A New Insight on Azathioprine Safety in pregnancy
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A 32-year-old (G2P0) that presented at 23 + 5 weeks` gestation with pruritus and a maculo-popular rash on all extremities and abdomen with worsening symptoms at night for 5 days before advocating medical assistance. The patient had Crohn`s disease, diagnosed at age 17, treated with 125 mg azathioprine daily, in remission a year and a half preceding pregnancy. She was otherwise healthy, with no known allergies or liver diseases. The patient received anti-histamines and various ointments for her symptoms based on dermatologist consults, a full workup was conducted including a normal white blood count without eosinophilia, normal levels of liver enzymes and an initial elevated serum bile acid level of 209.6 µmol/L (0-10 µmol/L).

ICP was diagnosed. Ursodeoxycholic-acid treatment (up to 2700 mg per day) had no clinical or laboratory effect, with bile acid levels rising to 348.2 µmol/L. Due to the early atypical stage of ICP and normal imaging tests, with no response to treatment, a multi-disciplinary consult was advocated.

The consultants requested testing levels of azathioprine metabolites including 6-methylmercaptopurine. 6-methylmercaptopurine levels were more than double the upper limit. Azathioprine treatment was halted and levels of bile acids dropped to 117.4 µmol/L in less than 48 hours. This led in turn to the diagnosis of azathioprine-induced ICP. Bile acids remained over 100 µmol/L throughout pregnancy, though the patient remained asymptomatic under Ursodeoxycholic-acid and anti-histamines treatment. The patient delivered by caesarean section per maternal request at 35.6 weeks` gestation due to non-reassuring fetal heart rate tracing and subjective decreased fetal movements. In the post-partum period, bile acid levels remained elevated 9 months, during which the patient required anti-histamine treatment on occasion for pruritus.
Azathioprine treatment was renewed by the gastroenterologist soon after delivery at the patient`s first follow-up postpartum 2 weeks after delivery.

Source: https://www.ejog.org/article/S0301-2115(20)30254-2/fulltext?rss=yes
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