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Contact dermatitis due to topical traditional Chinese medication
ELSEVIER
Contact Dermatitis due to Topical Traditional Chinese Medication YUNG
HIAN
LEOW,
MD
T
apical traditional Chinese medication (TTCM) has been a popular remedy for a variety of ailments in Asia. The substances can be loosely defined as medications that are herbs as prescribed by traditional Chinese medicine practitioners or patented proprietory products that can be purchased over-thecounter at Chinese medicine halls or pharmacies. They are used for the treatment of an assortment of ailments, but most commonly for the treatment of skin eruptions and symptoms of the musculoskeletal system. TTCM often contains Chinese herbal plant extracts as the main ingredients, notably terpenes (eg, camphor, menthol) and essential-oil extracts (eg, eucalyptus, cinnamon).l The exact formulations are often a potpourri of numerous ingredients, and they are guarded by most physicians and manufacturers of traditional Chinese medicine as trade secrets. Most users of TTCM have generally perceived such medicine as a group of timehonored methods of treatment that entail fewer harmful side effects, akin to homeotherapy. There are relatively few reports on contact dermatitis from TTCM in the English literature, but it has been reported extensively as a well-known entity in the Chinese literature.2 The adverse skin reactions are unique and unusual, especially taking into consideration the exotic names and complex lists of individual ingredients present in each medication. This paper reviews published reports on adverse skin reactions from TTCM that have appeared in the English literature over the past ten years. Almost all forms of dermatoses have been described, namely alirritant contact dermatitis, lergic contact dermatitis, contact urticaria, and other adverse skin reactions.
Allergic
Contact
Dermatitis
Investigators in Hong Kong, Singapore, China, and France have published reports of allergic contact dermatitis involving many topical Chinese medications (Fig 1). They include Yunnan Paiyao ( Z; r4ji $ g ), Mesonia Chinensis, 101 Hair regrowth liniment, bonesetter’s herb, musk and Tiger Bone plaster@, Tieh Ta Yao Gin (?$ fi g#), Wong Cheung Wah U 1 oil From the National Skin Centre, Singapore. Address correspondence to Dr. Yung Hian Leow, National 1 Mandalay Road, Singapore 308205, Singapore.
0 2997 by Elsevier Science Inc. 655 Auenue of the Americas, New York,
NY 20020
Skin Centre,
( 32 # -+ @ 3X @), Tiger Balm (& & A & &), Green grass oil (W @ a), Eagle brand medicated oil ( J@$5 bp, $& # ), Tjin Koo Lin (g # R), massage cream, Zheng Hong Hua oil, Ruyijinhuang paste, and Shexianghugu plaster (Table 1).1-q Most of these patients in the studies were exposed to the medications when they were used for the treatment of aches and sprains of the musculoskeletal system; however, unusual modes of sensitization have also been reported. Two investigators reported two patients who developed allergic contact dermatitis from an herbal hair-restoration liniment called 101 Hair Regrowth liniment. 5 It was marketed as an over-thecounter product in China, Hong Kong, and Japan. The exact putative allergen was not identified, because the manufacturer refused to reveal the exact formulation. The authors judged that the actual incidence of dermatitis to this liniment was probably higher, because their colleagues have seen similar cases that were not evaluated by patch testing. An investigator reported a case involving a 46-yearold Chinese worker in a soft-drink factory who developed dermatitis on his hands and forearms one week after handling Mesonia Chinensis.4 The dried leaf of this herb was used to prepare a traditional Chinese herbal tea, with purportedly medicinal value. He patch tested positive to the crushed leaf of the herb, but negative to chrysanthemum and poison ivy oleoresin. Patch testing on fifteen controls were negative. This is probably the only published report of allergic contact dermatitis to Chinese medication where the exposure was occupationally related through direct skin contact. A group of investigators reported the only case of allergic contact dermatitis to TTCM from the West.8 They reported a 26-year-old Chinese student who selftreated a contusion of his wrist with a Chinese adhesive plaster, musk and Tiger Bone plaster@. The patient patch-tested positive to the plaster and to colophony. With the help of a practitioner of Chinese medicine, they managed to obtain the composition of the plaster; and by means of infrared spectrometry they demonstrated that the plaster contained zinc resinate, which was composed of zinc oxide and colophony. In their report, they concluded that colophony was the putative allergen. These Chinese medicines were being sold and used in France.
PII
0738-082X/97/$32.00 SO738-OSZX~97~00062-8
Table 1. Allqrgic
Contact Dernmtifis Recommended ,uatch-test comenfratiol~ (‘%,)
Mcdicafiotz Wong Cheung 1 oil *igE
%I?
