Guidelines on Diagnosis and Management of Cow's Milk Protein Allergy.

JUSTIFICATION: Cow's milk protein allergy (CMPA) is increasingly being diagnosed in the West, while there is scant data on the subject from India. There is low awareness among pediatricians about its diagnosis and management; leading to improper diagnosis. PROCESS: A group of experts from the pediatric gastroenterology sub-specialty chapter of Indian Academy of Pediatrics (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition) met at Mumbai on 26 October, 2018 and discussed various issues relating to the subject. A broad consensus was reached and a writing committee was formed. They met again on 11 August, 2019 at Chennai for a detailed discussion. The statement was sent to the entire group by e-mail and their approval obtained. OBJECTIVE: To formulate a consensus statement enable proper diagnosis and management of Cow's milk protein allergy. RECOMMENDATIONS: Cow's milk protein allergy is most common in the first year of life. Gastrointestinal manifestations are usually non-IgE mediated and therefore skin prick test and specific IgE levels are not useful in diagnosis. Clinical response to elimination diet followed by a positive oral food challenge is diagnostic. In patients with only gastrointestinal manifestations, sigmoidoscopy and rectal biopsy may be considered as an alternative. Management involves strict avoidance of all forms of bovine milk protein. For infants who are artificially fed, an extensively hydrolyzed formula is the first choice. Soy formula is an alternative in those above six months of age. Since most infants outgrow the allergy, elimination diet is only for a limited period and re-evaluation should be done periodically.

Unusual causes of extrahepatic biliary obstruction in children: a case series with review of literature.

This paper highlights the etiology, diagnosis, management and outcome in nine unusual cases of extrahepatic biliary obstruction in children. Extrahepatic biliary atresia and choledochal cyst constituted 127 out of 136 (93%) cases of all pediatric surgical biliary disorders managed between March 2000 and February 2007 at the reporting centre. However, nine children (aged 1.5-15 years) presented with uncommon causes like (1) idiopathic benign non-traumatic inflammatory stricture (n = 3), (2) idiopathic fibrosing chronic pancreatitis (n = 2), (3) post-cholecystectomy type 4 benign biliary stricture (n = 1), (4) post-acute pancreatitis pseudo-cyst of pancreas (n = 1), (5) non-Hodgkin's lymphoma (NHL) with extramural common bile duct compression and gall bladder perforation (n = 1), and (6) Langerhan cell histiocytosis (LCH, n = 1). The clinical features and the diagnostic work up of each group are discussed. A preoperative endoscopic/percutaneous biliary drainage was required in four children because of cholangitis at presentation. A biliary-enteric anastomosis was performed for all seven children in groups (1)-(4). The patients with NHL and LCH were referred for chemotherapy after establishing tissue diagnosis at laparotomy. With a follow-up period of 3 months to 7 years, seven children (with the exception of patients with NHL and LCH) are currently anicteric. This paper draws attention to some infrequently discussed causes of extrahepatic biliary obstruction in children. The management entails a carefully planned combination of endoscopic interventions, interventional radiology and surgery. The outcome in benign cases is usually satisfactory.

Biliary atresia with a "cyst at porta": management and outcome as per the cholangiographic anatomy.

