Wildfire smoke can trigger a host of respiratory and cardiovascular symptoms, ranging from runny nose and cough to a potentially life-threatening heart attack or stroke. A new study suggests that the dangers posed by wildfire smoke may also extend to the largest organ in the human body, and our first line of defense against outside threat: the skin.
During the two weeks in November 2018 when wildfire smoke from the Camp Fire choked the San Francisco Bay Area, health clinics in San Francisco saw an uptick in the number of patients visiting with concerns of eczema, also known as atopic dermatitis, and general itch, compared to the same time of the year in 2015 and 2016, the study found.
The findings suggest that even short-term exposure to hazardous air quality from wildfire smoke can be damaging to skin health.
The report, carried out by physician researchers at the University of California, San Francisco, in collaboration with researchers at the University of California, Berkeley, appears on April 21 in the journal JAMA Dermatology.
“Existing research on air pollution and health outcomes has focused primarily on cardiac and respiratory health outcomes, and understandably so. But there is a gap in the research connecting air pollution and skin health,” said study lead author Raj Fadadu, a student in the UC Berkeley-UCSF Joint Medical Program.
“Skin is the largest organ of the human body, and it’s in constant interaction with the external environment. So, it makes sense that changes in the external environment, such as increases or decreases in air pollution, could affect our skin health.”
Air pollution from wildfires, which consists of fine particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAHs), and gases, can impact both normal and eczema-prone skin in a variety of ways.
These pollutants often contain chemical compounds that act like keys, allowing them to slip past the skin’s outer barrier and penetrate into cells, where they can disrupt gene transcription, trigger oxidative stress or cause inflammation.
Eczema, or atopic dermatitis, is a chronic condition which affects the skin’s ability to serve as an effective barrier against environmental factors. Because the skin’s barrier has been compromised, people with this condition are prone to flare-ups of red, itchy skin in response to irritants, and may be even more prone to harm from air pollution.
“Skin is a very excellent physical barrier that separates us and protects us from the environment,” said study senior author Dr. Maria Wei, a dermatologist and melanoma specialist at UCSF. “However, there are certain skin disorders, such as atopic dermatitis, in which the barrier is not fully functional.
It’s not normal even when you don’t have a rash. So, it would make sense that when exposed to significant air pollution, people with this condition might see an effect on the skin.”
Even short burst of air pollution during the camp fire harms skin health
Earlier studies have found a link between atopic dermatitis and air pollution in cities with high background levels of air pollution from cars and industry. However, this is the first study to examine the impacts of a very short burst of extremely hazardous air from wildfires.
Despite being located 175 miles away from the Camp Fire, San Francisco saw an approximately nine-fold increase in baseline PM2.5 levels during the time of the blaze.
To conduct the study, the team examined data from more than 8,000 visits to dermatology clinics by both adults and children between October of 2015, 2016 and 2018, and February of the following year. They found that, during the Camp Fire, clinic visits for atopic dermatitis and general itch increased significantly in both adult and pediatric patients.
“Fully 89 percent of the patients that had itch during the time of the Camp Fire did not have a known diagnosis of atopic dermatitis, suggesting that folks with normal skin also experienced irritation and/or absorption of toxins within a very short period of time,” Wei said.
While skin conditions like eczema and itch may not be as life-threatening as the respiratory and cardiovascular impacts of wildfire smoke, they can still severely impact people’s lives, the researchers say.
The study also documented increased rates of prescribed medications, such as steroids, during times of high air pollution, suggesting that patients can experience severe symptoms.
Individuals can protect their skin during wildfire season by staying indoors, wearing clothing that covers the skin if they do go outside, and using emollients, which can strengthen the skin’s barrier function. A new medication to treat eczema, called Tapinarof, is now in clinical trials and could also be a useful tool during times of bad air.
“A lot of the conversations about the health implications of climate change and air pollution don’t focus on skin health, but it’s important to recognize that skin conditions do affect people’s quality of life, their social interactions and how they feel psychologically,” Fadadu said. “I hope that these health impacts can be more integrated into policies and discussions about the wide-ranging health effects of climate change and air pollution.”