Wah
Vclziclr Olive
Chincsc Medicatiort
Number of pafieizfs~
oil
Vz&ber of jmtc!l-te5t posifiw C’Ollt UOk* 0 (88)
, liefhwm~ I
Singapore
Recommended test
’
’
Oil
Ea$
medicated
Massage cream Zheng Honghua Ruyijinhuang Shexianghugu
5
’
dRA4kh4l Green Grass ga!8
5
U
to Topical Traditiorznl
I+trolatum Olive
oil paste plaster
Suxiaoye-baojianxiangjing oil Fengshi paste Yunnan Paiyao 2;btkJR Mesonia Chinensis 101 Hair regrowth liniment Bonesetter’s herb Bonesetter’s herb Musk and Tiger Bone’“’ plaster Tieh Ta Yao Gin
As i5 As is
Oil
-I
As is As is
-. As is
Petrolatum
Crushed leaf (one drop)
Aqueous
As
is
-.
As is As is As is
-.-
As is
-
Almost all published reports emphasize the. difficulty in obtaining the exact formulation of these TTCM, because traditional recipes are regarded by most practitioners of Chinese medicine as being high&y confidential.s,6Even after determining the complete composition of a herbal medication, it may be extreme@ difficult to obtain the exact ingredients for patch testing;8 furthermore, even in Asia, rules and regulations pertaining to the control of sales and safety of Western medicine do not apply to traditional Chinese medication.‘” A team of investigators was able to identify the putative allergen in a Chinese herbal orthopedic solution, Tieh Ta Yao Gin. (@ fi f~# ), by patch testing three patients and ten controls with the eight individual ingredients of the herbal solution.9 The allergens. were identified as mastic and myrrh. Mastic is a gum resin obtained from Pistacin- knfiscus (Anacardiaceae), and myrrh is a gum resin obtained from the stem of-Cornmipihoramolmol englar. Both are widely used in traditional Chinese medicine as treatment for traumatic in-
.patch-
concmtrdti~m
t) (S7)
I
0 (87)
I
0 (%I)
I
Singapore
0 (86,
1
Singapore
ns (351)
2
China
ns (351)
2
China
17s (351 j
7
ns (351)
2
China China
ns (351)
7
China
ns (351)
2
No controls
3
China Hong Kong
0 (15)
4
Singapore
0 (20)
5
Hong
0 (20)
h
0 (20)
7 x
Hong Kong Hong Kong France
2411ergen: Allergen:
myrrh colophony
0 (IO)
‘j
Hong
Allergen:
mastic,
Kong
Kong
One -patient was not patch tested .~ Another patient had contact urticaria to plaster Tested by doing use test Tested
-by doing
use test
Herhal tea: occupanonal exposure Herbal hair restoratron liniment
-~
myr?h
juries.” Myrrh contains some known sensitizers, like eugenol and cinnamic aldehyde.12 These resins are used in Western medicine, but in a totally different wa~,~~> The same investigators also identified myrrh as the putative allergen, causing allergic contact dermatitis to another Chine* medicine.’ With the help of a bonesetter, who is a practitioner of traditional Chinese medir tine specializing in treatment of musculoskeletal injury, they obtained mixtures of bonesetter’s herbs, both with and without-the addition of myrrh and mastic, By systematically eliminating each allergerrd.uring patch testing on one patient and twenty controls,. they were able to conchrde that myrrh was the allergen. h-r Singaporei a group of investigators identified the ten most commonly used TTCMs that had previously been used by 116 patients who~attended their patch.&& ciinicr The alkzrgenic and irritant potentials of these ten medications were evaluated by means -of -patch testing patients and controls, with serial dilution- of each-medication. A par-& of these ten TTCMs, at. .the appropriate
Clinics in Dermatology
l
1997;15:601-605
TOPICAL
TRADITIONAL
CHINESE
MEDICINE
603
Table 2. Irritant Contact Dermatitis to Tovical Traditional Chinese Medication (Plaster) Patch-test concentration (%)
Medication Blackman
oil
Vehicle
Number of vatients
Number of patchtest positive controls*
Reference
2
15 (20)
10
Hong
Kong
14
Hong
Kong
17
Hong
Kong
As is
Country
Zh!!!g%9hui
As is
-
4
LZe!&
As is
-
2
As is
-
-
2 (20)
18
Hong
Kong
JaZnZn%
As is
-
-
3 (20)
18
Hong
Kong
Tig
zl?
As is
-
2 (20)
18
Hong
Kong
Huig
!!r
-
8 (20)
18
Hong
Kong
He2
(~%!!wn)
nst (351)
2
iwk, White flower
*Numerical
oil
51”
’
figures
in parentheses
As is
-
As is
-
denote
the number
2
8 (20) 13 (15)
China
Remarks Irritant: turpentine oil Also caused allergic contact dermatitis Irritant: venenum bufonis Evaluation of 11 common herbal topical medications
One patient tested
was not
of controls.
t ns = not stated.
