Allergic contact dermatitis from pantolactone and dexpanthenol in wound healing creams

Pantolactone is used in the production of D‐panthenol (dexpanthenol), the alcohol analogue of panthothenic acid (vitamin B5). ¹ It is used as an animal feed additive, but also in pharmaceutical, health care and food products, and in cosmetics as a humectant and conditioning agent. Panthenol is also widely used in cosmetics because of its antistatic, hair and skin conditioning properties and in pharmaceutical products to treat dry skin and minor irritant reactions, and for its wound healing and anti‐inflammatory properties. We report the first cases of allergic contact dermatitis (ACD) from pantolactone.

CASE REPORTS

1. Case 1

A 62‐year‐old Caucasian female had developed facial erythema due to mechanical irritation from a new oxygen mask. Her general physician had prescribed two wound healing creams, that is, Bepanthen Sensiderm and Dermacalm‐d (Bayer AG). During the following days, however, she developed a severe, focally bullous, erythema of the face and periorbital oedema (Figure 1A). The topical agents were stopped and the patient was treated with oral prednisolone followed by topical corticosteroids until reaching complete remission. Patch tests were performed with the European baseline, cosmetic, preservative and excipient series (Chemotechnique Diagnostics and AllergEAZE) and with the patient's own products (‘as is’). The patch test chambers used were IQ Ultra (Chemotechnique Diagnostics), fixed with Mefix for 48 h. Readings, performed on Day (D) 2 and D4 according to International Contact Dermatitis Research Group (ICDRG) criteria, showed a positive reaction Bepanthen Sensiderm (D2+, D4++) and Dermacalm‐d (D2++, D4+++) (Figure 1B). Their individual ingredients, kindly provided by the manufacturer, were subsequently patch tested and showed a positive reaction to pantolactone (D2++, D4+++), Dexpanthenol liquid (D2+/−, D4+) and Dexpanthenol Basf liquid (D2+/−, D4+) (Figure 1C). The three haptens were tested undiluted as provided by the manufacturer (gel and liquid forms). We thus confirmed ACD from dexpanthenol and pantolactone present in Bepanthen Sensiderm and Dermacalm‐d. Six unexposed controls were negative to the pantolactone and panthenol preparations.

FIGURE 1.

(A) Case 1: clinical manifestations of severe allergic contact dermatitis to dexpanthenol and pantolactone. (B) Positive patch test on D4 to Bepanthen Sensiderm (++) and Dermacalm‐d (+++). (C) Positive patch test on D4 to pantolactone (+++), dexpanthenol D‐panthenol liquide (+) and Dexpanthenol Basf liquide (+). (D) Case 2: positive reaction to pantolactone in pet. in a dilution series showing dose‐dependent reactions: 1% +, 3% ++, 5% and 10% +++. Positive reaction on D4 to Bepanthen Derma (++) and a doubtful reaction to Bepanthen Eczema, as well as to dexpanthenol provided by the manufacturer. (E) Name of medical devices tested containing dexpanthenol alone, or together with pantolactone

2. Case 2

A 38‐year‐old Caucasian female atopic patient consulted because of a persistent hand dermatitis treated with topical corticosteroids, and during the last 6 months also with Bepanthen Eczema and Bepanthen Derma (Bayer) with, however, only limited improvement. There was no clear correlation with her job (administration), nor any known allergies. Patch tests were performed, as in Case 1, and readings on D2 and D4 showed a positive reaction to Bepanthen Derma (D2+, D4++), and a doubtful reaction to Bepanthen Eczema. Other patch tests were negative, including dexpanthenol 5% pet. (Chemotechnique Diagnostics). The individual ingredients of Bepanthen Derma, kindly provided by the manufacturer, were patch tested and positive, dose‐dependent reactions were observed to a dilution series of pantolactone in pet. (1% +, 3% ++, 5% and 10% +++) (Figure 1D). The 5% concentration tested negatively in five controls.

DISCUSSION

A worsening skin condition upon application of a wound healing cream should raise suspicion of ACD. Both products reported here contained dexpanthenol, which is a well‐established contact allergen,^{1, 2} even in children. ³ Conflicting results have been published whether this allergen is a frequent or rare skin sensitizer, and in order to allow further surveillance it was recently included as a recommended addition to a newly proposed European cosmetic series. ⁴ Pantolactone is an impurity (~1%) of panthenol raw materials, and because it is likely formed from panthenol in acidic aquatic media (i.e., sweat), it might not be excluded that this here newly reported cosmetic allergen is the actual sensitizer in panthenol‐containing preparations (Figure 2).^{5, 6} A possible argument in this direction is that pantolactone was also the strongest reactor in our two patients. Our cases once again highlight the utmost importance of identifying new emerging allergens through testing individual ingredients from all personal products used.

FIGURE 2.

Chemical formulas of pantolactone and dexpanthenol. Dexpanthenol can disintegrate to pantolactone due to ‘lactonization’ in an acid aqueous environment such as the skin.

AUTHOR CONTRIBUTIONS

Gabriela Blanchard: Writing – original draft; conceptualization; writing – review and editing; methodology. Stefan Kerre: Conceptualization; investigation; writing – original draft; methodology; writing – review and editing. Anna Walker: Investigation; writing – review and editing. Ella Dendooven: Conceptualization; investigation; writing – review and editing; methodology. Olivier Aerts: Conceptualization; methodology; writing – review and editing; validation. An Goossens: Methodology; validation; conceptualization; writing – review and editing. Michel Gilliet: Writing – review and editing; conceptualization. Teofila Seremet: Conceptualization; methodology; investigation; writing – original draft; writing – review and editing; validation.

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

ETHICS STATEMENT

Discussed patients gave consent for her photographs and medical information to be published in print and online and with the understanding that this information may be publicly available.

Blanchard G, Kerre S, Walker A, et al. Allergic contact dermatitis from pantolactone and dexpanthenol in wound healing creams. Contact Dermatitis. 2022;87(5):468‐471. doi: 10.1111/cod.14198