Contact allergic potential of topical traditional Chinese medicaments in Singapore

ORIGINAL ARTICLES

Contact Allergic Potential of Topical Traditional Chinese Medicaments in Singapore Yung-Hian Leow, See-Ket Ng, Wai-Kee Wong, and Chee-Leok Goh Background: Western-based medication forms the basis of the health care system in Singapore. However, because Singapore is part of East Asia, there is still a high prevalence of use of topical traditional Chinese medicaments by the general population. Objective: This study was designed to determine the 10 most commonly used topical traditional Chinese medicaments by patients who were attending the Contact & Occupational Dermatoses Clinic. The final aim of the study was to put together a panel at the correct eliciting concentration for patch testing. Methods: Patients were interviewed and asked to identify the products that they had previously used from a panel of 74 medicaments. The 10 most commonly used topical traditional Chinese medicaments were then identified. Patients were then patch

tested to these 10 preparations at concentrations varying from 1%, 5%, 10%, 20%, and 50% in each respective vehicle and as is. Results: No contact reaction was detected with five medicaments, but allergic contact reactions were detected with the other five preparations. These patients also had positive reactions to fragrance mix and/or balsam of Peru. Conclusions: Development of special panels for unique contact allergens in different regions with different social and cultural backgrounds is essential. Patients with positive reactions to balsam of Peru and fragrance mix should be advised against excessive use of topical traditional Chinese medicaments.

E1STERN-BASED MEDICATION had argely dominated medical care in the health system in Singapore. However, being at the crossroads of the East and West, the multiracial population of Singapore still retains their unique blend of culture and heritage. This is shown by the relatively high prevalence of use of topical traditional Chinese medicaments for minor ailments even by the non-Chinese people. Lee and Lam I patch tested their patients to 11 herbal topical medicaments and reported irritant potential in only one embrocation. This seemed to be consistent with the common belief that traditional herbal preparations were fairly innocuous. This study was designed to determine the 10 topical traditional Chinese medicaments most commonly used by our patients at the National Skin Centre and to further evaluate the prevalence of contact allergy of these medicaments. The final aim

of the study was to put together a panel of topical traditional Chinese medicaments at the correct eliciting concentration for patch testing at our Contact Dermatitis Clinic.

From the National Skin Centre, Singapore. Address reprint requests to Y.H. Leow, MBBS, National Skin Centre, 1, Mandalay Rd, Singapore 1130. Copyright © 1995 by W..B. Saunders Company 1046-199X/95/0601-0002503.00/0

4

Copyright © 1995 by W.B. Saunders Company

MATERIALS AND METHODS The study was performed in two phases.

Phase A Phase A involved the determination of the l0 most commonly used topical traditional Chinese medicaments used by our patients at the Contact & Occupational Dermatoses Clinic. With the assistance of our pharmacist, we purchased a total of 74 topical traditional Chinese medicaments randomly selected from the numerous Chinese medicine shops in Singapore. All of the medications were bought over the counter and were finished products in creams, ointments, or lotions. Consecutive patients who were attending our clinic for patch testing were interviewed. At the interview, the patients were shown the range of 74 topical traditional Chinese medicaments and were asked to identify the products that they had previously used. A list of the 10 most commonly used topical traditional Chinese medicaments was then compiled.

Phase B Phase B involved the evaluation of the prevalence of contact allergy of the 10 most popular topical traditional

American Journal of Contact Dermatitis, Vol 6, No 1 (March), 1995: pp 4-8

TOPICAL TRADITIONAL CHINESE MEDICAMENTS

Chinese medicaments in patients attending our clinic. Because there were previous reports on the potential irritancy of topical Chinese medicaments, ~-3 we also determined the nonirritating concentration for patch testing with the panel of medicaments. Inclusion criteria for the patients were patients who were referred to the Contact & Occupational Dermatoses Clinic for evaluation of an allergic contact dermatitis not related to the usage of topical traditional Chinese medicaments and patients whose primary dermatitis was quiescient and under control. To ascertain the correct concentration for patch testing to avoid irritant reaction, the 10 topical traditional Chinese medicaments were prepared at concentrations ranging from 1%, 5%, 10%, 20%, and 50% in their respective vehicle and as is. Olive oil and yellow soft paraffin were chosen as the vehicles for oil base and ointment-based medication, respectively (Table 1). Patch tests were performed according to the International Contact Dermatitis Research Group recommendation4 using Finn chambers (Epitest Oy, Helsinki, Finland) on Scanpor tape (Norgesplaster A/S, Oslo, Norway). The substances used for patch testing included the standard series, other suspected substances relevant to the patient's problem, and the series of topical traditional Chinese medicaments. The reactions were observed after 48 and 96 hours and graded in the standard way. Patients were patch tested in different cohorts consisting of 10-20 patients at varying concentrations of the series of topical traditional Chinese medicaments. Patch test results were reviewed at regular intervals at completion of a particular concentration for each respective medicament. The highest concentration at which no contact reaction (irritant) was elicited was determined for each medicament.

