Autosomal Recessive Infantile Hyaline Fibromatosis Identified Using Artificial Intelligence-Assisted Rapid Whole Genome Sequencing: A Rare, Multisystemic, Hereditary Disorder.

Infantile hyaline fibromatosis syndrome (HFS) is an ultra-rare genetic condition characterized by the deposition of hyaline material in the skin, muscle, and viscera. Potential complications include debilitating joint contractures, coarse facial features, recurrent infections, failure to thrive, and death. Here, we present the case of a six-month-old infant with a history of painful extremity contractures, global developmental delay, neck hemangioma, and feeding intolerance presenting to our institution with abdominal distension. The multi-systemic, rapidly progressing, severe nature of her symptoms prompted consultation with inpatient pediatric genetics. Per their recommendation, rapid whole-genome sequencing (rWGS) was done with Fabric GEM®-assisted artificial intelligence (Fabric Genomics, Oakland, California, United States) at Rady Children's Hospital Institute for Genomic Medicine (San Diego, California, United States), revealing homozygous pathogenic variant c.652T>C; P.Cys218Arg in the ANTXR2 gene consistent with HFS. This case was significant not only for its rarity, but also its early manifestation of symptoms, wide range of affected body systems, and severity of symptoms, which together present a fascinating diagnostic dilemma for future clinicians that should be taken into consideration. It also highlights the increasing utility of AI-assisted rWGS as a diagnostic tool for medically complex patients with unknown multisystemic hereditary conditions.

Food insecurity screening practices in a pediatric gastroenterology population.

Food insecurity is a rising concern for US households and leads to adverse child health outcomes. Pediatric gastroenterology providers are uniquely equipped to help guide families experiencing this challenge given their specialized training in nutritional support and dietary therapy for disease management. Hence, this study aimed to evaluate food insecurity screening practices from the perspectives of patient caregivers and healthcare providers in a tertiary pediatric gastroenterology practice. A survey was administered to 1279 caregivers and 121 providers. Of the 248 completed caregiver responses, 10%-15% reported being asked about food insecurity. Among the 36 healthcare provider responses, 53% expressed comfort in conducting food insecurity screening but only 14% routinely screened. The most cited barrier to screening was the lack of readily available patient resources. Further research is imperative to address these screening barriers and assess the impact of food insecurity screening and interventions on pediatric gastrointestinal health outcomes.

Sudden-Onset Back Pain and Intermittent Dyspnea While Eating: A Case of Pediatric Achalasia.

A 14-year-old girl with a history of asthma was hospitalized because of sudden-onset back pain around her thoracic region that spread to her chest and abdomen. She had been experiencing dysphagia and breathing difficulties for two years, especially after overeating, which often resulted in vomiting undigested food. CT imaging revealed a severely dilated esophagus narrowing at the gastroesophageal junction, suggestive of type 1 achalasia. Further testing confirmed the diagnosis, with an esophageal manometry showing a lack of esophageal contractions and sphincter relaxation. She then underwent a laparoscopic Heller myotomy with relief to her symptoms. This case underscores the rarity of pediatric-onset achalasia with significant esophageal dilation and secondary airway compression, presenting with unusual musculoskeletal and respiratory symptoms. Timely diagnosis and treatment are crucial to prevent worsening and complications.

Refractory Chronic Constipation in an Adolescent Female Later Diagnosed With Internal Anal Sphincter Achalasia.

Internal anal sphincter achalasia (IASA) is a rare anorectal disorder that presents as chronic refractory constipation in pediatrics. With a poor response to conventional constipation-based therapy, it is often misdiagnosed as other conditions, such as ultra-short-segment Hirschsprung disease. This case report describes a rare case of IASA in an adolescent female, emphasizing the importance of ruling out other differentials, including Hirschsprung disease, via rectal biopsy and thus allowing for earlier targeted therapy to improve lifestyle conditions. A 20-year-old female with a history of IASA presents for semiannual botulism toxin injections. Despite initial relief, her constipation symptoms gradually returned after four to five months. She has had a history of ineffective conventional constipation treatments since childhood, which prompted a further workup. Biopsy results during her teenage years confirmed the presence of ganglionic cells, differentiating IASA from Hirschsprung disease. The management plan involved biannual perianal Botox injections, offering relief for approximately six months. IASA's physiological basis involves altered innervation, the absence of nitrergic nerves, and defective neuromuscular junctions in the internal anal sphincter. Diagnosis requires anorectal manometry and a rectal suction biopsy. Treatment options include botulism, toxin injections, and posterior internal anal sphincter myectomy. Botulism injections offer temporary relief, while myectomy provides long-term improvement.

