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Persistence of an allergen in hair after glyceryl monothioglycolate—containing permanent wave solutions
Persistence of an allergen in hair after glyceryl monothioglycolate-containing permanent wave solutions Lynne H. Morrison, M.D.,* and Frances J. Storrs, M.D.**
Baltimore, MD, and Portland, OR Glyceryl monothioglycolate, a reducing agent used in permanent waving solutions, is a recognized cause of allergic contact dermatitis. Because of an unexplained persistence of dermatitis in beauty shop clients after exposure to permanent wave solutions containing glyceryl monothioglycolate, we looked for the presence of this or a cross-reacting substance in permanent-waved hair as a possible source of continued exposure to the allergen. Seventeen subjects sensitive to glyceryl monothioglycolate underwent patch testing with hair samples collected before and at various times after a permanent wave containing glyceryl monothioglycolate. None reacted to hair that had not received a permanent, while 7 of 17 showed positive reactions to the permanent-waved hair. Positive reactions were seen in hair collected as long as 3 months after the permanent. This suggests that a glyceryl monothioglycolate-related allergen is retained in hair for up to 3 months after the permanent, which may explain the long-lasting dermatitis that occurs in clients sensitive to glyceryl monothioglycolate. (J AM ACAD DERMATOL 1988;19:52-9.)
Permanent waves create a long-lasting curl in hair by a two-step process that involves reducing disulfide bonds in keratin and then reforming them once the hair has been wound into the desired shape. 1 The most common permanent wave solutions today use thioglycolates as the active compounds to reduce disulfide bonds in the first step of the permanent wave process. 2 In 1943 the process of "cold permanent waving," which uses ammonium thioglycolate as the reducing agent, came into general use and for years has enjoyed great
From the Department of Dermatology, The Johns Hopkins Hospital, Baltimore,* and The Oregon Health Sciences University, Portland.** Accepted fdr publication Nov. 12, 1987. Reprint requests to: Dr. Lynne H. Morrison, Fellow in Dermatology, Department of Dermatology, The Johns Hopkins Hospitat, 600 N. Wolfe St., Baltimore, MD 21205.
52
popularity. 3,4 Although ammonium thioglycolate is a recognized irritant, it is very rarely a sensitizer, z'5"6 In contrast, Voss 7 has described various amides of thioglycolic acid as potential sensitizers, and both amide and ester derivatives have been reported to cause allergic contact dermatitis in the European literature.* In the mid 1970s another thioglycolate, the glycerylic ester of thioglycolic acid known as glyceryl monothioglycolate, was introduced in the United States. 6 This is the reducing agent used in what are commonly referred to as "acid permanent waves" or "hot permanent waves." They were introduced by the cosmetics industry in its search for a product that would be less damaging to hair during the waving process. Although this benefit *Schultz KH. Durch Thioglykolsaurederivate ausgeloste kontaktekzeme im friseurberuf. Berufsdermatosen 1961;9:244-57.
Volume 19 Number 1, Part 1 July 1988
Allergen in hair after glyceryl monothioglycolate exposure 5 3
has not been clearly proven, these permanents have gained wide acceptance in beauty salons. Manufacturers estimate that approximately 25% o f salon permanents are based on glyceryl monothioglycolate. 6 These solutions are not yet available over the counter but may be obtained through wholesale outlets. Glyceryl monothioglycolate has been recognized as a potential sensitizer and reported to cause allergic contact dermatitis in both hairdressers and clients. 6"8'9 Hairdressers most commonly manifest their allergy as a hand dermatitis, whereas the clients most often have a dermatitis involving the scalp, face, ears, and neck. In 1984 12 hair dressers and clients who were sensitive to glyceryl monothioglycolate were reported from our institution. 6 Since then we have continued to see additional cases and currently have identified more than 30 patients allergic to glyceryl monothioglycolate. An unusual feature of several clients is that their dermatitis has lasted months after exposure to the permanent wave solution. Additionally, some hairdressers who are allergic to this compound have indicated that recently permanentwaved hair makes their hands itch. In preliminary patch testing, hair recently permanent-waved with a solution containing glyceryl monothioglycolate produced positive results. These observations suggested that glyceryl monothioglycolate or a cross-reacting product may be retained in the permanent-waved hair. Our study investigates this possibility by patch testing subjects sensitive to glyceryl monothioglycolate with hair samples collected before and at various times after the hair was exposed to a permanent wave containing the compound. MATERIALS AND METHODS
Hair sample collection Part A. Hair samples were collected from five beauty shop clients (hair donors) who had dark brown hair that had not been dyed, tinted, or otherwise color treated and had not been permanent waved in the last year. These clients received a permanent wave containing glyceryl monothioglycolate. Hair samples were collected from each of the clients immediately before their permanents and then immediately after the permanent (same-day sample), and at 2 weeks, 6 weeks, and 3 months after their permanent. During this time the
Fig. 1. Finn Chambers containing substances used in patch testing. Left column, Permanent wave chemicals in petrolatum. Middle column, Hair from beauty shop clients. Right column, Antigen loss control hair and virgin hair.
