Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Advertise | Login 
Search Article 
Advanced search 
  Users Online: 85 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size  

Table of Contents
Year : 2013  |  Volume : 17  |  Issue : 7  |  Page : 254-256

Pigmentation in vitamin B12 deficiency masquerading Addison's pigmentation: A rare presentation

Department of Endocrinology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack, Odisha, India

Date of Web Publication11-Oct-2013

Correspondence Address:
Ritesh Kumar Agrawala
Department of Endocrinology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack - 753 001, Odisha
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2230-8210.119591

Rights and Permissions

A 35-year-female presented with generalized weakness, weight loss, and progressive pigmentation was worked up for suspicion of Addisons disease. On examination hyper pigmentation was noted on both palmar and dorsal aspect of hands involving knuckles, creases, feet, tongue, oral mucosa and gluteal region. There was no evidence of hypocortisolemia as initially suspected, and literature search revealed a possibility of vitamin B12 deficiency. She had megaloblastic anemia with a low serum vitamin B12, mostly due to poor dietary intake. Her hyper pigmentation resolved with vitamin B12 supplementation. Skin biopsy showed increased pigmentation at stratum spinosum and basal-layer. The mechanism of hyper pigmentation in vitamin B12 deficiency was due to an increase in melanin synthesis.

Keywords: Addisons disease, B12 deficiency, hyper pigmentation, vitamin B12 deficiency

How to cite this article:
Agrawala RK, Sahoo SK, Choudhury AK, Mohanty BK, Baliarsinha AK. Pigmentation in vitamin B12 deficiency masquerading Addison's pigmentation: A rare presentation. Indian J Endocr Metab 2013;17, Suppl S1:254-6

How to cite this URL:
Agrawala RK, Sahoo SK, Choudhury AK, Mohanty BK, Baliarsinha AK. Pigmentation in vitamin B12 deficiency masquerading Addison's pigmentation: A rare presentation. Indian J Endocr Metab [serial online] 2013 [cited 2020 Apr 7];17, Suppl S1:254-6. Available from: http://www.ijem.in/text.asp?2013/17/7/254/119591

   Introduction Top

Aetiology of acquired hyper pigmentation are many. In some patients it gives a clue to the diagnosis of systemic disorders. Pigmentation in vitamin B12 deficiency that simulates the pigmentation of Addison's disease is a rare initial presentation and early management can prevent various neurological complications. Herein, we report a rare case of hyper pigmentation due to vitamin B12 deficiency.

   Case Report Top

A 35-year-female presented with generalized weakness, weight loss and nausea along with progressive pigmentation involving both palmar and dorsal aspect of hands including knuckles, creases, feet, tongue, oral mucosa and gluteal region over a period of one year [Figure 1]. There was no history of fever, loose motion or steatorrhea, diabetes mellitus, tuberculosis, seizure disorder or any drug intake. She was unmarried, vegetarian, non-smoker, non-alcoholic and working in a hospital as a HIV counsellor.
Figure 1: Hyperpigmentation before treatment

Click here to view

On systemic examination the only significant finding was pallor. Haematological and other investigation were done [Table 1]. Her Serum Cortisol level at 8 A.M and 4 P.M was 14.1 μg/dl and 7.01 μg/dl respectively (normal 5-25 μg/dl), which ruled out hypocortisolemia. At this point, a literature search revealed pigmentation in vitamin B12 deficiency can masquerade as addisonian pigmentation. Skin biopsy taken from left great toe showed "Increase pigmentation at stratum spinosum and basal layer" [Figure 2]. Upper gastrointestinal endoscopy was normal and anti parietal cell antibody was weakly positive. Her serum vitamin B12 level was 67 pg/ml (normal 180-900 pg/ml) indicative of severe vitamin B 12 deficiency. After treatment improvement in subjective symptoms noticed within two weeks and skin pigmentation completely normalised within twelve weeks [Figure 3].
Table 1: Biochemical profile of the patient before and 12 weeks after treatment

Click here to view
Figure 2: Skin Biopsy (Increased pigmentation in stratum spinosum and basal layer)

Click here to view
Figure 3: Post treatment reversal of hyper pigmentation after 12 weeks of vitamin B12 supplementation