patch-test concentrations and vehicles, was compiled for patch testing in the clinic. The problem of falsepositive irritant reaction that had been encountered by other workers, can be overcome by the careful serial dilution of the test substances;14 however, some true positive reactions may have been missed. A group of investigators reported that there is a risk of false negatives associated with the serial dilution procedure that they used to identify the optimal patch test concentration for amalgam. 15 For purposes of practical identification, the authors attempted to classify the ten TTCMs into three main categories: herbal oils, bonesetters’ herbal oil, and topical antifungal medication; however, such a classification may be too simplistic in view of the vast variety of TTCMs available in the market. As patients are usually also patch tested with the standard screening series, several investigators have observed that concomitant positive patch-test reactions to fragrance mix and/or balsam of Peru is often present in patients with contact allergy to TTCM.l,* Chinese medications that contain essential-oil extracts are perfume essences,*6 and they probably cross react with the fragrance mix in the standard patch test series. Patients with positive patch-test reactions to fragrance mix and balsam of Peru should be advised to avoid using TTCM. Patch testing to the individual allergens in the fragrance mix of the standard series and allergens in the fragrance/flavor series may help to uncover the elusive putative allergen in traditional Chinese herbal medication.
Irritant
Contact
White flower oil (e j& *i), Jaminton oil (8 ‘J- jl~), Tiger Balm (& & 5 & a), Hung Far oil (h s a), and Zheng Gu Shui (Jo # ;Ik) (Table 2).10,*4,17,18A group of investigators identified Venenum Bufonis as the likely putative irritant, causing irritant contact dermatitis to Lu-Shen-Wan (A # A).” The former consists of the dried secretion of the skin glands of the toad, and it was used as an analgesic and detoxicant. They patch tested fifteen controls to Venenum Bufonis at 0.5%, 5%, and 50% in aqueous medium. None reacted to the 0.5% preparation, two had transient erythema to the 5% preparation, and thirteen of the fifteen controls developed strong irritant reactions to the 50% preparation. The instruction given on the label of this medicinal powder was to mix it with “a small amount of water”. The investigators felt that the imprecise instruction was the cause of this preventable side effect. The same authors also postulated that turpentine oil was the most likely putative irritant in Blackman oil (# % m), though patch testing to the individual ingredients of the medicinal oil was not performed.lO The presence of unknown solvents, possibly mineral oils, may be the cause for these irritant skin reactions; but without the knowledge of the precise formulation of these TTCMs, it remains a mere postulation. There is probably underreporting of cases of irritant contact dermatitis to TTCMs, because the exact mode of application of these medicinal embrocations is not standardized; and some users probably dismiss this adverse skin reaction as an expected side effect.
Dermatitis
Irritant contact dermatitis to topical traditional Chinese medication is not uncommon. It has been reported with Lu-Shen-Wan (fc # a), Blackman oil (R !& #I),
Contact
Urticaria
An investigator who developed
reported a 32-year-old Chinese patient contact urticaria after using Shexiang-
604 LEOW
hugu plaster. The reason for use was not stated in the report .(Table 1). The patient reacted to a use test with the plaster. In the same paper, other cases of contact urticaria and anaphylaxis that had previously been reported in China were summarized in a table;-however, not enough details on the clinical presentations and investigations were given to permit close scrutiny.
Other Adverse Skin Reactions A group of investigators reported a 2%year-old Chinese patient who developed exanthematous drug eruption eight days after ingesting a Sanjieling cappill sule (it9 $3 5QZ #RI and a Huoxuexiaoyan (# I& ff & A).‘9 The patient patch tested positive to the medications and myrrh, which was an ingredient in the capsule. The report did not state whether the patient was sensitized topically to the allergen previously. Systemic, phototoxic, and photoallergic contact dermatitis from ingestion of Chinese medication-had been reported in China, as referenced by the investigator. Unfortunately, little clinical information was available in the paper.2
Evaluation Traditional
of Contact Derrpatitis. to Topical Chinese Medication
The principle in evaluating patients with contact dermatitis to TTCM should be similar to the investigation of contact dermatitis to other typesof topical medicine. Patch testing should be performed-in the standard way, as recommended by the International. Contact Dermatitis Research Group .*OPatients should be patch tested to the standard series, and, if positive reactions to the fragrance mix and/or balsam of Peru are detected, to the fragrance and flavor series as well. Investigators often encounter a problem when patch testing to TTCM and its ingredients, because the patchtest concentration and- vehicle will have to :be determined on by trial and error, There are no text references on patch-test concentration to these relatively rare and exotic test substances;21in addition, the exa&constituents of the medication are often unknown. If the test medication is a suspected irritant,-it may be advisable to conduct an open test followed by serial dilutions. Patch testing on an adequate number of controls is imperative to exclude false positive reactions. A use test or a repeat open-application test may be used as an adjunct to confirm a doubtful weak positive patchtest reaction, which may be allergic in nature. The author recommends that patch&t clinics identify a panel of common TTCMs used in their countries. The clinic should then evaluate the irritancy of these medications and establish appropriate patch-test concentrations. Enlisting the help of a practitioner of traditional C-hinese medicine may be rewarding. He or she can some-
help to ascertain the constituents of the TTCM and help the dermatologist identify the putative contact allergen.7 Methods ~of investigating other adverse skin reactions, sueh as contact urticaria, should also be per formed in the standard yay.2Z Scientific chemical analysis, as has been utilhed by the French workers,x will make the identification of the putative allergen simpler and more fruitful for the investigating dermatologist. times
Conclusions Over the past few years, tnere nave oeen numerous reports in the English literature onthe beneficial effects of traditional Chinese medicine for the treatment of various illness, including atopic eczema.23-2sThese re-. ports often refer to orai traditional Chinese medicine.. TTCM may be included here as more people are using TTCM for various musculoskeletal symptoms. ,4s has been emphasized by an investigator, there are-many unresolved issues concerning the safety, side effects, standards, and quality control of traditional Chinese medicine.26 The. author encourages dermatologists to report any casesof contact dermatitis to TTCM, in order that awareness of their possible side effects be pro moted.
