Allergic contact dermatitis is an important disease with a high impact both in terms of patient morbidity and economics. The contact dermatitides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria.
Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-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. While 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
Allergic contact dermatitis, on the other hand, is a delayed type IV hypersensitivity reaction. The primary focus of this section is to highlight the educational component of allergic contact dermatitis.
Clinical Illustration
A woman was referred to the Univer-sity of Miami Contact Dermatitis Clinic for evaluation of a longstanding generalized eczematous dermatitis with bilateral ectropion. Of note, she had noticed flares associated with cinnamon buns.
The History of Fragrance
Since ancient times, fragrances have had great cultural impact — from the burning of tree resin incenses in religious practices in China, Palestine and Egypt to refining the early Egyptian art of mummification.3 As early as the year 3000 BC, Egyptians “welcomed the gods” and sanctified their homes by burning the sacred temple incense, Kyphi, into their dwellings.4 The esteemed Kyphi was thought to hold the power to heal, alleviate anxieties, increase dreaming, eliminate sorrow, treat asthma and act as a general antidote for toxins.5
Perfume was first brought to Greece with the conquests of Alexander the Great in the fourth century BC.3 When Alexander entered the tent of the defeated King Darius III, after the battle of Issos, he is said to have added insult to injury by destroying the king’s box of priceless ointments and perfumes. As he traveled through Asia, he became so addicted to aromas and anointment oils that he sent deputies on quests across distant lands to Yemen and Oman to find the source of the Arabian incenses.5
Before the domination of other Mediterranean nations, the use of fragrances and perfumes by early Romans was very limited. With the arrival of the conquered people from the ‘Orient’ into Rome under Julius Caesar, Nero and Heliogabale came a large number of Asian and Greek perfumes.3 The consumption of great quantities of fragrances by the Romans in the first century AD was so vast that new trade routes to Arabia, India and China abounded to keep up with the demands.6
In the Book of Matthew 2:1, it is said that Three Wise Men (Kings) came “from the east to Jerusalem” bearing gifts to the Infant Jesus. Of note, two of the three gifts were fragrances — frankincense and myrrh — which were thought to be more valuable than the gift of gold. Interestingly, some scholars speculate that the third gift of gold, may have been the gold-colored fragrant ambergris.5
The Use of Fragrance Expands
During the enlightenment of the Renaissance era (1450-1600), with the backdrop of the Black Plague in Europe, the utility of fragrances expanded. The Citizens of Paris believed that the disease traveled in corrupted air, thus the most common antidote recommended against the poisoned atmosphere was aromatics, such as herbs, flowers and perfumes that were thought to be protective.7 Persons also walked the streets with “pockets full of posie” to ward of the petulance; likewise, court physicians treated wounds with applications of aromatized wines and perfumed lotions.3
In the 13th and 14th centuries, the explorations of Marco Polo, Christopher Columbus, and Vasco de Gamma into new lands tremendously boosted the spice trade. The American New World was a delight to the senses, offering the exquisite scents of balsam of Peru and Tolu, juniper, American cedar, sassafras, and vanilla to the Old World.5
Modern-Day Famous Fragrances
These same scents became some of the many essential ingredients for the perfume industry, whose growth saw to the rapid emergence of department stores in Europe and the United States in the 20th century. In 1921, the first designer perfume using artificial scents [synthetic floral aldehydes] was launched when Coco Chanel unveiled her timeless classic No. 5. Two series of numbered samples (1 to 5 and 20 to 24) were designed for Chanel, but she chose No. 5 because her couture collection was scheduled for presentation on the fifth day of the fifth month, which she correctly interpreted as a good omen.8
Likewise, in the midst of a Great Depression, Joy by Patou, “the most expensive perfume in the world”, enjoyed unparalleled success. The outbreak of World War II, fascism and commodity rationing, was met with Hollywood’s “star culture” heydays and “character fragrances”, such as Christian Dior’s New Look.
