Vitamin B12–induced acneiform eruption

Abstract

Cutaneous acneiform eruptions are a side effect of many medications, including vitamin B12 therapy. However, reports of vitamin B12–induced acne are rare. We present a 67-year-old woman with a new diagnosis of pernicious anemia who developed a sudden acneiform eruption on the face after treatment with high-dose vitamin B12. Other medications that have been implicated in drug-induced acne include but are not limited to steroids, antibiotics, immunosuppressants, biologics, and vitamin B1 and B6. The pathogenesis is likely due to a transcriptome change in Propionibacterum acnes, the organism responsible for acne vulgaris. Cessation of the offending agent leads to a regression in symptoms.

KEY POINTS

• Several medications have been implicated in causing drug-induced acne, including steroids, oral contraceptives, and vitamin B12.

• First-line treatment of drug-induced acne is cessation of the drug.

• The pathogenesis likely involves upregulated porphyrins, which increase inflammation.

• Differences between drug-induced acne and acne vulgaris include the absence of comedones and cysts.

CME

CME Information: https://ce.bswhealth.com/BUMC_Proceedings_CME_info

Credit Claim Process: To claim CME for this activity, read the entire article and go to https://ce.bswhealth.com/2025BUMC_Proceedings_Jan_Enterohemorrhagic. You will register for the course, pay any relevant fee, take the quiz, complete the evaluation, and claim your CME credit.

Dates for credit: January 1, 2025, to January 1, 2026. For questions about CME credit, visit our website ce.bswhealth.com/contact-us.

Case summary

A 67-year-old woman presented to the hospital with a 6-month history of fatigue and unintentional weight loss from loss of appetite and was found to have antibodies against intrinsic factor on laboratory workup after undergoing upper endoscopy. The patient was subsequently diagnosed with pernicious anemia and started on vitamin B12 and folate therapy.

Two days after the first intramuscular B12 injection, the patient developed an acneiform eruption characterized by monomorphic erythematous papules and pustules involving the glabella, nose, cheeks, and perioral area (Figure 1). The patient did not have underlying comedones or cystic lesions. We hypothesized that her acneiform eruption was due to a rare adverse effect of vitamin B12 therapy. The patient was continued on vitamin B12 supplementation because treatment of the pernicious anemia was obligatory. In the case of a true allergic reaction to the intramuscular vitamin B12 supplement, alternative routes of administration (e.g., intrinsic factor–dependent enteral route) should be considered. Her symptoms were managed with clindamycin gel and ketoconazole cream, and she had near total resolution of her acneiform eruption 2 weeks after onset. However, at a subsequent follow-up, she reported similar acneiform eruptions after every infusion of vitamin B12. Cutaneous symptoms are currently being managed with metronidazole cream and oral minocycline.

Figure 1.

Diffuse, erythematous, papular acneiform eruption present on the medial forehead, nose, bilateral cheeks, and chin.

Clinical questions

1. A 50-year-old woman with a long-term history of severe facial eczema presents with nonpruritic facial erythema and scattered papules on the cheeks and forehead with no crusting, scaling, indentation, or comedones. What is the most likely cause of this patient’s rash?

   1. Chronic steroid use

   2. Adult-onset acne

   3. Eczema herpeticum

   4. Impetigo

2. Which is a feature of drug-induced acne but not acne vulgaris?

   1. Elderly age

   2. Absence of comedones

   3. Presence of microcysts

   4. Sudden onset

Answers are provided at the end of the article.

Discussion

Many medications have been associated with causing acneiform eruptions on the skin, including but not limited to steroids, immune modulators, and vitamins. Rarely, vitamin B12 has been implicated in acneiform eruptions, with only a few cases reported in the literature.^1,2

The pathogenesis of vitamin B12–induced acneiform eruption is not fully understood. Acneiform eruptions may be associated with higher individual vitamin B12 levels. This may be due to genetic variation² or through medication-induced changes. Zamil et al compared vitamin B12 levels in patients with postadolescent acne and healthy individuals and found an increase in B12 deficiency in the healthy cohort.³ Another study showed that vitamin B12 levels were significantly lower after 4 months of treatment with isotretinoin for acne vulgaris.⁴ Although acne formation involves a combination of increased sebum formation, follicular hyperkeratinization, proliferation of skin bacteria, and inflammation, the main organism thought to be responsible is Propionibacterum acnes.⁵ Furthermore, the anaerobic metabolism of Propionibacterum acnes is vitamin B12 dependent.² Vitamin B12 has been shown to alter the transcriptome of P. acnes. When vitamin B12 is supplemented, P. acnes downregulates its own synthesis pathway of vitamin B12 and upregulates porphyrins, which are known to induce inflammation in acne.⁵