clients cared for their hair according to their usual practices. As each hair sample was received, it was stored at 0 ~ C until ready for use in patch testing. Because the hair samples were collected at different times, all were stored at 0~ C to mininaize degradation of the antigen. P a r t B. Members of the hair care industry provided dark brown human hair tresses and stated these samples had never been permanent waved, dyed, or otherwise color treated ("virgin hair"). Two tresses, to be used as a negative control, were stored at 0 ~ C. The remaining tresses were given a permanent wave containing glyceryl monothioglycolate (One Better, by Helene Curtis) by a professional hairdresser according to manufacturer's directions. Immediately after the permanent, two of the tresses were air dried and stored at 0~ C, serving as same-day samples. The remaining tresses were washed twice weekly with Revlon Flex shampoo (primarily paraben preserved), rinsed, air dried, and stored at 0~ C between washes. No other products were used on these hair tresses. Two tresses were cared for in this manner for a total of 6 weeks, and two others for a total of 3 months. Two additional controls were used in both parts A and B. One was dark brown "virgin hair" that acted as an additional negative control. The other was an antigen loss control; this newly permanent-waved (with glyceryl monothioglycolate) hair was obtained from a sixth beauty shop client just before patch testing was started. This enabled us to control for antigen loss in
54
Journal of the American Academy of Dermatology
M o r r i s o n and S t o r r s
T a b l e I. Part A: Patch test results with beauty shop client's permanent-waved hair Atopic history Subject No.
Age (yr)
Personal
1
36
Hay fever
2
70
3 4 5 6 7 8 9 10
23 38 33 39 25 41 46 59
Hay fever, nummular dermatitis Hay fever Hay fever None None None None None None
II
46
Hay fever, dermatitis on hand
Hair samples Family
Other positive reactions
Hay fever, eczema Hay fever
Cinnamic aldehyde, thimerosal, PPD Formaldehyde
Hay fever Eczema None None None None None Eczema
Balsam Peru, EED, nickel Ethyl methacrylate EED Neomycin None Thiuram mix, carba mix Epoxy resin, neomycin, nickel Thiuram mix, carba mix, neomycin* Formaldehyde, quaternium- 15,
Hay fever, asthma
Before permanent
2 wk
6 wk
+
+
+
+
+
+
+
--
2
3
3
Same day
dichlorophene
Total positive reactions
0
ATG, Ammonium thioglycolate; DDG, diglyceryldithioglycolate;EED. ethylenediamine hydrochloride; GMTG. glyceryl monothioglycolate; PPD, p = phenylenediamine.
*History of nickel allergy.
