Abstract
In Japan, metal allergies are becoming increasingly prevalent, raising concerns for public health. This study examined metal allergy characteristics, patient histories, and clinical signs associated with patch test results over a 15-year period at the Dental Metal Allergy Clinic of Tokushima University Hospital. A retrospective analysis of 1085 patients revealed that 65.4% tested positive for at least one metal allergen, with palladium chloride, nickel sulfate, potassium dichromate, and cobalt chloride identified as the most common allergens. Female patients were disproportionately affected, accounting for 78.4% of the study population. Notably, there was a substantial increase in patients reporting inflammation due to pierced earrings, increasing from 5.0% in 2005 to 43.2% in 2020, particularly among females. Patients with a history of inflammation from earrings had an 81.3% prevalence of metal allergies, which was significantly higher than the 60.4% reported in those without such a history (chi-square test, pā<ā0.001). These findings suggest a strong link between earrings and metal allergies, underscoring the need for improved education, early detection, and preventive strategies to address the growing impact of metal allergies on public health.
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Introduction
The prevalence of allergic diseases in Japan, including allergic rhinitis, asthma, atopic dermatitis, and food allergies, has significantly increased. A 2011 survey by the Ministry of Health, Labor, and Welfare indicated that these diseases affect one in every two individuals in Japan1,2,3. Among them, metal allergy, a delayed-type (type IV) allergy, manifests as contact dermatitis4 and may also be on the rise. Daily and occupational exposure to metals, through items such as jewelry, accessories, electronic devices, and metal-rich foods, can trigger these allergies. Common metal allergens include nickel, chromium, and cobalt. Moreover, allergies to metals in medical devices, such as dental work and artificial joints, are emerging concerns5,6. Symptoms are not confined to the oral mucosa in patients with dental metal allergies but can lead to skin conditions across the body, such as palmoplantar pustulosis and systemic contact dermatitis syndrome7,8,9,10,11.
The patch test is a vital diagnostic tool for detecting metal allergies12,13, although alternative tests such as the lymphocyte transformation test (LTT) and memory lymphocyte immune stimulation assay (MELISA) are available14,15. However, their effectiveness is debated16. Previously, we investigated titanium allergy, allergic symptoms due to dental metals, and oral metal analysis methods10,17,18,19,20,21. Our retrospective study at Tokushima University Hospitalās Dental Metal Allergy (DMA) clinic over 15Ā years aimed to analyze patient characteristics, patch test results, and medical history. The purpose of this study was to investigate the epidemiology of metal allergies to determine the current situation, identify specific risk factors and symptoms, and develop effective preventive strategies to improve patientsā quality of life.
Results
Patient characteristics
In total, 1085 subjects, comprising 234 males (21.6%) and 851 females (78.4%), participated in the study. The mean age of the participants was 53.4āĀ±ā16.9Ā years (54.7āĀ±ā17.7Ā years for males, 53.1āĀ±ā16.7Ā years for females). Among the 1085 patients, 710 (65.4%) exhibited positive reactions to at least one allergen in the patch test. The rate of positive reactions was slightly higher in females (67.3%) than in males (58.5%), and this difference was statistically significant. (chi-square tests, pā=ā0.012) (Table 1). The prevalence of positive reactions generally decreased with age, except in adolescent patients (Supplementary Fig. S1). The age distribution was notably unimodal, peaking in the 60Ā s for both genders. (Supplementary Fig. S2). A comparison of the current data with historical records dating back to 1987 revealed a steady increase in the number of patients visiting the DMA Clinic at Tokushima University Hospital. The increase in female patients was more substantial, although the number of male patients also showed an increasing trend. The male-to-female ratio has remained relatively constant over the years as detailed in Table 2. The age distribution of the patients remained relatively consistent over the years (Supplementary Fig. S2)10,18.