RESULTS Phase A

A total of 116 patients were interviewed. Nine patients did not use any of the 74 topical traditional Chinese medicaments. The prevalence of use was 92.2% (107 of 116). The sex ratio of the patients was about equal (57 males and 50 females). Racial breakdown was as follows: 83% Chinese (89), 8.4% Malay (9), 7.5% Indian (8), and 1.1% other ethnic groups (1). The majority of the interviewees were 10-40 years old (78.5%). Most had a history of using 1-3 of the products shown (68%). Table 1. Topical Traditional Chinese Medicaments Agents

Vehicle

Axe brand medicated oil Green grass oil Eagle brand medicated oil Saw Hong Choon skin ointment Tiger balm Tiger oil White flower embrocation Wong Cheung Wah U I oil Zheng Gu Shui Tjin Koo Lin

Olive oil Olive oil Olive oil Yellow soft paraffin Yellow soft paraffin Olive oil Olive oil Olive oil Olive oil Olive oil

5

A list of the 10 most commonly used topical traditional Chinese medicaments was compiled for phase B of the study. The names and ingredients were as follows. (1) Axe brand medicated oil: menthol crystals 20%, eucalyptus oil 15%, methyl salicylate 15%, essential oil 12%, camphor 5%. (2) Saw Hong Choon skin ointment: salicylic acid 5%. (3) Tiger oil: methyl salicylate 38%, white oil 25%, camphor 17.5%, menthol 8%, eucalyptus oil 6%, lavender spike 5%, chloroform BP 0.5%. (4) White flower embrocation: wintergreen oil 40%, menthol crystals 30%, eucalyptus oil 18%, camphor 6%, lavender oil 6%. (5) Zheng Gu Shui: Radix pseudoginseng 25%, Croton tiglium 18%, Cinnamomum camphora nees et Eberm 15%, Radix angelicae 13%, Moghania macrophylla 12%, Inula cappa 12%, menthol 3%, camphor 2%. (6) Green grass oil: extract rheum palmatum and base to 100%, camphor 23.8%, menthol 3.5%. (7) Eagle brand medicated oil: mineral oil 36.15%, menthol 28.5%, methyl salicylate 18.6%, chlorophyll 1.15%, other essential oil 15.6%. (8) Tiger balm: wax and petrolatum 36.8%, camphor 24.9%, peppermint oil 15.9%, cajuput oil 12.9%, menthol 8%, clove oil 1.5%. (9) Tjin Koo Lin: wintergreen 10%, ethanol 10%, cinnamon oil 4%, clove oil 4%, nutmeg oil 4%, camphor 4%, peppermint oil 2%, cassia oil 2%, methyl salicylate, and others. (10) Wong Cheung Wah U I oil: peppermint oil 20%. Phase B

No skin reaction was elicited with 1%, 5%, 10%, 20%, 50%, and undiluted concentrations of five preparations, namely, Axe brand medicated oil, Saw Hong Choon skin ointment, Tiger oil, White flower embrocation, and Zheng Gu Shui (Table 2). These can be used undiluted for patch testing. Allergic reactions were recorded in the other five preparations, namely, Green grass oil, Eagle brand medicated oil, Tiger balm, Wong Cheung Wah U I oil, and Tjin Koo Lin. These were relevant allergic reactions because positive reactions were recorded at both 48 and 96 hours or only at 96 hours (Table 3). These 4 patients developed relevant positive allergic reactions to the above five medicaments. A summary of these four case reports is presented in Table 4. The final concentration determined for each topical traditional Chinese medicament for patch

LEOW ET AL Table 2. Patients With no Positive Patch Test Reaction to Topical Traditional Chinese Medicaments

Percentageof Agent in Vehicle (%) Agent

1

Axe brand medicated oil Saw Hong Choon skin ointment Tiger oil White flower embrocation Zheng Gu Shui

0 (11) 0 (11) 0 (11) 0 (11) 0 (11)

5 0 0 0 0 0

10

(10) (10) (20) (20) (20)

0 0 0 0 0

20

(10) (10) (12) (12) (11)

50

0 (11) 0 (11) 0 (11) 0 (11) O (11)

0 0 0 0 0

As Is

(11) (11) (11) (11) (11)

0 0 0 0 0

(34) (34) (24) (24) (24)

Total No. of Patients Tested 87 87 89 89 88

NOTE. Numerical figures in parentheses denote the number of patients tested at each concentration.

testing at our Contact & Occupational Dermatoses Clinic are listed in Table 5. DISCUSSION

