- Email: [email protected]
An adolescent with Budd-Chiari syndrome associated with myeloproliferative disorder
e106
Abstracts / Digestive and Liver Disease 46 (2014) e85–e127
ALAGILLE SYNDROME: IS IT ALWAYS CHOLESTASIS? Claudia Mandato 1,∗ , Daniele De Brasi 1 , Angela Boccieri 1 , Maria Iascone 2 , Pietro Vajro 3 , Paolo Siani 1 1
Dipartimento di Pediatria, AORN Santobono-Pausilipon, Napoli, Italy 2 Lab Genetica Molecolare - USSD LGM, AO Papa Giovanni XXIII, Bergamo, Italy 3 Dipartimento di Medicina e Chirurgia, Università di Salerno, Salerno, Italy
Fig. 1. Atypical urinary metabolites trend, patient 1.
Fig. 2. Atypical urinary metabolites trend, patient 2.
Methods: A 3-year-old Pakistani girl presented rickets, poor growth, hepatomegaly and jaundice without itching. Blood tests revealed mild hyperbilirubinaemia (total 1.73 mg/dl, direct 1.52), elevated aminotransferases (AST 108 U/L, ALT 84 U/L), normal ␥GT (15 U/L), low serum bile acids (1.3 mol/L, n.v. 2-10) and coagulopathy (PT 2.64, PTT 1.72). Vitamin D and E were low (0.87 g/mL, 14.4 mg/dL) with normal vitamin A (0.52 g/mL). UDCA and fatsoluble vitamins therapy was started. FAB-MS urinalysis revealed an increase of atypical bile salts peculiar to 3beta-HSD and genetic analysis revealed a novel homozygous mutation (HSD3B7 gene). Liver biopsy showed focal cirrhosis with moderate inflammatory infiltrate. CA therapy (10–15 mg/kg/daily) was then started. After two years, patient’s sister was born. Blood tests showed increased aminotransferase with normal ␥GT (AST 266 U/L, ALT 229 U/L, ␥GT 32 U/L), neonatal jaundice and normal serum bile salts (7.5 mol/L). Coagulation and fat-soluble vitamins were normal. FAB-MS urinalysis revealed a marked elevation of 3beta-HSD atypical metabolites. Diagnosis was confirmed by genetic analysis. Liver biopsy documented inflammatory infiltrate, steatosis and mild portal fibrosis. CA therapy (15 mg/kg/daily) was started. Results: Treatment with CA decreased atypical bile salts excretion (except for a transient increase in patient 2 due to neglecting therapy) (Figs. 1 and 2) and an improvement of aminotransferases were shown in both patients without side-effects. Conclusions: CA therapy (10-15 mg/kg/daily) is safe and effective for treatment of 3beta-HSD. http://dx.doi.org/10.1016/j.dld.2014.07.107
Background: Alagille syndrome (AS) is a rare multisystemic AD disease caused by an alteration of NOTCH 2 pathway (prevalently due to JAG1 mutation). It causes chronic cholestasis which is a frequent indication for pediatric liver transplantation. Diagnosis is suspected if chronic cholestasis is accompanied by at least three of the following features: congenital heart disease, vertebral segmentation anomalies, characteristic facies, posterior embryotoxon. Here we describe a patient with a novel mutation without chronic cholestasis. Case characteristics: VA was admitted at age 2 years for failure to thrive. She had isolated mild hypertransaminasemia (ALT, AST x 1,5 nv), with normal markers of cholestasis (serum bilirubin, GGT, ALP, biliary acids, serum lipids) and liver function. A peculiar face and heart murmur were noted. Ultrasonography showed peripheral pulmonary stenosis (PPS) and right double renal district. Eye examination showed left embriotoxon. Due to quite normal liver tests, a liver biopsy was considered unethical. Molecular analysis showed a novel mutation of JAG1 gene (p.Ala583fs: de novo mutation). Conclusions: Liver and heart disease are the prevalent features of AS, whereas the remaining body systems may show a wide spectrum of clinical presentations, thus representing a possible significant diagnostic challenge. Revised clinical criteria have been proposed in order to avoid underdiagnosis of a patient who does not meet classic criteria. In our case, clinical suspicion was based on dysmorphic features, PPS, embriotoxon, in absence of cholestasis and this lead to identification of a novel mutation at molecular testing. http://dx.doi.org/10.1016/j.dld.2014.07.108 AN ADOLESCENT WITH BUDD-CHIARI SYNDROME ASSOCIATED WITH MYELOPROLIFERATIVE DISORDER Maria Tufano 1,∗ , Fabiola Di Dato 1 , Giusy Ranucci 1 , Manila Candusso 2 , Giuliano Torre 2 , Raffaele Iorio 1 1