The purpose of this study is to classify biliary atresia (BA) with a "cyst at porta" according to the cholangiographic anatomy and to define management strategy and outcome in each group. A cyst at porta was identified in 13 of 58 babies (22.4%) with BA at first presentation. The cholangiographic anatomy was classified as; Group A (n = 7), type III BA with extrahepatic cyst; Group B (n = 2), type I or II BA with extrahepatic biliary cyst; and Group C (n = 4), type I or II BA with both extrahepatic and intrahepatic biliary cysts. The remaining 45 patients were comprised of type III BA without a cyst. A Kasai's portoenterostomy (PE) was performed for all Group A patients. Groups B and C were treated by hepaticojejunostomy (n = 5) or portoenterostomy (n = 1). All 45 patients with type III BA without a cyst were treated by a Kasai's PE. The median age at surgery was 92 days (ranges 28-342 days). There were three early post-operative deaths, all in patients with type III BA without cyst. Overall 18/55 (32.7%) patients achieved a jaundice free state. In Group A, 5/7 (71.4%) patients had bile flow, 2/7 (28.6%) are anicteric and 2/7(28.6%) had 1-2 episodes of post-operative cholangitis. In Group B, both patients are anicteric and none had post-operative cholangitis. In Group C, all four babies had bile flow but, significant morbidity because of recurrent severe cholangitis. Only one patient reached a jaundice free state. Of the remaining 42 patients with type III BA without a cyst, 27 (64.3%) had bile flow, 13 (31%) became jaundice free and 14 (33.3%) have had 1-2 episodes of post-operative cholangitis. In conclusion, thirteen of 58 (22.4%) babies with BA had a "cyst at porta" at first presentation in this series. The outcome was most satisfactory in type I BA without intrahepatic cystic dilatation (Group B) in terms of achieving a jaundice free state and freedom from recurrent cholangitis. However, intrahepatic biliary cysts (Group C) were associated with recurrent severe cholangitis and a poor eventual outcome despite a good initial bile flow. The outcome in type III BA with extrahepatic cyst was comparable to type III BA without cyst.

Management of portal hypertension.

Portal hypertension (PHT) is common in children and a majority of cases in India are constituted by extrahepatic portal venous obstruction or cirrhosis of liver. Morbidity and mortality in this condition is related to variceal bleeding, most commonly from esophageal varices. Acute variceal bleeding is best controlled by endoscopic therapy. Somatostatin and octreotide are useful in acute variceal bleeding as a supplementary therapy. Acute variceal bleeding uncontrolled by medical therapy merits preferably a shunt surgery or devascularization depending upon etiology of PHT and expertise of the surgeon. Acute variceal bleeding originating from gastric varices can be effectively controlled by endoscopic injection of tissue adhesive agent (n-butyl 2 cyanoacrylate). Eradication of esophageal varices by endoscopic measures (sclerotherapy or band ligation) is successful in prevention of recurrence of bleeding. Surgical portosystemic shunts especially in non-cirrhotic PHT are successful in achieving portal decompression and significant reduction in recurrence of variceal bleeding. Role of beta-blockers in primary prophylaxis of variceal bleeding in children still remains to be substantiated.

Autoimmune liver disease in children.

BACKGROUND AND AIM: Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment. METHODS: All patients with liver disease were evaluated with liver function tests, abdominal ultrasonography, endoscopy, liver biopsy, viral markers and investigations for Wilson's disease. Immunoglobin (Ig)M hepatitis A virus, hepatitis E virus (HEV) and IgM hepatitis B core antibody were tested if acute viral hepatitis was suspected. Antinuclear antibody (ANA), antismooth muscle antibody (SMA), and liver kidney microsomal antibody (anti-LKM-1) were done in all cases. Autoimmune liver disease was diagnosed when one or more autoantibodies tested positive (> 1:40), and no other etiology of liver disease was identified. We also applied criteria proposed by the International Autoimmune Hepatitis Group. Cases diagnosed to have AILD were treated with immunosuppressive drugs. RESULTS: Autoimmune liver disease constituted 3.9% (6/153; median age and duration of illness 8.5 years and 3 months, respectively) of chronic liver disease cases. Four patients had acute hepatitis-like presentation. Of the six cases, two each were ANA and SMA +; one was anti-LKM-1 +, and the other was positive for both SMA and anti-LKM-1. Three of the patients achieved remission with combination therapy of oral prednisolone (OP) and azathioprine (AZT), and one with only OP. The other two patients were not treated. Two of the patients in remission have been weaned off from immunosuppressive therapy, and one is in a withdrawal phase. Another patient, while in biochemical remission developed superimposed anicteric acute HEV infection. CONCLUSION: Although AILD is uncommon in children, its search is rewarding, as remission is achieved with immunosuppressive therapy. Superimposed acute viral hepatitis can occur in endemic areas.

Need for liver transplantation in Indian children.