References 1. Leow Y-H, 2
3 L(
Ng S-K, Wong ~W-K, et al. Contact
allergic
potential of topical traditional Chinese medicamentsin Singapore.Am J Contact Dern&titis 1995;6:1-8. Li L-F. A clinical and patch test study of contact dermatitis from traditional Chinese medicinal materials. C&tact Dermatitis 1995;33:392-5. Lee TY, Lam TH. Allergic contact dermatitis to Yunnan
Paiyao. Contact Dermatitis 1987;17:59-60. GohCL. Occupational dermatitis from Mesomia Chinensis. Contact~Dermatitis 1988;18:113. 5. Lee TY, Lam TH. Allergic contact dermatitis due to 101 hair regrowth liniment. Contact Dermatitis 19&9;20:389 90. 6. Lee TY, Lam TH. Bone-setter’s herbs dermatitis in Hong Kong. Contact Dermatitis 1991~24304-6. 7. Lee TY, Lam ?!H. Myrrh is the.putative allergen in bonesetter’s herbs dermatitis. Contact Dermati& 1993;29?79. 8. Barbaud A, Mongeolle JM, Tang JQ, et al. Contact allergy to colophony in Chinese-musk and Tiger-Bone pIa&+. Contact Dermatitis 1991;25:324-5. 9, Lee TY, Lam TEL Allergic contact- dermatitis .due to a Chinese orthopaedic solution Tieh Ta Yao GiTi. Contact 4.
Dermatitis 1993;28:89-90.
10. Lee
TY, Lam TH. Irritant contact dermatitis due toherbal oil, Black man oil. Contact Den&at& 1?X9~O:229-31)7. 11. Xie Z, Huang X, ed. Dictionary of traditional Chinese medicine. Hong Kong: Commercial Press, 1984:198. 12. Jiangsu Medical University, editor, A dictionary~of Chinese materia medica. Shanghai: Shanghai Science Pressr 1985, pp 1167-9. 13. Reynolds JEF, editor...Martindale. The extra pharmaccs
Clinics in Dermatology
14.
15.
16. 17.
18.
19.
l
1997;15:601-605
paeia. 29th edition. London: The Pharmaceutical Press, 1989, pp 1586-93. Lee TY, Lam TH. Contact dermatitis due to a Chinese herbal orthopaedic tincture, Zheng Gu Shui. Contact Dermatitis 1991;24:64-5. Von Mayenburg J, Rakoski J, Szliska C. Patch testing with amalgam at various concentrations. Contact Dermatitis 1991;24:266-9. Rietschel RL, Fowler JF Jr, editors. Fisher’s contact dermatitis. Baltimore: Williams & Wilkins, 1995, pp 461523. Lee TY, Lam TH. Irritant contact dermatitis due to a Chinese herbal medicine Lu-Shen-Wan. Contact Dermatitis. 1988;18:213-8. Lee TY, Lam TH. Patch testing of 11 common herbal topical medicaments in Hong Kong. Contact Dermatitis 1990;22:137-40. Li L-F, Zhao J, Li S-Y. Exanthematous drug eruption due to Chinese herbal medicines Sanjieling capsule and Huoxuexiaoyan pill. Contact Dermatitis 1994;30:252-3.
TOPICAL TRADITIONAL
CHINESE MEDICINE
605
20. Cronin E, editor. Contact dermatitis. Edinburgh: Churchill Livingstone, 1980:1-19. 21. De Groot AC, editor. Patch testing. Test concentrations for 3700 chemicals. Amsterdam, The Netherland: Elsevier Science Publishers, 1994. 22. Von Krogh G, Maibach HI. The contact urticaria syndrome-an update review. J Am Acad Dermatol 1981;5: 328-42. 23. Sheehan MI’, Atherton DJ. A controlled trial of traditional Chinese medicinal plants in widespread non-exudative atopic eczema. Br J Dermatol 1992;126:179-84. 24. Sheehan MI’, Rustin MHA, Atherton DJ, et al. Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis. Lancet 1992;340:13-7. 25. Latchman Y, Whittle B, Rustin M, et al. The efficacy of traditional Chinese herbal therapy in atopic eczema. Int Arch Allergy Immunol 1994;104:222-6. 26. Harper J. Traditional Chinese medicine for eczema. BMJ 1994;308:489-90.
