ABSTRACT
Introduction
Propolis is a sticky substance produced by honeybees from plant resins collected from locally growing vegetation. Its chemical composition varies depending on the plant species visited by the bees. Contact dermatitis is commonly reported following exposure to cosmetics containing propolis or following the intake of food supplements.
Objectives
To investigate the prevalence of contact allergy to propolis in two dermatology clinics in Europe.
Methods
From February to July 2023, consecutive adult dermatitis patients were patch tested in the Department of Dermatology in Genova, Italy and in the Department of Occupational and Environmental Dermatology in Malmö, Sweden, with propolis (10% in petrolatum) originating from China. In Genova, propolis (10% in petrolatum) originating from Brazil was also tested.
Results
Out of 257 consecutive dermatitis patients patch tested in Genova, 16 (6.2%) reacted to propolis. Of these, 13 patients (5.1%) reacted to Brazilian propolis, one patient (0.4%) reacted to Chinese propolis, and two patients (0.8%) reacted to both. On patch testing 329 consecutive Swedish dermatitis patients with Chinese propolis, three patients (0.9%) reacted.
Conclusion
A significant difference was observed in the number of reactors to Brazilian propolis and Chinese propolis within the Italian group. When testing with Chinese propolis, a low prevalence of contact allergy was observed in both countries.
Keywords: allergic contact dermatitis, cheilitis, contact allergy, cosmetics, patch tests, prevalence, propolis
1. Introduction
Propolis is a rather variable sticky substance produced by honeybees from plant resins collected from locally growing vegetation. Its chemical composition varies depending on the plant species visited by the bees. Bees add salivary enzymes (which include β‐glycosidase) to the collected resin and mix it with beeswax prior to using this partially digested material in their hive to fill holes and protect the hive [1].
The chemical composition of propolis depends on the vegetation in the locality of the beehive. Poplar, particularly Populus nigra , is the main plant from which propolis originates in Europe, except in some Mediterranean areas such as southern Greece, Crete, Malta, Cyprus and southern Italy, where Cupressus sempervirens is the main plant source. Poplar is also the main source of propolis in North America and in nontropical regions of Asia, including China. Exudates for European and non‐European propolis may be collected from other trees such as eucalyptus, conifers and fruit trees. Raw propolis is composed of about 50% resins and balsams, 35% waxes and 5%–10% aromatic oils [1].
Propolis has been used traditionally for several medical conditions including leg ulcers, psoriasis, burns and wounds, and as an anaesthetic in dental procedures. It has been demonstrated to have antiseptic, antimycotic, bacteriostatic, anti‐inflammatory, antioxidant and immunostimulant effects [1].
Propolis is used in cosmetic products and food supplements and can be present as an impurity in beeswax [2]. Allergic contact dermatitis, especially cheilitis, oral mucositis and allergic eczema, have been reported following exposure to cosmetic products containing propolis and/or beeswax or after intake of food supplements containing propolis [3, 4]. Cases of occupational allergic contact dermatitis in beekeepers and instrument makers have also been described [5, 6].
The primary objective of our study was to investigate and compare the prevalence of contact allergy to propolis in two European dermatology clinics, one in Sweden and one in Italy. The secondary aim was to compare the contact allergy rates to two differently sourced propolis patch test preparations in the Italian clinic.
2. Materials and Methods
2.1. Study Population and Data Collection
This study was conducted simultaneously at the Department of Occupational and Environmental Dermatology, Skåne University Hospital, Malmö, Sweden, and at the Department of Dermatology, IRCCS—Hospital Policlinico San Martino, Genova, Italy between February and July 2023.
2.2. Test Series and Allergens
Consecutive adult (≥ 18 years) dermatitis patients referred to the Department of Dermatology in Genova were patch tested with propolis (Brazilian origin) in petrolatum at 10% w/w from SmartPractice (Phoenix, AZ, USA) and propolis (Chinese origin) in petrolatum at 10% w/w from Chemotechnique Diagnostics AB (Vellinge, Sweden). These propolis preparations were added to the baseline series of the Italian Society of Occupational and Environmental Dermatology (SIDAPA).
