Abstract
The most common and perhaps the most important route of exposure to allergenic metals in modern humans is via everyday consumer objects, such as jewelry, clothing, leather, and technological devices. Nickel, cobalt, chromium and gold, especially, are ubiquitous in daily-use objects. Nickel release from jewelry is common and ear piercing remains the most important risk factor for the development of nickel contact allergy. Cobalt and chromium are frequently found in leather products and gold is commonly used in jewelry. There is abundant clinical evidence of allergic contact dermatitis from metals released from daily-use objects and many exposure studies have been performed seeking to better characterize which allergenic metals are released from which products. Exposure to allergenic metals via technological devices such as mobile phones, laptops, and tablets is likely growing. The pediatric population in particular seems at risk for metal allergic contact dermatitis from daily-use objects. Metal exposure via daily-use objects is frequent and clinicians should be aware of the ways these items can elicit metal allergic contact dermatitis.
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1 Introduction
Metal allergens are among the most common causes of allergic contact dermatitis (ACD), and modern humans are exposed to these allergens frequently in daily life. Nickel, cobalt, and chromium are often found in everyday consumer objects, such as jewelry, clothing, leather, technological devices, household items, and other daily-use objects [1]. Gold, palladium, mercury, copper, aluminum, titanium, iron, platinum, tin, zinc are also occasionally found in these items. Metal ACD due to daily-use objects is exceedingly common. Nickel is by far the most common cause of ACD and is ubiquitous in consumer goods [2, 3].
There are two general ways to report metal exposure via daily-use objects. First, there are exposure studies, or studies that survey a large sample of a certain type of product or item and assess metal content or release. These types of studies have been performed since the late 1970s and early 1980s when clinicians used new synthetic sweat methods to detect nickel ion release from jewelry and clothing snaps [4, 5]. Exposure studies do a good job describing the exposure patterns individuals may have when they use a certain type of product in a certain setting. However, it is not necessarily easy to apply these studies to clinical practice, as they can be very setting specific, e.g. studies reporting on metal release from jewelry from Asia may not be applicable to a clinical practice in Europe. Additionally, if they are not guided by clinical data they can be clinically irrelevant, e.g. an exposure study of metal release from computer components is not clinically relevant unless, clinically, individuals are having adverse reactions to computer components.
Secondly, one can use clinical reports to describe metal content in daily-use objects. Case reports, case series, and clinical vignettes provide important information regarding the clinical consequences of metal exposure via everyday devices and should be used as a basis for guiding exposure studies. A good example of this is a case report of nickel ACD from a laptop computer, prompting multiple exposure studies evaluating laptops and other technological devices for allergenic metal ion release [6, 7]. Like exposure studies, however, case reports and other clinical reports again are not necessarily generalizable given their case-specific nature.
2 Methods for Measuring Metal Content and Release
This topic is discussed in depth in other chapters (see Chap. 6). Briefly, there are two primary ways to evaluate metals in daily-use objects: there are methods that measure metal content and methods that measure metal release. Frustratingly, metal content does not always predict metal ion release or bioavailability [8]—for example, many nickel-containing stainless steel alloys do not release nickel in sufficient doses to elicit ACD in nickel-sensitized individuals. For this reason, measuring metal release is generally more clinically useful. Metal release is often qualitatively assessed by spot tests, such as the dimethylglyoxime (DMG) spot test for nickel release, and the newer cobalt and chromium spot tests. These are convenient, quick, economical, non-destructive screening tests which identify metal ion release from most metallic, non-porous surfaces [9,10,11]. These techniques are limited, however, both in scope—there are no release tests for other common metal allergens, such as copper and palladium—and in the range of items they can test—they cannot be used on non-metallic items, e.g. make-up, emollients/moisturizers, leather. Content tests, such as X-ray fluorescence spectroscopy and atomic absorption, can provide information on all metal elements and can be used to evaluate non-metallic items but can be impractical, expensive, and in some cases damaging to the item in question [8, 12, 13].
3 Metals in Jewelry
Worldwide, jewelry is the most common source of daily metal allergen exposure. In order of relative worldwide frequency, the most common metals found in jewelry are copper, iron, zinc, nickel, silver, chromium, tin, manganese, lead, and cobalt [8]. Among patients with metal allergy who develop dermatitis from jewelry, there is significant variation in severity of symptoms, ranging from minor irritation to severe dermatitis with id reaction or even systemic contact dermatitis. Metal exposure via jewelry is significant not only because of the ubiquitous use of metallic jewelry, but also because the friction, sweat, and occlusion that occur with jewelry use can facilitate release of metal ions from otherwise non-ion releasing alloys—a concept identified in even the earliest jewelry ACD case series [14, 15].
3.1 Nickel in Jewelry
Nickel is the most common cause of ACD from jewelry. Modern jewelry from Europe, North America, and Asia frequently releases nickel sufficient to cause ACD [8, 16,17,18,19]. Modern case reports of nickel dermatitis from jewelry date back to the early twentieth century—for example, one series of cases described dermatitis caused by nickel in bracelets, a wrist watch, and a wrist watch band [20]. Numerous case reports and exposure studies have detailed nickel ACD or nickel release from jewelry items including navel and genital rings [21,22,23], hair bands [24], and hair clips [25] (see Table 13.1). Unsurprisingly, nickel contact allergy has been shown to correlate with wrist, finger and ear dermatitis, common locations jewelry is worn (see Figs. 13.1 and 13.2) [26].