Dipartimento di Scienze Mediche Traslazionali, Settore di Pediatria, Università degli studi di Napoli Federico II, Napoli, Italy 2 Hepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children’s Hospital, Roma, Italy Introduction: Budd-Chiari syndrome (BCS) is a rare disorder, consequence of obstruction to hepatic venous outflow. In most cases it is possible to identify the underlying cause of thrombosis. Hereby a pediatric case of BCS associated with a myeloproliferative disorder is described. Clinical case: A 16-year-old girl was admitted in March 2014, with a history of abdominal pain and menstrual irregularity. Physical examination revealed abdominal distension, ascites and hepatosplenomegaly. Abdomen and pelvic ultrasound showed the
Abstracts / Digestive and Liver Disease 46 (2014) e85–e127
presence of an ovaric cyst, ascites, liver and spleen enlargement. Magnetic resonance confirmed hepatosplenomegaly and suspected obliteration of hepatic veins. The Angio-CT scan revealed thrombosis of inferior cava. Therefore BCS was diagnosed. Blood counts showed mild anemia (hemoglobin 11.5 g/dL), normality of WBC count (6500/L) and platelets (270,000/L). There was a mild prolongation of prothrombin time while the remaining liver function tests were normal. The main causes of liver disease were excluded. Esophageal varices with red spots were identified by endoscopy. Bone marrow aspiration was normal while bone biopsy showed the presence of myeloproliferative disorder. JAK2 V617F mutation was found. A complete thrombophilia screening revealed homozygosis polymorphism for methyltetraidropholate reductase. Anticoagulant (heparin) and diuretic therapy was initiated. Balloon angioplasty of inferior cava was performed and a stent in the accessory hepatic vein was placed. Conclusions: Despite the normality of cell blood count and bone marrow aspiration, a myeloproliferative disorder must be considered in patients with BCS. This suspect should be also encouraged by the absence of hypersplenism in presence of a severe portal hypertension. Finally, this clinical case confirms that analysis of JAK mutation should be also included in diagnostic work up of pediatric case of BCS. http://dx.doi.org/10.1016/j.dld.2014.07.109 A PARTICULAR CASE OF DUODENAL OBSTRUCTION DUE TO RARE PANCREATIC SEROUS CYSTADENOMA Maria Teresa Illiceto 1,∗ , Gabriele Lisi 2 , Marco Filippone 1 , Carlo Rossi 2 , Daniela Trotta 3 , Pierluigi Lelli Chiesa 2 , Giuliano Lombardi 1 1 UOS Gastroenterologia ed Endoscopia Digestiva Pediatrica, Ospedale Regionale Pescara, Pescara, Italy 2 Unità Operativa Clinicizzata di Chirurgia Pediatrica, Università “G.d’Annunzio”di Chieti-Pescara, Pescara, Italy 3 UOC Pediatria Medica, Ospedale Regionale di Pescara, Pescara, Italy
Objective: Pancreatic tumors are very rare in children, particularly serous cystadenoma. Although this tumor is not potentially malignant, all patients required accurate evaluation and attention should be paid to possible related complications. Methods: The authors present a particular case of duodenal obstruction due to a pancreatic serous cystadenoma. GA affected by epileptic encephalopathy, at 22 months was admitted for intestinal obstruction and acute pancreatitis secondary to duodenal hematoma for which underwent laparotomy, incision and drainage of the hematoma and packaging gastrostomy. Gradually improved, but the hypoechoic cystic lesion persisted. 2 months later, to the progressive reduction of the cystic lesion, corresponds the emergence of ascites and rise in amylase, with worsening eosinophilia. Results: The screening performed excluded infections, allergies, celiac and autoimmune disease, and metabolic pathologies. Endoscopy with multiple biopsies excluded eosinophilic gastroenteropathy. The ascites fluid showed presence of amylase. In suspected pancreatic cyst, we planned abdomen NMR. In the meantime, the child was again operated in urgency to occlusion by adhesions, and in the process of debridement it was highlighted and removed a cystic lesion of 4.5 × 4 × 2.6 cm suspected to pseudopancreatic cyst, which was histologically a pancreatic serous cystadenoma.
