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). However, few large-scale epidemiological studies have assessed the association between blood heavy metal levels and chronic pruritic dermatoses. Given that cutaneous nerve fibers traverse close to the external skin barrier, we hypothesized that pruritic dermatoses would be more frequent in patients exposed to specific pollutants. Herein, we investigate the association between chronic pruritic skin eruptions and blood levels of cadmium, lead, and mercury, which are common toxins associated with occupational exposure and industrial waste.
We first conducted a literature review using EMBASE, PubMed, and MEDLINE, with the following keywords: heavy metals, cadmium, lead, skin, rash, pruritus, and itch. We also conducted a cross-sectional analysis of the data from the National Health and Nutrition Examination Survey study, which was collected by the National Center for Health Statistics from 2005 to 2006 (
) and approved by its institutional review board. Presence of chronic pruritic dermatoses was assessed by participants answering affirmatively to having “an itchy rash which was coming and going for at least 6 months” at some point within the year prior. This cohort was compared both to participants reporting asthma, given the detrimental effect of pollution on asthma, and a healthy control group without asthma or pruritic dermatoses (
Whole blood samples were collected by certified phlebotomists trained in standardized laboratory procedures. Prescreened polyethylene vials and vacutainers stored at –20 °C were required for the specimen. All samples underwent extensive quality control procedures ensuring no background contamination. Any variation in procedure, equipment, storage, or transport resulted in specimen rejection by the lab. Unscheduled quality assurance site visits confirmed that all protocols met the 1988 Clinical Laboratory Improvement Act requirements. Heavy metal measurements were made with a PerkinElmer (model SIMAA 6000) simultaneous multielement atomic absorption spectrometer and inductively coupled plasma-mass spectrometer. Continuous data and categorical data were analyzed with Student t test and χ2 test, respectively. Associations were determined with multiple logistic regression reporting odds ratios weighted to the US Census. Two-sided P-values <0.05 indicate statistical significance.
Our literature review yielded 1,221 articles after removing duplicates. Unrelated pollutants, non-skin diseases, and nonhuman research were excluded; seven studies were included in our review. Although increased blood heavy metal levels were not found to be associated with eczema, increased exposure to lead (P = 0.008), copper (P = 0.04), and zinc (P = 0.01) was associated with more severe eczema (
In our National Health and Nutrition Examination Survey analysis, there were 10,348 survey respondents. We excluded 1,941 participants lacking laboratory data and 260 participants with incomplete questionnaires. Of the 8,147 eligible subjects with complete data, 473 (5.8%) reported chronic pruritic dermatoses. Demographic characteristics (Table 1) showed higher mean age with pruritic dermatoses but no significant difference in the sex, race, smoking status, heart disease history, or cancer history. Mean blood cadmium levels were 18.4% (P = 0.0039) higher in pruritic dermatoses compared with healthy controls, and 8.3% (P = 0.26) higher than asthma patients. Mean blood lead levels in pruritic dermatoses were 9.9% (P = 0.0366) higher than healthy controls, and 28.2% (P < 0.0001) higher than asthma patients. Mean blood mercury levels in pruritic dermatoses were 11.2% (P = 0.1023) and 20.5% (P = 0.0270) higher than healthy controls and asthma patients, respectively (Table 1). Multiple logistic regression, adjusted for age, sex, race, education, asthma, and smoking status, showed an association between pruritic dermatoses and increased blood cadmium levels (odds ratio = 1.23; 95% confidence interval = 1.02–1.48). A separate multiple logistic regression using the same variables also identified an association with increased blood lead levels (odds ratio = 1.07; 95% confidence interval = 1.01–1.13). An association with mercury levels was not observed (odds ratio = 1.03; 95% confidence interval = 0.97–1.09; Figure 1).
Table 1Demographics and Blood Toxin Levels
Healthy (n = 6,631)
Pruritic Dermatoses (n = 473)
Asthma (n = 1,043)
P-value Compared with Healthy Controls
P-value Compared with Pruritic Dermatoses
P-value Compared with Healthy Controls
Gender, n (%)
Race, n (%)
Married, n (%)
Heart disease, n (%)
Cancer, n (%)
Smoker, n (%)
Mean blood levels
P-values reflect Pearson chi-squared test for categorical variables and Student t test for continuous variables. Boldface indicates statistical significance defined as P < 0.05.
). Previous studies have described non-IgE–mediated mechanisms of pruritus with heavy metal exposure, suggesting that heavy metals may have a direct role that needs to be elucidated in further studies (
Lead inhalation and ingestion is attributed to tobacco, construction, hazardous waste, and industrial sites making batteries, ammunition, and roofing materials, whereas cadmium may be ingested from vegetables contaminated with fertilizer (
). As such, physicians should consider screening patients presenting with chronic pruritic dermatoses of uncertain etiology for pollution exposure given the association of elevated lead and cadmium levels in these patients.
SGK is on the advisory board for Menlo and Trevi Therapeutics and has received grant funding from Kiniksa Pharmaceuticals. He is also the recipient of a Dermatology Foundation Medical Dermatology Career Development Award. SK is an advisory board member of Almirall, Menlo, Sun Pharma, and Unilever. The other authors have no conflict of interest to declare.
The content in this manuscript has not been published or submitted for publication elsewhere. All authors have contributed significantly and are in agreement with the content of the manuscript.