A Case Report on Fever of Unknown Origin in a 10-Year-Old: Tubercular Liver Abscess.

The liver, which presents as a focal point for tuberculosis in pediatric cases, is rarely encountered, and reported instances are scarce. This atypical manifestation underscores the management of tuberculosis affecting this particular organ in the context of pediatric patients. The treatment of solitary tubercular liver abscesses in children necessitates a collaborative approach, engaging pediatricians, infectious disease specialists, and interventional radiologists. It also needs awareness among physicians to explore and treat early and to complete further assessments for a better outcome. In our instance, investigating the cause of fever led us to diagnose a tubercular liver abscess in a previously healthy 10-year-old male. The substantiation of this diagnosis was accomplished through a meticulous liver biopsy, wherein immunohistochemistry was employed to detect tubercular pathogens. Following the confirmation of the diagnosis, the initiation of a targeted therapeutic regimen resulted in the subsequent resolution of the fever.

Propofol Sedation in Pediatric Upper Endoscopy: A Study of Pharmacodynamics and the Effects of Gastroenterologists, Anesthesiologists, and Supervised Participants on the Procedure Time and Sedation Time.

Background and aims Propofol combined with fentanyl is a commonly used sedative for pediatric upper endoscopies (UEs). The primary aim was to study the association between propofol dose and procedure and sedation time. The secondary aims were to assess the pharmacodynamics of propofol use with fentanyl and evaluate if gastroenterologists' and anesthesiologists' years of experience or the presence of supervised participants (such as students, residents, and fellows) have any influence on the procedure and sedation time. Methods A retrospective study was performed at the Children's Hospital of Michigan on patients under 18 years who underwent UEs with propofol sedation with fentanyl over a two-year period. Results A correlation was found between the propofol amount used expressed per body mass index (BMI)/body surface area (BSA), procedure time, and sedation time (p < 0.0001). Throat pain was the most common post-procedural adverse event (4.48%). The impact of psychoactive drugs on these events was not statistically significant, but attention-deficit/hyperactivity disorder (ADHD) medication use was related to increased post-procedural pain complaints. The use of prescribed psychoactive medications was associated with larger propofol dose usage (p = 0.007) without a significant increase in sedation time. Individual gastroenterologists, their years of experience, and the presence of supervised participants were associated with different procedure times (p <0.0001, <0.0001, 0.01). Fellow participation was associated with a 1.11-minute procedure time increase (p = 0.04). Individual anesthesiologists, their years of experience, and the presence of supervised participants were associated with different sedation times (p <0.0001, <0.0001, 0.01). Conclusion We found a novel correlation between propofol dosing expressed by the BMI/BSA and sedation time. The UE procedure time and sedation time are associated with individual gastroenterologists and anesthesiologists, their years of experience, and the presence of supervised participants.

The Risks of Phosphate Enemas in Toddlers: A Life-Threatening Unawareness.

BACKGROUND: While oral laxatives represent the first-line treatment of fecal impaction, enemas are frequently used in clinical practice in pediatric emergency departments (PEDs) and by family pediatricians (FPs). OBJECTIVES: Phosphate-containing enemas (PcEs) are commonly employed, even causing the risk of rare but lethal toxicity. We investigated pediatricians' awareness of PcE risks. METHODS: We conducted an online survey by sending a multiple-choice questionnaire to the referents of 51 PEDs and 101 FPs. We collected and compared the answers with recommendations reported by the Italian Drug Agency (AIFA) and the available literature about PcE administration. RESULTS: Of the institutions and pediatricians receiving the questionnaire, 23 PEDs (45%) and 63 FP (62.3%) participated in the survey. Of PEDs, 95% and 33.0% of FPs treated fecal impaction with PcE. Moreover, 54% of PEDs and 86.0% of FPs did not provide treatment according to the AIFA recommendations for the daily dose. CONCLUSIONS: This study shows limited pediatricians' awareness of the potential risks related to PcE.

Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.

Combination biologic therapy in pediatric inflammatory bowel disease: Safety and efficacy over a minimum 12-month follow-up period.

OBJECTIVES: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD. METHODS: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ). RESULTS: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission. CONCLUSIONS: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.

The contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in pediatric inflammatory bowel disease.

BACKGROUND: Clinical disease activity associated with inflammatory bowel disease (IBD) can place physical limitations on youths' activities of daily living. In turn, functional limitations potentially contribute to youths' heightened experience of IBD-induced intrusions on a wide range of routine and valued activities (i.e., illness intrusiveness), which can increase their risk for depressive symptoms. The present study examined the contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in youth with IBD. METHODS: Youth (N = 180) completed the Functional Disability Inventory (FDI), Illness Intrusiveness Scale-Child (IIS-C), and Children's Depression Inventory-2 (CDI-2). Physicians completed the Physicians Global Assessment of disease activity (PGA). RESULTS: Results revealed a mediating effect for functional disability in the association between disease activity and depressive symptoms (PGA → FDI → CDI-2); illness intrusiveness mediated the association between functional disability and depressive symptoms (i.e., FDI → IIS-C → CDI-2). Serial mediation revealed that clinical disease activity conferred an indirect effect on youth depressive symptoms through the sequential effects of functional disability and illness intrusiveness (i.e., PGA → FDI → IIS-C → CDI-2). CONCLUSIONS: Taken together, these findings indicate that youth who encounter more physical limitations as a function of clinical disease activity are more likely to experience an amplified sense of IBD-related intrusions on their ability to participate in meaningful activities. In turn, heightened illness intrusiveness increases the likelihood of depressive symptoms. Clinical interventions that help youth maintain adequate functional ability in the face of IBD disease activity and encourage involvement in positively valued activities could decrease the negative impact of IBD on youths' emotional adjustment.

Post-surgical Outcomes of Different Surgical Techniques in Hirschsprung's Disease: A Literature Review.

Hirschsprung's disease (HD) is a rare condition that affects newborns and is characterized by the lack of ganglion cells in the colon. Typical symptoms include difficulty passing stool, vomiting, and trouble feeding. Various surgical methods are available to manage the condition. The aim of the study is to investigate and compare the post-surgical outcomes of different surgical techniques used in the treatment of HD. A thorough literature search was conducted using various electronic databases to identify relevant studies to be referred to. Double-blinded screening of the identified articles led to the final selection of 40 out of 440 HD, including transanal endorectal pull-through (TERPT), laparoscopic approaches, and modified techniques. Several studies have investigated surgical procedures for HD, including TERPT, laparoscopic methods, and modified techniques. These have shown positive outcomes, with fewer complications, improved bowel function, and favorable cosmetic results. Individual patient characteristics and surgeon expertise should guide procedure selection. Surgery for HD aims to restore normal bowel function, but post-surgical outcomes can include constipation or fecal incontinence. Complications like enterocolitis, anastomotic stricture, and sphincter damage may occur. Laparoscopic approaches have shorter hospital stays. However long-term follow-up is essential to assess quality of life, psychological well-being, and potential side effects.

Peeling Back the Layers: Sloughing Esophagitis in a Teenager with Chronic Vomiting.

Esophagitis dissecans superficialis (EsoDS) is a rare condition characterized by the shedding of superficial esophageal epithelium. Limited data exists on EsoDS in the pediatric population. We present a case of a 17-year-old female with chronic nausea and vomiting diagnosed with EsoDS. Endoscopy revealed esophageal mucosal sloughing, and histology confirmed esophagitis with mucosal necrosis. EsoDS is underrecognized, and its association with psychoactive medications remains unclear. Fortunately, EsoDS cases tend to resolve spontaneously without complications. Awareness of EsoDS is essential, and further research is needed to understand its prevalence and outcomes in pediatric patients.

