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Idiopathic Bile Acid Malabsorption a Review of Clinical Presentation

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Idiopathic Bile Acid Malabsorption a Review of Clinical Presentation 1004 Gut, 1991, 32, 1004-1006 Idiopathic bile acid malabsorption a review of clinical presentation, diagnosis, Gut: first published as 10.1136/gut.32.9.1004 on 1 September 1991. Downloaded from and response to treatment A J K Williams, M V Merrick, M A Eastwood Abstract ment of faecal bile acid excretion, but is much Between 1982 and 1989, the seven day reten- simpler to perform.I' 12 We have reviewed a total tion of 75SeHCAT was measured in 181 of 500 patients with diarrhoea investigated with patients with chronic diarrhoea that remained the 75SeHCAT test since 1982 in order to deter- unexplained after full investigation. Altogether mine its impact on the management ofindividual 121 of the 181 had a seven day 75SeHCAT patients when used as a routine clinical investiga- retention ¢15% and thus had no evidence of tion rather than a research one. abnormal bile acid turnover. Twenty one had a This study considers 181 of the 500 investi- seven day 75SeHCAT retention : 10% but gated because ofidiopathic diarrhoea - the group <15%. Their clinical features were typical of in whom no cause had been found after extensive the irritable bowel syndrome, and none ofeight investigation. treated with cholestyramine showed sympto- SeHCAT is the taurine conjugate of a synthe- matic improvement. Sixteen patients had a tic cholic acid analogue.'3 It is absorbed and seven day retention ¢"5% and <10%, six of excreted at the same rate as cholic acid'4 but is whom had improved symptoms after treatment resistant to deconjugation and dehydroxylation.6 with bile acid chelating agents. The remaining Because there is effectively no passive diffusion 23 patients had a 75SeHCAT retention of <5% of this compound, it is a pure tracer for active at seven days and responded to bile acid transport. chelators. This group had a characteristic 75SeHCAT has been shown to be a simple and illness with intermittent watery diarrhoea, but reliable method of assessing bile acid no constitutional upset. It was not possible to absorption." 12 15 The aim of the present study distinguish the patients with bile acid mal- was to determine the clinical characteristics of absorption exclusively on the basis of the patients with idiopathic bile acid malabsorption clinical symptoms and investigations, other and to identify their response to treatment. http://gut.bmj.com/ than "SeHCAT retention. We conclude that the measurement of 75SeHCAT retention is useful, appropriate, and necessary in patients Patients and methods with unexplained chronic diarrhoea. All patients referred for measurement of 75SeHCAT retention were entered prospectively into a departmental data base which recorded the Although bile acids are absorbed both actively a priori diagnosis and relevant diagnostic infor- on October 1, 2021 by guest. Protected copyright. and passively, symptomatic bile acid malabsorp- mation. This was scanned in mid-1989, and 181 tion results from failure of the active transport of patients were identified who had been referred bile acids in the terminal one metre of the ileum. during this period because of unexplained Three types ofbile acid malabsorption are recog- diarrhoea. Patients with inflammatory bowel nised as follows:24 disease who had undergone previous radio- Type 1, following ileal resection, disease, or therapy to the abdomen, any form of bowel bypass of the terminal ileum; resection, or other abdominal surgery were Type 2, primary idiopathic malabsorption; excluded. Stool culture, rigid sigmoidoscopy, Type 3, associated with cholecystectomy,5 I barium enema, barium follow through, jejunal peptic ulcer surgery, chronic pancreatitis, biopsy, and vitamin B-12 absorption studies coeliac disease,7 and diabetes mellitus. were performed in all patients, and were normal. The aetiology of types 2 and 3 is unclear. Only Those patients who were investigated as the dihydroxy bile acids (chenodeoxycholic acid inpatients underwent three day stool collection and deoxycholic acid) are cathartic to the human for weight and inspection. The notes of all colonic mucosa. They inhibit colonic sodium patients with a retention of less than 15% were Departments of Nuclear Medicine and reabsorption and thus reduce water transport retrieved between January and May 1989 and the Gastroenterology, when the concentration in the aqueous faecal final diagnosis, management, and any follow up Western General phase is greater than 1 5 mmol/1.1 determined. Hospital, Edinburgh Diarrhoea caused by primary idiopathic bile 75SeHCAT absorption was assessed as pre- A J K Williams M V Merrick acid malabsorption is considered very rare.9 One viously described, by administering one capsule M A Eastwood centre with a special interest in the disease saw containing 40 kBq (1 [iCi) 7'SeHCAT after an Correspondence to: only 12 cases in 10 years."' However, detection overnight fast. The 100% value for whole body Dr M A Eastwood, Department of by direct