ABSTRACT
Neomycin, an aminoglycoside antibiotic frequently employed in topical formulations, is a recognised allergen that is part of many baseline series and can cause contact allergy (CA) in both adults and children. It is an allergen of interest as it has a widespread use in over‐the‐counter and prescription products globally, but geographical variations may exist. This study aimed to establish prevalence estimates of CA to neomycin in dermatitis patients and to investigate potential geographical variations. Three databases (PubMed, Embase, and Web of Science) were screened, revealing 70 included studies comprising 456 372 adults and 17 720 children who underwent patch testing. The pooled prevalence of CA to neomycin was found to be 3.2% (95% confidence interval [CI]: 2.6%–3.8%) in adults and 4.3% (95% CI: 2.65%–6.3%) in children. The highest prevalences were observed in North America (adults: 6.4%; children: 8.1%) and South Asia (adults: 4.9%), while Europe showed lower rates (adults: 2.5%; children: 0.8%). Studies after the year 2000 indicated a prevalence of 2.1% in adults and 5.1% in children across geographical regions. These findings highlight a public health concern, particularly in regions with high prevalence rates. The study underscores the need for more restrictive use of neomycin to reduce the incidence of neomycin‐induced CA.
Keywords: allergic contact dermatitis, antibiotics, contact allergy, epidemiology, neomycin, prevalence
1. Introduction
Neomycin is an aminoglycoside antibiotic commonly used in topical formulations. Although beneficial for infection control, neomycin is a recognised allergen, and exposure may cause contact allergy (CA) in both adults and children [1]. Neomycin can be administered orally, whereas topical formulations are available for localised use [2]. Neomycin is found in over‐the‐counter and prescription products worldwide, such as antibiotic ointments, eye drops, eardrops, and as an excipient in vaccines widely utilised for its antimicrobial properties [2, 3, 4]. Antibiotic resistance is often highlighted as an argument for restrictive antibiotic use; however, contact allergy to antibiotics is another issue that needs to be addressed. In the European baseline series, neomycin has been tested in 20% pet [5]. and neomycin is also part of the TRUE test system.
Little is known about the worldwide prevalence of CA to neomycin in adults and children. While individual studies have explored the prevalence of CA to neomycin [1, 6, 7], a comprehensive synthesis of this evidence is lacking. The aim of this study is to establish prevalence estimates of CA to neomycin in adults and children and investigate the prevalence in different geographical regions.
2. Methods
A study protocol was conducted before initiating the study and registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024569404). The study was performed according to the Preferred Items for Systematic Review and Meta‐Analysis (PRISMA) guidelines [8].
2.1. Literature Search
A comprehensive literature search was conducted using the databases PubMed, Embase and Web of Science with the following search strategies: (neomycin) AND (“allergic contact dermatitis” OR “contact allergy” OR “contact dermatitis” OR “allergic reaction” OR “hypersensitivity” OR “contact sensitization” OR “contact sensitivity”). The search was conducted on July 16th, 2024, and no restrictions were placed on publication date.
2.2. Inclusion and Exclusion Criteria
Eligible studies were assessed by MBJ and DI. Inclusion criteria were: (I) Original studies (II) studies written in English (III) studies including ≥ 100 consecutively patch tested children and/or adults (≥ 18 years age) with dermatitis who were patch tested with neomycin of any concentration and vehicle. If different concentrations of neomycin were used for the same population, results would be presented separately if possible; otherwise, pooled data are provided. Exclusion criteria were: (I) studies specifically investigating dermatitis characterised by its anatomical location, such as hand dermatitis or scalp dermatitis, (II) studies examining samples from the general population, and (III) conference abstracts or letters to the editor. In the case of duplicate articles of the same population, the most comprehensive report was included. If inclusion criteria could not be determined based on title or abstract, the study was included for full‐text screening.
2.3. Data Extraction and Quality Assessment
Data were entered by MBJ and DI into a pre‐defined table including data on the author, publication year, study period, study country, concentration, vehicle, number of positive patch tests (PPTs), sex distribution (female, %), age distribution (mean, standard deviation (SD)), history of atopic dermatitis (AD) (%), and clinical relevance (%). The quality of the included cross‐sectional studies was assessed using the assessment tool for cross‐sectional studies (AXIS) [9].
2.4. Statistical Analysis
Statistical analyses were performed using StatsDirect version 3.1.4 (StatsDirect Ltd., Wirral, UK). Pooled proportions for the total population were calculated using random‐effects models with 95% confidence intervals (CI). In addition, stratified analysis was done for adults only, children only, and according to geographical areas and publication years. Heterogeneity between studies was assessed using the Cochran Q test and the I [2] statistic. Given the expected high heterogeneity among the included studies, pooled proportion analyses were performed using the DerSimonian‐Laird method with random‐effects models [10]. Forest plots were constructed, and the Egger's test and funnel plots were performed to assess the risk of publication bias. To assess differences in PPTs for both adults and children [2], tests of independence were conducted. A significance level of p < 0.05 was used to determine statistical significance. Due to limited data across different geographic subgroups, analyses were restricted to overall comparisons by time period within each age group.
3. Results
In total, 2878 studies were identified. After removing duplicates, 2142 unique studies remained for title and abstract screening. In total, 268 studies were included for full‐text evaluation. Of these, 198 studies were excluded after full‐text evaluation based on the predetermined criteria. No additional study was included after screening the reference lists of the included studies. Finally, 70 studies [1, 3, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75] were included in the analysis (Figure 1). Of these studies, 52 [1, 3, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57] and 18 [58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75] examined a population of adults and children, respectively. A tabular summary of the general characteristics of the included studies for adults and children is presented in Tables 1 and 2, respectively. Generally, studies had low or medium risk of bias based on the AXIS assessment (Tables S1 and S2).
FIGURE 1.
Preferred items for systematic reviews and meta‐analysis (PRISMA).
TABLE 1.
General characteristics of the included studies conducted on adults.
