Vedolizumab for Refractory Microscopic Colitis, Plus, Vedolizumab and Serious Infections

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LC Shipley et al. Clin Gastroenterol Hepatol 2022; 20: 455-457. Vedolizumab Therapy in Refractory Microscopic Colitis: A Single Center Case Series

In this report, the authors describe nine patients with refractory microscopic colitis (median age 55 years) who were treated with vedolizumab.

Key findings:

  • Clinical response with induction in 9 (100%); time to >50% response ranged from 1 to 7 weeks with 5 patients responding within 2 weeks.
  • Sustained response with maintenance therapy in 6 (67%); duration of follow-up ranged from 1 month to 15 months. The three patients without response had symptom duration of 10 yrs, 12 yrs, and 25 yrs prior to institution of vedolizumab.
  • Only two patients had histologic follow-up. While both had clinical response, the patient with lymphocytic colitis had histologic resolution whereas a patient with collagenous colitis had histologic persistent.

My take: Given vedolizumab’s favorable safety profile, further studies (with endoscopic endpoints) of vedolizumab are needed to define its efficacy for microscopic colitis.

Another study with vedolizumab: J Kirchgesner et al. Clin Gastroenterol Hepatol 2022; 20: 314-324. Risk of Serious Infections With Vedolizumab Versus Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease

Key finding: The risk of serious infections was not different between vedolizumab and anti-TNF in the overall IBD cohort (HR, 0.95; 95% CI, 0·79-1.13), while the risk was decreased for vedolizumab users in patients with UC (HR, 0.68; 95% CI, 0.50-0.93), but not CD (HR, 1.10; 95% CI, 0.87-1.38)

Related blog post/related article:

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.

Food Allergy in Liver Transplant Recipients

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F Mori et al. JPGN 2022; 74: 175-179. De Novo Food Allergy in Pediatric Recipients of Liver Transplant

This interesting review has several key points:

  • Reported prevalence of food allergy after liver transplant ranges from 5% to 40%
  • Younger age at transplantation is a risk factor for developing de novo post-transplant food allergy (dnPTFA)
  • Tacrolimus has been implicated as a risk factor for dnPTFA
  • Common dnPTFA are the same as in the general population: milk, egg, wheat, peanouts/nuts, fish, and soy

Management recommendations:

  • If the donor has a food allergy, the recipient should be tested within the first months of transplant for food-specific IgE and “it is advisable to introduce the suspected food in a controlled setting”
  • Elimination diet is mainstay of treatment. Some individuals may need modification of their immunosuppressive medications
  • Provide self-injectable epinephrine in those with food allergy
  • Monitoring of specific IgE/skin prick tests is advised

My take: There are increased allergy issues in kids who have had liver transplantation.

Related blog post: Lots of Allergy & Autoimmunity Issues Following Solid Organ Transplantation

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.

“Separating Fact from Fiction in the Diagnosis and Management of Food Allergy”

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This great article/commentary is available as open access: Separating Fact from Fiction in the Diagnosis and Management of Food Allergy EM Abrams et al. J Pediatr 2022; 241: 221-228.

Key points:

  • “The risk of fatal anaphylaxis is about 1 in 10 million (about equivalent to being struck by lightning)..and fatality on first ingestion of an allergen in infancy has never been described”
  • Food allergy causes considerable morbidity/worsens quality of life (QOL): bullying, meal preparation, stress, social activities, and school attendance (with 10% choosing home schooling because of a food allergy). Some of this detriment on QOL is due to fear “that accidental exposure could result in fatal anaphylaxis”
  • “The impact of peanut allergy on QoL has been noted to be significantly worse than the impact of other chronic childhood diseases such as rheumatologic disease and type 1 diabetes mellitus”
  • Uriticaria does not equal allergy. “Although urticaria is commonly equated with a food allergy, food allergy accounts for less than 10% of the causes of all acute urticaria and is not a cause of chronic urticaria.” Urticaria can be triggered by an acute infection (most common etiology)
  • “Food proteins are digested within several hours; therefore, urticaria associated with a food ingestion will occur within minutes to 2 hours of ingestion, but typically last no more than a few hours (and less with treatment)” (an exception is meat anaphylaxis owing to galactose-α-1,3-galactose allergy)
  • Other common symptoms that are often incorrectly attributed to food allergy include headaches, chronic behavioral symptoms, or chronic nonspecific abdominal pain
  • Allergy testing: “the presence of a food-specific IgE is not itself indicative of an allergy…Although both skin prick testing and food-specific IgE testing are highly sensitive (>90% for skin prick tests, 70%-90% for sIgE), the specificity and positive predictive values of testing are often very low. The rate of false-positive tests is up to 40%.” 
  • Broad “panel testing” (eg, to a panel of “common” foods), or any food allergy diagnostic testing in the absence of a convincing clinical history has high potential to overdiagnose food allergy and result in unnecessary food avoidances
  • Don’t do IgG testing. “There is no evidence that IgG testing marks food sensitivity; in fact, the presence of IgG is both expected and is a potential indicator of ongoing tolerance”
  • For first-line management anaphylaxis, (intramuscular) epinephrine is the “only life-saving intervention available.” Antihistamines are useful only in the treatment of cutaneous symptoms/urticaria.
  • “Although oral corticosteroids are often administered in the setting of anaphylaxis, there is no convincing evidence that their use prevents a biphasic reaction…their routine use is not recommended” (for anaphylaxis)

