Folic acid is the synthetic form of vitamin B9 or folate and it is not found in
nature. Folate conversion to the active form requires reduction to tetrahydrofolate, a
reaction that is catalyzed by dihydro-folate reductase, which is expressed in the
intestine and other peripheral tissues. Folic acid is the lonely vitamin able to induce
severe anaphylactic shock following its oral assumption or through any route of
administration, i.e. intravenously or intramuscularly. The sensitizing strength of the
folic acid might be due to its accumulation in blood, caused by its property to exhaust
the enzymatic pathways responsible for its metabolism. Specific IgE to folic acid has
been isolated by different research groups, thus suggesting immediate-type reactions to
folic acid have genuinely a reaginic pathomechanism. Furthermore, derivative drugs
like folinic acid or antifolate drugs like methotrexate have been produced and they may
show an allergic cross-reactivity with folic acid. Isolated cases of folic acid
desensitization have been performed but poorly described in literature whereas a wellelaborated
desensitization protocol would be desirable, given the importance of folic
acid during pregnancy to prevent neural tube malformations in the newborn.
Keywords: Anaphylaxis, Calcium Folinate, Cereals, Delayed-type Reaction,
Folate, Folic Acid, Folinic Acid, IgE, Immediate-type Reaction, Methotrexate,
Pteroyl-glutamic Acid, Skin Tests, Urticaria, Vitamin B9.