Traditional topical Chinese medicaments are currently freely available as over-the-counter items to the general public in Singapore. On close scrutiny of the labels, they mainly contain an assortment of plant extracts that are known sensitizers. Some of the more prominent extracts include terpenes, salicylates, and essential oil extracts. Terpenes are present in almost all of the 10 medicaments under investigation in our study. They are waste products of the plant metabolism and serve to repel or attract insects. They are structurally hydrocarbons. Examples of this group of extracts are menthol and camphor. 5 Essential oil extracts include eucalyptus (leaf extract) and cinnamon (bark extract). They are volatile, nonsaponifying oils with a characteristic odor and are often used as perfume essences. 5 Salicylates are not plant extracts but are known sensitizers when applied topically.6 They can be found in 5 of the 10 medicaments. The 10 topical traditional Chinese medicaments most commonly used by our patients can be grouped into three categories, namely, herbal oils, bone setters' herbal oils, and topical antifungal

medication. Herbal oils are used as soothing balms or oils for general purposes, including headache, abdominal colic, and skin rash. These preparations contain terpenes (namely, camphor and menthol) as their main ingredients. Medicaments in this category include Axe brand medicated oil, Tiger oil, White flower embrocation, Green grass oil, Eagle brand medicated oil, Tiger balm, and Wong Cheung Wah U I oil. Bone setters' herbal oils are herbal orthopedic lotions used for muscle sprains and strains. Medicaments in this categoryinclude Zheng Gu Shui and Tjin Koo Lin. Topical antifungal medications include Saw Hong Choon skin ointment, which contains salicylic acid as its main ingredient. In the discussion of traditional Chinese herbal medicaments, there is always difficulty uncovering the precise formulation of the concoction. This problem was also alluded to by Lee and Lain in their investigation of bone setters' herb dermatitis in Hong Kong. 7 Almost all reports on contact reactions to topical traditional Chinese medicaments are from Hong Kong with the exception of contact allergy to colophony in Chinese musk and Tiger bone plaster by the French workers. 8 Irritant reactions to Hung Far oil, l Lu-Shen-Wan, 2 and Black man oiP had been reported by Lee and Lam. Combined irritant

Table 3. Patients With Positive Allergic Contact Reactions to Topical Traditional Chinese Medicaments

Agent

1

5

10

20

50

Total No. of Patients Tested

Green grass oil Eagle brand medicated oil Tiger balm Wong Cheung Wah U I oil Tjin Koo Lin

0 (11) 0 (12) 0 (12) 0 (11) 0 (11)

1 (20) 1 (21) 1 (22) 1 (77) 1 (20)

1 (11) 1 (12) 3 (55) 1 (1) 1 (12)

2 (36) 1 (12) NT NT 2 (34)

1 (11) 0 (34) NT NT I (11)

89 91 89 89 88

Percentageof Agent in Vehicle (%)

NOTE. Numerical figures in parentheses denote the number of patients tested at each concentration. Abbreviations: NT, not tested.

TOPICAL TRADITIONAL CHINESE MEDICAMENTS

Table 4. Case Reports Relevant Patch Test Reactions

Case No.

Age (yr)

Sex (M/F)

Race

1

13

F

Chinese

2

3

52

44

F

M

Chinese

Chinese

History 1-year history of perioral eczema and

Yes

28

M

Chinese

48 Hours

96 Hours

Wong Cheung Wah U I oil 1%

-+

-

past history of using Wong Cheung

Wong Cheung Wah U I oil 5%

++

++

Wah U I oil

Wong Cheung Wah U I oil 10% Balsam of Peru 25%

+ +

+ +

Fragrance mix 5% Tiger balm 1% Tiger balm 5% Tiger balm 10%

+ -+ _+

+ + +

Balsam of Peru 25% Fragrance mix 8%

+ +

+ +

Green grass oil 5%

+

+

Green grass oil 10%

++

+

Green grass oil 20%

++

+

Eagle brand medicated oil 5%

++

+

Eagle brand Eagle brand Tjin Koo Lin Tjin Koo Lin

++ ++ + ++

+ ++ -+ +

++ + ++ ++ +++ +

+ + + ++ ++ +

12-year history of recurrent cheilitis and past history of using Tiger balm oil

1-year history of hand eczema and

No

No

past history of using Tjin Koo Lin

4

Agent

Atopy

medicated oil 10% medicated oil 20% 5% 10%

Tjin Koo Lin 20% Tiger balm 5% Tiger balm 10% Balsam of Peru 25% Fragrance mix 8% Green grass oil 20%

4-year history of persistent perianal itch and past history of self-medication with various topical Chinese medicaments, including Green grass

Tjin Koo Lin 20% Tjin Koo Lin 50% Tiger balm 10%

+ + +

+ + +

oil

Fragrance mix 8%

+

+

and/or allergic contact reactions to Zheng Gu Shui were also reported by the same workers. 9 This herbal preparation is also in our panel of the 10 topical traditional Chinese medicaments. Surprisingly, no irritant reaction was detected at all in our study. The problem of irritancy is probably overcome by the gradual increase in concentration for patch testing in our cohort of patients.

