The Need for Culturally Appropriate Food Allergy Management Strategies: The Indian Milk Ladder.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant's diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. METHODS: We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. RESULTS: Combining expert consensus and validation of milk protein content, we created the world's first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. CONCLUSIONS: This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the "The Indian Milk Ladder" will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

Gastrointestinal manifestations in children with primary immune deficiencies: A case series.

Gastrointestinal (GI) manifestations are the second most common complications of primary immune deficiencies (PIDs) after pulmonary disease, affecting up to one-half of children with PIDs. Non-infectious GI manifestations such as allergic, autoimmune, and inflammatory disorders can be the predominant manifestations of PIDs. We present a series of five children who presented predominantly with these GI manifestations of PID, not attributable to infections. Very early age of onset (infancy), parental consanguinity, and failure to respond to hypoallergenic formula led to strong suspicion for underlying PIDs. Next-generation sequencing led to the underlying genetic diagnosis. Early diagnosis and hematopoietic stem cell transplantation could be life-saving in these children.

Pediatric acute liver failure: An experience of a pediatric intensive care unit from resource limited settings.

Introduction: Pediatric acute liver failure is a rare and serious disease. Though liver transplantation is considered as the established treatment option for patients who are unlikely to recover with medical management, however, with the advancement of medical care there has been an increase in spontaneous regeneration of liver, obviating the need for liver transplantation. We identified the etiologies, outcome and prognostic factors of acute liver failure and the validity of the existing liver transplantation criteria to predict the outcome of pediatric acute liver failure. Materials and methods: This was a retrospective study done from January 2014 to December 2019 in a tertiary pediatric critical care unit in South India. All children aged between 1 month to 18 years admitted with acute liver failure were enrolled. Results: Of 125 children with acute liver failure, the main etiologies were infections (32%), indeterminate (23%), paracetamol toxicity (21%), metabolic (13%) and others (11%). Dengue was the most common infection (55%). The median pediatric logistic organ dysfunction score at admission was 12 (4-27). Of 125 patients, 63.2% (n = 79) had spontaneous regeneration which was higher in paracetamol induced (92.3%) compared to non-paracetamol induced acute liver failure (55.5%). Only two patients underwent liver transplantation and 35% died. Peak alanine transaminase and use of inotropes significantly predicted the outcome of disease. Of 38 children meeting King's College Hospital criteria for liver transplantation, 57.9% had spontaneous regeneration and 36.8% died. Of 74 children meeting INR > 4 criteria, 54% (n = 40) had spontaneous regeneration and 43.2% died. INR >4 criteria was more sensitive than King's College Hospital criteria for predicting the need for liver transplantation. Conclusion: Pediatric acute liver failure is caused by varied etiologies and infections were the commonest cause. Despite having a seriously ill cohort of patients, medical management resulted in spontaneous regeneration in the majority of children with acute liver failure. The use of inotropes, advanced hepatic encephalopathy, and peak alanine transaminase were predictors of poor outcome in children with acute liver failure and these patients could be considered for liver transplantation as available. Therefore, we may need to develop better predictors of pediatric acute liver failure in resource limited settings.

Giant Cell Hepatitis in Copper Toxicosis.

Cholestatic jaundice in new born and infants results from biliary obstruction or hepatocellular dysfunction. Biliary atresia (BA) and Idiopathic neonatal hepatitis comprises the major aetiology. Cholestasis due to toxins is rare in infants. Indian childhood cirrhosis (ICC) and ICC like diseases have been described in infants. Herein, authors are describing a case of infantile cholestasis presenting at 4 months of age who was diagnosed to have copper related hepatotoxicosis on liver biopsy. Copper tumblers were used for preparation of formula milk that likely was the source of exogenous copper and the child improved well after removing the source of exogenous copper.

CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature.

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

Biallelic Mutations in Ubiquitin-Specific Peptidase 53 (USP53) Causing Progressive Intrahepatic Cholestasis. Report of a Case With Review of Literature.

Whole-exome sequencing studies have recently identified novel genes implicated in normal- or low-GGT pediatric cholestasis including ubiquitin-specific peptidase 53 (USP53). We identified novel biallelic mutations in the USP53 gene in a 7-month-old infant with pruritus and progressive intrahepatic cholestasis. His liver biopsy showed portal and perivenular fibrosis with bland bilirubinostasis. His parents were asymptomatic heterozygous for the same mutation. He is currently on vitamin supplements and cholestyramine and his family has also been counseled for liver transplantation. Our report confirms that patients with biallelic mutation in USP53 develop cholestatic liver disease.

Paediatric inflammatory bowel disease in India: a prospective multicentre study.

