8 In rats, hepatic artery thrombosis may eventually result in biliary cirrhosis9; nonarterialized liver grafts display bile duct damage after 3 days, cellular infiltration and ductular proliferation after 4 weeks, and fibrosis after 6 months. In our patient, severe stenosis of the left hepatic duct was seen 3 months after the onset of disease. The liver first had portal fibrosis and ductular proliferation and then patent signs of biliary cirrhosis.
Figure 3. Repeat transhepatic cholangiogram obtained 35 months after the onset of Scho¨nlein–Henoch purpura. The left hepatic duct is almost completely stenosed.
¨ NLEIN–HENOCH PURPURA 213 BILIARY CIRRHOSIS AND SCHO
Figure 4. Native liver removed during transplantation. In the left parahilar region, bile ducts are irregular, dilated, and surrounded by fibrosis (B). Some ducts have been destroyed and replaced by scars. A network of arteries of various sizes can be seen, with fibromuscular hyperplasia (A). Portal phlebosclerosis is visible in the center of the field (V). Nerve hyperplasia is present with fibrosis (N) (H&E stain; original magnification 4⫻).
Liver transplantation was indicated in this patient because of the refractory bacterial cholangitis and the signs of biliary cirrhosis. In patients with severe Scho¨nlein–Henoch nephropathy, the original disease may relapse in the transplanted kidney.10–12 Its recurrence may be observed for up to 5 years after transplantation, despite an interval of 1 year between the last bout of purpura and the time of transplantation. The risk of relapse seems to be associated with a shorter duration of the original disease.12 In our patient, Scho¨nlein–Henoch purpura lasted less than 6 months, the interval between purpura and liver transplantation was 44 months, and 2 years after transplantation there were no biochemical or ultrasonographic signs of relapse in the transplanted liver.
Figure 5. Native liver removed during transplantation. In the hilum, there are vascular lesions with concentric fibrous thickening of small vessel walls reducing the diameter of the arterial lumina and subtotal occlusion with fibrosis (elastic-orcein stain; original magnification 12.5⫻).
214 VIOLA ET AL.
In conclusion, this patient’s history suggests that vasculitis of the peribiliary vessels may occur during Scho¨nlein–Henoch purpura, resulting in ischemic necrosis and stenosis of bile ducts and, ultimately, obstructive biliary cirrhosis. Therefore, Scho¨nlein–Henoch purpura may be added to the list of possible causes of ischemic cholangiopathies.
References 1. Amemoto K, Nagita A, Aoki S, Azumagawa K, Hirano K, Mino M. Ultrasonographic gallbladder wall thickening in children with Henoch–Scho¨nlein purpura. J Pediatr Gastroenterol Nutr 1994;19: 126–128. 2. De La Pena A, Yuste JR, Beloqui O, Prieto J. Acalculous cholecystitis in Scho¨nlein–Henoch purpura. A propos of a case. Rev Med Univ Navarra 1995;39:126–129. 3. Habib R, Niaudet P, Levy M. Scho¨nlein–Henoch purpura nephritis and Ig A nephropathy. In: Tisher CC, and Brenner BM, eds. Renal pathology: with clinical and functional correlations. 2d ed. Philadelphia: Lippincott, 1994:472–510. 4. Sanchez-Urdazpal L, Gores GJ, Ward EM, Maus TP, Buckel EG, Steers JL, Wiesner RH, Krom RAF. Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation. Hepatology 1993;17:605–609. 5. Ludwig J, Kim CH, Wiesner RH, Krom RA. Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy? Hepatology 1989;9:215–218. 6. Richardet JP, Lons T, Sibony M, Chowy A, Ajavon Y, Coderc E, Grimbert S, Hecht Y, Beaugrand M. Cholangite scle´rosante
GASTROENTEROLOGY Vol. 117, No. 1
7.
8.
9.
10. 11.
12.
secondaire et chimio-embolisation lipiodole´e. Gastrenterol Clin Biol 1994;18:168–171. Cherqui D, Palazzo L, Piedbois P, Charlotte F, Duvoux C, Duron JJ, Fagniez PL, Valla D. Common bile duct stricture as a late complication of upper abdominal radiotherapy. J Hepatol 1994;20: 693–697. Huong D, Valla D, Franco D, Wechsler B, De Gramont A, Auperin A, Godeau P. Cholangitis associated with paroxysmal nocturnal hemoglobinuria: another instance of ischemic cholangiopathy? Gastroenterology 1995;109:1338–1343. Zhao D, Zimmermann A, Kuznetsova LV, Wheatley AM. Regression of bile duct damage and bile duct proliferation in the nonrearterialized transplanted rat liver is associated with spontaneous graft rearterialization. Hepatology 1995;21:1353–1360. Weinreich T, Binswanger U. Does the primary disease recur in kidney transplantation? Ther Umsch 1995;52:566–71. Kessler M, Hiesse C, Hestin D, Mayeux D, Boudenider K, Charpentier B. Recurrence of immunoglobulin A nephropathy after renal transplantation in the cyclosporine era. Am J Kidney Dis 1996;28:99–104. Meulders Q, Pirson Y, Cosyns JP, Squifflet JP, Van-Ypersele, De-Strihou C. Course of Henoch–Scho¨nlein nephritis after renal transplantation. Report on ten patients and review of the literature. Transplantation 1994;58:1179–1186.
Received April 2, 1998. Accepted March 23, 1999. Address requests for reprints to: Sheila Viola, M.D., Service de Gastroente ´rologie et Nutrition Pe ´diatrique, Ho ˆpital Armand-Trousseau, 26 Avenue du Dr Arnold Netter, 75 571 Paris Cedex 12, France. The authors thank M. Dreyfus for revision of the manuscript.