(a) Earlobe dermatitis after contact with metal earrings in a known nickel-sensitive individual. (b) Positive DMG test from earring post. The gold colored plating had worn away from the portion of the earring post that came in contact with the skin revealing the silver-colored metal below. Only the silver-colored metal released nickel
Positive DMG test from a nickel-releasing ring
In contrast to cobalt and chromium, jewelry is the primary sensitizing exposure for nickel allergy. Worldwide prevalences of nickel allergy are increased in women compared to men due to nickel exposure in earrings and jewelry. For example, among North American dermatitis patients, 23% of female patients had positive nickel patch testing compared to only 7% of male patients [27]. Similarly, men with pierced ears have higher rates of positive nickel patch tests compared to men without ear piercings [28]. Ear piercing, body piercing, number of piercings, and young age at piercing are all significant risk factors for nickel allergy [27, 29,30,31].
Nickel is often used in jewelry alloys and platings due to its low cost, attractive white shiny appearance, and resistance to corrosion. While several studies found that inexpensive jewelry is more likely to release nickel [18, 19, 32, 33], another study found no association between price and likelihood of nickel release [34]. Expensive jewelry items and gold alloys—such as white gold, and rhodium-plated gold—may also release nickel [35,36,37]. Nickel release from jewelry items marketed as “nickel-free,” or labelled as stainless steel or sterling silver, has also been reported [38]. Stainless steel frequently contains nickel, but clinically relevant nickel release is uncommon [39].
Historically, eyeglasses and spectacle frames constituted an important source of nickel exposure [40]. In fact, some of the earliest reported cases of non-occupational nickel ACD were from glasses frames [15, 20, 41]. Glasses frame dermatitis was reported in 56% (43/77) of nickel-allergic patients in a large facial dermatitis cohort, many of whom had nickel-releasing frames on DMG testing [42]. Many eyeglasses frames are now made of plastics and other metals. For example, in one case of eyeglasses dermatitis, a known nickel-allergic patient reacted to palladium in nickel-free glasses frames [43]. Nevertheless, exposure studies continue to identify nickel release in large portions of glasses frames [40], and nickel glasses frame ACD is still reported [44].
Simple cases of nickel dermatitis from jewelry or glasses frames are uncommonly referred for patch testing. While jewelry dermatitis classically closely matches the anatomical site of exposure (i.e., neck dermatitis from a nickel-releasing necklace), jewelry must not be overlooked as a cause of distant dermatitis as well, particularly for the face. Transfer of nickel ions in jewelry may also be responsible for ear, eyelid, lip, or facial dermatitis (see Fig. 13.3) [45, 46].
(a) Bridge of the nose dermatitis corresponding to resting location of metal eyeglasses (b) Positive DMG test from metal eyeglasses
3.2 Cobalt in Jewelry
The classic historical example of relevant cobalt allergy is mid-twentieth century women with cobalt and nickel dermatitis due to garter suspenders [47, 48]. It is unclear, however, if cobalt exposure in jewelry or daily-use objects continues to drive cobalt contact allergy in the twenty-first century. For example, while jewelry from Europe, North America, and Asia often contain cobalt [8], cobalt is rarely released [21, 49], and jewelry dermatitis from cobalt is rarely seen in clinical practice. To our knowledge, there is only one published case of clear jewelry dermatitis to cobalt in the recent literature [50]. It has been demonstrated that jewelry and belts with a dark metallic finish are more likely to release cobalt [21, 51]. Most contemporary exposure studies in Europe and North America aimed at assessing cobalt release from daily-use objects are performed with a cobalt spot test and the majority of these studies find that cobalt release from jewelry is very rare—for example, in the USA and Denmark cobalt release from jewelry is found in ~1% or less [21, 49]. There are several studies of cobalt release from jewelry in Asia: one study from China and Thailand demonstrated very rare release of cobalt from jewelry while two others from Korea and Thailand found relatively frequent release of cobalt from belts and jewelry [16, 49, 52]. A recent study did evaluate cobalt release from earring components in Europe using the EU 1811 artificial sweat analysis rather than the spot test and found considerable release from at least one component of 44% of tested earrings [53]. Interestingly, cobalt and nickel co-sensitivity is frequently seen in patch tested patients and this has always been explained by co-exposure. It has been clearly demonstrated that ear piercing is associated with nickel allergy, but ear piercing does not appear to be a contemporary risk factor for cobalt allergy [27, 54]. This suggests that cobalt sensitization from earrings is not significant on a population level. Interestingly, in one study cobalt contact allergy was shown to correlate with wrist and finger dermatitis, common sites of jewelry use [26]. Ear dermatitis due to cobalt allergy is not a common clinical problem but dermatologists should be aware that jewelry may be a source of exposure for some cobalt-allergic patients.
3.3 Chromium in Jewelry
Chromium is a common component of most stainless steel alloys and is present in jewelry worldwide [8]. Despite jewelry frequently containing chromium, hexavalent chromium release was only found in 1/848 (0.1%) pieces of jewelry by the chromium spot test [11]. Dermatitis from chromium in jewelry is not a common clinical problem; however, occupational dermatitis after handling metallic items has been more frequently reported [55], and recent investigations have demonstrated significant levels of cutaneous chromium deposition after handling chromium-containing metal discs, even with short exposure times [56]. Like cobalt, on a population level chromium exposure via jewelry does not seem to be a significant cause of chromium ACD, but may be relevant to individual chromium-allergic patients.
