Severe cholestatic jaundice after a single administration of ajmaline; a case report and review of the literature

Benjamin H Mullish,Kirsty Lloyd,Robert D Goldin,Belinda C Smith,Rishi K Fofaria,Josephine Lloyd,Ameet Dhar

doi:10.1186/1471-230x-14-60

Benjamin H Mullish, Kirsty Lloyd + Show 5 more

Open Access

https://doi.org/10.1186/1471-230x-14-60

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Abstract

BackgroundAjmaline is a pharmaceutical agent now administered globally for a variety of indications, particularly investigation of suspected Brugada syndrome. There have been previous reports suggesting that repetitive use of this agent may cause severe liver injury, but little evidence exists demonstrating the same effect after only a single administration.Case presentationA 33-year-old man of Libyan origin with no significant past medical history underwent an ajmaline provocation test for investigation of suspected Brugada syndrome. Three weeks later, he presented with painless cholestatic jaundice which peaked in severity at eleven weeks after the test. Blood tests confirmed no evidence of autoimmune or viral liver disease, whilst imaging confirmed the absence of biliary tract obstruction. A liver biopsy demonstrated centrilobular cholestasis and focal rosetting of hepatocytes, consistent with a cholestatic drug reaction. Over the course of the next few months, he began to improve clinically and biochemically, with complete resolution by one year post-exposure.ConclusionWhilst ajmaline-related hepatotoxicity was well-recognised in the era in which the drug was administered as a regular medication, clinicians should be aware that ajmaline may induce severe cholestatic jaundice even after a single dose administration.

Highlights

Ajmaline is a pharmaceutical agent administered globally for a variety of indications, investigation of suspected Brugada syndrome
Whilst ajmaline-related hepatotoxicity was well-recognised in the era in which the drug was administered as a regular medication, clinicians should be aware that ajmaline may induce severe cholestatic jaundice even after a single dose administration
There is to date only very scant evidence of ajmaline causing liver injury after only a single administration, the predominant means in which the drug is delivered at present

Summary

Conclusion

There is strong evidence that this man’s illness represented the unusual syndrome of ajmaline-related cholestatic jaundice. It is recognised that 71% of European Caucasians have functional alleles of this enzyme, whilst this is only the case in approximately 50% of Asians and Africans [14] It may be the case in this patient that exposure to ajmaline in the context of a non-functional CYP2D6 allele, plus inheritance of a vulnerable HLA subtype, increased this patient’s propensity to drug-related liver injury. Hepatologists, pathologists, toxicologists and cardiologists should recognise the association between even a single administration of ajmaline and prolonged cholestatic jaundice with the presence of centrilobular cholestasis histologically This case highlights the importance of taking an accurate and thorough medication history from both the patient and his primary physician, including single-dose agents that patients may have been administered.

Background

Findings

14. Bradford LD