Sources and composition of air pollution
Table 1 summarizes the classes and sources of air pollutants. Most commonly, pollutants are generated through the burning of fossil fuels by vehicles and industries giving rise to components such as particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs). Additional pollutants are derived from a variety of unrelated sources, such as cigarette smoke, ultraviolet (UV) light, volatile organic compounds (VOCs), and tropospheric (ground-level) ozone.
Particulate pollutants with a diameter of 2.5 µm or less (PM2.5) and 10 µm or less (PM10) and nanoparticles are the main constituents of PM. PAHs and VOCs are mainly generated by power plants, industries, vehicles, and domestic agricultural sources. PAHs and VOCs are often coated on PM and can easily get through the cutaneous lipid barrier due to their lipophilic properties (Millis et al., 1992, Piao et al., 2018) A pollutant can be of natural origin or manmade. Pollutants are classified as primary or secondary.
Classes and sources of pollutants.
|Air pollutant class||Name/Examples||Potential sources of pollutants|
|Gaseous||Carbon monoxide||Fossil‐fuel combustion, vehicle emission|
|Nitrogen dioxide||Fuel combustion, wood burning, vehicle emissions, waste incineration|
|Ozone||Formed by interaction of VOCs and nitrogen oxide compounds upon UV photoactivation|
|Sulphur dioxide||Fuel combustion, vehicle emissions, maritime transport, electric utilities, industrial facilities, volcanoes|
|Heavy metals||Arsenic||Battery manufacture, minerals|
|Cadmium||Battery manufacturing, aircraft industry, television manufacturing|
|Lead||facilities, leaded fuel, lead‐based paint, plumbing material|
|Nickel||Casting, welding, battery manufacture|
|Particulate matter (PM)||Coarse PM10 (2.5–10 μm)||Road dust, unpaved roads, forest fires, waste degradation including electronic waste, cooking processes|
|Fine PM2.5 (<2.5 μm)||Fossil‐fuel combustion, industrial facilities, maritime transport, biomass burning, waste incineration, cooking|
|Ultrafine PM0.1 (<0.1 μm)||Vehicle emission, industrial facilities|
|Persistent organic compounds||Dioxins, dioxin‐like polychlorinated biphenyls||Herbicides, pesticides, industrial processes, forest fires, volcanic eruptions|
|Semi-volatile organic compounds||Butylated hydroxytoluene, diethyl phthalate, geranyl acetone, nicotine (in free‐base form), parabens||Solvents, fragrances, bactericides, antimicrobial agents, flooring, furniture|
|VOCs||Acetaldehyde, dimethylformamide, formaldehyde, hexane, styrene, toluene, xylene||Fuel combustion, aircraft emission, household products, chemical solvents, paints, varnishes, cigarette smoke|
Created with reference to Araviiskaia et al. (2019).
Primary pollutants are substances directly produced from a process. An example would be sulfur oxides released from factories. Other examples include ash from a volcanic eruption, black carbon, nitrogen oxides (NOx), carbon monoxide gas from motor vehicle exhaust, and heavy metals such as mercury and lead. Secondary pollutants are not emitted directly but instead form in the air when primary pollutants react or interact. Tropospheric ozone (O3) is an example of a secondary pollutant. The experimental evidence suggests a positive correlation of O3 exposure with oxidative damage, impaired antioxidant defense, and proinflammatory response in the skin (Fuks et al., 2019).
In time-series studies, it was observed that acute rises in O3 levels correlated with seeking medical help for skin conditions (Salvador et al., 2019). Other types of secondary pollutants include secondary PM (aka secondary inorganic aerosols) and oxidized VOCs (Centers for Disease Control and Prevention, 2020; WHO). Some pollutants can be both primary and secondary: They are both emitted directly and formed from other primary pollutants (WHO, 2017).