BACKGROUND: Liver transplantation (LT) is the most successful and accepted mode of therapy for failing liver in children. Pediatric LT has neither been widely attempted nor its need objectively assessed in our country. OBJECTIVE: To assess requirement of LT in children at a tertiary care hospital. METHODS: Data of children admitted to pediatric GE services (January 1992 to June 1997) were retrospectively analyzed. Subgroups of children with acute liver disease (ALD), chronic liver disease (CLD), neonatal cholestasis syndrome (NCS) and other etiology were evaluated for need for LT according to established criteria. RESULTS: Of the total 301 inpatients with liver diseases assessed at our center, ALD constituted 26% (n=79), CLD 35% (n=106), NCS 27% (n=82) and miscellaneous 11% (n=34). Among ALD, 19% (n=15) had FHF and 67% (n=10) qualified for LT (INR>4.0). Of CLD, LT was warranted in 13% (2/15) cases of Wilson's disease (Wilson's score > 6) and 60% of cirrhotics (n=40/66) with decompensation. NCS comprised extrahepatic biliary atresia (EHBA) in 43, choledochal cyst in 2, paucity of intralobular bile duct (PILBD) in 2, neonatal hepatitis in 23, and was of indeterminate etiology in 12 cases. Of NCS groups, LT was the only therapeutic option in 45% (n=36) of cases (EHBA 34, choledochal cyst 2). Of 34 cases of EHBA requiring LT, 32 presented after 4 months of age and other 2 children had decompensation before four months of age. Both children with choledochal cysts had decompensated liver disease. One patient of Crigler Najjar syndrome type I had kernicterus and qualified for LT. CONCLUSION: Our data shows need for LT in 30% of children with liver diseases constituted by cirrhosis (45%), biliary atresia (38%) and FHF (11%).

Endoscopic sclerotherapy for esophageal varices in children with extrahepatic portal venous obstruction: a follow-up study.

BACKGROUND: Results of treatment with endoscopic sclerotherapy for esophageal varices in children extrahepatic portal venous obstruction are limited. METHODS: A prospective study was undertaken of fifty children (mean age, 7.4 +/- 3.8 years; range, 4 months to 14 years) with esophageal variceal bleeding caused by extrahepatic portal venous obstruction (EHPVO) treated by repeated intravariceal endoscopic sclerotherapy (EST) at intervals of 2-3 weeks until eradication (no varices on endoscopy). RESULTS: Eradication of varices was achieved in 44 children (88%) with a mean of eight sessions per child. In six other cases, variceal grade decreased by 50% from the initial grades. Bleeding episodes at presentation were controlled in all of the children with first ET >. Over a mean follow-up period of 19 months (range, 12-36 months), a total of 15 episodes of rebleeding occurred in 13 children (26%) before the third session of EST and all were controlled with EST. Risk of rebleeding in children with eradicated varices (n = 44) significantly decreased from 0.2 episodes per month to nil after eradication. None of the children without eradicated varices had rebleeding. Thus, EST was successful in controlling rebleeding in all of the cases. Recurrence of varices was observed in five children (10%). None of our children either required surgery for EST failure or died. CONCLUSIONS: EST is a safe and effective nonsurgical mode of therapy in controlling esophageal variceal bleeding in children with EHPVO. Significant variceal bleeding did not occur during the relatively short follow-up in this series.

Current spectrum of hepatobiliary disorders in northern India.

OBJECTIVE: To evaluate the current spectrum of hepatobiliary disorders in children in Northern India. SETTING: Tertiary level referral hospital. METHODS: All children with hepatobiliary disorders presenting between January 1992 through July 1995 were evaluated by clinical assessment, liver function tests, viral and autoimmune markers, liver biopsy, copper studies and other relevant investigations. RESULTS: Two hundred and thirty five children with hepatobiliary disorders were seen over three and a half years period (67 cases per year). Acute hepatitis (28%), chronic liver disease (36%) and neonatal cholestasis syndrome (NCS) (26%) were the most common patterns of liver diseases. Chronic liver diseases were constituted by ICC (2%), post-hepatitic etiology (13%), Wilson's disease (21%), autoimmune (4%), non-Wilsonian metabolic diseases (16%), hepatic venous outflow obstruction (2%) and non-cirrhotic portal fibrosis (1%). Cirrhosis was documented in 71% and chronic hepatitis in 12% of cases with chronic liver disease. Fulminant hepatic failure was the presentation in 4% of children with liver diseases. CONCLUSION: Chronic liver diseases in Northern India are mainly constituted by post hepatitic, metabolic and cryptogenic etiology and ICC is rarely encountered. NCS is also one of the major subgroups of liver diseases in children.