The Chinese propolis preparation tested in Genova was delivered from Malmö and had the same batch number as the propolis patch test preparation added to the Malmö extended baseline series and tested in consecutive adult dermatitis patients referred to in Malmö.
All data on patients were collected from each clinic's local database, including age, sex, occupation, anatomical sites of dermatitis, relevance of the contact allergies and atopic dermatitis.
2.3. Patch Testing
In Malmö, patch testing was performed with Finn Chambers AQUA (Chemotechnique Diagnostics AB). Petrolatum patch test preparations of ~20 mg were applied in small Finn Chambers (diameter, 8 mm; inner area of 0.5 cm2; Epitest, Tuusula, Finland) on Scanpor tape (Norgesplaster, Vennesla, Norway) to each patient's back, left occluded for 2 days, and then removed by the patient.
Test reading occurred at Day (D) 3 or 4 and D7 in Malmö. Scoring of the test reactions was done according to the International Contact Dermatitis Research Group (ICDRG) and the European Society of Contact Dermatitis (ESCD) guidelines [7, 8].
AllergEAZE patch test chambers (SmartPractice, Phoenix, AZ, USA; diameter, 8 mm; 20 μL of test material) were used in Genova. Test reading occurred on removal at 48 h (D2) and at D3 according to the SIDAPA guidelines [9].
The standard reading days considered in the study were therefore D2, D3 and/or D4 (Tables 2 and 4).
TABLE 2.
Intensity of concomitant positive reactions at Day 3, sites of current dermatitis and relevance assessment of propolis allergy in patients tested in Genova and contact allergic to Chinese (C) and/or Brazilian (B) propolis.
| Patients tested | B | C | FM I 8% pet | Mp 25% pet | Sodium metabisulphite 1% pet | Nickel sulphate 5% pet | MCI/MI 0.02% w | FM II 14% pet | MI 0.2% w | 2‐HEMA 2% pet | MM 2% pet | Allyl disulphide 2% pet | Potassium dichromate 0.5% pet | Formaldehyde MM 2% pet | 1,3‐Diphenylguanidine 1% pet | Cobalt chloride 1% pet | Hydroxy‐propyl metacrylate 2% pet | Anatomical sites involved by the dermatitis | Source of exposure to propolis | Propolis allergy relevance |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | + | + | ++ | ++ | ++ | ++ | + | + | + | Trunk | Cosmetics | c | ||||||||
| 2* | + | + | ++ | + | Face | u | ||||||||||||||
| 3 | + | +++ | + | + | Face | u | ||||||||||||||
| 4 | + | + | + | Trunk, arms, neck | u | |||||||||||||||
| 5 | + | + | + | + | ++ | + | Hands (fingers) | u | ||||||||||||
| 6 | + | Eyelids | u | |||||||||||||||||
| 7 | + | + | Lips, eyelids | u | ||||||||||||||||
| 8 | + | + | + | Diffuse | u | |||||||||||||||
| 9 | + | Eyelids | Cosmetics | c | ||||||||||||||||
| 10* | + | Eyelids | Cosmetics | c | ||||||||||||||||
| 11 | + | Scalp, face | Cosmetics | c | ||||||||||||||||
| 12 | ++ | + | ++ | ++ | + | + | +++ | Hand (palms) | Cosmetics | c | ||||||||||
| 13* | + | + | Face | Waxing | c | |||||||||||||||
| 14 | + | Face | Cosmetics | c | ||||||||||||||||
| 15* | + | Hand (fingers, palms) | Cosmetics | c | ||||||||||||||||
| 16 | + | Legs | Waxing | c | ||||||||||||||||
| Total | 15 (5.84) | 3 (1.17) | 4 (1.56) | 2 (0.78) | 1 (0.39) | 5 (1.94) | 2 (0.78) | 3 (1.17) | 2 (0.78) | 2 (0.78) | 1 (0.39) | 1 (0.39) | 1 (0.39) | 1 (0.39) | 1 (0.39) | 2 (0.78) | 1 (0.39) |
Abbreviations: 2‐HEMA: 2‐hydroxy‐ethyl methacrylate; B: Brazilian propolis; C: Chinese propolis; c: current; FM: fragrance mix; MCI: methylchloroisothiazolinone; MI: methylisothiazolinone; MM: methyl methacrylate; Mp: Myroxylon pereirae ; p: previous; pet: petrolatum; u: unknown; w: water.
