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Hepatic rupture caused by peliosis hepatis
Hepatic Rupture Caused by Peliosis Hepatis By Stephanie Y. Wang, Scott Ruggles, Aruna Vade, Barry M. Newman, and Marc A. Borge Maywood, Illinois
Peliosis hepatis is a rare entity that can affect children and cause fatal hepatic hemorrhage or hepatic failure. Radiographic findings are nonspecific and can resemble other hepatic pathologies such as cysts, abscesses, metastases, and hemangiomatosis. Peliosis hepatis can resolve spontaneously or by withdrawal of inciting medications. Certain cases may require surgical resection of the involved portions of the liver. Recently, fatal liver hemorrhage was reported in 2 pediatric patients with a rare congenital muscle disorder known as myotubular (centronuclear) myopathy. One of these patients was found at autopsy to have peliosis hepatis.
P
ELIOSIS HEPATIS was first recognized in the German literature in 1861 by Wagner and named by Schoenlank in 1916.1 It is a rare condition characterized by multiple small cystic blood-filled spaces in the liver, which can be seen through the intact liver capsule.1 The etiology of this condition is unknown, but it is known to be associated with various prolonged wasting diseases, such as tuberculosis, solid-organ malignancies, and other hematologic disorders.2 Peliosis hepatis also has been reported in association with human immunodeficiency virus (HIV) disease, bacterial infections, and the presence of renal allografts.3-17 There also is evidence that drugs, primarily anabolic steroids, may be associated with this lesion.18-23 Hepatic peliosis sometimes is an incidental finding at autopsy or it may cause fatal liver failure or hepatic rupture and often is diagnosed only at autopsy.18,20,21 Only a few cases of this disease have been reported in children—in 5 of these, diagnosis was made at autopsy.24-28 In one infant the diagnosis was made by surgical biopsy of the resected lobe.29 We report imaging findings in a child with a rare congenital condition known as myotubular (centronuclear) myopathy and hepatic rupture secondary to peliosis hepatis, which resolved after surgical exploration for life-threatening hemorrhage.
From the Departments of Radiology and Surgery, Loyola University Medical Center, Maywood, IL. Address reprint requests to Aruna Vade, MD, Department of Radiology, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3609-0030$35.00/0 doi:10.1053/jpsu.2001.26397 1456
The authors report the first successful treatment of lifethreatening liver hemorrhage caused by peliosis hepatis in a child with myotubular myopathy. Awareness of this condition may reduce the catastrophic complications seen with peliosis hepatis. J Pediatr Surg 36:1456-1459. Copyright © 2001 by W.B. Saunders Company.
INDEX WORDS: Peliosis, hepatic, hemorrhage, myotubular myopathy, centronuclear myopathy.
CASE REPORT The patient is a 3-year-old boy with myotubular myopathy and a 1-week history of malaise, arthralgias, and postnasal drip. He recently had been treated with Suprax and amoxicillin for otitis media. His past medical history was significant for delayed milestones of motor, but not mental, development. He had undergone a Nissen fundoplication and placement of bilateral myringotomy tubes at birth. Medications included lactulose, Poly-vi-sol, levocarnitine solution, coenzyme Q, albuterol, and atrovent nebulizer treatments as needed, and several vitamins, minerals, and homeopathic medications. One older brother (age 7 years) also had myotubular myopathy and was ventilator dependent. Two other siblings (a brother, age 17, and a sister, age 9) were without clinical evidence of the disorder. On physical examination, the liver edge was palpable below the costal margin. The spleen was not palpable. A complete blood count was as follows: white blood cell count, 10.2 k/L; hemoglobin, 11.3 g/dL; hematocrit, 33%; and platelet count, 286 k/L. AST was 54 IU/L, alkaline phosphatase was 320 IU/L, and total bilirubin was 1.6 mg/dL. Coagulation studies were not performed. The patient was admitted with a viral upper respiratory infection and refractory otitis media. Amoxicillin/clavulanic acid was started. Routine urinalysis showed gulcosuria, and new-onset diabetic ketoacidosis was subsequently diagnosed. On hospital day 4 the patient rapidly became hypotensive and tachycardic. The abdomen was distended and tense. The hemoglobin dropped to 3.8 g/dL. Emergent ultrasound scan showed ascites and hepatomegaly with a complex cystic mass believed to be a hematoma in the inferior aspect of the right lobe of the liver. The patient was transfused rapidly