Three most common causes of infectious esophagitis in children: Candida, HSV and CMV. Asperigillus (& other fungi) as well as bacterial esophagitis are rarely seen. Rare viral infections include human papilloma, varicella zoster and EBV
For Candida, this is typically a benign commensal organism but can become pathogenic due to changes in immunity (immunocompromised including corticosteroids), altered motility and sometimes after antibiotics (with or without PPI therapy). EoE can present with similar-appearing mucosa; thus, biopsy and/or brushing is needed.
With HSV, pediatric case series have reported higher rates in immunocompetent children
Typical treatments: fluconazole for Candida, and Acyclovir for HSV. For CMV, potential treatments include ganciclovir, valganciclovir, foscarnet or cidofovir.
My take: This is a short, good review of the infections that can cause esophagitis in children.
Key findings from this retrospective review (2011-2019):
Of 1801 cases of histologic colitis, 11 patients had CMV found by histology (mean age 15.4, 72.7% female), with an incidence of 0.6%
Nine out of these 11 (81.8%) patients were immunocompromised and 4 (36.4%) had inflammatory bowel disease (IBD) as an underlying diagnosis of whom 2 had new-onset ulcerative colitis
5 of 6 post-transplant patients with CMV colitis had preexisting CMV viremia
An independent analysis of 54 consecutive IBD-associated colectomy cases at TCH showed no histologic evidence of CMV
The study finding that half of the cases of CMV in the IBD population were identified prior to treatment indicates that the underlying IBD may be a more important susceptibility factor than the immunosuppressive medications.
My take: This study indicates that CMV colitis remains important in the post-transplant population but is rarely consequential in the pediatric IBD population.
IBD Updates -January 2017 With regard to CMV and IBD, this study showed “that in most cases the virus is nonpathogenic and thus antiviral is usually ineffective”
Little O’Malley Peak Trail, near Anchorage AK. Denali is visible in background, even though it is ~180 miles away.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
“The study included data from 463 observed vedolizumab concentrations (59 peaks and 404 troughs) from 74 patients with IBD (52 with Crohn’s disease and 22 with ulcerative colitis or unclassified IBD, median age 16 years)…This study was part of the multicentre REFINE study, which aimed to investigate paediatric PK factors among different biological therapies. Both induction and maintenance doses were between 6 and 10 mg/kg for patients less than 30 kg and 300 mg for patients above 30 kg.”
Key findings:
“Using the new model in a simulation analysis of standard vedolizumab infusions (0, 2 and 6 weeks followed by every 8 weeks), we demonstrate that the expected cTrough at week 22 (infusion-5) in the majority of patients would result in drug exposure below current cTrough targets..The dosing simulations in our current study found that receiving standard dosing would lead to <20% of patients achieving a cTrough of 20 μg/ml at infusion-5.”
“The severity of hypoalbuminemia resulted in higher drug CL (lower cTrough) than the inflammatory burden (elevated ESR).”
Infusion-3 cTrough of at least 37 μg/ml and infusion-4 cTrough of at least 20 μg/ml best predicted SFCR (steroid-free clinical remission) at infusion-4. In contrast, we showed inadequate drug exposure during induction (AUCweek 14 of <134,580 μg h/ml) was associated with clinical non-response
My take: This study shows that therapeutic drug monitoring (TDM) is likely to be beneficial in improving outcomes in pediatric patients receiving vedolizumab. Low albumin in particular is associated with increased drug clearance. From this study, it looks like most pediatric patients will need dosing every 4 to 6 weeks to achieve good levels. The authors in their discussion reinforce the utility of TDM to “guide anti-TNF dose optimisations has been shown to improve durability and reduce both immunogenicity and loss of response.”
51 Strik AS, Löwenberg M, Mould DR, Berends SE, Ponsioen CI, van den Brande JMH, et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients: a randomized controlled trial. Scand J Gastroenterol 2021; 56: 145– 154.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Background: NSAIDs are well-known to cause gastrointestinal injury. While single center studies have suggested that NSAIDs are associated with increased IBD flares, a systemic review of 18 studies found no consistent association between NSAIDs and IBD exacerbation.
This study included 15,705 (44.8%) and 19,326 (55.2%) IBD patients with and without an NSAID exposure.
Key findings:
Findings from a Cox proportional hazards model suggest an association between NSAIDs and IBD exacerbation (HR 1.24; 95%CI 1.16-1.33)
However, the likelihood of an IBD exacerbation in the NSAID exposed arm preceding NSAID exposure was similar (HR 1.30; 95%CI 1.21-1.39).