Contact Dermatitis due to Topical Traditional Chinese Medication YUNG
HIAN
LEOW,
MD
T
apical traditional Chinese medication (TTCM) has been a popular remedy for a variety of ailments in Asia. The substances can be loosely defined as medications that are herbs as prescribed by traditional Chinese medicine practitioners or patented proprietory products that can be purchased over-thecounter at Chinese medicine halls or pharmacies. They are used for the treatment of an assortment of ailments, but most commonly for the treatment of skin eruptions and symptoms of the musculoskeletal system. TTCM often contains Chinese herbal plant extracts as the main ingredients, notably terpenes (eg, camphor, menthol) and essential-oil extracts (eg, eucalyptus, cinnamon).l The exact formulations are often a potpourri of numerous ingredients, and they are guarded by most physicians and manufacturers of traditional Chinese medicine as trade secrets. Most users of TTCM have generally perceived such medicine as a group of timehonored methods of treatment that entail fewer harmful side effects, akin to homeotherapy. There are relatively few reports on contact dermatitis from TTCM in the English literature, but it has been reported extensively as a well-known entity in the Chinese literature.2 The adverse skin reactions are unique and unusual, especially taking into consideration the exotic names and complex lists of individual ingredients present in each medication. This paper reviews published reports on adverse skin reactions from TTCM that have appeared in the English literature over the past ten years. Almost all forms of dermatoses have been described, namely alirritant contact dermatitis, lergic contact dermatitis, contact urticaria, and other adverse skin reactions.
Allergic
Contact
Dermatitis
Investigators in Hong Kong, Singapore, China, and France have published reports of allergic contact dermatitis involving many topical Chinese medications (Fig 1). They include Yunnan Paiyao ( Z; r4ji $ g ), Mesonia Chinensis, 101 Hair regrowth liniment, bonesetter’s herb, musk and Tiger Bone plaster@, Tieh Ta Yao Gin (?$ fi g#), Wong Cheung Wah U 1 oil From the National Skin Centre, Singapore. Address correspondence to Dr. Yung Hian Leow, National 1 Mandalay Road, Singapore 308205, Singapore.
0 2997 by Elsevier Science Inc. 655 Auenue of the Americas, New York,
NY 20020
Skin Centre,
( 32 # -+ @ 3X @), Tiger Balm (& & A & &), Green grass oil (W @ a), Eagle brand medicated oil ( J@$5 bp, $& # ), Tjin Koo Lin (g # R), massage cream, Zheng Hong Hua oil, Ruyijinhuang paste, and Shexianghugu plaster (Table 1).1-q Most of these patients in the studies were exposed to the medications when they were used for the treatment of aches and sprains of the musculoskeletal system; however, unusual modes of sensitization have also been reported. Two investigators reported two patients who developed allergic contact dermatitis from an herbal hair-restoration liniment called 101 Hair Regrowth liniment. 5 It was marketed as an over-thecounter product in China, Hong Kong, and Japan. The exact putative allergen was not identified, because the manufacturer refused to reveal the exact formulation. The authors judged that the actual incidence of dermatitis to this liniment was probably higher, because their colleagues have seen similar cases that were not evaluated by patch testing. An investigator reported a case involving a 46-yearold Chinese worker in a soft-drink factory who developed dermatitis on his hands and forearms one week after handling Mesonia Chinensis.4 The dried leaf of this herb was used to prepare a traditional Chinese herbal tea, with purportedly medicinal value. He patch tested positive to the crushed leaf of the herb, but negative to chrysanthemum and poison ivy oleoresin. Patch testing on fifteen controls were negative. This is probably the only published report of allergic contact dermatitis to Chinese medication where the exposure was occupationally related through direct skin contact. A group of investigators reported the only case of allergic contact dermatitis to TTCM from the West.8 They reported a 26-year-old Chinese student who selftreated a contusion of his wrist with a Chinese adhesive plaster, musk and Tiger Bone plaster@. The patient patch-tested positive to the plaster and to colophony. With the help of a practitioner of Chinese medicine, they managed to obtain the composition of the plaster; and by means of infrared spectrometry they demonstrated that the plaster contained zinc resinate, which was composed of zinc oxide and colophony. In their report, they concluded that colophony was the putative allergen. These Chinese medicines were being sold and used in France.
PII
0738-082X/97/$32.00 SO738-OSZX~97~00062-8
Table 1. Allqrgic
Contact Dernmtifis Recommended ,uatch-test comenfratiol~ (‘%,)
Mcdicafiotz Wong Cheung 1 oil *igE
%I?
