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 that patients should avoid when allergic to a specific allergen. Mechanism of Allergic Contact Dermatitis Allergic contact dermatitis (ACD) is an important disease with high impact in terms of patient morbidity and economics. ACD represents a T helper cell Type 1 (Th1)-dependent delayed-type (Type IV) hypersensitivity reaction. Most instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Da that link to proteins in the skin to form complete antigens. The exception to this are the metallic salts, such as nickel and cobalt, which complex with proteins similar to the binding of cobalt and vitamin B12.1 On direct antigen exposure to the skin or mucosa, an immunologic cascade is initiated that includes cytokines, such as interleukin 2 (IL-2) and interferon gamma (IFN-gamma), T cells, and Langerhan cells. This complex interaction leads to the clinical picture of ACD. Clinical Illustration A patient diagnosed with cobalt allergy by T.R.U.E testing was referred by orthopedics to the University of Miami Allergic Contact Dermatitis Clinic for a comprehensive “metals” evaluation prior to undergoing bilateral knee replacement surgery. The man had suffered oral erosions attributed to the cobalt in his dental prosthetics. Notably, clinical resolution followed complete removal of all metals from his oral cavity. The History of Cobalt and Dentistry To first understand the nature of the association between cobalt and dentistry, we first must explore the history of dental fillings. Since the 16th century, it has been recorded that people have had cavities in teeth filled. Some early materials used to fill cavities include lead, cork, stone chips and gold foil. Gold leaf was introduced as a filling agent by Arculanus (Giovanni d’ Arcoli) in 1848 followed by sponge gold in 1853 and cohesive gold in 1855. With the invention of the dental drill in 1871, there was an increased demand for inexpensive fillings. This provided impetus for the development of the first alloy fillings made from silver coins mixed with mercury. This mixture was poor in quality and prompted a decade of controversy over the effectiveness of mercury in dental fillings. Finally, in 1895, the alloy mixture was standardized to what we know today as dental amalgam.4 Today, amalgam fillings typically comprise 50% pure elemental mercury, 35% silver, 13% tin, 2% copper and a trace of zinc. The silver metal powder reacts with liquid mercury to produce an alloy that provides a flexible material that can be easily packed and shaped. More than 100 years ago, it was discovered that the addition of tin prevented excess expansion of this paste, but the tin-mercury interaction produced a byproduct that caused the breakdown of the filling. Adding copper to the mix resulted in preventing the tin-mercury degradation reaction, and the compatable dental amalgam base mixture still used today was formed.5 This base is often modified with materials such as cobalt in order to increase resistance to enzymatic breakdown, which is a reliable feature for prostheses, dental fillings, crowns, bridges and dentures. Cobalt has been implicated in amalgam-related oral hypersensitivity reactions. Oral lichenoid lesions (OLL) associated with amalgam fillings have been shown to have a combined sensitization to mercury and other metal salts within the amalgam.2 The efflux of these metal ions from amalgams/restorations and their penetration into dental tissues result in significant ion concentrations in both enamel and dentin.3 However, unlike the standard metal- associated ACD, the diagnosis of cobalt allergy is more difficult to make. Due to its association with nickel and its frequent combination with nickel in alloys, it is speculated that the cobalt-specific allergic reactions are often secondary to co-sensitization and/or cross-reactivity with nickel.6 Thus, a pure sample of nickel-free cobalt is essential in an epicutaneous patch test to establish an accurate diagnosis of cobalt ACD. Initially discovered in 1735, cobalt is a byproduct of nickel, silver, lead, copper and iron ores, from which it is most frequently obtained. It is a brittle, hard white metal often found naturally in soil, dust and seawater. The metal itself is relatively inert, making it well suited as a key ingredient in aircraft engines, and metal-plated objects such as buckles, zippers and utensils. Industries have used cobalt’s unique binding properties to create drills, cutting tools and mechanical parts. Interestingly, when exposed to high temperature cobalt gradually converts to a deep blue-colored oxide, CoO, which is often used in glass, pottery and porcelain, thus coining the term cobalt blue. Furthermore, cobalt is also inherent to the synthesis of vitamin B12. Vitamin B12, appropriately named cobalamin, is the only vitamin requiring a metal, trivalent cobalt, for its synthesis.7 Clinical Importance of Testing for Cobalt Sensitivity Allergen patch testing for cobalt can be accomplished with the T.R.U.E. test [site #12]. This patch test screening tool uses a pure sample of cobalt dichlorate. Our patient provides an illustration of the utility and inherent value of patch testing because artificial knees frequently contain cobalt, chromates, copper or titanium. Once the metal sensitivities are known, the patient can receive a custom composite knee. After an allergen is identified, patient education is of the utmost importance because the mainstay of treatment for allergic contact dermatitis is avoidance. Patch testing support, as well as patient education materials, are provided by the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column.
