1. Recommendation to include hydroxyethyl (meth)acrylate in the British Baseline Patch Test Series
S. Rolls1, M. M. Chowdhury2, S. Cooper3 , P. Cousen4, A. M. Flynn5, S. A. Ghaffar6, C. M. Green6, A. Haworth7, C. Holden8, G. A. Johnston9, K. Naidoo4, D. I. Orton10, C. Reckling11, R. A. Sabroe8, M. Scorer9, N. M. Stone12, D. Thompson13, S. Wakelin14, M. Wilkinson15, D. A. Buckley1.
Royal United Hospital Bath, U.K.1; University Hospital of Wales, Cardiff, U.K.2;Oxford University Hospital, U.K.3;South Tees Hospital NHS Foundation Trust, U.K.4; South Infirmary Victoria University Hospital, Cork, Ireland5; Ninewells Hospital, Dundee, U.K.6; Portsmouth Hospital NHS Trust, U.K.7; Sheffield Teaching Hospitals NHS Foundation Trust, U.K.8; Leicester Royal Infirmary, Leicester, U.K.9; Royal Free Hospital, London, U.K.10; Kent and Canterbury Hospital, Canterbury, U.K.11; Royal Gwent and Nevill Hall Hospitals, Newport, U.K.12;Sandwell and West Birmingham Hospitals NHS Trust, U.K.13; Imperial College Healthcare NHS Trust, London, U.K.14; Leeds Teaching Hospital NHS Trust, Leeds, U.K.15
British Journal of Dermatology. DOI: /bjd.17708

2. Lead Researcher
Dr Deirdre Buckley

3. Introduction What’s already known?
A significant rate of sensitisation to (meth)acrylates has been demonstrated worldwide.
Increasing demand for acrylic nail fashion is putting consumers and nail technicians at risk of sensitisation to (meth)acrylates.

4. Objective
To determine whether inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% in petrolatum (pet.) in the baseline patch test series detects cases of treatable (meth)acrylate allergic contact dermatitis (ACD).

5. Methods
Data were collected prospectively from 15 U.K. and Irish dermatology departments between December 2016 and November 2017.
A total of 5,920 consecutive patients with eczema referred to a dermatology clinic for patch testing were tested to the extended British baseline patch test series including 2-HEMA 2% pet.
Patients with a history of (meth)acrylate exposure were selectively tested with a short series of eight (meth)acrylate allergens.
Those who tested positive to 2-HEMA at the day 2 reading had the series of 8 (meth)acrylates added on day 2.

6. Methods
The eight (meth)acrylate allergens tested in the short series were:
2-hydroxypropyl methacrylate (2-HPMA)
Ethyl acrylate (EA)
Ethylene glycol dimethacrylate (EGDMA)
Tetraethylene glycol dimethacrylate (TEGDMA)
2-hydroxyethyl acrylate (2-HEA)
1,6-hexanediol diacrylate (1,6 HDDA)
Ethyl cyanoacrylate (ECA)
Triethylene glycol diacrylate (TREGDA)
Allergens were obtained from Chemotechnique Diagnostics (Vellinge, Sweden).

7. Methods
Readings were carried out according to European Society of Contact Dermatitis (ESCD) guidelines on day 2 and day 4, or on day 7 if patients had the short (meth)acrylate series added at day 2.
Allergic patch test reactions were scored according to International Contact Dermatitis Research Group criteria.
Patients who had the short (meth)acrylate series added at day 2 after a positive screening test to 2-HEMA were recorded, and were distinguished from those predicted to have (meth)acrylate allergy by history, who had the short series added at day 0.
Demographic details recorded were age, sex, occupation, history of atopy and history of use of nail products.
The primary site of dermatitis was recorded.

8. Results
5,920 consecutive eczema patients were patch tested to the extended baseline series, including 2-HEMA, at the 15 U.K. patch test centres.
Of these, 669 selected patients with a history of (meth)acrylate exposure (n=633), or who tested positive to 2-HEMA in the baseline series (n=36), were tested to the short (meth)acrylate series.
140 patients (2.4% of 5,920) tested positive to at least one (meth)acrylate allergen with a total of 416 positive reactions.
102 patients (1.7% of 5,920) tested positive to 2-HEMA.
Of the 140 patients with proven (meth)acrylate ACD, 104 had the (meth)acrylate series added at day 0, as they had a clear history of (meth)acrylate exposure.
36 patients (0.6% of 5,920) who had provided no history of (meth)acrylate exposure had the series added at day 2, following a positive reaction to 2-HEMA in the baseline series.

9. Results The top (meth)acrylates eliciting a positive reaction were:
2-HEMA (n=102; 1.7%)
2-HPMA (n=61; 1% minimum predicted value if tested in all patients)
2-HEA (n=57; 1% minimum predicted value if tested in all patients)
Irritant reactions were recorded in 2 patients.
34 patients with (meth)acrylate ACD did not test positive to 2-HEMA in the baseline patch test series, but had been suspected to have (meth)acrylate allergy based on their history.
ECA recorded the highest number of positive reactions (n=16) in these patients.
Positive reactions to (meth)acrylates not included in our short (meth)acrylate series included: diethyleneglycol diacrylate (DEGDA) 0.1% pet. in 23 patients; methyl methacrylate (MMA) 2% pet. in 16 patients and ethyl methacrylate (EMA) 2% pet. in 11 patients.

