Vitamin B12 gây ra phát ban mụn trứng cá (Thứ sáu, 23 tháng 06, 2017)

Accepted: 21 April 2017

DOI: 10.1111/jocd.12360

MASTER CASE PRESENTATION

Acneiform eruptions caused by vitamin B12: A report of five cases and review of the literature

Stefano Veraldi MD| Susanna Benardon MD| Marco Diani MD| Mauro Barbareschi MD

Department of Pathophysiology and Transplantation, Universita degli Studi diMilano, I.R.C.C.S. Foundation, `Ca Granda Ospedale Maggiore Policlinico, Milan, Italy Correspondence Prof Stefano Veraldi, Dermatology Unit, University of Milan, Via Pace 9, 20122Milan, Italy.

Email: stefano.veraldi@ unimi.it

Summary

We describe five cases of acneiform eruption caused by vitamin B12 in five females aged 37, 32, 62, 29, and 21 years, respectively. The eruption appeared from 1 week to 5 months after the beginning of the therapy with i.m. or oral vitamin B12. Clinical picture was characterized by papules and pustules located on the face. In three patients, similar lesions were also present on the neck, shoulders, chest, and upper portion of the back. Comedones and cysts were absent. In two patients, serum vita-min B12 levels were very high. Histopathologic examination in one patient revealed an eosinophilic folliculitis. Spontaneous and complete remission was observed in all patients 3-6 weeks after vitamin B12 discontinuation.

KEYWORDS: acne, acneiform eruptions, vitamin B12

1|INTRODUCTION

Acneiform eruptions can be induced by several drugs. Acneiform eruptions caused by vitamin B12, although well known, actually were rarely reported in the literature. We present five cases of acneiform eruption caused by vitamin B12 and a review of the literature. We also suggest some pathogenetic hypotheses.

2|CASE REPORTS

Case 1. A 37-year-old Caucasian woman was admitted because of an acneiform eruption. The patient stated that she was suffering from slight depression and asthenia, for which, 6 months before, she began a therapy with i.m. vitamin B12. The patient also stated that the rash had appeared approximately 1 month earlier. Dermatological examination revealed the presence of numerous papules and some pustules, located especially on the face; some lesions were also present on the neck, shoulders, chest, and upper portion of the back. Papules and pustules were round, red in color, with a diameter ranging from 1 to 3 mm (Figures 1 and 2). The patient complained of mild pruritus.

General physical examination did not reveal anything pathological. Gynecologic examination and pelvic ultrasounds were normal. All laboratory examinations, including hormone dosages, were within normal ranges or negative. Serum vitamin B12 was2840 pg/mL (immune enzymatic method; normal values: 180-900 pg/mL). Bacteriologic examinations of pustules were positive for Staphylococcus epidermidis. Histopathologic examination of a retroauricular 3-mm punch biopsy revealed an eosinophilic folliculitis.

Treatment with vitamin B12 was stopped. Spontaneous improve-ment was observed within 3 weeks. Complete remission was observed 3 weeks later. A 7-year follow-up was negative.

Case 2. A 32-year-old Caucasian woman was admitted because of chronic-relapsing acneiform eruptions. The patient declared that she was recently treated with two courses of i.m. vitamin B12. The patient observed the sudden appearance of a rash just a few days after each vitamin B12 i.m. injection as well as the spontaneous dis-appearance of the lesions 10 days later.

Dermatologic examination revealed the presence of papules and pustules located on the face, in particular the forehead and perioral region. They were round, red in color, with a diameter ranging from1 to 3 mm. All lesions were asymptomatic. General examination did not reveal anything pathological. Gynecologic examination and pelvic ultrasounds were normal.

All laboratory examinations, including hormone dosages, were within normal limits or negative. Serum vitamin B12 was 1839 pg/mL (immune enzymatic method). Bacteriologic examinations of pustules were negative.

Treatment with vitamin B12 was stopped. Spontaneous and complete remission was observed within 3 weeks. Follow-up(3 years) was negative.

Case 3. A 62-year-old Caucasian woman was admitted because of a papulo-pustular rash on the face. The patient stated that she was suffering from mild polyneuritis of unknown etiology, for which she was in therapy with i.m. pyridoxine and hydroxocobalamin. The patient also stated that this eruption had appeared 2 weeks earlier. Dermatologic examination revealed papules and pustules located in the forehead and cheeks. They were round, red in color, with a maximum diameter of 4 mm. All lesions were asymptomatic.