The evolution of fragrance had begun to define feminine American culture. By the early ’80s, the industry decided that men were ready for their own fragrances. New colognes hit the market with revved up sports car names, such as Camaro and Lamborghini GT. As the end of the millennium drew near, borders dissolved and unity was in the air, Calvin Klein captured this sentiment with his defining unisex fragrance, CK One.3
Animal-Derived Scents and Use of Synthetic Scents
Fragrances are defined as complex mixtures of natural and synthetic materials used for improving the quality of life for those who wear it, “presenting in their wearers with an opportunity to create for themselves a virtually unforgettable, personal trademark”.4
The natural ingredients are primarily distilled botanical extracts. There are, however, a few prized animal byproduct exceptions (e.g. ambergris, musk, civet, and castoreum). While these may have originated in the primal hunter’s respectful use of the whole animal, they became a highly valued commodity. For example, the sperm whale’s ambergris is a biliary concretion made to facilitate gastrointestinal passage of hard objects, such as inadvertently eaten bones.6,9
One of the most vivid descriptions of ambergris can be found in Melville’s Moby Dick: “Dropping his spade, he (Stubb) thrust both hands in, and drew out handfuls of something that looked like ripe Windsor soap, or rich mottled old cheese; very unctuous and savory withal. You might easily dent it with your thumb; it is of a hue between yellow and ash colour. And this, good friends, is ambergris, worth a gold guinea an ounce to any druggist . . . . . Who would think, then, that such fine ladies and gentlemen should regale themselves with an essence found in the inglorious bowels of a sick whale!”10
Whales are not the only animals prized for their scent-producing capabilities. Musk deer bucks and Canadian beavers have pheromone sacs in the front of their abdomen that secrete musk and castoreum, respectively.
To obtain the scent, the animal is sacrificed and the extracted and dried gland is then marketed as “musk in pod” (i.e. the whole glands) or “musk in grain” (in which the perfume has been extracted from its receptacle).9
Civet cats are also coveted for the civet that is excreted from their perianal glands. This musk, which the animal uses to mark its territory, is a prized commodity that’s forcefully expressed from the civet’s anal glands for use in the perfumery industry. When “blended to enhance other essences, the civet fecal odor becomes less disagreeable.”6
High price and scarcity of natural products, in addition to advances in the chemical industry, led to the development of synthetic ingredients. During the Industrial Revolution (1889 to 1910), major discoveries in synthetic fragrance chemicals were made: 1869 heliotropine, 1877 coumarin, 1888 artificial musk, 1890 vanillin, 1890 ionone, 1905 hydroxycitronellal.3
Currently, as many as 90% of available fragrances are synthetic chemicals rather than natural extracts, with more than 5,000 different compounds reported.11
Globally, the fragrance and flavor market sales are estimated to be between $12 billion and $15 billion per year. Perfume fragrances are thought to make up about $3 billion of the total.12
Who Is Affected by Fragrance Allergy and How?
Fragrances are found in a wide range of products that extend well beyond eau d’toilettes and colognes. These include cosmetics, cleaning supplies, medicaments, foods and flavored personal hygiene products.11,13 (See Table 1). Furthermore, cutting fluids, electroplating fluids, metalworking fluids, paints, rubber, plastics, insecticides, herbicides and additives used in air-conditioning water also contain fragrances.11
Fragrance allergy occurs predominantly in women, with a female-to-male ratio of 3-4:1, and may relate to an overall greater exposure to skincare products by women than men.6,13 This is not surprising since on average 30 to 50 chemicals are used to create the fragrance composition of a perfume, and complex formulations of upwards of 200 ingredients are not uncommon.4
Classic localizations for fragrance contact allergy are the face, behind the ears, the neck, the axilla, and hands.11
Severe reactions have also been reported from fragrance use. Thompson and Wansker reported a very rare case
of a 32-year-old female on prolonged corticosteroid therapy for nephrotic syndrome, who developed toxic epidermal necrolysis and ultimately died, after using a spray cologne.14
