A Review of Vitamin B12 in Dermatology

Jennifer Brescoll; Steven Daveluy


Am J Clin Dermatol. 2015;16(1):27-33. 

In This Article

Cutaneous Manifestations of Cobalamin Deficiency

There are various cutaneous findings associated with cobalamin deficiency, the majority of which are more prevalent in patients with darker pigmentation. A retrospective and prospective study of 63 individuals with vitamin B12 deficiency-related neurological syndromes in India showed that 41 % had skin and mucosal changes, with glossitis in 31 %, hyperpigmentation in 19 %, hair changes in 9 %, angular stomatitis in 8 %, and vitiligo in 3 %.[19] Additionally, a case report described erythema nodosum as a presenting sign of cobalamin deficiency in a 38-year-old female, where the erythema nodosum resolved with replacement of vitamin B12.[20]

The pattern of hyperpigmentation is generalized with accentuation in flexural areas, palms, soles, and the oral cavity. It may also be accentuated in areas of pressure, such as the terminal phalanges, knees, and elbows. Hyperpigmentation may be the first manifestation of vitamin B12 deficiency.[21] Additionally, you can see linear streaks on the nails and hair changes including poliosis.[22] These findings tend to reverse over months with replacement therapy.

The pathologic diagnosis of hyperpigmentation from vitamin B12 deficiency shows increased melanin in the basal layer of the epidermis. One electron microscopic study showed many melanosomes in melanocytes and surrounding keratinocytes. This study proposed that the dominant mechanism of hyperpigmentation due to vitamin B12 deficiency is an increase in melanin synthesis.[23] In one patient with a reddish hyperpigmentation due to chronic cobalamin deficiency that resolved with vitamin B12 injections, biopsy demonstrated an increased number of dermal blood vessels. The pathology showed weak expression of vascular endothelial growth factor, which may have promoted the angiogenesis in this patient and could represent a mechanism for the hyperpigmentation from cobalamin deficiency.[24] It has also been speculated that the increase in melanin could be due to the influence of cobalamin decreasing the level of reduced-type glutathione, which normally inhibits tyrosinase.[16]

Oral manifestations of cobalamin deficiency include glossitis, glossodynia, recurrent ulcers, lingual paresthesia, distortion of taste (dysgeusia), intolerance of dental prostheses, xerostomia, stomatitis, and cheilitis. Hunter's glossitis (or Moeller–Hunter) is the classic form of vitamin B12-related glossitis, with diffuse erythema and lingual atrophy found in up to 25 % of cases of cobalamin deficiency with oral manifestations. It has been proposed that a more specific and early finding of cobalamin deficiency is glossitis with atrophic linear lesions appearing on the tongue and hard palate. The linear lesions can manifest before anemia develops, making it a useful early diagnostic sign.[25]