e107
Conclusions: The authors believe that the pancreatic cystoadenoma caused the compression of the duodenum and pancreatic-biliary tract with onset of pancreatitis and probable chronic inflammation of deep soft tissues; that inconstant presence of the cyst at US controls corresponding the ups and downs of ascites were due to a perforation of the wall of the cyst, and that periferic eosinophilia was drugs-related. http://dx.doi.org/10.1016/j.dld.2014.07.110 HUGE HYDROPS OF THE GALLBLADDER IN A 3 YEARS OLD GIRL WITH KAWASAKI SYNDROME: CASE REPORT Rosa Maria Melino 1,∗ , Emanuela Sacco 1 , Caterina Campanale 1 , Rosa Lapolla 1 , Barbara Santangelo 1 , Mario Rocco D’Altilia 2 , Maria Pastore 2 , Filomena Frascolla 2 , Anna Simeone 3 , Massimo Pettoello-Mantovani 1 , Michele Sacco 2 1
Department of Pediatrics, University of Foggia, Foggia, Italy 2 Department of Pediatrics, “Casa Sollievo della Sofferenza”-IRCCS, San Giovanni Rotondo, Italy 3 Department of Radiological Science, “Casa Sollievo della Sofferenza”-IRCCS, San Giovanni Rotondo, Italy Background: Kawasaki Syndrome (KS) is an acute febrile illness associated with multiorgan vasculitis of unknown etiology. Hydrops of gallbladder is a rare manifestation of KS, which most commonly affects children aged from 17 months to 7 years. Case report: A 3 years old girl was admitted to our emergency department with a 2-day history of fever, maculopapular rash, jaundice, acholic stools and dark urine. On physical examination, her body temperature was 39.5 ◦ C, her oral mucosa and tongue were hyperemic; she also had bilateral conjunctivitis, angular cheilitis. Laboratory findings revealed neutrophilic leukocytosis and inflammatory markers elevated. Liver function tests results as follows: aspartate aminotransferase 52 U/l; alanine aminotransferase 125 U/l; alkaline phosphatase 250 U/l; total bilirubin 9.08 mg/dl; direct bilirubin 7.67 mg/dl. Renal function was normal, but urine analysis showed proteinuria, hemoglobinuria and bilirubinuria. Abdominal ultrasonography showed gallbladder hydrops with a longitudinal diameter of 10.9 cm. TC and MRCP confirmed gallbladder hydrops and excluded obstructive causes and surgical treatments. A diagnosis of KS was made based on the clinical findings. No coronary aneurysms at Doppler echocardiography. On the 3th day after her admission, she received 2 g/kg intravenous immunoglobulin G (IVIG) and acetylsalicylic acid at dosage of 80 mg/kg/die. During follow-up, we noted clinical remission, gradual normalization of laboratory tests and of gallbladder ultrasonography findings Discussion: Kawasaki Syndrome should always be suspected in children with non-obstructive hydrops of the gallbladder, because early therapy with IVIG is very important for the prevention of coronary complications. http://dx.doi.org/10.1016/j.dld.2014.07.111
Abstracts / Digestive and Liver Disease 46 (2014) e85–e127
ALAGILLE SYNDROME: IS IT ALWAYS CHOLESTASIS? Claudia Mandato 1,∗ , Daniele De Brasi 1 , Angela Boccieri 1 , Maria Iascone 2 , Pietro Vajro 3 , Paolo Siani 1 1
Dipartimento di Pediatria, AORN Santobono-Pausilipon, Napoli, Italy 2 Lab Genetica Molecolare - USSD LGM, AO Papa Giovanni XXIII, Bergamo, Italy 3 Dipartimento di Medicina e Chirurgia, Università di Salerno, Salerno, Italy
Fig. 1. Atypical urinary metabolites trend, patient 1.