3.4 Gold in Jewelry
Gold is a controversial allergen. While positive patch test reactions to gold salts such as gold sodium thiosulfate are common, the relevance of positive gold patch testing is often difficult to ascertain. Though not commonly found in cheap jewelry globally, gold is a precious metal commonly used in the alloys for expensive jewelry [8]. While gold salts are immunologically reactive and were previously used as inflammatory modulators for rheumatologic diseases [57], metallic gold has long been valued for being relatively inert and resistant to corrosion. In one study, gold was not released from gold-containing jewelry when assessed with artificial sweat and atomic absorption analysis and the authors concluded that jewelry was unlikely to provoke dermatitis, even in those with positive gold patch tests [58]. Another study confirmed insignificant release of gold from gold alloy discs in artificial sweat; however, they did find that gold was released when the discs were soaked in more complex mediums containing cysteine or glutathione [59]. Additionally, it was recently reported that gold is released from elemental gold discs and deposited onto the skin when applied under occlusion to the backs of healthy individuals [60]. Metallic gold in dental alloys and vascular stents has been shown to increase serum gold levels and correlates with positive gold patch testing [61].
Due to low relevance and unusual clinical presentations, experts disagree about the utility of patch testing with gold. However, there is some evidence that gold may be an important allergen. For example, nearly half of gold-allergic patients developed dermatitis when they were re-exposed to gold earrings in a blinded study [62]. This provides good evidence that jewelry may be a relevant exposure for gold allergic patients. Interestingly, gold ACD may not develop at the site of cutaneous exposure, as is common with other metal allergens. Rather, jewelry-related gold ACD may manifest only as periorbital or facial dermatitis which may resolve only after several months of avoidance of gold jewelry [63,64,65]. Gold may also cause persistent and granulomatous reactions both from patch testing and from exposure to jewelry [66, 67]. Gold allergy is more common in women compared to men, which also suggests that jewelry, rather than dental alloys or occupational exposures, may play a primary role in gold sensitization [65].
3.5 Palladium in Jewelry
Palladium contact allergy is most commonly associated with oral lichenoid reactions and stomatitis from dental alloys [68]. Palladium and nickel cross-react and true mono-palladium hypersensitivity (in the absence of nickel allergy) is rare [69]. However, there is some evidence that palladium allergy may be underdiagnosed given that the palladium salt historically most commonly used for patch testing, palladium dichloride, may have low sensitivity [70]. Nevertheless, there are reports of palladium ACD from eyeglasses frames [43] and palladium may be found in expensive jewelry. Interestingly, one palladium-sensitive patient with chronic pain and swelling adjacent to a palladium-containing dental implant developed finger dermatitis when challenged with a palladium ring, suggesting that cutaneous palladium exposure elicit produce ACD in strongly sensitized individuals [71]. When palladium allergy is seen after ear piercing, a granulomatous reaction may occur—sometimes called an allergic contact granuloma [72]. In one study of patients with palladium positive patch tests, no skin reactions were observed when they wore palladium-coated earrings for 9 weeks [73].
3.6 Presumed Jewelry Allergy and Other Clinical Considerations
Patients may self-diagnose nickel allergy and avoid jewelry and other items which clearly cause dermatitis at the site of cutaneous exposure. In addition, many primary care physicians and dermatologists are aware of nickel allergy and may diagnose and counsel patients who present with characteristic distributions of jewelry dermatitis without recommending patch testing. Suspected jewelry dermatitis is often considered a simple clinical problem. While in some cases patch testing is not required to make the diagnosis of nickel ACD from jewelry, we caution physicians against delaying patch testing if the dermatitis does not resolve promptly after removing the presumed offending source of exposure. Presuming a mono-allergy (i.e. nickel allergy only) in a patient may delay correct diagnosis and increase morbidity for patients with multiple contact allergies. In a study of 449 patients with a self-reported history of jewelry dermatitis, nearly half of all nickel-allergic patients also had a positive patch test reaction to either gold, cobalt, chromium, palladium, or platinum when patch tested to an expanded metal series [74]. As a clinical example, after a positive nickel patch test, a woman was counseled to avoid nickel-releasing jewelry but had continued difficulty with neck dermatitis. She was found to be both nickel and cobalt allergic on repeat patch testing and had a new cobalt-releasing necklace [50].
Furthermore, patients may be erroneously diagnosed in the absence of patch testing—for example, suspicions of titanium allergy are commonly unfounded, may delay orthopedic surgical procedures, and provoke significant patient distress. One woman began to react to her “titanium” eye-glasses and was erroneously given a diagnosis of presumed titanium allergy shortly before an orthopedic procedure. Upon patch testing, the patient was nickel-allergic and the glasses were subsequently found to release nickel, containing very little titanium [75]. Clinicians should not hesitate to perform patch testing for patients with unresolved presumed jewelry dermatitis.
4 Copper in Everyday Use Objects
Copper-containing alloys, including bronze, brass, and many others, are very commonly found in jewelry in North America, Europe, and Asia [8]. In addition, it has been demonstrated that earrings with copper content also release copper as assessed by artificial sweat leaching and inductively coupled plasma mass spectrometry [38].
Copper is an infrequent sensitizer, and the clinical relevance of positive patch testing to copper salts is controversial. The allergenicity of copper has been demonstrated by local lymph node assay in animal models [86]. Though not regularly tested, copper allergy has been assessed in patients with 1–5% copper sulfate in petrolatum or 1–2% copper sulfate in aqueous preparations. In large studies, copper patch test positivity is often seen in conjunction with positive patch tests to other metals; for example, in a Swedish study of 1190 dermatitis patients 9/13 (70%) patients with a positive patch test to copper sulfate 2% had a concomitant reaction to either nickel, cobalt, or chromium [87]. Though rare, copper ACD from jewelry has been reported [88]. Copper ACD was reported to cause chronic hand dermatitis in an electrician [88] and recurrent fingertip dermatitis in a child who often played with die-cast model cars containing copper [89]. In addition to jewelry, copper is also found in coins, electronics, dental alloys, and industrial applications. Copper-containing intrauterine devices for long-term reversible contraception are used worldwide. Localized and generalized dermatitis, as well as urticaria, in patients with copper IUDs has been reported, and many cases have resolved with removal of the copper device [90,91,92,93]. There is experimental evidence that copper may cross-react with nickel [94] and palladium [95]. Copper is an uncommon cause of ACD to daily-use objects; however, there is good evidence that copper may cause ACD and testing should be undertaken when clinical suspicion is high.
