American Journal of Clinical Dermatology

, Volume 16, Issue 1, pp 27–33 | Cite as

A Review of Vitamin B12 in Dermatology

  • Jennifer BrescollEmail author
  • Steven Daveluy
Review Article


Vitamin B12, also known as cobalamin, is a water-soluble vitamin that is important in the hematological and nervous systems, and it has a complex relationship with the skin. Altered cobalamin levels can lead to dermatological manifestations, which may indicate a deficiency or excess of this vitamin. The biochemistry and metabolism of cobalamin is complex, and diseases can be associated with alterations of this metabolic pathway. The cutaneous manifestations of cobalamin deficiency include hyperpigmentation (most commonly); hair and nail changes; and oral changes, including glossitis. Additionally, several dermatologic conditions, including vitiligo, aphthous stomatitis, atopic dermatitis, and acne are related to cobalamin excess or deficiency. The cutaneous complications of cobalamin therapy include acne, rosacea, and allergic site reactions, or anaphylaxis with cobalamin injections. As cobalt is a component of cobalamin, patients with cobalt sensitivity have been reported to have cutaneous manifestations when receiving cobalamin replacement therapy.


Atopic Dermatitis Homocysteine Isotretinoin Vitiligo Cobalamin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to prepare this review. Jennifer Brescoll and Steven Daveluy have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Stabler SP. Vitamin B12 Deficiency. N Engl J Med. 2013;368:149–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003;36(8):585–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie. 2013;95(5):1002–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM. 2013;106(6):505–15.PubMedCrossRefGoogle Scholar
  5. 5.
    Klion AD, Robyn J, Maric I, Fu W, Schmid L, Lemery S, Noel P, Law MA, Hartsell M, Talar-Williams C, Fay MP, Dunbar CE, Nutman TB. Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing. Blood. 2007;110(10):3552–6.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunol Allergy Clin North Am. 2007;27(3):415.PubMedCrossRefGoogle Scholar
  7. 7.
    Aparicio-Ugarriza R, Palacios G, Alder M, González-Gross M. A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population. Clin Chem Lab Med. 2014 (Epub ahead of print).Google Scholar
  8. 8.
    Adcock BB, McKnight JT. Cobalamin pseudodeficiency due to a transcobalamin I deficiency. South Med J. 2002;95(9):1060–2.PubMedCrossRefGoogle Scholar
  9. 9.
    Kalay Z, Islek A, Parlak M, Kirecci A, Guney O, Koklu E, Kalay S. Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid. J Matern Fetal Neonatal Med. 2014 (Epub ahead of print).Google Scholar
  10. 10.
    Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med. 1994;96:239–46.PubMedCrossRefGoogle Scholar
  11. 11.
    Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67(5):979–86.PubMedGoogle Scholar
  12. 12.
    Grarup N, Sulem P, Sandholt CH, Thorleifsson G, Ahluwalia TS, Steinthorsdottir V, Bjarnason H, Gudbjartsson DF, Magnusson OT, Sparsø T, Albrechtsen A, Kong A, Masson G, Tian G, Cao H, Nie C, Kristiansen K, Husemoen LL, Thuesen B, Li Y, Nielsen R, Linneberg A, Olafsson I, Eyjolfsson GI, Jørgensen T, Wang J, Hansen T, Thorsteinsdottir U, Stefánsson K, Pedersen O. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets. PLoS Genet. 2013;9(6):e1003530.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Froese DS, Gravel RA. Genetic disorders of vitamin B12 metabolism: eight complementation groups- eight genes. Expert Rev Mol Med. 2010;12:e37.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nürnberg P, Thiele H, Robenek H, Höhne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge E, Majewski J, Rosenblatt D, Fowler B, Rutsch F, Baumgartner M. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet. 2012;44:1152–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Kim JC, Lee NC, Hwu PW, et al. Late onset of symptoms in an atypical patient with the cblJ inborn error of vitamin B12 metabolism: diagnosis and novel mutation revealed by exome sequencing. Mol Genet Metabol. 2012;107:664–8.CrossRefGoogle Scholar
