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Allergen Focus

Focus on T.R.U.E. Test Allergen #1: Nickel

May 2005

T he thin-layer rapid-use epicutaneous (T.R.U.E) test of 23 common allergens is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where exactly a specific allergen is derived or what products should be avoided by patients who are allergic to that allergen. With this in mind, this column was developed to provide more educational information about the T.R.U.E. test allergens. A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight products patients should avoid when allergic to a specific allergen. Contact Dermatides Allergic Contact Dermatitis (ACD) is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental- and occupational-based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis; the foremost example of this would be latex hypersensitivity. Although this is beyond the scope of this section, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 The primary focus of this section is to highlight the educational component of allergic contact dermatitis. Clinical Illustration Our patient presented with a history of severe eyelid dermatitis. Specifically, her condition gradually worsened throughout the week at work with improvement during each weekend. She had given up all cosmeceuticals, soaps, lotions, medical creams and jewelry and was only using white petrolatum on her eyelids. Notably, she was first seen after work and was wearing an identification badge on a work-provided ball-socket chain, which she intermittently rolled in her fingers during the initial history. History of Nickel Nickel is the twenty-fourth most abundant element in the earth’s crust, comprising about 3% of the composition of the earth.3 In 1751, the Swedish chemist A. F. Cronstedt isolated nickel and denoted it as the element number 28 on the Periodic Table of Elements, where it is referred to as Ni.3 The name nickel comes from the German word kupfernickel, meaning devil’s copper or false copper. Historically, this silver-white metal has been used by man since antiquity for many reasons, for example, as a natural alloy for weaponry and armor.3 Notably in 1865, J. F. Wharton produced a malleable form of nickel for the now obsolete U.S. 3-cent piece. During World War II, nickel was highly valued for its use in vehicle armor plating, resulting in the removal of this metal from the five-cent piece in 1942. From that year, and lasting through the end of 1945, five-cent pieces were minted from an alloy of copper, silver and manganese. These coins now have a copper core, and an outer layer, the “clad,” is made of 75% copper and 25% copper-nickel alloy.4 (See Table I above: “Coins that Include Nickel.”) In the early 20th century, nickel sulfate was recommended as a medicinal agent for the treatment of chorea, epilepsy, migraine and neuralgia.3 Conversely, it wasn’t until the 1930s that nickel became recognized as a cause of contact dermatitis. Today, nickel is the most prevalent allergen detected by both the T.R.U.E. test and the North American Contact Dermatitis Group [NACDG], with a prevalence rate of approximately 14%.5,6 Clinically, nickel ACD can present as a pruritic, papular or papulovesicular dermatitis and when chronic, with lichenification. In children, ACD to nickel classically occurs on the earlobes, neck, wrists, and infra-umbilical area (corresponding to blue jean snaps). It is important to notice that women are more frequently affected than men, probably due to increased exposure because of jewelry, brassiere underwires, etc. Sweat can readily dissolve nickel and the corrosion of metallic nickel or nickel-bearing alloys combined with pressure, sweat, moisture and friction can increase the severity of nickel hypersensitivity.3 Interestingly, when nickel is compounded as stainless steel, it is so firmly bound that it does not leach out at levels significant enough to cause dermatitis. Today, this metal is widely used for producing nickel alloys and nickel cast iron. Subsequently, potential exposure sources include: zippers, safety pins, doorknobs, keys, scissors, bracelets, eyelash curlers, belt buckles, metal eyeglass frames, razors, thimbles, coins, tools, appliances, household utensils, alkaline batteries, and many more. Ear piercing is a major source of nickel sensitization: first, through the piercing procedure itself and then through subsequent use of nickel containing jewelry.7 Diet and inhalation (smoking/industrial) also represent significant sources of exposure. Most foods contain <0.5 mg Ni/kg wet weight, however certain ones contain notably higher concentrations. (See Table II: “Some Foods to Avoid that Contain Nickel.”) In sensitized patients, dietary nickel can cause a relapse or generalization of their dermatitis. In a study involving nickel-sensitive individuals, a low-nickel diet was effective in controlling the symptoms in 39.28% of the patients.8 Food processing and storage methods apparently add to the Ni levels already present in foodstuffs. The leaching of nickel from kitchen utensils, cookware and water pipes may add up to 1 mg to the daily intake of nickel.3 Smoking does represent a significant form of exposure since a typical cigarette contains 2.32 to 4.20 mg/kg Ni,9 and smoking one pack of cigarettes per day increases the daily amount of nickel inhaled by about 4 µg. In ambient air, the level of nickel is small [6 to 20 ng/m3], but higher levels are present in contaminated air (for example, foundries, sewage incinerators, diesel-fuel burners). Recycling products and processing the byproducts of copper mining are other