Patch testing sodium tetrachloropalladate is a better means to detect palladium sensitisation then palladium chloride—Results of a clinical–epidemiological study of the Information Network of Departments of Dermatology (<scp>IVDK</scp>) from 2003 to 2022

With great interest, we read the excellent publication ‘Less efficient skin penetration of the metal allergen Pd2+ compared to Ni2+ and Co2+ from patch test preparations’ from Simon et al. published in the recent issue of July 2024.1 Using Franz diffusion cell assays, the authors found that, after application of commercially available patch test preparations, the penetration of Pd2+ ions into pigskin was increased if derived from sodium tetrachloropalladate (Na2PdCl4) in comparison to palladium chloride (PdCl2). We, therefore, thought to investigate whether this observation also has implications for contact allergy diagnoses via patch testing in a clinical setting. Nickel sulphate (NiSO4) 5% in petrolatum (pet.), PdCl2(1% pet.) and Na2PdCl4 (3% pet.) were simultaneously patch tested following guidelines of the German Contact Dermatitis Research Group (DKG)2, 3 in 627 patients attending the departments of dermatology at the University Hospitals in Basel, Switzerland, and Leipzig, Germany, from 2003 to 2022, which are affiliated with the Information Network of Departments of Dermatology (IVDK). The results of these tests were retrospectively analysed. Routine operation procedures of the IVDK are published elsewhere.4 Reactions on day 3 were considered for the analyses and reactions with either just erythema (coded as ‘questionable’), infiltration and papules (‘+’) and/or vesicles (‘++’) or coalescing vesicles (‘+++’) were judged as positive (allergic). Irritant reactions are characterised by the soap effect, blisters or necrosis. The reaction index (RI) is calculated from the numbers of allergic (a), questionable (q) and irritant (i) reactions as follows: RI = (a − (q + i))/(a + (q + i)).5 The positivity ratio (PR) is defined as the percentage of weak positive (+) reactions among the total of positive reactions.6 Significant differences were concluded from non-overlapping 95% confidence intervals (CI). Written informed consent was obtained from all patients. The majority of the patients were female (n = 412, 65.7%) and aged 40 years or older (n = 532, 84.8%). Most frequently suspected allergen sources were metal implants (n = 224, 35.7%), other metal sources (e.g., jewellery, coins; n = 139, 22.1%), and dental protheses (n = 58, 9.3%). A significantly higher proportion of patients had positive patch test reactions to Na2PdCl4 (184 patients, 29.3% [95% CI: 25.8–33.1]), compared to PdCl2 (80 patients, 12.8% [95% CI: 10.2–15.6]) (Table 1). Fifty-four patients (26.0%) simultaneously showed positive reactions to all three preparations (NiSO4, PdCl2 and Na2PdCl4). With the exception of PdCl2, positive reactions were predominantly strong (‘++’) or extreme (‘+++’). Table 2 shows concomitant patch test reactivity in 208 patients with positive reactions to at least one of the test preparations concerned. Isolated reactions to NiSO4 were seen in 23 patients (11.1%), to PdCl2 in 1 patient (0.5%) and to Na2PdCl4 in 69 patients (33.2%) (Figure S1). Data on clinical relevance was available for 86 of 105 (81.9%) positive reactions to Na2PdCl4 in patients without positive reactions to PdCl2. Thirty-four (39.5%) reactions were found to be relevant (current relevance n = 27, occupational relevance n = 1, past relevance n = 6). In the present study, we show in a large patient population analysed over a long time period that positive patch test reactions to Na2PdCl4 (3% pet.) are more frequently observed than reactions to PdCl2 (1% pet.), among them a considerable number of clinically relevant reactions, indicating that Na2PdCl4 3% pet. is more suitable to detect palladium sensitisation. The test concentration of Na2PdCl4 (3% pet.) as well as the concentration of palladium in Na2PdCl4, which is almost doubled, are increased compared to PdCl2 (1% pet.) and constitute an obvious difference that might affect the diagnostic performance as well as the irritant potential of the test preparation. However, a significantly increased irritant property of Na2PdCl4 can largely be excluded by calculating the RI and PR (Table 1).5, 6 A European dose-finding multicentre study came to a similar conclusion, namely that Na2PdCl4 at 3% pet. is most appropriate and that the number of irritant reactions is low.7 In light of the recently published study by Simon et al., increased penetration of Na2PdCl4 in comparison to PdCl2 might be the major explanation for the observed significant increase of positive reactions to Na2PdCl4 compared to PdCl2 (Table 1). Similar results were published in a single-centre study from the Netherlands by Muris et al.,8 where a higher sensitivity was attributed to Na2PdCl4 compared to PdCl2 in 26 metal-allergic patients. The same applies to recently published patch test results in dental patients from Amsterdam.9 In contrast to a Canadian study on consecutive patients,10 we found a relatively high proportion of patients with nickel-independent palladium sensitisations, especially by using Na2PdCl4 (Table 2). S. Schubert: Conceptualization; writing – original draft; methodology; formal analysis; software; data curation; visualization; project administration. S. Forkel: Writing – review and editing; investigation; resources; visualization. C. Apfelbacher: Writing – review and editing; visualization; resources; supervision. M. Beigi: Writing – review and editing; investigation; visualization. K. Siewert: Conceptualization; writing – original draft; visualization. K. Hartmann: Writing – review and editing; investigation; resources; visualization. The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1. Concomitant patch test reactivity in 208 patients with positive reaction to nickel sulphate 5% in petrolatum (pet.), palladium chloride 1% pet. and/or sodium tetrachloropalladate 3% pet. The absolute numbers can be found in Table 2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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