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PA42 ALLGROVE SYNDROME IN TWO SIBLINGS
Abstracts of XVI National Congress of SIGENP / Digestive and Liver Disease 41S (2009), S199–S239 PA40 MULTIPLE AUTOIMMUNE DISEASES IN CELIAC DISEASE: A CASE REPORT G.M. Tronconi a , B. Parma a , P. Corsin a , G. Nebbia b , G. Weber a , G. Barera a a Department of Pediatrics, Scientific Institute H. San Raffaele, Vita-Salute University, Milan, Italy; b Department of Pediatrics and Liver Transplantation Unit, Fondazione Policlinico, Mangiagalli, Regina, Elena IRCCS, Milan University, Italy
Background: Hypertransaminase level in pediatric patients with Graves Disease (GD) is a rare condition. Increases in liver enzymes are often related to minor adverse effects of antithyroid drugs. GD can be associated with other autoimmune diseases such as Celiac Disease (CD). This may occur because of a common association with HLA-class II molecules, particularly DR3. CD can be related to 2 forms of liver damage: 1. a “celiac hepatitis” that reverses with gluten free-diet (GFD); 2. an autoimmune hepatitis (AIH) characterized by specific autoantibodies. A single case of multiple autoimmune disease including GD, CD and AIH has been described in childhood [1]. We report a 5 year-old girl with GD and CD treated with methimazole, showing persistent hypertransaminase level. Case Report: Family history: positive for autoimmune diseases. Clinical presentation: tachycardia and weight loss. Investigations demonstrated a decreased TSH concentration, increased fT3 and fT4, high titers of thyroid stimulating antibodies-receptor. Thyroid US pattern was diagnostic for autoimmune thyroiditis. Treatment with propanolol and methimazole was started. Clinical response was incomplete in normalizing thyroid function; biochemical examinations showed hypertransaminase level. Hepatitis, hepatotropic viruses, and alfa-1 anti-trypsin deficiency were ruled out. Hepatic US was normal. An hepatic adverse effect due to metimazole was suspected. Hypergammaglobulin level with selective IgA deficiency was documented. Serologic tests for CD were positive and the diagnosis was confirmed by a small bowel biopsy (M/O IIIc). The GFD did not result in reduction of serum transaminase levels in 6 ms. Screening for other organ and non-organ specific autoantibodies revealed elevated ANA. Liver biopsy was diagnostic for “lobular and interface hepatitis”. This histological finding, associated with elevated ANA, hypergammaglobulin and HLA DR3, was suggestive for autoimmune hepatitis type 1. Prednisolone and azathioprine were administered and steroid therapy is still ongoing. Serum transaminase levels normalized in 2 ys. Conclusion: This case report emphasizes the importance of accurate evaluations of hypertransaminasemia in pediatric GD, considering the possible occurrence of multiple autoimmune diseases (CD/AIH) and adverse effects of antithyroid drugs. References [1] Arvola T, Mustalahti K, Saha MT, Vehmanen P, Partanen J, Ashorn M. Celiac disease, Thyrotoxicosis and Autoimmune Hepatitis in a Child. J Pediatr Gastroenterol Nutr 2002; 35:90-92.
PA41 THE OUTCOME OF HEPATOPULMONARY SYNDROME AND LIVER TRANSPLANTATION IN CHILDREN M. Bosisio a , P. Stroppa a , M. Bravi a , V. Casotti a , D. Codazzi b , L. D’Antiga a , M. Colledan c a Paediatric Liver, GI and Transplantation Unit, b Paediatric Intensive Care Unit, c General Surgery III and Transplant Surgery Unit, Ospedali Riuniti, Bergamo, Italy
Background: Hepatopulmonary syndrome (HPS) is a pulmonary vas-
S237
cular disorder characterized by the clinical triad of liver disease, intrapulmonary right-to-left shunting, and arterial hypoxemia. HPS is associated with portal hypertension or porto-systemic shunts. Liver transplantation (OLT) cures this condition but the risk at operation is increased due to hypoxaemia. We aimed to calculate the proportion of children transplanted in our unit for HPS over the last 10 years and to review their features and outcome. Patients and Methods: We reviewed our database and then selected those patients transplanted with or because of HPS. We collected the following data: demographic features, degree of intrapulmonary shunting, gas exchanges, response to oxygen and nitric oxide, perioperative complications, outcome. The diagnosis of HPS was established if a patient with chronic liver disease had reduced pulse oxymetry and confirmed right-to-left shunting documented by bubble echocardiogram +/- pulmonary scintigraphy, and exlusion of other causes of hypoxaemia. Results: 13/402 (3,2%) children, M:F 4:9, median age 6.8 years (0.6– 11.4) median weight 22.8 kg (range 6–41) had been transplanted for HPS at our Unit. The underlying liver disease was biliary atresia in 7 children, cryptogenetic cirrhosis in 2, PFIC1 in 1, focal nodular hyperplasia in 1 and hepatoportal sclerosis in 2. The median time on the waiting list was 3.9 months (SD 2.2). At the time of diagnosis the median oxygen saturation was 80%: pCO2 levels 36.2 mmHg, arterial pH 7.4. All but one child received oxygen supplementation before transplant, on average 5.5 l/min for 9 months. The median PELD value in this series was 5.5, being more than 10 in only 2 children, both affected by biliary atresia; one child showed signs of liver insufficiency before transplant. Eight patients who were poor responders to oxygen administration responded to inhaled nitric oxide (iNO) with a statistically significant mean increase in PaO2/FiO2 ratio after the test (p=0.01). There was no perioperative mortality. All but one continued oxygen supplementation after OLTx for a median of 54 days (range 12–210). Conclusion: In our experience HPS is not a frequent indication for OLTx; patients with severe right to left shunting may benefit from perioperative administration of iNO. The outcome of these patients is overall good with no mortality and weaning from oxygen supply in a few months.