Clinical symptoms
Among the conditions leading to hospital visits, oral lichen planus/oral lichenoid lesions were reported in 209 patients (19.3%), palmoplantar pustulosis/dyshidrotic eczema in 157 patients (14.5%), and contact dermatitis and redness related to jewelry in 139 patients (12.8%) (Fig.Ā 1a, Supplementary Table S1). A gender differences revealed that females had a greater prevalence of oral lichen planus/oral lichenoid lesions and contact dermatitis and redness related to jewelry than males did. Compared with females, males presented a greater prevalence of palmoplantar pustulosis/dyshidrotic eczema and redness and eczema on their hands. In terms of age, contact dermatitis and redness related to jewelry were most common in younger patients (teens to 30s), whereas palmoplantar pustulosis/dyshidrotic eczema was most common in patients aged 40 to 50Ā years. Contact dermatitis and redness with pierced earrings, rings, and necklaces were more common in patients in their teens and twenties. In contrast, palmoplantar pustulosis/dyshidrotic eczema was commonly seen in patients aged 30 to 50Ā years. Oral lichen planus/oral lichenoid lesions were predominantly observed in patients aged 60Ā years and older (Fig.Ā 1b). These age-related prevalence patterns were significant (KruskalāWallis test, pā<ā0.001; Supplementary Table S2, Supplementary Fig. S3).
Proportion of clinical symptoms by (a) gender and (b) age.
Allergen prevalence and trends in patch test results
PdCl2 (1%) and NiSO4 (5%) were the most prevalent allergens, observed in 28.3% and 28.1% of patients, respectively, followed by K2Cr2O7 (0.5%) at 22.9% and CoCl2 (2%) at 19.4% as detailed in Table 3. Gender-specific differences in prevalence were observed; PdCl2 (1%) (pā<ā0.001), NiSO4 (5%) (pā=ā0.001), and HAuCl4 (0.2%) (pā=ā0.003) were significantly more common in females, whereas the prevalence of SnCl4 (1%) was greater in males (pā=ā0.023), as shown in Fig.Ā 2a. The prevalence of most allergens decreased with age, with notably high positive rates for PdCl2 (1%) and NiSO4 (5%) among individuals in their 20s and 30s.
Top 10 allergens are shown. (a) Prevalence by gender, comparisons were conducted via chi-square tests. (b) Prevalence by five-year period; the KruskalāWallis test adjusted via the Bonferroni correction was carried out (***pā<ā0.001, *pā<ā0.05).
Variations in positivity rates over time were examined for allergens with positive rates of 5% or greater. There was no change in the positive rate for NiSO4 (5%) or ZnCl2 (2%) over the 15-year period. In contrast, the prevalence of other allergens, particularly PdCl2 (1%) and K2Cr2O7 (0.5%), decreased significantly over all comparison periods. In addition, allergens such as CoCl2 (2%), SnCl4 (1%), H2PtCl6 (0.5%), IrCl4 (1%), and HAuCl4 (0.2%) also significantly decreased over different time periods (Fig.Ā 2b).
Correlations between metal allergies and medical history
We investigated correlations between the prevalence of metal allergies and several medical history factors, including age, gender, current disease, presence of implants, history of orthodontic treatment, history of rashes induced by jewelry, history of inflammation due to pierced earrings, history of rashes induced by watches, and reactions to individual allergens. Our study revealed a weak negative correlation (rā=āāĀ 0.219, pā<ā0.001) between the prevalence of metal allergies and age. This finding is consistent with our previous results, which suggest a general decrease in positive reactions with increasing age. However, no significant correlations were detected with other factors, including gender (rā=ā0.076, pā=ā0.012), medical history of inflammation due to pierced earrings (rā=ā0.188, pā<ā0.001), history of rashes induced by jewelry (rā=ā0.162, pā<ā0.001), or presence of implants (rā=āāĀ 0.003, pā=ā0.927).
While these correlations were not statistically significant and the coefficients suggested a weak relationship, a relatively greater correlation coefficient was found for history of inflammation due to pierced earrings (rā=ā0.188, pā<ā0.001). Despite its statistical insignificance in terms of broader clinical relevance, this was the highest correlation observed among the factors studied. On the basis of this observation, we decided to further investigate this particular medical history.
