Acetophenone azine: 2021 allergen of the year

By Kathryn Schwarzenberger, MD, July 1, 2021

In this month’s Clinical Applications column, Physician Editor Kathryn Schwarzenberger, MD, talks with Denis Sasseville, MD, and Nadia Raison-Peyron, MD, about their recent Dermatitis paper about the allergen of the year, "Acetophenone azine."

DermWorld: Many of us who love allergic contact dermatitis eagerly await the announcement of the “Contact Allergen of the Year.” The 2021 winner is acetophenone azine! I suspect many of our members will not be familiar with this. Can you explain what this is and where our patients may encounter it?

Dr. Sasseville and Raison-Peyron: Acetophenone azine is a chemical that belongs to the ketazine family, members of which are used as industrial biocides and intermediates in organic chemistry. It was, however, recently identified as a potent sensitizer in a dozen or so cases of severe allergic contact dermatitis from protective shin guards and sports footwear. The culprit objects were padded with ethyl vinyl acetate (EVA) foam that gave strong positive reactions when patch tested. Given that acetophenone azine is not an ingredient in the synthesis of EVA, it is believed to be formed “in situ” through reactions taking place between other additives.

DermWorld: Is this an allergy we are likely to be diagnosing? When should we suspect it and what other allergens could also be likely suspects?

Dr. Sasseville and Raison-Peyron: Allergic contact dermatitis from acetophenone azine should be suspected in any patient, often a child, who presents with dermatitis localized to areas in contact with sports or other equipment padded with EVA. The degree of suspicion is even greater if, when patch tested, the patient reacts positively to a fragment of the padding material but negatively to baseline, shoe, rubber, glues, and plastics series.

DermWorld: Is acetophenone azine commercially available for patch testing? If not now, do we have any hope that it might be soon?

Dr. Sasseville and Raison-Peyron: Unfortunately, acetophenone azine is not commercially available as an allergen for patch testing. It can be bought from suppliers of chemical products and mixed in petrolatum at a concentration of 0.1% for patch testing. We have suggested that it should be included in any patch testing shoe series.

“Unfortunately, acetophenone azine is not commercially available as an allergen for patch testing. It can be bought from suppliers of chemical products and mixed in petrolatum at a concentration of 0.1% for patch testing. We have suggested that it should be included in any patch testing shoe series.”

DermWorld: Do you have any tips for managing allergic contact dermatitis in patients in whom you suspect this allergy? Are there alternatives or other ways to avoid exposure?

Dr. Sasseville and Raison-Peyron: Affected patients need to stop further exposure to the suspected objects and require proper treatment. The initial sensitization is mostly due to shin guards (large area of contact, thin skin, sweating, and friction), with subsequent involvement of other body parts exposed to EVA-containing equipment (sport shoes, flip-flops, insoles, swimming goggles, bicycle saddles, etc.). Wearing long socks or layers of clothing under the shin guards may help preventing sensitization but will not afford adequate protection to an already sensitized individual. Patients should seek EVA-free shin guards or other equipment whose padding is made of urethane foam, felt, or silicone. Unfortunately, EVA is used extensively, and a study carried out by the French equivalent of the American FDA revealed that 14% of sampled footwear contained acetophenone azine. It is very likely that an unknown number of patients with foot or anterior leg dermatitis diagnosed as irritant contact dermatitis, or dyshidrosis, are in fact allergic to acetophenone azine.

“Patients should seek EVA-free shin guards or other equipment whose padding is made of urethane foam, felt, or silicone. Unfortunately, EVA is used extensively, and a study carried out by the French equivalent of the American FDA revealed that 14% of sampled footwear contained acetophenone azine.”

DermWorld: How are new allergens like this usually discovered?

Dr. Sasseville and Raison-Peyron: Identification of new allergens initially requires correspondence with the manufacturer of the suspected object or product, to obtain full disclosure of its constituents, and ideally samples for patch testing. Unfortunately, this approach is often unsuccessful, as the industry is notoriously secretive about its manufacturing processes. This is when interactive collaboration between dermatology and chemistry plays a crucial role in the discovery of new sensitizers, as exemplified by the superb detective work carried out by Dr. Raison-Peyron and her co-workers. The techniques usually employed consist of gas or liquid chromatography coupled with mass spectrometry. These assays are time consuming and costly, and are not readily available or accessible outside of academic centers.

DermWorld: Who decides which allergen gets the august title of “Contact Allergen of the Year”? Any hints about possible future candidates we might look forward to seeing?

Dr. Sasseville and Raison-Peyron: The decision to create a journal section titled “Allergen of the Year” was made by the Board of Directors of the American Contact Dermatitis Society (ACDS) more than 20 years ago. Dr. Don Belsito has been spearheading this initiative, and each year announces the winning entry at the annual meeting of the ACDS. For many years, this allergen was selected by the members of the North American Contact Dermatitis Group (NACDG). The selection is now made by a subcommittee of the ACDS, still headed by Dr. Belsito. Any member of the ACDS may submit suggestions of allergens deemed worthy of the title “Allergen of the Year.” This allergen is often new or emergent, but “older” allergens (i.e., cobalt, formaldehyde, etc.) may be chosen because of changing prevalence, presence in new sources of exposure, etc.

Denis Sasseville, MD, serves in the Division of Dermatology at McGill University Health Centre in Montreal, Quebec, Canada.

Nadia Raison-Peyron, MD, serves in the Department of Dermatology at the University of Montpellier in Montpellier, France.

Their paper appeared in Dermatitis.

Dr. Sasseville receives royalties from UpToDate for a contribution unrelated to contact dermatitis. Dr. Raison-Peyron has no conflicts of interest to disclose.

Disclaimer: The views and opinions expressed in this article do not necessarily reflect those of DermWorld.

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