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Focus on T.R.U.E. Test Allergen #12: Cobalt
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 that patients should avoid when allergic to a specific allergen. Mechanism of Allergic Contact Dermatitis Allergic contact dermatitis (ACD) is an important disease with high impact in terms of patient morbidity and economics. ACD represents a T helper cell Type 1 (Th1)-dependent delayed-type (Type IV) hypersensitivity reaction. Most instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Da that link to proteins in the skin to form complete antigens. The exception to this are the metallic salts, such as nickel and cobalt, which complex with proteins similar to the binding of cobalt and vitamin B12.1 On direct antigen exposure to the skin or mucosa, an immunologic cascade is initiated that includes cytokines, such as interleukin 2 (IL-2) and interferon gamma (IFN-gamma), T cells, and Langerhan cells. This complex interaction leads to the clinical picture of ACD. Clinical Illustration A patient diagnosed with cobalt allergy by T.R.U.E testing was referred by orthopedics to the University of Miami Allergic Contact Dermatitis Clinic for a comprehensive “metals” evaluation prior to undergoing bilateral knee replacement surgery. The man had suffered oral erosions attributed to the cobalt in his dental prosthetics. Notably, clinical resolution followed complete removal of all metals from his oral cavity. The History of Cobalt and Dentistry To first understand the nature of the association between cobalt and dentistry, we first must explore the history of dental fillings. Since the 16th century, it has been recorded that people have had cavities in teeth filled. Some early materials used to fill cavities include lead, cork, stone chips and gold foil. Gold leaf was introduced as a filling agent by Arculanus (Giovanni d’ Arcoli) in 1848 followed by sponge gold in 1853 and cohesive gold in 1855. With the invention of the dental drill in 1871, there was an increased demand for inexpensive fillings. This provided impetus for the development of the first alloy fillings made from silver coins mixed with mercury. This mixture was poor in quality and prompted a decade of controversy over the effectiveness of mercury in dental fillings. Finally, in 1895, the alloy mixture was standardized to what we know today as dental amalgam.4 Today, amalgam fillings typically comprise 50% pure elemental mercury, 35% silver, 13% tin, 2% copper and a trace of zinc. The silver metal powder reacts with liquid mercury to produce an alloy that provides a flexible material that can be easily packed and shaped. More than 100 years ago, it was discovered that the addition of tin prevented excess expansion of this paste, but the tin-mercury interaction produced a byproduct that caused the breakdown of the filling. Adding copper to the mix resulted in preventing the tin-mercury degradation reaction, and the compatable dental amalgam base mixture still used today was formed.5 This base is often modified with materials such as cobalt in order to increase resistance to enzymatic breakdown, which is a reliable feature for prostheses, dental fillings, crowns, bridges and dentures. Cobalt has been implicated in amalgam-related oral hypersensitivity reactions. Oral lichenoid lesions (OLL) associated with amalgam fillings have been shown to have a combined sensitization to mercury and other metal salts within the amalgam.2 The efflux of these metal ions from amalgams/restorations and their penetration into dental tissues result in significant ion concentrations in both enamel and dentin.3 However, unlike the standard metal- associated ACD, the diagnosis of cobalt allergy is more difficult to make. Due to its association with nickel and its frequent combination with nickel in alloys, it is speculated that the cobalt-specific allergic reactions are often secondary to co-sensitization and/or cross-reactivity with nickel.6 Thus, a pure sample of nickel-free cobalt is essential in an epicutaneous patch test to establish an accurate diagnosis of cobalt ACD. Initially discovered in 1735, cobalt is a byproduct of nickel, silver, lead, copper and iron ores, from which it is most frequently obtained. It is a brittle, hard white metal often found naturally in soil, dust and seawater. The metal itself is relatively inert, making it well suited as a key ingredient in aircraft engines, and metal-plated objects such as buckles, zippers and utensils. Industries have used cobalt’s unique binding properties to create drills, cutting tools and mechanical parts. Interestingly, when exposed to high temperature cobalt gradually converts to a deep blue-colored oxide, CoO, which is often used in glass, pottery and porcelain, thus coining the term cobalt blue. Furthermore, cobalt is also inherent to the synthesis of vitamin B12. Vitamin B12, appropriately named cobalamin, is the only vitamin requiring a metal, trivalent cobalt, for its synthesis.7 Clinical Importance of Testing for Cobalt Sensitivity Allergen patch testing for cobalt can be accomplished with the T.R.U.E. test [site #12]. This patch test screening tool uses a pure sample of cobalt dichlorate. Our patient provides an illustration of the utility and inherent value of patch testing because artificial knees frequently contain cobalt, chromates, copper or titanium. Once the metal sensitivities are known, the patient can receive a custom composite knee. After an allergen is identified, patient education is of the utmost importance because the mainstay of treatment for allergic contact dermatitis is avoidance. Patch testing support, as well as patient education materials, are provided by the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column.
