Acute allergic reaction to an iron compound in a milk‐allergic patient

A child allergic to cow's milk developed a mild systemic allergic reaction after the first dose of Ferplex 40® (iron proteinsuccinylate). Skin tests and in vitro studies were performed in the child, in three cow's milk-allergic controls and in a non-allergic control. Milk, casein and iron proteinsuccinylate (Ferplex 40®) were used for skin tests, specific immunoglobulin E (IgE) determination, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting and enzyme allergo sorbent test (EAST) inhibition. A review of the drug information sheet and contact with the manufacturer were also performed. Although proteinsuccinylate is indeed a succinylated casein (each dose containing about 575 mg of casein) there was no indication of the milk protein content in the prescribing information provided by the manufacturer. Skin tests and specific IgE were positive in the case and in all allergic controls, except for EAST to iron proteinsuccinylate in one control. In EAST, iron proteinsuccinylate in solid phase was 100% inhibited by casein and casein in solid phase was inhibited 74% by iron proteinsuccinylate. SDS-PAGE of iron proteinsuccinylate showed a broad 46 kDa band and a blur of aggregated material. On immunoblot, the patient's IgE reacted to this heavily aggregated material and in the native casein extract recognized a 35-kDa band. The allergenicity of succinylated casein (proteinsuccinylate) among milk-allergic children is demonstrated. The protein source used in drug-protein conjugates should always be indicated by the manufacturer (as it should be in foods) to avoid potential risks to allergic patients.