  16. 16.
    Takeichi T, Hsu CK, Yang HS, Chen HY, Wong TW, Tsai WL, Chao SC, Lee JY, Akiyama M, Simpson MA, McGrath JA. Progressive hyperpigmentation in a Taiwanese child due to an inborn error of vitamin B12 metabolism (cbIJ). Br J Dermatol. 2014 (Epub 2014 Sep 18).Google Scholar
  17. 17.
    Chiang TT, Hung CT, Wang WM, Lee JT, Yang FC. Recreational nitrous oxide abuse-induced vitamin B12 deficiency in a patient presenting with hyperpigmentation of the skin. Case Rep Dermatol. 2013;5(2):186–91.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Pope FM. Parasitophobia as the presenting symptom of vitamin B12 deficiency. Practitioner. 1970;204(221):421–2.PubMedGoogle Scholar
  19. 19.
    Aaron S, Kumar S, Vijayan J, Jacob J, Alexander M, Gnanamuthu C. Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Neurol India. 2005;53(1):55–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Volkov I, Rudoy I, Press Y. Successful treatment of chronic erythema nodosum with vitamin B12. J Am Board Fam Pract. 2005;18(6):567–9.Google Scholar
  21. 21.
    Srivastava N, Chand S, Bansal M, Srivastava K, Singh S. Reversible hyperpigmentation as the first manifestation of dietary vitamin B12 deficiency. Indian J Dermatol Venereol Leprol. 2006;72:389–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Niiyama S, Mukai H. Reversible cutaneous hyperpigmentation and nails with white hair due to vitamin B12 deficiency. Eur J Dermatol. 2007;17(6):551–2.Google Scholar
  23. 23.
    Mori K, Ando I, Kukita A. Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. J Dermatol. 2001;28(5):282–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Aroni K, Anagnostopoulou K, Tsagroni E, Ioannidis E. Skin hyperpigmentation and increased angiogenesis secondary to vitamin B12 deficiency in a young vegetarian woman. Acta Derm Venereol. 2008;88(2):191–2.PubMedCrossRefGoogle Scholar
  25. 25.
    Graells J, Ojeda RM, Muniesa C, Gonzalez J, Saavedra J. Glossitis with linear lesions: an early sign of vitamin B12 deficiency. J Am Acad Dermatol. 2009;60(3):498–500.PubMedCrossRefGoogle Scholar
  26. 26.
    Karadag AS, Tutal E, Ertugrul DT, Akin KO, Bilgili SG. Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in patients with vitiligo. Clin Exp Dermatol. 2012;37:62–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Shaker OG, El-Tahlawi SMR. Is there a relationship between homocysteine and vitiligo? A pilot study. Br J Dermatol. 2008;159:720–4.PubMedGoogle Scholar
  28. 28.
    Balci DD, Yonden Z, Yenin JZ, Okumus N. Serum homocysteine, folic acid and vitamin B12 levels in vitiligo. Eur J Dermatol. 2009;19:382–3.PubMedGoogle Scholar
  29. 29.
    Montes LF, Diaz ML, Lajous J, Garcia NJ. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis. 1992;50(1):39–42.PubMedGoogle Scholar
  30. 30.
    Tjioe M, Gerritsen MJ, Juhlin L, van de Kerkhof PC. Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12. Acta Derm Venereol. 2002;82(5):369–72.PubMedCrossRefGoogle Scholar
  31. 31.
    Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med. 2010;39(5):420–3.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R, Press Y. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med. 2009;22(1):9–16.Google Scholar