5 Metals in Clothing, Textiles, and Leather
Clothing, textiles, and leather are an underappreciated source of metal exposure in everyday life. While much of the historical metal exposure through clothing is likely no longer clinically relevant to today’s patch testing clinicians, e.g. nickel dermatitis to corset fasteners, etc. [41], metal exposure via clothing is still widespread. Historically metal exposure through clothing played an important step in the overall understanding of ACD; notably, the multitude of cases of suspender and garter dermatitis in the 1950s and blue jean button dermatitis in the 1970s and 1980s brought nickel ACD and contact dermatitis in general closer to the forefront of academic dermatology.
5.1 Leather
Perhaps the most common source of metal exposure via clothing is exposure to chromium and cobalt in leather products. Trivalent chromium (Cr[III]) has been used in the leather tanning process since the middle to late 1800s and is favored over vegetable or other mineral-based tanning due to its simplicity, cost-effectiveness, and more consistent performance [96]. It is estimated that 80–90% of worldwide tanned leather is tanned using chromium sulfates [97, 98]. Cr(III) is also used in secondary tanning, dyeing, and processing of leather products. Typically, chromium allergy is tested for using patch tests containing hexavalent chromium (Cr[VI]), and for many decades it was thought that Cr(IV) alone was responsible for clinical chromium allergy; however, new evidence suggests that the less-potent Cr(III) may also play a role [99,100,101]. While chromium used in the tanning process is universally used in its trivalent form, Cr(VI) is commonly found in finished leathers, likely a result of chromium oxidation secondary to changes in temperature and pH during the tanning process [102, 103]. Other metal allergens are also occasionally found in finished leather products. Aluminum is infrequently used as a mineral-tanning alternative to Cr(III), but aluminum is a rare allergen and no cases of leather-induced ACD have been reported. Similarly, cadmium, copper, mercury, nickel, and zinc have all been identified in finished leather samples, likely introduced in leather dyes, pigments, pesticides, or as a result of contaminated tanning equipment [98, 104]. Again, there have been no cases of leather ACD to any of these metal allergens; this may be secondary to underreporting, or simply because insufficient levels of these metals are released from the final leather products to elicit ACD.
There have been many exposure studies performed evaluating leather samples and products for chromium content and release. However, given chromium’s unambiguous use in the leather process, most of these studies aim to differentiate Cr(III) from the more troublesome Cr(VI) in finished leather and the processes that favor one or another [102, 103, 105,106,107], or seek to confirm the presence of chromium in leather products suspected to cause ACD [108]. All but a very few have robust selection methods aimed at identifying typical user exposure patterns. A recent study from Bregnbak et al. seeking to validate a new chromium spot test found Cr(VI) in 4/100 leather shoes and 6/11 leather gloves [83]. One study by Rydin et al. in 2002 on behalf of the Danish Environmental Protection Agency found that 15/43 (35%) leather items including watch-straps, baby shoes, gloves, shoes, and other leather clothing contained Cr(VI) above 3 mg/kg [109]. Another identified quantifiable levels of Cr(VI) in 11 out of 11 protective leather gloves [110]. However, when known chromium-sensitive individuals were patch tested with the same leather samples, zero of eight individuals reacted, again emphasizing the important clinical difference between metal content and release. A Swedish study in 2009 found chromium at levels of 42–29,000 mg/kg in 21/21 leather shoes [104]. However, none of the shoes contained detectable levels of Cr(VI). Other exposure studies on leather shoes [111], leather used in car manufacturing [112], and waste products from tanneries have also been performed [98]. The differences in findings between these studies likely reflect both discrepant selection methods, e.g. intentionally only selecting chromium-tanned leathers, and assessment tool used. See Chap. 4 for further information regarding chromium testing.
The most common clinical presentation of non-occupational chromium ACD secondary to leather is foot dermatitis [113]. This clinical presentation was noted in the early 1950s [114,115,116]. Chromium was also included in one of the first suggested supplementary screening trays, a foot dermatitis tray, proposed in 1959 [101]. Many case reports [117,118,119,120] and clinical data have confirmed that chromium is a common culprit for shoe dermatitis [121,122,123,124]. Chromium leather ACD has also been reported after contact with leather gloves (most commonly but not exclusively), leather work gloves [108, 115, 125, 126], leather gymnastic wrist supports [127], lederhosen [128] and increasingly, leather furniture [129, 130].
The only other metal allergen that has been shown to cause leather ACD in end-users is cobalt, and this is a relatively new clinical finding. Leather cobalt ACD was first reported in 2013 in a 66-year-old male who developed near-generalized dermatitis secondary to cobalt exposure in his leather sofa [131]. This 2013 study was also the first exposure study seeking to evaluate cobalt release from leather products. They found that 1/14 (7%) leather furniture samples from a single Danish furniture store contained cobalt, and all contained chromium by X-ray fluorescence spectroscopy. Previous exposure studies evaluating leather shoes and other items have identified cobalt content in leather but not specifically with regard to risk of ACD in the end consumer. Namely, a Swedish study that found detectable levels of cobalt in 20/21 (95%) leather shoes [104]. Another recent study found that 20/131 (15%) leather furniture samples contained cobalt by X-ray fluorescence spectroscopy [12]. Unfortunately, there is no reliable cobalt release measurement tool that can be used on leather. It is likely that cobalt is introduced into leather in the form of pigments during the leather dyeing process [132].