Endosonographic evaluation of the rectum in children with extrahepatic portal venous obstruction.

Rectal endoscopic ultrasonography (REUS) was performed using an Olympus EU-M3 ultrasound fiberscope in 25 children with extrahepatic portal venous obstruction (median age of 8, range 3-16 years) and in eight control subjects (median age of 8, range 6-13). Rectal varices (tortuous or nodular distended veins seen beneath the mucosa) and portal hypertensive rectopathy were diagnosed endoscopically. At rectal endosonography, rectal varices were seen as rounded, oval, or longitudinal echo-free structures in the submucosa. Perirectal veins outside the rectal wall were also seen in REUS. Portal hypertensive rectopathy was endoscopically observed in nine (36%) patients. Rectal varices were detected by endoscopy in nine (36%) and by endosonographic examination in 19 (76%) patients with extrahepatic portal venous obstruction. The number (2, range 0-10) and size (3, range 0-4.5 mm) of submucosal veins seen on endosonography in patients were greater than in controls (0, range 0-1, and 0, range 0-2 mm; p < 0.001 for both). The size of perirectal veins was greater in patients than in controls (3.5, range 3-5 mm versus 2.5, range 2-3 mm; p < 0.001). Communicating veins between the submucosal and perirectal veins were seen in nine (36%) patients. Rectal endoscopic ultrasonography was superior to endoscopy in detecting the presence of rectal varices (76% versus 35%, p < 0.005). Our study suggests that endosonography is useful in detecting changes in the rectal and perirectal vasculature in patients with extrahepatic portal venous obstruction.

Gastrointestinal bleeding in children.

We prospectively evaluated 139 consecutive children presenting to the Sanjay Gandhi Postgraduate Institute of Medical Sciences (Lucknow, India) with gastrointestinal (GI) bleeding from January 1991 to November 1994. Our aims were to find out whether the causes of GI bleeding in a developing country differed from developed countries and how the application of newer diagnostic techniques would help in the diagnosis of GI bleeding. Barium studies, endoscopy, technetium-99m-labelled (erythrocytes and pertechnetate) scans, selective abdominal angiography using a digital subtraction technique and rectal endoscopic ultrasonography were performed. Upper GI bleeding (n = 75) was variceal in 71 (95%) children (extrahepatic portal venous obstruction in 65, cirrhosis in six) and non-variceal in four (5%) cases (Henoch-Schonlein purpura, idiopathic thrombocytopenic purpura, drug-induced gastric erosions and pseudoaneurysm of the gastroduodenal artery due to idiopathic chronic calcific pancreatitis). Causes of lower GI bleeding (n = 64) were colitis (27 cases; 42%), colorectal polyps (26 cases; 41%), enteric fever (n = 3), solitary rectal ulcer (n = 3), portal hypertensive colopathy (n = 2), colonic arteriovenous malformation (n = 1) and internal haemorrhoids (n = 1). One patient remained undiagnosed. Angiography performed in four children was diagnostic in two. In one child with massive lower GI bleeding from portal colopathy, the bleeding site (caecum) was localized by intra-operative colonoscopy, while in the other child with portal colopathy, rectal endoscopic ultrasonography was performed to substantiate the diagnosis. We conclude that the causes of upper GI bleeding in children in developing countries are different from those in developed countries (variceal bleeding due to extrahepatic portal venous obstruction is the most common cause, while peptic ulcer is rare). However, the spectrum of lower GI bleeding is similar to that of developed countries. Application of newer diagnostic techniques is helpful and safe in the identification of the cause of GI bleeding in children.

Therapeutic gastrointestinal endoscopy.

