topiramate and Cystic-Fibrosis

Cystic fibrosis is the most common life-limiting genetic condition in Caucasians caused by Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene mutations. Sweat chloride is the current gold standard for diagnosis where values >60 mmol/L are diagnostic and values >30 mmol/L are indeterminate. There is limited literature on the effect of medications on the sweat chloride values. We report a case of topiramate being responsible for false-positive testing which resulted in overutilisation of medical resources and psychosocial stress on the family. Topiramate should be considered during the interpretation of the gold standard testing as one of the cause of false-positive sweat tests.

Topics: Adolescent; Anticonvulsants; Asthma; Chlorides; Cystic Fibrosis; False Positive Reactions; Female; Humans; Mass Screening; Sweat; Topiramate; Tourette Syndrome

Topiramate, which is used as an anticonvulsant and for migraine prophylaxis in children, causes oligohydrosis as a side-effect, but its effect on sweat chloride concentrations has not been studied systematically.. Twenty-one children receiving topiramate and 20 healthy controls with no signs or symptoms of pulmonary or gastrointestinal disease and a negative family history for cystic fibrosis (CF) underwent bilateral pilocarpine iontophoresis and sweat collection via Macroduct® system.. Adequate samples (>15 µl volume) were obtained from 17/19 topiramate subjects (89%), and 19/20 (95%) controls. The mean sweat chloride concentration was 37.7 ± 18.8 mmol/L for patients receiving topiramate, and 15.9 ± 6.9 mmol/L for controls (p = 0.0001). The mean sweat volume was 29.1 ± 17.4 µl for patients receiving topiramate, and 41.2 ± 17.5 µl for controls (p = 0.037). Overall 8/17 (47%) of patients on topiramate with a measurable sweat chloride had either an intermediate (>40 mmol/L but <60 mmol/L) or elevated (>60 mmol/L) sweat chloride test result, while 0/19 control subjects had elevated sweat chloride (p = 0.0008). Further analysis of the in vitro activity of topiramate on cultured human bronchial epithelial cells in modified Ussing chambers showed no differences in chloride conductance measured in cells exposed to 10 or 50 µg/ml of topiramate when compared to non-exposed cells.. This is the first report of a medication affecting sweat chloride values and shows that topiramate therapy can cause elevated sweat chloride concentrations in the absence of clinical manifestations of CF.

Topics: Adolescent; Analgesics; Anticonvulsants; Bronchi; Cells, Cultured; Child; Chlorides; Cystic Fibrosis; Female; Fructose; Humans; Iontophoresis; Male; Migraine Disorders; Pilocarpine; Sweat; Topiramate; Treatment Outcome