Table 5, Final Concentration for Patch Testing Medicaments

Concentration

Vehicle

Axe brand medicated oil Saw Hong Choon skin ointment Tiger oil White f l o w e r embrocation Zheng Gu Shui Green grass oil Eagle brand medicated oil Tiger balm

As is As is As is As is As is 10% 50% 5%

Won9 Cheung Wah U I oil Tjin Koo Lin

5% 20%

-----Olive oil Olive oil Yellow soft paraffin Olive oil Olive oil

Allergic contact reactions to Yunnan Paiyao l° and 101 hair regrowth liniment II were also reported by Lee and Lam. They also identified mastic and myrrh as the putative allergens in a Chinese herbal orthopedic solution. 12,I3 We are also pleasantly surprised I by the low incidence of allergenicity of these topical traditional Chinese medicaments. However, it is interesting to note that in our patients with positive allergic contact reactions to topical traditional medicaments, all of them also have positive reactions to fragrance mix and 3 of them have positive reactions to balsam of Peru. Strong suspicion of cross-sensitivity to fragrance should be considered because balsam of Peru and fragrance mix also contain plant extracts, which are recognized sensitizers. 5 Among such fragrances, cinnamic derivatives are recommended to be patch tested to confirm or rule out the role of cinnamic aldehyde, which is a main component of cinnamon balk (Kweipi), a common component of Chinese medicine.~4

8

LEOW ET AL

T h e n e x t step of the study will be to p e r f o r m f u r t h e r patch testing on patients who had positive reactions to individual ingredients of all 10 p r e p a r a tions to d e t e r m i n e the exact source of sensitivity in each subject. People f r o m different countries with different social and cultural backgrounds are exposed to a u n i q u e c o m b i n a t i o n of allergens, as exemplified by the high prevalence of use of topical traditional Chinese m e d i c a m e n t s in our patients. Hence, devel-

o p m e n t of special panels of allergens for p a t c h testing to c a t e r to a population with a unique usage p a t t e r n is essential. F u r t h e r patch testing to individual ingredients of each m e d i c a m e n t will help to uncover the u l t i m a t e t r u t h of these contact reactions. Patients with positive reactions to balsam of P e r u and fragrance mix should be advised against excessive use of topical traditional Chinese medicaments.

REFERENCES 1. Lee TY, Lam TH: Patch testing of 11 common herbal topical medicament in Hong Kong. Contact Dermatitis 22:137I40, 1990 2. Lee TY, Lam TH: Irritant contact dermatitis due to a Chinese herbal medicine Lu-Shen-Wan. Contact Dermatitis I8:213-218, 1988 3. Lee TY, Lam TH: Irritant contact dermatitis due to the herbal oil, Black man oil. Contact Dermatitis 20:229-230, 1989 4. Cronin E: Contact Dermatitis. Edinburgh, Churchill Livingstone, 1980 5. MitchellJC, Fisher AA: Dermatitis due to plants and spices, in Fisher AA (ed): Contact Dermatitis. Philadelphia, PA, Lea & Febiger, 1986, pp 418-453 6. RasmussenJE, Fisher AA: Allergic contact dermatitis to salicylicacid plaster. Contact Dermatitis 2:237, 1976 7. Lee TY, Lam TH: Bone-setter's herbs dermatitis in Hong Kong. Contact Dermatitis 24:304-306, 1991 8. Barbaud A, Mongeole JM, TangJQ, et ah Contact

allergy to colophony in Chinese musk and Tiger bone plaster. Contact Dermatitis 25:324-325, 1991 9. Lee TY, Lam TH: Contact dermatitis due to Chinese herbal orthopaedic tincture, Zheng Gu Shui. Contact Dermatitis 24:64-65, 1987 10. Lee TY, Lam TH: Allergic contact dermatitis to Yunnan Paiyao. Contact Dermatitis 17:59-60, 1987 11. Lee TY, Lam TH: Allergic contact dermatitis due to 101 hair regrowth liniment. Contact Dermatitis 20:389-390, 1989 12. Lee TY, Lam TH: Allergic contact dermatitis due to a Chinese orthopaedic solution, Tieh Ta Yao Gin. Contact Dermatitis 28:89-90, 1993 13. Lee TY, Lam TH: Myrrh is the putative allergen in bone setter's herbs dermatitis. Contact Dermatitis 29:279, 1993 I4. Nakyama H, Matsuo S, Nishikawa T: A case of drug eruption caused by cinnamic derivatives in a Chinese medicine. Hifu 24:297-304, 1982