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Photosensitivity from pyridoxine hydrochloride (vitamin B6)
Photosensitivity from pyridoxine hydrochloride (vitamin B6) Kohkichi Morimoto, MD, Akira Kawada, MD, PhD, Masataro Himma, MD, PhD, and Akira Ishibashi, MD, PhD Saitama, Japan We describe a 35-year-old female patient with photosensitivity due to pyridoxine hydrochloride (vitamin B6) in a multivitamin over-the-counter preparation. Photopatch and oral photochallenge tests using pyridoxine hydrochloride and UVA irradiation were positive. Larger doses for therapeutic use could cause photosensitivity. (J Am Acad Dermatol 1996;35:3045.)
Vitamin B6, a hydrophilic vitamin, is widely used in over-the-counter preparations as well as for medical therapy. W e report a case of photosensitivity due to pyridoxine hydrochloride, a compound referred to as vitamin B6, with a positive photopatch test. CASE REPORT A 35-year-old woman had pruritic erythema on sunexposed areas (Fig. 1) for 3 months. She had been taking two tablets of a multivitamin preparation twice daily for 4 months. Two tablets contain 100 mg of pyridoxine hydrochloride, 20 mg of riboflavin butyrate, 30 mg of nicotinic acid, 0.05 mg of biotin, and 50 mg of ascorbic acid. A biopsy specimen revealed a perivascular infiltrate of mononuclear cells and small number of eosinophils in the upper dermis. We performed a screening phototest, as previously described, 1 with a Dermaray, Model M-DMR- 1 (Eisai Co. Ltd., Tokyo) as a fight source2, 3 30 hours after a dose of the tablets. Her UVB minimum erythema dose was norreal (60 mJ/cm2), and irradiation with 13.5 J/cm 2 of UVA produced no response. In an oral photochallenge test 3 hours after oral administration of two tablets her minimum erythema dose was still normal (60 mJ/cm2), while 6.75 J/cm2 of UVA irradiation produced erythema in the irradiated area 24 hours after the irradiation. Patch and photopatch tests were carried out 4 weeks later with the OlqYl-tO Thisarticleis made possiblethrough an educationalgrant from the DermatologicalDivision, Ortho Pharmaceutical Corporation. From the Department of Dermatology,National Defense Medical College, Saitama. Reprintrequests: KohkichiMo"nmotoMD, Deparmaentof Dermatology, NationalDefenseMedical College,Namiki 3-2, Tokorozawa City, Saitama, 359, Japan. Copyright© 1996 by the AmericanAcademyof Dermatology,Inc. 0190-9622/96 $5.00+ 0 16/4/73148 304
Fig. 1. Erythema on neck.
five substances contained in the tablets. Only 10% and 1% pyridoxine hydrochloride in petrolatum with UVA irraNation (4.5 J/cm2) produced erythema and small papules with pruritus occurring 24 hours after the irradiation (Fig. 2). Patch and photopatch tests with pyridoxine hydrochloride in five healthy subjects produced no reaction. DISCUSSION Pyridoxine is one of three interchangeable, related natural compounds referred to as vitamin B6. The other two components are pyridoxal and pyridoxamine. These compounds are readily used after conversion in the liver to pyridoxal 5'-phosphate, the active form o f the vitamin. As a coenzyme, pyridoxal phosphate is involved in several metabolic transfor-
Journal of the American Academy of Dermatology Volume 35, Number 2, Part 2
Morimoto et al.
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unchanged and in part after oxidation to 4-pyridoxic acid, formed by the action o f hepatic aldehyde oxidase on free pyridoxal. 4 The plasma pyridoxine level of Americans and the blood vitamin B6 level o f Japanese are 3.6 to 18 tl and 6 to 30 ng/ml, 12 respectively. Sato et al. 13 reported that pyridoxine is a strong photosensitizer for U V A in a cell culture system and that a pyridoxine solution at concentrations o f even 10 and 100 ng/mi causes mild phototoxicity. A transient high concentration o f vitamin B 6 in the blood after oral intake o f a large dose of pyridoxine hydrochloride m a y have caused photosensitivity in our patient.