| Label | Study period (year) | Study country | Total tested [n] | PPTs [n] | PPTs [%] | Female [n (%)] | Age [mean (SD)] | History of atopic dermatitis [%] | Clinical relevance [%] |
|---|---|---|---|---|---|---|---|---|---|
| Baer et al. (1973) [1] | 1968–1970 | United States | 540 | 28 | 5.2 | NA | NA | NA | NA |
| Hirano & Yoshikawa (1982) [2] | 1976–1979 | Japan | 434 | 13 | 5.1 | NA | NA | NA | NA |
| Hogan et al. (1988) [3] | 1983–1987 | Canada | 542 | 31 | 5.7 | 330 (60.9) | 39.4 (18.0) | 30.1 | NA |
| Gollhausen et al. (1988) [4] | 1977–1983 | Germany | 11 962 | 419 | 3.5 | 7177 (60.0) | NA | NA | NA |
| Goh (1988) [5] | 1984–1985 | Singapore | 2471 | 142 | 5.7 | 1160 (46.9) | 32.0 (NA) | NA | NA |
| Goh (1989) [6] | 1985–1986 | Singapore | 1685 | 132 | 7.8 | 838 (49.7) | 31.8 (NA) | NA | NA |
| Leok et al. (1992) [7] | 1986–1990 | Singapore | 5557 | 381 | 6.9 | 2923 (52.6) | NA | NA | NA |
| Bruckner‐Tuderman et al. (1992) [8] | 1989–1989 | Switzerland | 921 | 63 | 6.8 | 543 (59) | 42.8 (NA) | NA | NA |
| el‐Rab & al‐Sheikh (1995) [9] | 1993–1994 | Saudi Arabia | 240 | 26 | 11.0 | 131 (54.9) | NA | NA | NA |
| Holness et al. (1995) [10] | 1985–1989 | United States a | 4055 | 292 | 7.2 | 2311 (57.0) | 43.8 (NA) | NA | NA |
| Liu et al. (1997) [11] | 1988–1996 | China | 1135 | 24 | 2.1 | 823 (72.5) | 34.3 (NA) | NA | NA |
| Husajn (1997) [12] | 1970–1973 | Scotland | 1312 | 55 | 4.2 | 709 (54.0) | NA | NA | NA |
| Sharma & Chakrabarti (1998) [13] | 1996–1997 | India | 200 | 10 | 5 | 78 (39) | 39.8 (NA) | NA | NA |
| Marinović‐Kulisić et al. (2004) [14] | 1998–2003 | Croatia | 4132 | 522 | 12.6 | 2940 (71.2) | 40.0 (NA) | 11.7 | NA |
| Piaserico et al. (2004) [15] | 1997–2001 | Italy c | 1444 | 37 | 2.4 | 980 (67.9) | 72.5 (5.7) | 7.1 | NA |
| Machovcova et al. (2005) [16] | 1997–2001 | Czech Republic | 12 058 | 234 | 1.9 | 7642 (63.4) | 41.7 (12.6) | 26.4 | NA |
| Bruynzeel et al. (2005) [17] | 1996–2000 | Europa d | 26 210 | 786 | 3.0 | 17 722 (67.6) | NA | NA | NA |
| Uter et al. (2005) [18] | 2002–2003 | Europa b | 10 511 | 304 | 2.9 | 6611 (62.9) | NA | 18.0 | NA |
| Menezes de Padua et al. (2005) [19] | 1998–2003 | Germany | 47 559 | 1208 | 2.5 | 29 386 (61.8) | NA | 16.7 | NA |
| Akyol et al. (2005) [20] | 1992–2004 | Turkey | 1038 | 25 | 2.4 | 705 (67.9) | 33.4 (13.7) | 19.7 | NA |
| Menezes de Pádua et al. (2006) [21] | 1995–2005 | Germany | 80 867 | 2022 | 2.5 | NA | NA | NA | NA |
| Lazarov (2006) [22] | 1998–2004 | Israel | 2156 | 23 | 1.1 | 1462 (67.8) | 45.5 (17.1) | 21.9 | 68.4 |
| Magen et al. (2006) [23] | 2002–2005 | Israel | 864 | 4 | 0.5 | 547 (63.3) | NA | 14.1 | NA |
| Bajaj et al. (2007) [24] | 1997–2006 | India | 1000 | 70 | 7.0 | 434 (43.4) | 35.9 (NA) | NA | 98.8 |
| Lindberg et al. (2008) [25] | 1992–2000 | Sweden | 7452 | 115 | 1.5 | 4780 (64.1) | NA | NA | NA |
| Carlsen et al. (2008) [26] | 1985–2005 | Denmark | 14 998 | 420 | 2.8 | 9524 (63.5) | 47.4 (NA) | NA | NA |
| Lam et al. (2008) [27] | 1995–1999 | Hong Kong | 2585 | 126 | 4.9 | 1535 (59.4) | NA | NA | NA |
| Bilcha et al. (2010) [28] | 2007–2008 | Ethiopia | 514 | 0 | 0 | 343 (66.7) | 36.3 (12.1) | 1.5 | NA |
| Janach et al. (2010) [29] | 2000–2004 | Switzerland | 4094 | 81 | 1.3 | 2388 (58.3) | 45.4 (17.9) | 10.6 | NA |
| Yin et al. (2011) [30] | 2004–2009 | China | 2758 | 17 | 0.6 | 1622 (58.8) | 38.5 (12.4) | 7.8 | NA |
| Landeck et al. (2011) [31] | 1990–2006 | United States | 1247 | 59 | 4.7 | 874 (70.1) | 46.2 (15.2) | 13.8 | 4.8 |
| Rodrigues et al. (2012) [6] | 2003–2010 | Brazil | 1406 | 88 | 6.3 | 955 (67.9) | 42.0 (16) | 34.1 | NA |
| Uter et al. (2012) [32] | 2007–2008 | Europa b | 25 181 | 161 | 0.6 | 16 421 (65.2) | NA | 12.9 | NA |
| Reduta et al. (2013) [33] | 2007–2011 | Poland | 1532 | 69 | 4.4 | 1010 (65.9) | 43.6 (15.5) | 4.5 | NA |
| Gilissen & Goossens (2016) [34] | 1990–2014 | Belgium | 14 578 | 269 | 1.8 | 9.856 (66.1) | 47 (NA) | 22.2 | NA |
| Uter et al. (2016) [35] | 2009–2012 | Europa b | 28 569 | 371 | 1.3 | NA | 45.0 (NA) | NA | NA |
| Kot et al. (2016) [36] | 2013–2014 | Poland | 126 | 2 | 1.6 | 80 (63.5) | 50.4 (NA) | NA | NA |
| Linauskienė et al. (2017) [37] | 2014–2015 | Lithuania | 297 | 7 | 2.4 | 257 (86.5) | NA | 23.6 | NA |
| Hassan et al. (2019) [38] | 2011–2018 | India | 582 | 16 | 2.8 | 371 (63.8) | 34.7 (11.3) | NA | 75.0 |
| Teo et al. (2019) [39] | 1984–2014 | United Kingdom | 43 443 | 1557 | 3.6 | 27 061 (58.5) | 41.0 (NA) | 29.4 | NA |
| Tagka et al. (2020) [40] | 2014–2016 | Greece | 1978 | 57 | 2.9 | 1359 (68.7) | 45.9 (18.6) | 35.0 | NA |
| Uter et al. (2021) [41] | 2008–2011 | Germany | 515 | 1 | 0.3 | 283 (54.9) | NA | 4.1 | NA |
| Silverberg et al. (2021) [42] | 2001–2016 | United States a | 36 896 | 3261 | 8.8 | NA | NA | 22.5 | NA |
| Uter et al. (2022) [43] | 2019–2020 | Europa b | 11 737 | 97 | 0.8 | NA | NA | NA | NA |
| Wee et al. (2022) [44] | 2007–2017 | Singapore | 4903 | 127 | 5.1 | 2860 (58.3) | 40.1 (16.3) | 51.6 | NA |
| Bizjak et al. (2022) [3] | 2019–2021 | Slovenia | 748 | 21 | 2.8 | 550 (73.5) | 45.0 (NA) | NA | NA |
| Ünal (2022) [45] | 2012–2022 | Turkey | 1012 | 2 | 0.3 | 579 (57.2) | 38.0 (NA) | 33.2 | NA |
| Scherrer et al. (2023) [46] | 2009–2018 | Brazil | 1162 | 71 | 6.0 | 755 (65.0) | 53.5 (NA) | 24.0 | 14 |
| Boonchai et al. (2023) [47] | 2001–2021 | Thailand | 5010 | 224 | 4.5 | 3844 (76.73) | 41.9 (15.3) | 43.1 | NA |
| Dekoven et al. (2023) [48] | 2019–2020 | United States a | 4221 | 259 | 6.3 | 3142 (73.8) | 47.7 (NA) | 31.8 | 33.2 |
| Larsen et al. (2024) [49] | 2000–2023 | Denmark | 17 849 | 255 | 1.4 | 12 022 (67.35) | 48.6 (16.9) | 17.8 | 18.5 |
| Slodownik et al. (2024) [49] | 2019–2022 | Israel | 2086 | 6 | 0.3 | 1401 (67.0) | NA | 19.0 | 17 |
Abbreviations: NA, not available; PPTs, positive patch tests; SD, standard deviation.
NACDG.
ESSCA.
NEICDG.
EECDRG.
TABLE 2.
General characteristics of the included studies conducted in children.