The importance of allergen concentration (i.e. occlusion), skin barrier (or disruption thereof, i.e. shaving) and constitutional factors are important risk factors in the likelihood of becoming sensitized and the extent of the clinical manifestation.11,13
Oral and perioral dermatitis are common to fragrance/flavoring allergens in toothpastes, chewing gums, mouthwashes and mentholated cigarettes.6 Besides direct contact with fragrances, “consort” or “connubial” contact dermatitis also can occur by contact with products used by partners, friends or co-workers, as well as airborne contact, and systemic exposure by inhalation and ingestion (flavor and spices in foods).11
Children may become sensitized to fragrances, especially through the use of baby products applied to areas of chronic dermatitis, such as diaper dermatitis.6
Increasing Rates of Sensitization
In fact, fragrances are the second-most common class of substances identified to cause allergic contact dermatitis, and
the most frequent cause of contact allergy to cosmetics. Cosmetics account for 30% to 45% of these allergic reactions, with perfumes accounting for 4% to 18% and deodorants/antiperspirants 5% to 17% of cases.11
Allergy to fragrance was first reported in the medical literature in 1957.15
Increasing rates of sensitization to perfumes called for fragrance identification measures to be established in late ’70s. Larsen proposed a mixture of ingredients as a screening tool for fragrance contact allergy, after identifying the eight primary substances present in the Mycolog cream.16 These fragrance ingredients are isoeugenol, eugenol, cinnamic aldehyde, cinnamic alcohol, hydroxycitronellal, geraniol, a-amyl cinnamic aldehyde, and oak moss absolute.13 This composite is still used today for fragrance screening, and in conjunction with balsam of Peru 90% of fragrance allergies are detected.17
Testing for Fragrance Mix Allergy
The fragrance mix is included on the T.R.U.E test panel 1.1, site #6. Additionally, it can be tested for through comprehensive testing with ‘fragrance mix’ 8% in petrolatum (5% sorbitan sesquiolate is added to this as an emulsifier, to increase penetration).
Using the later formulation, the North American Contact Dermatitis Group 2001-2002 patch test results showed fragrance mix as one of the 10 top allergens with a prevalence rate of 10.4%.21 Of note, the original testing composition was 16% in petrolatum (2% of each constituent); however, the concentration was lowered in 1984 to 8% (1% of each of these components) to reduce the risk of false positives.11
While fragrance mix is thought to be superior to balsam of Peru in detecting fragrance allergy in cosmetic products, false positive and false negative reactions do occur and clinical correlations should be made.9,11,13
The Value of This Patient Case
The patient was found to be allergic to fragrance and counseled on fragrance avoidance, which unfortunately is complicated by confusing terms and inadvertently misleading product labeling.
The term “unscented” generally refers to the addition of fragrance-masking chemicals, whereas fragrance-free refers to the absence of chemicals added to enhance aroma. Therefore, unscented and fragrance-free products are not synonymous.
Furthermore, according to the FDA code of federal regulations, title 21, volume 7, section 700.3(d), the term fragrance means any natural or synthetic substance or substances used solely to impart an odor to a cosmetic product.22
Strict adherence to the definition of a fragrance translates to the possibility “fragrance-free” labeled products containing fragrance based ingredients added to serve another purpose.23 For example, if a fragrance ingredient is added as a preservative or emollient, it could be included in a fragrance-free product.23
Our patient illustrates the importance of specific instruction on label reading and term definition.
Allergic contact dermatitis is an important disease with a high impact both in terms of patient morbidity and economics. The contact dermatitides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria.
Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-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. While 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
Allergic contact dermatitis, on the other hand, is a delayed type IV hypersensitivity reaction. The primary focus of this section is to highlight the educational component of allergic contact dermatitis.
Clinical Illustration
A woman was referred to the Univer-sity of Miami Contact Dermatitis Clinic for evaluation of a longstanding generalized eczematous dermatitis with bilateral ectropion. Of note, she had noticed flares associated with cinnamon buns.