exposure sources, as are electroplating and the output from glass and ceramic factories.3 The presence of nickel in some orthopedic prostheses can be as high as 35%.10 This is sufficient to induce ACD in nickel-sensitized individuals and the medical personnel working with these items.11 Testing for Nickel Sensitivity Patch testing for nickel allergy can be accomplished with the T.R.U.E. test [site #1]. The T.R.U.E test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that can be used by general dermatologists everywhere. In cases where the T.R.U.E. test is inadequate, the patient should undergo comprehensive patch testing. For now, the availability of comprehensive patch testing is limited, as suggested by the fact that the American Contact Dermatitis Society (ACDS) has roughly 450 members compared to the 14,000 members of the American Academy of Dermatology. Patch testing support, as well as patient education materials, can be obtained from the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). The Value of this Patient Case Our patient tested positive to nickel — importantly, so did her identification badge chain. Her eyelids were especially prone to dermatitis because of the more sensitive skin and the transfer of nickel particles from her fingers through rubbing. The presence of nickel in such a wide variety of products makes it an especially common, difficult-to-avoid, contactant in everyone’s daily activities. For this reason, “nickel spot tests” are commercially available for patients to test sources. This test uses dimethylglyoxime/ammonia [DMG-A]. When DMG-A is rubbed on a metallic surface, a pink precipitate forms if the nickel content is at least 1:10,000. This patient dramatically improved on a nickel avoidance regimen. This case illustrates the importance of appropriate patch testing and that subsequent patient education can not be overstated. ACD is a treatable disease once the allergen is identified and avoided.

T he thin-layer rapid-use epicutaneous (T.R.U.E) test of 23 common allergens is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where exactly a specific allergen is derived or what products should be avoided by patients who are allergic to that allergen. With this in mind, this column was developed to provide more educational information about the T.R.U.E. test allergens. A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight products patients should avoid when allergic to a specific allergen. Contact Dermatides Allergic Contact Dermatitis (ACD) is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental- and occupational-based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis; the foremost example of this would be latex hypersensitivity. Although this is beyond the scope of this section, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 The primary focus of this section is to highlight the educational component of allergic contact dermatitis. Clinical Illustration Our patient presented with a history of severe eyelid dermatitis. Specifically, her condition gradually worsened throughout the week at work with improvement during each weekend. She had given up all cosmeceuticals, soaps, lotions, medical creams and jewelry and was only using white petrolatum on her eyelids. Notably, she was first seen after work and was wearing an identification badge on a work-provided ball-socket chain, which she intermittently rolled in her fingers during the initial history. History of Nickel Nickel is the twenty-fourth most abundant element in the earth’s crust, comprising about 3% of the composition of the earth.3 In 1751, the Swedish chemist A. F. Cronstedt isolated nickel and denoted it as the element number 28 on the Periodic Table of Elements, where it is referred to as Ni.3 The name nickel comes from the German word kupfernickel, meaning devil’s copper or false copper. Historically, this silver-white metal has been used by man since antiquity for many reasons, for example, as a natural alloy for weaponry and armor.3 Notably in 1865, J. F. Wharton produced a malleable form of nickel for the now obsolete U.S. 3-cent piece. During World War II, nickel was highly valued for its use in vehicle armor plating, resulting in the removal of this metal from the five-cent piece in 1942. From that year, and lasting through the end of 1945, five-cent pieces were minted from an alloy of copper, silver and manganese. These coins now have a copper core, and an outer layer, the “clad,” is made of 75% copper and 25% copper-nickel alloy.4 (See Table I above: “Coins that Include Nickel.”) In the early 20th century, nickel sulfate was recommended as a medicinal agent for the treatment of chorea, epilepsy, migraine and neuralgia.3 Conversely, it wasn’t until the 1930s that nickel became recognized as a cause of contact dermatitis. Today, nickel is the most prevalent allergen detected by both the T.R.U.E. test and the North American Contact Dermatitis Group [NACDG], with a prevalence rate of approximately 14%.5,6 Clinically, nickel ACD can present as a pruritic, papular or papulovesicular dermatitis and when chronic, with lichenification. In children, ACD to nickel classically occurs on the earlobes, neck, wrists, and infra-umbilical area (corresponding to blue jean snaps). It is important to notice that women are more frequently affected than men, probably due to increased exposure because of jewelry, brassiere underwires, etc. Sweat can readily dissolve nickel and the corrosion of metallic nickel or nickel-bearing alloys combined with pressure, sweat, moisture and friction can increase the severity of nickel hypersensitivity.3 