with red cells, platelets, and fresh frozen plasma. Exploratory laparotomy was performed. Findings included a large hemoperitoneum, generalized hepatomegaly, and diffuse purple vascularlike lesions throughout the surface of the liver. Active bleeding was originating from the right lobe of the liver—this bleeding was associated with what appeared to be a large intraparenchymal mass. The liver was packed temporarily packed with laparotomy pads and topicalthrombin-soaked Gelfoam. The abdomen was left open and covered with a vacuum-pack dressing. The patient was returned to the intensive care unit. After surgery, the patient remained hypotensive despite blood and platelet transfusions. A hepatic angiogram was performed via the common hepatic artery (Fig 1). A large avascular mass in the caudal
Journal of Pediatric Surgery, Vol 36, No 9 (September), 2001: pp 1456-1459
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diagnosis of progressive hepatic dysfunction or massive hemorrhage because of its rarity. Peliosis has been linked to serious chronic debilitating diseases and often has been associated with administration of androgenic anabolic steroids and oral contraceptives.20-22 It has been reported in association with HIV infections.29 Many times, removal of the offending agent has caused regression of the disease.21 At least 4 of the children reported in the literature had been administered steroids.18,24-26 One infant had severe sepsis without drug intervention.27 The exact pathogenesis of peliosis is unknown. Peliosis hepatis is characterized by blood-filled cystic spaces a few mm to 1 cm in size, but can reach 4 to 5 cm.30 Two morphologic patterns of hepatic peliosis were described by Yanoff and Rawson.31 The parenchymal type is characterized by irregular blood-filled spaces, not lined by endothelium or fibrous tissue. They neither communicate with central veins nor compress adjacent parenchymal cells. They are associated with many areas of focal necrosis in the surrounding hepatic tissue. The second pattern, phlebectatic, shows minimal hepatocyte necroFig 1. Late arterial phase from a hepatic angiogram shows hepatic artery branches displaced by an avascular mass (hematoma) in the liver (solid arrows). Puddling of contrast from capillaries is seen (open arrows).
aspect of the right lobe of the liver was seen with vessels draping over the mass. Delayed images into the venous phase showed several areas of contrast puddling near the periphery of the lesion. Contrast extravasation was seen from a vessel in the lateral portion of the mass. Gelfoam embolization was performed until cessation of contrast extravasation was achieved. Diagnosis of a hemorrhaging hepatic hemangiomatosis with hematoma in the liver was made. On postoperative day 3, reexploration of the abdomen was performed. The packs were removed, and some persistent oozing was controlled with the argon beam coagulator. The fascia and skin were closed. A closed-suction drain was brought out through a separate incision. A contrast CT scan done 1 week later showed hepatomegaly with multiple round to oval low-density lesions of varying size in the liver (Fig 2A). Most of them opacified with contrast on the delayed images. A nonenhancing, hypodense lobular mass and another even more hypodense irregularly shaped subcapsular mass consistent with hematomas in different stages of resolution were seen in the right lobe of the liver along with ascites (Fig 2B). At this time, the possibility of peliosis hepatis with hepatic rupture and hematoma involving the right lobe of the liver was considered. The patient was treated conservatively. Repeat computed tomography (CT) scan done 3 weeks later showed complete resolution of the multiple hypodense liver lesions. There was progressive resolution of hepatic hematoma noted on a follow-up CT scan done 3 months later. Hepatic function results normalized by 5 months.
DISCUSSION
Peliosis is an abnormality of the reticuloendothelial system and most commonly involves the liver. Occasionally, this condition may occur in the spleen and bone marrow.2 Peliosis often is not included in the differential
Fig 2. (A) A contrast axial CT scan through the upper abdomen shows multiple round hypodense areas within the liver caused by peliosis (arrows). Free intraperitoneal fluid is seen surrounding the liver (curved arrows). (B) Contrast axial scan at a lower level than (A) shows a large hematoma in the inferior aspect of the liver (arrows) which is denser than the subcapsular hematoma seen in the (arrow heads) in the periphery. High-density fluid caused by hemoperitoneum is seen adjacent to the liver (white arrow).