*Patients with history of atopic dermatitis.
TABLE 4.
Pattern of positive reactions at test reading Day 3, sites of current dermatitis and propolis allergy relevance assessment in patients tested in Malmö with Chinese (C) propolis.
| Swedish patients (total = 3) | C propolis 10% pet | Nickel sulphate hexahydrate 5% pet | Quaternium 15 1% pet | Colophony 20% pet | Hydroperoxide of limonene 0.3% pet | Tea tree oil oxidised 5% pet | Sites of the dermatitis | Source of exposure | Propolis allergy relevance |
|---|---|---|---|---|---|---|---|---|---|
| Patient 1 | + | 0 | 0 | 0 | 0 | 0 | Lips | Topical medicaments | c |
| Patient 2 | ++ | ++ | 0 | 0 | 0 | 0 | Diffuse | Lip cosmetics | u |
| Patient 3 | ++ | 0 | + | + | + | + | Lips | Lip cosmetics/medicaments | c |
Abbreviations: C: Chinese; c: current; p: previous; pet: petrolatum; u: unkown.
2.4. Ethics
The study was approved by the Swedish Ethical Review Authority (Dnr 2020‐02190) and by the local research ethics committee in Genova (N. CET—Liguria: 176/2023).
2.5. Statistical Analysis
Positive reactions to the simultaneously tested propolis preparations from Brazil and China in Genova were compared intra‐individually with McNemar's two‐sided test. p < 0.05 was considered statistically significant.
Fisher's exact test, two sided, was used to compare the frequencies of contact allergy to propolis between the two populations studied in Malmö and Genova. For the analysis of concomitant allergies, we compared three groups of allergens: markers of fragrances, metals and preservatives. Categorical data (sex, atopic dermatitis) were investigated with Fisher's exact test, two sided. p < 0.05 was considered statistically significant. Univariable logistic regression analysis was performed to estimate the odds ratio (OR) for anatomical sites and concomitant allergies.
3. Results
Out of 257 consecutive dermatitis patients patch tested in Genova, 16 patients (14 females and two males) (6.2%), aged 20–71 years, reacted to propolis. Of these 16 patients, 13 aged 20–57 years (11 females and two males) (5.1%) reacted to Brazilian propolis; four had a history of atopic dermatitis. One patient (aged 47 years, female) (0.4%) reacted only to Chinese propolis, and two females (0.8%), mean age 55 years, reacted to both propolis preparations (Tables 1 and 3). In these Italian patients, Brazilian propolis produced more positive patch test reactions than did Chinese propolis (p = 0.0033) (Table 1). Current relevance for the propolis allergy was detected in nine of the 16 patch test positive patients (56.2%) (Table 2). Nine of the 16 (56.2%) suffered from eczema on the face, one had cheilitis and the rest suffered from eczema at different sites (Table 2). Four of the 16 patients allergic to propolis suffered from atopic dermatitis (Table 3).
TABLE 1.
Number of patients tested in Genova and in Malmö with Brazilian (B) and Chinese (C) propolis.
| Patients tested in Genova with B and C propolis | Comparison between reactors to B propolis versus C propolis in Genova | Comparison between reactors to C propolis in Genova and in Malmö | Patients tested in Malmö with C propolis | |||||
|---|---|---|---|---|---|---|---|---|
| Total N tested | N of individuals reacting to propolis | N positive to B propolis | N positive to C propolis | N positive to both B and C propolis | Total N tested | N positive to C propolis | ||
| 257 | 16 (6.2%) | 15 (5.8%) | 3 (1.2%) | 2 (0.8) | p = 0.0033 | p = 0.8 | 329 | 3 (0.9%) |
Note: The statistically significant values are presented in bold.
Abbreviations: B: Brazilian; C: Chinese; N: number.
TABLE 3.