The safety, efficacy and utility of various therapeutic gastrointestinal (GI) endoscopic procedures performed on children (January 1992 to July 1995) at a tertiary referral centre in India were studied. A total of 1,030 sessions (upper GI 972 and lower GI 58) of therapeutic GI endoscopy were performed in 162 children (mean age 7.4 +/- 4 years; upper GI 115, lower GI 47). Various upper GI endoscopic procedures done were injection sclerotherapy (EIS), endoscopic variceal ligation (EVL), bougie dilatation of oesophageal strictures, balloon dilatations of oesophageal stricture/pyloric obstruction and retrieval of foreign bodies in 75%, 6%, 9%, 4% and 12% of children respectively. Therapy for bleeding from oesophageal varices constituted the major group (75%). Repeated EIS (sessions total--876, mean 8, range 5-15) performed on 86 children resulted in control of bleeding in all and eradication of oesophageal varices in 85% of cases. Minor complications (oesophageal ulcers and oesophageal strictures) due to EIS were observed in 9% of children. EVL (10 sessions in 7 children) was effective in controlling bleeding and substantial decrease of varices in all without any complication. Oesophageal dilation either by bougie (61 sessions in 10 children) or balloon (6 sessions in 3 children) were performed for benign strictures. Balloon dilatation of pyloric obstruction was successfully done in 2 children. Foreign bodies (retained or sharp) were retrieved from upper GI tract in 14 children. No complications were observed with stricture dilatation/foreign body retrieval. Therapeutic lower GI endoscopies were performed in 47 children (colonoscopic polypectomy in 92%, anal dilatation and piles banding in 4% each). One child with juvenile polyposis coli developed sigmoid colon performation following colonoscopic polypectomy which required surgical correction. We conclude that upper and lower GI endoscopic therapeutic procedures in children are highly effective and safe. The risk of major complication is very small in experienced hands and occasional minor complications, can be managed conservatively.

Neonatal cholestasis syndrome: an appraisal at a tertiary center.

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.

Portal hypertensive gastropathy in children with extrahepatic portal venous obstruction: role of variceal obliteration by endoscopic sclerotherapy and Helicobacter pylori infection.

We aimed to determine the frequency of portal hypertensive gastropathy (PHG) in children with extrahepatic portal venous obstruction (EHPVO) and to find out the role of esophageal variceal obliteration by endoscopic injection sclerotherapy (EIS) and Helicobacter pylori (H. pylori) infection in the pathogenesis of PHG. Twenty consecutive children were studied before EIS and 20 after esophageal varices obliteration. Diagnosis of PHG was established by endoscopic assessment. Helicobacter pylori infection was diagnosed by rapid urease test, H. pylori culture, smear, and histopathologic examination of antral biopsy specimens. Portal hypertensive gastropathy was characterized and graded by endoscopy according to previously established criteria. In the pre-EIS group, eight (40%) had PHG (mild in all) compared with 16 (80%; mild in eight, severe in eight) in the post-EIS group (p < 0.05). Portal hypertensive gastropathy was more extensive in the post-EIS group. There was no significant difference between frequency of gastric varices and H. pylori infection in the pre-EIS and post-EIS groups. We conclude that PHG is common in children with EHPVO; its frequency, extent, and severity increase after esophageal variceal obliteration by EIS, and H. pylori infection does not play any role in its development.

Retained esophageal foreign bodies in children.

Foreign-body (FB) ingestion is common in children. Retained FBs in the esophagus can produce serious complications. We report five children with retained esophageal FBs: one presented with massive hematemesis due to an esophago-carotid fistula and the others had FB impaction above esophageal strictures. The hazards of impaction of small FBs above the strictures and delayed referral are highlighted.

Calcific pancreatitis-induced gastroduodenal artery pseudoaneurysm: non-surgical management.

Hemorrhage associated with pancreatitis has a high morbidity and mortality in the early phase of the illness. In a small number of patients, bleeding is from major pancreatic or peripancreatic vessels which necessitates emergency intervention. However, most such reports are confined to adults. We report a 6-year-old girl with chronic calcific pancreatitis who presented with hematemesis and melena without any acute exacerbation of her underlying illness. Pseudoaneurysm of the gastroduodenal artery was detected by angiography which was then effectively treated at the same time by embolization with gel foam and a steel coil, thus obviating the need for surgical intervention.