olmesartan is an angiotensin ii receptor blocker ( arb ) that was approved as an antihypertensive agent in 2002 in the united states and in 2004 in japan . olmesartan - induced enteropathy was first reported by rubio - tapia et al . in 2012 it is a condition in which the patient presents with the chief complaints of severe chronic diarrhea and weight loss , and duodenal biopsy specimens show villous atrophy with inflammation on histopathological examination . although olmesartan - induced enteropathy shares a similar pathology with celiac disease , the serology of celiac disease was negative and a gluten - free diet was found to be ineffective ( 1 ) . enteropathy as an adverse effect of olmesartan and other arbs such as irbesartan ( 2 cases ) ( 2 , 3 ) , valsartan ( 4 ) , telmisartan ( 3 ) , and eprosartan ( 5 ) , have sporadically been reported since then , and their most prominent and characteristic manifestation is severe diarrhea . we herein report the first case of olmesartan - induced enteropathy causing wernicke encephalopathy with only minimally increased bowel movements , in which the diagnosis was therefore challenging . a 76-year - old japanese man had experienced a decreased appetite , nausea , and abdominal distension since late february 2011 . the results of blood tests performed by the primary care physician ( pcp ) between april and june were all normal , but upper and lower gastrointestinal endoscopy showed atrophic gastritis . therefore , we assessed the patient for helicobacter pylori antibodies and performed the rapid urease test and a histopathological evaluation , all of which were negative . in june , the patient received medication from a mental health clinic , but because the symptoms did not improve and his body weight further decreased by 23 kg , he stopped the medication ; he was referred to our department in november . amlodipine ( 5 mg / day ) administration was initiated in 2005 , and olmesartan from may 2008 ; the patient is currently receiving 30 mg / day of olmesartan . he denied the use of any other new medications or nonsteroidal anti - inflammatory drugs . physical examination showed that the patient had a height of 165 cm , a body weight of 47 kg , and body mass index of 17 kg / m . his body temperature was 36.3 ; pulse rate , 101/min ; blood pressure , 101/81 mmhg ; respiratory rate , 12 breaths / min ; and saturation from pulse oximetry ( spo2 ) was 98% . the patient had bilateral pitting edema on his lower legs and presented with unilateral gaze - evoked nystagmus as well as a mildly reduced tactile sensation and thermal nociception in the toes and dorsal regions of both feet . moreover , the finger - to - nose test results and tandem gait were poor , and his patellar and achilles tendon reflexes had disappeared . confabulation was observed in the patient , and the revised hasegawa dementia scale ( hds - r ) score was 17/30 ( cut - off point : 20 ) . the hematologic findings were as follows : white blood cell count , 6,200 /l ; hemoglobin level , 12.5 g / dl ; mean corpuscular volume , 88.4 ; platelet count , 230,000 /l ; sodium level , 136 meq / l ; potassium level , 3.8 meq / l ; chlorine level , 103 meq / l ; iron level , 57 g / dl ( reference value : 64 - 187 g / dl ) ; ferritin level , 366 ng / ml ( reference value : 50 - 200 ng / ml ) ; b - type natriuretic peptide ( bnp ) level , 125.3 pg / ml ( reference value : -18.4 pg / ml ) ; and vitamin b1 level , 8 ng / ml ( reference value : 24 - 66 ng / ml ) . an electrocardiogram was normal and chest x - rays showed a normal cardiothoracic ratio ( 40.8% ) without either pulmonary congestion or pleural effusion . cranial fluid - attenuated inversion recovery - magnetic resonance imaging findings revealed periaqueductal hyperintensities ( fig . 1 ) ; therefore , wernicke encephalopathy was diagnosed . moreover , as sinus tachycardia and a tendency towards hypotension were noted , no clear symptoms of heart failure or dehydration were observed ; it was thus inferred that the vitamin b1 deficiency had likely played a role in both of the conditions . the antihypertensive agents were discontinued , and 10 days after the intravenous administration of vitamin b1 , the patient 's loss of appetite , nausea , and gait disturbance disappeared , and his body weight increased by 3 kg . nystagmus was ameliorated on physical examination , but the patient still had confabulations , and the hds - r score and absence of deep tendon reflexes did not improve . cranial fluid - attenuated inversion recovery - magnetic resonance imaging shows periaqueductal hyperintensities . 