Fig. 2. Atypical urinary metabolites trend, patient 2.
Methods: A 3-year-old Pakistani girl presented rickets, poor growth, hepatomegaly and jaundice without itching. Blood tests revealed mild hyperbilirubinaemia (total 1.73 mg/dl, direct 1.52), elevated aminotransferases (AST 108 U/L, ALT 84 U/L), normal ␥GT (15 U/L), low serum bile acids (1.3 mol/L, n.v. 2-10) and coagulopathy (PT 2.64, PTT 1.72). Vitamin D and E were low (0.87 g/mL, 14.4 mg/dL) with normal vitamin A (0.52 g/mL). UDCA and fatsoluble vitamins therapy was started. FAB-MS urinalysis revealed an increase of atypical bile salts peculiar to 3beta-HSD and genetic analysis revealed a novel homozygous mutation (HSD3B7 gene). Liver biopsy showed focal cirrhosis with moderate inflammatory infiltrate. CA therapy (10–15 mg/kg/daily) was then started. After two years, patient’s sister was born. Blood tests showed increased aminotransferase with normal ␥GT (AST 266 U/L, ALT 229 U/L, ␥GT 32 U/L), neonatal jaundice and normal serum bile salts (7.5 mol/L). Coagulation and fat-soluble vitamins were normal. FAB-MS urinalysis revealed a marked elevation of 3beta-HSD atypical metabolites. Diagnosis was confirmed by genetic analysis. Liver biopsy documented inflammatory infiltrate, steatosis and mild portal fibrosis. CA therapy (15 mg/kg/daily) was started. Results: Treatment with CA decreased atypical bile salts excretion (except for a transient increase in patient 2 due to neglecting therapy) (Figs. 1 and 2) and an improvement of aminotransferases were shown in both patients without side-effects. Conclusions: CA therapy (10-15 mg/kg/daily) is safe and effective for treatment of 3beta-HSD. http://dx.doi.org/10.1016/j.dld.2014.07.107
Background: Alagille syndrome (AS) is a rare multisystemic AD disease caused by an alteration of NOTCH 2 pathway (prevalently due to JAG1 mutation). It causes chronic cholestasis which is a frequent indication for pediatric liver transplantation. Diagnosis is suspected if chronic cholestasis is accompanied by at least three of the following features: congenital heart disease, vertebral segmentation anomalies, characteristic facies, posterior embryotoxon. Here we describe a patient with a novel mutation without chronic cholestasis. Case characteristics: VA was admitted at age 2 years for failure to thrive. She had isolated mild hypertransaminasemia (ALT, AST x 1,5 nv), with normal markers of cholestasis (serum bilirubin, GGT, ALP, biliary acids, serum lipids) and liver function. A peculiar face and heart murmur were noted. Ultrasonography showed peripheral pulmonary stenosis (PPS) and right double renal district. Eye examination showed left embriotoxon. Due to quite normal liver tests, a liver biopsy was considered unethical. Molecular analysis showed a novel mutation of JAG1 gene (p.Ala583fs: de novo mutation). Conclusions: Liver and heart disease are the prevalent features of AS, whereas the remaining body systems may show a wide spectrum of clinical presentations, thus representing a possible significant diagnostic challenge. Revised clinical criteria have been proposed in order to avoid underdiagnosis of a patient who does not meet classic criteria. In our case, clinical suspicion was based on dysmorphic features, PPS, embriotoxon, in absence of cholestasis and this lead to identification of a novel mutation at molecular testing. http://dx.doi.org/10.1016/j.dld.2014.07.108 AN ADOLESCENT WITH BUDD-CHIARI SYNDROME ASSOCIATED WITH MYELOPROLIFERATIVE DISORDER Maria Tufano 1,∗ , Fabiola Di Dato 1 , Giusy Ranucci 1 , Manila Candusso 2 , Giuliano Torre 2 , Raffaele Iorio 1 1
