Britishjournal of Dermatology (1976) 94, 451.
Contact dermatitis from propolis BIRGITTE WANSCHER Department of Dermatology, University of Copenhagen, Rigshospital, Blegdamsvej 9, 2100 Copenhagen 0 , Denmark Accepted for publication 14 July 1975
SUMMARY
Two patients with contact dermatitis due to the natural product propolis (bee glue) are reported. They presented perioral eczema and stomatitis which were recalcitrant until propolis was considered as the cause. Patch tests with propolis preparations were positive in both patients, and, furthermore, in the second patient the lesions relapsed after provocation tests. European standard patch tests including balsam of Peru were negative. The complexity of propolis, its supposed anti-inflammatory efl'ect due to flavonoids, and the sensitizing agents originating mainly from the poplar trees are discussed together with the cross-sensitization to balsam of Peru. Contact dermatitis due to propolis should be considered in unexplained eczemas, mainly perioral but also in other areas, as propolis preparations are available also as ointments and cosmetic creams.
In many Western European countries, notably Scandinavia, Germany, Great Britain and Holland, propolis or bee glue has been known for many years. As a natural product it is sold now without prescription for several purposes as tablets, solid propolis in large or small pieces, powder, ointment, and recently as cosmetic moisture creams. Beekeeper's dermatitis due to propolis is well known (Umansky, 1934; Borlin, 1947; Rothenborg, 1967; Bunney, 1968), and Winklcr (1956) noted the apparent association between sensitivity to propolis and to poplar resins. By contrast, contact dermatitis due to propolis in persons without contact with poplar trees and in non-beekeepers has not been described previously. With increasing use of propolis it will probably be encountered more frequently by dermatologists. Furthermore, recalcitrant often periorally located eczema may remain unexplained until propolis as a cause is considered. At Rigshospital, we have seen recently two patients with contact dermatitis due to propolis.
CASE REPORTS Case I
A woman, aged 59 years, who had suffered from dry lips for many years. In 1968 she had been treated for contact dermatitis due to lipstick. During August-September 1974 she chewed, drank and ate propolis for mental depression and tiredness. After this period she continued to eat the honey. In 451
452
Birgitte Wanscher
October she noticed that her lips became unusually dry, stiff, and crusted. She did not use lipstick during these months. In an attempt to improve the condition, she tried to apply propolis honey directly to her lips. However, this caused severe pain and a burning sensation. The discomfort continued, and her lips became red and swollen despite the fact that she was treated with a corticosteroid cream. At this time the patient revealed to the dermatologist, who had treated her for 3 weeks, that all the time she had been eating propolis honey daily. Patch testing with granular propolis was subsequently performed, and a positive reaction was observed 2 days later. She was admitted to our department for recalcitrant cheilitis. On admission, an acute oozing and crusted eczema was found around her mouth and on her chin. On her back, a positive patch test from granular propolis, applied 7 days earlier, was still visible. Other patch tests including balsam of Peru were negative. The intake of propolis was stopped before admission. Her eczema cleared in a few days on treatment with carbowax 1500 containing 10% propylene glycol, lidocain ointment and a corticosteroid cream. Case 2
A woman, aged 67 years, who had suffered from Meniere's disease and migraine for many years. From 1969 to 1972 she was treated for ano-perineal prurigo and genital candidiasis. In 1972, a hysterectomy with salpingo-oophorectomy was performed for cancer. After this operation she suffered from vaginal fluor, which, according to her statement, disappeared completely within 1-2 months of using propolis. In August 1974 she started taking one tablet of propolis daily and chewing propolis for a gingival infection. Because of increasing soreness of the gums, chewing had to be given up now and then. As the gingival infection was unimproved, she tried to apply chewed propolis directly in the alveolobuccal suki, as recommended in leaflets from the producers. However, this resulted in oedema, erythema and severe pain. Three days before she was seen in the hospital she stopped taking propolis with slight improvement. On examination two aphthae and slight erythema and oedema of the mucous membrane were found in the right inferior alveolo-buccal sulcus. Patch tests with propolis honey, ointment 5",', and granular propolis in water were positive after 48 and 72 h. In April, i.e. 3 months after the first examination, the patient returned for a provocation test. In the meantime she had continued to take propolis tablets for i month. Before provocation, slight erythema was seen on the inferior gingiva corresponding to the two middle and the right lateral incisors (Fig. i). Apart from this, the mucous membranes were normal. Granular propolis, chewed for i min and placed in the inferior alveolo-buccal sulcus for i h for provocation, was used. The following evening the procedure was repeated and the time extended to 2-3 h resulting in severe pain, difficulty with talking, and in blisters. A planned provocation test on the third evening could not be performed because of the pain. Oedema, erythema, and a 6 x 7 mm white blister were found on examination on the fourth day (Fig. 2). The patient herself had made a patch test on her arm, which was positive.