Other molecules that may be implicated in the pathogenesis of vitamin B12–induced acne include deoxyadenosylcobalamin, methylcobalamin, and iodine.² Deoxyadenosylcobalamin and methylcobalamin are the metabolically active forms of vitamin B12.² Iodine is used in the isolation of vitamin B12 and has been widely reported to induce acne.³ It has been hypothesized that the association between acne eruptions and dairy products may be due to iodine content in the milk from iodine-containing animal feeds and milk sanitizing solutions.³

A more extensive list of drugs associated with acneiform eruptions includes halogenated aromatic hydrocarbons, antibiotics, nystatin, corticotropin, naproxen, hydroxychloroquine, oral contraceptives, halogenated chemicals, immunosuppressants, lithium, anticonvulsants, epidermal growth factor receptor inhibitors, tumor necrosis factor alpha antagonists, and vitamins B1 and B6 (Table 1).⁶ Corticosteroids have been shown to induce acne on a dose-dependent basis. Anabolic steroids including androgens and testosterone have long been associated with acneiform eruptions in body builders and in those who abuse anabolic steroids.⁶ The mechanism of lithium-induced acneiform eruptions is associated with direct follicular plugging and induction of the inflammatory cascade through neutrophil degranulation.⁶ In contrast, the pathogenesis of halogen-induced acne includes activation of intracellular aryl hydrocarbon receptor, which activates cytochrome p450 1A1 leading to comedogenesis.⁶

Table 1.

Additional drugs that induce acneiform eruptions⁶

Drug class	Examples
Macrolide antibiotics	Azithromycin, clarithromycin
Anti-tuberculosis antibiotics	Isoniazid, rifampin
Antifungals	Nystatin
Hormones	Oral contraceptives
Tetracyclines	Doxycycline, tetracycline
Systemic steroids	Prednisone, triamcinolone
Halogens	Bromide or iodine-containing chemicals
Immunosuppressants	Azathioprine, cyclosporine
Mood stabilizers	Lithium
Anticonvulsants	Phenobarbital, phenytoin
Epidermal growth factor receptor inhibitors	Gefitinib, vandetanib
Vitamins	B1, B6

Presentation of vitamin B12–induced acneiform eruptions are characterized by a papulopustular rash without comedones or cysts that can cover the face, forehead, chin, neck, shoulders, chest, and back.^1,2 The diagnosis of vitamin B12–induced acneiform eruption can be made clinically and does not require a biopsy.² Vitamin B12–induced acne can be differentiated from acne vulgaris by the presence of pruritus, correlation between drug use and eruption, sudden onset, patient age, and the absence of comedones and microcysts. Most of these reactions occur within several days of initiation of therapy.⁷ Acneiform eruptions do not scar and regress with cessation of the offending agent.² Additionally, increased dosing or length of therapy does not lead to a more severe eruption.^2,7

We conclude that our patient’s acneiform eruption was most likely due to an adverse effect of vitamin B12 therapy. Healthcare providers should be aware of this potential adverse effect and perform a thorough drug review when a patient experiences an acneiform eruption, including reviewing drug and eruption onset.

Answers to clinical questions

Question 1, a, chronic steroid use. Drug-induced acne is characterized by a sudden onset of erythematous papules on the face, neck, shoulders, and/or back without pustules, crusting, pruritus, or comedones. Drugs that commonly cause acne include corticosteroids and oral contraceptives. This patient with a history of severe facial eczema is likely chronically applying a topical steroid, which led to her subsequent acneiform eruption. The rash was described as nonpruritic and lacked both crusting and vesicles (options c and d). Adult-onset acne most commonly occurs in patients in their early 20s and is rarer in patients over 50 years old (option b).^1,2,7

Question 2, c, presence of microcysts. Drug-induced acne can present similarly to acne vulgaris. However, distinguishing features of drug-induced acne include an older age of onset (option a), sudden onset (option d), and correlation between drug use and onset of symptoms. Acne vulgaris can be differentiated from drug-induced acne by the presence of microcysts and comedones (option b). Drug-induced acne is treated with cessation of the offending agent, while treatment of acne vulgaris includes benzoyl peroxide, topical and oral antibiotics, and topical and oral retinoids. Differentiation between these two conditions is essential because the treatments are very different.^1,2,7

Disclosure statement

The planners and faculty for this activity have no relevant financial relationships to disclose. The authors report no funding. The patient consented to publication of this case report.