REFERENCES
Fig. 2. Positive photopatch test with 10% and 1% pyridoxine hydrochloride in petrolatum 24 hours after UVA .Irradiation. "
mations o f amino acids, including decarboxylation, transamination, and racemization, as well as in enzymatic steps in metabolism of sulfur-containing and hydroxy-amino acids. 4 Photosensitivity from pyridoxine hydrochloride or other forms o f vitamin B6 has not been previously reported, although Baer and Stillman 5 described a patient with skin changes probably from pyridoxine and suggested that sunlight might be involved. Only three patients with photosensitivity to pyritinol, a compound o f two molecules o f pyridoxine bounded through -S-S-linkage, have been described. 6' 7 It has been proposed that the free sulfhydryl (SH-) group in thiol drugs contributes to the induction o f the skin lesions.S, 9 Thus the sulfhydryl group could be a factor in photosensitivity from pyritinol. Pyridoxine hydrochloride, however, has no S H groups. The r e c o m m e n d e d dietary allowance for pyridoxine is 2 mg/day for men and 1.6 mg/day for women. 4 T w o tablets o f the preparation taken b y our patient contain 100 mg. In the liver, pyridoxine is phosphorylated by a specific kinase and then oxidized to pyridoxal phosphate by a specific flavoprotein. 1° Excessive amounts o f vitamin B6 over and above tissue requirements are excreted in part
1. Morimoto K, Kawada A, Himma M, et al. Photosensitivity to simvastatin with an unusual response to photopatch and photo tests. Contact Dermatitis 1995;33:274. 2. Kawada A. UVB-induced erythema, delayed tanning, and UVA-induced immediate tanning in Japanese skin. Photodermatol Photoimmunol Photomed 1986;3:327-33. 3. Kawada A, Hiruma M, Nakada R, et al. An evaluation of broad-spectrum sunscreens against topical PUVA-induced erythema. Acta Derm Venereol (Stockh) 1989;69:335-7. 4. Marcus R, Coulston AM. Water-soluble vitamins. In: Gilman AG, Rail TW, Nies AS, et al. editors. Goodman and Gilman's the pharmacological basis of therapeutics. New York: Pergamon Press, 1990:1530-52. 5. Baer RL, Stillman MA. Cutaneous skin changes probably due to pyridoxine abuse [letter]. J Am Acad Dermatol 1984;10:527-8. 6. Ishibashi A, Hirano K, Nishiyama Y. Photosensitive dermatitis due to pyrifiJaol.Arch Dermatol 1973;107:427-8. 7. Dupr6 A, Carr6re S, Launais B, et al. Lichen plan avec photosensibilisationapr6s pyritinol et PUVA th6rapie.Ann Dermatol Venereol (Paris) 1980;107:557-9. 8. Kitamura K, Aihara M, Osawa J, et al. Sullhydryl drag-induced eruption: A clinical and histological study. J Dermatol 1990;17:44-51. 9. Nachbar F, Korting HC, Vogl T. Erythema multiforme-like eruption in association with severe headache following pyritinol. Dermatology 1993;187:42-6. 10. Snell EE. Vitamin B6. In: Florkin M, Stotz EH, editors. Comprehensive biochemistry, volume 11, Water-soluble vitanfins, hormones, antibiotics. New York: Elsevier Pubfishing Company, 1963:48-57. 11. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. 12. Uwatoko H. Studies on the differential estimation of the three forms of vitamin B6 of the blood and urine and the nature of these three forms in certain disease. J Nagoya Med Assoc 1958;76:170-86. (in Japanese) 13. Sato K, Taguchi H, Maeda T, et al. Pyridoxine toxicity to cul~aredfibroblasts caused by near-ultraviolettight. J Invest Dermatol 1993;100:266-70.
Vitamin B6, a hydrophilic vitamin, is widely used in over-the-counter preparations as well as for medical therapy. W e report a case of photosensitivity due to pyridoxine hydrochloride, a compound referred to as vitamin B6, with a positive photopatch test. CASE REPORT A 35-year-old woman had pruritic erythema on sunexposed areas (Fig. 1) for 3 months. She had been taking two tablets of a multivitamin preparation twice daily for 4 months. Two tablets contain 100 mg of pyridoxine hydrochloride, 20 mg of riboflavin butyrate, 30 mg of nicotinic acid, 0.05 mg of biotin, and 50 mg of ascorbic acid. A biopsy specimen revealed a perivascular infiltrate of mononuclear cells and small number of eosinophils in the upper dermis. We performed a screening phototest, as previously described, 1 with a Dermaray, Model M-DMR- 1 (Eisai Co. Ltd., Tokyo) as a fight source2, 3 30 hours after a dose of the tablets. Her UVB minimum erythema dose was norreal (60 mJ/cm2), and irradiation with 13.5 J/cm 2 of UVA produced no response. In an oral photochallenge test 3 hours after oral administration of two tablets her minimum erythema dose was still normal (60 mJ/cm2), while 6.75 J/cm2 of UVA irradiation produced erythema in the irradiated area 24 hours after the irradiation. Patch and photopatch tests were carried out 4 weeks later with the OlqYl-tO Thisarticleis made possiblethrough an educationalgrant from the DermatologicalDivision, Ortho Pharmaceutical Corporation. From the Department of Dermatology,National Defense Medical College, Saitama. Reprintrequests: KohkichiMo"nmotoMD, Deparmaentof Dermatology, NationalDefenseMedical College,Namiki 3-2, Tokorozawa City, Saitama, 359, Japan. Copyright© 1996 by the AmericanAcademyof Dermatology,Inc. 0190-9622/96 $5.00+ 0 16/4/73148 304
Fig. 1. Erythema on neck.
five substances contained in the tablets. Only 10% and 1% pyridoxine hydrochloride in petrolatum with UVA irraNation (4.5 J/cm2) produced erythema and small papules with pruritus occurring 24 hours after the irradiation (Fig. 2). Patch and photopatch tests with pyridoxine hydrochloride in five healthy subjects produced no reaction. DISCUSSION Pyridoxine is one of three interchangeable, related natural compounds referred to as vitamin B6. The other two components are pyridoxal and pyridoxamine. These compounds are readily used after conversion in the liver to pyridoxal 5'-phosphate, the active form o f the vitamin. As a coenzyme, pyridoxal phosphate is involved in several metabolic transfor-
Journal of the American Academy of Dermatology Volume 35, Number 2, Part 2
Morimoto et al.