DISCUSSION
Such patients with perioral eczema and stomatitis would escape an aetiological diagnosis unless the clinician is aware of the fact that propolis can give rise to contact dermatitis. In both cases propolis was mentioned by chance, and both patients believed that a preparation sold without prescription ought to be harmless. The diagnosis was confirmed by a positive provocation test in one patient, and patch tests were positive in both patients. It is well known that propolis causes allergic and not toxic patch test responses (Umansky, 1934; Borlin, 1947; Rothenborg, 1967; Bunney, 1968).
Contact dermatitis from propolis
FIGURE I. Patient 2 before provocation.
FIGURE 2. Patient 2 after provocation (see text). Oedema, erythema and a blister were seen.
453
454
Birgitte Wanscher
Jn Great Britain, several cases of contact dermatitis in beekeepers in contact with propolis have been described, and the incidence of the dermatitis among beekeepers is estimated to be 0-05/,'', (Bunney, 1968). With increasing use of propolis, more cases of contact dermatitis must be expected. Propolis, which means 'before city', is a dark yellowish-brown resinous substance with strong adhesive properties. Mixed with wax, it is used by the bees to seal up crevices in the hives, to smooth the surfaces and to protect the entrance from intruders. It is collected by the honeybees from the resinous exudations of plants and trees such as horse-chestnut {Arbor castanea), spruce {Abies nobilis), willow {Salix), larch {Larix),fir(Pinus), and especially poplar trees {Populus). Owing to the different places of origin, propolis specimens vary. However, ordinarily it contains wax 30"/,;, resins and balsams 55%, essential oils 10%, pollen 5",;, and cinnamic alcohol, minerals and flavonoids (B.R.A.; Umansky, 1934; Villaneuva et al., 1964, 1970). Since ancient times, antiseptic and healing properties in veterinary and in human medicine have been attributed to propolis. Russian dentists have called propolis a better anaesthetic than cocaine, and in Russia it is used as toothpaste, skin cream and toilet lotions. An antibacterial and antifungal action is also attributed to propolis (Lindenfclser, 1967; Lavie, 1968) and it has been foixnd to improve some skin diseases (Molnar-Toth, 1965). The main effect—if any—of propolis is supposed to be due to the flavonoids. The mechanism is considered to be a stabilization of the connective tissue and the vessels through protection of vitamin C against oxidation, which may be of some importance in the formation of collagen and in the synthesis of steroid hormones. Stabilization is caused also by the flavonoids by a decreased activity of the mucopolysaccharide-destroying enzymes (Niebes & Laszt, 1971). The effect of this stabilization could prevent the spread of infection. With the complex composition of propolis, a great number of sensitizing agents should be considered. Bunney (1968) carried out patch tests with propolis from different sources and with poplar and other tree resins. She found that ten of thirteen patients reacted to propolis and fifteen of fifteen patients reacted to poplar resin extracts. Also, Rothenborg (1967) found that his patients sensitive to poplar resins reacted to propolis, which suggested that the sensitizing allergen in propolis is derived mainly from the poplar tree resins. Similarly, Winkler (1956) found, in two patients both in contact with popular trees and not with bees, positive