Mechanisms of injury from air pollution
Air pollution causes oxidative stress. Air pollutants enter the skin via nanoparticles and generate quinones, which are redox-cycling chemicals that produce reactive oxygen species (ROS). This increase in the amount of ROS and free radicals within the cell and its mitochondria overcomes the skin’s innate antioxidant defenses, including depletion of enzymatic (glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase) and nonenzymatic (vitamin E, vitamin C, and glutathione) antioxidant capacities (Thiele et al., 1997). T
he ROS and free radicals interact with the lipid-rich plasma membrane, initiating a lipid peroxidation reaction that unleashes proteolytic activity, causing further tissue injury. This cascade in turn triggers an increase of metalloproteinases (Farage et al., 2008, Millis et al., 1992). ROS also stimulate the release of proinflammatory mediators, which results in the accumulation of neutrophils and other phagocytic cells that further generate free radicals, thereby resulting in a vicious cycle of inflammation and metabolic impairments.
Oxidative stress initiates complex biological processes resulting in genetic damage, activation of transcription factors such as activator protein 1 and nuclear factor-κB and signaling pathways such as extracellular signal-regulated kinases, c-Jun N-terminal kinases, and p38 mitogen-activated protein kinases, involved in cell growth and differentiation and in the degradation of the connective tissue of the dermis (Baek and Lee, 2016).
These effects can be amplified by the deleterious synergy between pollution and sunlight (Burke and Wei, 2009). Repeated and frequent exposure to high levels of these pollutants may have deleterious effects on the skin, which include association with or causation of premature aging, photodamage, solar lentigines, melasma, and increased incidences of atopic dermatitis, psoriasis, skin cancers, and acne (Mancebo and Wang, 2015, Puri et al., 2017).
The role of the aryl hydrocarbon receptor (AHR) in causing the deleterious effects of pollution are being elucidated (Vogel et al., 2020). The AHR is a ligand-activated transcription factor that regulates the expression of genes, including those encoding the cytochrome P450 monooxygenases, CYP1A1, and CYP1A2, which are important enzymes in metabolism of xenobiotics.
The AHR is activated upon binding of PAHs, persistent organic pollutants, and related ubiquitous environmental chemicals to mediate their biological and toxic effects. In addition, several endogenous and natural compounds can bind to AHR, thereby modulating a variety of physiologic processes. In recent years, ambient PM associated with traffic-related air pollution has been found to contain significant amounts of PAHs. PM containing PAHs are of increasing concern as a class of agonists, which can activate the AHR (Fig. 1).
How pollution enters the skin
Skin interfaces with the atmosphere. Studies show that pollutants gain entrance to the skin by direct accumulation on the skin surface, absorption via the hair follicles, inhalation, ingestion, and circulation of pollutants in plasma that diffuse into deeper dermal tissues. PAHs can be detected not only in the air but also in all human bodily fluids and in hair (Krutmann et al., 2014).
There are two documented ways for pollution to permeate the skin: transepidermal and absorption through hair follicles and sweat ducts. The transepidermal route can be divided into the shorter, transcellular and the longer, intercellular routes for penetration of hydrophilic and lipophilic compounds, respectively. Absorption through hair follicles and sweat ducts is the shortest route. Although skin adnexal structures are 0.1% of the total skin surface of 18,000 cm2, they excel as a pathway for percutaneous penetration (Koohgoli et al., 2017).
Dermal uptake depends on the deposition of the hazardous substances on the skin surface, the composition and physical properties of epidermal lipids, and diffusion through the epidermis to the blood vessels (Rinnerthaler et al., 2015). Pesticides, solvents, mercury, isocyanates, polychlorinated biphenyls, acrylates, and PAHs are some of the main chemical groups that have been recognized as posing health problems via percutaneous absorption (Rinnerthaler et al., 2015; Soeur et al., 2020).
Inhalation uptake of pollution is dependent on two factors: alveolar concentration of inhalation agents and diffusion and solubility, which is also called the blood–gas partition coefficient (Weschler and Nazaroff, 2014). Pollutants can also be ingested, as in grilled meats. All these sources—percutaneous, inhaled, and ingested—can provide access to the bloodstream and systemic distribution.