1458
sis. The regularly spherical, centrilobular blood-filled spaces are lined by endothelial cells and fibrotic tissue and freely communicate with the hepatic sinusoids. They are an integral part of the central vein causing compression on the adjacent parenchymal cells and contain mural fibrin clot. Senf considered the 2 morphological patterns as one process initiated by focal necrosis of liver parenchyma, which transforms into an area of hemorrhage (parenchymal pattern).1 This pattern may progress to fibrous wall formation and endothelial lining around the hemorrhage (phlebectatic pattern) or heal by resorption of blood. The phlebectatic pattern may heal by fibrin deposition, thrombosis and sclerosis of the vascular spaces.1 The prevalence of peliosis hepatis is not known. One study examined the appearance of reddish-purple areas on the liver surface during laparoscopy. In 3,035 laparoscopies, reddish-purple patches appeared on the liver surface in 20 cases (0.65%). In 15 of these cases, liver biopsy results showed dilatation of sinusoids. In 4 cases, peliosis hepatis was identified. In 2 cases, intralobular hemorrhage was found. The indications for the laparoscopies were not specified. The investigators postulated that these findings could represent different stages in the development of peliosis.32 The roentgenographic diagnosis of peliosis hepatis is difficult. Only one pediatric patient reported in the literature underwent imaging studies. Ultrasound scan may show cystic lesions in the liver parenchyma, which may correspond to the venous lakes commonly seen pathologically.30 These can be mistaken for congenital cysts or abscesses. Occasionally, only subtle inhomogeniety is seen in the liver, which also can be seen in other diffuse liver parenchymal diseases.2 CT scan may show small lesions a few mm to 1 to 4 cm in diameter in the liver.30 The lesions typically are hypodense in early arterial phase and enhance on late venous phase scans. However, they may remain isodense to the liver parenchyma on contrast CT images.2,23,27,29 Thrombosed cavities will remain as nonenhancing nodules.29 The CT appearance of peliosis hepatis can be difficult to differentiate from multiple abscesses, hemangiomatosis, and metastasis. A liver hematoma associated with peliosis hepatis can appear as a space-occupying lesion and be mistaken for a liver tumor. Magnetic resonance images show multiple hepatic foci of mixed signal intensity on both T1- and T2-weighted images presumably reflecting various stages of subacute hemorrhage.2 Radionuclide scans with Technetium (Tc) 99m–sulfur colloid may not show any abnormality or be nonspecific showing large filling defects.18,26,31 The diagnosis of hepatic peliosis on angiography is made by visualizing multiple small accumulations of contrast material on late arterial phase, which persists into the venous phase.19,27,30 This can be
WANG ET AL
confused with the irregular tumor vessels of focal nodular hyperplasia and adenomas. However, as in our case, the angiographic findings also can be mistaken for liver hemangiomatosis.19 Percutaneous needle biopsy has been performed to confirm the diagnosis; however, caution is warranted because of the vascular nature of peliotic lesions.18,27 The natural course of peliosis hepatis is not well understood. Reports have described outcomes ranging from resolution to hepatic failure to fatal intraperitoneal hemorrhage. Several reports have described resolution of peliosis hepatis on withdrawal of the associated drug21,33-38 or with treatment of the associated condition.3,4,39 In other reports, patients presented in fulminant hepatic failure eventually resulting in death.3,20 Fatal intraperitoneal hemorrhage has been reported as another complication.8,20,40-42 At least 1 of these cases involves a child—a 9-year-old boy with Fanconi’s anemia.40 Successful surgical treatment of hemoperitoneum secondary to peliosis hepatis in an adult was reported by Hayward et al.43 A recent report describes a child with hemorrhagic peliosis hepatis secondary to Eschericia coli urosepsis. This child underwent emergent laparotomy and survived.3 Patients with myotubular myopathy, a rare muscle disorder usually affecting children, that died from peliotic liver hemorrhage also have been reported.28 Myotubular myopathy is a genetic disorder characterized by varying degrees of generalized hypotonia. Muscle biopsies typically show characteristic central nuclei resembling fetal myotubes.44 At least 3 modes of inheritance have been described. The most severe form is the xlinked form. In a recent series of 55 patients with x-linked myotubular myopathy, 6 patients had biochemical evidence of liver dysfunction. Two patients died after liver hemorrhage—the one who underwent an autopsy was found to have peliosis hepatis.28 The patient in our report is the first child with myotubular myopathy and life-threatening hemorrhage from peliosis hepatis to be treated successfully with surgical and radiologic intervention. Although we did not prove the presence of this condition with a biopsy, we believe the clinical presentation and resolution of the laboratory and radiologic findings is most consistent with peliosis hepatis. The etiology in this case is unclear. Given the other reported cases of peliosis associated with myotubular myopathy, this case may have a genetic basis. But with the history of several prescription and homeopathic drugs, and of the recent infection, pharmacologic side effects and infectious causes cannot be ruled out. Peliosis hepatis is most often asymptomatic and an incidental finding at autopsy. In symptomatic patients, surgery should be reserved for those cases in which hemorrhage becomes life threatening. Familiarity with
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the imaging characteristics and awareness of this condition as a cause of hepatomegaly, hepatic failure, hepatic rupture, and hepatic hemorrhage can help in the early diagnosis of peliosis hepatis. Early removal of a known
inciting agent may cause regression of hepatic peliosis and prevent catastrophic complications. Spontaneous regression of peliosis hepatis also can occur in some patients.
