Abstract
To the Editor:
Benzoic acid and its salts (“benzoates”) are found in foods and personal care products and can trigger contact urticaria and allergic contact dermatitis (ACD). 1 They rank among the top 5 allergens in US health care hand sanitizers. 2 With increasing use in consumer products, reports of benzoate reactivity are rising.3,4 Benzoates are a component of Balsam of Peru (BOP), a fragrance compound in many personal products, potentially expanding their cross-reactivity and clinical relevance.2,5
This prospective cohort study examines benzoic acid and sodium benzoate reactivity rates and associated patient characteristics with positive patch tests (PPT) to benzoates.
Patch test data from an IRB-approved REDCap™ registry of patients from an academic center in Northern California from December 2018 to July 2024 was reviewed. Characteristics such as age, sex, race, ethnicity, body areas of involvement, history of atopic dermatitis, relevance, and final diagnosis were analyzed. Statistical analysis was performed with STATA®.
Of the 1,008 patch-tested patients, 104 (10.3%) tested positive for benzoic acid (85, 8.4%), sodium benzoate (20, 2.0%), or both (Table 1). Cases were frequently relevant, with 90% of PPT to sodium benzoate and 92% to benzoic acid showing current possible, probable, or definite relevance. Patients positive to benzoates had a median of 4 total PPT reactions, compared to 2 in the general patch population (P < 0.0001).
Total Number of Patients in Study and MOAHLFA Characteristicsa
Proportion of patients with positive reactions to at least one baseline allergen is not applicable since only benzoate positivity was analyzed in this study.
Benzoate-positive patients had a median age of 58.2 years, significantly older than benzoate-negative patients, 49.4 years (P < 0.0001). There were no significant differences in history of atopic dermatitis, asthma, or seasonal allergies, symptom duration, or number of patches placed between the two groups, nor in benzoate positivity between different races, ethnicities, or Fitzpatrick skin types.
Patients with benzoate positivity more often had involvement of the eyelid, trunk, lower extremities (P = 0.025, P = 0.005, P = 0.013), with no significant differences in other body areas.
Fifty-three (50.96%) of 104 benzoate-positive patients tested positive for BOP. 53 of 203 (26.11%) BOP-positive patients tested positive for benzoates. There was a significant moderate positive correlation between benzoates and BOP (Pearson correlation coefficient: 0.26; P < 0.00001). There was a weak but significant correlation between fragrance mix 1/2 and benzoate positivity; however, this relationship lost significance when accounting for BOP positivity, suggesting that a subgroup of patients reactive to fragrance is independent of those reactive to benzoates.
On univariate analysis, each increase in age category (1≤18 years old, 2 = 18–39, 3 = 40–64, 4≥65) increased odds of benzoate positivity: odds ratio, OR: 1.84 (95% confidence interval, CI: 1.41–2.41), P < 0.0001. Male sex increased odds of benzoate positivity: OR: 1.82 (95% CI: 1.18–2.82), P = 0.007. Benzoate-positive individuals had increased odds of being diagnosed with systemic contact dermatitis: OR: 2.26 (95% CI: 1.09–4.66), P = 0.028. On multivariable analysis, the older age category, OR: 1.87 (95% CI: 1.42–2.47), and male sex, OR: 1.86 (95% CI: 1.18–2.94), remained significantly associated with benzoate positivity, P < 0.0001 and 0.007, respectively.
This experience reflects data from a single institution, with some data captured during the COVID-19 pandemic, which may limit generalizability.
This study highlights the rising significance of benzoate-related ACD in patch-tested patients, possibly driven by increased exposure in consumer products. Our analysis revealed significant associations between benzoate positivity and concomitant allergens like BOP, highlighting potential cross-reactivity. Additionally, older age and male sex emerged as significant risk factors for benzoate sensitization.