| Label | Study period (year) | Study country | Total tested [n] | PPTs [n] | PPTs [%] | Female [n (%)] | Age [mean (SD)] | History of atopic dermatitis [%] | Clinical relevance [%] |
|---|---|---|---|---|---|---|---|---|---|
| Manzini et al. (1998) [50] | 1988–1994 | Italy | 670 | 24 | 3.9 | NA | NA | 75.5 | NA |
| Giordano‐Labadie et al. (1999) [51] | 1998–1999 | France | 137 | 3 | 2.2 | 67 (48.9) | 4.5 (NA) | 100 | NA |
| Roul et al. (1999) [52] | 1995–1997 | France | 337 | 12 | 3.5 | NA | NA | 76.0 | NA |
| Mortz et al. (2000) [53] | 1995–1996 | Denmark | 1146 | 2 | 0.2 | 620 (54.1) | 14.1 (NA) | 21.3 | 0 |
| Seidenari et al. (2005) [54] | 1995–2001 | Italy | 1094 | 144 | 13.2 | 585 (53.5) | 5.4 (3.1) | 36.9 | 70.0 |
| Goon & Goh (2006) [55] | 1986–2003 | Singapore | 1063 | 43 | 4.0 | 583 (54.8) | NA | 38.0 | NA |
| Clayton et al. (2006) [56] | 1995–2004 | United Kingdom | 500 | 4 | 0.8 | 310 (62.0) | 12.0 (3.8) | 61.0 | 100 |
| Hogeling & Pratt (2008) [57] | 1996–2006 | United States | 100 | 7 | 7.0 | 62 (50.8) | 13.7 (3.4) | 41.0 | 55.8 |
| Fortina et al. (2011) [58] | 2002–2008 | Italy | 320 | 16 | 5.0 | 177 (55.3) | 2.3 (0.4) | 7.3 | 31.25 |
| Moustafa et al. (2011) [59] | 2002–2008 | United Kingdom | 110 | 7 | 6.4 | 68 (62.0) | 12.0 (NA) | 51.0 | 59.1 |
| Machovcova (2012) [60] | 2005–2006 | Czech Republic | 218 | 25 | 11.5 | 104 (47.7) | 12.6 (NA) | 27.0 | 39.0 |
| Simonsen et al. (2014) [61] | 2003–2011 | Denmark | 2592 | 12 | 0.5 | 1709 (65.9) | NA | 44.8 | NA |
| Rodrigues & Goulart (2015) [62] | 2003–2010 | Brazil | 125 | 8 | 6.4 | 96 (76.8) | 14.3 (3.8) | 44.8 | 45.6 |
| Fortina et al. (2015) [63] | 2002–2010 | Europa b | 6708 | 215 | 3.2 | 3965 (59.1) | NA | NA | NA |
| Yılmaz & Özkaya (2021) [64] | 1996–2017 | Turkey | 146 | 4 | 1.3 | 109 (74.6) | 14.0 (NA) | 13.7 | 25.0 |
| Bonamonte et al. (2022) [65] | 2017–2018 | Italy | 432 | 8 | 1.9 | 232 (53.7) | 10.4 (NA) | 23.8 | NA |
| Silverberg et al. (2022) [66] | 2001–2018 | United States a | 1110 | 118 | 6.3 | 706 (63.6) | 12.4 (3.9) | 52.6 | NA |
| Johnson et al. (2023) [67] | 2018–2022 | United States | 912 | 56 | 6.1 | 561 (61.5) | 11.3 (4.7) | 67.4 | NA |
Abbreviations: NA, not available; PPTs, positive patch tests; SD, standard deviation.
NACDG.
ESSCA.
3.1. Qualitative Assessment of the Included Studies
3.1.1. Characteristics of Studies Conducted on Adults
Across 52 studies [1, 3, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57], the study periods ranged from 1968 to 2022. The percentage of females in the studies ranged from 39% to 86.5%, with a mean of 62.9% (SD: 10.5%), reported in 46 studies [1, 3, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 37, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57]. The mean age of participants ranged from 25.3 to 72.5 years, with a mean of 43.4 years (SD: 8.4), reported in 33 studies. A history of atopic dermatitis was reported in 29 studies [3, 6, 7, 11, 13, 14, 15, 16, 28, 30, 31, 32, 33, 35, 37, 38, 39, 40, 42, 45, 46, 47, 48, 49, 50, 51, 56, 57, 76], with values ranging from 1.5% to 51.6% and a mean of 21.0% (SD: 11.7%). The clinical relevance of neomycin contact allergy was reported in eight studies [6, 7, 31, 41, 48, 55, 57], ranging from 4.8% to 98.8% (Table 1).
Most studies originated from Europe (n = 26) [1, 3, 7, 12, 13, 14, 15, 16, 18, 21, 27, 34, 36, 37, 39, 40, 42, 43, 44, 45, 46, 50, 51, 52, 53, 76] and North America (n = 6) [20, 28, 29, 31, 38, 48], followed by the Middle East (n = 5) [11, 30, 33, 56, 57], Southeast Asia (n = 5) [23, 24, 25, 32, 35], East Asia (n = 4) [19, 26, 49, 54], South Asia (n = 3) [17, 41, 55], South America (n = 2) [6, 47] and Western Asia (n = 1) [22].
3.1.2. Characteristics of Studies Conducted in Children
Across 18 studies [1, 3, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57], the study periods ranged from 1986 to 2022. The percentage of girls in the studies ranged from 47.7% to 76.8%, with a mean of 59.7% (SD: 8.2%), reported in 16 studies [58, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75]. The mean age of participants ranged from 2.3 to 14.3 years, with a mean of 10.7 years (SD: 4.0), reported in 13 studies [60, 62, 63, 64, 65, 66, 67, 70, 71, 72, 73, 74, 75]. A history of atopic dermatitis was reported in 17 studies [58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70, 71, 72, 73, 74, 75], with values ranging from 7.3% to 100% and a mean of 46.6% (SD: 23.9%). A study by Giordano‐Labadie et al. [60] from 1999 involved 137 children with atopic dermatitis. Of these, three exhibited PPTs yielding an estimate of CA to neomycin of 2.2%. The clinical relevance of neomycin CA was reported in 9 studies [62, 63, 64, 65, 66, 67, 71, 72, 75], ranging from 0.0% to 100%, with a mean of 43.0% (SD: 30.2%) (Table 2).
Most studies originated from Europe (n = 12) [59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70] and North America (n = 3) [72, 73, 74], followed by the Middle East (n = 1) [71], South America (n = 1) [75] and Asia (n = 1) [58].
3.2. Quantitative Assessment
3.2.1. CA To Neomycin in Adults
The prevalence of PPTs to neomycin in adults was reported in 52 studies [1, 3, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57] encompassing 456,372 patients with 14,590 PPTs yielding a pooled prevalence of 3.2% (95% CI, 2.6%–3.8%) (Figure 2, Table 3 and Figure S1).
FIGURE 2.
Proportion meta‐analysis plot with random effects for adults tested with neomycin. The figure displays the author, publication year, prevalence, confidence intervals, and the pooled prevalence for all studies.
TABLE 3.
Prevalences of positive patch tests to neomycin in adults and children.
| Population | Studies [n] | Patients [n] | PPTs [n] | Proportion of positive reactions [%] | 95% CI | p‐value for Q test | I2 (95% CI) [%] | Egger's bias (95% CI) | Egger's bias p‐value |
|---|---|---|---|---|---|---|---|---|---|
| Adults | 52 | 456 372 | 14 590 | 3.2 | 2.6–3.8 | < 0.0001 | 99.2 (99.2–99.2) | 5.6 (1.5–9.7) | 0.0084 |
| Children | 18 | 17 720 | 708 | 4.3 | 2.6–6.3 | < 0.0001 | 96.9 (96.3–97.4) | 4.7 (1.9–7.5) | 0.0025 |
Abbreviations: CI, confidence interval; PPTs, positive patch tests.
3.2.2. CA To Neomycin in Children
The prevalence of PPTs to neomycin in children was reported in 18 studies [58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75] encompassing 17 720 patients with 708 PPTs, yielding a pooled prevalence of 4.3% (95% CI, 2.6%–6.3%) (Figure 3 and Table 3).
FIGURE 3.
Proportion meta‐analysis plot with random effects for children tested with neomycin. The figure displays the author, publication year, prevalence, confidence intervals, and the pooled prevalence for all studies.
3.2.3. Differences in CA to Neomycin According to Time Period in Adults and Children
In adults, PPTs showed a significant decrease when comparing data from before and after 2000 [χ [2] (1, N = 169 209) =11.52, p < 0.001]. Conversely, in children, there was a significant increase in PPTs between the two periods [χ [2] (1, N = 13 280) = 20.46, p < 0.001].
3.2.4. CA To Neomycin According to Geographical Regions
For adults, the highest pooled prevalences of CA to neomycin were 6.4% (95% CI, 5.0%–7.9%; n = 6 studies [20, 28, 29, 31, 38, 48]) in North America, 6.2% (95% CI, 5.3%–7.2%; n = 2 studies [6, 47]) in South America, 5.3% (95% CI, 3.6%–7.4%; n = 5 studies [23, 24, 25, 32, 35]) in Southeast Asia, and 4.9% (95% CI, 2.3%–8.3%; n = 3 studies [17, 41, 55]) in South Asia. The lowest prevalences of CA to neomycin were 2.5% (95% CI, 2.0%–3.0%; n = 26 studies [3, 7, 12, 13, 14, 15, 16, 18, 21, 27, 34, 36, 37, 39, 40, 42, 43, 44, 45, 46, 50, 51, 52, 53, 76]) in Europe, 2.4% (95% CI, 0.6%–5.3%; n = 4 studies [19, 26, 49, 54]) in East Asia, and 0.8% (95% CI, 0.2%–1.5%; n = 5 studies [11, 30, 33, 56, 57]) in the Middle East (Figure 4a and Table 4).
