In 1997 the Food and Drug Administration gave indication to the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis. Many dermatologists and allergists use this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen.
Specifically, the T.R.U.E. test screens for 46 distinct allergens in addition to the balsam of Peru mixture and is thought to adequately identify an allergen in approximately 24.5% of patients.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious Allergens of the Year and other clinically relevant allergens identified by the North American Contact Dermatitis Group.
In this month’s column, we discuss propolis, a beeswax-based organic substance, which has long been valued for its healing properties and is used as an ingredient in numerous products, including cosmetics, salves and ointments, some cough syrups, hair products, and even some toothpastes.
Contact Dermatides
The contact dermatides include irritant contact dermatitis (ICD), contact urticaria (CU) and allergic contact dermatitis (ACD). The most common form, ICD 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 protein hypersensitivity. Although that 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 resources.2,3,4
Allergic contact dermatitis is a T-cell dependent delayed-type (Type IV) hypersensitivity reaction, which has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade, which leads to the clinical picture of ACD.
Case Illustration
A teenage girl presented to the University of Miami Allergic Contact Dermatitis Clinic for evaluation of a recurrent perioral dermatitis that she had been treating with a “green cosmetic” lip balm.
Zeus and the Highly Regarded Bee
Ancient fossils have suggested that the honeybees, Apis mellifera, evolved approximately 65 millions years ago, before the age of the dinosaur.5 As one of the earliest forms of animal life still in existence today, the honeybee has proven to be one of the most celebrated creatures. Furthermore, it has been held in high regard by man for its “various products from the hive.”
As early as 2000 B.C., the Egyptians discovered the “magical” healing properties of a complex wax material that they had obtained from the hive. They proceeded to melt down the entire hive and utilize this wax for both coating bandages and as a healing salve. This practice was so favored that many ancient cultures such as the Sumerians, Babylonians, and Greeks adopted this custom in their wound-healing practices.4 For example, the Assyrians used this substance for treating tumors and wounds, while the Greeks were known to use the wax for healing abscesses.5
In various cultures around the world, bees (and their products) became the topic of legends and mythologies, and it was generally believed that the bee was empowered by the deities. According to Greek legend, Zeus, the ruler of Mount Olympus, is said to have personally granted the honeybee the power to inflict pain in times of danger and strife and equipped it with a stinger.6 And likewise, the Roman god Jupiter is said to have transformed the beautiful nymph Melissa into the bee goddess, so that she could produce honey and other healing substances,7 signifying the birth of apitherapy.
Alexander and the Art of Apitherapy
Apitherapy, the medicinal art of using honeybee products for the prevention or treatment of various diseases or conditions, dates back to the beginnings of modern medicine itself.8 In fact, Hippocrates (460 to 377 B.C.), the Father of Modern Medicine, soundly believed in the health benefits of beeswax and frequently prescribed it for the treatment of various types of medical ailments.9
Legend is that this wax healing substance was first identified and described by an early astute naturalist student who named it propolis derived from the Greek words “pro”, meaning before, and “polis” meaning city.9
Many believe this student to have been Aristotle (circa 384 to 322 B.C.), as it was he who noted that the honeybees used this substance to narrow the opening of their “cities” (hives).7,10
A famous student of Aristotle, Alexander the Great, is renowned for the influence his conquests had on the cultural practices across nations. Interestingly, just prior to his 33rd birthday Alexander died in the palace of Nebuchadrezzar II of Babylon (either from a relapse of his malaria or a poisoning at the hands of the sons of Antipater), and per his request, his body was submerged in a clay vessel of honey and covered with beeswax-propolis, in order to preserve his body.11
By the first century B.C., the Roman republic had absorbed most of Alexander’s Hellenistic territories of the west, and because Alexander was so admired, Alexandrian Greek was spoken in Rome for philosophical and intellectual discourse. Historical accounts report that Alexander was the inspiration for the legend of Achilles, and that his tomb and remains were on display until “late anti-quity.”12 Unfortunately, unrest in Rome led to looting and the unexplained disappearance of both the body and tomb.
During the period of scientific progress and discovery, Roman scholars including Pliny and Galen (130 to 200 A.D.) noted the medicinal properties of propolis and other bee products; however, much stagnation later ensued with the fall of the great empires, signified by the wars and civil unrest that ravaged the Dark Ages.13
With the dawn of the modern age came a renewed interest in the art of medicine, and specifically in propolis and the possibility for a more diverse utilization. For example, in 12th century Europe and North Africa, propolis was used for treating mouth and throat infections because of its antibacterial properties. Notably, in Africa it is still used today for this purpose. Additionally, it is also used in Africa as an adhesive for tuning drums and as a sealant for cracked canoes and water containers.13
Apitherapy Introduced to America
It wasn’t until the 15th and 16th centuries in Europe that popular interest in propolis was sustained.
