The Teen Who Can’t Swallow–What is it?

What is the most likely diagnosis?  How did you do compared to your colleagues?

       Your Colleagues Responded:
  GERD    28%
  Eosinophilic esophagitis Correct Answer  67%
  Celiac disease    4%
  Irritable bowel syndrome    1%
 

Eosinophilic Esophagitis: Definition, Epidemiology, and Pathophysiology

Clinical Definition–summary only.

  • Eosinophilic esophagitis (EoE) is chronic, inflammatory esophageal clinico-pathological condition. The diagnosis is made following a biopsy confirming ≥ 15 eosinophils(eos)/high-powered field (hpf), at a minimum of at least 2 esophageal levels (eg, distal and proximal) because the process does not uniformly affect one particular area.
  • Clinical symptoms indicative of esophageal dysfunction, such as dysphagia, odynophagia, and vomiting are present. Additionally, patients generally also note reflux often presenting as chest pain and regurgitation. These symptoms are not diagnostic in the absence of a positive biopsy.

    Eosinophilic esophagitis--both endoscopy & biopsy illustrated
  • Gross features found on esophagogastroduodenoscopy (EGD) may include narrowing, ulcers, or furrowing. Additional histologic features may be seen, such as microabscess formation or fibrosis.
  • However, no histologic or gross finding is diagnostic of EoE beyond peak cell count.

Epidemiology

The earliest literature reports of EoE date to the late 1970s, as case reports of GERD patients unresponsive to H2-receptor antagonists who were found to have numerous eosinophils on esophageal biopsies. Recent evidence suggests that EoE has likely been present for decades, but was poorly recognized. When I was a resident & fellow in the early 90’s we diagnosed many children with “functional abdominal pain”.  Wonder how many of those cases were EoE!

Studies in the mid-1990s demonstrated the role that diet and steroids (both systemic and topical) could play in the disease treatment, which provided evidence that allergy had a relevant role in the pathogenesis and fit the observations that many of these patients were atopic (this means allergic!) Some studies have noted that less treatment-responsive patients tend to have either a personal or family history of atopy. However, up to 25% of all known cases are not associated with atopy.

EoE appears to disproportionally affect non-Hispanic, white, atopic males.  The male-to-female ratio is 3:1, and EoE tends to congregate within families, although no true hereditary link has been established. EoE has been reported on every continent to date except Africa, and across all age ranges, although the typical age of onset is the third or fourth decade of life.

Presenting symptoms vary drastically across the ages, and are summarized in the Table.

Table. Presentation of Eosinophilic Esophagitis: Children and Adults

Children: Appear SICK Adults: Appear WELL!
Failure to thrive (5%-19%) Dysphagia (29%-100%)
Vomiting (5%-38%) Food impaction (25%-100%)
Abdominal pain (5%-68%) GERD (7%-100%)
Diarrhea (1%-24%) Chest pain (1-58%)
GERD (5%-82%) Mild eosinophilia (5%-50%)
Chest pain (17%-20%) Delay in diagnosis!
Dysphagia (16%-100%)  
Food impaction (10%-50%)  

With both age groups, a history of eating slowly, taking small bites, excessive drinking after each bite, and avoidance of textured foods is common and represents compensatory mechanisms.

Pathophysiology

EoE is an allergic disease, but it’s not that simple.  In affected esophageal tissue there is upregulation of interleukin (IL)-4, IL-5, and IL-13 expression.  However, both immune globulin E(IgE) and non-IgE (cellular-mediated) mechanisms contribute, as is seen in atopic dermatitis.

This means that sometimes skin testing is helpful and sometimes it is not.  Foods to eliminate with negative skin tests comes down to trial and error.  IL-5 is the main cytokine responsible for eosinophil maturation, bone marrow development, esophageal remodeling, and signals for eotaxin-3, the most crucial eosinophil chemotaxis factor.  IL-5 deficient mice cannot develop EoE, and intratracheal IL-13 induces dose-dependent EoE. In mice, anti-IL-13 blocked development of EoE. IL-13 induces eotaxin-3 production, and may be an independent factor inducing tissue remodeling.  IL-13 is central to an emerging hypothesis of epidermal barrier dysfunction as a mediator of EoE and directly downregulates gene transcription of filaggrin and involrucin.   

Is there a genetic basis for EoE?  Eotaxin-3 SNP’s are present in 14% of cases, and researchers have identified an “EoE Transcriptome” — a unique set of approximately 1% of genes that are overexpressed in EoE. More recently, a genome wide association study identified a disease susceptibility locus at 5q22, and a polymorphism in TSLP (thymic stromal lymphoprotein).  So in short, yes, genetics play a role, but more research is needed.

Ok, enough of the basic science stuff.  Tomorrow I’ll discuss how to evaluate a patient you suspect has EoE.  And how do you spell that again?

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