Mucosal Eosinophilia –A Marker for Nonceliac Wheat Sensitivity?

A recent prospective study (A Carrocio et al. Gastroenterol 2019; 17: 682-90) with 78 patients who were diagnosed with “nonceliac gluten or wheat sensitivity” (NCGWS) by double-blind challenge had duodenal and rectal biopsies collected and analyzed. More commonly NCGWS is referred to as NCGS.

Key findings:

  • Duodenal tissues from patients with NCGWS had hihger numbers of eosinophils than non-NCGWS controls as did rectal mucosa.  Other elevated markers included epithelial CD3+ T cells, and lamina proppria CD45+ cells.
  • Rectal mean eosinophil infiltrations was more than 2.5-fold the upper limit of normal and it was almost 2-fold increased in the duodenum.
  • Sensitivity and specificity of rectal eosionphilia, defined by >9 eos in the lamina propria) was 94% and 70% respectively.

My take: This study is intriguing but needs more confirmation. Overall, it appears that the frequency of NCGS is very low.

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Synagogue of Santa María la Blanca. Toledo Spain

Is Autoimmunity Associated with Nonceliac Wheat Sensitivity?

According to a recent study (A Carroccio, et al. Gastroenterol 2015; 149: 596-603), patients with nonceliac wheat sensitivity (NCWS) (aka. nonceliac gluten sensitivity or wheat intolerance syndrome) are more prone to developing autoimmune disorders compared with patients with irritable bowel syndrome.

Given the difficulty identifying NCWS, the findings must be viewed cautiously; in addition, much of this study was a retrospective study.

Background: The authors identified 131 patients diagnosed with NCWS (121 female) with a mean age of 29 years.  They compared these individuals to control groups of patients with either celiac disease (CD) or irritable bowel syndrome (IBS).  In addition to the retrospective study, the authors prospectively examined 42 patients diagnosed with NCWS (2011-2014).  These diagnoses were established by double-blind placebo-controlled wheat challenge.

Key findings:

  • In the retrospective analysis, 29% of NCWS patients and 29% of CD developed autoimmune diseases (mainly Hashimoto’s thyroiditis, 29 cases) compared with a smaller proportion of subjects with IBS (4%) (P<.001).
  • In the retrospective analysis, 46% of NCWS, 24% of CD and 2% of IBS developed ANA antibodies (median titer 1:80).
  • In the prospective arm, 24% of NCWS, 20% of CD, and 2% of IBS subjects developed autoimmune disease.
  • Similarly, in the prospective arm,  28% of NCWS, 7.5% of CD and 6% of U+IBS developed ANA antibodies (median titer 1:80).
  • ANA positivity was associated with the presence of HLA DQ2/DQ8 haplotypes (P<.001).  ANA positivity, to a lesser extent, was associated with the presence of duodenal lymphocytosis (grade A histology).

The authors note that “these associations strongly suggest a celiac condition, but it must be emphasized that all the patients we included were negative for CD-specific antibodies and showed normal intestinal villi” with a gluten challenge.

Potential limitations included a selection bias of patients referred to this tertiary center.

My take: This study suggests significant overlap between CD and NCWS.  The real frequency of autoimmunity in NCWS is unclear as this study population is not likely representative of most patients who go gluten-free.

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Atlanta Botanical Gardens

Atlanta Botanical Gardens