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\begin{document}

\title{Systemic pigmented contact dermatitis to cobalt following ingestion of
cobalamin supplement}



\author[1]{Thanet Pongcharoensuk}%
\author[1]{Supitchaya Thaiwat}%
\affil[1]{Phramongkutklao Hospital}%


\vspace{-1em}



  
  \date{May 08, 2024}


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\selectlanguage{english}
\begin{abstract}
Systemic contact dermatitis (SCD) is a condition occurring in previously
sensitized individuals after systemic re-exposure to the same or
cross-reacting substance. Pigmented systemic contact dermatitis after
intake of cobalt containing diet has never been reported.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Cobalt is an essential element to humans in the form of cobalamin
(vitamin B12). The human body contains approximately 1 mg of cobalt,
which around eighty percent is a component of vitamin B12. Human dietary
intake of inorganic cobalt including green leafy vegetables, dairy
products, liver and cereal grains varies between 5 and 50 \selectlanguage{greek}μ\selectlanguage{english}g/day, while
vitamin B12 represents cobalt only in minute amounts. Cobalt does not
accumulate in the body and is rapidly excreted in urine. (1, 2)

We report a case of systemic pigmented contact dermatitis, presenting as
hyperpigmented lesions on face, neck and upper back caused by ingesting
cobalt (cobalamin, vitamin B12). This patient had a history of ingesting
cobalamin (vitamin B12) to treat her neuropathic pain 2 years earlier.

\textbf{Case description}

A 55-year-old non-atopic woman with an underlying condition of herniated
nucleus pulposus presented slate-grey hyperpigmented macules and patches
on face, neck and upper back for 2 years (Fig. 1). She had a history of
taking vitamin B12 supplement 600 \selectlanguage{greek}µ\selectlanguage{english}g daily due to her neuropathic pain
for 3 months before onset of hyperpigmented lesion. She denied having
direct contact with cobalt, or any other metals and also agents which
can induce slate grey hyperpigmentation including fragrances, rubber
products or hair dye. Histopathology of the lesions showed focal
vacuolar degeneration of the epidermis with superficial perivascular
infiltration of lymphocytes and marked increase of dermal melanophages
(Fig. 2).

\textbf{Fig. 1} . Slate-grey hyperpigmented macules and patches on both
cheeks

\textbf{Fig. 2} . Histopathology from hyperpigmented lesions showed
focal vacuolar degeneration of the epidermis and marked increase of
dermal melanophages (black arrows) with superficial perivascular
lymphocytic infiltration (H\&E x40, x100).

Systemic pigmented contact dermatitis was suspected, so patch testing
was performed using the European Society of Contact Dermatitis guideline
standard and cosmetic series (3). Readings were performed at 48 and 72
hours according to the International Contact Dermatitis Research Group
criteria. Pigmented reactions to cobalt showed positive
hyperpigmentation after 48 and 72 hours, while other standard and
cosmetic allergens were negative (Fig. 3). We further performed tissue
biopsy on the positive pigmented reaction. Histopathology showed focal
parakeratosis with focal vacuolar interface dermatitis at the
dermo-epidermal junction and superficial perivascular infiltration with
lymphocytes and melanophages consistent with pigmented systemic contact
dermatitis similar to her previous active lesions (Fig. 4). The patient
was advised to avoid taking oral vitamin B12. One year after diagnosis,
the hyperpigmentation gradually faded after discontinuing cobalamin and
adjunctive treatment with topical low potency corticosteroid and topical
retinoic acid.

\textbf{Fig. 3.} Patch test read at 72 hours gave hyperpigmented
reactions to cobalt (No.22).

\textbf{Fig. 4} . Histopathology from positive patch test pigmented
reaction showed focal vacuolar degeneration of the epidermis with dermal
melanophages (black arrows) with superficial perivascular lymphocytic
infiltration (H\&E x40, x100).

\textbf{Discussion}

Cobalt is an ingredient of vitamin B12 or cobalamin, reaction to cobalt
may cause problems in patients receiving vitamin B12 replacement
therapy. Several cutaneous manifestations have been reported in patients
with allergic contact dermatitis to cobalt undergoing oral cobalamin
replacement including atopic dermatitis, chronic vesicular hand
dermatitis, cheilitis, and stomatitis. (4)

Systemic contact dermatitis (SCD) is a condition occurring in previously
sensitized individuals after systemic re-exposure to the same or
cross-reacting substance. Sensitization occurs due to varying exposures
to antigens via multiple routes through the circulatory system, and
thereby produces systemic allergic dermatitis, which may result in a
variety of skin eruptions and systemic flare. The exact mechanisms
behind SCD are not fully understood, but is thought to be a T-cell
mediated delayed type hypersensitivity reaction. (5) The common
allergens inducing systemic contact dermatitis include nickel, zinc and
cobalt. (6-8) Several systemic agents are associated with pigmentation
including cytotoxic agents, antimalarial, analgesics and silver but
pigmented systemic contact dermatitis after intake of cobalt containing
diet has never been reported.