The famous English botanist John Gerard was one of the first people to acclaim its tributes in his book The General History of Plants (circa 1579), which referred to this substance as something that “can provide swift and effective healing for many conditions.”10
Propolis became further prized when it was reportedly used by Italian music instrument maker Antonio Stradivari to varnish his violins and other stringed instruments.14
With the increasing awareness of this product’s versatility, it was not long until its usage spread to the New World.
The first introduction of the European honeybee to the Americas is thought to have occurred in 1622 when a ship full of beehives, on either the Bona Nova or the Hopewell, was sent from the Council of the Virginia Company in London to Jamestown in North America. With news of the high potential for economic gain, residents of Newbury, MA, later tried to develop the first municipal apiary (also known as a bee yard). Unfortunately, they failed shortly afterward because of inexperience with habitat planning.
Continued interest in beekeeping and the production of various honeybee-based goods for export was maintained with minimal changes until the mid-1800s when improved hive construction was introduced.
After a while, apiaries became more prevalent and colonists became further aware of the medicinal uses of bee products, particularly the use of propolis. In fact, early colonists practiced the traditional old wives’ tale of keeping a piece of propolis in the mouth as a remedy for a sore throat.15
Exploring the Science of Apitherapy
The science of apitherapy made headway in 1888 when Austrian physician Phillip Terc published reports on the interaction of intentional bee stings and rheumatism. Having had severe arthritis himself, Terc was accidentally stung by a number of bees and noticed that his condition subsequently improved.
He decided to use this method of treatment in his practice. (We now know that it is the principal peptide, mellitin, found in bee venom that can inhibit the DNA binding activity of NF-kB [nuclear factor kappa B] and control many of the genes that are involved in immune reactions.)
In the 1930s in America, the late beekeeper Charles Mraz from a small town in Vermont pioneered bee venom as a therapy for various autoimmune disorders. He believed that venom stimulates the production of cortisol, as well as endorphins, making it a particularly useful compound.16
Subsequent research conducted in the 1970s confirmed his theory by showing an increase in serum cortisol levels in canines post-venom injection.17 But it was Terc’s original findings that led to the idea that bee venom may be beneficial in treating a variety of conditions such as chronic back pain, acute tendonitis, and rheumatoid arthritis.18
Likewise, during the late 19th century, long-standing medical essays from Arabic, Greek, and Roman antiquity that were filled with information regarding the use of propolis for treating skin disease, infection, joint, and respiratory problems such as asthma and bronchitis were discovered in Europe.13
These documents indicated the anti-inflammatory characteristics of propolis and eventually led to the discovery that propolis contained hyaluronidase, an enzyme with an inhibitory effect on inflammatory processes, particularly in the lungs.19
Early 20th century physicians continued to use propolis in their antimicrobial armamentarium until the discovery of antibiotics in the 1940s. Although Western Europe and America placed an emphasis on these agents, Eastern Europe and China continued to use propolis and conduct medical research on its effects.
By the 1960s and 1970s, Western Europe had a renewed interest in propolis because Drs. Aagard Lund (Denmark) and Dr. Remy Chauvin (France) published information about mouth, throat and nose infections and chronic immune disorders, respectively, that had been treated with propolis. Since then, numerous research studies have been conducted to assess its clinical usefulness.13,19
Current-Day Apitherapy
Over the past 60 years, bee products for healing measures have become an established form of “alternative” medicine. More recently through laboratory studies, researchers have found that propolis exhibits liver-protecting, antioxidant, anti-cancer, and anti-inflammatory properties.20,21
The antimicrobial properties make it effective in dental care and may be protective against parasitic infections in the gastrointestinal tract.21 Furthermore, propolis-containing topical creams and ointments have entered the consumer market for treating herpes simplex virus type 2, as well as other dermatological problems such as eczema, ulcers, tissue regeneration, and wound healing.22
Of interest, beyond propolis, other bee products such as royal jelly and honey have become significant staples in our daily wares. (See Table 1.) For example, honey (specifically, Manuka honey) has been used in wound-healing preparations to inhibit the growth of several organisms that are responsible for wound infections.10
With all bee products, composition varies from hive to hive and region to region, as the bees utilize whatever plant sources are available. Manuka honey is an especially valued variety because of its high antibacterial properties.
Beeswax Versus Propolis
To formulate propolis, the worker bee gathers resinous substances from a variety of tree buds and bark (horse chestnut, spruce, willow, larch, fir, and especially poplars).
Research has suggested that during the collection process the bees process the resin with their saliva and then add beeswax to the resin, thereby altering its chemical structure. The chemically altered resin is then passed to their pollen sacs by their back legs for storage before transportation back to the hive.7 This mixture (propolis) is then used to fill in cracks in the hive and for the live embalming of unwanted intruders.7,23
Emerging evidence suggests that propolis also has an immunologic function in the beehive, preventing disease and parasites.8 It is thought that propolis gains its immunologic properties because tree resins often contain high concentrations of polyphenols, which have anti-microbial action against viruses, bacteria and fungi.