Number of females/males and atopic dermatitis patients in propolis‐positive patients in the Swedish and Italian populations.
| Propolis positive | Propolis negative | Total (%) | |
|---|---|---|---|
| Sweden (total = 329) | |||
| F | 2 | 207 | 209 (63.5) |
| M | 1 | 119 | 120 (36.5) |
| Italy (total = 257) | |||
| F | 14 (87.5%) | 177 | 191 (74.3) |
| M | 2 (12.5%) | 64 | 66 (25.7) |
| Sweden (total = 329) | |||
| AD positive | 0 | 94 | 94 (28.6) |
| AD negative | 3 | 232 | 235 (71.4) |
| Italy (total = 257) | |||
| AD positive | 4 (25%) | 38 | 42 (16.3) |
| AD negative | 12 (75%) | 203 | 215 (83.7) |
Abbreviations: AD: atopic dermatitis; F: females; M: males.
Out of 329 consecutive Swedish dermatitis patients patch tested, three patients (two females and one male) (0.9%), aged 47, 54 and 72 years, reacted to Chinese propolis (Tables 1 and 3). Current relevance was found in two of the three patients (Table 4). Two of them suffered from cheilitis, one had a widespread eczema. In the two Swedish patients with current allergy, the triggers were medicaments in one and medicaments and cosmetic products in the second patient. None of these three patients reported being affected by atopic dermatitis (Table 3).
Comparing the number of positive reactions to Chinese propolis in the Italian and Swedish clinics, there were no significant differences (p = 0.8) (Table 1).
None of the propolis‐allergic patients worked as beekeepers.
In the Italian group, concomitant reactions to the fragrances tested in the baseline series were common, with 26.7% of patients who reacted to Brazilian propolis reacting to fragrance mix (FM) I and 20% to FM II (Table 5). 13.3% of the Brazilian propolis‐positive patients were allergic to 2‐hydroxyethyl methacrylate (2‐HEMA) (Table 5). Concomitant contact allergy to fragrances (FM I and II), Myroxylon pereirae (balsam of Peru), hydroxyisohexyl 3‐cyclohexene carboxaldehyde, colophony was observed in almost half of the Italian patients allergic to Brazilian propolis but in only about 13% of patients who did not react to propolis, this being a significant difference (p = 0.0012) (Table 6).
TABLE 5.
Simultaneous reactions to Brazilian (B) propolis and other allergens in the Italian population.
| Substance, concentration % | Brazilian propolis‐positive patients | Brazilian propolis‐negative patients | p | OR (95% Cl) | ||
|---|---|---|---|---|---|---|
| Positive reactions, n (%) | n positive to B | Positive reactions, n (%) | n | Univariate | ||
| Fragrance/flavours | ||||||
| FM I, 8.0 pet | 4 (26.7) | 15 | 16 (6.6) | 242 | 0.024 | 4.03 (1.2–13.6) |
| FM II, 14.0 pet | 3 (20) | 15 | 3 (1.2) | 242 | 0.0012 | 16.1 (3–86.8) |
| Myroxylon pereirae, 25.0 pet | 2 (13.3) | 15 | 13 (5.4) | 242 | 0.3 | 2.5 (0.5–12) |
| Metals | ||||||
| Nickel sulphate, 5.0 pet | 5 (33.3) | 15 | 48 (19.8) | 242 | 0.3 | 1.68 (0.6–4.8) |
| Cobalt chloride, 1.0 pet | 2 (13.3) | 15 | 13 (5.4) | 242 | 0.2 | 2.5 (0.5–12) |
| Potassium dichromate, 0.5 pet | 1 (6.6) | 15 | 8 (3.3) | 242 | 0.5 | 2.1 (0.2–17.1) |
| Preservatives | ||||||
| MCI/MI 0.02 aq | 2 (13.3) | 15 | 13 (5.4) | 242 | 0.3 | 2.5 (0.5–12) |
| MI 0.2 aq | 2 (13.3) | 15 | 6 (2.5) | 242 | 0.050 | 5.4 (0.9–28.9) |
| Sodium metabisulphite, 1.0 aq | 1 (6.6) | 15 | 8 (3.3) | 242 | 0.5 | 2.0 (0.2–17.2) |
| Formaldehyde, 2.0 pet | 1 (6.6) | 15 | 2 (0.8) | 242 | 0.096 | 8.1 (0.7–94.1) |
| Methacrylates | ||||||
| Hydroxypropyl methacrylate, 2.0 pet | 1 (6.6) | 15 | 3 (42.8) | 7 | 0.13 | 0.15 (0.0136–1.8) |
| 2‐hydroxyethyl methacrylate, 2.0 pet | 2 (13.3) | 15 | 0 (0) | 242 | 0.0055 | 78.2 (3.6–1701.3) |
| Methyl‐methacrylate, 5.0 pet | 1 (6.6) | 15 | 1 (20) | 5 | 0.46 | 0.3 (0.0174–6.4) |
| Others | ||||||
| Allyl disulphide, 2.0 pet | 1 (6.6) | 15 | 1 (50) | 2 | 0.21 | 0.1 (0.0058–3.1) |
| 1,3‐diphenylguanidine, 1.0 pet | 1 (6.6) | 15 | 2 (15.4) | 13 | 0.5 | 0.4 (0.0351–5.3) |
Note: The statistically significant values are presented in bold.