BACKGROUND: Paediatric inflammatory bowel disease (PIBD) is increasing across the world. However, information from India is sparse. This multicentre study evaluated the demographics, clinical phenotype and outcome of PIBD from India. METHODS: Data of children (≤18 years) with PIBD were collected using a proforma containing details of demographics, clinical profile, extraintestinal manifestations (EIM), investigations, disease extent and treatment. RESULTS: Three hundred twenty-five children [Crohn's disease: 65.2%, ulcerative colitis: 28.0%, IBD unclassified (IBDU): 6.7%, median age at diagnosis: 11 (interquartile range 6.3) years] were enrolled. 6.9% children had family history of IBD. Pancolitis (E4) was predominant in ulcerative colitis (57.8%) and ileocolonic (L3, 55.7%) in Crohn's disease. Perianal disease was present in 10.9% and growth failure in 20.9% of Crohn's disease cases. Steroids were the initial therapy in 84.2%, 5-amino salicylic acid in 67.3% and exclusive enteral nutrition (EEN) in 1.3% cases. Overall, immunomodulators and biologics were given to 84.3 and 17.9% cases, respectively, and 2.9% cases underwent surgery. Very early onset IBD (VEOIBD) was seen in 60 (19.2%) children. IBDU was commoner in the VEOIBD than the older-PIBD (18/60 vs 4/253; P < 0.001). VEOIBD-Crohn's disease patients more often had isolated colonic disease than the older Crohn's disease (45.4% vs 11.8%; P < 0.001). Prevalence of perianal disease, EIM, therapeutic requirements and outcome were not different between VEOIBD and older-PIBD. CONCLUSION: Disease location and phenotype of PIBD in Indian children is similar to the children from the west. However, the therapeutic options of EEN, biologics and surgery are underutilized. VEOIBD accounted for 19.2% of PIBD.

Corrigendum to "Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for the Study of Liver (INASL), The Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN) and the Movement Disorders Society of India (MDSI)" [J Clin Exp Hepatol 9 (2019) 74-98].

[This corrects the article DOI: 10.1016/j.jceh.2018.08.009.].

Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Ushering a New Era in the Management of Hepatitis C in Children with Hematological Disorders.

Transfusion-transmitted hepatitis C is a major concern among thalassemia patients. Our aim is to estimate the prevalence of Hepatitis C infection among thalassemia patients and to assess the treatment response, adverse effects of Peg-interferon based regimen and the new direct-acting antiviral drugs. Patients with thalassemia receiving regular blood transfusions with positive anti HCV antibodies during a period from January 2012 to June 2017 were analyzed. Serial HCV viral load and genotype and liver function tests were performed. Peg interferon and Ribavirin were used in patients diagnosed before January 2016 and patients diagnosed after January 2016 were started on the combination of Ledipasvir/Sofosbuvir. Thirty-two patients aged between 2 and 28 years were analyzed. Genotype 1 was the predominant type. Twenty-one patients were initiated on Peg Interferon with Ribavirin, and 14 achieved sustained virological response. All of them had increased blood transfusion requirements with significant compliance issues. All eleven patients started on Ledipasvir and Sofosbuvir including 4 undergoing hematopoietic stem cell transplantation and 7 interferon failures showed sustained viral clearance with good compliance. Ledipasvir/Sofosbuvir combination can be safely used in thalassemia patients and in young children. The cost of therapy is less compared to peg interferon based regimen with good compliance and superior efficacy.

Incidentally Detected Elevated Liver Enzymes: From Liver to Muscle.

We describe 8 children - with incidentally detected isolated elevation of liver enzymes aspartate aminotansferase and alanine aminotransferase - who were extensively evaluated for hepatic causes before finally being diagnosed to have muscular dystrophy. Serum creatinine phosphokinase levels, if performed early during the work-up, may help in diagnosis of muscle disease and avoid unnecessary investigations for liver disease.

A questionnaire survey of pediatric inflammatory bowel disease in India.

BACKGROUND: Inflammatory bowel disease (IBD) is not uncommon in children and is an important cause of morbidity. Since information on IBD in Indian children is sparse, the study aimed at highlighting the salient features in them. MATERIALS AND METHODS: A questionnaire survey was done among 221 children and adolescents with IBD [ulcerative colitis (UC) 93 (42.1 %); Crohn's disease (CD) 122 (55.2 %); unclassified (IBD-U) 6 (2.7 %)] across seven centers in India. The cut-off age was 18 years and below. RESULTS: The mean age of presentation for UC and CD was 10.2 ± 4.4 and 11.0 ± 4.5 years, respectively, with no gender difference. Diarrhea (69.9 %, p = 0.001) and blood in the stools (90.3 %, p = 0.0001) were common in UC, whereas abdominal pain (73.8 %, p = 0.01), fever (39.3 %, p = 0.0001), anemia (64.7 %, p = 0.001), and growth failure (76.2 %, p = 0.0001) were common in CD. Extraintestinal manifestations (EIM) were a feature in 23.6 % and 36.1 % of UC and CD, respectively. Pancolitis (E3) was predominant in UC (70.9 %) and 88 % required steroids. Ileocolonic CD (L3) was common in 72.9 %; 76.2 % required azathioprine for maintenance. Of the children with UC, 11.8 % had complications like massive hemorrhage and toxic megacolon, while 27 % of CD had fistulae, perianal abscess, stricture, and perforation. Biologicals were used in 0.8 % of severe UC and in 12.2 % of CD. In UC, 4.3 % required surgical intervention. CONCLUSION: Pediatric inflammatory bowel disease (P-IBD) in India shares similarities with adult-onset IBD. Distinctive features were growth failure and more severe forms of the disease necessitating immunomodulators.