FIGURE 4.
Prevalence estimates of contact allergy to neomycin according to geographical regions in adults (a) and children (b). Each bullet represents one study. Standard deviation (SD) was calculated for regions where two or more studies were included. There was only one study on children in Asia, and thus it could not be made more region‐specific.
TABLE 4.
Prevalences of positive patch tests to neomycin according to geographical regions in adults and children.
| Europe | Middle East | North America | South America | East Asia | South Asia | Southeast Asia | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Population | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] |
| Adults | 26 | 2.5 (2.0–3.0) | 5 | 0.8 (0.2–1.5) | 6 | 6.4 (5.0–7.9) | 2 | 6.2 (5.3–7.2) | 4 | 2.4 (0.6–5.3) | 3 | 4.9 (2.3–8.3) | 5 | 5.3 (3.6–7.4) |
| Children | 12 | 0.8 (0.4–1.5) | NA | NA | 3 | 8.1 (4.9–11.9) | NA | NA | NA | NA | NA | NA | NA | NA |
Abbreviations: CI, confidence interval; NA, not applicable; PPTs, positive patch tests.
For children, the pooled prevalence of CA to neomycin was 0.8% (95% CI, 0.4%–1.5%; n = 12 studies [59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70]) in Europe, and 8.1% (95% CI, 4.9%–11.9%; n = 3 studies [72, 73, 74]) in North America. Pooled prevalences of CA to neomycin in children in the Middle East, South America, East Asia, South Asia, and Southeast Asia could not be calculated due to a limited number of studies (Figure 4b and Table 4).
3.2.5. CA To Neomycin According to Publication Year and/or Region in Adults and Children
For adults, the prevalence of CA to neomycin in studies with study periods before the year 2000 was 5.2% (95% CI, 4.2%–6.4%; n = 15 studies [17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 53, 54]). For studies after the year 2000, the prevalence was 2.1% (95% CI, 1.1%–3.3%; n = 24 studies [6, 7, 13, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 49, 50, 51, 56]). European studies after the year 2000 (n = 13 studies [7, 13, 34, 36, 37, 39, 42, 43, 44, 45, 46, 50, 51]) revealed a prevalence of CA to neomycin of 1.6 (95% CI, 1.1%–2.1%), while high prevalences were found in North America (7.4%, 95% CI: 5.0%–10.3%; n = 2 studies [31, 38]) after the year 2000 (Table 5).
TABLE 5.
Prevalence of positive patch tests to neomycin across geographical regions in adults and children, categorised by study periods before and after the year 2000. Studies overlapping 2000 were excluded from the analysis. Pooled meta‐analyses with random effects were conducted for groups with two or more studies. Single‐study data are indicated with ( a ).
| Study period | All countries | Europe | Middle East | North America | |||||
|---|---|---|---|---|---|---|---|---|---|
| Year | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | |
| Adults | < 2000 | 15 | 5.2 [4.2–6.4] | 4 | 0.4 [0.3–0.5] | NA | NA | 3 | 6.4 [5.0–7.7] |
| > 2000 | 24 | 2.1 [1.1–3.3] | 13 | 1.6 [1.1–2.1] | 3 | 0.3 [0.1–0.5] | 2 | 7.4 [5.0–10.3] | |
| Children | < 2000 | 3 | 2.0 [1.3–6.1] | 3 | 2.0 [1.3–6.1] | NA | NA | NA | NA |
| > 2000 | 9 | 5.1 [2.7–8.2] | 6 | 3.9 [1.7–6.9] | NA | NA | 2 | 8.3 [4.5–13.2] | |
| South America | East Asia | South Asia | Southeast Asia | Western Asia | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | Studies [n] | Proportion of PPTs (95% CI) [%] | |
| Adults | NA | NA | 3 | 3.3 [1.7–5.5] | 1 a | 5.0 | 3 | 6.8 [5.8–7.8] | 1 a | 10.4 |
| NA | NA | 1 a | 0.6 | 1 a | 2.7 | 2 | 3.5 [1.8–5.5] | NA | NA | |
| Children | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 1a | 6.4 | NA | NA | NA | NA | NA | NA | NA | NA | |
Abbreviations: CI, confidence interval; NA, not applicable; PPTs, positive patch tests.
One study.
For children, the prevalence before year 2000 was 2.0% (95% CI; 1.3%–6.1%; n = 3 studies [59, 61, 62]) and after year 2000 was 5.1% (95% CI: 2.7%–8.2%; n = 9 studies [65, 66, 67, 68, 69, 70, 73, 74, 75]). In Europe, the prevalence before year 2000 was 2.0% (95% CI, 1.3%–6.1%; n = 3 studies [59, 61, 62]) and after year 2000 was 3.9% (95% CI, 1.7%–6.9%; n = 6 studies [65, 66, 67, 68, 69, 70]). For North America, the prevalence of CA to neomycin after year 2000 was 8.3% ((95% CI, 4.5%–13.2%); n = 2 studies [73, 74]) (Table 5).
4. Discussion
In this systematic review and meta‐analysis of 70 studies encompassing 456 372 adults and 17 720 children undergoing patch testing, the overall prevalence of CA to neomycin was 3.2% in adults and 4.3% in children across all included studies. Based on geographical regions, the highest prevalences of CA to neomycin were found in North America (Adults: 6.4%, children: 8.1%) and South Asia (Adults: 4.9%), while European data showed lower prevalences of 2.5% and 0.8% in adults and children, respectively. Based on newer studies after the year 2000, the overall prevalence was 2.1% in adults and 5.1% in children. These high rates of CA to neomycin emphasise the important role of neomycin as a sensitiser, particularly in comparison to more well‐known allergens. For example, prevalences of CA have been reported to be 2.0%–2.7% for rubber accelerators [77, 78], 7% for fragrance mix I and 3.7% for fragrance mix II [78, 79], and 5.0% for preservatives like methylisothiazolinone (MI) [36, 80], which often have comparable prevalence rates. The prevalence of CA to neomycin in this study was even higher in North America and South Asia, highlighting an overlooked problem in these regions.
For children, the estimate found in this study is slightly higher than that of a recent systematic review and meta‐analysis on CA in children from 2010 to 2024 revealing an overall prevalence of 3.2% [81]. The differences in these findings may rely on the methodology of the two studies, as the current study did not have any restrictions on the publication year. Further, the discrepancies may be attributed to the fact that the present study encompasses a diverse range of geographical regions, each with distinct policies governing the utilisation of neomycin and varying degrees of leniency in antibiotic prescription.
The presence of neomycin as an excipient in vaccines may contribute to the development of contact allergy, particularly in younger individuals. A previous study demonstrated notable age‐related differences in CA to both neomycin and thimerosal among children and teenagers with eczema [82]. The prevalence of CA to neomycin was 4.9% in 7–8‐year‐olds, whereas no cases were observed among 16–17‐year‐olds [82]. This contrast aligns with differences in vaccine exposure: the older cohort received multiple thiomersal‐containing vaccines, while the younger cohort had fewer thiomersal‐containing vaccines but increased exposure to vaccines with trace amounts of neomycin. These findings highlight the importance of considering vaccine composition as a potential factor influencing variations in neomycin allergy prevalence across age groups and geographical locations [83, 84, 85]. Since aminoglycosides such as neomycin are used as preservatives in certain vaccines, repeated exposure during early childhood may induce sensitisation in susceptible individuals [84, 85]. Future studies should investigate the relationship between vaccine‐related exposure and neomycin sensitisation and assess whether changes in vaccine formulations over time affect trends in contact allergy prevalence.
Differences in geographical variation of CA to neomycin were exploited in sub‐analyses. The high prevalence of contact allergy in especially southeast Asia and north America compared to Europe may be explained by less regulation on neomycin medication in these first mentioned regions. For example, over‐the‐counter preparations are widely available in the USA and many Asian countries, unlike Europe. In Denmark, neomycin was withdrawn as a medical product in October 2009. In a cross‐sectional study by Kursawe Larsen et al., it was shown that this action significantly decreased CA to neomycin in Denmark from 1.8% in the period from 2000 to 2009 to 1.2% in the period from 2010 to 2023 (p < 0.005) [7].
