Seronegative Villous Atrophy

A recent large retrospective study (R Mandile et al. JPGN 2021; 72: 282-287. Seronegative Villous Atrophy in Children: Clinical and Immunohistochemical Features) provides information about conditions, besides celiac disease (CD) which present with villous atrophy. 64 of 1282 pediatric patients were seronegative with villous atrophy; seronegative was defined as testing negative twice for serology (TTG IgA/EMA or if IgA-deficient, IgG antibody serology).

Key findings:

  • Diagnoses were: inflammatory bowel diseases (IBD) (21/64), food allergy (8/64), infections (7/64, of which 3 HIV infections), immune deficiency (3/64), short bowel syndrome (3/64), congenital diarrhea (2/64), other/inconclusive diagnosis (8/64). In addition, there were 12 with Gastro-Esophageal Reflux Disease (GERD) & the authors speculate that perhaps hyperacidity could play a role in some of these cases.
  • Only one quarter of the seronegative patients had an increased number of intraepithelial lymphocytosis (IELs)
  • Among those with villous atrophy attributed to IBD, this was nearly equally-split between Crohn’s disease and ulcerative colitis, 10 and 11 patients respectively (according to Table 1)
  • The authors note that the ~5% of patients with seronegative villous atrophy with alternative diagnosis than Celiac disease may be an overestimation as more individuals are being diagnosed without biopsy based on serology
  • Despite the large cohort, there are still other rare conditions that were not identified in this study (eg. autoimmune enteropathy, CTLA4B deficiency,drug-induced enteropathy, and tropical sprue)

My take: This article provides a good starting point for patients with villous atrophy and negative serology.

Related article: J Devara et al. JPGN 2021; 72: 288-293. The Significance and Clinical Outcome of Lymphocytic Duodenosis in Children: Mayo Clinic Experience and Systematic Review Background: Lymphocytic duodenosis (LD) defined as increased intraepithelial lymphocytes >25 intraepithelial lymphocytes (IELs) per 100 epithelial cells with normal villous architecture is associated with many gastrointestinal (GI) disorders.

Key findings:

  • During the study period 12,744 children underwent an EGD with biopsies. Of those, we identified 426 children with LD (3%).
  • Among the LD (compared to control group), 5% had celiac disease (vs 0%, P < 0.001), 9% had Crohn disease (3%, P = 0.003) and 3% had Helicobacter pylori gastritis (1%, P = 0.021).

Related blog post: @AmyOxentenkoMD: Celiac Disease and Mimics

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  1. Pingback: Double Whammy: Coexistent IBD and Celiac Disease in Children | gutsandgrowth

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