Dipartimento di Scienze Mediche Traslazionali, Settore di Pediatria, Università degli studi di Napoli Federico II, Napoli, Italy 2 Hepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children’s Hospital, Roma, Italy Introduction: Budd-Chiari syndrome (BCS) is a rare disorder, consequence of obstruction to hepatic venous outflow. In most cases it is possible to identify the underlying cause of thrombosis. Hereby a pediatric case of BCS associated with a myeloproliferative disorder is described. Clinical case: A 16-year-old girl was admitted in March 2014, with a history of abdominal pain and menstrual irregularity. Physical examination revealed abdominal distension, ascites and hepatosplenomegaly. Abdomen and pelvic ultrasound showed the
Abstracts / Digestive and Liver Disease 46 (2014) e85–e127
presence of an ovaric cyst, ascites, liver and spleen enlargement. Magnetic resonance confirmed hepatosplenomegaly and suspected obliteration of hepatic veins. The Angio-CT scan revealed thrombosis of inferior cava. Therefore BCS was diagnosed. Blood counts showed mild anemia (hemoglobin 11.5 g/dL), normality of WBC count (6500/L) and platelets (270,000/L). There was a mild prolongation of prothrombin time while the remaining liver function tests were normal. The main causes of liver disease were excluded. Esophageal varices with red spots were identified by endoscopy. Bone marrow aspiration was normal while bone biopsy showed the presence of myeloproliferative disorder. JAK2 V617F mutation was found. A complete thrombophilia screening revealed homozygosis polymorphism for methyltetraidropholate reductase. Anticoagulant (heparin) and diuretic therapy was initiated. Balloon angioplasty of inferior cava was performed and a stent in the accessory hepatic vein was placed. Conclusions: Despite the normality of cell blood count and bone marrow aspiration, a myeloproliferative disorder must be considered in patients with BCS. This suspect should be also encouraged by the absence of hypersplenism in presence of a severe portal hypertension. Finally, this clinical case confirms that analysis of JAK mutation should be also included in diagnostic work up of pediatric case of BCS. http://dx.doi.org/10.1016/j.dld.2014.07.109 A PARTICULAR CASE OF DUODENAL OBSTRUCTION DUE TO RARE PANCREATIC SEROUS CYSTADENOMA Maria Teresa Illiceto 1,∗ , Gabriele Lisi 2 , Marco Filippone 1 , Carlo Rossi 2 , Daniela Trotta 3 , Pierluigi Lelli Chiesa 2 , Giuliano Lombardi 1 1 UOS Gastroenterologia ed Endoscopia Digestiva Pediatrica, Ospedale Regionale Pescara, Pescara, Italy 2 Unità Operativa Clinicizzata di Chirurgia Pediatrica, Università “G.d’Annunzio”di Chieti-Pescara, Pescara, Italy 3 UOC Pediatria Medica, Ospedale Regionale di Pescara, Pescara, Italy
Objective: Pancreatic tumors are very rare in children, particularly serous cystadenoma. Although this tumor is not potentially malignant, all patients required accurate evaluation and attention should be paid to possible related complications. Methods: The authors present a particular case of duodenal obstruction due to a pancreatic serous cystadenoma. GA affected by epileptic encephalopathy, at 22 months was admitted for intestinal obstruction and acute pancreatitis secondary to duodenal hematoma for which underwent laparotomy, incision and drainage of the hematoma and packaging gastrostomy. Gradually improved, but the hypoechoic cystic lesion persisted. 2 months later, to the progressive reduction of the cystic lesion, corresponds the emergence of ascites and rise in amylase, with worsening eosinophilia. Results: The screening performed excluded infections, allergies, celiac and autoimmune disease, and metabolic pathologies. Endoscopy with multiple biopsies excluded eosinophilic gastroenteropathy. The ascites fluid showed presence of amylase. In suspected pancreatic cyst, we planned abdomen NMR. In the meantime, the child was again operated in urgency to occlusion by adhesions, and in the process of debridement it was highlighted and removed a cystic lesion of 4.5 × 4 × 2.6 cm suspected to pseudopancreatic cyst, which was histologically a pancreatic serous cystadenoma.