With sensitization rates for children in this study exceeding 8% in North America, and for adults being 6.4% in North America, 5.3% in Southeast Asia, and 4.9% in South Asia, there is an immediacy call for better regulation on neomycin medical products in these regions. Redundant use of antibiotics is increasingly problematic, not only due to the well‐documented issue of antibiotic resistance [86], but also because of its role in CA. We propose that neomycin should be withdrawn as a medical product in countries still using it, or at least legislation requiring a prescription to buy neomycin‐containing medicine should be implemented.
Cross‐reactivity between neomycin and other aminoglycosides, including framycetin, paromomycin, gentamycin, and tobramycin, exists primarily due to their similarities in chemical structure [87]. Thus, cross‐reactivity is an important factor to consider when interpreting rates of PPTs. Aminoglycosides are frequently used in topical formulations, both as prescription and over‐the‐counter products, and prior exposure to these structurally related compounds may contribute to sensitisation and PPTs [83]. Therefore, it may be likely that this phenomenon influences the reported prevalence of CA to neomycin and should be recognised as a potential confounder. Further, clinicians prescribing neomycin should be aware of this when prescribing topical aminoglycosides and when diagnosing and treating patients with known CA to neomycin.
The strengths of this study are (I) the comprehensive literature review including 70 studies encompassing 456,372 adults and 17,720 children, (II) the concentration or vehicle for neomycin has not changed during the study period, and (III) sub‐analyses were conducted based on geographical regions to reveal differences and trends based on local regulations to further strengthen the estimates presented in our study. However, when interpreting the results of the current study, some limitations should be noted. While we report the prevalence of CA to neomycin, only a few studies report clinically relevant PPTs leading to allergic contact dermatitis. Further, estimates on prevalences of CA to neomycin in various regions relied on few studies and should be interpreted with caution.
5. Gaps in Knowledge
While this meta‐analysis consolidates available data on the prevalence of CA to neomycin in dermatitis patients, several knowledge gaps limit our understanding of the allergen's epidemiology, diagnosis, and management. These gaps highlight areas where further research could provide valuable insights and enhance clinical practice. Firstly, longitudinal studies including clinical relevance are highly needed. While PPTs confirm sensitization to neomycin, the clinical relevance is not well understood, though understanding these factors could provide valuable insights into disease severity, chronicity, and quality of life in dermatitis patients. Further, more knowledge is needed on the cross‐reactivity between neomycin and other aminoglycosides [87, 88].
6. Conclusion
CA to neomycin is frequent in both adults and children throughout the study period. However, the prevalence varies significantly according to geographical regions. We recommend a withdrawal of neomycin in regions still utilising it or limiting over‐the‐counter sale with legislation requiring a prescription to buy neomycin medication.
Author Contributions
Mikkel Bak Jensen: investigation, validation, visualization, software, formal analysis, supervision, writing – review and editing, writing – original draft, conceptualization, project administration, methodology. Daniel Isufi: investigation, validation, writing – original draft, writing – review and editing, project administration, methodology. Christoffer Kursawe Larsen: investigation, writing – original draft, writing – review and editing, supervision, conceptualization. Jakob Ferløv Baselius Schwensen: writing – original draft, writing – review and editing, validation, project administration, supervision. Farzad Alinaghi: supervision, project administration, conceptualization, investigation, validation. Jeanne Duus Johansen: writing – original draft, writing – review and editing, project administration, supervision, validation.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Data S1.
Funding: This work was supported by The Danish Environmental Protection Agency under the Ministry of Environment of Denmark.
Mikkel Bak Jensen shared first authorship.
Contributor Information
Mikkel Bak Jensen, Email: mikkel.bak.jensen@regionh.dk.
Daniel Isufi, Email: daniel.isufi@regionh.dk.
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.
References
- 1. De Púdua C. A. M., Schnuch A., Lessmann H., Geier J., Pfahlberg A., and Uter W., “Contact Allergy to Neomycin Sulfate: Results of a Multifactorial Analysis,” Pharmacoepidemiology and Drug Safety 14, no. 10 (2005): 725–733, 10.1002/PDS.1117. [DOI] [PubMed] [Google Scholar]
- 2. Veirup N. and Kyriakopoulos C., Neomycin. Kucers the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, 7th ed. (CRC Press, 2023), 1046–1052, 10.1201/9781498747967. [DOI] [Google Scholar]
- 3. Gilissen L. and Goossens A., “Frequency and Trends of Contact Allergy to and Iatrogenic Contact Dermatitis Caused by Topical Drugs Over a 25‐Year Period,” Contact Dermatitis 75, no. 5 (2016): 290–302, 10.1111/COD.12621. [DOI] [PubMed] [Google Scholar]
- 4. McNeil M. M. and DeStefano F., “Vaccine‐Associated Hypersensitivity,” Journal of Allergy and Clinical Immunology 141, no. 2 (2018): 463–472, 10.1016/J.JACI.2017.12.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Wilkinson S. M., Gonçalo M., Aerts O., et al., “The European Baseline Series and Recommended Additions: 2023,” Contact Dermatitis 88, no. 2 (2023): 87–92, 10.1111/COD.14255. [DOI] [PubMed] [Google Scholar]
- 6. Scherrer M. A. R., Abreu É. P., and Rocha V. B., “Neomycin: Sources of Contact and Sensitization Evaluation in 1162 Patients Treated at a Tertiary Service,” Anais Brasileiros de Dermatologia 98, no. 4 (2023): 487–492, 10.1016/J.ABD.2022.07.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Kursawe Larsen C., Jensen M. B., and Schwensen J. F. B., “Contact Allergy to Neomycin in Consecutively Patch Tested Danish Eczema Patients From 2000 to 2023: A Cross‐Sectional Study,” Contact Dermatitis 91, no. 5 (2024): 392–397, 10.1111/COD.14653. [DOI] [PubMed] [Google Scholar]
- 8. Moher D., Liberati A., Tetzlaff J., and Altman D. G., “Preferred Reporting Items for Systematic Reviews and Meta‐Analyses: The PRISMA Statement,” BMJ 339, no. 7716 (2009): 332–336, 10.1136/BMJ.B2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Downes M. J., Brennan M. L., Williams H. C., and Dean R. S., “Development of a Critical Appraisal Tool to Assess the Quality of Cross‐Sectional Studies (AXIS),” BMJ Open 6, no. 12 (2016): e011458, 10.1136/BMJOPEN-2016-011458. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. DerSimonian R. and Laird N., “Meta‐Analysis in Clinical Trials Revisited,” Contemporary Clinical Trials 45 (2015): 139–145, 10.1016/j.cct.2015.09.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Akyol A., Boyvat A., Peksari Y., and Gürgey E., “Contact Sensitivity to Standard Series Allergens in 1038 Patients With Contact Dermatitis in Turkey,” Contact Dermatitis 52, no. 6 (2005): 333–337, 10.1111/J.0105-1873.2005.00608.X. [DOI] [PubMed] [Google Scholar]