ACD to cobalt in leather is likely underreported given its novelty in the medical literature. As such there are currently only two case reports published, the case discussed previously and a case of a child who developed pretibial dermatitis from a leather chair [133]. However, clinical data on shoe dermatitis [124] and among leather workers [134, 135] has noted increased cobalt sensitization for many years. Additionally, in some of the reported leather chromium ACD cases, authors note a concomitant reaction to cobalt, perhaps representing co-sensitization via leather exposure [118, 119]. Further emphasizing the likely role cobalt has in clinical leather ACD, a recent questionnaire-based case–control study on 183 dermatitis patients with positive patch test reactions to cobalt chloride and negative patch test reactions to potassium dichromate were more likely than controls to report non-occupational dermatitis caused by leather exposure [136].
5.2 Textiles
Metals are seldom the culprit in textile dermatitis. However, metal textile dermatitis has been reported. Metals are used in textile manufacturing in the form of complex dyes, oxidizing agents, dye stripping agents, fastness improvers, and finishers [132]. Additionally, some raw textile materials such as cotton, flax, and hemp may naturally contain trace levels of metals accumulated via bio-absorption. However, these levels are typically far below ACD elicitation or sensitization rates at levels typically below 10 mcg/g and often below 1 mcg/g [137, 138]. Allergenic metals that have shown to be contained in some finished textiles include nickel, cobalt, copper, chromium, mercury, and others [139, 140].
The most relevant source of metal exposure via textiles are textile dyes. In particular, chromium, cobalt, copper, and nickel are used in metal complex dyeing, for wool, nylon, cotton, and leather [132, 139, 141]. Chromium-based dyes are used extensively in wool and nylon dyeing; in fact, all mordant wool dyes contain chromium [141]. Despite their known environmental risks and potential, if infrequent, to cause contact allergy, these metals continue to be used in textile manufacturing because they are the most efficient and at times the only method to achieve certain hues in the final product, namely turquoise, brilliant green, and some violet, blue and navy shades [141].
Reports of textile-induced metal dermatitis are rare, and many of the reported cases are decades old. It is not clear if this is because of a reporting bias or a general decrease in dyes that use chromium and cobalt in favor of the more environmentally friendly iron [142]. Chromium ACD from textiles was reported as early as 1948 in a case series of men who developed dermatitis to khaki clothing thought to be secondary to chromium-based dyes [143]. Cr(III) was extracted from textiles that caused chromium ACD in two Swedish military servicemen [144]. Military uniforms were also reported to cause chromium sensitization and dermatitis in Nigeria [145]. In a Korean case report, chromium-based dyes were suspected of causing dermatitis to a dark-colored bra [146]. Another case report highlights a nurse practitioner who developed cobalt ACD to her blue cobalt-dyed scrub pants [147]. Chromium textile ACD has also been reported after contact with men’s trousers, women’s outerwear, and a woman’s dress [128, 148]. Clinical reporting of textile dermatitis often highlights contact allergy to disperse blue dyes and other non-metal allergenic dyes. However, high rates of chromium patch test reactivity are sometimes noted in these clinical reports, possibly representing either misdiagnosis or co-sensitization. For example, in one cohort of 82 patients with clinical textile ACD who reacted to one or more allergens in a textile colors and finish series, 13% also reacted to potassium dichromate [149]. Likewise, in some textile ACD case report/case series thought to be secondary to non-metal dyes, concomitant reactions to cobalt or chloride are noted but rarely commented on [150, 151].
5.3 Clothing and Belts
Metals are frequently found in the snaps, rivets, buckles, and clasps used in clothing and have been extensively documented as elicitors of metal ACD. In fact, metal exposure via clothing snaps, buckles, rivets, and clasps has historically played a large role in driving clinical contact allergy. While the bulk of nickel contact allergy in the early 1900s was driven by occupational exposure, in the 1930s through 1950s there was a proliferation of nickel use in consumer products [152]. Case reports of ACD to clasps on stocking garters were first published in the 1930s [41]. ACD from stocking suspenders or garters was reported through the 1950s [14, 152,153,154]. For the most part nickel was the offending allergen in these cases; however, chromium garter dermatitis was also reported [155]. Nickel ACD was also reported to corset fasteners, bra clasps, and suspenders [14, 41].
With changing styles and types of clothing commonly worn, stocking garter dermatitis became less and less prevalent, but the use of metals in clothing clasps, snaps, and buttons did not. Beginning in the 1970s, ACD from metal release from pants buttons and rivets began to be reported [156]. Classically this clinical picture was periumbilical dermatitis secondary to nickel release from metallic blue jeans buttons [156]. In 1979 Brandrup and Larsen presented a case series of 79 nickel allergic patients with clinically relevant dermatitis from contact with blue jeans buttons [156]. Ten blue jean buttons brought in by patients were tested by DMG and seven were found to release nickel. This study’s novel combination of clinical reporting and exposure evaluation by the relatively new DMG method prompted a series of exposure studies in 1979 and the early 1980s (see Table 13.2; Fig. 13.4) [4, 76, 157].