The History of Fragrance
Since ancient times, fragrances have had great cultural impact — from the burning of tree resin incenses in religious practices in China, Palestine and Egypt to refining the early Egyptian art of mummification.3 As early as the year 3000 BC, Egyptians “welcomed the gods” and sanctified their homes by burning the sacred temple incense, Kyphi, into their dwellings.4 The esteemed Kyphi was thought to hold the power to heal, alleviate anxieties, increase dreaming, eliminate sorrow, treat asthma and act as a general antidote for toxins.5
Perfume was first brought to Greece with the conquests of Alexander the Great in the fourth century BC.3 When Alexander entered the tent of the defeated King Darius III, after the battle of Issos, he is said to have added insult to injury by destroying the king’s box of priceless ointments and perfumes. As he traveled through Asia, he became so addicted to aromas and anointment oils that he sent deputies on quests across distant lands to Yemen and Oman to find the source of the Arabian incenses.5
Before the domination of other Mediterranean nations, the use of fragrances and perfumes by early Romans was very limited. With the arrival of the conquered people from the ‘Orient’ into Rome under Julius Caesar, Nero and Heliogabale came a large number of Asian and Greek perfumes.3 The consumption of great quantities of fragrances by the Romans in the first century AD was so vast that new trade routes to Arabia, India and China abounded to keep up with the demands.6
In the Book of Matthew 2:1, it is said that Three Wise Men (Kings) came “from the east to Jerusalem” bearing gifts to the Infant Jesus. Of note, two of the three gifts were fragrances — frankincense and myrrh — which were thought to be more valuable than the gift of gold. Interestingly, some scholars speculate that the third gift of gold, may have been the gold-colored fragrant ambergris.5
The Use of Fragrance Expands
During the enlightenment of the Renaissance era (1450-1600), with the backdrop of the Black Plague in Europe, the utility of fragrances expanded. The Citizens of Paris believed that the disease traveled in corrupted air, thus the most common antidote recommended against the poisoned atmosphere was aromatics, such as herbs, flowers and perfumes that were thought to be protective.7 Persons also walked the streets with “pockets full of posie” to ward of the petulance; likewise, court physicians treated wounds with applications of aromatized wines and perfumed lotions.3
In the 13th and 14th centuries, the explorations of Marco Polo, Christopher Columbus, and Vasco de Gamma into new lands tremendously boosted the spice trade. The American New World was a delight to the senses, offering the exquisite scents of balsam of Peru and Tolu, juniper, American cedar, sassafras, and vanilla to the Old World.5
Modern-Day Famous Fragrances
These same scents became some of the many essential ingredients for the perfume industry, whose growth saw to the rapid emergence of department stores in Europe and the United States in the 20th century. In 1921, the first designer perfume using artificial scents [synthetic floral aldehydes] was launched when Coco Chanel unveiled her timeless classic No. 5. Two series of numbered samples (1 to 5 and 20 to 24) were designed for Chanel, but she chose No. 5 because her couture collection was scheduled for presentation on the fifth day of the fifth month, which she correctly interpreted as a good omen.8
Likewise, in the midst of a Great Depression, Joy by Patou, “the most expensive perfume in the world”, enjoyed unparalleled success. The outbreak of World War II, fascism and commodity rationing, was met with Hollywood’s “star culture” heydays and “character fragrances”, such as Christian Dior’s New Look.
The evolution of fragrance had begun to define feminine American culture. By the early ’80s, the industry decided that men were ready for their own fragrances. New colognes hit the market with revved up sports car names, such as Camaro and Lamborghini GT. As the end of the millennium drew near, borders dissolved and unity was in the air, Calvin Klein captured this sentiment with his defining unisex fragrance, CK One.3
Animal-Derived Scents and Use of Synthetic Scents
Fragrances are defined as complex mixtures of natural and synthetic materials used for improving the quality of life for those who wear it, “presenting in their wearers with an opportunity to create for themselves a virtually unforgettable, personal trademark”.4
The natural ingredients are primarily distilled botanical extracts. There are, however, a few prized animal byproduct exceptions (e.g. ambergris, musk, civet, and castoreum). While these may have originated in the primal hunter’s respectful use of the whole animal, they became a highly valued commodity. For example, the sperm whale’s ambergris is a biliary concretion made to facilitate gastrointestinal passage of hard objects, such as inadvertently eaten bones.6,9
One of the most vivid descriptions of ambergris can be found in Melville’s Moby Dick: “Dropping his spade, he (Stubb) thrust both hands in, and drew out handfuls of something that looked like ripe Windsor soap, or rich mottled old cheese; very unctuous and savory withal. You might easily dent it with your thumb; it is of a hue between yellow and ash colour. And this, good friends, is ambergris, worth a gold guinea an ounce to any druggist . . . . . Who would think, then, that such fine ladies and gentlemen should regale themselves with an essence found in the inglorious bowels of a sick whale!”10
Whales are not the only animals prized for their scent-producing capabilities. Musk deer bucks and Canadian beavers have pheromone sacs in the front of their abdomen that secrete musk and castoreum, respectively.