- 12. Bruynzeel D. P., Diepgen T. L., Andersen K. E., et al., “Monitoring the European Standard Series in 10 Centres 1996‐2000,” Contact Dermatitis 53, no. 3 (2005): 146–149, 10.1111/J.0105-1873.2005.00541.X. [DOI] [PubMed] [Google Scholar]
- 13. Uter W., Hegewald J., Aberer W., et al., “The European Standard Series in 9 European Countries, 2002/2003 – First Results of the European Surveillance System on Contact Allergies,” Contact Dermatitis 53, no. 3 (2005): 136–145, 10.1111/J.0105-1873.2005.00673.X. [DOI] [PubMed] [Google Scholar]
- 14. Machovcova A., Dastychova E., Kostalova D., et al., “Common Contact Sensitizers in The Czech Republic. Patch Test Results in 12,058 Patients With Suspected Contact Dermatitis*,” Contact Dermatitis 53, no. 3 (2005): 162–166, 10.1111/J.0105-1873.2005.00676.X. [DOI] [PubMed] [Google Scholar]
- 15. Marinović‐Kulišić S., Lipozenčić J., Ljubojević S., and Milavec‐Puretić V., “Retrospective Survey of Patch Testing at Department of Dermatology and Venerology, Zagreb University Hospital Center in Zagreb, Croatia,” Acta Dermatovenerologica Croatica 12 (2004): 4. [PubMed] [Google Scholar]
- 16. Piaserico S., Larese F., Recchia G. P., et al., “Allergic Contact Sensitivity in Elderly Patients,” Aging Clinical and Experimental Research 16, no. 3 (2004): 221–225, 10.1007/BF03327387. [DOI] [PubMed] [Google Scholar]
- 17. Sharma V. K., Chakrabarti A., and Sharma V. K., “Common Contact Sensitizers in Chandigarh, India. A Study of 200 Patients With the European Standard Series,” Contact Dermatitis 38, no. 3 (1998): 127–131, 10.1111/J.1600-0536.1998.TB05677.X. [DOI] [PubMed] [Google Scholar]
- 18. Husajn S. L., “Contact Dermatitis in the West of Scotland,” Contact Dermatitis 3, no. 6 (1977): 327–332, 10.1111/J.1600-0536.1977.TB03697.X. [DOI] [PubMed] [Google Scholar]
- 19. Liu Y. Q., Zhao B., Zhuang L. H., and Fan W. X., “Patch Test Reactions to the Chinese Standard Screening Allergens in 1,135 Patients Investigated for Allergic Contact Dermatitis,” American Journal of Contact Dermatitis 8, no. 3 (1997): 141–143, 10.1016/S1046-199X(97)90093-2. [DOI] [PubMed] [Google Scholar]
- 20. Holness D. L., Nethercott J. R., Adams R. M., et al., “Concomitant Positive Patch Test Results With Standard Screening Tray in North America 1985‐1989,” Contact Dermatitis 32, no. 5 (1995): 289–292, 10.1111/J.1600-0536.1995.TB00783.X. [DOI] [PubMed] [Google Scholar]
- 21. Bruckner‐Tuderman L., König A., and Schnyder U. W., “Patch Test Results of the Dermatology Clinic Zurich in 1989: Personal Computer‐Aided Statistical Evaluation,” Dermatology 184, no. 1 (1992): 29–33, 10.1159/000247495. [DOI] [PubMed] [Google Scholar]
- 22. El‐Rab M. O. G. and Al‐Sheikh O. A., “Is the European Standard Series Suitable for Patch Testing in Riyadh, Saudi Arabia?,” Contact Dermatitis 33, no. 5 (1995): 310–314, 10.1111/J.1600-0536.1995.TB02044.X. [DOI] [PubMed] [Google Scholar]
- 23. Goh C. L. and Med M., “Contact Sensitivity to Topical Medicaments,” International Journal of Dermatology 28, no. 1 (1989): 25–28, 10.1111/J.1365-4362.1989.TB01304.X. [DOI] [PubMed] [Google Scholar]
- 24. Leok J. T. E., Goh C. L., Ng S. K., and Wong W. K., “Changing Trends in the Epidemiology of Contact Dermatitis in Singapore,” Contact Dermatitis 26, no. 5 (1992): 321–326, 10.1111/J.1600-0536.1992.TB00127.X. [DOI] [PubMed] [Google Scholar]
- 25. Goh C. L., “Epidemiology of Contact Allergy in Singapore,” International Journal of Dermatology 27, no. 5 (1988): 308–311, 10.1111/j.1365-4362.1988.tb02358.x. [DOI] [PubMed] [Google Scholar]
- 26. Hirano S. and Yoshikawa K., “Patch Testing With European and American Standard Allergens in Japanese Patients,” Contact Dermatitis 8, no. 1 (1982): 48–50, 10.1111/J.1600-0536.1982.TB04134.X. [DOI] [PubMed] [Google Scholar]
- 27. Gollhausen R., Enders F., Przybilla B., Burg G., and Ring J., “Trends in Allergic Contact Sensitization,” Contact Dermatitis 18, no. 3 (1988): 147–154, 10.1111/J.1600-0536.1988.TB04501.X. [DOI] [PubMed] [Google Scholar]
- 28. Hogan D. J., Hill M., and Lane P. R., “Results of Routine Patch Testing of 542 Patients in Saskatoon, Canada,” Contact Dermatitis 19, no. 2 (1988): 120–124, 10.1111/J.1600-0536.1988.TB05508.X. [DOI] [PubMed] [Google Scholar]
- 29. Baer R. L. and Ramsey D. L., “The Most Common Contact Allergens 1968‐1970,” Archives of Dermatology 108, no. 1 (1973): 74–78, 10.1001/ARCHDERM.1973.01620220046011. [DOI] [PubMed] [Google Scholar]
- 30. Slodownik D., Bar J., and Daniely D., “Trends in Contact Sensitization, Results, and Implications From a Contact Dermatitis Clinic in Israel,” Contact Dermatitis 90, no. 6 (2024): 556–565, 10.1111/COD.14524. [DOI] [PubMed] [Google Scholar]
- 31. Dekoven J. G., Warshaw E. M., Reeder M. J., et al., “North American Contact Dermatitis Group Patch Test Results: 2019‐2020,” Dermatitis 34, no. 2 (2023): 90–104, 10.1089/DERM.2022.29017.JDK. [DOI] [PubMed] [Google Scholar]
- 32. Boonchai W., Likittanasombat S., Viriyaskultorn N., and Kanokrungsee S., “Gender Differences in Allergic Contact Dermatitis to Common Allergens,” Contact Dermatitis 90, no. 5 (2024): 458–465, 10.1111/COD.14479. [DOI] [PubMed] [Google Scholar]
- 33. Ünal A., “Analysis of Patch Testing Results in Patients With Contact Dermatitis in Istanbul, Turkey, From 2012 to 2022,” Journal of Cosmetic Dermatology 22, no. 10 (2023): 2831–2838, 10.1111/JOCD.15791. [DOI] [PubMed] [Google Scholar]
- 34. Bizjak M., Adamič K., Bajrovič N., et al., “Patch Testing With the European Baseline Series and 10 Added Allergens: Single‐Centre Study of 748 Patients,” Contact Dermatitis 87, no. 5 (2022): 439–446, 10.1111/COD.14178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Wee C., Tan C. H., Zhao X., Yew Y. W., and Goon A., “Pattern of Contact Sensitization in Patients With and Without Atopic Dermatitis in an Asian Dermatology Center,” Contact Dermatitis 86, no. 5 (2022): 398–403, 10.1111/COD.14068. [DOI] [PubMed] [Google Scholar]
- 36. Uter W., Wilkinson S. M., Aerts O., et al., “Patch Test Results With the European Baseline Series, 2019/20‐Joint European Results of the ESSCA and the EBS Working Groups of the ESCD, and the GEIDAC,” Contact Dermatitis 87, no. 4 (2022): 343–355, 10.1111/COD.14170. [DOI] [PubMed] [Google Scholar]
- 37. Uter W., Zetzmann A., Ofenloch R., et al., “Prevalence of Contact Allergies in the Population Compared to a Tertiary Referral Patch Test Clinic in Jena/Germany,” Contact Dermatitis 85, no. 5 (2021): 563–571, 10.1111/COD.13923. [DOI] [PubMed] [Google Scholar]
- 38. Silverberg J. I., Hou A., Warshaw E. M., et al., “Prevalence and Trend of Allergen Sensitization in Adults and Children With Atopic Dermatitis Referred for Patch Testing, North American Contact Dermatitis Group Data, 2001‐2016,” Journal of Allergy and Clinical Immunology. In Practice 9, no. 7 (2021): 2853–2866.e14, 10.1016/J.JAIP.2021.03.028. [DOI] [PubMed] [Google Scholar]