PA42 ALLGROVE SYNDROME IN TWO SIBLINGS L. Maestri a , M. Estienne b , G. Fava a , M. Meroni a , G. Riccipetitoni a a Ospedale
dei Bambini “V. Buzzi” – Milano – SC di Chirurgia Pediatrica; b IRCCS Istituto Neurologico “C. Besta” – Milano – SC di Neuropsichiatria Infantile Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. We report the cases of two siblings affected by Allgrove syndrome. Patient 1 was a male, 14 years old at the time of our first observation. When he was 7 years old, he received the diagnosis of adrenal insufficiency and alacrima. We evaluated him for severe dysphagia and barium meal, upper digestive endoscopy and esophageal manometry showed a picture of esophageal achalasia. We performed a laparoscopic Heller’s myotomy plus a Dor’s fundoplication. The postoperative course was uneventful and the boy is symptoms free two years after the surgical procedure. Patient 2 was a female who received a diagnosis of adrenal insufficiency and alacrima when she was 2 years old. We evaluated her when she was 10 years old for mild dysphagia. Barium meal, upper digestive endoscopy and esophageal manometry showed a picture of “vigorous” esophageal achalasia.The girl is actually treated by nifedipine and she is symptoms free. In both cases, mutation analyses confirmed diagnosis of Allgrove syndrome.
Background: Hypertransaminase level in pediatric patients with Graves Disease (GD) is a rare condition. Increases in liver enzymes are often related to minor adverse effects of antithyroid drugs. GD can be associated with other autoimmune diseases such as Celiac Disease (CD). This may occur because of a common association with HLA-class II molecules, particularly DR3. CD can be related to 2 forms of liver damage: 1. a “celiac hepatitis” that reverses with gluten free-diet (GFD); 2. an autoimmune hepatitis (AIH) characterized by specific autoantibodies. A single case of multiple autoimmune disease including GD, CD and AIH has been described in childhood [1]. We report a 5 year-old girl with GD and CD treated with methimazole, showing persistent hypertransaminase level. Case Report: Family history: positive for autoimmune diseases. Clinical presentation: tachycardia and weight loss. Investigations demonstrated a decreased TSH concentration, increased fT3 and fT4, high titers of thyroid stimulating antibodies-receptor. Thyroid US pattern was diagnostic for autoimmune thyroiditis. Treatment with propanolol and methimazole was started. Clinical response was incomplete in normalizing thyroid function; biochemical examinations showed hypertransaminase level. Hepatitis, hepatotropic viruses, and alfa-1 anti-trypsin deficiency were ruled out. Hepatic US was normal. An hepatic adverse effect due to metimazole was suspected. Hypergammaglobulin level with selective IgA deficiency was documented. Serologic tests for CD were positive and the diagnosis was confirmed by a small bowel biopsy (M/O IIIc). The GFD did not result in reduction of serum transaminase levels in 6 ms. Screening for other organ and non-organ specific autoantibodies revealed elevated ANA. Liver biopsy was diagnostic for “lobular and interface hepatitis”. This histological finding, associated with elevated ANA, hypergammaglobulin and HLA DR3, was suggestive for autoimmune hepatitis type 1. Prednisolone and azathioprine were administered and steroid therapy is still ongoing. Serum transaminase levels normalized in 2 ys. Conclusion: This case report emphasizes the importance of accurate evaluations of hypertransaminasemia in pediatric GD, considering the possible occurrence of multiple autoimmune diseases (CD/AIH) and adverse effects of antithyroid drugs. References [1] Arvola T, Mustalahti K, Saha MT, Vehmanen P, Partanen J, Ashorn M. Celiac disease, Thyrotoxicosis and Autoimmune Hepatitis in a Child. J Pediatr Gastroenterol Nutr 2002; 35:90-92.