To obtain the scent, the animal is sacrificed and the extracted and dried gland is then marketed as “musk in pod” (i.e. the whole glands) or “musk in grain” (in which the perfume has been extracted from its receptacle).9
Civet cats are also coveted for the civet that is excreted from their perianal glands. This musk, which the animal uses to mark its territory, is a prized commodity that’s forcefully expressed from the civet’s anal glands for use in the perfumery industry. When “blended to enhance other essences, the civet fecal odor becomes less disagreeable.”6
High price and scarcity of natural products, in addition to advances in the chemical industry, led to the development of synthetic ingredients. During the Industrial Revolution (1889 to 1910), major discoveries in synthetic fragrance chemicals were made: 1869 heliotropine, 1877 coumarin, 1888 artificial musk, 1890 vanillin, 1890 ionone, 1905 hydroxycitronellal.3
Currently, as many as 90% of available fragrances are synthetic chemicals rather than natural extracts, with more than 5,000 different compounds reported.11
Globally, the fragrance and flavor market sales are estimated to be between $12 billion and $15 billion per year. Perfume fragrances are thought to make up about $3 billion of the total.12
Who Is Affected by Fragrance Allergy and How?
Fragrances are found in a wide range of products that extend well beyond eau d’toilettes and colognes. These include cosmetics, cleaning supplies, medicaments, foods and flavored personal hygiene products.11,13 (See Table 1). Furthermore, cutting fluids, electroplating fluids, metalworking fluids, paints, rubber, plastics, insecticides, herbicides and additives used in air-conditioning water also contain fragrances.11
Fragrance allergy occurs predominantly in women, with a female-to-male ratio of 3-4:1, and may relate to an overall greater exposure to skincare products by women than men.6,13 This is not surprising since on average 30 to 50 chemicals are used to create the fragrance composition of a perfume, and complex formulations of upwards of 200 ingredients are not uncommon.4
Classic localizations for fragrance contact allergy are the face, behind the ears, the neck, the axilla, and hands.11
Severe reactions have also been reported from fragrance use. Thompson and Wansker reported a very rare case
of a 32-year-old female on prolonged corticosteroid therapy for nephrotic syndrome, who developed toxic epidermal necrolysis and ultimately died, after using a spray cologne.14
The importance of allergen concentration (i.e. occlusion), skin barrier (or disruption thereof, i.e. shaving) and constitutional factors are important risk factors in the likelihood of becoming sensitized and the extent of the clinical manifestation.11,13
Oral and perioral dermatitis are common to fragrance/flavoring allergens in toothpastes, chewing gums, mouthwashes and mentholated cigarettes.6 Besides direct contact with fragrances, “consort” or “connubial” contact dermatitis also can occur by contact with products used by partners, friends or co-workers, as well as airborne contact, and systemic exposure by inhalation and ingestion (flavor and spices in foods).11
Children may become sensitized to fragrances, especially through the use of baby products applied to areas of chronic dermatitis, such as diaper dermatitis.6
Increasing Rates of Sensitization
In fact, fragrances are the second-most common class of substances identified to cause allergic contact dermatitis, and
the most frequent cause of contact allergy to cosmetics. Cosmetics account for 30% to 45% of these allergic reactions, with perfumes accounting for 4% to 18% and deodorants/antiperspirants 5% to 17% of cases.11
Allergy to fragrance was first reported in the medical literature in 1957.15
Increasing rates of sensitization to perfumes called for fragrance identification measures to be established in late ’70s. Larsen proposed a mixture of ingredients as a screening tool for fragrance contact allergy, after identifying the eight primary substances present in the Mycolog cream.16 These fragrance ingredients are isoeugenol, eugenol, cinnamic aldehyde, cinnamic alcohol, hydroxycitronellal, geraniol, a-amyl cinnamic aldehyde, and oak moss absolute.13 This composite is still used today for fragrance screening, and in conjunction with balsam of Peru 90% of fragrance allergies are detected.17
Testing for Fragrance Mix Allergy
The fragrance mix is included on the T.R.U.E test panel 1.1, site #6. Additionally, it can be tested for through comprehensive testing with ‘fragrance mix’ 8% in petrolatum (5% sorbitan sesquiolate is added to this as an emulsifier, to increase penetration).