the hair by our storage methods. The antigen loss control was used again in part B, after having been stored 10 to 12 months at 0 ~ C. Patch testing Part A. Our patch test subjects in part A were 11 women aged 23 to 70 years. Six of the 11 had at least one marker for atopy, but none fit the Hanifin criteria for atopy. ~~ Three were clients and eight were hairdressers. They all underwent testing with the North American Contact Dermatitis Group's standard and vehicle and preservative trays (Appendix 1). In three patients this was done during the study, while in the remaining eight it was done before the study. All were tested to client hair samples described above in part A, the two control samples, and to glyceryl monothioglycolate 1% in petrolatum, ammonium thioglycolate 2.5% in petrolatum, and diglyceryldithioglycolate I% in petrolatum. Hair samples from the five clients were not combined; each hair sample was tested separately on one or more patch test subjects. Allergens were applied to aluminum discs (Finn Chambers) and secured to the upper portion of the subject's backs by
porous tape (Scanpor; Norgesplaster AS, Oslo, Norway). The discs were placed 5 cm apart on the subject's back. Lengths of hair sufficient to fill the aluminum disks (1 to 1.5 cm) were used and were held to the Finn Chambers with petrolatum (Fig. 1). The discs were left in place 48 hours, then removed and read 30 minutes later. A second reading was done at 7 days. Only reactions present at the 7-day reading were recorded as positive. Part B. Patch test subjects were six women aged 23 to 70 years. Two subjects had also participated in the first part of the study. Four had at least one marker for atopy, although none fit all the Hanifin criteria for atopy. *~Two were hairdressers and four were clients. All underwent patch testing as described above, except that the hair used for patch testing was human hair tresses, not samples from beauty shop clients. None of the subjects in either part had any significant degree of active dermatitis during patch testing. Hair samples permanent waved with solutions containing glyceryl monothioglycolate were tested for irritancy by including them with allergens on the standard tray used to evaluate patients with suspect allergic con-
Volume 19 Number 1, Part 1 July 1988
Hair
3 mo
--
samples
Antigen Io~
Allergen in hair after glyceryl monothioglycolate exposure 55
control
+
Virgin hair
-
GMTG
+
DDG
+
ATG
-
-
+
-
+
+
+
-
-t-
-
+
-
-
-
-k
-
+
-
-
- -
- -
- -
"Jl-
- -
- -
--
+
--
+
+
-
--
+
--
+
+
--
--
+
--
+
+
--
0
7
0
11
5
1
tact dermatitis in our clinics. Thirty-three patients were tested to hair obtained 6 weeks after a permanent containing glyceryl monothioglycolate. RESULTS The hair permanent waved with glyceryl monothioglycolate used for irritancy screening caused no irritant or allergic reactions in any of the 33 patients tested. The results of part A aa'e summarized in Table I and those of part B are listed in Table II. A total of 11 subjects positive to glyceryl monothioglycolate underwent patch testing with hair from beauty shop clients and six subjects were tested with hair tresses. In part A, 7 of 11 subjects and in part B all six subjects had at least one positive reaction to hair permanent waved with a glyceryl monothioglycolate solution. Excluding the antigen loss control, 4 of 11 subjects in part A and 3 of 6 subjects in part B reacted positively to hair collected from the five different clients or tresses, respectively (Fig. 2). The antigen loss control sample gave the highest number of positive reactions in both parts of the study. None of the subjects had positive reactions to either virgin hair,
2. Seven-day patch test results with permanentwaved hair tresses. The antigen loss control is labeled "control perm."
Fig.
beauty shop client hair that had not been waved, or hair tresses that had not received a permanent. All subjects were sensitive to glyceryl monothioglycolate. Five of the 11 in part A and 4 of the 6 in part B were positive to diglyceryldifhioglycolate. One subject who participated in both parts A and B was positive to ammonium thioglycolate. This result was confirmed 6 months after the end of the study by patch testing of the subject to ammonium thioglycolate alone. The donor's hair care practices and brand name of permanent wave they received were correlated with the number of subjects who had positive reactions to the hair from each of the five separate donors. Results are summarized in Table I[1. DISCUSSION We found 7 of 17 subjects to have positive reactions to permanent-waved hair collected from the various clients and tresses, but none had positive reactions to virgin hair or client hair and hair
56
Journal of the American Academy of Dermatology
M o r r i s o n and Storr.~
T a b l e II. Part B: Patch test results with permanent-waved hair tresses (lab-washed hair) Atopie history
Hair samples
Subject No.
Age (yr)
1
41
None
None
2
64
None
None
3 4 5* 6*
-56 23 70
Hay fever Hay fever Hay fever Nummular dermatitis, hay fever
? Asthma Hay fever Hay fever
Personal
Family
Other positive reactions
Cinnamic aldehyde, cinnamic alcohol, formaldehyde, PPD, quaternium- 15 Thiuram mix, fragrance mix, nickel, frullania Thimerosal PPD Balsam Peru, nickel, EED Formaldehyde
Total positive patients
Before permanent
Same day
2 wk
-
+
+
-
+ + -
+ + -
0
3
3
6 wk
ATG, Ammoniumthioglycolate;DDG, diglyceryldithioglycolate;EED, ethylenediaminehydrochloride;GMTG, glyceryl rnonothioglycolate; PPD, p = phenylenediamine.
