Vitamin K is mainly used in patients with hypoprothrombinemia.
52 cases of cutaneous hypersensitivity reactions to vitamin K from 1964 to 1995 (Europe and North America).
94 cases of cutaneous hypersensitivity reactions to vitamin K up to 1988 (Japan).
General (intravenous vitamin K1): anaphylactic shock, facial flush, abdominal pain, loss of consciousness.
- erythematous plaque like dermatitis: after 4 to 21 days, at the injection site (IM or SC) with oil soluble vitamin K1 (phytomenadione)
- pseudo-sclerodermatous lesion: from 2 months to 1.5 years following administration of vitamin K1 around the injection site
- contact dermatitis: occupational handling of vitamin K3 (pig feed, pharmaceutical factory, pharmaceutical or veterinary laboratory)
- urticaria: one patient after IM injection of vitamin K1.
Intradermal skin-tests: 0.02 ml phytomenadione 0.05% in NaCl 0.9%.
Patch-tests: phytomenadione 0.03% and 0.1% in pet.
Patch-tests are positive in contact dermatitis, intradermal skin-tests are usually positive in erythematous plaque-like dermatitis and pseudo-sclerodermatosis lesions.
Skin-biopsy: erythematous plaque like lesions: parakeratosis, spongiosis, intraepidermal vesiculation.
Cremophor EL used in some countries as a solvent for intravenous formulation of vitamin K1 is thought to be the culprit in anaphylactoid reactions.
Type IV hypersensitivity (positive patch-tests).
The phytyl moiety contained in phytomenadione, but not in other forms of vitamin K, could be the antigenic site.
Vitamin K exists in 4 different pharmacological forms:
- vitamin K1 (phytomenadione): naturally occurring form (oil soluble)
- vitamin K2 (menaquinone): synthesized by bacteria in intestine
- vitamin K3 (menadione): synthetic analogue (oil soluble)
- vitamin K4 (menadiol): synthetic analogue (water soluble).
When administered orally, vitamins K1, K3, and K4 do not result in skin disease.
Cross-reactivity between vitamin K3 and K4 has been described, but not between vitamin K1 and other vitamin K derivatives.
Prefer oral and water-soluble formulations of vitamin K
Slow infusion of vitamin K1 diluted in a physiological solution may decrease the rate of anaphylactic reactions.