Click here to view

   Discussion Top

Vitamin B12 deficiency was first described by Cook in 1944 and later by Baker et al., in 1963. Currently, vitamin B12 deficiency was defined as a plasma concentration of <148 pmol/L (200 pg/ml) and marginal status defined as a concentration of 148-221 pmol/L. [1] The main source of vitamin B12 (cobalamin) in humans is the consumption of meat, poultry and dairy products. The Recommended Dietary Allowances (RDA) varies with age [Table 2]. [2] Prevalence of B12 deficiency varies from 3% to 5% in the general population and 5% to 20% among people older than 65 years. [3] Inadequate intake and low consumption of animal-source foods with pernicious anemia (low intrinsic factor) in younger adults and food bound cobalamin malabsorption in part due to gastric atrophy in older persons are the main cause of low serum vitamin B12 and likely the main cause in poor populations worldwide. [1],[2] In the present case the cause of vitamin B12 deficiency was decrease intake with low intrinsic factor. The common systemic features reported were fatigue, glossitis, weight loss and anorexia that was found in 34%, 31%, 27% and 22% of cases respectively. [4] Hyper pigmentation of skin has been reported only rarely as the presenting manifestation of vitamin B12 deficiency as found in this patient. [5] There are only two such Indian reports found in Indian literature. [6],[7] After the treatment, hematologic response begins after several days and, moreover, the final hematologic landmark is the blood count, including mean corpuscular volume (MCV) that should be completely normal by the eighth week. [8] The cutaneous manifestation of vitamin B12 deficiency is skin hyper pigmentation, vitiligo, hair changes, and recurrent angular stomatitis. Hyper pigmentation of the extremities especially over the dorsum of the hands and feet, with accentuation over the inter-phalangeal joints and terminal phalanges associated with pigmentation of oral mucosa is characteristic of vitamin B12 deficiency. Aaron et al., reported that 12 out of 63 (19%) patients had glossitis (31%), which was the most common mucocutaneous manifestation, followed by skin hyper pigmentation (19%), hair changes (9%), angular stomatitis (8%), and vitiligo (3%). [4] However, the present case had hyper pigmentation only. As evidenced by James et al., histology from the hyper pigmented area showed irregular epidermal atrophy, absence of basal orientation of epidermal cells, patchy pigmentation of the lower epidermis, and numerous pigment-laden macrophages in the upper dermis and increase of melanin in the basal layer. It is suggested that deficiency of vitamin B12 causes decrease in intracellular reduction potential that leads to oxidation of the reduced glutathione and decrease in GSH/GSSG ratio. The epidermal melanocytes are then stimulated to produce melanin as the tyrosinase inhibiting effect of GSH has been diminished. [9] So, the predominant mechanism of hyper pigmentation in vitamin B12 is hypothesised as 1) Deficiency of vitminB12 decreases the level of reduced glutathione, which activate tyrosinase and thus leads to transfer to melanosomes. 2) Defect in the melanin transfer between melanocytes and keratinocytes, resulting in pigmentary incontinence. [10] We consider that in present case the dominant mechanism of hyper pigmentation is not a defect in melanin transport but is rather an increase in melanin synthesis.
Table 2: Recommended dietary allowances for vitamin B12/daily

Click here to view

This patient was treated with intramuscular injection of vitamin B12 (1000 mg) daily for ten days, then weekly for one month and then monthly for two months. Subsequently, the patient has been receiving a multivitamin tablet daily containing vitamin B12 (1 mg) and showed improvement in her presentation. [7]

   Conclusion Top

Though a rare presentation, pigmentation due to vitamin B12 deficiency do mimic Addisons pigmentation. Vitamin B12 deficiency on the background history of vegetarian dietary intake should always be kept in mind after excluding Addisons disease.

   References Top

1.Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr 2009;89:S693-6.  Back to cited text no. 1
2.Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington DC: National Academy Press, 1998.  Back to cited text no. 2
3.Gupta A, Damji A, Uppaluri A. Vitamin B12 defiency. Prevalence among South Asians in Toronto clinic. Can Fam Physician 2004;50:743-7.  Back to cited text no. 3
4.Aaron S, Kumar S, Vijayan J, Jacob J, Alexzander M, Gnanamuthu C. Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Neurol India 2005;53:55-8.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.Hoffman CF, Palmer DM, Papadopoulos D. Vitamin B12 deficiency: A case report of ongoing cutaneous hyperpigmentation. Cutis 2003;71:127-30.  Back to cited text no. 5
6.Ahuja SR, Sharma RA. Reversible cutaneous hyperpigmentation in vitamin B12 deficiency. Indian Pediatr 2003;40:170-1.  Back to cited text no. 6
7.Srivastava N, Chand S, Bansal M, Srivastava K, Singh S. Reversible hyperpigmentation as the first manifestation of dietary vitamin B 12 deficiency. Indian J Dermatol Venereol Leprol 2006;72:389-90.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood 2008;112:2214-21.  Back to cited text no. 8
9.Gilliam JN, Cox AJ. Epidermal changes in vitamin B12 deficiency. Arch Dermatol 1973;107:231-6.  Back to cited text no. 9
10.Mori K, Ando I, Kukita A. Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. J Dermatol 2001;28:282-5.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]

This article has been cited by
1 Knuckle pigmentation, peripheral neuropathy, madness and abnormal movement: is it B12 deficiency?
Sanjeev Kumar Bhoi,Menka Jha,Suprava Naik,Gayatri Devi Palo
Neurological Sciences. 2019;
[Pubmed] | [DOI]
2 Une hyperpigmentation révélant un déficit sévère en vitamine B12
H. Sahel
Journal de Pédiatrie et de Puériculture. 2019; 32(2): 99
[Pubmed] | [DOI]
3 Vitamin B12 Deficiency Induces Imbalance in Melanocytes Homeostasis—A Cellular Basis of Hypocobalaminemia Pigmentary Manifestations
Zuzanna Rzepka,Michalina Respondek,Jakub Rok,Artur Beberok,Keith ó Proinsias,Dorota Gryko,Dorota Wrzesniok
International Journal of Molecular Sciences. 2018; 19(9): 2845
[Pubmed] | [DOI]
4 Histopathologic Findings of Cutaneous Hyperpigmentation in Addison Disease and Immunostain of the Melanocytic Population
Angel Fernandez-Flores,David S. Cassarino
The American Journal of Dermatopathology. 2017; 39(12): 924
[Pubmed] | [DOI]
5 Knuckle Pigmentation: A Clue to Systemic Illness
Arjun Lakshman,Ram V. Nampoothiri,Sreejesh Sreedharanunni,Pankaj Malhotra,Subhash Varma
Indian Journal of Hematology and Blood Transfusion. 2016;
[Pubmed] | [DOI]
6 Pernicious anaemia presenting as hyperpigmentation
W. Y. Tham,C. C. Oh,H. Y. Koh
Clinical and Experimental Dermatology. 2015; : n/a
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded633    
    Comments [Add]    
    Cited by others 6    

Recommend this journal