Penicillin Allergy - The Root of the Cause

A recent study published this year reported they may have found a connection between penicillin allergies and a vulnerability on the HLA-B gene. This information is particularly useful, as approximately 10% of people report having an allergic reaction to penicillin to varying degrees. Symptoms can include rash, breathing difficulty, and abnormal heart rhythms. The immune system gene in question - HLA-B - is a major histocompatibility complex gene that aids in detecting self from foreign entities. HLA-B mutations have also been associated with adverse reactions to the HIV/AIDS drug abacavir and allopurinol used to treat gout. 

The study in question reviewed over 600,000 electronic health records that included genetic data with self-reported penicillin allergies.  The specific variant, HLA-B*55:01, was found on chromosome 6. They then cross-referenced over 1.1 million people of European ancestry in the 23andMe (that's a soapbox for another day lol) and found the same genetic connection. Other ethnicities were evaluated, but a similar mutation was not found in the small population sample sizes. 

Further research will need to evaluate data from ethnic minorities and verify actual penicillin allergies versus misreported allergies.  One posed issue regarded the distinction between verified penicillin allergies and reported.  Many people either have or have been told they had a childhood penicillin allergy that was either misreported or no longer an allergy.  This affects clinical decision-making, as less appropriate antibiotics may be prescribed in lieu of first generation antibiotics. Increased medication costs could potentially burden patients when they could safely take a lower cost antibiotic. 

Krebs, K., Bovijn, J., Zheng, N., Lepamets, M., Censin, J. C., Jürgenson, T., Särg, D., Abner, E., Laisk, T., Luo, Y., Skotte, L., Geller, F., Feenstra, B., Wang, W., Auton, A., 23andMe Research Team, Raychaudhuri, S., Esko, T., Metspalu, A., Laur, S., … Fadista, J. (2020). Genome-wide Study Identifies Association between HLA-B∗55:01 and Self-Reported Penicillin Allergy. American journal of human genetics, 107(4), 612–621. https://doi.org/10.1016/j.ajhg.2020.08.008