Those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89 – 1.01).
“A self-controlled case series analysis of 3,968 patients who had both an NSAID exposure and IBD exacerbation demonstrated similar exacerbation rates in the 1-year preceding exposure, 2-6 weeks post-exposure, and 6-weeks to 6-months post-exposure, but higher incidence 0-2 weeks post-exposure, suggesting potential confounding by reverse causality.” The self-controlled part of the study allowed patients to serve as their own controls which allowed adjustment for many factors that are difficult to control with retrospective studies.
75% of patients with IBD who were prescribed an NSAID did not have an IBD exacerbation during a mean of 5.9 years of follow-up
NSAIDs were commonly used: 36.5% of patients with IBD had received at least one NSAID prescription
NSAIDs use was prescribed more frequently in patients with immune targeted therapy (likely a marker for moderate to severe disease)
Discussion points:
The estimated prior event ratio of 0.95 suggests that the risk of IBD flares in NSAID-exposed patients preceded the use of NSAIDs. The risk of IBD exacerbation did not increase in the 2 weeks to 6 months after NSAID exposure.
The overall association of increased IBD flare is likely related to reverse causation. Patients may take NSAIDs due to arthropathy or other symptoms that may be an early manifestation of a flare.
My take: This study challenges the prevailing view that NSAID use worsen inflammatory bowel disease; it is more likely that IBD exacerbations are due to underlying risk from more severe disease and residual confounding/reverse causality. The study provides reassurance that short-duration use is likely to be well-tolerated in most patients with IBD.
No Exaggeration: Too Many Children Are Dying in the U.S. “The sad fact is that a child or adolescent in the United States is 57% more likely to die by the age of 19 years than those in other wealthy nations.” This is due mainly to more deaths from MVAs and from gun violence.
Link (12-page) Le Bonheur Dysphagia -Thickeners The algorithms suggest starting with oatmeal and then rice cereal for thickening in infants. Recipes are available for how much cereal is needed for each formula based on desired consistency.
This guide reviews the common thickeners including SimplyThick, Nestle ThickenUp Clear, Hormel: Thick & Easy Clear, Gelmix (see below), Purathick, DysphagiAide, Thick-It, Gerber Rice Cereal, Beechnut Oatmeal Cereal
On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96)
The discussion in this paper makes some important points, as there are some populations in which proactive TDM is more likely to be beneficial.
Pediatrics:
“The impact of proactive TDM in pediatric patients also merits further consideration. This concept may be particularly important in pediatrics due to the variability in size of patients, which may not be adequately addressed by weight-based dosing.33 This is especially important in younger children, where it has been shown that standard TNFα antagonist regimens and trough levels may not be applicable in this age group, and may require more frequent escalation of therapy.34,35 In the PAILOT trial, proactive TDM in children with clinical response to adalimumab was associated with higher rates of maintaining sustained corticosteroid-free clinical remission at all visits from week 8–72, compared with reactive TDM in which physicians were informed of trough concentration only after loss of response.”
Induction Dosing (Adults and Children):
“It is possible that the early measurement of biologic drug concentrations, to identify patients who may have accelerated clearance, and optimization of a subset of these patients early in the course of therapy may offer benefit.1,30 …Ongoing trials such as OPTIMIZE (NCT04835506) and TITRATE (NCT03937609) in which infliximab is optimized during the induction phase through a pharmacokinetic dashboard in patients with Crohn’s disease and acute severe ulcerative colitis will shed further light on this.”
My take: So far, studies in adults have not shown that proactive therapeutic drug monitoring has been effective in improving clinical outcomes. This may change particularly if studies focus on patients on monotherapy who are at increased risk of subtherapeutic levels. No matter what happens in adults, there is sufficient data showing that proactive therapeutic drug monitoring is essential in children. This is especially important as ‘routine” dosing of infliximab in children may be subtherapeutic in nearly 80%.
This article makes a compelling case that most U.S. consumers do not know the true risks of alcohol intake; this is likely in part due to the >$1 billion spent each year on marketing by the alcohol industry.