*Also includedin partA. T a b l e IlI. Donor's hair care practices
donor
Brand of permanent
I Shmpoon frequency
Day Into Night (Redken)
Daily
2
Synerfusion (Matrix)
Daily
3
One Better (Helene Curtis)
Once
Heated hair care appliances
Blow dry daily Curling iron every other day None
weekly 4
Apple Pectin (La Maur)
Daily
5
One Better (Helene Curtis)
3 times weekly
Blow dry daily Blow dry 3 times weekly
Other hair care products
Positive subjeets*/total subjeets testedt
None
1/3
None
1/3
Setting lotion and hair spray None
0/1 0/1
None
2/3
*Number of subjectshavingpositive patch test reactions. tTotal numberof subjectstestedto each donor'shair. tresses that had not received a permanent. This indicates that the reactions we saw were not directed against the hair itself, but rather to an allergen in the hair. Because this allergen was detected only in permanent-waved hair, it is probably a product related to the permanent solution containing glyceryl monothioglycolate. To help eliminate the possibility that the reactions might have resulted from a retained extraneous hair care prod-
uct (such as shampoo or conditioners) used by any of the five clients, we carried out part B of the study, in which we completely controlled the care of the hair tresses receiving a permanent. Under these conditions, in which the only potential allergens would be those contained in either the shampoo or the permanent wave solutions, three subjects had positive reactions to the permanent-waved tresses. Glyceryl monothiogly-
V o l u m e 19 N u m b e r 1, P a r t 1 J u l y 1988
Hair
3 mo --
Allergen in hair after glyceryl monothioglycolate exposure 57
samples
Antigen loss control
Virgin hair
GMTG
DDG
ATG
+
--
+
+
--
+
+
+
+
--
+
+
--
+
--
+
+
--
+
--
+ +
---
+ +
+ +
+ --
2
6
0
6
5
1
--
colate was the only allergen common to all three subjects, and only one was positive to any potentially allergenic ingredient of the shampoo or other ingredient of the permanent wave solution (e.g., fragrance). It therefore seems unlikely that the positive reactions are caused by the shampoo or preservative or sequestering agents in the permanent wave solution; it is most probable that the positive reactions result from a glyceryl rnonothioglycolate-derived product bound to the hair. The data indicate that the allergen can persist up to 3 months. Thirty-three percent of the subjects in part B reacted to hair that had been permanent waved 3 months earlier. This persistence of the allergen in hair for weeks to months correlates with the long-lasting dermatitis occurring in our sensitive patients after receiving a permanent containing glyceryl monothioglycolate and it provides a possible explanation for the phenomenon. Patch test subjects 2 and 7 had positive reactions to hair samples obtained 2 to 6 weeks after the permanent but no reaction to permanented hair that had been collected earlier--an unexpected finding. This may be due to false-negative responses. Subject 7 had a questionably positive reaction to sameday and 2-week samples, so for the purposes of this study she was considered to have no reaction. Subject 2 had a questionably positive reaction to the same-day sample at 48 hours. If these do represent false-negative responses, they may result
from a combination of high subject threshold, variable concentration of allergen within the hair, and minor variations in test site or degree of occlusion. It is interesting that the antigen loss control consistently gave the greatest number of positive resuits. The reason for this is not clear because the hair was treated in the same fashion as the other five same-day samples. It is possible that, because of a difference in the technique of giving the permanent wave (such as a brief rinse of waving solution), there was a greater amount of retained allergen. In a report of 121 patients, Schulz found that 29% o f those allergic to the glycolic ester of thioglycolic acid and 35% of those allergic to the hydrazide were also sensitive to ammonium thioglycolate, suggesting cross-reactivity.* We had one subject react positively to both glyceryl monothioglycolate and ammonium thioglycolate. Given the rarity of allergic contact dermatitis to ammonium thioglycolate, the coexistence of glyceryl monothioglycolate and ammonium thioglycolate sensitivity suggests that development of a glyceryl monothioglycolate allergy may "unlock" sensitization to ammonium thioglycolate. 11 Therefore, patients suspected or known to be allergic to glyceryl monothioglycolate should also undergo patch testing with ammonium thioglycolate. The identity of the antigen is not yet precisely known. We do not suspect that it is diglyceryldithioglycolate, because there was no correlation between sensitivity to diglyceryldithioglycolate and positive reactions to permanent-waved hair. In fact, three subjects who were not sensitive to diglyceryldithioglycolate had positive reactions to permanent-waved hair. Diglyceryldithioglycolate may cross-react with the antigen, but it is doubtful that it itself is the retained antigen. We have preliminary data suggesting that the allergen may be a mixed disulfide, which is an intermediate compound formed in the process of disulfide bond reduction and consists of glyceryl monothioglycolate covalently linked to keratin. Samples of hair from one of our clients were submitred to Redken Research Laboratories for amino *Schultz KH. Durch Thioglykolsaurederivate ausgeloste kontaktekzeme im friseurberuf. Berufsdermatosen 1961;9:244-57.