Furthermore, “sterilization” of the honey and honeycomb cells (which contain the honey and larvae, respectively) is also maintained through the use of propolis.
Even the entrance of the hive is constructed with this substance in order to form an intricate tight tunnel through which the bees must crawl in order to enter and exit the hive. This practice ensures that the bees themselves are cleansed of any microbes, as they traverse the entrance.7
A Complex Substance
It is important to recognize that propolis is a complex substance, containing a complex mixture of more than 50 constituents. This mixture is primarily made of resins and vegetable balsams (50% to 55%), while waxes (30%), essential oils (10%), pollen (5%), vitamins A, B, C and E (nutrients required for normal metabolic reactions in the body) from plant materials, and various minerals account for the remainder.15 Bio-flavonoids, key vitamins also found in propolis, have been shown to improve circulation of the blood, stimulate urine elimination and bile and endocrine secretion, in addition to having powerful anti-bacterial and anti-fungal effects.12
Allergy to Propolis
While propolis was once ingested among beekeepers to ward off colds, it later became recognized as a significant occupational problem among this population.24 It has also been recognized for its role in the sensitization of musicians and instrument manufacturers to this agent.
Moreover, reports have also included department store workers who were exposed to untreated or unfinished wood products or shoes that contained beeswax that was contaminated with propolis.25
The recent increased usage of propolis (which can also be called “bee glue”) and nonpharmacological-grade beeswax (pure beeswax contaminated by propolis), especially in “green cosmetics”, has resulted in hundreds of cases of non-occupational ACD to propolis reported worldwide.26
Variability exists in the presentations of these incidents, and they range from psoriasiform to eczema-like dermatides. In one case report, propolis contact allergy mimicked pemphigus vulgaris, while another report showed an unusual presentation of the formation of a papule, which developed into an erythematous nodule, accompanied by lymphadenopathy and fever.26
With these growing reports, it has been proposed that propolis-induced dermatitis should be considered in patients who present with unusual or unexplained eczema.23
In 2007, the NACDG included propolis on its standard 65-allergen screening panel. This important addition will help to establish the prevalence data on this allergen in the United States. It has been suggested that approximately 1.2% to 6.6% of patients display sensitivity to propolis when patch-tested.27
It is also thought that components such as caffeic acid phenylester, as well as flavonoid aglycones, are the main sensitizing agents. The importance of sensitivity recognition to other compounds such as Peruvian balsam, salicylates, and poplar or conifer sap should be recognized because patients may need to avoid these as well as propolis and beeswax because of nature identical chemical ingredients (cinnamic acid, cinnamyl alcohol and vanillin).28 (See Table 2.)
Value of This Case
Propolis has increasingly been recognized for its role in sensitization in association with “green cosmetics”. Our patient used Clear Hills Honey Company all-natural lip balm with propolis and honey to heal her lips. When we conducted patch testing to this product, propolis and balsam of Peru demonstrated positive patch tests. Therefore, we advised our patient to avoid propolis and beeswax (because of the possibility of contamination with propolis) and balsam of Peru. Through avoidance, this patient cleared her perioral dermatitis.
In 1997 the Food and Drug Administration gave indication to the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis. Many dermatologists and allergists use this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen.
Specifically, the T.R.U.E. test screens for 46 distinct allergens in addition to the balsam of Peru mixture and is thought to adequately identify an allergen in approximately 24.5% of patients.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious Allergens of the Year and other clinically relevant allergens identified by the North American Contact Dermatitis Group.
In this month’s column, we discuss propolis, a beeswax-based organic substance, which has long been valued for its healing properties and is used as an ingredient in numerous products, including cosmetics, salves and ointments, some cough syrups, hair products, and even some toothpastes.
Contact Dermatides
The contact dermatides include irritant contact dermatitis (ICD), contact urticaria (CU) and allergic contact dermatitis (ACD). The most common form, ICD 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 protein hypersensitivity. Although that 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 resources.2,3,4
Allergic contact dermatitis is a T-cell dependent delayed-type (Type IV) hypersensitivity reaction, which has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade, which leads to the clinical picture of ACD.
Case Illustration
A teenage girl presented to the University of Miami Allergic Contact Dermatitis Clinic for evaluation of a recurrent perioral dermatitis that she had been treating with a “green cosmetic” lip balm.
Zeus and the Highly Regarded Bee
Ancient fossils have suggested that the honeybees, Apis mellifera, evolved approximately 65 millions years ago, before the age of the dinosaur.5 As one of the earliest forms of animal life still in existence today, the honeybee has proven to be one of the most celebrated creatures. Furthermore, it has been held in high regard by man for its “various products from the hive.”
