D3.55 - Synthetic folic acid allergy
Case report
Background:
Synthetic folic acid allergy is rare with only 16 case reports published. Clinical presentation can vary from urticaria to anaphylaxis. There is no clear management strategy in these cases.
Folate is a generic term for the group of water-soluble vitamin B9 compounds. Folic acid is a synthetic form of folate that does not exist naturally. There are subtle differences between folate and folic acid in terms of their molecular structure and intestinal absorption.
Folate plays an important role as a coenzyme in nucleic acid synthesis and the metabolism of amino acids including synthesis of vitamin B12. Folate deficiency can result in macrocytic anaemia and neonatal neural tube defects. Folic acid has a more stable molecular structure and higher bioavailability compared to natural folate (>70% versus 50%). Folic Acid is commonly used to prevent and treat folate deficiency.
Case history:
A 39-year-old female with folate deficiency was referred to the allergy service for presumed allergy to multi-vitamin tablets.
On several occasions on ingestion of multivitamins (Berocca energy tablet and Berocca boost) she developed urticaria within 15 minutes.
On one occasion, she developed more severe symptoms of facial and tongue swelling, vomiting, dyspnoea and chest heaviness.
Folic acid tablets subsequently taken during pregnancy caused immediate symptoms of itching, vomiting, dyspnoea, facial swelling and urticaria. Similar symptoms developed with folic acid oral suspension.
Foods fortified with folic acid were tolerated.
No common excipients were identified in the different folate products.
Skin prick testing was positive for folic acid tablets (20mm).
A non-synthetic folate, Active folic by Solvotrin therapeutics containing 5 methyltetrahydrofolic acid glucosamine salt was identified. Skin testing was negative and direct provocation test was performed without reaction.
Learning Points:
Folic acid allergy is rare and challenging especially in the setting of folate deficiency.
The exact mechanism for folic acid allergy is unclear but there are differences in molecular structural, absorption and metabolism between folate and folic acid, which may contribute in mechanism.
Use of non-synthetic forms of folic acid containing 5 methyltetrahydrofolic acid can be considered in cases of folic acid.