REFERENCES 1. Zak FG: Peliosis hepatis. Am J Pathol 26:1-6, 1950 2. Maves CK, Caron KH, Bisset III GS, et al: Splenic and hepatic peliosis: MR findings. AJR 158:75-76, 1992 3. Jacquemin E, et al: Peliosis hepatis with initial presentation as acute hepatic failure and intraperitoneal hemorrhage in children. J Hepatol 30:1146-1150, 1999 4. Imai Y, et al: Regression of peliosis hepatis after resolution of a liver abscess. Gas Endoscopy 32:298-299, 1986 5. Van Schil P, et al: Peliosis hepatis associated with liver and retroperitoneal abscesses. Digestion 41:55-60, 1988 6. Ahsan N, et al: Peliosis hepatis due to bartonella henslae in transplantation: A hemato-hepato-renal syndrome. Transplantation 65: 1000-1003, 1998 7. Koehler J, Dederberg L: Intra-abdominal mass associated with gastrointestinal hemorrhage: A new manifestation of bacillary angiomatosis. Gastroenterology 109:2011-2014, 1995 8. Tappero JW, et al: The epidemiology of bacillary angiomatosis and bacillary peliosis. JAMA 269:770-775, 1993 9. Garcia-tsao G, et al: Bacillary peliosis hepatis as a cause of acute anemia in a patient with the acquired immunodeficiency syndrome. Gastroenterology 102:1065-1070, 1992 10. Marullo S: Identification of the rochalimaea henselae 16S rRNA sequence in the liver of a french patient with bacillary peliosis hepatis. JID 166:1462, 1992 11. Welch DF, et al: Rochalimaea henslae sp. Nov., a cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiology 30:275-280, 1992 12. Relman DA, et al: Peliosis hepatis: Old disease, new cause. Gastroenterology 101:864-866, 1991 13. Perkocha LA, et al: Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection. N Engl J Med 323:1581-1586, 1990 14. Cavalcanti R, et al: Impact and evolution of peliosis hepatis in renal transplant recipients. Transplantation 58:315-316, 1994 15. Hankey GJ, Saker BM: Peliosis hepatis in a renal transplant recipient and in a haemodialysis patient. Med J Aust 146:102-104, 1987 16. Degott C, et al: Peliosis hepatis in recipients of renal transplants. Gut 19:748-753, 1978 17. Rao KV, et al: Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients. Am J Med 94:241, 1993 18. Usatin MS, Wigger J: Peliosis hepatis in a child. Arch Pathol Lab Med 100:419-421, 1976 19. Pliskin M: Peliosis Hepatis. Radiology 114:29-30, 1975 20. Bagheri SA: Peliosis hepatis associated with androgen anabolic steroid therapy. A severe form of hepatic injury. Ann Intern Med 81:610-618, 1974 21. Nadell J, Kosek J: Peliosis hepatis twelve cases associated with oral androgen therapy. Archiv Pathol Lab Med 101:405-410, 1977 22. Naeim F, Copper PH, Semion AA: Peliosis hepatis, possible etiology role of anabolic steroids. Arch Pathol 95:284-185, 1973 23. Smathers RL, Heiken JP, Lee J, et al: Computed tomography of fatal hepatic rupture due to peliosis hepatis. J Comput Assist Tomogr 8:768-769, 1984
