Recurrent anaphylaxis to synthetic folic acid

Abstract

Food fortifi cation with synthetic folic acid (pteroyl monoglutamic acid) remains a source of debate in terms of benefi t versus issues of safety and consumer choice. Several countries have adopted mandatory folic acid fortifi cation. A decision to proceed in Australasia was made in June, 2007. We report the case of a woman who had three episodes of type I hypersensitivity, including ana phylaxis, after synthetic folic acid exposure. Her fi rst episode occurred within minutes of taking a 5 mg folic acid tablet. She devel oped an itchy throat, nausea, gener alised rash, diarrhoea, and lightheaded ness; she was treated with anti hista mines. The second episode followed consumption of 800 mL lime-fl avoured water fortifi ed with 20 μg/100 mL folic acid. Within minutes of fi nishing the drink she developed an itchy throat, generalised pruritus, and nausea. She was treated with adrena line and antihistamines. A further episode occurred within minutes of drinking 150 mL of a beverage containing feijoa (a fruit of the Myrtaceae family) and supple ments including 53·5 μg/100 mL folic acid. She developed gener alised rash, vomiting, and lightheaded ness. Adrenaline was given en route to hospital, with good response. Intradermal testing with folic acid 0·05 μg/mL solution containing folic acid, bicarbonate, and water was positive (9 mm wheal, 35 mm fl are). A control patient was negative. Skin-prick tests to other food and beverage products were negative. A graded, blinded chal lenge to the folic acid solu tion led to wide spread urticaria at a dose of 160 μg. Before her fi rst episode she had taken a multivitamin B supplement and recalled recurrent episodes of urticaria, and presumably sensitisation to folic acid occurred at this time. She seems to tolerate dietary folates (pteroylpolyglutamates). Hypersensitivity to synthetic folic acid has been rarely described. One report documents sensitivity to synthetic folic acid in medication, as a food supplement, and possibly to dietary folate. In a further case of anaphylaxis after folic acid exposure in multivitamin preparations, development of IgE antibody to folic acid was shown by in-vivo and in-vitro testing. In IgE-mediated reactions, folic acid, with a molecular weight of only 441 D, probably acts as a hapten by conjugation with self-proteins. Folic acid fortifi cation must be accompanied by clear food labelling to enable those who develop allergy to avoid life-threatening reactions. Folic acid allergy should be considered in the diff erential diagnosis of idiopathic anaphylaxis and suspected cereal allergy where skin-prick or RAST testing to standard grains is inconclusive.