patch tests to poplar resin as well as to propolis, suggesting that the allergen is the same. Several authors (Borlin, 1947; Rothenborg, 1967; Bunney, 1968) have shown cross-sensitivity to balsam of Peru, assuming that there must be some common sensitizing agent in propolis and balsam of Peru. However, neither of our patients had a positive patch test to balsam of Peru. Hjorth (1961) reported that poplar buds contain esters of cinnamic alcohol, and he found a positive reaction to an extract of poplar buds in three of fourteen patients with a positive patch test to balsam of Peru. As propolis contains cinnamic alcohol (Umansky, 1934) and balsam of Peru contains cinnamic acid, a cross-reaction between the various cinnamic derivates is a possibility. However, in her fifteen patients, Bunney (1968) found none positive to balsam of Peru and only one positive to the cinnamic derivates tested. Among five persons positive to poplar extracts, Rothenborg found one positive to cinnamic derivates and two to balsam of Peru. Thus, it is generally believed that the allergens in propohs are mainly derived from the poplar trees, whereas the significance of the cinnamic derivates is not yet solved. The conclusion is that in patients with recalcitrant, unexplained, periorally located eczema, contact dermatitis due to propolis should be considered as a possibility. It should be considered also in eczemas occurring in other areas because of the increasing use of propolis preparations as ointment and cosmetic moisture creams, the latter having been introduced recently otito the market.
Contact dermatitis from propolis
455
REFERENCES B.R.A. (Bee Research Associatloti) (1973) Research News No. 9. Repritited from Bee World, 54, 71. BUNNEY, M.H. (1968) Contact dermatitis in beekeepers due to propolis (Bee Glue). British Journal of Dermatology, 80, 17. BORLIN, E . (1947) Berufsekzeme bei Bienenzuchtern. Dermatologica, 94, 109. HjORTH, N. (1961) Eczematous allergy to balsams, allied perfumes and flavouring agents. Acta dermato-venereologica (Stockholm), 41, Suppl. 46. LAVIE, P. (1968) Traite de biologie de I'abeille (Ed. by R.Chauvin), Vol. 3, p. r. Masson et Cie, Paris. LiNDENFELSER, L.A. (1967) Antimicrobial activity of propolis. American Bee Journal, 107, 90, 130. MOLNAR-ToTH, M. (1965) Therapeutische Ergebnisse bei Anwendung von Propolis bei vcrschiedenen Hautkrankheiten. Apimondia der 20. Internationale Jubilaumskongress der Bienemuchter, III, 37, i. NiEBES, P. & LASZT, L . (1971) Influence in vitro d'une serie de flavonoides sur des enzymes du metabolisme des mucopolysaccaharidcs de veines saphenes humaines et bovines. Angiologica, 8, 297. ROTHENBORG, H.W. (1967) Occupational dermatitis in beekeeper due to poplar resins in beeswax. Archives of Dermatology, 95, 381. UMANSKY, G.I. (1934) Uber eine professionelle Dermatitis, verruascht durch Bienenharz Propolis. Dermatologische Wochenschrift, 98, 177. ViLLANEuvA, V.R., BoGDANOVSKY, D., BARBIER, M . , GONNET, M . & LAVIE, P. (1964) Sur I'isolement et l'identification de la 3, 5, 7 trihydroxy flavone (Galangine) a partir de la Propolis. Annales de Flnstitute Pasteur, 106, 292. ViLLANEuvA, V.R., BARBIER, M . , GONNET, M . & LAVIE, P. (1970) Les flavonoides de la Propolis isolement d'une nouvelle substance bacteriostatique: La pinocembrine [dihydroxy 5,7 flavonone]. Annales de Flnstitut Pasteur, 118,84. WiNKLER, A. (1956) Dermatitis durch Pappelharz. Dermatologische Wochenschrift, 133, 81.