Journal of the American Academy of Dermatology
58 Morrison and Storrs
acid analysis. Results show that a significant amount of cysteine in this client's hair was coupled with glyceryl monothioglycolate in the same-day, 2-week, 6-week, and 3-month samples. No mixed disulfide was found in the hair sample that had not been permanent waved. These findings will require further investigation but implicate the mixed disulfide as the retained product in hair permanent waved with solutions containing glyceryl monothioglycolate. We found no relationship between the hair care practices of the clients or the brand of permanent wave solution and the number o f positive reactions obtained with the hair samples. Although these data are from a small number o f clients, they suggest that there is no routine hair care practice that is important in helping to remove the bound allergen. It is hoped that further study of this allergen will provide methods for efficiently removing it from permanent-waved hair. Presently the available options include trimming off the hair exposed to the waving solution or, as has been suggested by the hair care industry, rinsing or washing the permanent-waved hair in an alkaline solution, which causes instability o f the mixed disulfide and may help remove this substance. We thank Constance Strawn for her valuable assistance with this study. REFERENCES 1. Foussereau J, Benezra C, Maibach H. Hairdressers and barbers. In: Occupational contact dermatitis. Clinical and chemical aspects. Philadelphia: WB Saunders, 1982:31323. 2. James J, Calnan CDE. Dermatitis of the hands in ladies' hairdressers. Trans St Johns Hosp Dermatol Soc 1959; 42:19-42. 3. Wilkinson JB, Moore RJ, eds. Permanent waving and hair strengtheners. In: Harry's cosmeticology. 7th ed. New York: Chemical Publishing, 1982:555-80. 4. Cronin E. Contact dermatitis. New York: Churchill Livingstone, 1980:93-170. 5. Ishihara M. The composition of hair preparations and their skin hazards. In: Kobori T, Montagna W, eds. Biology and disease of the hair. Tokyo: University of Tokyo, 1976:603-29. 6. Storrs FJ. Permanent wave contact dermatitis: Contact allergy to glyceryl monothioglycolate. J AM ACADDERMATOL1984;11:74-85. 7. Voss JG. Skin sensitization by mercaptans of low molecular weight. J Invest Dermatol 1958;31:273-9.