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Siesta Beach, FL (2021)

Too Good To Be True: Two Lessons For Eosinophilic Esophagitis

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LE Irastorza et al. JPGN 2022; 74: 267-271. Eosinophil-Derived Neurotoxin Predicts Response to Proton-Pump Inhibitor Treatment in Pediatric Eosinophilic Esophagitis

In this prospective study, the authors compared Eosinophil-Derived Neurotoxin (EDN) levels in pediatric patients with eosinophilic esophagitis (EoE) who responded PPIs (n=15) to those who did not respond to PPIs (n=21). The publication states that EDN levels of 10 mcg/mL or greater are diagnostic for EoE (sensitivity 97%, specificity 89%) but EDN levels have not previously been studied as a marker for PPI responsiveness.

Key finding: EDN concentration was significantly higher in the PPI-nonresponsive group than in the PPI-responsive group (219.1 ± 229 mcg/mL vs 75.7 ± 60 mcg/mL, respectively, P = 0.036).

However, Figures 1 (see below) and 2 show that EDN levels while generally higher in those who did not respond to PPIs are not likely to help much at all in predicting who will respond to PPIs, mainly due to a lot of overlap in the levels. While very elevated levels (above ~300 mcg/mL) all occurred in PPI non-responders, this only accounted for 5 patients out of 36 in the entire cohort.

My take: This article’s title is quite misleading. EDN levels are generally higher in PPI-nonresponders but they do not predict response.

Figure 1

AA Wenzel et al. JPGN 2022; 74: e31-e34. Continued Basal Zone Expansion After Resolution of Eosinophilia in a Child With Eosinophilic Esophagitis on Benralizumab

This case report examined the effect of benralizumab, a monoclonal antibody against the interleukin-5 receptor (IL5Rα) on eosinophils in 20 year old with asthma and EoE. Histology was notable for resolution of esophageal eosinophilia but demonstrated marked basal zone hyperplasia (BZH) in association with high numbers of CD3+ T cells and tryptase+ mast cells. Subsequently, she improved with the institution of dupilumab with resolution of BZH and mast cell inflammation with significant reduction in T cells.

My take: Even with resolution of eosinophilia, mast cells and T cells appear to be capable of coordinating mucosal inflammation and symptoms of EoE (at least in some patients). This study mirrors my limited experience, in which patients receiving benralizumab had a grossly abnormal-appearing esophagus but resolution of the eosinophils.

Related blog posts:

Mitigation Efforts for Button Batteries

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EM Sinclair et al. JPGN 2022; 74: 236-243. This retrospective study (n=63) describes the increased utilization of cross-sectional imaging, adoption of acetic acid irrigations, increased intensive care/hospitalizations after the implementation of consensus institutional guidelines for button battery management (see visual abstract below). An estimate in the increase in costs would have been a good addition to this study.

One of the references (EM Sinclair et al. J Pediatr Surg Case Rep 2021; 66: 101782. doi: 10.1016/j.epsc.2021.101782. Open Access: Development and repair of aorto-esophageal fistula following esophageal button battery impaction: A case report) describes one of the goals of prolonged hospitalization, namely preventing catastrophic bleeding. In this case report, though, the 6 yo had been discharged 12 days after presentation and represented on day 25 with hematemesis from a new aorto-esophageal fistula, requiring emergent cardiac catheterization with successful, life-saving aortic stent placement; “however a multidisciplinary approach to procedure planning is necessary with availability of surgical support for open repair if necessary.” This report has a lot of good images. The discussion notes that the National Capital Poison Center (NCPC) database reports a total 64 deaths in children following button battery ingestion worldwide since 1977; 61% (39/64) of which were due to documented arterio-esophageal fistulae (the actual numbers of deaths is likely much higher). This report also highlights the fact that serial MRIs “may not predict the development of severe complications.”

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Trends in Pediatric IBD Epidemiology & More on Formula Recall

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E Kuenzig et al. Gastroenterology 2022; DOI:https://doi.org/10.1053/j.gastro.2021.12.282. Open Access: Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review

Key finding:  Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence

App Website: The Global Epidemiology of Pediatric Inflammatory Bowel Disease

Yesterday, this blog noted the recall of several formulas (FDA Warns Consumers Not to Use Certain Powdered Infant Formula Produced in Abbott Nutrition’s Facility in Sturgis, Michigan). Our office has made a substitution table for the Abbott formulas:

FDA Warns Consumers Not to Use Certain Powdered Infant Formula Produced in Abbott Nutrition’s Facility in Sturgis, Michigan

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Here’s the link: FDA Warns Consumers Not to Use Certain Powdered Infant Formula Produced in Abbott Nutrition’s Facility in Sturgis, Michigan

2/17/22: Today, the U.S. Food and Drug Administration announced it is investigating consumer complaints of Cronobacter sakazakii and Salmonella Newport infections. All of the cases are reported to have consumed powdered infant formula produced from Abbott Nutrition’s Sturgis, Michigan facility ..The FDA is investigating complaints of four infant illnesses from three states.