Abbreviations: B: Brazilian; FM: fragrance mix; MCI: metylchloroisothiazolinone; MI: methylisothiazolinone; n: number.
TABLE 6.
Simultaneous reactions to fragrances, metals and preservatives in Brazilian (B) propolis‐allergic individuals tested in Genova.
| Concomitant allergies | Brazilian propolis‐positive patients | Brazilian propolis‐negative patients | p | OR (95% Cl) | ||
|---|---|---|---|---|---|---|
| Total n | Contact allergy, n (%) | Total n | Contact allergy, n (%) | Univariate | ||
| Fragrances a | Propolis pos = 15, fragrances pos = 38 | 7 (46.67) | Propolis neg = 242, fragrances neg = 219 | 31 (12.8) | 0.0012 | 5.9 (2.0–17.6) |
| Metals b | Propolis pos = 15, metals pos = 63 | 5 (33.33) | Propolis neg = 242, metals neg = 194 | 58 (23.97) | 0.4 | 1.6 (0.5–4.8) |
| Preservatives c | Propolis pos = 15, preservatives pos = 31 | 3 (20) | Propolis neg = 242, preservatives neg = 226 | 28 (11.57) | 0.3 | 1.9 (0.5–7.2) |
Note: The statistically significant values are presented in bold.
Abbreviations: B: Brazilian; n: number.
Fragrance mix (FM) I, FM II, Myroxylon pereirae (MP), hydroxyisohexyl 3‐cyclohexene carboxaldehyde, colophony.
Nickel sulphate, cobalt chloride, potassium dichromate.
Methylchloroisothiazolinone/methylisothiazolinone (MI), MI, sodium metabisolfite, formaldehyde, paraben mix.
Cheilitis was the clinical presentation of dermatitis in two Swedish patients with relevant contact allergy to Chinese propolis (66.7% in the Swedish group vs. 6.7% in the Italian group) while facial dermatitis was the most frequent manifestation among Italian propolis‐allergic patients (Table 7). Among Italian patients allergic to propolis with current relevance, the localization of the eczema involved eyelids in two, face in two, hands in two, face and scalp in one, trunk in one and legs in one (Table 2). The use of cosmetic products was considered the source of exposure in propolis‐allergic patients of both cohorts, including waxing in two patients (Tables 2 and 4).
TABLE 7.
Localization of the dermatitis in Italian and Swedish populations tested with Brazilian (B) and Chinese (C) propolis.