8. Lynde CW, Mitchell JC. Patch test results in 66 hairdressers. Contact Dermatitis 1982;8:302-7. 9. Warshawshki L, Mitchell JC, Storrs FJ. Allergic contact dermatitis from glyceryl monothioglycolate in hairdressers. Contact Dermatitis 1982;7:351-2. 10. Hanifin JM, Lobitz WC Jr. Newer concepts of atopie dermatitis. Arch Dermatol 1977;113:663-70. 11. Dupuis G, Benezra C. Allergic contact dermatitis to simple chemicals: A molecular approach. New York: Marcel Dekker, 1982. APPENDIX I. NORTH AMERICAN CONTACT DERMATITIS GROUP'S PATCH TEST TRAYS
Standard tray Benzocaine 5% in petrolatum Mercaptobenzothiazole 1% in petrolatum Colophony 20% in petrolatum Diazolidinyl urea 1% in petrolatum p-Phenylenediamine 1% in petrolatum Imidazolidinyl urea 2% in aqueous solution Cinnamic aldehyde 1% in petrolatum Wool (lanolin) alcohols 30% in petrolatum Carba mix 3% in petrolatum Neomycin sulfate 20% in petrolatum Thiuram mix 1% in petrolatum Formaldehyde 2% in aqueous solution Ethylenediamine dihydrochloride 1% in petrolatum Epoxy resin 1% in petrolatum Quatemium-15 2% in petrolatum p-tertiary-butylphenol formaldehyde resin 1% in petrolatum Mercapto mix 1% in petrolatum Diazolidinyl urea 1% in aqueous solution Black rubber mix (PPD mix) 0.6% in petrolatum Thimerosal 0.1% in petrolatum Imidazolidinyl urea 2% in petrolatum Potassium dichromate 0.25% in petrolatum Balsam Peru 25% in petrolatum Diaminodiphenyl methane 0.5% in petrolatum Cinnamic alcohol 5% in petrolatum d/-a-Tocopherol acetate 4% in petrolatum Colophony mix 60% in petrolatum Nickel sulfate 2.5% in petrolatum Vehicle and preservative tray Benzophenone 1% in petrolatum 2-Bromo-2-nitropropane-l,3-diol (Bronopol) 0.5% in petrolatum p-Chloro-m-cresol 1% in petrolatum Dichlorophene 1% in petrolatum Polyethylene glycol 400 (as is) Sorbic acid 2% in petrolatum DMDM hydantoin 1% in petrolatum
Volume 19 Number 1, Part 1 July 1988
Allergen in hair after glyceryl monothioglycolate exposure
Propylene glycol 10% in aqueous solution Ortho-phenylphenol 1% in petrolatum 5-Chloro-2-methyl-4-isothiasolin-3-one and 2methyl-4-isothiazolin-3-one (Kathon CG) 0.1% in petrolatum Captan 0.25% in petrolatum Chloroxylenol (para-chloro-meta-xylenol) 1% in petrolatum
I
5-Chloro-2-methyl-4-isothiazolin-3-one and 2methyl-4-isothiazotin-3-one (Kathon CG) 0.01% in aqueous solution DMDM hydantoin 1% in aqueous solution Chloroacetamide 0.1% in petrolatum Paraben mix 12% in petrolatum Ammoniated mercury 1% in petrolatum Tween 85 2.5% in petrolatum
1 I
The duration of local control of classic (non-AIDS-associated) Kaposi's sarcoma by radiotherapy Jay S. Cooper, M.D., John Sacco, M.D., and Joseph Newall, M.D. New York, NY We report the short- and long-term responses to radiotherapy of 82 classic Kaposi's sarcomas. Doses were prescribed ab initio and no attempt was made to discontinue treatment as soon as shrinkage was observed, as has been recommended by others. More than 50% of the lesions regressed completely and nearly all underwent some regression. Almost all recurrences were detected within 2 years of treatment and virtually all occurred in lesions that had not regressed completely within 2 weeks of radiotherapy. We conclude that classic Kaposi's sarcoma should be treated with sufficient radiotherapy from the beginning to provide long-term control. (J AM ACADDERMATOL 1988;19:59-66.)
Classic Kaposi's sarcoma is an incurable, multicentric disease that generally occurs in elderly patients of Mediterranean origin who have no k n o w n immunologic suppression. Typically the disease progresses slowly and confines itself to the l o w e r extremities. Local treatment by radiation allows patients to coexist with and often outlive the disease. Because of the relative rarity of classic Kaposi's From the New York University Medical Center. Accepted for publication Dec. 17, 1987. Reprint requests to: Dr. Jay S, Cooper, 560 First Ave., New York, NY 10016.