24. Bank JI, Lykkebo D, Hagerstrand I: Peliosis hepatis in a child. Acta Pediatr Scand 67:10-107, 1978 25. Shapiro P, Ikeda RM, Ruebner BH, et al: Multiple hepatic tumor and peliosis patis in Fanconiı´s anemia treated with androgens. Am J Dis Child 131:1104-1106, 1977 26. Nuerenberger SP, Ramos CV: Peliosis hepatis in an infant. J Pediatr 87:424-426, 1975 27. Cragg A, Castaneda-Zujniga W, Lund E, et al: Infantile peliosis hepatis. Pediatr Radiol 14:340-342, 1984 28. Herman GH, et al: Medical complications in long-term survivors with x-linked myotubular myopathy. J Pediatr 134:206-214, 1999 29. Radin R, Kanel GC: Peliosis hepatis in a patient with human immunodeficiency virus infection. AJR 156:91-92, 1991 30. Tsukamoto T, Nakata H, Kimoto T, et al: CT and angiography of peliosis hepatis. AJR 142:539-540, 1984 31. Yanoff M, Rawson AJ: Peliosis hepatis, an anatomic study with demonstration of two varieties. Arch Pathol 77:159-164, 1964 32. Solis-Herruzo JA, et al: Ressish-purple areas on the liver surface: The laparoscopic picture of peliosis hepatis. Endoscopy 15:95100, 1983 33. Arnold GL, Kaplan MM: Peliosis hepatis due to oxymetholone—A clinically benign disorder. Am J Gastroenterology 71: 213-216, 1979 34. Larrey D, et al: An additional argument for a toxic mechanism of peliosis hepatis in man. Hepatology 11:322-323, 1990 35. Groos G, et al: Peliosis hepatis after long-term administration of oxymetholone. Lancet May 4:874, 1974 36. Johnson FL, et al: Association of androgenic-anabolic steroid therapy with development of hepatocellular carcinoma. Lancet Dec 16:1273-1276, 1972 37. Izumi S, et al: Laparascopic study of peliosis hepatis and nodular transformation of the liver before and after renal transplantation: Natural history and aetiology in follow-up cases. J Hepatol 20:129-137, 1994 38. Chopra S, et al: Peliosis hepatis in hematologic disease: Report of two cases. JAMA 240:1153-1155, 1978 39. Lachaux A, et al: Intravenous immunoglobulin therapy in an infant with autoimmune hemolytic anemia associated with necrotic hepatits and peliosis. J Pediatr Gastroenterology Nutr 22:99-102, 1996 40. Benjamin DR, Shunk B: A fatal case of peliosis of the liver and spleen. Am J Dis Child 132:207-208, 1978 41. Makdisi WJ, et al: Fatal peliosis of the liver and spleen in a patient with agnogenic myeloid metaplasia treated with danazol. AJG 90:317-318, 1995 42. Baer PA, et al: Severe weight loss and fatal intra-peritoneal hemorrhage in an elderly man. Can Med Assoc J 131:319-324, 1984 43. Hayward SR, et al: Recurrent spontaneous intrahepatic hemorrhage from peliosis hepatis. Arch Surg 126:782-783, 1991 44. Spiro AJ, et al: Myotubular myopathy: Persistence of fetal muscle in an adolescent boy. Arch Neurol 14:1-14, 1966 45. Herrera LO, Glassman CI, Teixido RA, et al: Peliosis associated with cavernous hemangioma and hepatocarcinoma. Am Surg 47:502506, 1981
Peliosis hepatis is a rare entity that can affect children and cause fatal hepatic hemorrhage or hepatic failure. Radiographic findings are nonspecific and can resemble other hepatic pathologies such as cysts, abscesses, metastases, and hemangiomatosis. Peliosis hepatis can resolve spontaneously or by withdrawal of inciting medications. Certain cases may require surgical resection of the involved portions of the liver. Recently, fatal liver hemorrhage was reported in 2 pediatric patients with a rare congenital muscle disorder known as myotubular (centronuclear) myopathy. One of these patients was found at autopsy to have peliosis hepatis.