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 that patients should avoid when allergic to a specific allergen. Mechanism of Allergic Contact Dermatitis Allergic contact dermatitis (ACD) is an important disease with high impact in terms of patient morbidity and economics. ACD represents a T helper cell Type 1 (Th1)-dependent delayed-type (Type IV) hypersensitivity reaction. Most instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Da that link to proteins in the skin to form complete antigens. The exception to this are the metallic salts, such as nickel and cobalt, which complex with proteins similar to the binding of cobalt and vitamin B12.1 On direct antigen exposure to the skin or mucosa, an immunologic cascade is initiated that includes cytokines, such as interleukin 2 (IL-2) and interferon gamma (IFN-gamma), T cells, and Langerhan cells. This complex interaction leads to the clinical picture of ACD. Clinical Illustration A patient diagnosed with cobalt allergy by T.R.U.E testing was referred by orthopedics to the University of Miami Allergic Contact Dermatitis Clinic for a comprehensive “metals” evaluation prior to undergoing bilateral knee replacement surgery. The man had suffered oral erosions attributed to the cobalt in his dental prosthetics. Notably, clinical resolution followed complete removal of all metals from his oral cavity. The History of Cobalt and Dentistry To first understand the nature of the association between cobalt and dentistry, we first must explore the history of dental fillings. Since the 16th century, it has been recorded that people have had cavities in teeth filled. Some early materials used to fill cavities include lead, cork, stone chips and gold foil. Gold leaf was introduced as a filling agent by Arculanus (Giovanni d’ Arcoli) in 1848 followed by sponge gold in 1853 and cohesive gold in 1855. With the invention of the dental drill in 1871, there was an increased demand for inexpensive fillings. This provided impetus for the development of the first alloy fillings made from silver coins mixed with mercury. This mixture was poor in quality and prompted a decade of controversy over the effectiveness of mercury in dental fillings. Finally, in 1895, the alloy mixture was standardized to what we know today as dental amalgam.4 Today, amalgam fillings typically comprise 50% pure elemental mercury, 35% silver, 13% tin, 2% copper and a trace of zinc. The silver metal powder reacts with liquid mercury to produce an alloy that provides a flexible material that can be easily packed and shaped. More than 100 years ago, it was discovered that the addition of tin prevented excess expansion of this paste, but the tin-mercury interaction produced a byproduct that caused the breakdown of the filling. Adding copper to the mix resulted in preventing the tin-mercury degradation reaction, and the compatable dental amalgam base mixture still used today was formed.5 This base is often modified with materials such as cobalt in order to increase resistance to enzymatic breakdown, which is a reliable feature for prostheses, dental fillings, crowns, bridges and dentures. Cobalt has been implicated in amalgam-related oral hypersensitivity reactions. Oral lichenoid lesions (OLL) associated with amalgam fillings have been shown to have a combined sensitization to mercury and other metal salts within the amalgam.2 The efflux of these metal ions from amalgams/restorations and their penetration into dental tissues result in significant ion concentrations in both enamel and dentin.3 However, unlike the standard metal- associated ACD, the diagnosis of cobalt allergy is more difficult to make. Due to its association with nickel and its frequent combination with nickel in alloys, it is speculated that the cobalt-specific allergic reactions are often secondary to co-sensitization and/or cross-reactivity with nickel.6 Thus, a pure sample of nickel-free cobalt is essential in an epicutaneous patch test to establish an accurate diagnosis of cobalt ACD. Initially discovered in 1735, cobalt is a byproduct of nickel, silver, lead, copper and iron ores, from which it is most frequently obtained. It is a brittle, hard white metal often found naturally in soil, dust and seawater. The metal itself is relatively inert, making it well suited as a key ingredient in aircraft engines, and metal-plated objects such as buckles, zippers and utensils. Industries have used cobalt’s unique binding properties to create drills, cutting tools and mechanical parts. Interestingly, when exposed to high temperature cobalt gradually converts to a deep blue-colored oxide, CoO, which is often used in glass, pottery and porcelain, thus coining the term cobalt blue. Furthermore, cobalt is also inherent to the synthesis of vitamin B12. Vitamin B12, appropriately named cobalamin, is the only vitamin requiring a metal, trivalent cobalt, for its synthesis.7 Clinical Importance of Testing for Cobalt Sensitivity Allergen patch testing for cobalt can be accomplished with the T.R.U.E. test [site #12]. This patch test screening tool uses a pure sample of cobalt dichlorate. Our patient provides an illustration of the utility and inherent value of patch testing because artificial knees frequently contain cobalt, chromates, copper or titanium. Once the metal sensitivities are known, the patient can receive a custom composite knee. After an allergen is identified, patient education is of the utmost importance because the mainstay of treatment for allergic contact dermatitis is avoidance. Patch testing support, as well as patient education materials, are provided by the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column.