| Reactors to B (n 15), n (%) tested in Genova | C (n 3), n (%) tested in Genova | C propolis (n 3), n (%) tested in Malmö | p | OR (95% Cl) | |
|---|---|---|---|---|---|
| Univariate | |||||
| Sites od dermatitis | |||||
| Intraoral or lip | 1 (6.7) | 0 | 2 (66.7) | 0.038 | 0.0357 (0.0015–0.8) |
| Face | 8 (53.3) | 2 (66.7) | 0 | 0.7 | 0.6 (0.0422–7.7) |
| Head or neck | 2 (13.3) | 0 | 0 | 0.9 | 1.3 (0.0500–33.6) |
| Hands | 3 (20) | 0 | 0 | 0.7 | 2 (0.0806–47.7) |
| Lower extremity | 1 (6.7) | 0 | 0 | 0.8 | 0.7 (0.0240–21.8) |
| Trunk | 2 (13.3) | 1 (33.3) | 0 | 0.9 | 1.3 (0.0500–33.6) |
| Widespread | 1 (6.7) | 0 | 1 (33.3) | 0.2 | 0.1 (0.0062–3.3) |
Note: The statistically significant values are presented in bold.
Abbreviations: B: Brazilian propolis; C: Chinese propolis; n: number.
In the Italian group, there were more females than males both in the population tested (191 female vs. 67 male patients) and in the propolis‐positive group (14 female vs. two male patients) (p = 0.25, Fisher's exact test, two sided). Similarly, females were more prevalent both in the Swedish population tested (209 female vs. 120 male patients) and in the propolis‐positive group (two female vs. one male patient) (Table 3).
Italian and Swedish propolis‐positive patients were not more affected by atopic dermatitis than propolis‐negative patients. However, significantly more Swedish patients had a history of atopic dermatitis than did Italian patients (28.9% vs. 16.3%; p = 0.0006, Fisher's exact test, two sided). And significantly more Italian atopic dermatitis patients had contact allergy to propolis than did Swedish atopic dermatitis patients (p = 0.04) (Table 3).
A further 35 out of 257 (13.6%) Italian patients tested showed doubtful reactions, 30 of those to Brazilian propolis and five to Brazilian and Chinese propolis. Out of 329 Swedish patients, seven (2.1%) patients showed doubtful reactions to Chinese propolis. There were no irritant reactions nor late reactions appearing beyond D10 registered.
4. Discussion
In 2013–2014, a prevalence of contact allergy in the range 0.3%–4.4% was observed when testing propolis 10% pet in 11469 consecutive dermatitis patients within the European Surveillance System on Contact Allergies (ESSCA) network [10].
This led to a proposal to include propolis 10% pet in the European Baseline series, where it has been included since 2019. Frequencies of contact allergy to propolis between 0.5% and 6.2% have been reported among dermatitis patients in further studies [2, 11, 12, 13].
The natural local flora in the vicinity of beehives determines the chemical composition of propolis. In temperate areas, the buds and the bark of poplars, and particularly from P. nigra L. (black poplar) are the main source of propolis, but other plants are also used by bees to produce propolis in different parts of the world. In tropical regions, Baccharis dracunculifolia DC is the source of Brazilian green propolis and Dalbergia species are the source of Brazilian red propolis [1, 14, 15]. Current knowledge on the plant sources of propolis is based on observational studies of bee behaviour or comparative studies of the composition of resins from plants and propolis found in nearby beehives [16].
It has been reported that different origins of propolis change the efficacy in terms of biological activity [17, 18, 19]. But how the plant origin impacts upon the allergenicity of different propolis materials remains understudied. Previous studies have compared the frequencies of contact allergy to propolis of diverse origins in different European countries. Although small differences in frequencies were found, there were no statistically significant differences in the number of positive reactions between four different types of propolis, with one exception: positive reactions to propolis from Lithuania were significantly more frequent (p = 0.039) than to propolis originating from Sweden [13]. Nyman et al. tested propolis with different origins (western Sweden, China, North America, Lithuania) observing the highest frequencies of allergic reactions to propolis from China (3.6%) and the lowest to propolis from Sweden (2.2%), although the differences were not statistically significant [20]. One explanation for the only small difference in frequency between the two materials could be that the propolis used to produce cosmetic or other consumer products all originated from the same geographical area, that is, China [13, 20].
Data regarding the production of propolis in both Italy and Sweden and the origin of propolis in products present on the market of the two countries are difficult to collect. According to the manufacturer of patch test materials used in this study, the most common propolis used in diagnostics of contact allergy in Europe, and particularly in Italy and Sweden, originates from China and Brazil. The optimal scenario when patch testing propolis would be to test the same propolis material as was used in the manufacture of the cosmetic product or food supplement to which a patient has been exposed.