Wah
Vclziclr Olive
Chincsc Medicatiort
Number of pafieizfs~
oil
Vz&ber of jmtc!l-te5t posifiw C’Ollt UOk* 0 (88)
, liefhwm~ I
Singapore
Recommended test
’
’
Oil
Ea$
medicated
Massage cream Zheng Honghua Ruyijinhuang Shexianghugu
5
’
dRA4kh4l Green Grass ga!8
5
U
to Topical Traditiorznl
I+trolatum Olive
oil paste plaster
Suxiaoye-baojianxiangjing oil Fengshi paste Yunnan Paiyao 2;btkJR Mesonia Chinensis 101 Hair regrowth liniment Bonesetter’s herb Bonesetter’s herb Musk and Tiger Bone’“’ plaster Tieh Ta Yao Gin
As i5 As is
Oil
-I
As is As is
-. As is
Petrolatum
Crushed leaf (one drop)
Aqueous
As
is
-.
As is As is As is
-.-
As is
-
Almost all published reports emphasize the. difficulty in obtaining the exact formulation of these TTCM, because traditional recipes are regarded by most practitioners of Chinese medicine as being high&y confidential.s,6Even after determining the complete composition of a herbal medication, it may be extreme@ difficult to obtain the exact ingredients for patch testing;8 furthermore, even in Asia, rules and regulations pertaining to the control of sales and safety of Western medicine do not apply to traditional Chinese medication.‘” A team of investigators was able to identify the putative allergen in a Chinese herbal orthopedic solution, Tieh Ta Yao Gin. (@ fi f~# ), by patch testing three patients and ten controls with the eight individual ingredients of the herbal solution.9 The allergens. were identified as mastic and myrrh. Mastic is a gum resin obtained from Pistacin- knfiscus (Anacardiaceae), and myrrh is a gum resin obtained from the stem of-Cornmipihoramolmol englar. Both are widely used in traditional Chinese medicine as treatment for traumatic in-
.patch-
concmtrdti~m
t) (S7)
I
0 (87)
I
0 (%I)
I
Singapore
0 (86,
1
Singapore
ns (351)
2
China
ns (351)
2
China
17s (351 j
7
ns (351)
2
China China
ns (351)
7
China
ns (351)
2
No controls
3
China Hong Kong
0 (15)
4
Singapore
0 (20)
5
Hong
0 (20)
h
0 (20)
7 x
Hong Kong Hong Kong France
2411ergen: Allergen:
myrrh colophony
0 (IO)
‘j
Hong
Allergen:
mastic,
Kong
Kong
One -patient was not patch tested .~ Another patient had contact urticaria to plaster Tested by doing use test Tested
-by doing
use test
Herhal tea: occupanonal exposure Herbal hair restoratron liniment
-~
myr?h
juries.” Myrrh contains some known sensitizers, like eugenol and cinnamic aldehyde.12 These resins are used in Western medicine, but in a totally different wa~,~~> The same investigators also identified myrrh as the putative allergen, causing allergic contact dermatitis to another Chine* medicine.’ With the help of a bonesetter, who is a practitioner of traditional Chinese medir tine specializing in treatment of musculoskeletal injury, they obtained mixtures of bonesetter’s herbs, both with and without-the addition of myrrh and mastic, By systematically eliminating each allergerrd.uring patch testing on one patient and twenty controls,. they were able to conchrde that myrrh was the allergen. h-r Singaporei a group of investigators identified the ten most commonly used TTCMs that had previously been used by 116 patients who~attended their patch.&& ciinicr The alkzrgenic and irritant potentials of these ten medications were evaluated by means -of -patch testing patients and controls, with serial dilution- of each-medication. A par-& of these ten TTCMs, at. .the appropriate
Clinics in Dermatology
l
1997;15:601-605
TOPICAL
TRADITIONAL
CHINESE
MEDICINE
603
Table 2. Irritant Contact Dermatitis to Tovical Traditional Chinese Medication (Plaster) Patch-test concentration (%)
Medication Blackman
oil
Vehicle
Number of vatients
Number of patchtest positive controls*
Reference
2
15 (20)
10
Hong
Kong
14
Hong
Kong
17
Hong
Kong
As is
Country
Zh!!!g%9hui
As is
-
4
LZe!&
As is
-
2
As is
-
-
2 (20)
18
Hong
Kong
JaZnZn%
As is
-
-
3 (20)
18
Hong
Kong
Tig
zl?
As is
-
2 (20)
18
Hong
Kong
Huig
!!r
-
8 (20)
18
Hong
Kong
He2
(~%!!wn)
nst (351)
2
iwk, White flower
*Numerical
oil
51”
’
figures
in parentheses
As is
-
As is
-
denote
the number
2
8 (20) 13 (15)
China
Remarks Irritant: turpentine oil Also caused allergic contact dermatitis Irritant: venenum bufonis Evaluation of 11 common herbal topical medications
One patient tested
was not
of controls.
t ns = not stated.
