Patch testing with aluminium Finn Chambers could give false-positive reactions in patients with contact allergy to aluminium

Background: Earlier laboratory studies have shown that sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride trigger the release of aluminium (Al) from Finn Chambers (FC). Objectives: To investigate whether aluminium realease from FC could influence the diagnostic outcome of patch testing with FC. Method: A retrospective analysis of patch test results from 2010 to 2019 was performed. A two-sided Fisher's exact test was used to calculate any overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. Results: A total of 5446 patients had been tested with FC during the study period. There was a significant overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. Patients with a strong Al allergy had significantly higher amounts of concomitant reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride compared to patients with weak Al allergy. These results were not seen for patients tested with Finn Chambers AQUA. Conclusion: In patients with contact allergy to Al, patch testing with Finn chambers could give false-positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, palladium chloride.

metal. When in contact with air or water it forms a thin surface layer of Al oxide, which makes the metal resistant to corrosion. 8 As with most passive metals, it might, however, locally corrode under certain conditions, such as in the presence of salts. 8 The prevalence of contact allergy to Al is low 9 and patients with contact allergy to Al do not normally react to an empty FC. 10 This suggests that FCs are a safe choice in standard patch testing. A new system, Finn Chamber AQUA (FCA), has been developed, for which the Al chamber is coated with absorbent paper. This test system was developed to resist moisture and remain in place even during exercise and showers. 11 New chemical analyses from Hedberg et al. show, however, that various patch test preparations can induce Al release from Finn chambers in vitro due to Al corrosion. 12 In the study, different batches of FC and FCA were investigated with 32 different baseline preparations. These were exposed to artificial sweat containing 5.0 g/L NaCl, 1.0 g/L urea, 1.0 g/L lactic acid, with the pH adjusted to 6.5. 12 It was found that sodium tetrachloropalladate hydrate (Na-Pd) 3% pet. and caine mix II (CM II), 10% pet. released significantly higher amounts of Al compared to an Al Finn Chamber in artificial sweat. Palladium chloride (Pd-Cl) 2% pet. and Myroxolon pereirae (MP) 25% pet. also induced increased Al release in FC, although not statistically significant. 12 The explanation for the Al release is that surface-available chlorides from metal salts can cause localised corrosion (pitting corrosion) to Al metal. 8,12 Several metal salts used for patch testing contain chloride ions. Acids, especially in the combination with chlorides from sweat, can also cause corrosion to Al metal. 13 MP contains high amounts of organic acid and CM II contains hydrochloric acid, which is corrosive to Al. 12 The Al -release from FC into artificial sweat was found to be 16-4100-fold higher than the Al release from FCA. Contact allergies to nickel and palladium are known to crossreact. [14][15][16] In an earlier study, 17 we discussed the relevance of contact allergy to palladium when the patient was not allergic to nickel. After discussion on preliminary results on triggered Al release from FC, later published in, 12 we raised the question whether positive reactions to Na-Pd and Pd-Cl without concomitant reactions to nickel sulphate hexahydrate (Ni) could be an expression of contact allergy to Al.

| Ethics
The study was approved by the Regional Ethical Review Board, Lund Sweden (Dnr 2020/02190). When patients are patch tested they are informed that data may be used for comparisons on a group level and approval is mandatory if the patients´data are stored in the computer system.

| Definition
Contact allergy to Al was defined as either a positive reaction to Al-Cl and/or Al-lac.
Isolated palladium allergy was defined as positive reactions to Na-Pd and/or Pd-Cl without concomitant reactions to Ni, independent of any other contact allergy.

| Statistical analysis
A two-sided Fisher's exact test was performed using SPSS software, version 26 (IBM, Armonk, NY) and was used to calculate whether the difference in prevalence of MP, CMII, Na-Pd, Pd-Cl, isolated palladium allergy, FM1, Ni, K-Cr, and TP between patients with and without contact allergy to Al was statistically significant.
The test was also used to calculate whether there was a statistically significant difference in concomitant reactions in patients with a strong Al allergy (3+/2+) compared to patients with a weak Al allergy (1+).  Table 2 shows the prevalence and distribution of contact allergy to the test substances among patients with and without Al allergy. Table 3 shows the prevalence of concomitant reactions to MP, CM II, Na-Pd, and Pd-Cl and concomitant reactions to FM 1, Ni, K-Cr, and TP in those with and without Al allergy.

| RESULTS
Five hundred and twenty-five (9.6%) patients were positive to either Na-Pd or Pd-Cl. Ten of the palladium-allergic patients had contact allergy to Al (patients 4-10 and 24-26, sided Fisher's exact test, P = .015). These results are illustrated in Figure 1. Figure 2 illustrates that the increased number of concomitant reactions in the group with strong Al allergy was due to an increased number of patients reacting to one or more of the

| DISCUSSION
Because contact allergy to Al is rare, Al-Cl or Al-lac are not included in the European baseline series. The earlier recommended patch test concentration of Al-Cl (2.0%) is lower than the elicitation threshold for many Al-allergic patients. 10 Today, the recommended test preparation for tracing Al allergy is Al-Cl, 10% pet. 10,18,19 In Malmö, we have tested this preparation and a preparation with Al-lac 12% pet. since  (Table 2). These overrepresentations of simultaneous contact allergies to Na-Pd, MP, CM II, and Pd-Cl in Al-allergic patients indicated that one explanation for some of these simultaneous contact allergies was false-positive reactions.
Positive reactions to palladium often follow nickel allergy and have most often been explained as cross-sensitization, because nickel and palladium have similar chemical structures. 14,17 The palladium reaction is, therefore, often neglected if the patient is also allergic to nickel. However, if a patient has an isolated palladium reaction, it is often difficult to explain the exposure and clinical relevance, at least in Sweden, where palladium is not used in dental alloys. 21 In one of our earlier studies, 17 which was performed while we still used FC, we suggested that isolated palladium allergy could be due to contact allergy to Al. The group of palladium-allergic patients, thus, consists of those with and without simultaneous contact allergy to nickel. We found that Al allergy was overrepresented among patients with an isolated palladium allergy (P < .001, Table 2). The results, thus, support our previous hypothesis that a positive reaction to palladium alone, apart from being a true palladium allergy, may actually be a falsepositive reaction due to a strong contact allergy to Al when patch testing with FC.
It was apparent that patients with Al allergy tested with FC more often had concomitant reactions to more than one of the four substances (MP, CM II, Na-Pd, and Pd-Cl), compared to Al-negative patients (Table 3). Also, patients with a strong Al allergy hade more concomitant reactions to MP, CM II, Na-Pd and Pd-Cl than patients with a weak Al allergy (Figures 1 and 2). Al on the surface in the chambers, they concluded that pet, which is used routinely as vehicle in patch testing, seems to protect the surface in the chambers from corrosion from these two metal salts. 26 This is very much in line with the results from Hedberg et al. 12 investigating Al release from an empty FC exposed to artificial sweat and FC with 32 different baseline preparations. They found that many patch test preparations resulted in a significantly lower release of Al compared with an empty FC, 12

| CONCLUSION
Testing with Al FC may give false-positive reactions to MP, CM II, Na-Pd, and Pd-Cl due to contact allergy to Al and triggered Al corrosion by these substances. Patients with a strong Al allergy could have more false-positive reactions as compared to patients with a weak Al allergy. The use of patch test chambers not releasing Al, for example FCA, or a plastic chamber, such as Van der Bend and IQ chambers, will eliminate the risk of false-positive reactions to MP, CMII, Na-Pd, and Pd-Cl in Al-allergic patients.

DISCLOSURE
The authors declare no conflicts of interest.