Positive DMG test from a nickel-releasing jeans button
Further exposure studies conducted in the 2000s expanded to also evaluate zippers, buckles, clasps, and other metallic clothing components. Studies that investigated articles of clothing suspected of causing nickel ACD show high rates of nickel release. Studies that investigated convenience samplings of metallic clasps, buttons, rivets, etc. found a wide range of nickel release rates, from ~5 to ~75% of items releasing nickel. This wide range likely represents differences in sampling methods between studies, changes in clothing production through time, and changes in clothing types and styles tested. Only one recent study evaluated cobalt release from clothing snaps, rivets, and other accessories and found that 11/76 (15%) items released cobalt, compared with 58/76 (76%) that released nickel [16]. Exposure studies evaluating clothing snaps, rivets, buttons, and other accessories for other metal allergen content or release have not been performed.
As previously discussed, exposure to nickel-releasing jewelry, and in particular earrings, represents the most important source of nickel exposure and nickel sensitization for both pediatric and adult populations. However, clothing snaps, rivets, and other accessories, in particular, seem to play a large role in pediatric nickel ACD elicitation. The majority of periumbilical dermatitis patients in Brandrup et al.’s original case series were below thirty years of age and many were younger than 20. In 1999 the clinical syndrome of prominent pruritic periumbilical papules was described by Rencic et al. She proposed that this clinical picture could be used as a possible diagnostic criteria for pediatric atopic dermatitis diagnosis [158]. However, after publication, four letters to the editor were published strongly suggesting that prominent pruritic periumbilical papules were characteristic of nickel ACD in their pediatric populations [159,160,161,162]. Also in response to Rencic’s clinical syndrome, Sharma et al. published a case series in 2002 describing 38 children with “prominent pruritic periumbilical papules,” all who were nickel allergic. Other case series have illustrated that periumbilical dermatitis is common in children with nickel allergy [163]. And other case reports have highlighted periumbilical excoriated papules as a common presentation of pediatric nickel ACD from metal buttons [164,165,166]. Additionally, clinical studies on general ACD in children often identify nickel as a frequent contact allergen and cite metallic snaps as a possible culprit [167, 168].
Clinically, it is sometimes recommended that patients with nickel ACD from clothing snaps or buttons apply a coat of nail polish to the offending item [168]. This technique seems effective at preventing nickel release, even after up to seven wash-dry cycles in a standard washer/dryer [169]. Interestingly one study showed that buttons and snaps on pre-worn jeans released less nickel compared with new jeans [169]. Another study showed that ten DMG-negative snaps on jeans remained DMG-negative after washing [170]. There is some evidence that smooth metal buttons may release more nickel than ridged buttons [170].
In part stimulated by these studies documenting “prominent pruritic periumbilical papules,” the role of metal belt buckles was raised as another contributing element in this clinical picture. In particular, in 2004, Byer and Morrell evaluated both jean snaps and belt buckles for nickel release and found that over 50% of belt buckles released nickel compared with 10% of jean buttons (see Fig. 13.5) [170]. Belts had previously been evaluated for nickel release by Lidén and Johnsson in 2001 as a part of a larger survey of nickel release from various metallic items available for purchase in Sweden [78]. Since then belt buckles have been evaluated in many exposure studies (see Table 13.3). Nickel release was found in between ~40% and ~80% of belt buckles evaluated across eleven studies.
(a) An adolescent with pruritic periumbilical papules secondary to nickel exposure via a belt (b) Positive DMG test from nickel-releasing belt
Belts have also been evaluated for possible cobalt release; other than two Asian studies, one in South Korea [16] and one in Thailand [52] that found 40% of 21 and 29% of 28 belt buckles to release cobalt, cobalt was not identified in more than 1% of belts [51, 171]. It is unclear if the large differences between these results reflect differences in belt cobalt release in different international markets or simply variability in selection criteria and testing methodology. Of note, cobalt allergy is very common in Thailand, with some reports as high as 16%, perhaps reflecting increased sensitization from belt exposure [172].
Despite the relatively high prevalence of nickel release from belts and belt buckles, there are few clinical data published on nickel ACD secondary to belt exposure. This is likely secondary to a perceived lack of novelty, but may reflect an actual dearth of clinical cases. One recent case series described 11 nickel allergic patients with relevant nickel-releasing belt exposure [173]. Another case series published in 2003 documents 20 patients with nickel allergy and relevant exposure to either metallic belts or clothing snaps [174]. Among 204 nickel allergic patients in a large cohort from Singapore, clinically relevant exposure to belts was identified in 36 (18%) [175]. Case reports have also been published illustrating the possibility of nickel ACD-induced periumbilical dermatitis [176,177,178,179,180,181,182]. Interestingly, however, most of these case reports are case reports of nickel ACD at other sites, e.g. mobile phone preauricular ACD, in which the authors also note a periumbilical dermatitis and presumed belt-induced ACD. Despite the relatively infrequent clinical reports of belt ACD, avoidance of metallic belt buckles is often highlighted in more general ACD guidelines [168, 183]. While belts may contain cobalt and other allergenic metals, to our knowledge there have been no reported cases of ACD to any other metals from belts.
5.4 Other Clothing Exposures
The most common routes of exposure to nickel, chromium, and other allergenic metals in clothing are via leather, textiles, clothing snaps, buttons and belts; however, more esoteric exposure sources have also been reported. ACD from nickel and cobalt secondary to exposure via dyes used in plastic shoes has been reported [184], as has systemic ACD to mercury after contact with mercury containing ply-vinyl boots [185]. Metal charms on bras as well as bra clasps have been reported as sources of nickel ACD [14, 186, 187]. More recently a bra underwire was reported as a cause of nickel ACD elicitation [188]. Metallic threads used in traditional Indian embroidery have also been reported to cause nickel ACD [189, 190]. Other clothing accessories such as handbags, wallets, and umbrellas have been shown to release nickel but no case reports illustrating their clinical significance have been published [191].