sarcoma in the United States, literature describing the results of treatment of large numbers of patients is uncommon, Published reports tend to describe the results of radiotherapy in terms of response, analogous to response of lesions to chemotherapy. What is rarely, if ever, discussed is the duration of control. We herein describe the duration of local control after radiotherapy and its relationship to initial tumor response. MATERIALS AND METHODS
From 1972 to 1986 we irradiated 82 Kaposi's sarcomas that occurred in patients who did not have acquired immunodeficiency disease, an organ transplant, 59
Baltimore, MD, and Portland, OR Glyceryl monothioglycolate, a reducing agent used in permanent waving solutions, is a recognized cause of allergic contact dermatitis. Because of an unexplained persistence of dermatitis in beauty shop clients after exposure to permanent wave solutions containing glyceryl monothioglycolate, we looked for the presence of this or a cross-reacting substance in permanent-waved hair as a possible source of continued exposure to the allergen. Seventeen subjects sensitive to glyceryl monothioglycolate underwent patch testing with hair samples collected before and at various times after a permanent wave containing glyceryl monothioglycolate. None reacted to hair that had not received a permanent, while 7 of 17 showed positive reactions to the permanent-waved hair. Positive reactions were seen in hair collected as long as 3 months after the permanent. This suggests that a glyceryl monothioglycolate-related allergen is retained in hair for up to 3 months after the permanent, which may explain the long-lasting dermatitis that occurs in clients sensitive to glyceryl monothioglycolate. (J AM ACAD DERMATOL 1988;19:52-9.)
Permanent waves create a long-lasting curl in hair by a two-step process that involves reducing disulfide bonds in keratin and then reforming them once the hair has been wound into the desired shape. 1 The most common permanent wave solutions today use thioglycolates as the active compounds to reduce disulfide bonds in the first step of the permanent wave process. 2 In 1943 the process of "cold permanent waving," which uses ammonium thioglycolate as the reducing agent, came into general use and for years has enjoyed great
From the Department of Dermatology, The Johns Hopkins Hospital, Baltimore,* and The Oregon Health Sciences University, Portland.** Accepted fdr publication Nov. 12, 1987. Reprint requests to: Dr. Lynne H. Morrison, Fellow in Dermatology, Department of Dermatology, The Johns Hopkins Hospitat, 600 N. Wolfe St., Baltimore, MD 21205.
52
popularity. 3,4 Although ammonium thioglycolate is a recognized irritant, it is very rarely a sensitizer, z'5"6 In contrast, Voss 7 has described various amides of thioglycolic acid as potential sensitizers, and both amide and ester derivatives have been reported to cause allergic contact dermatitis in the European literature.* In the mid 1970s another thioglycolate, the glycerylic ester of thioglycolic acid known as glyceryl monothioglycolate, was introduced in the United States. 6 This is the reducing agent used in what are commonly referred to as "acid permanent waves" or "hot permanent waves." They were introduced by the cosmetics industry in its search for a product that would be less damaging to hair during the waving process. Although this benefit *Schultz KH. Durch Thioglykolsaurederivate ausgeloste kontaktekzeme im friseurberuf. Berufsdermatosen 1961;9:244-57.
Volume 19 Number 1, Part 1 July 1988
Allergen in hair after glyceryl monothioglycolate exposure 5 3
has not been clearly proven, these permanents have gained wide acceptance in beauty salons. Manufacturers estimate that approximately 25% o f salon permanents are based on glyceryl monothioglycolate. 6 These solutions are not yet available over the counter but may be obtained through wholesale outlets. Glyceryl monothioglycolate has been recognized as a potential sensitizer and reported to cause allergic contact dermatitis in both hairdressers and clients. 6"8'9 Hairdressers most commonly manifest their allergy as a hand dermatitis, whereas the clients most often have a dermatitis involving the scalp, face, ears, and neck. In 1984 12 hair dressers and clients who were sensitive to glyceryl monothioglycolate were reported from our institution. 6 Since then we have continued to see additional cases and currently have identified more than 30 patients allergic to glyceryl monothioglycolate. An unusual feature of several clients is that their dermatitis has lasted months after exposure to the permanent wave solution. Additionally, some hairdressers who are allergic to this compound have indicated that recently permanentwaved hair makes their hands itch. In preliminary patch testing, hair recently permanent-waved with a solution containing glyceryl monothioglycolate produced positive results. These observations suggested that glyceryl monothioglycolate or a cross-reacting product may be retained in the permanent-waved hair. Our study investigates this possibility by patch testing subjects sensitive to glyceryl monothioglycolate with hair samples collected before and at various times after the hair was exposed to a permanent wave containing the compound. MATERIALS AND METHODS
Hair sample collection Part A. Hair samples were collected from five beauty shop clients (hair donors) who had dark brown hair that had not been dyed, tinted, or otherwise color treated and had not been permanent waved in the last year. These clients received a permanent wave containing glyceryl monothioglycolate. Hair samples were collected from each of the clients immediately before their permanents and then immediately after the permanent (same-day sample), and at 2 weeks, 6 weeks, and 3 months after their permanent. During this time the
Fig. 1. Finn Chambers containing substances used in patch testing. Left column, Permanent wave chemicals in petrolatum. Middle column, Hair from beauty shop clients. Right column, Antigen loss control hair and virgin hair.
