ABSTRACT
Azathioprine keeps an important place in the treatment of inflammatory bowel disease and autoimmune hepatitis. This molecule has a narrow therapeutic margin, associated with a risk of toxicity, particularly hematological and hepatic. Its complex metabolism is subject to genetic polymorphisms that are reflected in the inter-individual variability observed in the response to treatment and its tolerance profile. Hence, its use requires a good knowledge of this molecule. Treatment is initiated after a preliminary workup, followed by a progressive titration of the dosage while closely monitoring possible toxicities. Monitoring of blood levels of metabolites (including active ones) helps guide personalized dose adjustment.
L'azathioprine garde actuellement une place importante dans le traitement des maladies inflammatoires chroniques de l'intestin et de l'hépatite autoimmune. Il s'agit d'une molécule à marge thérapeutique étroite, associée à un risque de toxicité, notamment hématologique et hépatique. Son métabolisme complexe est influencé par des polymorphismes génétiques qui sont reflétés dans la variabilité interindividuelle observée dans la réponse au traitement et le profil de tolérance. Son utilisation nécessite donc une bonne connaissance de cette molécule. L'instauration du traitement se fait après un bilan préalable, puis une titration progressive des posologies, tout en surveillant étroitement les éventuelles toxicités. Le monitoring des concentrations sanguines des métabolites (notamment actifs) permet de guider l'adaptation personnalisée des posologies.
Subject(s)
Gastroenterology , Inflammatory Bowel Diseases , Azathioprine/metabolism , Azathioprine/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapyABSTRACT
BACKGROUND: D-lactic acidosis is an uncommon and challenging form of metabolic acidosis that may develop in short bowel syndrome. It has been documented exclusively in case reports and small case series. METHODS: We performed a review of the literature in the National Library of Medicine and Excerpta Medica databases. RESULTS: We identified 84 original reports published between 1977 and 2017. D-lactic acidosis was observed in 98 individuals ranging in age from 7 months to 86 years with short bowel syndrome. The clinical presentation included Kussmaul breathing, confusion, slurred speech, and gait disturbances. Furthermore, among 99 consecutive patients with short bowel syndrome, 21 reported having episodes with symptoms consistent with D-lactic acidosis. In addition, D-lactic acid might also contribute to acidosis in diabetes mellitus. Finally, abnormally high D-lactic acid was documented after administration or ingestion of large amounts of propylene glycol, as paraneoplastic phenomenon and perhaps also in a so far poorly characterized inherited inborn error of metabolism. CONCLUSIONS: In humans with short bowel syndrome (or carbohydrate malabsorption), D-lactic acidosis is likely rather common and under-recognized. This condition should be included in the differential diagnosis of unexplained high-gap metabolic acidosis where the anion causing the acidosis is not known. Furthermore, diabetic acidosis might be caused by accumulation of both ketone bodies and D-lactic acid. Finally, there are endogenous sources of D-lactic acid in subjects with propylene glycol intoxication.