Hypermobility spectrum disorders and irritable bowel syndrome: A nationwide study of 1.6 million adolescents.

BACKGROUND AND AIM: The association between hypermobility spectrum disorders/hypermobile type Ehlers-Danlos syndrome (HDS/hEDS) and irritable bowel syndrome (IBS) is yet to be clarified. We aimed to assess this association in a national sample of adolescents. METHODS: A population-based cross-sectional study included 1 627 345 Israeli adolescents (58% male; mean age 17 years) who were medically assessed before compulsory military service during 1998-2020. Diagnoses of HSD/hEDS and IBS were confirmed by board-certified specialists. The prevalence and odds ratios (ORs) for IBS in adolescents with and without HSD/hEDS were computed. RESULTS: A total of 4686 adolescents (2553 male) with HSD/hEDS were identified, of whom 71 were diagnosed with IBS (prevalence = 1.5%). Of the 1 621 721 adolescents in the control group, 8751 were diagnosed with IBS (prevalence = 0.5%). Unadjusted logistic regression revealed a significant association between HSD/hEDS and IBS (OR = 2.16 [95% confidence interval, CI, 1.90-2.45]), which persisted in multivariable adjusted models (OR = 2.58 [95% CI, 2.02-3.24]), and in several sensitivity analyses. The association was evident in both male and female adolescents with ORs of 2.60 (95% CI, 1.87-3.49), and 2.46 (95% CI, 1.66-3.49), respectively. The association was accentuated in a sensitivity analysis accounting for other medical and psychiatric comorbidities. CONCLUSIONS: We found a significant association between HSD/hEDS and IBS in both male and female adolescents. Clinical awareness of the association can promote early diagnosis of IBS and appropriate multidisciplinary treatment. Further research is required to identify the common pathological pathways of the conditions and to develop new IBS treatment strategies for people with HSD/hEDS.

A Case of Severe Hepatitis in Infant Twins With COVID-19.

We report a case of nine-month-old twins who presented with bright green diarrhea along with progressively worsening jaundice over one week. On initial evaluation, they were found to have significantly elevated liver enzymes, bilirubin, and alkaline phosphatase levels but without signs of liver failure. They were tested for multiple causes of liver injury including autoimmune and infectious etiologies, which were negative as well. Both twins were incidentally found to be positive for COVID-19 on testing per hospital protocol but did not have any respiratory symptoms. They were monitored closely during their hospital stay and showed clinical stability but with only slight improvement in abnormal lab levels. Ultimately, they were discharged with close outpatient follow-up. They demonstrated full resolution of all lab abnormalities and symptoms two months post discharge.

A Systematic Review to Manage Avoidant/Restrictive Food Intake Disorders in Pediatric Gastroenterological Practice.

Avoidant/Restrictive food intake disorder (ARFID) is a feeding disorder characterized by persistent difficulty eating, such as limited choices of preferred foods, avoidance or restriction of certain foods or food groups, and negative emotions related to eating or meals. Although ARFID mainly affects children, it can also occur in adolescents and adults. ARFID can have serious physical and mental health consequences, including stunted growth, nutritional deficiencies, anxiety, and other psychiatric comorbidities. Despite its increasing importance, ARFID is relatively underrecognized and undertreated in clinical practice. Treatment consists of a multidisciplinary approach involving pediatric gastroenterologists, nutritionists, neuropsychiatrists, and psychologists. However, there are several gaps in the therapeutic approach for this condition, mainly due to the lack of interventional trials and the methodological variability of existing studies. Few studies have explored the nutritional management of ARFID, and no standardized guidelines exist to date. We performed a systematic literature review to describe the different nutritional interventions for children and adolescents diagnosed with ARFID and to assess their efficacy and tolerability. We identified seven retrospective cohort studies where patients with various eating and feeding disorders, including ARFID, underwent nutritional rehabilitation in hospital settings. In all studies, similar outcomes emerged in terms of efficacy and tolerability. According to our findings, the oral route should be the preferred way to start the refeeding protocol, and the enteral route should be generally considered a last resort for non-compliant patients or in cases of clinical instability. The initial caloric intake may be adapted to the initial nutritional status, but more aggressive refeeding regimens appear to be well tolerated and not associated with an increased risk of clinical refeeding syndrome (RS). In severely malnourished patients, however, phosphorus or magnesium supplementation may be considered to prevent the risk of electrolyte imbalance, or RS.