patch-test concentrations and vehicles, was compiled for patch testing in the clinic. The problem of falsepositive irritant reaction that had been encountered by other workers, can be overcome by the careful serial dilution of the test substances;14 however, some true positive reactions may have been missed. A group of investigators reported that there is a risk of false negatives associated with the serial dilution procedure that they used to identify the optimal patch test concentration for amalgam. 15 For purposes of practical identification, the authors attempted to classify the ten TTCMs into three main categories: herbal oils, bonesetters’ herbal oil, and topical antifungal medication; however, such a classification may be too simplistic in view of the vast variety of TTCMs available in the market. As patients are usually also patch tested with the standard screening series, several investigators have observed that concomitant positive patch-test reactions to fragrance mix and/or balsam of Peru is often present in patients with contact allergy to TTCM.l,* Chinese medications that contain essential-oil extracts are perfume essences,*6 and they probably cross react with the fragrance mix in the standard patch test series. Patients with positive patch-test reactions to fragrance mix and balsam of Peru should be advised to avoid using TTCM. Patch testing to the individual allergens in the fragrance mix of the standard series and allergens in the fragrance/flavor series may help to uncover the elusive putative allergen in traditional Chinese herbal medication.
Irritant
Contact
White flower oil (e j& *i), Jaminton oil (8 ‘J- jl~), Tiger Balm (& & 5 & a), Hung Far oil (h s a), and Zheng Gu Shui (Jo # ;Ik) (Table 2).10,*4,17,18A group of investigators identified Venenum Bufonis as the likely putative irritant, causing irritant contact dermatitis to Lu-Shen-Wan (A # A).” The former consists of the dried secretion of the skin glands of the toad, and it was used as an analgesic and detoxicant. They patch tested fifteen controls to Venenum Bufonis at 0.5%, 5%, and 50% in aqueous medium. None reacted to the 0.5% preparation, two had transient erythema to the 5% preparation, and thirteen of the fifteen controls developed strong irritant reactions to the 50% preparation. The instruction given on the label of this medicinal powder was to mix it with “a small amount of water”. The investigators felt that the imprecise instruction was the cause of this preventable side effect. The same authors also postulated that turpentine oil was the most likely putative irritant in Blackman oil (# % m), though patch testing to the individual ingredients of the medicinal oil was not performed.lO The presence of unknown solvents, possibly mineral oils, may be the cause for these irritant skin reactions; but without the knowledge of the precise formulation of these TTCMs, it remains a mere postulation. There is probably underreporting of cases of irritant contact dermatitis to TTCMs, because the exact mode of application of these medicinal embrocations is not standardized; and some users probably dismiss this adverse skin reaction as an expected side effect.
Dermatitis
Irritant contact dermatitis to topical traditional Chinese medication is not uncommon. It has been reported with Lu-Shen-Wan (fc # a), Blackman oil (R !& #I),
Contact
Urticaria
An investigator who developed
reported a 32-year-old Chinese patient contact urticaria after using Shexiang-
604 LEOW
hugu plaster. The reason for use was not stated in the report .(Table 1). The patient reacted to a use test with the plaster. In the same paper, other cases of contact urticaria and anaphylaxis that had previously been reported in China were summarized in a table;-however, not enough details on the clinical presentations and investigations were given to permit close scrutiny.
Other Adverse Skin Reactions A group of investigators reported a 2%year-old Chinese patient who developed exanthematous drug eruption eight days after ingesting a Sanjieling cappill sule (it9 $3 5QZ #RI and a Huoxuexiaoyan (# I& ff & A).‘9 The patient patch tested positive to the medications and myrrh, which was an ingredient in the capsule. The report did not state whether the patient was sensitized topically to the allergen previously. Systemic, phototoxic, and photoallergic contact dermatitis from ingestion of Chinese medication-had been reported in China, as referenced by the investigator. Unfortunately, little clinical information was available in the paper.2
Evaluation Traditional
of Contact Derrpatitis. to Topical Chinese Medication
The principle in evaluating patients with contact dermatitis to TTCM should be similar to the investigation of contact dermatitis to other typesof topical medicine. Patch testing should be performed-in the standard way, as recommended by the International. Contact Dermatitis Research Group .*OPatients should be patch tested to the standard series, and, if positive reactions to the fragrance mix and/or balsam of Peru are detected, to the fragrance and flavor series as well. Investigators often encounter a problem when patch testing to TTCM and its ingredients, because the patchtest concentration and- vehicle will have to :be determined on by trial and error, There are no text references on patch-test concentration to these relatively rare and exotic test substances;21in addition, the exa&constituents of the medication are often unknown. If the test medication is a suspected irritant,-it may be advisable to conduct an open test followed by serial dilutions. Patch testing on an adequate number of controls is imperative to exclude false positive reactions. A use test or a repeat open-application test may be used as an adjunct to confirm a doubtful weak positive patchtest reaction, which may be allergic in nature. The author recommends that patch&t clinics identify a panel of common TTCMs used in their countries. The clinic should then evaluate the irritancy of these medications and establish appropriate patch-test concentrations. Enlisting the help of a practitioner of traditional C-hinese medicine may be rewarding. He or she can some-
help to ascertain the constituents of the TTCM and help the dermatologist identify the putative contact allergen.7 Methods ~of investigating other adverse skin reactions, sueh as contact urticaria, should also be per formed in the standard yay.2Z Scientific chemical analysis, as has been utilhed by the French workers,x will make the identification of the putative allergen simpler and more fruitful for the investigating dermatologist. times
Conclusions Over the past few years, tnere nave oeen numerous reports in the English literature onthe beneficial effects of traditional Chinese medicine for the treatment of various illness, including atopic eczema.23-2sThese re-. ports often refer to orai traditional Chinese medicine.. TTCM may be included here as more people are using TTCM for various musculoskeletal symptoms. ,4s has been emphasized by an investigator, there are-many unresolved issues concerning the safety, side effects, standards, and quality control of traditional Chinese medicine.26 The. author encourages dermatologists to report any casesof contact dermatitis to TTCM, in order that awareness of their possible side effects be pro moted.