  33. 33.
    Karadag AS, Tutal E, Ertugrul DT, Akin KO. Effect of isotretinoin treatment on plasma holotranscobalamin, vitamin B12, folic acid, and homocysteine levels: non-controlled study. Int J Dermatol. 2011;50(12):1564–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Volkov I, Press Y, Rudoy I. Vitamin B12 could be A “master key” in the regulation of multiple pathological processes. J Nippon Med Sch. 2006;73:65–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Stücker M, Pieck C, Stoerb C, Niedner R, Hartung J, Altmeyer P. Topical vitamin B12—a new therapeutic approach in atopic dermatitis—evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial. Br J Dermatol. 2004;150:977–83.PubMedCrossRefGoogle Scholar
  36. 36.
    Yamashiki M, Nishimura A, Kosaka Y. Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cells. J Clin Lab Immunol. 1992;37(4):173–82.PubMedGoogle Scholar
  37. 37.
    Jung SH, Cho YS, Jun SS, Koo JS, Cheon HG, Shin BC. Topical application of liposomal cobalamin hydrogel for atopic dermatitis therapy. Pharmazie. 2011;66(6):430–5.PubMedGoogle Scholar
  38. 38.
    Dupré A, Albarel N, Bonafe JL, Christol B, Lassere J. Vitamin B-12 induced acnes. Cutis. 1979;24(2):210–1.PubMedGoogle Scholar
  39. 39.
    Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol. 2001;15(5):484–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Bilwani F, Adil SN, Sheikh U, Humera A, Khurshid M. Anaphylactic reaction after intramuscular injection of cyanocobalamin (vitamin B12): a case report. J Pak Med Assoc. 2005;55(5):217–9.PubMedGoogle Scholar
  41. 41.
    Tordjman R, Genereau T, Guinnepain MT, Weyer A, Lortholary O, Royer I, Casassus P, Guillevin L. Reintroduction of vitamin B12 in 2 patients with prior B12-induced anaphylaxis. Eur J Haematol. 1998;60(4):269–70.PubMedCrossRefGoogle Scholar
  42. 42.
    Moloney FJ, Hughes R, O’Shea D, Kirby B. Type I immediate hypersensitivity reaction to cyanocobalamin but not hydroxycobalamin. Clin Exp Dermatol. 2008;33(4):412–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Kartal O, Gulec M, Demirel F, Yesillik S, Caliskaner Z, Sener O. Vitamin B12 allergy and successful desensitisation with cyanocobalamin: a case report. Allergol Immunopathol. 2012;40(5):324–5.CrossRefGoogle Scholar
  44. 44.
    Price ML, MacDonald DM. Cheilitis and cobalt allergy related to ingestion of vitamin B12. Contact Dermatitis. 1981;7(6):352.PubMedCrossRefGoogle Scholar
  45. 45.
    Veien NK, Hattel T, Justesen O, Norholm A. Oral challenge with nickel and cobalt in patients with positive patch tests to nickel and/or cobalt. Acta Derm Venereol. 1987;67:321–5.PubMedGoogle Scholar
  46. 46.
    Stuckert J, Nedorost S. Low-cobalt diet for dyshidrotic eczema patients. Contact Dermatitis. 2008;59:361–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Thyssen JP, Menné T, Møller P, Jellesen MS, Johansen JD. A cobalt spot test was useful in the diagnostic work-up of a cobalt allergic patient suffering from oral hypersensitivity to cobalt. J Am Acad Dermatol. 2011;65(3):659–60.PubMedCrossRefGoogle Scholar
  48. 48.
    Veien NK. Systemic contact dermatitis. Int J Dermatol. 2011;50(12):1445–56.PubMedCrossRefGoogle Scholar
  49. 49.
    Midander K, Julander A, Skare L, Thyssen JP, Liden C. The cobalt spot test—further insights into its performance and use. Contact Dermatitis. 2013;69(5):280–7.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Henry Ford HospitalDetroitUSA
  2. 2.Department of DermatologyWayne State University, Oakwood Dearborn Medical ParkDearbornUSA

Personalised recommendations