Urticarial Reaction From Cadmium Contamination After Vaping: A Public Health Concern
Introduction. A 48-year-old woman presented to the office of an academic dermatologist specializing in contact dermatitis for evaluation of transient and migrating ill-defined erythematous smooth lesions on unexposed areas of the trunk, chest, and neck (Figure 1). The eruptions began about 1 year prior to presentation.
Figure 1. Transient and migrating ill-defined erythematous plaques on the neck, consistent with an urticarial reaction.
History. The patient was an otherwise healthy woman who had an 8 pack-year history of e-cigarette use and a 10-year history of intermittent smoking of traditional cigarettes (3-15 cigarettes daily). Other than the skin eruption, she had no significant clinical findings. The patient had no history of any dermatologic conditions, other substance use, recent antibiotic treatment, or surgeries.
She did not develop any hive-like lesions following a scratch test. There were no signs of lichenification or koebnerization.
Diagnostic testing. Patch testing was completed which noted a mild response to gold. Prick testing completed by an allergist did not reveal any reactions to common allergens. Rheumatology and pulmonary work-up were within normal limits. The patient was referred to an otolaryngologist, who administered an endoscopy. On examination, the patient's vocal cords were 80% closed at baseline, suggesting an inhalation source causing vagal nerve–driven paradoxical vocal cord spasm.
On further investigation, toxic and essential elements in whole blood were evaluated, which noted elevated levels of cadmium at 2.8 µg/L (95% confidence interval for healthy non-exposed, nonsmokers is 0.4 µg/L, while the Occupational Safety and Health Administration considers ≥5 µg/L hazardous).1 Due to the urticarial nature of the condition, allergen-specific immunoglobulin E (IgE) and histamine levels were tested, showing 24.7 kU/L (normal range, <114 kU/L) and 131 ng/mL (normal range, 12-127 ng/mL), respectively. Following these results, the patient was diagnosed with an urticarial reaction from cadmium after use of e-cigarettes.
Differential diagnoses. The differential diagnosis included irritant contact dermatitis, allergic contact dermatitis, atopic dermatitis, urticarial vasculitis, drug eruptions, mastocytosis, viral exanthem, and polymorphic light eruption.
There were no relevant drug interactions, or recent infections. Allergic contact dermatitis was ruled out by the patch testing. Other diagnoses were ruled out after comprehensive evaluation by dermatology, rheumatology, otolaryngology, allergy, and pulmonology specialists.
Treatment and management. The patient was started on a trial of loratadine 10mg in the morning and cetirizine 10mg nightly. However, she continued to have ongoing eruptions after 3 months of treatment. The regimen was thus increased to cetirizine HCl 20mg in the morning and cetirizine 20mg nightly. Six weeks later, the severity of the patient’s eruptions on this regimen were self-reported to have decreased by 75%, indicating that there might be a histaminergic component to the eruptions.
Outcome and follow-up. In clinical follow-up 3 months later, the patient reported a continued stable 75% reduction in the intensity of the eruptions. Given that smoking e-cigarettes was the suspected cause of the eruptions, it was recommended the patient enroll in a smoking cessation program. However, she was not prepared to fully stop smoking e-cigarettes and continues to smoke. Ongoing clinical follow-up was recommended.
Discussion. Cigarette smoking has declined by almost 50% since 2005 with the help of public health policies and educational initiatives.2 However, the use of e-cigarettes has grown in popularity since its inception in 2003, with approximately 27.5% of high school students partaking in nicotine vaping in 2019.3 Vapes are marketed as an alternative to traditional nicotine cigarettes and a way to aid cessation, but they do not come without risk.4 Adverse effects such as lung injury correlated with vitamin E acetate and mortality among young adults have been documented.5 Malfunctioning e-cigarettes can overheat, leading to burns; allergies to propylene glycol or nickel can lead to skin eruptions; and oral immunosuppression results in bacterial or yeast overgrowth.6 Cases of systemic urticarial reactions to e-cigarettes have also been reported on vaping online forums.
Public health concerns have led to regulations and limitations on the accessibility of vaping products, including bans on selling flavored products and increasing the minimum age for purchase.7 Educational initiatives and resources tend to focus on the negative effects of the product's main ingredients. However, harm may be associated with contaminants that consumers may not understand. For example, clotrimazole and ranitidine were recalled due to the presence of carcinogenic contaminants, and levamisole has been found in adulterated cocaine, leading to many systemic effects.8-10 It also may take time for such contaminants to reach critical levels for users to experience adverse effects. By the time those levels are detected, the contaminants may have dangerous effects on multiple organ systems.