References 1. Leow Y-H, 2
3 L(
Ng S-K, Wong ~W-K, et al. Contact
allergic
potential of topical traditional Chinese medicamentsin Singapore.Am J Contact Dern&titis 1995;6:1-8. Li L-F. A clinical and patch test study of contact dermatitis from traditional Chinese medicinal materials. C&tact Dermatitis 1995;33:392-5. Lee TY, Lam TH. Allergic contact dermatitis to Yunnan
Paiyao. Contact Dermatitis 1987;17:59-60. GohCL. Occupational dermatitis from Mesomia Chinensis. Contact~Dermatitis 1988;18:113. 5. Lee TY, Lam TH. Allergic contact dermatitis due to 101 hair regrowth liniment. Contact Dermatitis 19&9;20:389 90. 6. Lee TY, Lam TH. Bone-setter’s herbs dermatitis in Hong Kong. Contact Dermatitis 1991~24304-6. 7. Lee TY, Lam ?!H. Myrrh is the.putative allergen in bonesetter’s herbs dermatitis. Contact Dermati& 1993;29?79. 8. Barbaud A, Mongeolle JM, Tang JQ, et al. Contact allergy to colophony in Chinese-musk and Tiger-Bone pIa&+. Contact Dermatitis 1991;25:324-5. 9, Lee TY, Lam TEL Allergic contact- dermatitis .due to a Chinese orthopaedic solution Tieh Ta Yao GiTi. Contact 4.
Dermatitis 1993;28:89-90.
10. Lee
TY, Lam TH. Irritant contact dermatitis due toherbal oil, Black man oil. Contact Den&at& 1?X9~O:229-31)7. 11. Xie Z, Huang X, ed. Dictionary of traditional Chinese medicine. Hong Kong: Commercial Press, 1984:198. 12. Jiangsu Medical University, editor, A dictionary~of Chinese materia medica. Shanghai: Shanghai Science Pressr 1985, pp 1167-9. 13. Reynolds JEF, editor...Martindale. The extra pharmaccs
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paeia. 29th edition. London: The Pharmaceutical Press, 1989, pp 1586-93. Lee TY, Lam TH. Contact dermatitis due to a Chinese herbal orthopaedic tincture, Zheng Gu Shui. Contact Dermatitis 1991;24:64-5. Von Mayenburg J, Rakoski J, Szliska C. Patch testing with amalgam at various concentrations. Contact Dermatitis 1991;24:266-9. Rietschel RL, Fowler JF Jr, editors. Fisher’s contact dermatitis. Baltimore: Williams & Wilkins, 1995, pp 461523. Lee TY, Lam TH. Irritant contact dermatitis due to a Chinese herbal medicine Lu-Shen-Wan. Contact Dermatitis. 1988;18:213-8. Lee TY, Lam TH. Patch testing of 11 common herbal topical medicaments in Hong Kong. Contact Dermatitis 1990;22:137-40. Li L-F, Zhao J, Li S-Y. Exanthematous drug eruption due to Chinese herbal medicines Sanjieling capsule and Huoxuexiaoyan pill. Contact Dermatitis 1994;30:252-3.
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20. Cronin E, editor. Contact dermatitis. Edinburgh: Churchill Livingstone, 1980:1-19. 21. De Groot AC, editor. Patch testing. Test concentrations for 3700 chemicals. Amsterdam, The Netherland: Elsevier Science Publishers, 1994. 22. Von Krogh G, Maibach HI. The contact urticaria syndrome-an update review. J Am Acad Dermatol 1981;5: 328-42. 23. Sheehan MI’, Atherton DJ. A controlled trial of traditional Chinese medicinal plants in widespread non-exudative atopic eczema. Br J Dermatol 1992;126:179-84. 24. Sheehan MI’, Rustin MHA, Atherton DJ, et al. Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis. Lancet 1992;340:13-7. 25. Latchman Y, Whittle B, Rustin M, et al. The efficacy of traditional Chinese herbal therapy in atopic eczema. Int Arch Allergy Immunol 1994;104:222-6. 26. Harper J. Traditional Chinese medicine for eczema. BMJ 1994;308:489-90.