Contact dermatitis from propolis BIRGITTE WANSCHER Department of Dermatology, University of Copenhagen, Rigshospital, Blegdamsvej 9, 2100 Copenhagen 0 , Denmark Accepted for publication 14 July 1975
SUMMARY
Two patients with contact dermatitis due to the natural product propolis (bee glue) are reported. They presented perioral eczema and stomatitis which were recalcitrant until propolis was considered as the cause. Patch tests with propolis preparations were positive in both patients, and, furthermore, in the second patient the lesions relapsed after provocation tests. European standard patch tests including balsam of Peru were negative. The complexity of propolis, its supposed anti-inflammatory efl'ect due to flavonoids, and the sensitizing agents originating mainly from the poplar trees are discussed together with the cross-sensitization to balsam of Peru. Contact dermatitis due to propolis should be considered in unexplained eczemas, mainly perioral but also in other areas, as propolis preparations are available also as ointments and cosmetic creams.
In many Western European countries, notably Scandinavia, Germany, Great Britain and Holland, propolis or bee glue has been known for many years. As a natural product it is sold now without prescription for several purposes as tablets, solid propolis in large or small pieces, powder, ointment, and recently as cosmetic moisture creams. Beekeeper's dermatitis due to propolis is well known (Umansky, 1934; Borlin, 1947; Rothenborg, 1967; Bunney, 1968), and Winklcr (1956) noted the apparent association between sensitivity to propolis and to poplar resins. By contrast, contact dermatitis due to propolis in persons without contact with poplar trees and in non-beekeepers has not been described previously. With increasing use of propolis it will probably be encountered more frequently by dermatologists. Furthermore, recalcitrant often periorally located eczema may remain unexplained until propolis as a cause is considered. At Rigshospital, we have seen recently two patients with contact dermatitis due to propolis.
CASE REPORTS Case I
A woman, aged 59 years, who had suffered from dry lips for many years. In 1968 she had been treated for contact dermatitis due to lipstick. During August-September 1974 she chewed, drank and ate propolis for mental depression and tiredness. After this period she continued to eat the honey. In 451
452
Birgitte Wanscher
October she noticed that her lips became unusually dry, stiff, and crusted. She did not use lipstick during these months. In an attempt to improve the condition, she tried to apply propolis honey directly to her lips. However, this caused severe pain and a burning sensation. The discomfort continued, and her lips became red and swollen despite the fact that she was treated with a corticosteroid cream. At this time the patient revealed to the dermatologist, who had treated her for 3 weeks, that all the time she had been eating propolis honey daily. Patch testing with granular propolis was subsequently performed, and a positive reaction was observed 2 days later. She was admitted to our department for recalcitrant cheilitis. On admission, an acute oozing and crusted eczema was found around her mouth and on her chin. On her back, a positive patch test from granular propolis, applied 7 days earlier, was still visible. Other patch tests including balsam of Peru were negative. The intake of propolis was stopped before admission. Her eczema cleared in a few days on treatment with carbowax 1500 containing 10% propylene glycol, lidocain ointment and a corticosteroid cream. Case 2
A woman, aged 67 years, who had suffered from Meniere's disease and migraine for many years. From 1969 to 1972 she was treated for ano-perineal prurigo and genital candidiasis. In 1972, a hysterectomy with salpingo-oophorectomy was performed for cancer. After this operation she suffered from vaginal fluor, which, according to her statement, disappeared completely within 1-2 months of using propolis. In August 1974 she started taking one tablet of propolis daily and chewing propolis for a gingival infection. Because of increasing soreness of the gums, chewing had to be given up now and then. As the gingival infection was unimproved, she tried to apply chewed propolis directly in the alveolobuccal suki, as recommended in leaflets from the producers. However, this resulted in oedema, erythema and severe pain. Three days before she was seen in the hospital she stopped taking propolis with slight improvement. On examination two aphthae and slight erythema and oedema of the mucous membrane were found in the right inferior alveolo-buccal sulcus. Patch tests with propolis honey, ointment 5",', and granular propolis in water were positive after 48 and 72 h. In April, i.e. 3 months after the first examination, the patient returned for a provocation test. In the meantime she had continued to take propolis tablets for i month. Before provocation, slight erythema was seen on the inferior gingiva corresponding to the two middle and the right lateral incisors (Fig. i). Apart from this, the mucous membranes were normal. Granular propolis, chewed for i min and placed in the inferior alveolo-buccal sulcus for i h for provocation, was used. The following evening the procedure was repeated and the time extended to 2-3 h resulting in severe pain, difficulty with talking, and in blisters. A planned provocation test on the third evening could not be performed because of the pain. Oedema, erythema, and a 6 x 7 mm white blister were found on examination on the fourth day (Fig. 2). The patient herself had made a patch test on her arm, which was positive.