6 Metals and Technology
Mobile phones, computers, handheld tablets, and other modern technological devices represent a new source of exposure to metals in everyday life. These devices may contain and release metal and can cause ACD. In particular ACD secondary to metal exposure in mobile phones is increasingly common [193].
6.1 Mobile Phones
Mobile phone use is exceedingly common. Over 95% of Americans own mobile phones, and over 70% own smartphones [194]. Nickel ACD from a phone was first reported in 1985 in a nickel-allergic patient who reacted to her nickel-releasing phone receiver [76]. Mobile phone ACD was first reported by Pazzaglia in 2000 in a small case series of nickel-allergic patients with relevant nickel-releasing cell phone exposure [195]. Since then there have been over twenty case series or case reports describing ACD from metal release from mobile phones. These are clearly documented in a recent review article (see Fig. 13.6, Table 13.4) [193].
Positive DMG test from a nickel-releasing mobile phone
The most commonly clinical presentation of mobile phone dermatitis is, unsurprisingly, facial dermatitis. Both unilateral [195,196,197,198,199,200,201,202,203,204] and bilateral [182, 202, 204, 205] facial dermatitis have been reported; more specifically, the distribution is typically preauricular, buccal, or mental, however auricle and tragus involvement has also been reported [197, 205]. More atypical presentations include thigh dermatitis secondary to storage of the offending mobile phone [182] and breast or chest dermatitis in women who secure their phone inside their bra [206, 207]. In general nickel is most often identified as the offending allergen [195, 198,199,200,201, 204,205,206,207]; however, chromium is also a frequent culprit [196, 197, 203, 204]. Many of these patients presented with other manifestations of nickel allergy, for example concomitant umbilical dermatitis from contact with belt buckles [181, 206], or wrist dermatitis from contact with a nickel-releasing watch band [180]. Bluetooth headsets [202] and metallic phone cases [208] have also been reported to cause nickel ACD. Most mobile phone metal ACD is from normal everyday use; however, occupational cases have been reported [180, 182, 199]. Metal ACD from mobile phones disproportionately affects younger patients. A recent review estimated that ~40% of reported mobile phone dermatitis cases were in patients under 18 [193]. If occupational cases were removed, this estimate would increase greatly.
There are no clear cases of non-nickel, non-chromium mobile phone dermatitis. In one case series a patient with mobile phone ACD tested positive to chromium, the suspected contact allergen, but also to cobalt [197]. In that case the offending phone was not tested for chromium or cobalt release or content. In the same series two patients had doubtful positive reactions to indium; again chromium allergy was the presumptive diagnosis [197]. In another case series a nickel allergic patient with mobile phone ACD also reacted to palladium, a known nickel cross-sensitizer; however, palladium content of the offending phone was not investigated [209]. In a third case series three individuals with mobile phone dermatitis tested positive to both nickel and cobalt; all three were given a diagnosis of nickel ACD but the phones were not tested for nickel or cobalt release or content [181].
Most case reports of nickel mobile phone dermatitis described above used the DMG technique to confirm nickel release. The first systematic evaluation of nickel exposure via mobile phones was performed in South Korea by Kim et al. [204] They found that 22% of 104 metallic mobile phone components released nickel. Other exposure studies in the United States and Europe found between ~5% and ~40% of mobile phones to release nickel. Two exposure studies evaluating mobile phone cobalt release found it in 0% of 50 and 14% of 72 phones in Denmark and the United States, respectively [210, 211].
It is clear that traditional mobile phones, in contrast to so-called “smartphones,” release more nickel, and possibly more cobalt. This is evidenced by exposure studies [211], as well as the paucity of clinical cases of smartphone ACD, in contrast to the slew of traditional phone ACD reports [179, 180, 195, 198, 201,202,203, 205, 209]. There are multiple possible explanations for this phenomenon. The most simple is that changes in phone design and production are resulting in phones that release less allergenic metal. A second possibility is that the European Nickel Directive limiting the amount of nickel that can be released from items in prolonged contact with the skin to 0.5 mcg nickel/cm2/week was extended to include mobile phones in 2009, thus prompting a change in mobile phone manufacturing practices [216]. It is also possible that the discrepancy in smartphone vs. traditional mobile phone metal ACD reporting is secondary to a publication bias that reduces continued mobile phone ACD reporting due to perceived un-originality. Interestingly it has been reported that the relatively new iPhone5 does, in fact, release nickel [217].
6.2 Laptops
The first case of metal laptop ACD was published in 2012 by Jensen et al. He described a case of a 50-year-old woman who developed a pruritic vesicular dermatitis on the ulnar surfaces of both hands after extensive use of a Macintosh laptop. The laptop released nickel by DMG testing and she was found to be nickel allergic [6]. A second case was reported two years later in a 11-year-old boy with recalcitrant generalized dermatitis most severe on the wrists and antecubital fossae found to be allergic to his nickel-releasing laptop [218].
Prompted by this first case report, an exposure study focusing specifically on Macintosh brand laptops was performed in 2012. It found that 7/20 (35%) MacBook laptops released nickel. Interestingly the 20 different models encompassed only 3 different models [7]. No explanation for these discrepant results was offered in the original study; however, none of the seven nickel-releasing laptops were over one-year-old in contrast to the 9 of 113 (69%) non-nickel-releasing laptops that were 2 years or older—suggesting that Macintosh laptops may release less and less nickel as they are used. A more recent laptop exposure study evaluating laptops from five different brands found that 12/31 (39%) released nickel by DMG testing and 2/31 (6%) released cobalt by the cobalt spot test [219]. Similar to the previous study only 8% (1/12) of the nickel-releasing laptops were 2 years or older, in contrast to the 68% (13/19) of the non-nickel-releasing laptops. Additionally, in this study one nickel-releasing laptop was tested in the same location repeatedly with the DMG test and after ten testing cycles the laptop no longer released nickel at that location, further evidencing that nickel is likely used predominantly in surface layers of these laptops and may wear off after prolonged use. A third laptop exposure study performed in Sweden found that 13/14 (100%) of laptops released nickel by DMG testing [191].