General physical examination did not reveal anything pathological. Gynecologic examination and pelvic ultrasounds were normal.All laboratory examinations, including hormone dosages, were within normal ranges or negative. Bacteriologic examinations of pustules were negative. Hydroxocobalamin and pyridoxine were stopped. Spontaneous and complete remission was observed within 3 weeks. A 3-year follow-up was negative.

Case 4. A 29-year-old Arab woman began in November 2014 a therapy with i.m. cyanocobalamin (1 g/week). In April 2015, she developed an acneiform eruption characterized by papules and pustules located on the face, shoulders, chest, and upper portion of the back. The lesions were round, red in color, with diameter ranging from 1 to 5 mm. All lesions were asymptomatic.

The patient refused general physical examination, gynecologic examination, and pelvic ultrasounds. All laboratory examinations, including hormone dosages, were within normal ranges or negative.

Bacteriologic examinations of pustules were negative. Cyanocobalamine was stopped. Spontaneous and complete remission was observed within 3 weeks. A 7-month follow-up was negative.

Case 5. A 21-year-old Caucasian woman, in therapy with oral vitamin B6 hydrochloride, vitamin B1 nitrate, vitamin B2, and vitaminB12 for weight loss, in March 2015 developed an acute papulopustular eruption on the face, neck, shoulders, chest, and back. This eruption appeared approximately 4 weeks after the beginning of the therapy. Clinical picture was similar to that of patient no. 4 (Fig-ures 3-5). General physical examination did not reveal anything pathological. Gynecologic examination and pelvic ultrasounds were normal. All laboratory examinations, including hormone dosages, were within normal ranges or negative. Bacteriologic examinations of pustules were negative. The therapy was stopped: Spontaneous and complete remission was observed 6 weeks later. An 8-month follow-up was negative.

3|DISCUSSION

Acneiform eruption caused by vitamin B12 was first reported in1958 by Jadassohn et al. Since then, very few articles about this topic were published. Therefore, this eruption may be considered as rare. However, it is possible that the incidence of vitamin B12-induced acneiform rash is underestimated, considering the wide use of vitamin B12 in several Western European countries.

High daily dosages and/or long periods of therapy8with vitamin B12 were suggested as possible pathogenetic factors in these eruptions; however, pharmacologic history in our five patients does not confirm these statements. It is possible that only predisposed subjects, with a specific susceptibility to vitamin B12 action, can develop these acneiform eruptions.

Rare cases of eruptions were caused by the association of vita-min B12 with vitamins B1 (thiamine) or B2 (riboflavin) or B6 (pyridoxine).

Vitamin B12-induced eruptions have been observed especially inadult (or elderly) women9, because in the past, this vitamin was mainly used in pregnancy. It was also used for the treatment ofanorexia, weight loss, anemia, and neuritis. To date, only two malecases were described.5,7The eruption is often acute and begins days or weeks after the beginning of the therapy with vitamin B12.3,5,7,10It is characterized clinically by inflammatory papules and pustules located especially on the face, but also on the neck, shoulders, chest, and back1,3,9. Comedones and cysts are usually absent.10Sponta-neous and complete remission is observed 1-8 weeks after vitaminB12 interruption (usually 2-3 weeks).

Teawry et al. detected that anaerobe metabolism of Propioni-bacterium acnes is vitamin B12-dependent. Another pathogenetic hypothesis of vitamin B12-acneiform rash is based on the possible role of iodine, which is used for extraction of vitamin B12. It is also possible that these eruptions are due to desoxy-adenosylcobalamin and/or methylcobalamin, that is, the metabolically active forms of vitamin B12. Recently, it was demonstrated that vitamin B12 supplementation in P. acnes cultures promotes the synthesis of porphyrins, which induce inflammation in acne.