clients cared for their hair according to their usual practices. As each hair sample was received, it was stored at 0 ~ C until ready for use in patch testing. Because the hair samples were collected at different times, all were stored at 0~ C to mininaize degradation of the antigen. P a r t B. Members of the hair care industry provided dark brown human hair tresses and stated these samples had never been permanent waved, dyed, or otherwise color treated ("virgin hair"). Two tresses, to be used as a negative control, were stored at 0 ~ C. The remaining tresses were given a permanent wave containing glyceryl monothioglycolate (One Better, by Helene Curtis) by a professional hairdresser according to manufacturer's directions. Immediately after the permanent, two of the tresses were air dried and stored at 0~ C, serving as same-day samples. The remaining tresses were washed twice weekly with Revlon Flex shampoo (primarily paraben preserved), rinsed, air dried, and stored at 0~ C between washes. No other products were used on these hair tresses. Two tresses were cared for in this manner for a total of 6 weeks, and two others for a total of 3 months. Two additional controls were used in both parts A and B. One was dark brown "virgin hair" that acted as an additional negative control. The other was an antigen loss control; this newly permanent-waved (with glyceryl monothioglycolate) hair was obtained from a sixth beauty shop client just before patch testing was started. This enabled us to control for antigen loss in
54
Journal of the American Academy of Dermatology
M o r r i s o n and S t o r r s
T a b l e I. Part A: Patch test results with beauty shop client's permanent-waved hair Atopic history Subject No.
Age (yr)
Personal
1
36
Hay fever
2
70
3 4 5 6 7 8 9 10
23 38 33 39 25 41 46 59
Hay fever, nummular dermatitis Hay fever Hay fever None None None None None None
II
46
Hay fever, dermatitis on hand
Hair samples Family
Other positive reactions
Hay fever, eczema Hay fever
Cinnamic aldehyde, thimerosal, PPD Formaldehyde
Hay fever Eczema None None None None None Eczema
Balsam Peru, EED, nickel Ethyl methacrylate EED Neomycin None Thiuram mix, carba mix Epoxy resin, neomycin, nickel Thiuram mix, carba mix, neomycin* Formaldehyde, quaternium- 15,
Hay fever, asthma
Before permanent
2 wk
6 wk
+
+
+
+
+
+
+
--
2
3
3
Same day
dichlorophene
Total positive reactions
0
ATG, Ammonium thioglycolate; DDG, diglyceryldithioglycolate;EED. ethylenediamine hydrochloride; GMTG. glyceryl monothioglycolate; PPD, p = phenylenediamine.
*History of nickel allergy.
the hair by our storage methods. The antigen loss control was used again in part B, after having been stored 10 to 12 months at 0 ~ C. Patch testing Part A. Our patch test subjects in part A were 11 women aged 23 to 70 years. Six of the 11 had at least one marker for atopy, but none fit the Hanifin criteria for atopy. ~~ Three were clients and eight were hairdressers. They all underwent testing with the North American Contact Dermatitis Group's standard and vehicle and preservative trays (Appendix 1). In three patients this was done during the study, while in the remaining eight it was done before the study. All were tested to client hair samples described above in part A, the two control samples, and to glyceryl monothioglycolate 1% in petrolatum, ammonium thioglycolate 2.5% in petrolatum, and diglyceryldithioglycolate I% in petrolatum. Hair samples from the five clients were not combined; each hair sample was tested separately on one or more patch test subjects. Allergens were applied to aluminum discs (Finn Chambers) and secured to the upper portion of the subject's backs by
porous tape (Scanpor; Norgesplaster AS, Oslo, