Clinical spectrum & changing presentation of celiac disease in Indian children.

Background & objectives: Celiac disease (CD) is a genetic immune mediated disorder characterised by gluten intolerance. This single centre study, from north India was aimed to assess the clinical, serological and histological profile of CD in a large cohort of children and the changing trends in its presentation. Methods: A review of clinical details of CD children diagnosed between 2000 and 2019 and currently on follow up was performed. Information on demography, symptoms, associated conditions, serology, biopsy findings and gluten-free diet were analyzed. Results: The mean age (±standard deviation) of 891 children included in the study, at onset and at diagnosis was 4.0±2.7 and 6.2±3.1 yr, respectively. Growth faltering, abdominal pain, abdominal distension and diarrhoea were presenting symptoms in 70, 64.2, 61.2 and 58.2 per cent, respectively. A positive family history of CD was present in 14 per cent and autoimmune conditions in 12.3 per cent of children. Thyroid disorders were seen in 8.5 per cent of children and Type 1 diabetes mellitus (T1DM) in 5.7 per cent. The duration of breastfeeding had a weak positive correlation with age at onset and diagnosis of CD (P<0.001). Non-classical CD was significantly more common in children aged >10 yr and in those presenting after 2010 (P<0.01). T1DM and hypothyroidism occurred more frequently in non-compliant children. Interpretation & conclusions: This was the largest single centre study, pertaining to the presentation and follow up of CD in children. Infants and young children were more likely to present with classical symptoms of diarrhoea, abdominal distension and growth failure while older children presented with non-classical CD. There was a trend towards non-classical forms of CD in recent years.

Role of Serology, Dietary Assessment, and Fecal Gluten Immunogenic Peptides for Predicting Histologic Recovery in Children with Celiac Disease.

BACKGROUND: A strict lifelong gluten-free diet (GFD) remains the only treatment of celiac disease (CD). Adherence to gluten-free diet is best reflected by mucosal healing. Noninvasive tools capable of predicting mucosal recovery in CD patients need to be identified. AIMS: To compare the ability of various modalities used to assess compliance to GFD, for predicting persistent mucosal damage in children with CD. METHODS: A prospective, single-center, observational study on children with CD on a GFD was conducted between January 2020 and April 2021. Children with CD on GFD were consecutively enrolled and various modalities used to assess adherence to GFD were compared. RESULTS: One hundred and fifty children (Mean age 12.2 ± 3.6 years, 58% Boys) on GFD (Mean duration 6 ± 3.1 years) were enrolled in the study. Persistent mucosal damage was seen in 88% of the enrolled. Fecal gluten immunogenic peptide (GIP) was positive in 87.8% (129/147). Antibodies to tissue transglutaminase (TGA-IgA) and/or deamidated gliadin peptide (DGP) were positive in 32% (48/150) whereas antibody to synthetic neoepitopes of TGA-IgA was positive in 24.8% (37/149). Non-compliance as assessed by local questionnaire, Biagi score, and dietitian detailed interview were 62.7%, 60%, and 75.3%, respectively. Serology had the highest specificity (83%) and fecal GIP had the highest sensitivity (89%). On logistic regression analysis, only non-compliance by Biagi score predicted poor mucosal recovery. CONCLUSION: Fecal GIP may be sensitive to detect only "one-point dietary transgression." None of the existing modalities used to assess compliance to GFD accurately predict persistent mucosal damage. A subset of patients may develop gluten tolerance.

Treatment of hepatitis C in children and adolescents: how far have we reached?

BACKGROUND: Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. DATA SOURCES: This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. RESULTS: Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. CONCLUSION: The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.

Liver Abscess in Children-experience From a Single Tertiary Care Center of North India: Etiology, Clinical Profile and Predictors of Complications.

BACKGROUND: Liver abscess (LA), a common problem in children in the tropics, is believed to be mostly pyogenic (PLA), sometimes amebic (ALA). We aimed to analyze the clinical profile, etiology, risk factors for complications, management and outcomes of LA in children. METHODS: The details of 81 children with LA managed in a tertiary set up over a period of 3 years were analyzed. A comparison of different parameters was performed with respect to etiology and complications. RESULTS: ALA, PLA and mixed infection LA were diagnosed in 40 (49.4%), 32 (39.5%) and 9 (11.1%) children. The triad of fever, hepatomegaly and right upper quadrant tenderness was seen in 65 (80.2%). Coagulopathy was observed in 60 (77%) and jaundice in 12 (14.8%). Majority (71.6%) had a single LA in the right lobe (69%). Conservative, percutaneous needle aspiration, percutaneous catheter drainage and surgical drainage were done in 11.1%, 3.7%, 82.7% and 2.5%, respectively. Forty-three (53.1%) had complicated LA with rupture in 55.8% and vascular thrombosis in 16.2%. Children with complicated LA had higher alanine transaminase, prolonged prothrombin time/international normalized ratio, low serum protein and albumin levels (P < 0.05). Median duration of follow-up was 2 months and mean time to resolution of LA was 48.5 ± 18 days. CONCLUSIONS: ALA is the commonest cause of pediatric LA in endemic regions and is difficult to differentiate from PLA clinically. Percutaneous catheter drainage is safe and effective modality for the management of LA in children. A higher alanine transaminase, prolonged prothrombin time/international normalized ratio and low serum albumin levels (<3 g/dL) at presentation identify complicated LA.

Pancreatic ascites and Pleural Effusion in Children: Clinical Profile, Management and Outcomes.

BACKGROUND: Pancreatic ascites (PA) and pleural effusion (PPE) are rarely encountered in children. They develop due to disruption of the pancreatic duct (PD) or leakage from an associated pancreatic fluid collection (PFC). The literature on childhood PA/PPE and its management is scarce. METHODS: A retrospective review of children with PA/PPE diagnosed and managed at our center over the last 4 years was performed. The clinical, biochemical, radiological and management profiles were analyzed. Conservative management included nil per oral, octreotide and drainage using either percutaneous catheter or repeated paracentesis. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) and transpapillary stenting. RESULTS: Of the 214 children with pancreatitis, 15 (7%) had PA/PPE. Median age was 9 years with a third under 2 years. Median ascitic fluid amylase was 8840 U/L and all had elevated protein (>2.5 g/dl) and low serum ascites-albumin gradient ascites (<1.1). While PA/PPE was the first manifestation of underlying chronic pancreatitis (CP) in 10 children (67%), trauma was seen in 4 (26%) and hypertriglyceridemia in 1 (7%). On imaging, PD disruption could be identified in 10 (67%) children. ERCP and stenting was done in 10 children. Conservative management alone (n = 4) and endotherapy (n = 10) was successful in 93% with only one requiring surgery. The younger children (n = 4), were managed conservatively and only 1 of them required surgery. Resolution of PA/PPE was achieved in all with no recurrences. CONCLUSIONS: Conservative management and ERCP plus transpapillary stenting results in resolution of majority of pediatric PA/PPE. Children presenting with PA/PPE needs to be evaluated for CP.

Etiological Spectrum of Precocious Puberty: Data from Northwest India.

We retrospectively analyzed clinic records of 55 children (36 girls) with precocious puberty. Majority (34, 62%) had central precocious puberty, out of which 19 were idiopathic. Peripheral precocious puberty was seen in 14 children. Congenital adrenal hyperplasia was the commonest cause of peripheral precocious puberty (6, 42.8%).

An intriguing case of precocious puberty due to an ovarian mass in an infant.

We present a rare occurrence of precocious puberty (PP) probably due to an autonomous ovarian cyst in a 15-month-old girl who presented to us with growth spurt, breast and pubic hair development, and vaginal bleeding over the last few months. The clinical presentation was suggestive of central precocious puberty (CPP). However, the rapid progression of pubertal changes and occurrence of menarche at breast Tanner stage 2 indicated peripheral precocious puberty (PPP). Due to uncertainty of clinical diagnosis, investigations were conducted for CPP as well as PPP. The basal and peak stimulated LH concentrations were < 0.3 IU/l and < 2 IU/l, respectively, indicating PPP. However, the peak LH : FSH ratio was > 1, which is consistent with CPP. Abdominal imaging revealed an ovarian mass, which was laparoscopically excised, but the true nature of the mass could not be ascertained because the excised specimen showed only haemorrhage and features of ovarian torsion on histopathological examination. Regression of pubertal development occurred over a three-month period postoperatively.

Severe Early Onset Obesity due to a Novel Missense Mutation in Exon 3 of the Leptin Gene in an Infant from Northwest India

Monogenic obesity, caused by mutations in one of the genes involved in the control of hunger and satiety, is a rare cause of early onset obesity (EOO). The most common of the single gene alterations affect the leptin gene (LEP), resulting in congenital leptin deficiency that manifests as intense hyperphagia, EOO and severe obesity associated with hormonal and metabolic alterations. Only eight mutations of (LEP associated with congenital leptin deficiency have been described in humans to date. In this study, we report a novel, homozygous, missense mutation in exon 3 of the (LEP gene (chr7:127894610;c.298G>A) resulting in the amino acid substitution of asparagine for aspartic acid at codon 100 (p.Asp100Asn) in a 10-month-old infant who presented to us with severe hyperphagia and EOO. She was subsequently found to have low serum leptin concentrations. Additionally, a homozygous missense variation of unknown significance in exon 11 of Bardet-Biedl syndrome-1 gene (chr11:66291279; G>A; Depth 168x) was detected. Significant abnormalities of lipid parameters were also present in our patient. Both parents were thin but there was a family history suggestive of EOO in a paternal uncle and a cousin. In conclusion, we report the second patient from India with a novel mutation of the (LEP gene associated with severe obesity.