As early as 2000 B.C., the Egyptians discovered the “magical” healing properties of a complex wax material that they had obtained from the hive. They proceeded to melt down the entire hive and utilize this wax for both coating bandages and as a healing salve. This practice was so favored that many ancient cultures such as the Sumerians, Babylonians, and Greeks adopted this custom in their wound-healing practices.4 For example, the Assyrians used this substance for treating tumors and wounds, while the Greeks were known to use the wax for healing abscesses.5
In various cultures around the world, bees (and their products) became the topic of legends and mythologies, and it was generally believed that the bee was empowered by the deities. According to Greek legend, Zeus, the ruler of Mount Olympus, is said to have personally granted the honeybee the power to inflict pain in times of danger and strife and equipped it with a stinger.6 And likewise, the Roman god Jupiter is said to have transformed the beautiful nymph Melissa into the bee goddess, so that she could produce honey and other healing substances,7 signifying the birth of apitherapy.
Alexander and the Art of Apitherapy
Apitherapy, the medicinal art of using honeybee products for the prevention or treatment of various diseases or conditions, dates back to the beginnings of modern medicine itself.8 In fact, Hippocrates (460 to 377 B.C.), the Father of Modern Medicine, soundly believed in the health benefits of beeswax and frequently prescribed it for the treatment of various types of medical ailments.9
Legend is that this wax healing substance was first identified and described by an early astute naturalist student who named it propolis derived from the Greek words “pro”, meaning before, and “polis” meaning city.9
Many believe this student to have been Aristotle (circa 384 to 322 B.C.), as it was he who noted that the honeybees used this substance to narrow the opening of their “cities” (hives).7,10
A famous student of Aristotle, Alexander the Great, is renowned for the influence his conquests had on the cultural practices across nations. Interestingly, just prior to his 33rd birthday Alexander died in the palace of Nebuchadrezzar II of Babylon (either from a relapse of his malaria or a poisoning at the hands of the sons of Antipater), and per his request, his body was submerged in a clay vessel of honey and covered with beeswax-propolis, in order to preserve his body.11
By the first century B.C., the Roman republic had absorbed most of Alexander’s Hellenistic territories of the west, and because Alexander was so admired, Alexandrian Greek was spoken in Rome for philosophical and intellectual discourse. Historical accounts report that Alexander was the inspiration for the legend of Achilles, and that his tomb and remains were on display until “late anti-quity.”12 Unfortunately, unrest in Rome led to looting and the unexplained disappearance of both the body and tomb.
During the period of scientific progress and discovery, Roman scholars including Pliny and Galen (130 to 200 A.D.) noted the medicinal properties of propolis and other bee products; however, much stagnation later ensued with the fall of the great empires, signified by the wars and civil unrest that ravaged the Dark Ages.13
With the dawn of the modern age came a renewed interest in the art of medicine, and specifically in propolis and the possibility for a more diverse utilization. For example, in 12th century Europe and North Africa, propolis was used for treating mouth and throat infections because of its antibacterial properties. Notably, in Africa it is still used today for this purpose. Additionally, it is also used in Africa as an adhesive for tuning drums and as a sealant for cracked canoes and water containers.13
Apitherapy Introduced to America
It wasn’t until the 15th and 16th centuries in Europe that popular interest in propolis was sustained.
The famous English botanist John Gerard was one of the first people to acclaim its tributes in his book The General History of Plants (circa 1579), which referred to this substance as something that “can provide swift and effective healing for many conditions.”10
Propolis became further prized when it was reportedly used by Italian music instrument maker Antonio Stradivari to varnish his violins and other stringed instruments.14
With the increasing awareness of this product’s versatility, it was not long until its usage spread to the New World.
The first introduction of the European honeybee to the Americas is thought to have occurred in 1622 when a ship full of beehives, on either the Bona Nova or the Hopewell, was sent from the Council of the Virginia Company in London to Jamestown in North America. With news of the high potential for economic gain, residents of Newbury, MA, later tried to develop the first municipal apiary (also known as a bee yard). Unfortunately, they failed shortly afterward because of inexperience with habitat planning.
Continued interest in beekeeping and the production of various honeybee-based goods for export was maintained with minimal changes until the mid-1800s when improved hive construction was introduced.
After a while, apiaries became more prevalent and colonists became further aware of the medicinal uses of bee products, particularly the use of propolis. In fact, early colonists practiced the traditional old wives’ tale of keeping a piece of propolis in the mouth as a remedy for a sore throat.15
Exploring the Science of Apitherapy
The science of apitherapy made headway in 1888 when Austrian physician Phillip Terc published reports on the interaction of intentional bee stings and rheumatism. Having had severe arthritis himself, Terc was accidentally stung by a number of bees and noticed that his condition subsequently improved.
He decided to use this method of treatment in his practice. (We now know that it is the principal peptide, mellitin, found in bee venom that can inhibit the DNA binding activity of NF-kB [nuclear factor kappa B] and control many of the genes that are involved in immune reactions.)