Using the later formulation, the North American Contact Dermatitis Group 2001-2002 patch test results showed fragrance mix as one of the 10 top allergens with a prevalence rate of 10.4%.21 Of note, the original testing composition was 16% in petrolatum (2% of each constituent); however, the concentration was lowered in 1984 to 8% (1% of each of these components) to reduce the risk of false positives.11
While fragrance mix is thought to be superior to balsam of Peru in detecting fragrance allergy in cosmetic products, false positive and false negative reactions do occur and clinical correlations should be made.9,11,13
The Value of This Patient Case
The patient was found to be allergic to fragrance and counseled on fragrance avoidance, which unfortunately is complicated by confusing terms and inadvertently misleading product labeling.
The term “unscented” generally refers to the addition of fragrance-masking chemicals, whereas fragrance-free refers to the absence of chemicals added to enhance aroma. Therefore, unscented and fragrance-free products are not synonymous.
Furthermore, according to the FDA code of federal regulations, title 21, volume 7, section 700.3(d), the term fragrance means any natural or synthetic substance or substances used solely to impart an odor to a cosmetic product.22
Strict adherence to the definition of a fragrance translates to the possibility “fragrance-free” labeled products containing fragrance based ingredients added to serve another purpose.23 For example, if a fragrance ingredient is added as a preservative or emollient, it could be included in a fragrance-free product.23
Our patient illustrates the importance of specific instruction on label reading and term definition.
Allergic contact dermatitis is an important disease with a high impact both in terms of patient morbidity and economics. The contact dermatitides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria.
Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-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. While 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
Allergic contact dermatitis, on the other hand, is a delayed type IV hypersensitivity reaction. The primary focus of this section is to highlight the educational component of allergic contact dermatitis.
Clinical Illustration
A woman was referred to the Univer-sity of Miami Contact Dermatitis Clinic for evaluation of a longstanding generalized eczematous dermatitis with bilateral ectropion. Of note, she had noticed flares associated with cinnamon buns.
The History of Fragrance
Since ancient times, fragrances have had great cultural impact — from the burning of tree resin incenses in religious practices in China, Palestine and Egypt to refining the early Egyptian art of mummification.3 As early as the year 3000 BC, Egyptians “welcomed the gods” and sanctified their homes by burning the sacred temple incense, Kyphi, into their dwellings.4 The esteemed Kyphi was thought to hold the power to heal, alleviate anxieties, increase dreaming, eliminate sorrow, treat asthma and act as a general antidote for toxins.5
Perfume was first brought to Greece with the conquests of Alexander the Great in the fourth century BC.3 When Alexander entered the tent of the defeated King Darius III, after the battle of Issos, he is said to have added insult to injury by destroying the king’s box of priceless ointments and perfumes. As he traveled through Asia, he became so addicted to aromas and anointment oils that he sent deputies on quests across distant lands to Yemen and Oman to find the source of the Arabian incenses.5
Before the domination of other Mediterranean nations, the use of fragrances and perfumes by early Romans was very limited. With the arrival of the conquered people from the ‘Orient’ into Rome under Julius Caesar, Nero and Heliogabale came a large number of Asian and Greek perfumes.3 The consumption of great quantities of fragrances by the Romans in the first century AD was so vast that new trade routes to Arabia, India and China abounded to keep up with the demands.6
In the Book of Matthew 2:1, it is said that Three Wise Men (Kings) came “from the east to Jerusalem” bearing gifts to the Infant Jesus. Of note, two of the three gifts were fragrances — frankincense and myrrh — which were thought to be more valuable than the gift of gold. Interestingly, some scholars speculate that the third gift of gold, may have been the gold-colored fragrant ambergris.5
The Use of Fragrance Expands
During the enlightenment of the Renaissance era (1450-1600), with the backdrop of the Black Plague in Europe, the utility of fragrances expanded. The Citizens of Paris believed that the disease traveled in corrupted air, thus the most common antidote recommended against the poisoned atmosphere was aromatics, such as herbs, flowers and perfumes that were thought to be protective.7 Persons also walked the streets with “pockets full of posie” to ward of the petulance; likewise, court physicians treated wounds with applications of aromatized wines and perfumed lotions.3
In the 13th and 14th centuries, the explorations of Marco Polo, Christopher Columbus, and Vasco de Gamma into new lands tremendously boosted the spice trade. The American New World was a delight to the senses, offering the exquisite scents of balsam of Peru and Tolu, juniper, American cedar, sassafras, and vanilla to the Old World.5
Modern-Day Famous Fragrances
These same scents became some of the many essential ingredients for the perfume industry, whose growth saw to the rapid emergence of department stores in Europe and the United States in the 20th century. In 1921, the first designer perfume using artificial scents [synthetic floral aldehydes] was launched when Coco Chanel unveiled her timeless classic No. 5. Two series of numbered samples (1 to 5 and 20 to 24) were designed for Chanel, but she chose No. 5 because her couture collection was scheduled for presentation on the fifth day of the fifth month, which she correctly interpreted as a good omen.8
Likewise, in the midst of a Great Depression, Joy by Patou, “the most expensive perfume in the world”, enjoyed unparalleled success. The outbreak of World War II, fascism and commodity rationing, was met with Hollywood’s “star culture” heydays and “character fragrances”, such as Christian Dior’s New Look.