Osmundsen et al. first described pigmented contact dermatitis (PCD) as a
non-eczematous variant of contact dermatitis, clinically characterized
by hyperpigmentation with little or no signs of dermatitis by
observations that the melanosis was due to contact dermatitis caused by
an optical whitener containing pyrazoline present in a washing powder.
(9) The exact mechanism which allergens induce hyperpigmentation remains
unknown. Some experimental studies have shown that allergens having a
special affinity for melanin induced cutaneous inflammation increasing
the number and size of the melanocytes and enhancing their enzymatic
activity (9, 10). The common allergens responsible for pigmented contact
dermatitis are listed in Table 1. Related studies have demonstrated
cases of pigmented contact dermatitis and histopathological examination
revealed focal vacuolar degeneration of the epidermis and increased
dermal melanophages with superficial perivascular lymphocytic
infiltration. (11, 12) Although the exact mechanism of how cobalt
induces systemic contact dermatitis remains unknown (13), one related
study revealed the increasing prevalence of cobalt allergy in the
general population and the high popularity of food supplements
containing cobalt, e.g., vitamin B12 supplement. (14)

\textbf{Conclusion}

We reported the case as first presenting hyperpigmented macules and
patches on the face, neck and upper back after vitamin B12 ingestion.
The results of the patch test with the cobalt also showed hyperpigmented
reactions consistent with the clinical presentation suggesting the
diagnosis of systemic pigmented contact dermatitis resulting from oral
administration of cobalamin. The diagnosis was confirmed by
histopathological results of the positive patch test results
corresponding to the previous active lesions. We suggest investigating
systemic pigmented contact dermatitis in reaction to cobalt when
patients present unexplained hyperpigmented lesions.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Cosmetic & Fragrances, Preservative, Hair dyes, Lipsticks\tabularnewline
\midrule
\endhead
Fragrances & Benzyl salicylate, ylang-ylang oil, Jasmine,
Hydroxy-citronellal, Benzyl alcohol, Cinnamic alcohol, Lavender
oil\tabularnewline
Textiles & Azo dyes, Optical whiteners\tabularnewline
Toiletries & Chromium hydroxide, Fragrances, Nickle oxide\tabularnewline
Others & Minoxidil, Nickel sulfate\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 1.} Common allergens causing pigmented contact dermatitis

\textbf{Acknowledgement}

Published with written consent of the patients.

\textbf{Conflict of interest}

The authors have no conflict of interest to report.

\textbf{Author contributions}

TP: wrote the article, provided pathologic photography and features. ST:
corrected the manuscript.

\textbf{Ethical approval}

We confirm that the manuscript has been read and approved by all named
authors. The protection of intellectual property associated with this
manuscript had been in our consideration.

\textbf{References}

1. Lison D. CHAPTER 25 - Cobalt. In: Nordberg GF, Fowler BA, Nordberg M,
Friberg LT, editors. Handbook on the Toxicology of Metals (Third
Edition). Burlington: Academic Press; 2007. p. 511-28.

2. MacPherson A, Dixon J. COBALT. In: Caballero B, editor. Encyclopedia
of Food Sciences and Nutrition (Second Edition). Oxford: Academic Press;
2003. p. 1431-6.

3. Johansen JD, Aalto-Korte K, Agner T, Andersen KE, Bircher A, Bruze M,
et al. European Society of Contact Dermatitis guideline for diagnostic
patch testing - recommendations on best practice. Contact Dermatitis.
2015;73(4):195-221.

4. Brescoll J, Daveluy S. A review of vitamin B12 in dermatology. Am J
Clin Dermatol. 2015;16(1):27-33.

5. Jacob SE, Zapolanski T. Systemic contact dermatitis. Dermatitis.
2008;19(1):9-15.

6. Zirwas MJ, Molenda MA. Dietary nickel as a cause of systemic contact
dermatitis. J Clin Aesthet Dermatol. 2009;2(6):39-43.

7. Panaszek B, Nowak D, Cie\selectlanguage{polish}ś\selectlanguage{english}lik K, Dziemieszonek P, Gomu\selectlanguage{polish}ł\selectlanguage{english}ka K. Systemic
contact dermatitis caused by cobalt chloride and palladium in a
26-year-old woman with allergic type I reactions, non-steroidal
anti-inflammatory drug hypersensitivity and autoimmune thyroiditis.
Postepy Dermatol Alergol. 2017;34(4):388-90.

8. Yoshihisa Y, Shimizu T. Metal allergy and systemic contact
dermatitis: an overview. Dermatol Res Pract. 2012;2012:749561.

9. Osmundsen PE. Pigmented contact dermatitis. Br J Dermatol.
1970;83(2):296-301.

10. Papa CM, Kligman AM. The behavior of melanocytes in inflammation. J
Invest Dermatol. 1965;45(6):465-73.

11. Shin J-W, Choi J, Huh C-H, Na J-I. Two Cases of Pigmented Contact
Dermatitis Caused by Pure Henna Hair Dyes. Annals of Dermatology.
2018;30:735.

12. Serrano G, Pujol C, Cuadra J, Gallo S, Aliaga A. Riehl's melanosis:
pigmented contact dermatitis caused by fragrances. J Am Acad Dermatol.
1989;21(5 Pt 2):1057-60.

13. Arslan S, Aksan S, Ucar R, Caliskaner AZ. Contact dermatitis to
cobalt chloride with an unusual mechanism. Prosthet Orthot Int.
2015;39(5):419-21.

14. Thyssen JP, Menne T. Metal allergy--a review on exposures,
penetration, genetics, prevalence, and clinical implications. Chem Res
Toxicol. 2010;23(2):309-18.\selectlanguage{english}
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