In the 1930s in America, the late beekeeper Charles Mraz from a small town in Vermont pioneered bee venom as a therapy for various autoimmune disorders. He believed that venom stimulates the production of cortisol, as well as endorphins, making it a particularly useful compound.16
Subsequent research conducted in the 1970s confirmed his theory by showing an increase in serum cortisol levels in canines post-venom injection.17 But it was Terc’s original findings that led to the idea that bee venom may be beneficial in treating a variety of conditions such as chronic back pain, acute tendonitis, and rheumatoid arthritis.18
Likewise, during the late 19th century, long-standing medical essays from Arabic, Greek, and Roman antiquity that were filled with information regarding the use of propolis for treating skin disease, infection, joint, and respiratory problems such as asthma and bronchitis were discovered in Europe.13
These documents indicated the anti-inflammatory characteristics of propolis and eventually led to the discovery that propolis contained hyaluronidase, an enzyme with an inhibitory effect on inflammatory processes, particularly in the lungs.19
Early 20th century physicians continued to use propolis in their antimicrobial armamentarium until the discovery of antibiotics in the 1940s. Although Western Europe and America placed an emphasis on these agents, Eastern Europe and China continued to use propolis and conduct medical research on its effects.
By the 1960s and 1970s, Western Europe had a renewed interest in propolis because Drs. Aagard Lund (Denmark) and Dr. Remy Chauvin (France) published information about mouth, throat and nose infections and chronic immune disorders, respectively, that had been treated with propolis. Since then, numerous research studies have been conducted to assess its clinical usefulness.13,19
Current-Day Apitherapy
Over the past 60 years, bee products for healing measures have become an established form of “alternative” medicine. More recently through laboratory studies, researchers have found that propolis exhibits liver-protecting, antioxidant, anti-cancer, and anti-inflammatory properties.20,21
The antimicrobial properties make it effective in dental care and may be protective against parasitic infections in the gastrointestinal tract.21 Furthermore, propolis-containing topical creams and ointments have entered the consumer market for treating herpes simplex virus type 2, as well as other dermatological problems such as eczema, ulcers, tissue regeneration, and wound healing.22
Of interest, beyond propolis, other bee products such as royal jelly and honey have become significant staples in our daily wares. (See Table 1.) For example, honey (specifically, Manuka honey) has been used in wound-healing preparations to inhibit the growth of several organisms that are responsible for wound infections.10
With all bee products, composition varies from hive to hive and region to region, as the bees utilize whatever plant sources are available. Manuka honey is an especially valued variety because of its high antibacterial properties.
Beeswax Versus Propolis
To formulate propolis, the worker bee gathers resinous substances from a variety of tree buds and bark (horse chestnut, spruce, willow, larch, fir, and especially poplars).
Research has suggested that during the collection process the bees process the resin with their saliva and then add beeswax to the resin, thereby altering its chemical structure. The chemically altered resin is then passed to their pollen sacs by their back legs for storage before transportation back to the hive.7 This mixture (propolis) is then used to fill in cracks in the hive and for the live embalming of unwanted intruders.7,23
Emerging evidence suggests that propolis also has an immunologic function in the beehive, preventing disease and parasites.8 It is thought that propolis gains its immunologic properties because tree resins often contain high concentrations of polyphenols, which have anti-microbial action against viruses, bacteria and fungi.
Furthermore, “sterilization” of the honey and honeycomb cells (which contain the honey and larvae, respectively) is also maintained through the use of propolis.
Even the entrance of the hive is constructed with this substance in order to form an intricate tight tunnel through which the bees must crawl in order to enter and exit the hive. This practice ensures that the bees themselves are cleansed of any microbes, as they traverse the entrance.7
A Complex Substance
It is important to recognize that propolis is a complex substance, containing a complex mixture of more than 50 constituents. This mixture is primarily made of resins and vegetable balsams (50% to 55%), while waxes (30%), essential oils (10%), pollen (5%), vitamins A, B, C and E (nutrients required for normal metabolic reactions in the body) from plant materials, and various minerals account for the remainder.15 Bio-flavonoids, key vitamins also found in propolis, have been shown to improve circulation of the blood, stimulate urine elimination and bile and endocrine secretion, in addition to having powerful anti-bacterial and anti-fungal effects.12
Allergy to Propolis
While propolis was once ingested among beekeepers to ward off colds, it later became recognized as a significant occupational problem among this population.24 It has also been recognized for its role in the sensitization of musicians and instrument manufacturers to this agent.