Schubert et al. analysed import and export data for propolis in Germany from 2016 to 2019 [21]. Their study revealed a decrease in the export and an increase in the import of material originating mainly from China (29.9%), but also from Spain (11.2%), the United States (10.9%), Italy (8.1%) and Brazil (6.9%) [21]. In a recent report from Kocabas et al. [22], the prevalence of contact allergy to propolis in dermatitis patients tested in Amsterdam with the European baseline series increased significantly when the manufacturer of test preparations (SmartPractice) changed the site of collection of propolis from China to Brazil.
Simultaneously testing Brazilian propolis (SmartPractice) and Chinese propolis (Chemotechnique Diagnostics AB) on 143 consecutive patients, Piontek et al. [23] observed nine (6.3%) positive reactors to Brazilian propolis but none of them reacted to Chinese propolis. Similarly, we observed a statistically significant difference between the frequency of positive reactions to Brazilian propolis and Chinese propolis simultaneously tested in Italy (Table 1) and the same frequency of positive reactions to Chinese propolis, although tested in two different geographic areas that we supposed might have different patterns of exposure to propolis‐based products (Table 1). One possible explanation for the significantly higher frequency of positive reactions to Brazilian propolis is that Brazilian propolis is more commonly used in the manufacture of cosmetic products and natural medicines/food supplements to which the patients have been exposed.
Piontek et al. [23] ascribed the discrepancy in the number of reactors to Chinese and Brazilian propolis to the presence of possible impurities in the Brazilian preparation that, according to the manufacturer, does not undergo a purification treatment with ethanolic extraction, resulting in a possible contamination with microbial and allergenic impurities.
Several studies have been performed with the aim of identifying the contact allergens in propolis. Strong sensitising activity was demonstrated only for the esters of caffeic acid [24, 25, 26].
Furthermore, propolis contains cinnamic alcohol, cinnamic acid, benzoic acid and benzyl alcohol, which are constituents also of M. pereirae (balsam of Peru). Cinnamic alcohol is also a component in fragrance mix I (FM I). The chemical complexity of propolis, which includes known fragrance sensitizers, can explain the high rate of concomitant reactions with fragrance test material (statistically significant with FM I p = 0.0243, FM II p = 0.0012) observed in patients reacting also to Brazilian propolis (Table 5). Previously, Nyman et al. [13, 20] have detected concomitant reactions between propolis and M. pereirae (balsam of Peru), FM I, and colophony in accordance with earlier studies [27].
Further insights into the composition of propolis of different origins are necessary to inform the diagnosis of contact allergy to propolis and to understand the pattern of cross‐reactivity between propolis and fragrance raw materials used in cosmetic products.
5. Conclusion
A significant difference was observed in the number of reactors to Brazilian propolis and Chinese propolis within the Italian group. When testing with Chinese propolis, a low prevalence of contact allergy was observed in both countries. Testing with natural products is difficult and, ideally, the choice of test material should reflect actual exposure in any geographic region. Testing with a patient's own products is therefore of utmost importance. Further studies of the chemical composition of propolis, focusing on the identification of individual contact sensitizers and on features of exposure to propolis in different geographical regions, will improve the accuracy of the diagnosis of contact allergy to propolis.
Author Contributions
Annarita Antelmi: methodology, data curation, supervision, writing – original draft, writing – review and editing, conceptualization, investigation. Ilaria Trave: investigation, writing – review and editing, data curation, writing – original draft, methodology. Rosella Gallo: investigation, writing – review and editing, supervision. Emanuele Cozzani: investigation, supervision, writing – review and editing. Aurora Parodi: investigation, supervision. Magnus Bruze: investigation, conceptualization, methodology, supervision, writing – review and editing. Cecilia Svedman: project administration, conceptualization, methodology, writing – review and editing, investigation, supervision.
Conflicts of Interest
Bruze Magnus is a member of the Expert Panel for Fragrance Safety—http://fragrancesafetypanel.org/. The other authors declare no conflicts of interest.
Funding: This work was supported by C.M. Lerici Foundation.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.