- 39. Tagka A., Lambrou G. I., Nicolaidou E., Gregoriou S. G., Katsarou‐Katsari A., and Rigopoulos D., “The Effect of Atopy in the Prevalence of Contact Sensitization: The Experience of a Greek Referral Center,” Dermatology Research and Practice 2020 (2020): 1–16, 10.1155/2020/3946084. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Teo Y., McFadden J. P., White I. R., Lynch M., and Banerjee P., “Allergic Contact Dermatitis in Atopic Individuals: Results of a 30‐Year Retrospective Study,” Contact Dermatitis 81, no. 6 (2019): 409–416, 10.1111/COD.13363. [DOI] [PubMed] [Google Scholar]
- 41. Hassan I., Akhtar S., Zeerak S., et al., “Clinicoepidemiological and Patch Test Profile of Patients Attending the Contact Dermatitis Clinic of a Tertiary Care Hospital in North India: A 7‐Year Retrospective Study,” Indian Dermatology Online Journal 10, no. 6 (2019): 669–675, 10.4103/IDOJ.IDOJ_26_19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Linauskienė K., Malinauskienė L., and Blažienė A., “Time Trends of Contact Allergy to the European Baseline Series in Lithuania,” Contact Dermatitis 76, no. 6 (2017): 350–356, 10.1111/COD.12726. [DOI] [PubMed] [Google Scholar]
- 43. Kot M., Bogaczewicz J., Kręcisz B., and Woźniacka A., “Contact Hypersensitivity to European Baseline Series and Corticosteroid Series Haptens in a Population of Adult Patients With Contact Eczema,” Acta Dermatovenerologica Croatica 24 (2016): 29. [PubMed] [Google Scholar]
- 44. Uter W., Spiewak R., Cooper S. M., et al., “Contact Allergy to Ingredients of Topical Medications: Results of the European Surveillance System on Contact Allergies (ESSCA), 2009‐2012,” Pharmacoepidemiology and Drug Safety 25, no. 11 (2016): 1305–1312, 10.1002/PDS.4064. [DOI] [PubMed] [Google Scholar]
- 45. Reduta T., Bacharewicz J., and Pawłoś A., “Patch Test Results in Patients With Allergic Contact Dermatitis in the Podlasie Region,” Postepy Dermatologii I Alergologii 30, no. 6 (2013): 350–357, 10.5114/PDIA.2013.39433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46. Uter W., Aberer W., Armario‐Hita J. C., et al., “Current Patch Test Results With the European Baseline Series and Extensions to It From the “European Surveillance System on Contact Allergy” Network, 2007‐2008,” Contact Dermatitis 67, no. 1 (2012): 9–19, 10.1111/J.1600-0536.2012.02070.X. [DOI] [PubMed] [Google Scholar]
- 47. Rodrigues D. F., Neves D. R., Pinto J. M., Alves M. F. F., and Fulgêncio A. C. F., “Results of Patch‐Tests From Santa Casa de Belo Horizonte Dermatology Clinic, Belo Horizonte, Brazil, From 2003 to 2010,” Anais Brasileiros de Dermatologia 87, no. 5 (2012): 800–803, 10.1590/S0365-05962012000500028. [DOI] [PubMed] [Google Scholar]
- 48. Landeck L., Schalock P., Baden L., and González E., “Contact Sensitization Pattern in 172 Atopic Subjects,” International Journal of Dermatology 50, no. 7 (2011): 806–810, 10.1111/j.1365-4632.2010.04754.x. [DOI] [PubMed] [Google Scholar]
- 49. Yin R., Huang X. Y., Zhou X. F., and Hao F., “A Retrospective Study of Patch Tests in Chongqing, China From 2004 to 2009,” Contact Dermatitis 65, no. 1 (2011): 28–33, 10.1111/J.1600-0536.2010.01854.X. [DOI] [PubMed] [Google Scholar]
- 50. Janach M., Kühne A., Seifert B., French L. E., Ballmer‐Weber B., and Hofbauer G. F. L., “Changing Delayed‐Type Sensitizations to the Baseline Series Allergens Over a Decade at the Zurich University Hospital,” Contact Dermatitis 63, no. 1 (2010): 42–48, 10.1111/J.1600-0536.2010.01727.X. [DOI] [PubMed] [Google Scholar]
- 51. Bilcha K. D., Ayele A., Shibeshi D., and Lovell C., “Patch Testing and Contact Allergens in Ethiopia–Results of 514 Contact Dermatitis Patients Using the European Baseline Series,” Contact Dermatitis 63, no. 3 (2010): 140–145, 10.1111/J.1600-0536.2010.01740.X. [DOI] [PubMed] [Google Scholar]
- 52. Lindberg M., Edman B., Fischer T., and Stenberg B., “Time Trends in Swedish Patch Test Data From 1992 to 2000. A Multi‐Centre Study Based on Age‐ and Sex‐Adjusted Results of the Swedish Standard Series,” Contact Dermatitis 56, no. 4 (2007): 205–210, 10.1111/J.1600-0536.2006.01063.X. [DOI] [PubMed] [Google Scholar]
- 53. Carlsen B. C., Menné T., and Johansen J. D., “Associations Between Baseline Allergens and Polysensitization,” Contact Dermatitis 59, no. 2 (2008): 96–102, 10.1111/J.1600-0536.2008.01400.X. [DOI] [PubMed] [Google Scholar]
- 54. Lam W. S., Chan L. Y., Ho S. C. K., Chong L. Y., So W. H., and Wong T. W., “A Retrospective Study of 2585 Patients Patch Tested With the European Standard Series in Hong Kong (1995‐99),” International Journal of Dermatology 47, no. 2 (2008): 128–133, 10.1111/J.1365-4632.2008.03437.X. [DOI] [PubMed] [Google Scholar]
- 55. Bajaj A., Saraswat A., Mukhija G., Rastogi S., and Yadav S., “Patch Testing Experience With 1000 Patients,” Indian Journal of Dermatology, Venereology and Leprology 73, no. 5 (2007): 313–318, 10.4103/0378-6323.34008. [DOI] [PubMed] [Google Scholar]
- 56. Magen E., Mishal J., and Schlesinger M., “Sensitizations to Allergens of TRUE Test in 864 Consecutive Eczema Patients in Israel,” Contact Dermatitis 55, no. 6 (2006): 370–371, 10.1111/J.1600-0536.2006.00878.X. [DOI] [PubMed] [Google Scholar]
- 57. Lazarov A., “European Standard Series Patch Test Results From a Contact Dermatitis Clinic in Israel During the 7‐Year Period From 1998 to 2004,” Contact Dermatitis 55, no. 2 (2006): 73–76, 10.1111/J.0105-1873.2006.00875.X. [DOI] [PubMed] [Google Scholar]
- 58. Goon A. T. J. and Goh C. L., “Patch Testing of Singapore Children and Adolescents: Our Experience Over 18 Years,” Pediatric Dermatology 23, no. 2 (2006): 117–120, 10.1111/J.1525-1470.2006.00193.X. [DOI] [PubMed] [Google Scholar]
- 59. Manzini B. M., Ferdani G., Simonetti V., Donini M., and Seidenari S., “Contact Sensitization in Children,” Pediatric Dermatology 15, no. 1 (1998): 12–17, 10.1046/J.1525-1470.1998.1998015012.X. [DOI] [PubMed] [Google Scholar]
- 60. Giordano‐Labadie F., Rancé F., Pellegrin F., Bazex J., Dutau G., and Schwarze H. P., “Frequency of Contact Allergy in Children With Atopic Dermatitis: Results of a Prospective Study of 137 Cases,” Contact Dermatitis 40, no. 4 (1999): 192–195, 10.1111/J.1600-0536.1999.TB06032.X. [DOI] [PubMed] [Google Scholar]
- 61. Roul S., Ducombs G., and Taieb A., “Usefulness of the European Standard Series for Patch Testing in Children. A 3‐Year Single‐Centre Study of 337 Patients,” Contact Dermatitis 40, no. 5 (1999): 232–235, 10.1111/J.1600-0536.1999.TB06054.X. [DOI] [PubMed] [Google Scholar]
- 62. Mortz C. G., Lauritsen J. M., Bindslev‐Jensen C., and Andersen K. E., “Prevalence of Atopic Dermatitis, Asthma, Allergic Rhinitis, and Hand and Contact Dermatitis in Adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis,” British Journal of Dermatology 144, no. 3 (2001): 523–532, 10.1046/J.1365-2133.2001.04078.X. [DOI] [PubMed] [Google Scholar]
- 63. Seidenari S., Giusti F., Pepe P., and Mantovani L., “Contact Sensitization in 1094 Children Undergoing Patch Testing Over a 7‐Year Period,” Pediatric Dermatology 22, no. 1 (2005): 1–5, 10.1111/J.1525-1470.2005.22100.X. [DOI] [PubMed] [Google Scholar]