Over the past 15Ā years, the number of patients with a medical history of inflammation has significantly increased due to pierced earrings. (Fig.Ā 3a). Specifically, the data revealed a significant increase, particularly among female patients. The percentage of females with this history increased from 5.0% (representing 2 out of 40 patients) in the period from July 2005 to June 2006, to 43.2% (41 out of 95 patients) in the period from July 2019 to June 2020 (Fig.Ā 3b). Furthermore, our analysis revealed a distinct pattern in the age distribution that was related to age: patients without a medical history of inflammation due to pierced earrings showed a peak in their 60s. In contrast, patients with a medical history of inflammation due to pierced earrings were more likely to be in their 30s (Fig.Ā 3c).
The number of patients, and prevalence of inflammation due to pierced earrings according to medical history. (a) Changes in the number of all patients. (b) The percentage of patients with a medical history of inflammation due to pierced earrings. (c) Age distribution according to medical history of inflammation due to pierced earrings. (d) The prevalence of 13 allergens was shown to be greater in patients with a medical history of inflammation due to pierced earrings than in those without such a history. Comparisons were conducted via chi-square tests. (***pā<ā0.001, **pā<ā0.01).
We analyzed the prevalence of patients with a medical history of inflammation due to pierced earrings. Our findings indicate that patients with a history of inflammation due to pierced earrings had a significantly greater prevalence than did those without this history (213 out of 262, 81.3% vs. 497 out of 823, 60.4%). Notably, among female patients, the prevalence of metal allergies with a medical history involving inflammation due to pierced earrings was even greater, reaching 81.7%. Furthermore, when considering the medical history of inflammation caused by not only pierced earrings but also other jewelry, such as necklaces, rings, and metal products, the prevalence was 76.6%. These findings indicate a greater incidence of inflammation in patients with a history of irritation caused by pierced earrings (Table 4). In addition, the prevalence of 13 allergens was greater in patients with a medical history of inflammation due to pierced earrings than in those without such a history. In particular, the prevalence of certain allergens such as NiSO4 (5%), PdCl2 (1%), CoCl2 (2%), ZnCl2 (2%), and HAuCl4 (0.2%) was significantly greater (Fig.Ā 3d).
Correlation analysis of patch test reagents
Our correlation analysis of patch test reagents revealed significant positive correlations between certain allergens. Specifically, we found a strong positive correlation between PdCl2 (1%) and NiSO4 (5%) in all patient groups (rā=ā0.446, pā<ā0.001). Notably, in the subgroup of patients with a medical history of inflammation due to pierced earrings, there was a stronger correlation between PdCl2 (1%) and NiSO4 (5%) (rā=ā0.562, pā<ā0.001).
Additionally, we examined the prevalence of reactions to nickel and palladium. Among all the patients, 16.9% tested positive for both nickel and palladium. In contrast, 11.1% tested positive only for nickel, and 11.3% tested positive only for palladium. This trend was more pronounced in patients with a history of inflammation due to pierced earrings. In this group, 40.2% of the patients tested positive for both palladium and nickel, 16.1% of the patients tested positive only for nickel, and 6.5% tested positive only for palladium. In contrast, patients without a history of inflammation due to pierced earrings showed different results. In this group, 9.5% tested positive for both palladium and nickel, whereas 9.5% tested positive solely for nickel and 12.8% tested positive solely for palladium (Fig.Ā 4).
Proportion of patients with positive reactions to palladium and nickel. (a) The percentage of patients who underwent patch tests for both nickel and palladium. (b) The percentage of patients with a medical history of inflammation due to pierced earrings. (c) The percentage of patients without a medical history of inflammation due to pierced earrings. Data are presented as percentages (numbers of patients).
Discussion
Our study highlights the increasing prevalence of metal allergies in Japan, particularly among females with a medical history of inflammation due to pierced earrings. Patch tests revealed high sensitivity to palladium chloride, nickel sulfate, potassium dichromate, and cobalt chloride which aligns with previous studies in Japan22,23,24, underscoring the growing concern about metal allergies in the general population. One possible explanation for this increase is heightened public awareness, which has led to more frequent referrals to specialized clinics such as those at Tokushima University Hospital10,19,20. Although the number of patients has increased since July 1987, the prevalence of metal allergies has remained consistently high, with no significant fluctuations. In our study, the prevalence of allergies was greater than that reported when similar or other patch test methods were used. This could be due to the specific referral patterns in our clinic, which specializes in metal allergy diagnosis and management. The high referral rate of patients with suspected metal allergies likely contributes to the elevated prevalence observed in our cohort8,25,26,27,28,29,30,31.