Alogens (bromine, fluorine, iodine, halothane), antidepressants (amineptine, lithium, and imipramine), anti-epileptics (hydantoin, phenobarbital, and trimethadione), and hormones (anabolic steroids, androgens, corticosteroids, and gonadotropins) can maintain or worse a preexisting acne or cause acneiform eruptions.13,14Amio-darone, azathioprine, cyclosporin, disulfiram, ethionamide, isoniazid, maprotiline, quinine, rifampicin, sirolimus, tetraethylthiuram, thioura-cil, thiourea, troxidone, and group D vitamins are more rarelyinvolved. Also radiotherapy and PUVA-therapy must me included.

Acneiform eruptions have some common features: (i) They usually occur in adults; (ii) the onset is often acute and characterized especially by papules and pustules which may involve the face, neck, shoulders, chest, and upper back; (iii) comedones and cysts are usually absent; (iv) the eruption may be accompanied by more or less severe pruritus; (v) the remission is spontaneous and complete after discontinuation of the responsible medicament; however, time of remission depends on the drug elimination rate; (vi) no scar development; and (vii) lack of relapses. We believe that, in these five patients, vitamin B12 played a pathogenetic role in the development of acneiform eruptions for several rea-sons: (i) the sudden appearance of the rash when all patients were in therapy with vitamin B12; (ii) spontaneous and complete remission after vitamin B12 discontinuation; (iii) the lack of relapses.

These factors are highly suggestive for the existence of a correlation between vitaminB12 and the appearance of acneiform eruption: In all five patients, the score according to Naranjo et al. algorithm17was 9; this suggests a high probability that acneiform eruptions were due to vitamin B12.

A careful pharmacologic history is therefore necessary in all patients with acneiform eruptions.

REFERENCES

1. Jadassohn W, Paillard R, Hofer R, et al. Vitamine B12 et pousseeacne€ıforme. Dermatologica. 1958;116:349.

2. Ade G. Poussees d’eczema seborrheique ou acne€ıforme probable-ment consecutivesa un traitementa la vitamine B12. Dermatologica.1958;116:366.

3. Jadassohn W, Paillard R. Vitamine B12 et poussee acne€ıforme.Dermatologica. 1960;120:128.

4. Goldblatt S. Der Vitamin B12-Gehalt im Blitserum bei acneiformenHautkrankheiten. Hautarzt. 1966;17:106-108.

5. Puissant A, Vanbremeersch F, Monfort J, et al. Une nouvelle der-matose iatrogene: l’acne provoquee par la vitamine B12. Bull Soc FrDermatol Syphiligr. 1967;74:813-815.

6. Michel PJ. Un cas d’acne importante du visage consecutifal’adminis-tration de vitamine B12. Bull Soc Fr Dermatol Syphiligr. 1968;75:131-132.

7. Dugois P, Amblard P, Imbert R, et al. Acnesa la vitamine B12. BullSoc Fr Dermatol Syphiligr. 1969;76:382-383.

8. Leoni A. Quadri acneiformi da vitamina B12. Giorn It Dermatol.1972;47:210-211.

9. Braun-Falco O, Lincke H. The problem of vitamin B6/B12 acne. Acontribution on acne medicamentosa. Munch Med Wochenschr.1976;118:155-160.

10. Dupre A, Albarel N, Bonafe JL, et al. Vitamin B-12 induced acnes.Cutis. 1979;24:210-211.

11. Sherertz EF. Acneiform eruption due to “megadose” vitamins B6 andB

12. Cutis. 1991;48:119-120.12. Tewary M, Taibjee S, Ladoyanni E. Vitamin B12 induced acneiformeruption. Abstract. Vienna: “16th Congress of the European Academyof Dermatology and Venereology”; 2007: P6.

13. Trevisan V, Veraldi S. Eruzione acneiforme da vitamina B12. J Acne.2008;8:17-19.

14. Benardon S, Trevisan V, Barbareschi M, et al. Acneiform eruptionscaused by vitamin B12: a report of three cases and revie w of the lit-erature. Eur J Acne. 2012;3:69-72.

15. Balta I, Ozuguz P. Vitamin B12-induced acneiform eruption. CutanOcul Toxicol. 2014;33:94-95.

16. Kang D, Shi B, Erfe MC, et al. Vitamin B12 modulates the transcrip-tome of the skin microbiota in acne pathogenesis. Sci Transl Med.2015;7:293ra103.

17. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating theprobability of adverse drug reactions. Clin Pharmacol Ther.1981;30:239-245.