DISCUSSION
Such patients with perioral eczema and stomatitis would escape an aetiological diagnosis unless the clinician is aware of the fact that propolis can give rise to contact dermatitis. In both cases propolis was mentioned by chance, and both patients believed that a preparation sold without prescription ought to be harmless. The diagnosis was confirmed by a positive provocation test in one patient, and patch tests were positive in both patients. It is well known that propolis causes allergic and not toxic patch test responses (Umansky, 1934; Borlin, 1947; Rothenborg, 1967; Bunney, 1968).
Contact dermatitis from propolis
FIGURE I. Patient 2 before provocation.
FIGURE 2. Patient 2 after provocation (see text). Oedema, erythema and a blister were seen.
453
454
Birgitte Wanscher
Jn Great Britain, several cases of contact dermatitis in beekeepers in contact with propolis have been described, and the incidence of the dermatitis among beekeepers is estimated to be 0-05/,'', (Bunney, 1968). With increasing use of propolis, more cases of contact dermatitis must be expected. Propolis, which means 'before city', is a dark yellowish-brown resinous substance with strong adhesive properties. Mixed with wax, it is used by the bees to seal up crevices in the hives, to smooth the surfaces and to protect the entrance from intruders. It is collected by the honeybees from the resinous exudations of plants and trees such as horse-chestnut {Arbor castanea), spruce {Abies nobilis), willow {Salix), larch {Larix),fir(Pinus), and especially poplar trees {Populus). Owing to the different places of origin, propolis specimens vary. However, ordinarily it contains wax 30"/,;, resins and balsams 55%, essential oils 10%, pollen 5",;, and cinnamic alcohol, minerals and flavonoids (B.R.A.; Umansky, 1934; Villaneuva et al., 1964, 1970). Since ancient times, antiseptic and healing properties in veterinary and in human medicine have been attributed to propolis. Russian dentists have called propolis a better anaesthetic than cocaine, and in Russia it is used as toothpaste, skin cream and toilet lotions. An antibacterial and antifungal action is also attributed to propolis (Lindenfclser, 1967; Lavie, 1968) and it has been foixnd to improve some skin diseases (Molnar-Toth, 1965). The main effect—if any—of propolis is supposed to be due to the flavonoids. The mechanism is considered to be a stabilization of the connective tissue and the vessels through protection of vitamin C against oxidation, which may be of some importance in the formation of collagen and in the synthesis of steroid hormones. Stabilization is caused also by the flavonoids by a decreased activity of the mucopolysaccharide-destroying enzymes (Niebes & Laszt, 1971). The effect of this stabilization could prevent the spread of infection. With the complex composition of propolis, a great number of sensitizing agents should be considered. Bunney (1968) carried out patch tests with propolis from different sources and with poplar and other tree resins. She found that ten of thirteen patients reacted to propolis and fifteen of fifteen patients reacted to poplar resin extracts. Also, Rothenborg (1967) found that his patients sensitive to poplar resins reacted to propolis, which suggested that the sensitizing allergen in propolis is derived mainly from the poplar tree resins. Similarly, Winkler (1956) found, in two patients both in contact with popular trees and not with bees, positive