305
unchanged and in part after oxidation to 4-pyridoxic acid, formed by the action o f hepatic aldehyde oxidase on free pyridoxal. 4 The plasma pyridoxine level of Americans and the blood vitamin B6 level o f Japanese are 3.6 to 18 tl and 6 to 30 ng/ml, 12 respectively. Sato et al. 13 reported that pyridoxine is a strong photosensitizer for U V A in a cell culture system and that a pyridoxine solution at concentrations o f even 10 and 100 ng/mi causes mild phototoxicity. A transient high concentration o f vitamin B 6 in the blood after oral intake o f a large dose of pyridoxine hydrochloride m a y have caused photosensitivity in our patient.
REFERENCES
Fig. 2. Positive photopatch test with 10% and 1% pyridoxine hydrochloride in petrolatum 24 hours after UVA .Irradiation. "
mations o f amino acids, including decarboxylation, transamination, and racemization, as well as in enzymatic steps in metabolism of sulfur-containing and hydroxy-amino acids. 4 Photosensitivity from pyridoxine hydrochloride or other forms o f vitamin B6 has not been previously reported, although Baer and Stillman 5 described a patient with skin changes probably from pyridoxine and suggested that sunlight might be involved. Only three patients with photosensitivity to pyritinol, a compound o f two molecules o f pyridoxine bounded through -S-S-linkage, have been described. 6' 7 It has been proposed that the free sulfhydryl (SH-) group in thiol drugs contributes to the induction o f the skin lesions.S, 9 Thus the sulfhydryl group could be a factor in photosensitivity from pyritinol. Pyridoxine hydrochloride, however, has no S H groups. The r e c o m m e n d e d dietary allowance for pyridoxine is 2 mg/day for men and 1.6 mg/day for women. 4 T w o tablets o f the preparation taken b y our patient contain 100 mg. In the liver, pyridoxine is phosphorylated by a specific kinase and then oxidized to pyridoxal phosphate by a specific flavoprotein. 1° Excessive amounts o f vitamin B6 over and above tissue requirements are excreted in part
1. Morimoto K, Kawada A, Himma M, et al. Photosensitivity to simvastatin with an unusual response to photopatch and photo tests. Contact Dermatitis 1995;33:274. 2. Kawada A. UVB-induced erythema, delayed tanning, and UVA-induced immediate tanning in Japanese skin. Photodermatol Photoimmunol Photomed 1986;3:327-33. 3. Kawada A, Hiruma M, Nakada R, et al. An evaluation of broad-spectrum sunscreens against topical PUVA-induced erythema. Acta Derm Venereol (Stockh) 1989;69:335-7. 4. Marcus R, Coulston AM. Water-soluble vitamins. In: Gilman AG, Rail TW, Nies AS, et al. editors. Goodman and Gilman's the pharmacological basis of therapeutics. New York: Pergamon Press, 1990:1530-52. 5. Baer RL, Stillman MA. Cutaneous skin changes probably due to pyridoxine abuse [letter]. J Am Acad Dermatol 1984;10:527-8. 6. Ishibashi A, Hirano K, Nishiyama Y. Photosensitive dermatitis due to pyrifiJaol.Arch Dermatol 1973;107:427-8. 7. Dupr6 A, Carr6re S, Launais B, et al. Lichen plan avec photosensibilisationapr6s pyritinol et PUVA th6rapie.Ann Dermatol Venereol (Paris) 1980;107:557-9. 8. Kitamura K, Aihara M, Osawa J, et al. Sullhydryl drag-induced eruption: A clinical and histological study. J Dermatol 1990;17:44-51. 9. Nachbar F, Korting HC, Vogl T. Erythema multiforme-like eruption in association with severe headache following pyritinol. Dermatology 1993;187:42-6. 10. Snell EE. Vitamin B6. In: Florkin M, Stotz EH, editors. Comprehensive biochemistry, volume 11, Water-soluble vitanfins, hormones, antibiotics. New York: Elsevier Pubfishing Company, 1963:48-57. 11. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. 12. Uwatoko H. Studies on the differential estimation of the three forms of vitamin B6 of the blood and urine and the nature of these three forms in certain disease. J Nagoya Med Assoc 1958;76:170-86. (in Japanese) 13. Sato K, Taguchi H, Maeda T, et al. Pyridoxine toxicity to cul~aredfibroblasts caused by near-ultraviolettight. J Invest Dermatol 1993;100:266-70.