Vitamin K


Vitamin K is mainly used in patients with hypoprothrombinemia.
 
Incidence
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).
 
Clinical manifestations
General (intravenous vitamin K1): anaphylactic shock, facial flush, abdominal pain, loss of consciousness.
 
Cutaneous:
  • 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.
Diagnostic methods
Cutaneous testing.
 
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.
 
Mechanisms
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.
 
Management
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.

References

  1. Moreau-Cabarrot A, Giordano-Labadie F, Bazex J, "Hypersensibilité cutanée au point d’injection de vitamine K1", Ann. Dermatol. Venereol., 1996; 123 (3): 177-9
  2. Bruynzeel I, Hebeda C.L, Folkers E, Bruynzeel D.P, "Cutaneous hypersensitivity reactions to vitamin K: 2 case reports and a review of the literature", Contact. Dermatitis, 1995; 32 (2): 78-82
  3. Lemlich G, Green M, Phelps R, Lebwohl M, Don P, Gordon M, "Cutaneous reactions to vitamin K1 injections", J. Am. Acad. Dermatol., 1993; 28 (2.2): 345-7
  4. Martinez-Abad M, Delgado F, Palop V, Morales-Olivas F.J, "Vitamin K1 and anaphylactic shock", DICP, 1991; 25 (7-8): 871-2

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.