Moreover, reports have also included department store workers who were exposed to untreated or unfinished wood products or shoes that contained beeswax that was contaminated with propolis.25
The recent increased usage of propolis (which can also be called “bee glue”) and nonpharmacological-grade beeswax (pure beeswax contaminated by propolis), especially in “green cosmetics”, has resulted in hundreds of cases of non-occupational ACD to propolis reported worldwide.26
Variability exists in the presentations of these incidents, and they range from psoriasiform to eczema-like dermatides. In one case report, propolis contact allergy mimicked pemphigus vulgaris, while another report showed an unusual presentation of the formation of a papule, which developed into an erythematous nodule, accompanied by lymphadenopathy and fever.26
With these growing reports, it has been proposed that propolis-induced dermatitis should be considered in patients who present with unusual or unexplained eczema.23
In 2007, the NACDG included propolis on its standard 65-allergen screening panel. This important addition will help to establish the prevalence data on this allergen in the United States. It has been suggested that approximately 1.2% to 6.6% of patients display sensitivity to propolis when patch-tested.27
It is also thought that components such as caffeic acid phenylester, as well as flavonoid aglycones, are the main sensitizing agents. The importance of sensitivity recognition to other compounds such as Peruvian balsam, salicylates, and poplar or conifer sap should be recognized because patients may need to avoid these as well as propolis and beeswax because of nature identical chemical ingredients (cinnamic acid, cinnamyl alcohol and vanillin).28 (See Table 2.)
Value of This Case
Propolis has increasingly been recognized for its role in sensitization in association with “green cosmetics”. Our patient used Clear Hills Honey Company all-natural lip balm with propolis and honey to heal her lips. When we conducted patch testing to this product, propolis and balsam of Peru demonstrated positive patch tests. Therefore, we advised our patient to avoid propolis and beeswax (because of the possibility of contamination with propolis) and balsam of Peru. Through avoidance, this patient cleared her perioral dermatitis.
In 1997 the Food and Drug Administration gave indication to the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis. Many dermatologists and allergists use this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen.
Specifically, the T.R.U.E. test screens for 46 distinct allergens in addition to the balsam of Peru mixture and is thought to adequately identify an allergen in approximately 24.5% of patients.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious Allergens of the Year and other clinically relevant allergens identified by the North American Contact Dermatitis Group.
In this month’s column, we discuss propolis, a beeswax-based organic substance, which has long been valued for its healing properties and is used as an ingredient in numerous products, including cosmetics, salves and ointments, some cough syrups, hair products, and even some toothpastes.
Contact Dermatides
The contact dermatides include irritant contact dermatitis (ICD), contact urticaria (CU) and allergic contact dermatitis (ACD). The most common form, ICD 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 protein hypersensitivity. Although that 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 resources.2,3,4
Allergic contact dermatitis is a T-cell dependent delayed-type (Type IV) hypersensitivity reaction, which has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade, which leads to the clinical picture of ACD.
Case Illustration
A teenage girl presented to the University of Miami Allergic Contact Dermatitis Clinic for evaluation of a recurrent perioral dermatitis that she had been treating with a “green cosmetic” lip balm.
Zeus and the Highly Regarded Bee
Ancient fossils have suggested that the honeybees, Apis mellifera, evolved approximately 65 millions years ago, before the age of the dinosaur.5 As one of the earliest forms of animal life still in existence today, the honeybee has proven to be one of the most celebrated creatures. Furthermore, it has been held in high regard by man for its “various products from the hive.”
As early as 2000 B.C., the Egyptians discovered the “magical” healing properties of a complex wax material that they had obtained from the hive. They proceeded to melt down the entire hive and utilize this wax for both coating bandages and as a healing salve. This practice was so favored that many ancient cultures such as the Sumerians, Babylonians, and Greeks adopted this custom in their wound-healing practices.4 For example, the Assyrians used this substance for treating tumors and wounds, while the Greeks were known to use the wax for healing abscesses.5
In various cultures around the world, bees (and their products) became the topic of legends and mythologies, and it was generally believed that the bee was empowered by the deities. According to Greek legend, Zeus, the ruler of Mount Olympus, is said to have personally granted the honeybee the power to inflict pain in times of danger and strife and equipped it with a stinger.6 And likewise, the Roman god Jupiter is said to have transformed the beautiful nymph Melissa into the bee goddess, so that she could produce honey and other healing substances,7 signifying the birth of apitherapy.
