Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN).

Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.

Spectrum and trend of pediatric inflammatory bowel disease: A two-decade experience from northern India.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) has been known to be a disease predominant in the west. There is scarcity of data on pediatric IBD (P-IBD) from northern India. The objective of our study was to analyze the clinical spectrum of P-IBD in northern India. METHODS: A retrospective analysis of 126 children (<18-year old) diagnosed with IBD from January 1999 to December 2019 was done on a pre-designed proforma. It was systematically entered in a MS Excel spreadsheet and analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0. The descriptive phenotypes of Ulcerative colitis (UC) and Crohn's disease (CD) were revised according to the Paris classification. RESULTS: Of 126 children, UC was diagnosed in 76 (60.3%), CD in 44 (34.9%) and IBD-unclassified (IBD-U) in six (4.76%) patients. The mean age at diagnosis was 11.3 years; 38.8% were < 10 years with the male: female ratio of 1.6:1. Sixteen children (12.7%) had very early onset IBD (VEOBD). Overall, the median time to diagnosis in IBD was 12 months (interquartile range [IQR]: 3.25-24), which was as high as 52.5 months (IQR: 11-98) in CD. Pancolitis with bleeding per rectum and ileocolonic involvement with pain in abdomen were the commonest presentations in UC and CD, respectively. Stricturing disease was seen in 27% of CD cases. Relapses were seen in 46% (35/76) of U.C and 23% (10/44) of CD kids. Step-up treatment protocol was employed in them with the use of biologicals in 12% of cases. There was a 2.75-fold rise in the IBD cases in the last 10 years (2010-20). There was reduction in time to diagnosis (21 months vs. 90 months; p - 0.012) and empirical anti-tubercular therapy use (90% vs. 5.8%) in CD over two decades. CONCLUSION: From our experience in a tertiary care centre in northern India, P-IBD is on the rise. UC is more common than CD. Pancolitis and ileocolonic disease are the commonest disease sites in UC and CD, respectively There is a significant delay in the time to diagnosis in CD. Stricturing disease was seen in a quarter of children with CD.

Microvillous inclusion disease as a cause of severe congenital diarrhea in a newborn.

Microvillous inclusion disease (MVID), also known as congenital microvillus atrophy remains an important differential diagnosis of intractable secretory diarrhea in neonatal period. The condition is inherited as an autosomal recessive disorder with no sex predilection and more commonly reported in those tribes with consanguineous marriages. The pathognomonic electron microscopic findings includes villous atrophy with the formation of intracellular microvillous inclusions. Definite treatment includes either isolated small bowel or combined small bowel and liver transplantation. Herein, we are describing a case of intractable diarrhea in a preterm neonate with MVID phenotype presented on second day of life with intractable diarrhea. The diagnosis was established by classical electron microscopic findings in the intestinal biopsy sample.

The reliability of Juvenile Arthritis Magnetic Resonance Imaging Scoring system in the evaluation of the shoulder joint in juvenile idiopathic arthritis.

Objectives: We aimed to evaluate shoulder joint by magnetic resonance imaging (MRI) using the Juvenile Arthritis Magnetic Resonance Imaging Scoring (JAMRIS) system in children with juvenile idiopathic arthritis (JIA) and to compare clinical, laboratory parameters and disease activity scores with MRI parameters. Patients and methods: A total of 32 shoulder joints of 20 patients (16 males, 4 females; mean age: 8.9±3.5 years; range, 2.5 to 14 years) with a known diagnosis of JIA and a clinical suspicion of shoulder joint involvement and underwent MRI were included. Reliability was determined by inter- and intra-observer correlation coefficients. Correlation of the clinical and laboratory parameters with JAMRIS scores was done using the non-parametric tests. Sensitivity of clinical examination to detect shoulder joint arthritis was also determined. Results: Of the 32 joints, 27 joints in 17 patients showed MRI changes. Seven joints in five patients fulfilled the definition of clinical arthritis, all revealed MRI changes. In 25 joints without clinical arthritis, early and late MRI changes were seen in 19 (67%) and 12 (48%) joints, respectively. The inter- and intra-observer correlation coefficients for JAMRIS system were excellent. No correlation was found between MRI parameters, clinical, laboratory, and disease activity scores. The sensitivity of clinical examination to detect shoulder joint arthritis was 25.9%. Conclusion: The JAMRIS system is reliable and reproducible to determine shoulder joint inflammation in JIA. Detection of shoulder joint arthritis by clinical examination has a poor sensitivity.

Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review.

Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. The metabolism of AZA is complex and mediated by multiple enzymes. After absorption and getting converted to 6MP, it is converted to 6-thiouric acid, 6-methyl mercaptopurine (6MMP) and 6-thioguanine (6TG) by different enzymes. Elevated 6MMP levels are associated with hepatotoxicity and also poor efficacy due to simultaneous lower levels of 6TG, which is the active drug metabolite related to both efficacy and myelosuppression. Allopurinol, a xanthine oxidase inhibitor shifts the metabolism of AZA away from 6MMP toward 6TG. This combination of allopurinol with reduced dose of AZA is an alternative to more expensive and toxic second line therapy to induce remission in patients with AIH. This article discusses the mechanism of action of allopurinol in inducing response to AZA, reviews the published literature on this combination therapy and gives guidelines on the use of allopurinol in patients with AIH.

Primary Carnitine Deficiency - A Rare Treatable Cause of Cardiomyopathy and Massive Hepatomegaly.

Systemic primary carnitine deficiency (CDSP) is a rare autosomal recessive disorder caused by a defect in plasma membrane uptake of carnitine due to SLC22A5 gene mutations. A nine-mo-old boy presented with hypertrophic cardiomyopathy, massive hepatomegaly and jaundice. Metabolic testing revealed very low free carnitine levels. Genetic analysis using Sanger sequencing method revealed compound heterozygous mutations in SLC22A5 gene, c. 1354 G > A (p. Glu452Lys, previously reported) and c.231_234del (novel frame-shift). Oral carnitine supplementation resulted in improved clinical outcome with ejection fraction to 75 % and normalization of liver size and enzymes after 3 mo.

Prevalence of functional gastrointestinal disorders among adolescents in Delhi based on Rome III criteria: A school-based survey.

BACKGROUND: Functional gastrointestinal diseases (FGIDs) are emerging as an important cause of morbidity in adolescents globally. The prevalence of FGIDs among Indian children or adolescents is not clear. METHODS: A cross-sectional school-based survey conducted in 1115 children aged 10-17 years attending four semi urban government schools of National capital territory (NCT) of Delhi. Rome III questionnaire was translated into Hindi and was filled by the students under supervision. Prevalence of FGIDs was calculated. RESULTS: Ten percent (112) adolescents had FGIDs. Out of 112, 52 % (58) were boys, and 48 % (54) were girls. 2.7 % (30) had functional dyspepsia, 1.3 % (15) had irritable bowel syndrome, 1.4 % (16) had abdominal migraine, 1.5 % (17) had aerophagia, 0.4 % (5) had functional abdominal pain syndrome, and 0.3 % (4) had functional abdominal pain. Prevalence of functional constipation, adolescent rumination syndrome, cyclical vomiting syndrome, and non-retentive fecal incontinence were 0.5 % (6), 0.3 % (4), 0.3 % (3), 0.4 % (5), respectively. Functional abdominal pain-related FGID were present in 6.3 % (70) children (35 boys and 35 girls). Functional constipation (4 vs. 2) and functional abdominal pain syndrome (4 vs. 1, p < 0.05) were significantly more in females. CONCLUSIONS: The prevalence of functional gastrointestinal disorders in our study was 10 %. The most frequent FGID noted was functional dyspepsia.

Homozygous familial hypercholesterolaemia in two boys aged 5 and 10 years.