- 64. Clayton T. H., Wilkinson S. M., Rawcliffe C., Pollock B., and Clark S. M., “Allergic Contact Dermatitis in Children: Should Pattern of Dermatitis Determine Referral? A Retrospective Study of 500 Children Tested Between 1995 and 2004 in One U.K. Centre,” British Journal of Dermatology 154, no. 1 (2006): 114–117, 10.1111/J.1365-2133.2005.06845.X. [DOI] [PubMed] [Google Scholar]
- 65. Belloni Fortina A., Romano I., Peserico A., and Eichenfield L. F., “Contact Sensitization in Very Young Children,” Journal of the American Academy of Dermatology 65, no. 4 (2011): 772–779, 10.1016/J.JAAD.2010.07.030. [DOI] [PubMed] [Google Scholar]
- 66. Moustafa M., Holden C. R., Athavale P., Cork M. J., Messenger A. G., and Gawkrodger D. J., “Patch Testing Is a Useful Investigation in Children With Eczema,” Contact Dermatitis 65, no. 4 (2011): 208–212, 10.1111/J.1600-0536.2011.01900.X. [DOI] [PubMed] [Google Scholar]
- 67. Machovcova A., “The Frequency of Contact Allergy in Children and Adolescents in The Czech Republic,” Acta Dermatovenerologica Croatica 20, no. 2 (2012): 75–79, accessed November 6, 2024, https://pubmed.ncbi.nlm.nih.gov/22726278/. [PubMed] [Google Scholar]
- 68. Simonsen A. B., Deleuran M., Mortz C. G., Johansen J. D., and Sommerlund M., “Allergic Contact Dermatitis in Danish Children Referred for Patch Testing ‐ a Nationwide Multicentre Study,” Contact Dermatitis 70, no. 2 (2014): 104–111, 10.1111/COD.12129. [DOI] [PubMed] [Google Scholar]
- 69. Belloni Fortina A., Cooper S. M., Spiewak R., Fontana E., Schnuch A., and Uter W., “Patch Test Results in Children and Adolescents Across Europe. Analysis of the ESSCA Network 2002‐2010,” Pediatric Allergy and Immunology 26, no. 5 (2015): 446–455, 10.1111/PAI.12397. [DOI] [PubMed] [Google Scholar]
- 70. Bonamonte D., Hansel K., Romita P., et al., “Contact Allergy in Children With and Without Atopic Dermatitis: An Italian Multicentre Study,” Contact Dermatitis 87, no. 3 (2022): 265–272, 10.1111/COD.14130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71. Yılmaz Z. and Özkaya E., “Patch‐Test Results in Terms of the Recently Recommended Allergens in Children and Adolescents: A Retrospective Cohort Study Over 22 Years From Turkey,” Contact Dermatitis 85, no. 2 (2021): 198–210, 10.1111/COD.13842. [DOI] [PubMed] [Google Scholar]
- 72. Hogeling M. and Pratt M., “Allergic Contact Dermatitis in Children: The Ottawa Hospital Patch‐Testing Clinic Experience, 1996 to 2006,” Dermatitis 19, no. 2 (2008): 86–89, 10.2310/6620.2008.07099. [DOI] [PubMed] [Google Scholar]
- 73. Silverberg J. I., Hou A., Warshaw E. M., et al., “Age‐Related Differences in Patch Testing Results Among Children: Analysis of North American Contact Dermatitis Group Data, 2001‐2018,” Journal of the American Academy of Dermatology 86, no. 4 (2022): 818–826, 10.1016/J.JAAD.2021.07.030. [DOI] [PubMed] [Google Scholar]
- 74. Johnson H., Aquino M. R., Snyder A., et al., “Prevalence of Allergic Contact Dermatitis in Children With and Without Atopic Dermatitis: A Multicenter Retrospective Case‐Control Study,” Journal of the American Academy of Dermatology 89, no. 5 (2023): 1007–1014, 10.1016/J.JAAD.2023.06.048. [DOI] [PubMed] [Google Scholar]
- 75. Rodrigues D. F. and Goulart E. M. A., “Patch Test Results in Children and Adolescents. Study From the Santa Casa de Belo Horizonte Dermatology Clinic, Brazil, From 2003 to 2010,” Anais Brasileiros de Dermatologia 90, no. 5 (2015): 671–683, 10.1590/ABD1806-4841.20153902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 76. De Menezes Pádua C. A., Uter W., and Schnuch A., “Contact Allergy to Topical Drugs: Prevalence in a Clinical Setting and Estimation of Frequency at the Population Level,” Pharmacoepidemiology and Drug Safety 16, no. 4 (2007): 377–384, 10.1002/PDS.1268. [DOI] [PubMed] [Google Scholar]
- 77. Kursawe Larsen C., B Schwensen J. F., Zachariae C., Johansen J. D., Hospital G., and Correspondence Christoffer Kursawe Larsen D , “Contact Allergy to Rubber Accelerators in Consecutively Patch Tested Danish Eczema Patients: A Retrospective Observational Study From 1990 to 2019,” Contact Dermatitis 90, no. 2 (2024): 116–125, 10.1111/COD.14421. [DOI] [PubMed] [Google Scholar]
- 78. Uter W., Bauer A., Belloni Fortina A., et al., “Patch Test Results With the European Baseline Series and Additions Thereof in the ESSCA Network, 2015‐2018,” Contact Dermatitis 84, no. 2 (2021): 109–120, 10.1111/COD.13704. [DOI] [PubMed] [Google Scholar]
- 79. Botvid S., Bennike N. H., Simonsen A. B., Johansen J. D., and Uter W., “Contact Sensitization to Fragrance Mix I and Fragrance Mix II Among European Dermatitis Patients: A Systematic Review,” Contact Dermatitis 91, no. 3 (2024): 177–185, 10.1111/COD.14618. [DOI] [PubMed] [Google Scholar]
- 80. Schwensen J. F. B., Uter W., Aerts O., et al., “Current Frequency of Contact Allergy to Isothiazolinones (Methyl‐, Benz‐ and Octylisothiazolinone) Across Europe,” Contact Dermatitis 91, no. 4 (2024): 271–277, 10.1111/COD.14641. [DOI] [PubMed] [Google Scholar]
- 81. Isufi D., Jensen M. B., Kursawe Larsen C., Alinaghi F., Schwensen J. F. B., and Johansen J. D., “Allergens Responsible for Contact Allergy in Children From 2010 to 2024: A Systematic Review and Meta‐Analysis,” Contact Dermatitis (2025): 1–17, 10.1111/COD.14753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82. Czarnobilska E., Obtulowicz K., Dyga W., and Spiewak R., “The Most Important Contact Sensitizers in Polish Children and Adolescents With Atopy and Chronic Recurrent Eczema as Detected With the Extended European Baseline Series,” Pediatric Allergy and Immunology 22, no. 2 (2011): 252–256, 10.1111/J.1399-3038.2010.01075.X. [DOI] [PubMed] [Google Scholar]
- 83. Childs‐Kean L. M., Shaeer K. M., Varghese Gupta S., and Cho J. C., “Aminoglycoside Allergic Reactions,” Pharmacy (Basel) 7, no. 3 (2019): 124, 10.3390/PHARMACY7030124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 84. Georgitis J. W. and Fasano M. B., “Allergenic Components of Vaccines and Avoidance of Vaccination‐Related Adverse Events,” Current Allergy Reports 1, no. 1 (2001): 11–17, 10.1007/S11882-001-0091-6. [DOI] [PubMed] [Google Scholar]
- 85. Heidary N. and Cohen D. E., “Hypersensitivity Reactions to Vaccine Components,” Dermatitis 16, no. 3 (2005): 115–120, 10.1097/01206501-200509000-00004. [DOI] [PubMed] [Google Scholar]
- 86. Aslam B., Wang W., Arshad M. I., et al., “Antibiotic Resistance: A Rundown of a Global Crisis,” Infection and Drug Resistance 11 (2018): 1645–1658, 10.2147/IDR.S173867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 87. Gehrig K. A. and Warshaw E. M., “Allergic Contact Dermatitis to Topical Antibiotics: Epidemiology, Responsible Allergens, and Management,” Journal of the American Academy of Dermatology 58, no. 1 (2008): 1–21, 10.1016/J.JAAD.2007.07.050. [DOI] [PubMed] [Google Scholar]
- 88. Maxwell A., Ghate V., Aranjani J., and Lewis S., “Breaking the Barriers for the Delivery of Amikacin: Challenges, Strategies, and Opportunities,” Life Sciences 284 (2021): 119883, 10.1016/J.LFS.2021.119883. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1.
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.