Villous atrophy and negative celiac serology: a diagnostic and therapeutic dilemma

Am J Gastroenterol. 2013 May;108(5):647-53. doi: 10.1038/ajg.2013.45.


Objectives: Patients with villous atrophy (VA) and negative celiac disease (CD) serologies pose a diagnostic and therapeutic dilemma. When a definitive etiology for VA is not determined, patients are characterized as having unclassified sprue (US), the optimal management of which is unknown.

Methods: We studied adult patients with VA on biopsy and negative celiac serologies, evaluated at our tertiary referral center over a 10-year period. Testing for HLA DQ2/8 alleles, antienterocyte antibodies, giardia stool antigen, bacterial overgrowth, total serum immunoglobulins, and HIV was noted. Treatment, response, and repeat-biopsy findings were recorded.

Results: The most common diagnoses of the 72 patients were seronegative CD, medication-related villous atrophy, and US. Of those with US, the majority reported symptomatic improvement with immunosuppressive therapy. Some patients initially labeled as unclassified were found to have VA associated with olmesartan use.

Conclusions: The role of medications in the development of VA and the optimal dose and length of immunosuppression for patients with US should be investigated further.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Atrophy / etiology
  • Autoantibodies / blood
  • Biopsy
  • Celiac Disease / diagnosis*
  • Celiac Disease / drug therapy
  • Celiac Disease / immunology
  • Databases, Factual
  • Duodenum / drug effects
  • Duodenum / immunology
  • Duodenum / pathology*
  • Female
  • HLA-DQ Antigens / blood
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Immunoglobulins / blood
  • Immunosuppressive Agents / therapeutic use*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tetrazoles / administration & dosage
  • Tetrazoles / adverse effects


  • Angiotensin II Type 1 Receptor Blockers
  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Imidazoles
  • Immunoglobulins
  • Immunosuppressive Agents
  • Tetrazoles
  • olmesartan