Study Suggests Villous Atrophy Not Necessarily Definitively Diagnostic

According to a UK study, the majority of patients, particularly non-whites, with seronegative [blood test negative] villous atrophy (SNVA) do not have celiac disease (CD).(Reuters Health)¹

“Physicians commonly cite celiac disease as the cause of SNVA and prescribe a gluten-free diet without further investigations,” said Dr. Imran Aziz, the study’s lead author. “However, the causes of SNVA are vast and we performed the largest prospective study comprehensively overseeing all newcomers with SNVA.”

Over a 15-year period, Dr. Aziz of the Royal Hallamshire Hospital, Sheffield and colleagues studied 200 patients with SNVA and a control group of 343 seropositive CD patients.

As reported September 7 online in Gut,

Only 62 subjects (31%) had seronegative celiac disease (SNCD); the remaining 138 (69%) had seronegative non-celiac disease (SN-non-CD). The human leukocyte antigen (HLA)-DQ2 and/or DQ8 genotype, present in 61%, had a 51% positive predictive value for SNCD.
Identifiable causes in the SN-non-CD group were infections (27%), inflammatory/immune-mediated disorders (17.5%) and drugs (6.5%). Two cases were related to angiotensin-2-receptor-blockers.
However, no cause was found in 36 patients (18%). Moreover, in 26 of these patients, duodenal biopsies had normalized after gluten rechallenge, suggesting transient villous atrophy.
Being non-white was independently associated with SN-non-CD (odds ratio, 10.8). “In fact,” say the investigators “66% of non-whites had GI infections.”

One limitation of the study, the authors allowed, is that subjects carrying the HLA-DQ genotype “may still belong to the spectrum of CD and have simply experienced an unexplained GI insult transiently manifesting as SNVA but having not yet reached the cumulative threshold required for CD to become apparent.”

Summing up, Dr. Aziz added, “We found that most patients with SNVA did not have celiac disease, in particular those of non-white ethnicity. Our findings therefore suggest caution in empirically prescribing a gluten-free diet without diagnostic confirmation. SNVA is increasingly being diagnosed and with the current interest in the wide use of a gluten-free diet it is very important to draw attention to this findings in the UK where the authors provide evidence that the majority of patients with subtotal villous atrophy do not have celiac disease and a gluten-free diet is not necessary.”

Dr. Pena, professor emeritus of gastrointestinal immunology at VU Medical Center in Amsterdam, concluded, “The frequency of the disorders is likely to change in different countries such as in the U.S. and the UK. Therefore other countries will need to assess their own epidemiology.”