The evolution of fragrance had begun to define feminine American culture. By the early ’80s, the industry decided that men were ready for their own fragrances. New colognes hit the market with revved up sports car names, such as Camaro and Lamborghini GT. As the end of the millennium drew near, borders dissolved and unity was in the air, Calvin Klein captured this sentiment with his defining unisex fragrance, CK One.3
Animal-Derived Scents and Use of Synthetic Scents
Fragrances are defined as complex mixtures of natural and synthetic materials used for improving the quality of life for those who wear it, “presenting in their wearers with an opportunity to create for themselves a virtually unforgettable, personal trademark”.4
The natural ingredients are primarily distilled botanical extracts. There are, however, a few prized animal byproduct exceptions (e.g. ambergris, musk, civet, and castoreum). While these may have originated in the primal hunter’s respectful use of the whole animal, they became a highly valued commodity. For example, the sperm whale’s ambergris is a biliary concretion made to facilitate gastrointestinal passage of hard objects, such as inadvertently eaten bones.6,9
One of the most vivid descriptions of ambergris can be found in Melville’s Moby Dick: “Dropping his spade, he (Stubb) thrust both hands in, and drew out handfuls of something that looked like ripe Windsor soap, or rich mottled old cheese; very unctuous and savory withal. You might easily dent it with your thumb; it is of a hue between yellow and ash colour. And this, good friends, is ambergris, worth a gold guinea an ounce to any druggist . . . . . Who would think, then, that such fine ladies and gentlemen should regale themselves with an essence found in the inglorious bowels of a sick whale!”10
Whales are not the only animals prized for their scent-producing capabilities. Musk deer bucks and Canadian beavers have pheromone sacs in the front of their abdomen that secrete musk and castoreum, respectively.
To obtain the scent, the animal is sacrificed and the extracted and dried gland is then marketed as “musk in pod” (i.e. the whole glands) or “musk in grain” (in which the perfume has been extracted from its receptacle).9
Civet cats are also coveted for the civet that is excreted from their perianal glands. This musk, which the animal uses to mark its territory, is a prized commodity that’s forcefully expressed from the civet’s anal glands for use in the perfumery industry. When “blended to enhance other essences, the civet fecal odor becomes less disagreeable.”6
High price and scarcity of natural products, in addition to advances in the chemical industry, led to the development of synthetic ingredients. During the Industrial Revolution (1889 to 1910), major discoveries in synthetic fragrance chemicals were made: 1869 heliotropine, 1877 coumarin, 1888 artificial musk, 1890 vanillin, 1890 ionone, 1905 hydroxycitronellal.3
Currently, as many as 90% of available fragrances are synthetic chemicals rather than natural extracts, with more than 5,000 different compounds reported.11
Globally, the fragrance and flavor market sales are estimated to be between $12 billion and $15 billion per year. Perfume fragrances are thought to make up about $3 billion of the total.12
Who Is Affected by Fragrance Allergy and How?