Skin disorders associated with pollution
We have known for decades that smoking leads to premature aging (Morita, 2007, Morita et al., 2009). Epidemiological studies discovered a direct link between airborne PM exposure and the occurrence of prominent skin aging signs especially pigment spots, as well as wrinkles (Okada et al., 2013). Another study documented that an increase in soot and particles from traffic were associated with 20% more pigment spots on forehead and cheeks (Huls et al., 2016). Before industrialization, the skin of farmers had extensive photoaging, which may have been due to the perfect storm of agricultural pollutants such as VOCS and unprotected UV exposure. With urbanization, the cities became the new pollution pockets, with PAH and PM from industry and traffic as major culprits. Pollution with and without UV synergy has been proven to be causative in premature ephelides, lentigines, and rhytids (Huls et al., 2016, Yin et al., 2001).
A lentigo (plural lentigines) is a small brown macule located typically on the face, hands, and chest. Variously called liver spots, Hori’s macules, solar lentigines, and senile lentigines, they are typically associated with advancing age but may be seen in some unique dermatologic syndromes (Hamm et al., 2019). Solar lentigines can be considered a sign of premature aging. In a well-done study, Peng et al. (2017) demonstrated that exposure to PM2.5 was significantly associated with senile lentigines on the cheeks and on the back of hands; the higher the PM, the more lentigines. Other variables associated with skin aging were secondhand smoke and exposure to fossil fuels. Both were associated with a higher number of spots on the cheeks. In another study, investigators found that a distance of 100 m or less from a busy road was associated with 35% more senile lentigines on the forehead and 15% more on the cheeks (Huls et al., 2016). NO2 exposure has been linked to pigment spot formation on the cheeks in both Caucasian and Asian women (Schikowski and Krutmann, 2019).
In one proposed mechanism, organic compounds present on the surface of PM may penetrate the skin and directly affect viable skin cells, such as keratinocytes and melanocytes. In addition, it has been shown that both UV radiation and PAH‐loaded particles activate AHR in human skin and thereby contribute to lentigenes. Notably, recent studies demonstrate that AHR activation in skin cells induced skin pigmentation in a variety of pigmentary disorders (Napolitano and Patruno, 2018, Schikowski and Krutmann, 2019).
Melasma is a benign, acquired, irregularly patterned, light- to dark-brown hyperpigmentation, with symmetric distribution mostly over the face but at times also involving the neck, chest, and shoulders. The etiology of melasma includes genetic predisposition, hormones, and most importantly UV radiation (Trivedi et al., 2017). Recent studies suggest pollution as a possible emerging risk factor for the development of melasma (Roberts, 2015). Airborne PM and PAHs present in the polluted air enter the skin via nanoparticles and generate quinones that lead to the generation of ROS. These ROS then trigger high metalloproteinase levels that lead to skin pigmentation. Interestingly, the incidence of melasma is higher in persons with skin type III-VI residing in India, China, Southeast Asia, and the United States, countries that are also the most polluted geographical regions in the world (Handel et al., 2014, Mannucci and Franchini, 2017, Roberts, 2015).
Atopic dermatitis (AD) is a common, heterogenous, chronic‐intermittent, eczematous skin disorder that starts at infancy or early childhood and persists for a large part of life. It is characterized by frequent relapse with intense pruritus that deteriorates the quality of life and decreases treatment satisfaction of afflicted patients (Kim et al., 2019).
The lifetime incidence of AD is as high as 20% in the general population (Kim et al., 2013, Mannucci and Franchini, 2017) The incidence in children may be higher (Schachtel et al., 2020) Despite the large number of clinical, laboratory, and experimental studies, the pathophysiology of AD remains to be clarified. We know that AD is characterized by T-helper cell (Th2)–deviated skin inflammation, barrier disruption, and chronic pruritus (Bonamonte et al., 2019, Rerknimitr et al., 2017). The increasing prevalence of AD parallels a global rise in industrialization, urban living, and increasing air pollution over recent decades (Bonamonte et al., 2019, Kim et al., 2013).
We have strong evidence-based medicine demonstrating that outdoor air pollution is related to exacerbation of preexisting asthma, development of atopic diseases, and allergic sensitization (Bonamonte et al., 2019). In contrast, there are few studies to our knowledge that show the association between outdoor air pollution and AD. In one study, investigators in Seoul collected symptom records of 1,880 person-days (Kim et al., 2019). They found that AD symptoms were associated with the levels of outdoor air pollutants such as PM, toluene, and VOC. Interestingly, this association varied according to season.
