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The mechanism of hypersensitivity to vitamin B12 has not been finally explained, and although some authors indicate an IgE-dependent basis for these reactions [78,82,95,96] (Type I (immediate) hypersensitivity reaction (Figure 2A)), histopathological examinations of samples from the skin lesions do not allow to unequivocally confirm this hypothesis or exclude the cellular nature (Type IV (late) hypersensitivity reaction (Figure 2B)) of the immune response to this vitamin