PA41 THE OUTCOME OF HEPATOPULMONARY SYNDROME AND LIVER TRANSPLANTATION IN CHILDREN M. Bosisio a , P. Stroppa a , M. Bravi a , V. Casotti a , D. Codazzi b , L. D’Antiga a , M. Colledan c a Paediatric Liver, GI and Transplantation Unit, b Paediatric Intensive Care Unit, c General Surgery III and Transplant Surgery Unit, Ospedali Riuniti, Bergamo, Italy
Background: Hepatopulmonary syndrome (HPS) is a pulmonary vas-
S237
cular disorder characterized by the clinical triad of liver disease, intrapulmonary right-to-left shunting, and arterial hypoxemia. HPS is associated with portal hypertension or porto-systemic shunts. Liver transplantation (OLT) cures this condition but the risk at operation is increased due to hypoxaemia. We aimed to calculate the proportion of children transplanted in our unit for HPS over the last 10 years and to review their features and outcome. Patients and Methods: We reviewed our database and then selected those patients transplanted with or because of HPS. We collected the following data: demographic features, degree of intrapulmonary shunting, gas exchanges, response to oxygen and nitric oxide, perioperative complications, outcome. The diagnosis of HPS was established if a patient with chronic liver disease had reduced pulse oxymetry and confirmed right-to-left shunting documented by bubble echocardiogram +/- pulmonary scintigraphy, and exlusion of other causes of hypoxaemia. Results: 13/402 (3,2%) children, M:F 4:9, median age 6.8 years (0.6– 11.4) median weight 22.8 kg (range 6–41) had been transplanted for HPS at our Unit. The underlying liver disease was biliary atresia in 7 children, cryptogenetic cirrhosis in 2, PFIC1 in 1, focal nodular hyperplasia in 1 and hepatoportal sclerosis in 2. The median time on the waiting list was 3.9 months (SD 2.2). At the time of diagnosis the median oxygen saturation was 80%: pCO2 levels 36.2 mmHg, arterial pH 7.4. All but one child received oxygen supplementation before transplant, on average 5.5 l/min for 9 months. The median PELD value in this series was 5.5, being more than 10 in only 2 children, both affected by biliary atresia; one child showed signs of liver insufficiency before transplant. Eight patients who were poor responders to oxygen administration responded to inhaled nitric oxide (iNO) with a statistically significant mean increase in PaO2/FiO2 ratio after the test (p=0.01). There was no perioperative mortality. All but one continued oxygen supplementation after OLTx for a median of 54 days (range 12–210). Conclusion: In our experience HPS is not a frequent indication for OLTx; patients with severe right to left shunting may benefit from perioperative administration of iNO. The outcome of these patients is overall good with no mortality and weaning from oxygen supply in a few months.
PA42 ALLGROVE SYNDROME IN TWO SIBLINGS L. Maestri a , M. Estienne b , G. Fava a , M. Meroni a , G. Riccipetitoni a a Ospedale
dei Bambini “V. Buzzi” – Milano – SC di Chirurgia Pediatrica; b IRCCS Istituto Neurologico “C. Besta” – Milano – SC di Neuropsichiatria Infantile Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. We report the cases of two siblings affected by Allgrove syndrome. Patient 1 was a male, 14 years old at the time of our first observation. When he was 7 years old, he received the diagnosis of adrenal insufficiency and alacrima. We evaluated him for severe dysphagia and barium meal, upper digestive endoscopy and esophageal manometry showed a picture of esophageal achalasia. We performed a laparoscopic Heller’s myotomy plus a Dor’s fundoplication. The postoperative course was uneventful and the boy is symptoms free two years after the surgical procedure. Patient 2 was a female who received a diagnosis of adrenal insufficiency and alacrima when she was 2 years old. We evaluated her when she was 10 years old for mild dysphagia. Barium meal, upper digestive endoscopy and esophageal manometry showed a picture of “vigorous” esophageal achalasia.The girl is actually treated by nifedipine and she is symptoms free. In both cases, mutation analyses confirmed diagnosis of Allgrove syndrome.