The association between pierced earrings and metal allergies is particularly noteworthy. Over the past 15Ā years, the proportion of patients reporting inflammation from pierced earrings has increased dramatically, especially among females. This inflammation is associated with an increased risk of metal allergy, with 81.3% of patients with a history of inflammation due to pierced earrings testing positive for metal allergies, whereas 60.4% of patients do not have such a history. Pierced earrings may pose a greater risk than other types of jewelry because moisture, such as bodily fluids and sweat, can more easily release metal ions, especially if the skin around the pierced hole has not completely healed. Additionally, patients with a history of inflammation from pierced earrings were found to have a significantly greater prevalence of nickel, palladium, cobalt, zinc and gold allergies than those without such a history. The ease with which nickel, palladium, cobalt, and zinc ionize may indicate the likelihood of these metals causing allergies. In addition, the significantly higher prevalence of gold, a precious metal that typically does not ionize easily, may be due in part to the presence of gold plating on less expensive jewelry. Pierced earrings have been popular in Europe for a long time. Studies have reported a relationship between pierced earrings and nickel allergy since the 1980s32,33. Research has shown that nickel allergies are more closely linked to pierced earrings than to pollution from nearby nickel refineries or atopic dermatitis27. The European Union (EU) has established regulations regarding the release of nickel from alloys and coatings used in products that make direct and prolonged contact with the skin34. These regulations were revised and rereleased as EN12472:2005ā+āA1:2009. Following the implementation of nickel-exposure regulations, a decrease in nickel sensitization among schoolgirls was reported in Denmark35. Nickel-exposure regulations have been implemented in Denmark and Sweden, resulting in a decrease in nickel sensitization rates among schoolgirls36,37,38. In contrast, Japan has yet to implement such regulations. In our previous study39,40, 36 earrings sold on the market and 45 earrings of patients were nondestructively analyzed in regard to their composition using an energy-dispersive X-ray fluorescence EDX-900 spectrometer (Shimazu Corporation, Kyoto, Japan). The earrings on the market contained high concentrations and frequencies of copper, nickel, and iron. In addition, patients who used nickel-containing earrings had stronger positive reactions to nickel in patch tests than did patients who used earrings containing less nickel. We were unable to assess the release amount, but we did find a clear relationship between the positive metal elements in patientsā patch tests and the composition of the pierced earrings. This strongly suggests a substantial risk associated with wearing pierced earrings. This study emphasizes the importance of regulatory measures in mitigating the risk of metal allergies. In parallel with successful regulations on nickel exposure in the EU, Japan could benefit from similar interventions. Introducing comparable regulations or labeling requirements could significantly reduce the risk of metal allergies, particularly those related to pierced earrings, and serve as a preventive strategy before clinical intervention becomes necessary.
An interesting aspect of our study is the cross-reactivity between palladium and nickel. Many patients who are sensitized to nickel also show positive reactions to palladium. This finding is particularly relevant for patients with a history of inflammation from pierced earrings. Cross-reaction with palladium from nickel sensitization, which is a congener element, has been reported to cause palladium sensitization41,42,43,44,45,46,47. Our results revealed that the proportion of patients positive for both PdCl2 and NiSO4 was greater than that positive for PdCl2 or NiSO4 alone. Our previous analysis of earring composition39,40 revealed high levels of nickel and low levels of palladium, suggesting that palladium sensitization may arise from cross-reactivity rather than direct exposure from earrings. The potential for cross-reactivity between these two metals is important to consider when diagnosing and managing metal allergies in clinical practice. Animal experiments, such as those conducted with guinea pigs, reported that the palladium-sensitized model reacted to both nickel and palladium and that the nickel-sensitized model reacted only to nickel. Some researchers have suggested that the high proportion of humans reacting to both nickel and palladium, as well as to other metal salts, is not cross-reactive but reflects a subpopulation highly reactive to a variety of allergens48,49. Interestingly, many patients in the noninflammatory pierced earring group tested positive for palladium only. This may be linked to the frequent use of palladium in dental restorations in Japan, often in combination with other metals such as silver, copper, and gold. These alloys are covered by Japanās national health insurance system and are commonly used in fixed prosthetics, which could explain the higher prevalence of palladium sensitization in our study than in overseas reports. These findings underscore the need for further research into the impact of dental metal restorations on metal allergies in Japan. Additionally, Faurschou et al.50 recommended restricting the use of palladium in jewelry until the risks associated with palladium sensitization are better understood. Palladium is congener to nickel and may also be a high-risk metallic element similar to nickel.