P
ELIOSIS HEPATIS was first recognized in the German literature in 1861 by Wagner and named by Schoenlank in 1916.1 It is a rare condition characterized by multiple small cystic blood-filled spaces in the liver, which can be seen through the intact liver capsule.1 The etiology of this condition is unknown, but it is known to be associated with various prolonged wasting diseases, such as tuberculosis, solid-organ malignancies, and other hematologic disorders.2 Peliosis hepatis also has been reported in association with human immunodeficiency virus (HIV) disease, bacterial infections, and the presence of renal allografts.3-17 There also is evidence that drugs, primarily anabolic steroids, may be associated with this lesion.18-23 Hepatic peliosis sometimes is an incidental finding at autopsy or it may cause fatal liver failure or hepatic rupture and often is diagnosed only at autopsy.18,20,21 Only a few cases of this disease have been reported in children—in 5 of these, diagnosis was made at autopsy.24-28 In one infant the diagnosis was made by surgical biopsy of the resected lobe.29 We report imaging findings in a child with a rare congenital condition known as myotubular (centronuclear) myopathy and hepatic rupture secondary to peliosis hepatis, which resolved after surgical exploration for life-threatening hemorrhage.
From the Departments of Radiology and Surgery, Loyola University Medical Center, Maywood, IL. Address reprint requests to Aruna Vade, MD, Department of Radiology, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3609-0030$35.00/0 doi:10.1053/jpsu.2001.26397 1456
The authors report the first successful treatment of lifethreatening liver hemorrhage caused by peliosis hepatis in a child with myotubular myopathy. Awareness of this condition may reduce the catastrophic complications seen with peliosis hepatis. J Pediatr Surg 36:1456-1459. Copyright © 2001 by W.B. Saunders Company.
INDEX WORDS: Peliosis, hepatic, hemorrhage, myotubular myopathy, centronuclear myopathy.
CASE REPORT The patient is a 3-year-old boy with myotubular myopathy and a 1-week history of malaise, arthralgias, and postnasal drip. He recently had been treated with Suprax and amoxicillin for otitis media. His past medical history was significant for delayed milestones of motor, but not mental, development. He had undergone a Nissen fundoplication and placement of bilateral myringotomy tubes at birth. Medications included lactulose, Poly-vi-sol, levocarnitine solution, coenzyme Q, albuterol, and atrovent nebulizer treatments as needed, and several vitamins, minerals, and homeopathic medications. One older brother (age 7 years) also had myotubular myopathy and was ventilator dependent. Two other siblings (a brother, age 17, and a sister, age 9) were without clinical evidence of the disorder. On physical examination, the liver edge was palpable below the costal margin. The spleen was not palpable. A complete blood count was as follows: white blood cell count, 10.2 k/L; hemoglobin, 11.3 g/dL; hematocrit, 33%; and platelet count, 286 k/L. AST was 54 IU/L, alkaline phosphatase was 320 IU/L, and total bilirubin was 1.6 mg/dL. Coagulation studies were not performed. The patient was admitted with a viral upper respiratory infection and refractory otitis media. Amoxicillin/clavulanic acid was started. Routine urinalysis showed gulcosuria, and new-onset diabetic ketoacidosis was subsequently diagnosed. On hospital day 4 the patient rapidly became hypotensive and tachycardic. The abdomen was distended and tense. The hemoglobin dropped to 3.8 g/dL. Emergent ultrasound scan showed ascites and hepatomegaly with a complex cystic mass believed to be a hematoma in the inferior aspect of the right lobe of the liver. The patient was transfused rapidly with red cells, platelets, and fresh frozen plasma. Exploratory laparotomy was performed. Findings included a large hemoperitoneum, generalized hepatomegaly, and diffuse purple vascularlike lesions throughout the surface of the liver. Active bleeding was originating from the right lobe of the liver—this bleeding was associated with what appeared to be a large intraparenchymal mass. The liver was packed temporarily packed with laparotomy pads and topicalthrombin-soaked Gelfoam. The abdomen was left open and covered with a vacuum-pack dressing. The patient was returned to the intensive care unit. After surgery, the patient remained hypotensive despite blood and platelet transfusions. A hepatic angiogram was performed via the common hepatic artery (Fig 1). A large avascular mass in the caudal
Journal of Pediatric Surgery, Vol 36, No 9 (September), 2001: pp 1456-1459
HEPATIC RUPTURE FROM PELIOSIS HEPATIS
1457
diagnosis of progressive hepatic dysfunction or massive hemorrhage because of its rarity. Peliosis has been linked to serious chronic debilitating diseases and often has been associated with administration of androgenic anabolic steroids and oral contraceptives.20-22 It has been reported in association with HIV infections.29 Many times, removal of the offending agent has caused regression of the disease.21 At least 4 of the children reported in the literature had been administered steroids.18,24-26 One infant had severe sepsis without drug intervention.27 The exact pathogenesis of peliosis is unknown. Peliosis hepatis is characterized by blood-filled cystic spaces a few mm to 1 cm in size, but can reach 4 to 5 cm.30 Two morphologic patterns of hepatic peliosis were described by Yanoff and Rawson.31 The parenchymal type is characterized by irregular blood-filled spaces, not lined by endothelium or fibrous tissue. They neither communicate with central veins nor compress adjacent parenchymal cells. They are associated with many areas of focal necrosis in the surrounding hepatic tissue. The second pattern, phlebectatic, shows minimal hepatocyte necroFig 1. Late arterial phase from a hepatic angiogram shows hepatic artery branches displaced by an avascular mass (hematoma) in the liver (solid arrows). Puddling of contrast from capillaries is seen (open arrows).