Alexander and the Art of Apitherapy
Apitherapy, the medicinal art of using honeybee products for the prevention or treatment of various diseases or conditions, dates back to the beginnings of modern medicine itself.8 In fact, Hippocrates (460 to 377 B.C.), the Father of Modern Medicine, soundly believed in the health benefits of beeswax and frequently prescribed it for the treatment of various types of medical ailments.9
Legend is that this wax healing substance was first identified and described by an early astute naturalist student who named it propolis derived from the Greek words “pro”, meaning before, and “polis” meaning city.9
Many believe this student to have been Aristotle (circa 384 to 322 B.C.), as it was he who noted that the honeybees used this substance to narrow the opening of their “cities” (hives).7,10
A famous student of Aristotle, Alexander the Great, is renowned for the influence his conquests had on the cultural practices across nations. Interestingly, just prior to his 33rd birthday Alexander died in the palace of Nebuchadrezzar II of Babylon (either from a relapse of his malaria or a poisoning at the hands of the sons of Antipater), and per his request, his body was submerged in a clay vessel of honey and covered with beeswax-propolis, in order to preserve his body.11
By the first century B.C., the Roman republic had absorbed most of Alexander’s Hellenistic territories of the west, and because Alexander was so admired, Alexandrian Greek was spoken in Rome for philosophical and intellectual discourse. Historical accounts report that Alexander was the inspiration for the legend of Achilles, and that his tomb and remains were on display until “late anti-quity.”12 Unfortunately, unrest in Rome led to looting and the unexplained disappearance of both the body and tomb.
During the period of scientific progress and discovery, Roman scholars including Pliny and Galen (130 to 200 A.D.) noted the medicinal properties of propolis and other bee products; however, much stagnation later ensued with the fall of the great empires, signified by the wars and civil unrest that ravaged the Dark Ages.13
With the dawn of the modern age came a renewed interest in the art of medicine, and specifically in propolis and the possibility for a more diverse utilization. For example, in 12th century Europe and North Africa, propolis was used for treating mouth and throat infections because of its antibacterial properties. Notably, in Africa it is still used today for this purpose. Additionally, it is also used in Africa as an adhesive for tuning drums and as a sealant for cracked canoes and water containers.13
Apitherapy Introduced to America
It wasn’t until the 15th and 16th centuries in Europe that popular interest in propolis was sustained.
The famous English botanist John Gerard was one of the first people to acclaim its tributes in his book The General History of Plants (circa 1579), which referred to this substance as something that “can provide swift and effective healing for many conditions.”10
Propolis became further prized when it was reportedly used by Italian music instrument maker Antonio Stradivari to varnish his violins and other stringed instruments.14
With the increasing awareness of this product’s versatility, it was not long until its usage spread to the New World.
The first introduction of the European honeybee to the Americas is thought to have occurred in 1622 when a ship full of beehives, on either the Bona Nova or the Hopewell, was sent from the Council of the Virginia Company in London to Jamestown in North America. With news of the high potential for economic gain, residents of Newbury, MA, later tried to develop the first municipal apiary (also known as a bee yard). Unfortunately, they failed shortly afterward because of inexperience with habitat planning.
Continued interest in beekeeping and the production of various honeybee-based goods for export was maintained with minimal changes until the mid-1800s when improved hive construction was introduced.
After a while, apiaries became more prevalent and colonists became further aware of the medicinal uses of bee products, particularly the use of propolis. In fact, early colonists practiced the traditional old wives’ tale of keeping a piece of propolis in the mouth as a remedy for a sore throat.15
Exploring the Science of Apitherapy
The science of apitherapy made headway in 1888 when Austrian physician Phillip Terc published reports on the interaction of intentional bee stings and rheumatism. Having had severe arthritis himself, Terc was accidentally stung by a number of bees and noticed that his condition subsequently improved.
He decided to use this method of treatment in his practice. (We now know that it is the principal peptide, mellitin, found in bee venom that can inhibit the DNA binding activity of NF-kB [nuclear factor kappa B] and control many of the genes that are involved in immune reactions.)
In the 1930s in America, the late beekeeper Charles Mraz from a small town in Vermont pioneered bee venom as a therapy for various autoimmune disorders. He believed that venom stimulates the production of cortisol, as well as endorphins, making it a particularly useful compound.16
Subsequent research conducted in the 1970s confirmed his theory by showing an increase in serum cortisol levels in canines post-venom injection.17 But it was Terc’s original findings that led to the idea that bee venom may be beneficial in treating a variety of conditions such as chronic back pain, acute tendonitis, and rheumatoid arthritis.18
Likewise, during the late 19th century, long-standing medical essays from Arabic, Greek, and Roman antiquity that were filled with information regarding the use of propolis for treating skin disease, infection, joint, and respiratory problems such as asthma and bronchitis were discovered in Europe.13
These documents indicated the anti-inflammatory characteristics of propolis and eventually led to the discovery that propolis contained hyaluronidase, an enzyme with an inhibitory effect on inflammatory processes, particularly in the lungs.19
Early 20th century physicians continued to use propolis in their antimicrobial armamentarium until the discovery of antibiotics in the 1940s. Although Western Europe and America placed an emphasis on these agents, Eastern Europe and China continued to use propolis and conduct medical research on its effects.