Interestingly, when nickel is compounded as stainless steel, it is so firmly bound that it does not leach out at levels significant enough to cause dermatitis. Today, this metal is widely used for producing nickel alloys and nickel cast iron. Subsequently, potential exposure sources include: zippers, safety pins, doorknobs, keys, scissors, bracelets, eyelash curlers, belt buckles, metal eyeglass frames, razors, thimbles, coins, tools, appliances, household utensils, alkaline batteries, and many more. Ear piercing is a major source of nickel sensitization: first, through the piercing procedure itself and then through subsequent use of nickel containing jewelry.7 Diet and inhalation (smoking/industrial) also represent significant sources of exposure. Most foods contain <0.5 mg Ni/kg wet weight, however certain ones contain notably higher concentrations. (See Table II: “Some Foods to Avoid that Contain Nickel.”) In sensitized patients, dietary nickel can cause a relapse or generalization of their dermatitis. In a study involving nickel-sensitive individuals, a low-nickel diet was effective in controlling the symptoms in 39.28% of the patients.8 Food processing and storage methods apparently add to the Ni levels already present in foodstuffs. The leaching of nickel from kitchen utensils, cookware and water pipes may add up to 1 mg to the daily intake of nickel.3 Smoking does represent a significant form of exposure since a typical cigarette contains 2.32 to 4.20 mg/kg Ni,9 and smoking one pack of cigarettes per day increases the daily amount of nickel inhaled by about 4 µg. In ambient air, the level of nickel is small [6 to 20 ng/m3], but higher levels are present in contaminated air (for example, foundries, sewage incinerators, diesel-fuel burners). Recycling products and processing the byproducts of copper mining are other exposure sources, as are electroplating and the output from glass and ceramic factories.3 The presence of nickel in some orthopedic prostheses can be as high as 35%.10 This is sufficient to induce ACD in nickel-sensitized individuals and the medical personnel working with these items.11 Testing for Nickel Sensitivity Patch testing for nickel allergy can be accomplished with the T.R.U.E. test [site #1]. The T.R.U.E test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that can be used by general dermatologists everywhere. In cases where the T.R.U.E. test is inadequate, the patient should undergo comprehensive patch testing. For now, the availability of comprehensive patch testing is limited, as suggested by the fact that the American Contact Dermatitis Society (ACDS) has roughly 450 members compared to the 14,000 members of the American Academy of Dermatology. Patch testing support, as well as patient education materials, can be obtained from the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). The Value of this Patient Case Our patient tested positive to nickel — importantly, so did her identification badge chain. Her eyelids were especially prone to dermatitis because of the more sensitive skin and the transfer of nickel particles from her fingers through rubbing. The presence of nickel in such a wide variety of products makes it an especially common, difficult-to-avoid, contactant in everyone’s daily activities. For this reason, “nickel spot tests” are commercially available for patients to test sources. This test uses dimethylglyoxime/ammonia [DMG-A]. When DMG-A is rubbed on a metallic surface, a pink precipitate forms if the nickel content is at least 1:10,000. This patient dramatically improved on a nickel avoidance regimen. This case illustrates the importance of appropriate patch testing and that subsequent patient education can not be overstated. ACD is a treatable disease once the allergen is identified and avoided.

T he thin-layer rapid-use epicutaneous (T.R.U.E) test of 23 common allergens is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where exactly a specific allergen is derived or what products should be avoided by patients who are allergic to that allergen. With this in mind, this column was developed to provide more educational information about the T.R.U.E. test allergens. A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight products patients should avoid when allergic to a specific allergen. Contact Dermatides Allergic Contact Dermatitis (ACD) is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental- and occupational-based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis; the foremost example of this would be latex hypersensitivity. Although this is beyond the scope of this section, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 The primary focus of this section is to highlight the educational component of allergic contact dermatitis. Clinical Illustration Our patient presented with a history of severe eyelid dermatitis. Specifically, her condition gradually worsened throughout the week at work with improvement during each weekend. She had given up all cosmeceuticals, soaps, lotions, medical creams and jewelry and was only using white petrolatum on her eyelids. Notably, she was first seen after work and was wearing an identification badge on a work-provided ball-socket chain, which she intermittently rolled in her fingers during the initial history. History of Nickel Nickel is the twenty-fourth most abundant element in the earth’s crust, comprising about 3% of the composition of the earth.3 In 1751, the Swedish chemist A. F. Cronstedt isolated nickel and denoted it as the element number 28 on the Periodic Table of Elements, where it is referred to as Ni.3 The name nickel comes from the