aspect of the right lobe of the liver was seen with vessels draping over the mass. Delayed images into the venous phase showed several areas of contrast puddling near the periphery of the lesion. Contrast extravasation was seen from a vessel in the lateral portion of the mass. Gelfoam embolization was performed until cessation of contrast extravasation was achieved. Diagnosis of a hemorrhaging hepatic hemangiomatosis with hematoma in the liver was made. On postoperative day 3, reexploration of the abdomen was performed. The packs were removed, and some persistent oozing was controlled with the argon beam coagulator. The fascia and skin were closed. A closed-suction drain was brought out through a separate incision. A contrast CT scan done 1 week later showed hepatomegaly with multiple round to oval low-density lesions of varying size in the liver (Fig 2A). Most of them opacified with contrast on the delayed images. A nonenhancing, hypodense lobular mass and another even more hypodense irregularly shaped subcapsular mass consistent with hematomas in different stages of resolution were seen in the right lobe of the liver along with ascites (Fig 2B). At this time, the possibility of peliosis hepatis with hepatic rupture and hematoma involving the right lobe of the liver was considered. The patient was treated conservatively. Repeat computed tomography (CT) scan done 3 weeks later showed complete resolution of the multiple hypodense liver lesions. There was progressive resolution of hepatic hematoma noted on a follow-up CT scan done 3 months later. Hepatic function results normalized by 5 months.
DISCUSSION
Peliosis is an abnormality of the reticuloendothelial system and most commonly involves the liver. Occasionally, this condition may occur in the spleen and bone marrow.2 Peliosis often is not included in the differential
Fig 2. (A) A contrast axial CT scan through the upper abdomen shows multiple round hypodense areas within the liver caused by peliosis (arrows). Free intraperitoneal fluid is seen surrounding the liver (curved arrows). (B) Contrast axial scan at a lower level than (A) shows a large hematoma in the inferior aspect of the liver (arrows) which is denser than the subcapsular hematoma seen in the (arrow heads) in the periphery. High-density fluid caused by hemoperitoneum is seen adjacent to the liver (white arrow).