Skin barrier dysfunction
Skin barrier dysfunction is associated with the reduced production of terminal differentiation molecules such as filaggrin (Del Rosso et al., 2016). Abnormal skin barrier integrity also causes an increased colonization of microbes such as Staphylococcus aureus, which further exacerbate Th2-deviated skin inflammation (Del Rosso et al., 2016, Furue et al., 2019). There are new molecules and drugs in the therapeutic pipeline for AD (Schachtel et al., 2020). One such treatment under study includes the drug tapinarof (Psomadakis and Han, 2019), which has gained increased attention because its topical application is efficacious for patients with AD. In clinical trials, tapinarof activates the AHR/CYP1A1 axis and augments the expression of filaggrin and involucrin. Tapinarof is a high-affinity AHR ligand with antioxidative activity via NRF2 (nuclear factor-erythorid2-related factor-2) activation and a ROS-scavenging structure. Earlier in this article, we discussed AHR high-affinity ligands such as PM, which promoted oxidative stress by activating the cytokine class I cascade to increase ROS resulting in inflammation. Even in barrier-disrupted AD patients, systemic absorption of topical tapinarof is limited and likely decreases during the treatment course in parallel with treatment success that restores the barrier function (Cotter et al., 2018, Psomadakis and Han, 2019).
We know that pollution negatively affects psoriasis by the same mechanism seen in AD (Puri et al., 2017). Cadmium, found in battery and television manufacturing and the aircraft industry, is one of the newly identified air pollutants that affect the pathogenesis of psoriasis (Kamiya et al., 2019). In this study, patients with severe psoriasis had higher blood cadmium compared with the general population. It is proposed that environmental exposure to cadmium may compromise immunity, and microenvironmental perturbations can predispose to worsening of psoriasis (Kamiya et al., 2019, Liaw et al., 2017).
A robust body of evidence indicates a link between pollution and inflammatory acne (Dréno et al., 2018, Krutmann et al., 2017, Liu et al., 2018). The prevalence of acne is similar between Asian and Caucasian women, but Asian women were reported to have a higher prevalence of inflammatory than comedonal acne (20 vs 10%), compared with Caucasian women, for whom comedonal acne was more prevalent (14%) than inflammatory acne (10%; Perkins et al., 2011).
In addition to a higher prevalence of inflammatory acne, Asian women also report that their symptoms are exacerbated during periods of high air pollution. Subsequent studies provided evidence for this impression (Krutmann et al., 2017). Lefebvre et al., 2015, Lefebvre et al., 2016) looked at skin quality changes, defined as reduced vitamin E and squalene levels, in acne patients residing in Shanghai and Mexico City, two cities with heavy pollution levels. They observed that these measures of skin quality declined with chronic exposures to ambient pollution. Although both markers are signs of sebum oxidation, clinical signs of acne severity were not assessed. Nevertheless, increased sebum is known to be an early pathophysiological pillar of acne (Eudier et al., 2019, Gollnick and Dreno, 2015).
As discussed in detail earlier in this journal (Parker, 2020), pollution is associated with an increased risk for skin cancer (Baudouin et al., 2002). The “pollutants” that react most specifically with the skin are UV radiation, PAHs (eg, benzo[a]pyrene), VOCs (eg, benzene), heavy metals, and O3. UV radiation, a “physical” pollutant, is thought to be the factor responsible for most skin cancers in humans. The genotoxicity of UV light is well documented and its carcinogenic effect is clearly demonstrated in vivo in humans. A few epidemiological studies describe the carcinogenicity of certain pollutants such as arsenic or lead on the skin. However, most of the evidence for the role of pollutants in skin cancers comes from in vivo animal studies or from in vitro studies using PAHs.
In addition to advocating for clean air, non-fossil fuel energy sources, and environmental protections, we need to protect ourselves and our patients from the deleterious effects of pollution. Here we discuss some strategies for personal protection.
Water may dilute the toxin load within the bloodstream. The recommended daily water intake for an adult is 2 L or 0.5 gallons per day (Jéquier and Constant, 2010).