patch tests to poplar resin as well as to propolis, suggesting that the allergen is the same. Several authors (Borlin, 1947; Rothenborg, 1967; Bunney, 1968) have shown cross-sensitivity to balsam of Peru, assuming that there must be some common sensitizing agent in propolis and balsam of Peru. However, neither of our patients had a positive patch test to balsam of Peru. Hjorth (1961) reported that poplar buds contain esters of cinnamic alcohol, and he found a positive reaction to an extract of poplar buds in three of fourteen patients with a positive patch test to balsam of Peru. As propolis contains cinnamic alcohol (Umansky, 1934) and balsam of Peru contains cinnamic acid, a cross-reaction between the various cinnamic derivates is a possibility. However, in her fifteen patients, Bunney (1968) found none positive to balsam of Peru and only one positive to the cinnamic derivates tested. Among five persons positive to poplar extracts, Rothenborg found one positive to cinnamic derivates and two to balsam of Peru. Thus, it is generally believed that the allergens in propohs are mainly derived from the poplar trees, whereas the significance of the cinnamic derivates is not yet solved. The conclusion is that in patients with recalcitrant, unexplained, periorally located eczema, contact dermatitis due to propolis should be considered as a possibility. It should be considered also in eczemas occurring in other areas because of the increasing use of propolis preparations as ointment and cosmetic moisture creams, the latter having been introduced recently otito the market.
Contact dermatitis from propolis
455
REFERENCES B.R.A. (Bee Research Associatloti) (1973) Research News No. 9. Repritited from Bee World, 54, 71. BUNNEY, M.H. (1968) Contact dermatitis in beekeepers due to propolis (Bee Glue). British Journal of Dermatology, 80, 17. BORLIN, E . (1947) Berufsekzeme bei Bienenzuchtern. Dermatologica, 94, 109. HjORTH, N. (1961) Eczematous allergy to balsams, allied perfumes and flavouring agents. Acta dermato-venereologica (Stockholm), 41, Suppl. 46. LAVIE, P. (1968) Traite de biologie de I'abeille (Ed. by R.Chauvin), Vol. 3, p. r. Masson et Cie, Paris. LiNDENFELSER, L.A. (1967) Antimicrobial activity of propolis. American Bee Journal, 107, 90, 130. MOLNAR-ToTH, M. (1965) Therapeutische Ergebnisse bei Anwendung von Propolis bei vcrschiedenen Hautkrankheiten. Apimondia der 20. Internationale Jubilaumskongress der Bienemuchter, III, 37, i. NiEBES, P. & LASZT, L . (1971) Influence in vitro d'une serie de flavonoides sur des enzymes du metabolisme des mucopolysaccaharidcs de veines saphenes humaines et bovines. Angiologica, 8, 297. ROTHENBORG, H.W. (1967) Occupational dermatitis in beekeeper due to poplar resins in beeswax. Archives of Dermatology, 95, 381. UMANSKY, G.I. (1934) Uber eine professionelle Dermatitis, verruascht durch Bienenharz Propolis. Dermatologische Wochenschrift, 98, 177. ViLLANEuvA, V.R., BoGDANOVSKY, D., BARBIER, M . , GONNET, M . & LAVIE, P. (1964) Sur I'isolement et l'identification de la 3, 5, 7 trihydroxy flavone (Galangine) a partir de la Propolis. Annales de Flnstitute Pasteur, 106, 292. ViLLANEuvA, V.R., BARBIER, M . , GONNET, M . & LAVIE, P. (1970) Les flavonoides de la Propolis isolement d'une nouvelle substance bacteriostatique: La pinocembrine [dihydroxy 5,7 flavonone]. Annales de Flnstitut Pasteur, 118,84. WiNKLER, A. (1956) Dermatitis durch Pappelharz. Dermatologische Wochenschrift, 133, 81.