1458
sis. The regularly spherical, centrilobular blood-filled spaces are lined by endothelial cells and fibrotic tissue and freely communicate with the hepatic sinusoids. They are an integral part of the central vein causing compression on the adjacent parenchymal cells and contain mural fibrin clot. Senf considered the 2 morphological patterns as one process initiated by focal necrosis of liver parenchyma, which transforms into an area of hemorrhage (parenchymal pattern).1 This pattern may progress to fibrous wall formation and endothelial lining around the hemorrhage (phlebectatic pattern) or heal by resorption of blood. The phlebectatic pattern may heal by fibrin deposition, thrombosis and sclerosis of the vascular spaces.1 The prevalence of peliosis hepatis is not known. One study examined the appearance of reddish-purple areas on the liver surface during laparoscopy. In 3,035 laparoscopies, reddish-purple patches appeared on the liver surface in 20 cases (0.65%). In 15 of these cases, liver biopsy results showed dilatation of sinusoids. In 4 cases, peliosis hepatis was identified. In 2 cases, intralobular hemorrhage was found. The indications for the laparoscopies were not specified. The investigators postulated that these findings could represent different stages in the development of peliosis.32 The roentgenographic diagnosis of peliosis hepatis is difficult. Only one pediatric patient reported in the literature underwent imaging studies. Ultrasound scan may show cystic lesions in the liver parenchyma, which may correspond to the venous lakes commonly seen pathologically.30 These can be mistaken for congenital cysts or abscesses. Occasionally, only subtle inhomogeniety is seen in the liver, which also can be seen in other diffuse liver parenchymal diseases.2 CT scan may show small lesions a few mm to 1 to 4 cm in diameter in the liver.30 The lesions typically are hypodense in early arterial phase and enhance on late venous phase scans. However, they may remain isodense to the liver parenchyma on contrast CT images.2,23,27,29 Thrombosed cavities will remain as nonenhancing nodules.29 The CT appearance of peliosis hepatis can be difficult to differentiate from multiple abscesses, hemangiomatosis, and metastasis. A liver hematoma associated with peliosis hepatis can appear as a space-occupying lesion and be mistaken for a liver tumor. Magnetic resonance images show multiple hepatic foci of mixed signal intensity on both T1- and T2-weighted images presumably reflecting various stages of subacute hemorrhage.2 Radionuclide scans with Technetium (Tc) 99m–sulfur colloid may not show any abnormality or be nonspecific showing large filling defects.18,26,31 The diagnosis of hepatic peliosis on angiography is made by visualizing multiple small accumulations of contrast material on late arterial phase, which persists into the venous phase.19,27,30 This can be
WANG ET AL
confused with the irregular tumor vessels of focal nodular hyperplasia and adenomas. However, as in our case, the angiographic findings also can be mistaken for liver hemangiomatosis.19 Percutaneous needle biopsy has been performed to confirm the diagnosis; however, caution is warranted because of the vascular nature of peliotic lesions.18,27 The natural course of peliosis hepatis is not well understood. Reports have described outcomes ranging from resolution to hepatic failure to fatal intraperitoneal hemorrhage. Several reports have described resolution of peliosis hepatis on withdrawal of the associated drug21,33-38 or with treatment of the associated condition.3,4,39 In other reports, patients presented in fulminant hepatic failure eventually resulting in death.3,20 Fatal intraperitoneal hemorrhage has been reported as another complication.8,20,40-42 At least 1 of these cases involves a child—a 9-year-old boy with Fanconi’s anemia.40 Successful surgical treatment of hemoperitoneum secondary to peliosis hepatis in an adult was reported by Hayward et al.43 A recent report describes a child with hemorrhagic peliosis hepatis secondary to Eschericia coli urosepsis. This child underwent emergent laparotomy and survived.3 Patients with myotubular myopathy, a rare muscle disorder usually affecting children, that died from peliotic liver hemorrhage also have been reported.28 Myotubular myopathy is a genetic disorder characterized by varying degrees of generalized hypotonia. Muscle biopsies typically show characteristic central nuclei resembling fetal myotubes.44 At least 3 modes of inheritance have been described. The most severe form is the xlinked form. In a recent series of 55 patients with x-linked myotubular myopathy, 6 patients had biochemical evidence of liver dysfunction. Two patients died after liver hemorrhage—the one who underwent an autopsy was found to have peliosis hepatis.28 The patient in our report is the first child with myotubular myopathy and life-threatening hemorrhage from peliosis hepatis to be treated successfully with surgical and radiologic intervention. Although we did not prove the presence of this condition with a biopsy, we believe the clinical presentation and resolution of the laboratory and radiologic findings is most consistent with peliosis hepatis. The etiology in this case is unclear. Given the other reported cases of peliosis associated with myotubular myopathy, this case may have a genetic basis. But with the history of several prescription and homeopathic drugs, and of the recent infection, pharmacologic side effects and infectious causes cannot be ruled out. Peliosis hepatis is most often asymptomatic and an incidental finding at autopsy. In symptomatic patients, surgery should be reserved for those cases in which hemorrhage becomes life threatening. Familiarity with
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the imaging characteristics and awareness of this condition as a cause of hepatomegaly, hepatic failure, hepatic rupture, and hepatic hemorrhage can help in the early diagnosis of peliosis hepatis. Early removal of a known
inciting agent may cause regression of hepatic peliosis and prevent catastrophic complications. Spontaneous regression of peliosis hepatis also can occur in some patients.
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