Contact sensitization to propolis in the Information Network of Departments of Dermatology (IVDK) 2013 to 2019 and market survey of propolis commerce in Germany.

Abstract

Propolis is a natural product that consists of more than 100 compounds and shows great compositional variation depending on its origin.1 The most common poplar-type propolis is produced by honeybees in China, Europe, and North America, and is characterized by several caffeates as major allergens.2 The Information Network of Departments of Dermatology (IVDK) and others recently observed increasing rates of propolis sensitization.3, 4 We aimed to identify causes of increasing sensitization to propolis using IVDK and German trade data. From 2013 to 2019, 66 104 of 79 120 consecutive IVDK patients were patch tested with propolis (10% pet.) in the baseline series. According to information from Allmiral Hermal and SmartPractice Europe, patch test (PT) preparations contained the same or rather similar poplar-type propolis. PTs were performed following German and European guidelines and read on day 3 (day 4 in a few exceptional cases).5-8 Statistical significance on a 5% level was concluded from non-overlapping 95% confidence intervals (95% CIs) in corresponding comparisons. In the study period, 2598 patients (3.9%; 95% CI 3.8%-4.1%) showed positive PT reactions to propolis. Reaction frequencies in female (3.8%; 95% CI 3.6%-4.0%) and male (4.2%; 95% CI 3.9%-4.4%) patients did not differ significantly. Concerning population characteristics and PT results, Table 1 displays differences between 2598 propolis-positive patients and 61 032 propolis-negative patients. Patients with doubtful (n = 1883, 2.8%) or irritant reactions (n = 591, 0.9%) were excluded from this analysis. Among propolis-positive patients, there were significantly more patients aged 40 or older, males, and with leg or face dermatitis, whereas occupational and hand dermatitis were diagnosed less often (Table 1). As expected, patients sensitized to propolis reacted significantly more often to balsam of Peru (Myroxylon pereirae) and colophonium, most probably due to common ingredients, such as (aromatic) resin acids and monoterpenes.1 In addition, propolis-positive patients were significantly more often sensitized to other fragrances, essential oils, and compounds found in topical preparations (Table 1). The upward trend from 3.5% (95% CI 3.2%-3.9%) positive propolis reactions in 2013 to 4.7% (95% CI 4.2%-5.1%) in 2019 (Figure 1) was significant (asymptotic Cochran-Armitage trend test; P < .0001). If this trend was based on variations in allergen content or concentration in different types of propolis used in consumer products or PT preparations, one would expect that epidemiological (clinical) markers reflect such changes. However, items presented in Table 1 showed no substantial variation between the single years of the study period, and hence cannot explain this increase (data not shown in detail). An analysis of propolis import and export in Germany using tridge.com, an internet platform that connects suppliers and buyers,9 revealed that, from 2016 to 2019, propolis export decreased while its import increased dramatically (Figure 1). Imported propolis mainly originated from China (29.9%), Spain (11.2%), the USA (10.9%), Italy (8.1%), and Brazil (6.9%). According to de Groot's classification,1 poplar-type propolis dominated in Germany every single year. Propolis import from the USA peaked in 2014 (20.4%) and 2016/2017 (nearly 17%). Propolis from Brazil, which is chemically different from the poplar type,1 consistently had a relatively small market share (maximum 16.9% in 2015). Considering patient characteristics, suspected allergen sources, and concomitant PT reactions, sensitization to propolis shows an association with skin care and topical medical preparations (Table 1). Since 2016, increased import and decreased export of propolis to and from Germany, respectively, probably indicate increased propolis use and exposure, which most likely explains the upward trend of propolis sensitization. Nevertheless, one has to be aware that differences in propolis composition, even between poplar-type propolis species, and heterogeneity of the propolis used in PT preparations as well as in propolis on the (cosmetics) market do exist and affect diagnostic accuracy in patch tested patients, as recently demonstrated in a Swedish study.10 The compositional (chemical) heterogeneity of commercially available PT preparations year on year should be studied. Open Access funding enabled and organized by Projekt DEAL. The authors have no personal conflicts of interests. The IVDK, maintained by the IVDK e.V., of which J. Geier and S. Schubert are employees, is sponsored by the cosmetic and fragrance industry (associations) as well as by public funds. Steffen Schubert: Conceptualization (equal); software (equal); writing; original draft (equal). Johannes Geier: Conceptualization (equal); writing; review and editing (equal). Heinrich Dickel: Investigation (equal); methodology (equal); writing; review and editing (equal). Timo Buhl: Investigation (equal); methodology (equal); writing; review and editing (equal). Franziska Ruëff: Investigation (equal); methodology (equal); writing; review and editing (equal). Harald Löffler: Investigation (equal); methodology (equal); writing; review and editing (equal).