Acute Recurrent Pancreatitis in a Pediatric Patient in the Setting of Viral Infection and COVID-19 Vaccination.

Acute pancreatitis within pediatric populations is predominately caused by mechanical obstruction, trauma, medications, and infections. We present a case of an adolescent female without any known anatomic or metabolic pre-disposition, developing recurrent acute pancreatitis that is seemingly related to acute viral infection and COVID-19 vaccination.

Coeliac Disease Case-Control Study: Has the Time Come to Explore beyond Patients at Risk?

The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

The Influence of SARS-CoV-2 Pandemic on the Diagnosis of Celiac Disease and Clinical Practice in Pediatric Gastroenterology.

Celiac disease (CD) has a high prevalence but remains largely underdiagnosed. Although extensive studies have confirmed that children with CD do not have an increased risk of severe COVID-19, public health regulations associated with the SARS-CoV-2 pandemic may have exacerbated this problem. The aim of this study was to assess the effect of SARS-CoV-2 on the number of new-onset CD cases. Additionally, the role of SARS-CoV-2 in autoimmune diseases and its influence on clinical practice in pediatric gastroenterology were briefly reviewed. We described the data from the hospital electronic registry of new-onset CD, during the COVID-19 pandemic and 2 years before. A total of 423 children were diagnosed with CD between March 2018 and February 2022: 228 in the 2-year pre-COVID-19 period and 195 during the pandemic. The number of patients during the COVID-19 pandemic was 14.5% lower than in the previous years. The quarterly comparison of CD diagnoses showed a reduction in all quarters. A reduction in diagnoses during the lockdown and in the following months was evident and not compensated thereafter. This is the first study to evaluate the impact of SARS-CoV-2 on the diagnosis of CD in children. Further studies are necessary to improve the system of biopsy-sparing diagnosis and to evaluate the effect of the diagnostic delay. Special attention should be given to the implementation of telemedicine services.

Development of Very-Early-Onset Inflammatory Bowel Disease After Multiple Early-Life Antibiotic Exposures: A Case Report and Literature Review.

The use of antibiotics has increased drastically over the last few decades. Many antibiotics can target the commensal microbiota and promote gut dysbiosis. These alterations contribute to disease onset and exacerbation. Although the etiology of inflammatory bowel disease (IBD) is mostly unknown, it involves a complex interaction among host genetics, microbiota, environmental factors, and aberrant immune responses. Studies have shown a relationship between very-early-onset inflammatory bowel disease (VEO-IBD) and microbiota alterations. The case discussed in this report endorses the current clinical evidence for this interaction. This is an anonymous record review with no identifiers involving a 23-month-old female patient who was brought to the emergency department by her parents due to persistent bloody diarrhea. Eight days before the presentation, she had experienced watery diarrhea that progressed to bloody stools. The patient had a history of acute otitis media, acute enteritis, and right-arm cutaneous abscess, for which she had received multiple antibiotic therapies. Strategies to manipulate the microbiome through diet, probiotics, antibiotics, or fecal microbiota transplantation (FMT) may be used therapeutically to modulate disease activity. A high index of clinical suspicion for VEO-IBD should be maintained for patients with a history of multiple, recurrent antibiotic use. We believe this case report will raise awareness about the issue of early anaerobic antibiotic exposure and help prevent its unnecessary use and, consequently, prevent gut microbiota dysbiosis that can lead to VEO-IBD. Also, our literature review will hopefully prompt clinicians to consider alternative therapeutic options for this patient population, such as rebuilding intestinal microbiota composition to improve VEO-IBD activity.