measurement of faecal bile acids is a retention was obtained at 30 minutes and the Gastroenterology, Western difficult and unpleasant procedure in patients measurement was repeated at seven days using a General Hospital, Crewe Road, Edinburgh EH4 2XU. experiencing multiple bowel actions. The shadow shield whole body counter. During the Accepted for publication 75SeHCAT test has previously been shown to initial evaluation of 75SeHCAT a lower limit of 19 November 1990 correlate very closely with the direct measure- 15% retention at seven days was established on Idiopathic bile acid malabsorption - a review ofclinicalpresentation, diagnosis, and response to treatment 1005 TABLE I Characteristics of23 patients with severe bile acid TABLE III Characteristics of21 patients with mild bile acid malabsorption (<5% retention of"SeHCAT) malabsorption (¢'10%, <15% retention of5SeHCAT) Sex (M/F) 10/13 Sex (M/F) 18/13 Age (yrs), mean (range) 45 (17-77) Age (yrs), mean (range) 30 (13-72) Gut: first published as 10.1136/gut.32.9.1004 on 1 September 1991. Downloaded from Duration of symptoms (yrs), mean (range) 3-3 (0-08-5) Duration of symptoms (yrs), mean (range) 7 (1-25)j Stool frequency (motions/24 hrs), mean (range) 8 (4-12)* Stool frequency (motions/24 hrs), mean (range) 4 (2-10) Stool weight (g), mean (range) 450 (400-800)* Stool weight (g), mean (range) 160 (8-200)* Nocturnal diarrhoea (%) 11/23 (48) Dose of cholestyramine (g), mean (range) 12 (8-24) *Data from 8 patients. *Data from 8 patients nocturnal diarrhoea. The patients who responded to bile acid chelators could not be the basis of comparison with normal controls.'4 distinguished from those who did not respond. Sixty patients had a "SeHCAT retention of Twenty one patients had a 75SeHCAT reten- <15% at seven days and were therefore con- tion of ¢ 10% but <15% at seven days (Table sidered abnormal by our published criteria. III). All complained of intermittent watery These patients were subdivided into three diarrhoea but none had a nocturnal component, groups - those with a retention <5%, those with and in five the diarrhoea was confined to the a retention 2 5% but <10%, and those with morning. Eight patients complained of urgency, a retention -10% but <15%. The clinical lower abdominal pain relieved by defaecation, characteristics of each group were identified by and bloating. None of the eight patients who reference to the clinical notes and the response to received cholestyramine were improved. bile acid chelators when administered. Discussion Results The cut off value of 15% was based on a Table I lists the characteristics of patients with a comparison between normal controls and seven day retention of <5%. All these patients patients with known disease.'2 It is well known complained of intermittent watery diarrhoea, that such studies, although necessary in the with a nocturnal component in 11 of the 23. initial stages ofevaluating a new test, are likely to The diarrhoeal illness was of variable require modification on the basis of further duration with no associated constitutional upset. clinical experience. It is clear from the present In all cases it began abruptly and was not study that the lower limit of normal should be associated with any other discernible illness. In revised downwards - in any patient with a seven two it started while the patient was abroad. day 75SeHCAT retention of 10% or more, bile Twenty one patients were treated with chole- acid malabsorption is not the cause of the styramine, which resulted in a reduction in stool diarrhoea. frequency and improvement in stool consist- The sustained response to specific treatment http://gut.bmj.com/ ency. Cholestyramine was administered in in all patients with a retention of <5% confirms divided doses in powder form (4 g sachets) that these patients did indeed have bile acid during the day. A therapeutic response was induced diarrhoea. The aetiology of this condi- defined as a reduction in stool frequency to -2 tion remains obscure. None of the patients had bowel actions/day with a concomitant increase in any systemic upset; all responded to treatment stool consistency occurring within 48 hours of within 48 hours, and the response was sustained. on October 1, 2021 by guest. Protected copyright. beginning treatment. The mean dose of choles- This pattern is similar to that previously des- tyramine was 12 g. Four patients required doses cribed. '° Although initially characterised as greater than 12 g/day to control their symptoms. causing continuous watery diarrhoea, two pre- One patient was intolerant of cholestyramine but viously reported cases had intermittent responded to aluminium hydroxide. The diarrhoea with large volume stools which never- remaining patient responded to aluminium theless responded overnight to cholestyramine.'o hydroxide as the initial treatment. The nocturnal component seen in half of our Sixteen patients had a seven day 75SeHCAT patients has not previously been described and is retention of ¢e5% but <10% and 13 received a useful diagnostic indicator when present. treatment with bile acid chelators (Table II).
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