Two studies have evaluated computer mice for nickel release. In one, six Macintosh computer mice were evaluated for nickel release and all were positive [7]. In the second, 1/8 (13%) computer mice from 5 different brands released nickel by DMG. No clinical metal ACD from computer mice has yet been reported; other allergens such as phthalates and acrylates have been reported as causes of computer mice ACD [220].
6.3 Other Technological Devices
Like mobile phones and laptop computers, other technological devices such as tablets, fitness trackers, and videogame systems are increasingly ubiquitous. However, given their relative novelty in modern society there is relatively little in the way of clinical or exposure studies published. Generalized dermatitis thought to be secondary to nickel ACD from a nickel-releasing tablet was reported in an 11-year-old boy [221]. In another case report, worsening atopic dermatitis in a 9-year-old boy was attributed to nickel ACD from a nickel-releasing button on an Xbox controller [222]. No systematic exposure studies evaluating tablets or video game systems have yet been performed, nor have any robust case series been published.
Wearable fitness trackers have received much attention in the media due to perceived skin intolerance and possible allergic reactions. The popular fitness tracker Fitbit issued a recall in 2014 at first thought to be secondary to nickel ACD but eventually confirmed by the manufacturer to be primarily an issue with ACD to acrylates used in the band adhesive (http://www.fitbit.com/dk/forcesupport, last accessed January 2017). It seems like none of these cases, however, were ever published in the medical literature. Similarly, no confirmed metal ACD cases to wearable fitness trackers have been reported. Contact urticaria has been reported after contact with an Apple brand smart watch but neither the watch nor patient was tested for nickel release/sensitivity [223]. One recent exposure study did find that 1/8 (13%) selected wearable fitness trackers did release nickel [191], given that nickel release from watches can elicit ACD in nickel-sensitive individuals, it is not unlikely that nickel-releasing fitness trackers may as well [20, 41, 180].
7 Specific Pediatric Concerns
The pediatric population seems to be at particular risk of metal ACD from daily-use objects. Nickel ACD in children is especially common in the United States, with estimates of nickel contact allergy over 25% in some populations [224], compared to ~20% or lower in pooled pediatric and adult populations [225]. This relationship is similar in Europe where estimates of nickel allergy prevalence are ~5% higher in pediatric versus pooled populations [226, 227]. Additionally, pediatric patients seem disproportionately represented in metal ACD case reports from daily-use objects, e.g. the majority of clothing snap ACD cases, laptop ACD and mobile phone ACD cases are reported in children.
Toys are an additional metal exposure source relatively unique to children. Toys were first noted in the literature in 2009 as a potential cause of nickel exposure in children, when a plush toy and toy purse were found to have nickel-releasing components by DMG testing [228]. This prompted a second study that found nickel released from a harmonica and other toy instruments [229]. The first large scale exposure study seeking to assess metal ion release from children’s toys was performed in 2014 and found that 73/212 (34%) of toys with metal components purchased from 8 different retail and online stores in the United States and Denmark released nickel by DMG [230]. None released cobalt. This exposure study also described three cases of nickel toy ACD, and is, to the best of our knowledge, the first report of toy metal ACD. Since then another case of metal ACD has been reported: copper ACD in a child who often played with copper-containing die-cast cars [89]. Another exposure study found 11/24 (46%) of metallic toys and toy jewelry available for purchase in the United States contained over 930 mg/kg nickel (the EU limit for scrapped toy material) [231]. Interestingly, this study also found significant chromium content (968 mg/kg) in red paint scrapings from a toy car. An exposure study performed on textile-containing toys in Turkey found that 9/9 (100%) of toys contained nickel at levels of 0.4–21.11 mg/kg by atomic absorption spectrometry, although they did not test for nickel release [232]. Toy make-up has also been assessed for allergenic metal content; an Italian study that analyzed 52 toy make-ups with atomic absorption spectroscopy found more than 5 ppm of nickel in 14/52 (27%), more than 5 ppm of chromium in 28/52 (54%), and over 5 ppm of cobalt in 5/52 (10%) toy make-ups [233]. Other specific pediatric everyday use objects known to cause metal ACD include studs on school chairs [234,235,236], orthodontic equipment [237], school-issued musical instruments [238], and pediatric sports equipment [150]. More general pediatric metal allergy is discussed further elsewhere (see Chap. 37).
8 Conclusion and Clinical Considerations
Items with prolonged skin contact, such as jewelry, are more common sources of relevant metal allergen exposure, compared to items with intermittent or transient contact, such as toys or keys. Exposures also are constantly changing, and a permanent definitive list of metal exposures is impossible. However, common metal allergens may be found in many daily-use objects which the clinician should keep in mind (see Table 13.5). Additionally, occupational and consumer exposures may overlap, so basic understanding of occupational metal allergy may also inform consumer metal allergy. In short, metal allergy is very common and clinicians should investigate any metallic item or dyed item as a potential source of exposure to consumers with positive metal patch tests.
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Hamann, C.R., Hamann, D. (2018). Metals in Everyday Life. In: Chen, J., Thyssen, J. (eds) Metal Allergy. Springer, Cham. https://doi.org/10.1007/978-3-319-58503-1_13
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