10. Results 94% (n=131) of (meth)acrylate allergic patients were female.
The mean age was 41.2 years (median 38; range ).
40% of patients (56) were atopic.
The mean duration of dermatitis was 24 months (median 24; range 2 – 216).
97 patients were exposed to (meth)acrylates in their professionally-applied nail cosmetics.
38 patients were exposed occupationally (37 to cosmetic nail (meth)acrylates & 1 to (meth)acrylates in printing).
5 patients were exposed to medical devices (3 to surgical glue, 1 to a stoma device, 1 to a TENS machine).

11. Patient-reported sources of exposure

12. Discussion
This large multi-centre prospective audit has confirmed that the proportion of consecutively patch tested patients in the U.K. with a positive test to 2-HEMA is 1.7%.
This is well above the ESCD recommended threshold of % for inclusion in a baseline patch test series.

13. Discussion
We have shown an increase in the number of cases of (meth)acrylate ACD identified when 2-HEMA is included in the baseline series.
We would have missed almost 1/3 of cases of (meth)acrylate ACD had 2- HEMA not been incorporated in the baseline series.
2-HEMA was the most frequent (meth)acrylate allergen to test positive.

14. Discussion
Coupled reactivity amongst the acrylate class is well documented.
416 positive reactions were seen in 140 patients (mean 3 reactions per patient)
2-HEMA is the allergen most likely to show coupled reactivity, supporting its use as a screening allergen.
No cases of patch test active sensitisation were recorded in this audit or identified in our literature review spanning two decades.
Experienced clinicians interpreted results in all our participating units.
Only two irritant reactions were recorded.

15. Discussion
The frequency of (meth)acrylate allergy has increased in recent years with a shift in exposure from occupational to recreational use.
Most (meth)acrylate exposure now occurs through the beauty industry.
69% of our patients were consumers of professionally-applied acrylic nails but did not work in the industry.
27% of our patients were professional nail workers (all were also consumers).
3% were sensitised by medical devices.
1% were sensitised by working with printing ink.

16. Discussion
There are numerous points during the application of acrylic nails whereby a consumer is at risk of sensitisation.
Nail technicians are often unaware of health risks, inadequately trained and do not wear personal protective equipment.
The epidemic of allergy to (meth)acrylates, if not controlled, could mirror the recent epidemic of allergy to the preservative methylisothiazolinone.

17. Discussion
A false sense of security has been provided to the nail and beauty industry by regulators including The Scientific Committee on Consumer Safety (SCCS) of the EU. It stated that “2-HEMA is unlikely to pose a risk of sensitisation when applied appropriately to the nail plate at concentrations up to 35%”, that “the normal nail plate acts as a good barrier to the penetration of chemical substances" and that "2-HEMA polymerises rapidly under UV-curing, leaving little chance for monomers to be absorbed”. It determined that any risk of sensitisation is posed by “inappropriate application by a consumer, or constant exposure in a nail technician.”

18. Discussion
Cyanoacrylates, (such as ECA (Superglue®) and 2-octyl cyanoacrylate (Dermabond®)), in nail, eyelash, surgical and instant glue do not usually show concomitant sensitisation to (meth)acrylates including 2-HEMA.
10 of our patients with (meth)acrylate ACD (9%) reacted to ECA alone and were not detected by testing to 2-HEMA.
Cyanoacrylate ACD is often clinically obvious and the need for patch testing with a (meth)acrylate series detected in these cases by history.

19. BSCA (Meth)acrylate series 2019
Our short series of 8 (meth)acrylates did not identify all patients with (meth)acrylate allergy.
Some units tested extra (meth)acrylates and identified cases which were missed with the short series of 8 plus 2-HEMA.
As the results of these findings and a literature review, we have identified 15 (meth)acrylates of interest.
We believe that this series of 15 will detect relevant allergy, while avoiding unnecessary morbidity from multiple strongly positive patch test reactions from related allergens.

20. BSCA (Meth)acrylate Series 2019
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Ethyl cyanoacrylate (ECA) 10% pet
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Expected to become commercially available in 2019

21. Conclusions: What does this study add?
Inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% pet. in the baseline series detects treatable (meth)acrylate ACD.
Identifying (meth)acrylate ACD is important as it can have adverse health consequences for patients who require composite fillings, surgical glue and bone cement, all of which contain (meth)acrylates.
We recommend that 2-HEMA 2% pet. be added to the British baseline patch test series, and to baseline series used in other countries.
We also suggest a standardised (meth)acrylate series which is likely to detect most cases of (meth)acrylate allergy.

22. Photographs of the research team

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