Familial hypercholesterolaemia (FH) is an autosomal dominant lipid disorder. Homozygous FH (HFH), though rare, presents in early childhood. Two different presentations of HFH are reported. The first child presented at 5 years of age with xanthomas on the knees, elbows and buttocks and failure to thrive since the second year of life. He was found to be hypertensive with moderate aortic regurgitation. He is now stable on statins and antihypertensives. The second child presented at 10 years of age with multiple xanthomas and severe aortic stenosis. He died of refractory cardiac failure despite emergency aortic balloon valvoplasty due to diffuse coronary artery disease. Strong clinical suspicion can aid early diagnosis and delay cardiovascular complications.

Causes of unnatural deaths among children and adolescents in northern India - a qualitative analysis of postmortem data.

Aim of the study was to ascertain the various causes of unnatural deaths among 1-19 years analysing the postmortem data in a regional referral centre of northern India. A retrospective observational study from the data base was done for the same. All unnatural deaths in children aged 1-19 years from April 2010 to March 2011 were identified from the postmortem database. The children were classified into 3 groups-1-5 years, 6-10 years and 11-19 years separately for males and females. The various modes of unnatural deaths were identified and analysed. Retrospective analysis of Postmortem data during one year revealed total of 434 unnatural deaths in children aged 1-19 years. The most vulnerable age group included children between 11-19 years (74.5%). Females (51.6%) marginaly outnumbered the males (48.4%). Flame Burns (58.3%) was the commonest cause of death in all age followed by road traffic accidents 15%, electrocution 7.8% & Poisoning accounted for 6%. The most frequent victims were adolescents (74%) almost 3 times that of other age group. This study showed Adolescents were the most common victims of the unnatural death with flame burn being the most common cause followed by RTA, electrocution and poisoning.

The unusual presentation of a usual organism - the changing spectrum of the clinical manifestations of Plasmodium vivax malaria in children: a retrospective study.

BACKGROUND: Malaria is a major public health problem in the south-east Asian region. Among all countries in the SE Asian region the highest number of cases and deaths are reported from India. Children below 14 years of age contribute to approximately 42% of all the deaths. A majority of the deaths are attributed to severe malaria which is caused by Plasmodium falciparum. It is considered that causes a benign causing febrile illness without significant complications. However, in recent years, the spectrum of is shifting from being the cause of benign fever, to more severe complications. There have been case reports of complications like thrombocytopaenia, cerebral malaria, a disseminated intravascular coagulation, the acute respiratory distress syndrome, hepatic dysfunction and renal involvement. Most of the case reports are from the adult population, with an occasional occurrence of paediatric cases. OBJECTIVE: To highlight the increasing number of severe manifestations in P.vivax malaria in the children who were admitted in the malaria transmission season of 2011, at a tertiary care hospital. DESIGN: A descriptive, cross-sectional study. STUDY SUBJECTS: Children with an acute febrile illness of a duration of < 7 days, which was confirmed as Plasmodium vivax positive malaria by testing the peripheral smears and/or by Rapid Diagnostic Testing, who were admitted in the paediatric ward of a tertiary care hospital in New Delhi (India), during May 2011 to October 2011, Case records of context cases were analysed retrospectively. STATISTICS: The data was summarised by calculating the rates, ratios, proportions, means, standard deviations and the 95% confidence intervals. The Chi square test was applied to assess the significant difference between two qualitative variables. RESULTS: Among the case records of 54 patients, 40.7% were below 5 years. 61% were males and 38.9% were females. Besides hepatomegaly and splenomegaly which were the most common symptoms, which were seen in 81.5% and 72.2% children respectively, the various unusual manifestations seen were severe thrombocytopaenia (37%), jaundice with deranged LFT values (25.9%), abnormal bleeding (18.5%), impaired consciousness with a GCS of < 9 (18.5%), severe anaemia (14.8%), hypotension (11.1%), repeated convulsions (7.6%), pulmonary oedema/ARDS (5.6%) and ascites (5.6%). One case each showed haemoglobinuria, and pleural effusion. CONCLUSION: Plasmodium vivax is emerging as a cause of severe malaria. There is a further need to study the pathophysiology, virulence factors and the molecular mechanisms which are involved in malaria.