Fragrances are found in a wide range of products that extend well beyond eau d’toilettes and colognes. These include cosmetics, cleaning supplies, medicaments, foods and flavored personal hygiene products.11,13 (See Table 1). Furthermore, cutting fluids, electroplating fluids, metalworking fluids, paints, rubber, plastics, insecticides, herbicides and additives used in air-conditioning water also contain fragrances.11
Fragrance allergy occurs predominantly in women, with a female-to-male ratio of 3-4:1, and may relate to an overall greater exposure to skincare products by women than men.6,13 This is not surprising since on average 30 to 50 chemicals are used to create the fragrance composition of a perfume, and complex formulations of upwards of 200 ingredients are not uncommon.4
Classic localizations for fragrance contact allergy are the face, behind the ears, the neck, the axilla, and hands.11
Severe reactions have also been reported from fragrance use. Thompson and Wansker reported a very rare case
of a 32-year-old female on prolonged corticosteroid therapy for nephrotic syndrome, who developed toxic epidermal necrolysis and ultimately died, after using a spray cologne.14
The importance of allergen concentration (i.e. occlusion), skin barrier (or disruption thereof, i.e. shaving) and constitutional factors are important risk factors in the likelihood of becoming sensitized and the extent of the clinical manifestation.11,13
Oral and perioral dermatitis are common to fragrance/flavoring allergens in toothpastes, chewing gums, mouthwashes and mentholated cigarettes.6 Besides direct contact with fragrances, “consort” or “connubial” contact dermatitis also can occur by contact with products used by partners, friends or co-workers, as well as airborne contact, and systemic exposure by inhalation and ingestion (flavor and spices in foods).11
Children may become sensitized to fragrances, especially through the use of baby products applied to areas of chronic dermatitis, such as diaper dermatitis.6
Increasing Rates of Sensitization
In fact, fragrances are the second-most common class of substances identified to cause allergic contact dermatitis, and
the most frequent cause of contact allergy to cosmetics. Cosmetics account for 30% to 45% of these allergic reactions, with perfumes accounting for 4% to 18% and deodorants/antiperspirants 5% to 17% of cases.11
Allergy to fragrance was first reported in the medical literature in 1957.15
Increasing rates of sensitization to perfumes called for fragrance identification measures to be established in late ’70s. Larsen proposed a mixture of ingredients as a screening tool for fragrance contact allergy, after identifying the eight primary substances present in the Mycolog cream.16 These fragrance ingredients are isoeugenol, eugenol, cinnamic aldehyde, cinnamic alcohol, hydroxycitronellal, geraniol, a-amyl cinnamic aldehyde, and oak moss absolute.13 This composite is still used today for fragrance screening, and in conjunction with balsam of Peru 90% of fragrance allergies are detected.17
Testing for Fragrance Mix Allergy
The fragrance mix is included on the T.R.U.E test panel 1.1, site #6. Additionally, it can be tested for through comprehensive testing with ‘fragrance mix’ 8% in petrolatum (5% sorbitan sesquiolate is added to this as an emulsifier, to increase penetration).
Using the later formulation, the North American Contact Dermatitis Group 2001-2002 patch test results showed fragrance mix as one of the 10 top allergens with a prevalence rate of 10.4%.21 Of note, the original testing composition was 16% in petrolatum (2% of each constituent); however, the concentration was lowered in 1984 to 8% (1% of each of these components) to reduce the risk of false positives.11
While fragrance mix is thought to be superior to balsam of Peru in detecting fragrance allergy in cosmetic products, false positive and false negative reactions do occur and clinical correlations should be made.9,11,13
The Value of This Patient Case
The patient was found to be allergic to fragrance and counseled on fragrance avoidance, which unfortunately is complicated by confusing terms and inadvertently misleading product labeling.
The term “unscented” generally refers to the addition of fragrance-masking chemicals, whereas fragrance-free refers to the absence of chemicals added to enhance aroma. Therefore, unscented and fragrance-free products are not synonymous.
Furthermore, according to the FDA code of federal regulations, title 21, volume 7, section 700.3(d), the term fragrance means any natural or synthetic substance or substances used solely to impart an odor to a cosmetic product.22
Strict adherence to the definition of a fragrance translates to the possibility “fragrance-free” labeled products containing fragrance based ingredients added to serve another purpose.23 For example, if a fragrance ingredient is added as a preservative or emollient, it could be included in a fragrance-free product.23
Our patient illustrates the importance of specific instruction on label reading and term definition.