The presence of oral lichen planus/oral lichenoid lesions in older patients is another noteworthy finding in our study. These conditions are likely related to long-term exposure to metals used in dental restorations. Frequent contact with metals in the oral cavity, particularly in patients with multiple metal restorations, may trigger allergic reactions over time. Future studies should investigate the relationship between metal exposure from dental restorations and the onset of oral lichen planus and related lesions. On the other hand, the proportion of palmoplantar pustulosis/dyshidrotic eczema cases peaked in the 50s. Since palmoplantar pustulosis/dyshidrotic eczema is diagnosed separately from psoriasis in Japan, the proportion of cases may differ from that reported in other countries. In this study, some patients developed palmoplantar pustulosis from dyshidrotic eczema; therefore, they were classified into the same category as palmoplantar pustulosis/dyshidrotic eczema. The difference in age distribution between oral lichen planus/oral lichenoid lesions and palmoplantar pustulosis/dyshidrotic eczema suggests distinct underlying mechanisms of these conditions, although further research is needed to clarify the pathophysiology.
The findings of our study have important public health implications, particularly with respect to the prevention and management of metal allergies. The high prevalence of metal allergies related to pierced earrings underscores the need for public education on the risks associated with wearing metal jewelry. Public awareness campaigns could inform individuals about the potential for allergic reactions, particularly to metals such as nickel, chromium, and cobalt, which are commonly used in inexpensive jewelry. Additionally, the implementation of regulations to limit the release of allergenic metals from jewelry, such as those in the EU, could significantly reduce the incidence of metal allergies in other countries. Such regulatory measures could serve as important preventive strategies, reducing the need for clinical interventions and improving the quality of life for individuals at risk of developing metal allergies.
This retrospective study, despite its comprehensiveness, has several limitations. First, the reliance on patient self-reports for some of the data introduces the potential for recall bias, affecting the accuracy and reliability of the findings. Such errors in information or distortions in memory within self-reports can significantly affect the reliability of the study. The single-institution design and the potential lack of representativeness of the patient cohort in relation to the broader Japanese demographic could limit the generalizability of these findings. Owing to being confined to a specific patient cohort and a particular timeframe, the applicability of these findings to broader contexts, especially those with diverse cultural or socioeconomic characteristics, might be limited. Hence, caution should be exercised when extending these results to different geographic regions or demographic subsets. Additionally, this study may have restricted information on patient history and diagnosis and may have lacked comprehensive data on other influential factors, such as smoking, lifestyle, and occupational exposures. This gap necessitates more expansive studies to explore these associations in greater detail. Another inherent limitation of retrospective studies is the difficulty in capturing changes in a patientās disease progression. Because the data represent snapshots at specific time points, information about subsequent pathological changes may be incomplete.
Given these limitations, a careful approach is required in interpreting and generalizing the results. Further epidemiological studies, involving larger and more diverse patient populations, are essential to increase the reliability and applicability of these findings. This study clearly demonstrates the need for ongoing research, particularly in understanding the pathophysiology of metal allergies. Future research could explore the genetic basis of metal sensitization, the role of environmental factors in allergy development, and the long-term health impacts of chronic exposure to allergenic metals. Such studies could pave the way for innovative approaches in allergy prevention and treatment. We would like to conduct a prospective cohort study to track the development of metal allergies over time in various populations. This approach will provide more precise data on the progression of these allergies and their triggers.