E-cigarettes often contain small amounts of heavy metals, including cadmium, which carries the risk of accumulating over time due to its low excretion rate and long half-life. Cadmium elimination follows a two-compartment model with a fast half-life of 15 to 120 days in the blood and a long half-life as high as 30 years with accumulation in the kidney, liver, and intestines. 11,12 Cadmium is a natural metal found in many products, including batteries, metal coatings, plastics, and cigarettes. Its ingestion or inhalation may be related to occupational and environmental exposures.13 Stomach irritation, lung damage, and kidney disease are a few of the systemic reactions associated with consuming large quantities of cadmium, however, chronic low-dose exposure may also result in systemic effects, including heightened IgE sensitization.14,15
Interestingly in our case patient, her IgE level was within normal limits while her histamine level was elevated, possibly highlighting a nonimmunological urticaria from molecular binding of cadmium directly to mast cells, activating the release of histamine.16
The 95% confidence Iimit of blood cadmium levels for healthy nonexposed individuals is 0.4 µg/L, while levels over 5 µg/L are consistent with significant health concerns.16 However, even subcritical levels may result in symptoms such as urticaria that significantly reduce a patient’s quality of life.
Conclusion. In this case, a woman who was vaping for many years before the onset of symptoms developed an urticarial reaction with elevated levels of cadmium and improvement of symptoms upon cessation of vaping. Dermatologic manifestations such as urticaria may signal an underlying reaction and accumulation of toxins. Contaminants within vaping devices, including cadmium, should continue to be investigated to further educate patients on the risks and underlying effects of using these products.
1Massachusetts General Hospital, Boston, MA
2Gilbert Dermatology, New York, NY
3Harvard Medical School, Boston, MA
Silence C, Gilbert E, Kourosh AS. Urticarial reaction from cadmium contamination after vaping: a public health concern. Consultant. 2023;63(9):e2. doi:10.25270/con.2023.08.000007.
Received July 27, 2022. Accepted December 28, 2022. Published online August 10, 2023.
The authors report no relevant financial relationships.
Channi Silence, Department of Dermatology, Massachusetts General Hospital, 55 Fruit Street, BAR 622, Boston, MA 02114 (email@example.com)
- Clinical Assessment – Laboratory Tests. Agency for Toxic Substances and Disease Registry. Updated May 23, 2023. Accessed June 24, 2023. www.atsdr.cdc.gov/csem/cadmium/Laboratory-Evaluation.html
- Current cigarette smoking among adults in the United States. Centers for Disease Control and Prevention. Updated March 17, 2022. Accessed January 31, 2023. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm
- Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Centers for Disease Control and Prevention. Updated August 3, 2021. Accessed January 31, 2023. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html
- Cullen KA, Gentzke AS, Sawdey MD, et al. E-cigarette use among youth in the United States, 2019. JAMA. 2019;322(21):2095-2103. doi:10.1001/jama.2019.18387
- Hussain S, Shahid Z, Foroozesh MB, Sofi UF. E-cigarettes: A novel therapy or a looming catastrophe. Ann Thorac Med. 2021;16(1):73-80. doi:10.4103/atm.ATM_190_20
- Public health consequences of e-cigarettes. The National Academies Press. Published January 23, 2018. Accessed December 3, 2022. https://nap.nationalacademies.org/catalog/24952/public-health-consequences-of-e-cigarettes
- Sindelar JL. Regulating vaping - policies, possibilities, and perils. N Engl J Med. 2020;382(20):e54. doi:10.1056/NEJMp1917065
- FDA requests removal of all ranitidine products (Zantac) from the market. News release. US Food and Drug Administration; April 1, 2020. Accessed January 31, 2023. https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market
- Bayer issues voluntary recall of specific Lotrimin® and Tinactin® spray products due to the presence of benzene. News release. US Food and Drug Administration; October 1, 2021. Accessed January 31, 2023. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/bayer-issues-voluntary-recall-specific-lotriminr-and-tinactinr-spray-products-due-presence-benzene
- Solomon N, Hayes J. Levamisole: a high performance cutting agent. Acad Forensic Pathol. 2017;7(3):469-476. doi:10.23907/2017.039
- Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A. The effects of cadmium toxicity. Int J Environ Res Public Health. 2020;17(11):3782. doi:10.3390/ijerph17113782
- World Health Organization. Health risks of heavy metals from long range trans-boundary air pollution. World Health Organization Regional Office for Europe; 2007:40-45. Accessed January 31, 2023. http://www.euro.who.int/document/E91044.pdf
- Cadmium factsheet. Centers for Disease Control and Prevention. Updated April 7, 2017. Accessed January 31, 2023. https://www.cdc.gov/biomonitoring/Cadmium_FactSheet.html
- Satarug S, Garrett SH, Sens MA, Sens DA. Cadmium, environmental exposure, and health outcomes. Environ Health Perspect. 2010;118(2):182-190. doi:10.1289/ehp.0901234
- Kim E, Bonnegarde-Bernard A, Opiyo SO, et al. Pollutants enhance IgE sensitization in the gut via local alteration of vitamin D-metabolizing enzymes. Mucosal Immunol. 2022;15(1):143-153. doi:10.1038/s41385-021-00440-4
- Hennino A, Bérard F, Guillot I, Saad N, Rozières A, Nicolas JF. Pathophysiology of urticaria. Clin Rev Allergy Immunol. 2006;30(1):3-11. doi:10.1385/CRIAI:30:1:003