German word kupfernickel, meaning devil’s copper or false copper. Historically, this silver-white metal has been used by man since antiquity for many reasons, for example, as a natural alloy for weaponry and armor.3 Notably in 1865, J. F. Wharton produced a malleable form of nickel for the now obsolete U.S. 3-cent piece. During World War II, nickel was highly valued for its use in vehicle armor plating, resulting in the removal of this metal from the five-cent piece in 1942. From that year, and lasting through the end of 1945, five-cent pieces were minted from an alloy of copper, silver and manganese. These coins now have a copper core, and an outer layer, the “clad,” is made of 75% copper and 25% copper-nickel alloy.4 (See Table I above: “Coins that Include Nickel.”) In the early 20th century, nickel sulfate was recommended as a medicinal agent for the treatment of chorea, epilepsy, migraine and neuralgia.3 Conversely, it wasn’t until the 1930s that nickel became recognized as a cause of contact dermatitis. Today, nickel is the most prevalent allergen detected by both the T.R.U.E. test and the North American Contact Dermatitis Group [NACDG], with a prevalence rate of approximately 14%.5,6 Clinically, nickel ACD can present as a pruritic, papular or papulovesicular dermatitis and when chronic, with lichenification. In children, ACD to nickel classically occurs on the earlobes, neck, wrists, and infra-umbilical area (corresponding to blue jean snaps). It is important to notice that women are more frequently affected than men, probably due to increased exposure because of jewelry, brassiere underwires, etc. Sweat can readily dissolve nickel and the corrosion of metallic nickel or nickel-bearing alloys combined with pressure, sweat, moisture and friction can increase the severity of nickel hypersensitivity.3 Interestingly, when nickel is compounded as stainless steel, it is so firmly bound that it does not leach out at levels significant enough to cause dermatitis. Today, this metal is widely used for producing nickel alloys and nickel cast iron. Subsequently, potential exposure sources include: zippers, safety pins, doorknobs, keys, scissors, bracelets, eyelash curlers, belt buckles, metal eyeglass frames, razors, thimbles, coins, tools, appliances, household utensils, alkaline batteries, and many more. Ear piercing is a major source of nickel sensitization: first, through the piercing procedure itself and then through subsequent use of nickel containing jewelry.7 Diet and inhalation (smoking/industrial) also represent significant sources of exposure. Most foods contain <0.5 mg Ni/kg wet weight, however certain ones contain notably higher concentrations. (See Table II: “Some Foods to Avoid that Contain Nickel.”) In sensitized patients, dietary nickel can cause a relapse or generalization of their dermatitis. In a study involving nickel-sensitive individuals, a low-nickel diet was effective in controlling the symptoms in 39.28% of the patients.8 Food processing and storage methods apparently add to the Ni levels already present in foodstuffs. The leaching of nickel from kitchen utensils, cookware and water pipes may add up to 1 mg to the daily intake of nickel.3 Smoking does represent a significant form of exposure since a typical cigarette contains 2.32 to 4.20 mg/kg Ni,9 and smoking one pack of cigarettes per day increases the daily amount of nickel inhaled by about 4 µg. In ambient air, the level of nickel is small [6 to 20 ng/m3], but higher levels are present in contaminated air (for example, foundries, sewage incinerators, diesel-fuel burners). Recycling products and processing the byproducts of copper mining are other exposure sources, as are electroplating and the output from glass and ceramic factories.3 The presence of nickel in some orthopedic prostheses can be as high as 35%.10 This is sufficient to induce ACD in nickel-sensitized individuals and the medical personnel working with these items.11 Testing for Nickel Sensitivity Patch testing for nickel allergy can be accomplished with the T.R.U.E. test [site #1]. The T.R.U.E test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that can be used by general dermatologists everywhere. In cases where the T.R.U.E. test is inadequate, the patient should undergo comprehensive patch testing. For now, the availability of comprehensive patch testing is limited, as suggested by the fact that the American Contact Dermatitis Society (ACDS) has roughly 450 members compared to the 14,000 members of the American Academy of Dermatology. Patch testing support, as well as patient education materials, can be obtained from the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). The Value of this Patient Case Our patient tested positive to nickel — importantly, so did her identification badge chain. Her eyelids were especially prone to dermatitis because of the more sensitive skin and the transfer of nickel particles from her fingers through rubbing. The presence of nickel in such a wide variety of products makes it an especially common, difficult-to-avoid, contactant in everyone’s daily activities. For this reason, “nickel spot tests” are commercially available for patients to test sources. This test uses dimethylglyoxime/ammonia [DMG-A]. When DMG-A is rubbed on a metallic surface, a pink precipitate forms if the nickel content is at least 1:10,000. This patient dramatically improved on a nickel avoidance regimen. This case illustrates the importance of appropriate patch testing and that subsequent patient education can not be overstated. ACD is a treatable disease once the allergen is identified and avoided.