  since the gastrointestinal symptoms were ameliorated and his blood pressure increased to 160/90 mmhg , the pcp resumed the administration of olmesartan on late december , 2011 . one week later , the patient complained of recurrent decreased appetite and nausea . after experiencing diarrhea ( five bowel movements during a 2-day period ) , he passed soft stools once daily , and his body weight decreased to 47 kg so he came to our hospital again 3 weeks after the resumption of olmesartan for treatment . his vital signs were as follows : body temperature , 35.1 ; pulse rate , 93/min ; and blood pressure , 132/75 mmhg . the laboratory findings were as follows : sodium level , 139 meq / l ; potassium level , 2.9 meq / l ; and chlorine level , 116 meq / l . hyperchloremia was noted , and the serum sodium level minus chloride level ( 139 - 116 ) was 23 meq / l ; additionally , the arterial blood gas findings were as follows : ph , 7.25 ; pco2 , 25 mmhg , and hco3 , 11 mmol / l . the urinalysis findings were as follows : sodium level , 15 meq / l ; potassium level , 13 meq / l ; chlorine level , 100 meq / l ; and urine anion gap , -72 meq / l , and there was no apparent increase in bowel movements ; however , this seemed to be due to the absence of hco3 from the gastrointestinal tract ( 6 ) . plain abdominal radiography and abdominal computed tomography findings revealed the continuous dilation of the entire intestinal tract ( fig . 2 ) ; therefore , the patient was diagnosed with intestinal pseudo - obstruction . after discontinuing olmesartan , duodenal biopsy findings after discontinuing olmesartan showed that the inflammation observed before discontinuation as well as the fold structure had both clearly ameliorated ( fig . 3 ) . 
 plain abdominal radiography and abdominal computed tomography show continuous dilation of the entire intestinal tract . ( a ) villous atrophy with a flattening and widening of villi , and increased number of intraepithelial lymphocytes . this was the first case of olmesartan - induced enteropathy manifesting as wernicke - korsakoff syndrome with recurrent nonspecific chronic gastrointestinal symptoms . however , in cases of olmesartan - induced enteropathy , the symptom onset was months to years after the initiation of olmesartan , and therefore the diagnosis in this case was challenging . moreover it was uncommon that the patient had only mimimally increased bowel movements , not severe diarrhea as previously reported . nonetheless the measurement of the urine anion gap indicated malabsorption syndrome , which was thought to have been caused by intestinal pseudo - obstruction without producing severe diarrhea . intestinal pseudo - obstruction has also been reported in celiac disease ( 7 ) , and in addition to malnutrition and anorexia due to enteropathy in this case , intestinal pseudo - obstruction led to bacterial overgrowth thus causing the vitamin b1 deficiency ( 8) . additionally , the ferritin levels were observed to have increased in our patient and this may be a difference in comparison to celiac disease in which the ferritin levels decrease ( 9 ) . from the point of view of drug - induced enteropathy , the crude incidence rate for intestinal malabsorption associated with angiotensin - converting enzyme ( ace ) inhibitors ( aceis ) , olmesartan , and other arbs has been reported to be 2.4 per 100,000 person years ( py ) , 5.6 per 100,000 py and 1.8 per 100,000 py , respectively . olmesartan was associated with an adjusted rate ratio of 2.49 ( 95% confidence interval ( ci ) 1.72 to 3.57 , p<0.0001 ) of hospitalization with a discharge diagnosis of intestinal malabsorption compared with acei and a rate ratio of 3.17 ( 95% ci 2.22 to 4.53 , p<0.0001 ) compared with other arbs . therefore , basson et al . said that olmesartan exposure is associated with an increased risk of hospitalization for intestinal malabsorption and coeliac disease based on an observational cohort study ( 10 ) . sprue - like enteropathy associated with arbs other than olmesartan have been reported ( 2 - 5 ) , so if such a patient is prescribed some kind of arbs , it is important for general physicians to consider drug - induced enteropathy . we should also pay close attention to other drugs that can cause enteropathy , such as non - steroidal anti - inflammatory drugs , antibiotics , laxatives , vasoconstrictive agents , corticosteroids , chemotherapy agents and so on . unfortunately , in the present patient confabulation remained despite treatment with thiamine for 6 months . therefore , when patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms , such as a decreased appetite or a decreased body weight , it is important to consider changing the drugs before serious malabsorption syndrome develops .
cases of sprue - like enteropathy associated with olmesartan have sporadically been encountered since it was first reported in 2012 , and their most characteristic manifestation is severe diarrhea . 
 we herein report the first case of sprue - like enteropathy manifesting as wernicke - korsakoff syndrome due to vitamin b1 malabsorption with only minimally increased bowel movements . when patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms , it is important to consider changing the drugs before any serious malabsorption syndrome develops .