e107
Conclusions: The authors believe that the pancreatic cystoadenoma caused the compression of the duodenum and pancreatic-biliary tract with onset of pancreatitis and probable chronic inflammation of deep soft tissues; that inconstant presence of the cyst at US controls corresponding the ups and downs of ascites were due to a perforation of the wall of the cyst, and that periferic eosinophilia was drugs-related. http://dx.doi.org/10.1016/j.dld.2014.07.110 HUGE HYDROPS OF THE GALLBLADDER IN A 3 YEARS OLD GIRL WITH KAWASAKI SYNDROME: CASE REPORT Rosa Maria Melino 1,∗ , Emanuela Sacco 1 , Caterina Campanale 1 , Rosa Lapolla 1 , Barbara Santangelo 1 , Mario Rocco D’Altilia 2 , Maria Pastore 2 , Filomena Frascolla 2 , Anna Simeone 3 , Massimo Pettoello-Mantovani 1 , Michele Sacco 2 1
Department of Pediatrics, University of Foggia, Foggia, Italy 2 Department of Pediatrics, “Casa Sollievo della Sofferenza”-IRCCS, San Giovanni Rotondo, Italy 3 Department of Radiological Science, “Casa Sollievo della Sofferenza”-IRCCS, San Giovanni Rotondo, Italy Background: Kawasaki Syndrome (KS) is an acute febrile illness associated with multiorgan vasculitis of unknown etiology. Hydrops of gallbladder is a rare manifestation of KS, which most commonly affects children aged from 17 months to 7 years. Case report: A 3 years old girl was admitted to our emergency department with a 2-day history of fever, maculopapular rash, jaundice, acholic stools and dark urine. On physical examination, her body temperature was 39.5 ◦ C, her oral mucosa and tongue were hyperemic; she also had bilateral conjunctivitis, angular cheilitis. Laboratory findings revealed neutrophilic leukocytosis and inflammatory markers elevated. Liver function tests results as follows: aspartate aminotransferase 52 U/l; alanine aminotransferase 125 U/l; alkaline phosphatase 250 U/l; total bilirubin 9.08 mg/dl; direct bilirubin 7.67 mg/dl. Renal function was normal, but urine analysis showed proteinuria, hemoglobinuria and bilirubinuria. Abdominal ultrasonography showed gallbladder hydrops with a longitudinal diameter of 10.9 cm. TC and MRCP confirmed gallbladder hydrops and excluded obstructive causes and surgical treatments. A diagnosis of KS was made based on the clinical findings. No coronary aneurysms at Doppler echocardiography. On the 3th day after her admission, she received 2 g/kg intravenous immunoglobulin G (IVIG) and acetylsalicylic acid at dosage of 80 mg/kg/die. During follow-up, we noted clinical remission, gradual normalization of laboratory tests and of gallbladder ultrasonography findings Discussion: Kawasaki Syndrome should always be suspected in children with non-obstructive hydrops of the gallbladder, because early therapy with IVIG is very important for the prevention of coronary complications. http://dx.doi.org/10.1016/j.dld.2014.07.111