In conclusion, our study highlights the increasing prevalence of metal allergies in Japan, particularly among females with a medical history of inflammation caused by pierced earrings. The high prevalence of allergies to nickel, palladium, and other metals underscores the need for public health interventions, including regulatory measures and public awareness campaigns. Future research should focus on understanding the genetic and environmental factors that contribute to metal sensitization, as well as investigating new approaches to prevention and treatment. By addressing the growing burden of metal allergies, we can improve the quality of life for affected individuals and reduce the long-term health impacts of these conditions.
Methods
Patients
We conducted a retrospective analysis of patients with suspected metal allergies who visited the DMA clinic at Tokushima University Hospital from July 2005 to June 2020. Patients were referred by general dentists and oral surgeons when they had a history of metal rash and were planning to undergo metal dental treatment, or when mucosal diseases such as oral lichen planus or stomatitis did not improve with drug treatment. Patients were also referred for suspected metal allergies because their skin disease did not improve with oral drug therapy or ointment application. A small number of patients were included in the study with the patientās consent if a patch test had been performed prior to the DMA clinic visit but the skin reaction had not been evaluated by Day 7 or if the diagnosis was missing the type of metal planned to be used in the dental treatment. For the majority of patients, a patch test was not performed previously. This analysis also included a comparison with epidemiological studies conducted every five years since 198710,20.
Ethical considerations
The study adhered to the tenets of the Declaration of Helsinki and received approval from the Ethics Committee of Tokushima University Hospital (protocol code 1036). Informed consent was obtained from all the subjects involved in the study.
Patch test
For the patch test, 18 reagents (allergens) were used, including 16 patch test reagent metals (Torii Pharmaceutical Co., Ltd., Tokyo, Japan), and 2 types of in-house preparations of titanium chloride. In accordance with Nakajimaās method51, titanium chloride solution (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) mixed with purified water at concentrations of 0.1% and 0.05% was used as a reagent. Allergens were applied to the backs of patients for 48Ā h using specialized adhesive plaster āpatch tester toriiā (Torii Pharmaceutical Co., Ltd., Tokyo, Japan). Skin reactions were evaluated on the basis of the criteria set by the International Contact Dermatitis Research Group (ICDRG)52,53,54, with assessments conducted on Days 2, 3, and 7, and a comprehensive assessment was made according to the method of Inoue et al.55 (Supplementary Table S3).
Clinical symptoms
Patients were interviewed about their age, gender, main disease or symptoms, medical history, and specific risk factors such as skin reactions to jewelry or metal-rich foods and a history of orthodontic or implant treatment.
Correlation analysis
The correlations between the incidence of metal allergies and various factors, including age, gender, and medical history, were analyzed via Spearmanās rank correlation coefficient. Additionally, the correlation between different allergens was assessed using the same statistical method.
Statistical analysis
Data analysis was performed using SPSS ver.27 (IBM Japan, Ltd, Tokyo, Japan).
Data availability
Data supporting the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
This study was supported in part by JSPS KAKENHI (Grant Number JP24K13027,Ā JP21K10022, JP20K10038). We would like to express our gratitude to Springer Nature Author Services for their professional English language editing services, which greatly improved the quality of our manuscript.
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T.T., M.H. and M.M. designed the study and wrote the manuscript. T.T., M.H., M.M., M.I., A.O., M.S. and M.N. contributed to clinical data collection, implementation of the study, and interpretation of the data. T.T., M.H., M.M., M.I., A.O. and M.S. performed the statistical analysis and interpretation of the results. Y.K., S.R., P.C., K.K. and Y.M. reviewed the manuscript. All authors read and approved the final manuscript.
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Tajima, T., Hosoki, M., Miyagi, M. et al. Correlation between pierced earrings and the prevalence of metal allergies at Tokushima university hospital: a 15-year retrospective analysis. Sci Rep 15, 10939 (2025). https://doi.org/10.1038/s41598-025-86868-1
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DOI: https://doi.org/10.1038/s41598-025-86868-1
