Olmesartan causing prominent diarrhea and malabsorption
Janssen, J.J.B., Nijeboer, P., Mulder, C.J.J.
Voorzitter(s): mw. prof.dr. M.M.E. Schneider, Utrecht & dr. W.G. Meijer, Hoorn
Locatie(s): Zaal 0.11
Categorie(ën):
Introduction: Diarrhea is a frequently reported complaint and has a broad differential diagnosis. The differential diagnosis of diarrhea in combination with villous atrophy is much narrower and mainly includes coeliac disease. Here we present an olmesartan induced enteropathy.
Case description: A 63-year-old man, with a history of hypertension and paroxysmal atrial fibrillation presented with recurring symptoms of severe diarrhea (7,5-10 liters a day), acute renal failure (creatinine 692 umol/L and a GFR 7 ml/min/1) and a metabolic acidosis (pH 7.19, PCO2 1,9kpa, PO2 14kpa, Bic 5,1mmol/l) which required several hospitalizations. Psychical examination showed no diagnostic clues, only signs of dehydration. Differential diagnosis included infectious diseases (viral, bacterial and parasitic) and inflammatory diseases (M. Crohn, colitis ulcerosa and coeliac disease). Stool cultures were repeatedly negative, ultrasound showed no thickened bowel wall and coloscopy only atypical redness of the flexura lienanis, with a chronic aspecific inflammation, without signs of an inflammatory bowel disease after pathological examination. Gastroscopy showed a radially antrumgastritis and a mild duodenitis. Pathological work-up revealed a total villous atrophy (Marsh IIIC), but no other deviations (no tropheryma whipplei, giardia lamblia, collagenic enteritis or TBC). Coeliac serology was repeatedly negative, with a HLA-DQ2 haplotype. MRI-enteroclyse showed no deviations, especially no signs of lymphoma. Because of the possibility of seronegative coeliac disease, a gluten free diet was started. This did not have any effect on the episodes of severe diarrhea. Antihypertensive medications were temporarily discontinued at every admission, and restarted at discharge because of ascending blood pressures. This in combination met recent literature eventually raised the suspicion of an association between the severe enteropathy and the anti-hypertensivum olmesartan. And indeed, permanent withdrawal of olmesartan resulted in a total and persistent clinical response.
Discussion: Olmesartan is a selective type I angiotensin-II-receptor-antagonist and procurable in the Netherlands since 2008. Recent American and German literature describes case series of similar patients with olmesartan-associated enteropathy, even after months to years of usage. Since this side effect is reported more often, other causes of villous atrophy were excluded and the symptoms disappeared after discontinuation and reappeared after restarting olmesartan, we consider this, according to the Naranjo causality scale, as a probable ‘adverse drug event’. The pathophysiological mechanism underlying olmesartan-associated enteropathy is still unknown, although cell-mediated immunity is suspected to play a role. Since olmesartan is increasingly prescribed in the Netherlands, it should be considered as a cause for diarrhea. Treatment consists of discontinuation of the olmestartan.