Seronegative villous atrophy is commonly attributed to celiac disease.
However, there are other causes of seronegative villous atrophy.
More recently angiotensin-2-receptor-blockers have been reported as an association but data on seronegative villous atrophy have been limited to centers evaluating complex case referrals, and not seronegative villous atrophy in general.
Dr David Sanders and colleagues from the United Kingdom provide clinical outcomes and associations in a large prospective study overseeing all newcomers with seronegative villous atrophy.
Over a 15-year period, the team evaluated 200 adult patients with seronegative villous atrophy at a UK center.
|Of the 200 seronegative villous atrophy cases, seronegative-non-celiac disease represented 69%|
A diagnosis of either seronegative celiac disease or seronegative non-celiac disease was reached.
The researchers made baseline comparisons between the groups, with 343 seropositive celiac disease subjects serving as controls.
Of the 200 seronegative villous atrophy cases, seronegative celiac disease represented 31% and seronegative-non-celiac disease 69%.
The researchers observed that human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for seronegative-non-celiac disease.
The breakdown of identifiable causes in the seronegative-non-celiac disease group comprized infections, inflammatory/immune-mediated disorders, and drugs.
However, the research team found no cause in 18%, and of these, 72% spontaneously normalized duodenal histology while consuming a gluten-enriched diet.
The researchers observed that an independent factor associated with seronegative-non-celiac disease was non-white ethnicity.
The team noted that 66% of non-whites had GI infections.
On immunohistochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes.
However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in seronegative-non-celiac disease mimicking the changes associated with refractory celiac disease.
Dr Sanders' team concluded, "Most patients with seronegative villous atrophy do not have celiac disease, in particular those who are not white."
"Furthermore, a subgroup with no obvious etiology will show spontaneous histological resolution while consuming gluten."
"These findings suggest caution in empirically prescribing a gluten-free diet without investigation."