“The I-SEE has three domains: (1) symptoms and complications, (2) inﬂammatory features and (3) ﬁbrostenotic.
I-SEE can be used at initial diagnosis and then at each subsequent visit, with the recall being only between visits so that the severity can be assessed over time and ultimately (when data supports this step) treatment and monitoring adjusted based on severity.
As the number of children and adults with EoE increases worldwide, a simple system to assess and track disease activity in a meaningful way in a clinical setting is needed.
I-SEE is for use in adult and pediatric patients with EoE. It was created by an international team of more than 30 experts in allergy, gastroenterology and pathology.”
GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis—an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD.
Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases.
In this multicenter, retrospective study with 82 participants (mean age 37 years), the authors examined swallowed topical corticosteroids (STC) for maintenance of histologic remission (<15 eos/hpf). Low dose STC (22 budesonide, 60 fluticasone) was considered 0.5 mg/day or less. Key findings:
Histological relapse occurred in 67% of patients. This rate was comparable in patients treated with low-dose (72%) and high-dose (54%) STCs.
Histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030)
Esophageal candidiasis was identified in 6% of subjects
The authors conclude that most of the histological relapse that occurred was due to true steroid failure since “low adherence and treatment cessation during follow-up were exclusion criteria.” Also, they note that “the recently finished but not yet fully published Maintenance of Remission With Budesonide Orodispersible Tablets vs Placebo in Eosinophilic Eosphagitis (EOS2 trial) (NCT02493335) comparing budesonide maintenance doses of 2 mg/d vs 1 mg/d suggest that there is no additional benefit of daily doses higher than 1 mg (1-year remission rates of 75.0% and 73.5%, respectively).
My take: Low dose STCs do not appear to be as effective in maintaining histologic remission; however, there is a high rate of relapse even in those with higher doses.
Researchers (first author Tetsuo Shodaand senior author Marc Rothenberg) at “Cincinnati Children’s have identified two rare gene variants associated with inherited forms of eosinophilic esophagitis (EoE) that may also play roles as acquired mutations among the larger population of people with non-familial EoE.”
Citation of article: Shoda, T., Kaufman, K.M., Wen, T. et al. Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis. Nat Commun12, 6795 (2021). https://doi.org/10.1038/s41467-021-26939-9
Methods: Using whole-genome sequencing, the researchers discovered the variants among five members of a family that had multiple generations of members with EoE. The team tested another 61 families with familial EoE and found 13 having either the DSP or PPL variants.
The authors “estimate that these gene variants account for about 21% of patients with familial EoE”
“A series of functional analyses using an organotypic-like ALI culture system demonstrated that modulating wild-type DSP and PPL expression in vitro was functionally sufficient to induce changes in epithelial integrity (e.g., acantholysis) and barrier impairment, processes that are dysregulated in EoE”
“DSP and PPL loss occurs in non-familial EoE, substantiating that the pathway identified initially by rare familial EoE cases is broadly applicable to familial and non-familial EoE”
This article provides data showing that genetic alterations affecting the epithelial barrier are important in the pathophysiology of EoE.
Often EoE is compared to eczema. This finding of altered epithelial barrier is analogous to eczema where many cases are due to a mutation in a protein called filaggrin, which is important in reducing the gap between skin cells (related blog: Eczema Rarely Linked to Food Allergy).
Taft et al performed a retrospective study of 103 adult patients with eosinophilic esophagitis. Patients completed the following questionnaires immediately before to endoscopy:
Esophageal Hypervigilance and Anxiety Scale (EHAS)
Brief Esophageal Dysphagia Questionnaire (BEDQ)
Eosinophilic Esophagitis Symptom Activity Index (EEsAI)
Northwestern Esophageal Quality of Life Scale (NEQOL).
Endoscopic severity of EoE was graded using the EoE Endoscopic Reference Score System (EREFS). Dysphagia was the primary symptom in 73% of the patients.
Patient’s symptom severity (via EEsAI or BEDQ) did not correlate with histology (distal or proximal peak eosinophil count), endoscopic severity of the disease (EREFS), or the distensibility index (measured via functional lumen imaging probe)
Symptom severity was correlated with the Esophageal Hypervigilance and Anxiety Scale (EHAS)
There was no correlation between EHAS and histologic activity, endoscopic severity (EREFS), or the presence of a stricture
The associated commentary emphasizes some of the study limitations including taking surveys prior to endoscopy (increased anxiety).
My take: This study indicates that with eosinophilic esophagitis, similar to other organic diseases (eg. IBD), patient symptoms do not always correlate with disease severity, and addressing the impact of anxiety and hypervigilance is critical, especially in refractory symptoms.
In this study with 109 adults who were newly diagnosed with eosinophilic esophagitis (EoE), the authors consecutively performed high-resolution manometry (HRM). Key findings:
68 (62%) had normal findings from HRM
8 (7.3%) had achalasia (1 with type 1, 4 with type 2, and 3 with type 3)
9 (8.3%) had major motor disorders of esophagus (& not achalasia) and 24 (15.6%) had minor motor disorders
These findings are important because the diagnosis of EoE could result in a diagnostic delay of concurring achalasia and because the presence of esophageal eosinophilia could perhaps play a role in the pathogenesis of achalasia (or vice versa). The finding of achalasia in 7.3% of this population is exponentially higher than the estimated prevalence of achalasia in the general population (10-16 cases per 100,000).
My take: In patients with EoE, further diagnostic workup is indicated if there are persistent symptoms.
Topical steroids were most effective in inducing histologic remission: 54.8% compared to 36.1% for PPIs and 18.5% for empiric elimination diet; histologic remission and response was 67.7%, 49.7%, and 48.1% respectively.
Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%).
However, PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%).
My take: This data (and others) indicate that topical steroids are most effective pharmacologic therapy; at some point, I expect that they will become the most frequently used.
“Layering two less specialized masks on top of each other can provide comparable protection [to N95]. Dr. Marr recommended wearing face-hugging cloth masks over surgical masks, which tend to be made with more filter-friendly materials but fit more loosely. An alternative is to wear a cloth mask with a pocket that can be stuffed with filter material, like the kind found in vacuum bags.”
Methods: Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given budesonide orodispersible tablet (BOT) 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks
At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo)
Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment
In the discussion, the authors state that “we recommend monitoring symptoms and signs of adrenal insufficiency when administrating topical-acting corticosteroids over prolonged time periods, in particular in children and when using higher dosages.”
My take (from discussion): “EoE requires a proper long-term anti-inflammatory therapy because, without active treatment, the vast majority of patients experience a relapse within the first 100 days after cessation of the medication.”