Skip to main content
Log in

A Review of Vitamin B12 in Dermatology

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stabler SP. Vitamin B12 Deficiency. N Engl J Med. 2013;368:149–60.

    Article  CAS  PubMed  Google Scholar 

  2. Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003;36(8):585–90.

    Article  CAS  PubMed  Google Scholar 

  3. Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie. 2013;95(5):1002–7.

    Article  CAS  PubMed  Google Scholar 

  4. Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM. 2013;106(6):505–15.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunol Allergy Clin North Am. 2007;27(3):415.

    Article  PubMed  Google Scholar 

  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).

  8. Adcock BB, McKnight JT. Cobalamin pseudodeficiency due to a transcobalamin I deficiency. South Med J. 2002;95(9):1060–2.

    Article  PubMed  Google Scholar 

  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).

  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.

    Article  CAS  PubMed  Google Scholar 

  11. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67(5):979–86.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Froese DS, Gravel RA. Genetic disorders of vitamin B12 metabolism: eight complementation groups- eight genes. Expert Rev Mol Med. 2010;12:e37.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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).

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Pope FM. Parasitophobia as the presenting symptom of vitamin B12 deficiency. Practitioner. 1970;204(221):421–2.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

  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.

    Article  PubMed  Google Scholar 

  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.

  23. Mori K, Ando I, Kukita A. Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. J Dermatol. 2001;28(5):282–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  27. Shaker OG, El-Tahlawi SMR. Is there a relationship between homocysteine and vitiligo? A pilot study. Br J Dermatol. 2008;159:720–4.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed Central  PubMed  Google Scholar 

  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.

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  38. Dupré A, Albarel N, Bonafe JL, Christol B, Lassere J. Vitamin B-12 induced acnes. Cutis. 1979;24(2):210–1.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  44. Price ML, MacDonald DM. Cheilitis and cobalt allergy related to ingestion of vitamin B12. Contact Dermatitis. 1981;7(6):352.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  46. Stuckert J, Nedorost S. Low-cobalt diet for dyshidrotic eczema patients. Contact Dermatitis. 2008;59:361–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  48. Veien NK. Systemic contact dermatitis. Int J Dermatol. 2011;50(12):1445–56.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer Brescoll.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brescoll, J., Daveluy, S. A Review of Vitamin B12 in Dermatology. Am J Clin Dermatol 16, 27–33 (2015). https://doi.org/10.1007/s40257-014-0107-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-014-0107-3

Keywords

Navigation