Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers— results of theESSCAnetwork, 2015‐2018

Abstract

Background Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. Objectives To determine the frequency of sensitization to formaldehyde 2% aq. and co‐reactivity with FRs. To establish whether there is justification for including FRs in the EBS. Materials and Methods A 4‐year, multi‐center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. Results A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co‐reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium‐15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3‐dimethylol‐5, 5‐dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2‐bromo‐2‐nitropropane‐1,3‐diol 0.5% pet. This demonstrates that co‐reactivity varies between FRs and formaldehyde, from being virtually non‐existent in 2‐bromo‐2‐nitropropane‐1,3‐diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] −0.02 to 0.02)], to only weak concordance for quaternium‐15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. Conclusions Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.

Patch test results with the European baseline series and additions thereof in the ESSCA network, 2015‐2018

“…The question as to whether different formaldehyde releasers, including quaternium‐15, which is a longstanding constituent of the EBS, should be tested in addition to formaldehyde (ideally 2% aq.) has been addressed by another, dedicated analysis and shall not be discussed here 55 . The present results with the different formaldehyde releasers are largely similar to the more detailed, department‐wise analysis of 2013/2014 data 56 .…”

“…has been addressed by another, dedicated analysis and shall not be discussed here. 55 The present results with the different formaldehyde releasers are largely similar to the more detailed, department-wise analysis of 2013/2014 data. 56 The mixture of MDBGN and 2-phenoxyethanol 1:4 (eg, Euxyl K 400 as trademark) is still tested to a limited extent by some departments.…”

Patterns of positive patch test reactions to formaldehyde and formaldehyde releasers at the Finnish Institute of Occupational Health from 2007 to 2020

“…We compared our results with three other studies: a multicentre study from Spain by Latorre et al, 10 a study from Denmark by Lundov et al, 11 and an ESSCA network study by Whitehouse et al, 3 all presenting patterns of concomitant reactions to formaldehyde and the five releasers: quaternium-15, diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin, and 2-bromo-2-nitropropane-1,3-diol. Frequencies of positive reactions to formaldehyde and quaternium-15 in these studies were lower than ours (formaldehyde positivity varied between 1.7% and 3.1%, and that of quaternium-15 between 0.74% and 1.0%).…”

“…Of the 93 included patients, 20% had a mild reaction, while in a recent European Surveillance System on Occupational and non-occupational Allergens (ESSCA) study, mild reactions were more common than extreme and strong reactions combined. 3 It is possible that multiple positive tests lead to stronger individual reactions: close proximity of the reactions might have an enhancing effect. 8 As 80% of our formaldehyde-positive patients had co-reactions to formaldehyde releasers, we assume that most of our formaldehyde diagnoses were true contact allergies and not falsepositive results.…”

“…formaldehyde releasers as the percentage of isolated reactions varied between 46.8% and 96.3% for quaternium-15, imidazolidinyl urea, diazolidinyl urea, DMDM hydantoin, and 2-bromo-2-nitropropane-1,-3-diol. 3 On the other hand, a Dutch study found that stronger reactions to formaldehyde were associated with a higher frequency of positive quaternium-15 patch tests, which suggested an important causative role for formaldehyde in quaternium-15 patch test reactions. 4 At the Finnish Institute of Occupational Health (FIOH), we routinely perform patch tests with four concentrations of formaldehyde and many formaldehyde-releasing agents.…”