The FDA is advising consumers not to use Similac, Alimentum, or EleCare powdered infant formulas if:

  • the first two digits of the code are 22 through 37; and 
  • the code on the container contains K8, SH or Z2; and 
  • the expiration date is 4-1-2022 (APR 2022) or later. 
  • Products that do not contain the information listed above are not impacted. The FDA advisory does not include liquid formula products or any metabolic deficiency nutrition formulas. Consumers should continue to use all products not covered by the advisory. 

AAP News: FDA issues warning for potentially contaminated infant formula

From USAToday: Baby formula recall 2022: FDA warns consumers not to use select Similac, Alimentum and EleCare: “More information is available at Similacrecall.com where you can type in the code on the bottom of the package. You can also call 1-800-986-8540 and follow the instructions provided.”

Ultraprocessed Food and the Risk of Inflammatory Bowel Disease

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N Narula at al. BMJ 2021; 374: n1554. Open Access: Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study

Background: “Processed foods often include many non-natural ingredients and additives such as artificial flavours, sugars, stabilisers, emulsifiers, and preservatives. Detergents and emulsifiers that are added to foods might have a detrimental effect on the gut barrier. Carboxymethylcellulose has been shown to increase bacterial adherence to intestinal epithelium and might lead to bacterial overgrowth and infiltration of bacteria into the spaces between intestinal villi. Polysorbate 80, an emulsifier commonly used in processed foods, increases translocation of bacteria such as Escherichia coli across M cells and Peyer’s patches in people with Crohn’s disease.”

Methods: Using food questionnaires, the authors prospectively followed 116 087 adults aged 35-70 years from 21 low, middle, and high income countries from 2003 to 2016 (median follow-up of 9.7 years).

Key findings:

  • After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD with a hazard ratio of 1.82 for ≥5 servings/day and 1.67 for 1-4 servings/day (compared to <1 serving/day)

Since this is an observational study, this does not prove a causal association between these foods and inflammatory bowel disease. Nevertheless, limiting the consumption of ultraprocessed foods is a good idea as these foods may increase the risk of other health problems as well, including cardiometabolic disease and cancer (Gastroenterol 2022; 162: 652-54). This will be difficult, though, as in the U.S. more than half of calories consumed are from ultraprocessed foods.

My take: This study supports the notion that more fresh foods in our diets is beneficial.

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Artist near Azalea Drive (Chattahoochee River, Atlanta)

Liver Shorts: Biliary Atresia Organoids, AIH Pregnancy Outcomes, ALT Levels in Primary Care, Polyreactive IgG for AIH

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SP Amarachintha et al. Hepatology 2022; 75: 89-103. Open Access: Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia

This is a super cool article documenting a new human model for studying biliary atresia. The authors “generated biliary organoids from liver biopsies of infants with biliary atresia and normal and diseased controls…Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell-cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.”

The authors note that delayed development of cholangiocytes impair barrier function and leave the liver susceptible to various insults which can trigger an inflammatory response with potential progression to obliteration of the bile ducts.

CW Wang et al. Hepatology 2022; 75: 5-12. Open Access: Outcomes of pregnancy in autoimmune hepatitis: A population-based study

Among 18,595,345 pregnancies, 935 (<0.001%) had AIH (60 with cirrhosis) and 120,100 (0.006%) had other CLD (845 with cirrhosis). Key findings:

  • AIH was not associated with postpartum hemorrhage, maternal, or perinatal death
  • AIH was associated with preterm births when compared with women without CLD (OR: 2.0)
  • The odds of gestational diabetes (GDM) and hypertensive complications (pre-eclampsia, eclampsia, or hemolysis, elevated liver enzymes, low platelets) were significantly higher in AIH compared to other CLD (GDM: OR 2.2 and hypertensive complications: OR: 1.8) and also compared to no CLD in pregnancy (GDM: OR: 2.4 and  hypertensive complications: OR: 2.4)

SJ Wu et al. J Pediatr 2022; 240: 280-283. The Prevalence of Elevated Alanine Aminotransferase Levels Meeting Clinical Action Thresholds in Children with Obesity in Primary Care Practice

In this brief report, the authors identified 7.8% of children from a cross-sectional California cohort (n=12,945) with ALT >44 U/L and BMI in the 95% or higher (2012-2014). Males were twice as likely to have elevated ALT. Ethnicity rates were higher in hispanics, asians than white and black children (in males: 12%, 10.4%, 7.3% and 3.1%, respectively)

R Taubert et al. Hepatology 2022; 75: 13-27. Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis

Key findings: Polyreactive IgGs (pIgGs) are a common finding in untreated AIH and have “the highest overall accuracy for the distinction between AIH and non-AIH LD compared to the most common conventional autoantibodies.” In addition, in this study with 1568 adutls, pIgGs were present in “up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non-AIH-LD.”