Leading causes of alcohol-related harms:
Fatal and nonfatal injuries resulting from acute intoxication (including injuries caused by motor vehicle crashes)
Chronic diseases including hypertensive heart disease, cirrhosis, pancreatitis and several types of cancer.2 Even light or moderate drinking increases the risk of these conditions, particularly cancer (eg. breast, colon, and stomach)2
Risks during pregnancy include miscarriage, preterm birth, and fetal alcohol syndrome (these risks are not specifically addressed in this commentary)
Also not noted in this article, alcohol is considered a major contributor to violence, including intimate partner violence
Key points –Scope of Problem and Informing Consumers:
“In April 2022, the Centers for Disease Control and Prevention (CDC) released new mortality statistics showing that alcohol consumption now accounts for more than 140,000 deaths per year in the United States, or more than 380 deaths per day. The Covid-19 pandemic has exacerbated alcohol-associated harm in the United States, with alcohol-related deaths increasing by 25% during the first year of the pandemic as compared with the previous year”(White AM, Castle IP, Powell PA, Hingson RW, Koob GF. Alcohol-related deaths during the Covid-19 pandemic. JAMA 2022;327:1704-1706).
“A national survey of U.S. adults, for example, found that nearly 70% are unaware that alcohol consumption increases the risk of cancer.3…Some alcohol companies even seek to link their products to health campaigns. Several companies, for example, have sold seasonal, pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast-cancer research — despite compelling evidence that alcohol increases the risk of developing breast cancer.”
The authors advocate for better warning labels. They argue that “updated alcohol warnings would provide new risk information to many Americans, … implementing such warnings would be a sensible policy for addressing industry dominance over alcohol-related information, even if warnings’ effects on consumption are fairly small.”
Eric Topol: Paxlovid and Long Covid This in-depth article reviews the benefits of paxlovid (early) and later, including the reduction of Long Covid in 26% in a recent study. It also provides a table for potential drug interactions (Thanks to Jeff Lewis for sharing).
This clinical problem-solving case: “3-year-old boy was brought to the hospital with a 4-day history of vomiting and abdominal pain in the left lower quadrant. He had associated chills without fever, nonbloody and nonbilious emesis, constipation, reduced urinary output, and a decreased activity level.” He developed a rash more than 5 days after presentation.
This turns out to be a good review of IgA Vasculitis (HSP).
A few excerpts:
IgA vasculitis is the most common vasculitis of childhood.1 The disease is classified as a small-vessel vasculitis and most commonly affects White and Asian children, with a slight male predominance. It results from the deposition of IgA immune complexes in involved organ systems and is preceded by infection in most patients.2 This is perhaps unsurprising given the primary function of IgA in mucosal immunity. The most commonly implicated organism is group A β-hemolytic streptococcus.1
IgA vasculitis primarily involves the skin, gastrointestinal tract, joints, and kidneys, with involvement in 95%, 70%, 70 to 90%, and 40 to 50% of cases, respectively, in case series3; other data suggest that kidney involvement is even more common, with microhematuria present in the majority of patients.4 Less common manifestations include orchitis (in 14% of male patients) and, in rare cases, central nervous system involvement.3 Skin involvement is almost universal; a petechial or purpuric rash in dependent areas (typically the buttocks and lower legs) is the classic manifestation, but other skin manifestations, including bullae, edema, and necrosis, can be seen.1,3
IgA vasculitis affecting the gastrointestinal tract can manifest as upper or lower gastrointestinal bleeding. Bowel edema can create a lead point, causing intussusception in up to 3% of patients, as occurred in our patient.1 …In the majority of cases, the rash precedes the onset of gastrointestinal symptoms; our patient was among the minority (approximately 25%) of patients in whom this order is reversed.5 Rare gastrointestinal complications include bowel infarction, perforation, strictures, and protein-losing enteropathy.2,5
I read this article shortly after convincing a surgical colleague to explore a well-appearing 6 month old with gastrointestinal bleeding for a Meckel’s diverticulum rather than undergo endoscopy.
In this retrospective cohort study of hospitalized infants (n=56, =/< 12 months) with gastrointestinal bleeding, the authors reviewed endoscopic procedures (EGD, Colonoscopy, Flexible Sigmoidoscopy) with respect to identifying diagnosis and in terms of outcomes.
Key points:
Seven endoscopies identified sources of GIB: gastric ulcers, a duodenal ulcer, gastric angiodysplasia, esophageal varices, and an anastomotic ulcer.
Intervention for bleeding control occurred in just 3 cases (5.4%); two of these had liver disease.
Most (55%) had no abnormalities on endoscopy
The authors detail two fatal cases in which GIB started in the first week of life. Both had complications occurring within 3 hours of endoscopy, one with a gastric perforation and one with necrotizing enterocolitis.
My take: Endoscopy in infants with GIB is rarely beneficial. Supportive care and surgical interventions should be considered, especially in those without underlying liver disease.
Savage Alpine Trail at Denali National Park. Parts of Denali can be seen in the background
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