By the 1960s and 1970s, Western Europe had a renewed interest in propolis because Drs. Aagard Lund (Denmark) and Dr. Remy Chauvin (France) published information about mouth, throat and nose infections and chronic immune disorders, respectively, that had been treated with propolis. Since then, numerous research studies have been conducted to assess its clinical usefulness.13,19
Current-Day Apitherapy
Over the past 60 years, bee products for healing measures have become an established form of “alternative” medicine. More recently through laboratory studies, researchers have found that propolis exhibits liver-protecting, antioxidant, anti-cancer, and anti-inflammatory properties.20,21
The antimicrobial properties make it effective in dental care and may be protective against parasitic infections in the gastrointestinal tract.21 Furthermore, propolis-containing topical creams and ointments have entered the consumer market for treating herpes simplex virus type 2, as well as other dermatological problems such as eczema, ulcers, tissue regeneration, and wound healing.22
Of interest, beyond propolis, other bee products such as royal jelly and honey have become significant staples in our daily wares. (See Table 1.) For example, honey (specifically, Manuka honey) has been used in wound-healing preparations to inhibit the growth of several organisms that are responsible for wound infections.10
With all bee products, composition varies from hive to hive and region to region, as the bees utilize whatever plant sources are available. Manuka honey is an especially valued variety because of its high antibacterial properties.
Beeswax Versus Propolis
To formulate propolis, the worker bee gathers resinous substances from a variety of tree buds and bark (horse chestnut, spruce, willow, larch, fir, and especially poplars).
Research has suggested that during the collection process the bees process the resin with their saliva and then add beeswax to the resin, thereby altering its chemical structure. The chemically altered resin is then passed to their pollen sacs by their back legs for storage before transportation back to the hive.7 This mixture (propolis) is then used to fill in cracks in the hive and for the live embalming of unwanted intruders.7,23
Emerging evidence suggests that propolis also has an immunologic function in the beehive, preventing disease and parasites.8 It is thought that propolis gains its immunologic properties because tree resins often contain high concentrations of polyphenols, which have anti-microbial action against viruses, bacteria and fungi.
Furthermore, “sterilization” of the honey and honeycomb cells (which contain the honey and larvae, respectively) is also maintained through the use of propolis.
Even the entrance of the hive is constructed with this substance in order to form an intricate tight tunnel through which the bees must crawl in order to enter and exit the hive. This practice ensures that the bees themselves are cleansed of any microbes, as they traverse the entrance.7
A Complex Substance
It is important to recognize that propolis is a complex substance, containing a complex mixture of more than 50 constituents. This mixture is primarily made of resins and vegetable balsams (50% to 55%), while waxes (30%), essential oils (10%), pollen (5%), vitamins A, B, C and E (nutrients required for normal metabolic reactions in the body) from plant materials, and various minerals account for the remainder.15 Bio-flavonoids, key vitamins also found in propolis, have been shown to improve circulation of the blood, stimulate urine elimination and bile and endocrine secretion, in addition to having powerful anti-bacterial and anti-fungal effects.12
Allergy to Propolis
While propolis was once ingested among beekeepers to ward off colds, it later became recognized as a significant occupational problem among this population.24 It has also been recognized for its role in the sensitization of musicians and instrument manufacturers to this agent.
Moreover, reports have also included department store workers who were exposed to untreated or unfinished wood products or shoes that contained beeswax that was contaminated with propolis.25
The recent increased usage of propolis (which can also be called “bee glue”) and nonpharmacological-grade beeswax (pure beeswax contaminated by propolis), especially in “green cosmetics”, has resulted in hundreds of cases of non-occupational ACD to propolis reported worldwide.26
Variability exists in the presentations of these incidents, and they range from psoriasiform to eczema-like dermatides. In one case report, propolis contact allergy mimicked pemphigus vulgaris, while another report showed an unusual presentation of the formation of a papule, which developed into an erythematous nodule, accompanied by lymphadenopathy and fever.26
With these growing reports, it has been proposed that propolis-induced dermatitis should be considered in patients who present with unusual or unexplained eczema.23
In 2007, the NACDG included propolis on its standard 65-allergen screening panel. This important addition will help to establish the prevalence data on this allergen in the United States. It has been suggested that approximately 1.2% to 6.6% of patients display sensitivity to propolis when patch-tested.27
It is also thought that components such as caffeic acid phenylester, as well as flavonoid aglycones, are the main sensitizing agents. The importance of sensitivity recognition to other compounds such as Peruvian balsam, salicylates, and poplar or conifer sap should be recognized because patients may need to avoid these as well as propolis and beeswax because of nature identical chemical ingredients (cinnamic acid, cinnamyl alcohol and vanillin).28 (See Table 2.)
Value of This Case
Propolis has increasingly been recognized for its role in sensitization in association with “green cosmetics”. Our patient used Clear Hills Honey Company all-natural lip balm with propolis and honey to heal her lips. When we conducted patch testing to this product, propolis and balsam of Peru demonstrated positive patch tests. Therefore, we advised our patient to avoid propolis and beeswax (because of the possibility of contamination with propolis) and balsam of Peru. Through avoidance, this patient cleared her perioral dermatitis.
