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Two coincident cases of easily curable ‘refractory sprue’
  1. Dietmar Schiller1,
  2. Alexander Ziachehabi1,
  3. Rene Silye2,
  4. Rainer Schöfl1
  1. 1 Department of Internal Medicine IV, Elisabethinen Hospital, Linz, Austria
  2. 2 Institute of Clinical Pathology, Linz General Hospital, Linz, Austria
  1. Correspondence to Dr Dietmar Schiller, Department of Internal Medicine IV, Elisabethinen Hospital, Fadingerstr. 1, Linz 4020, Austria; dietmar.schiller{at}elisabethinen.or.at

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Clinical presentation

On two consecutive days, two women, 82 and 76 years of age, were admitted with severe watery diarrhoea lasting for about 8 months. They presented with serious deconditioning and a weight loss of 16 and 20 kg, respectively. An extensive workup had yielded virtually identical results in both patients and led to the diagnosis of ‘refractory seronegative sprue’. There was no history of foreign travel or previous GI symptoms. Duodenal biopsy showed subtotal villous atrophy (VA) (figure 1) with an increased number of intraepithelial lymphocytes (figure 2). IgA and IgG tissue transglutaminase and endomysial antibodies, serum immunoglobulins, HIV serology, T-cell receptor rearrangement of intestinal lymphocytes, antienterocyte antibodies, colonoscopy with biopsies, video capsule enteroscopy and stool examination for giardia antigen were normal or negative. Human leukocyte antigen (HLA) DQ2+ and DQ8− genotyping was consistent with coeliac disease (CD). A strictly followed gluten-free diet (GFD) and a trial of antibiotics were ineffective, whereas oral budenoside had brought some relief.

Figure 1

Biopsy of the duodenum with partial villous atrophy and crypt hyperplasia.

Figure 2

Biopsy of the duodenum. Immunohistochemistry staining of intraepithelial cluster of differentiation (CD) 3 positive T lymphocytes.

Question

What is the diagnosis?

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See page 1714 for question

Answer

In patients with VA and negative coeliac serology the most frequent diagnosis is seronegative CD.1 It would be unusual for CD, however, to cause a syndrome of severe, unrelenting malabsorption within 8 months in a previously healthy elderly patient despite several hospital admissions and supervised adherence to a GFD.

We therefore considered other causes of VA and were surprised to find that both patients had been taking olmesartan for hypertension at a dose of 40 mg daily for 6 and 4 years, respectively. The complete cessation of diarrhoea within 2 weeks after stopping the drug allowed a diagnosis of olmesartan associated spruelike enteropathy. Follow-up biopsy of the duodenum, carried-out in both patients 8 weeks later, showed complete recovery of VA with a normal count of intraepithelial lymphocytes (figure 3).

Figure 3

Follow-up duodenal biopsy with regular villous and crypt architecture and a normal number of intraepithelial lymphocytes.

Drug-induced enteropathy from medication constitutes the largest group of patients with VA unrelated to CD.1 The angiotensin receptor blocker olmesartan is by far the most frequently implicated drug and has been described in 22 patients from the Mayo Clinic.2 The median weight loss in this series was 18 kg. All patients had negative coeliac antibodies. Numbers of intraepithelial lymphocytes range from <20 to >40/100 enterocytes. The mean duration of exposure to olmesartan before the onset of diarrhoea was 3.1 years. This long delay suggests cell-mediated immunity, the pathogenetic mechanism of which remains to be elucidated. As was observed in our patients, withdrawal of the drug typically leads to a prompt clinical response. Among the other sartans so far only telbisartan and irbesartan have been reported to produce similar side effects.3

Acknowledgments

We are indebted to Dr Nadine Cerf-Bensussan, Intestinal Immunity Laboratory, Paris for providing antienterocyte antibody testing and helpful clinical advice.

References

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Footnotes

  • Correction notice This article has been corrected since it as published online first. DQ8− has been corrected in the sentence ‘Human leukocyte antigen (HLA) DQ2+ and DQ8 genotyping...’

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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