Free radicals are unstable molecules that can cause inflammation and are postulated to underlie a number of age-related chronic diseases, as well as the aging response, itself (Rinnerthaler et al., 2015, Sies, 1997). Antioxidants neutralize the free radicals produced as a result of toxic air pollutants entering the body. Thus, a diet rich in antioxidants may help protect from the damage caused by air pollution. The most important antioxidant supplements are vitamins B3, C, and E; omega-3; β-carotene; selenium; coenzyme Q10; polypodium leucotomos; green tea; and lipoic acid (Prasad et al., 2017).
The Mediterranean diet involves the consumption of foods high in antioxidants, such as fruits, vegetables, whole grains, legumes, olive oil, fish, and poultry (Widmer et al., 2015). For more than17 years, researchers at New York University School of Medicine prospectively collected data from 550,000 individuals with an average age of 62 years from around the United States. This cohort was grouped on how closely their eating habits mirrored the Mediterranean diet and on estimates of their long-term exposures to air pollution, including PM2.5, nitric oxide, NOx, and O3 (Lim et al., 2019).
Among the individuals who least adhered to the Mediterranean eating pattern, death from all causes increased by 5% for every 10 parts per billion increase in long-term average nitrous oxide exposure, compared with only 2% among the cohort who were best at following the diet. Deaths from cardiovascular disease increased 17% for every 10 μg/m3 increase in long-term average PM2.5 exposure among the individuals who did not closely follow the diet, compared with 5% among those who did. Similar patterns were seen for deaths from heart attacks (Lim et al., 2019). There is certainly a case to be made for eating a healthy, high-antioxidant diet. Although its benefits for skin health have not yet been studied, it seems plausible to predict that it would benefit.
Anti-pollution skin care regimen
Cleansing the skin is the backbone of an anti-pollution skin regimen because airborne pollutants can bind to the skin and weaken the skin barrier, rendering it more susceptible to UV damage, dryness, wrinkles, and hyperpigmentation. Evidence-based data have demonstrated improved cleansing with an ultrasonic vibrational handheld brush (Peterson et al., 2017). Although the cost of this device may put it out of reach for some, good facial cleansing can be accomplished manually. Protecting skin during the daytime with sun protective skin care products is another critical cornerstone of prevention. Emollients augmented with evidence-based topical antioxidants, such as vitamins A, B3 (niacinamide), C, and E; green tea; coenzyme Q10; and resveratrol is another important preventive strategy (Burke, 2019).
We advise a twice-daily skin care regimen, starting each time with a cleanse. The morning cleanse prepares the face for the anticipated environmental impacts of the day. After cleansing, one attempts to “build a shield” can protect facial skin from environmental pollutants. Acne-prone patients should be recommended products that will not induce disease flares. This regimen is also beneficial for patients with melasma because it creates additional barriers to decrease the skin’s UV absorption. The skin care program we recommend in our clinic includes the following sequence:
- 1)Use of a gentle cleanser, washing the face with hands or a washcloth.
- 2)Apply witch hazel or an alcohol-based toner/serum to help close pores.
- 3)Use of a silicone-based primer and/or moisturizer (select a vehicle that is most compatible with dry, T-zone, or oily skin type) as an additional barrier to environmental pollutants.
- 4)Use of a broad-spectrum sunscreen with protection against all UV wavelengths as well as infra-red radiation.
- 5)Finally, use a foundation makeup if desired to complete the skin pollution barrier.
The evening cleanse is designed to remove airborne particles, soot, and other possible skin contaminants that may lie at the skin surface. Because PM is being removed, this cleanse should be longer and stronger than the morning cleanse. The evening regimen should follow this sequence:
- 1.Cleanse with a handheld sonic/vibrational cleansing device (with or without grains for sensitive skin types) to stretch pores and help expel surface debris. If this device is not available, cleanse well using a washcloth in contact with all areas of the face.
- 2.Use a makeup removal wipe to ensure all makeup was removed by cleansing.
- 3.Finally, use an evening moisturizer containing repair ingredients, such as some DNA repair creams, or products containing one or more of the following: resveratrol, retinoids, or hyaluronic/chondroitin sulfate. Product rotation may offer patients the benefit of synergism.
More information: JAMA Dermatology (2021). DOI: 10.1001/jamadermatol.2021.0179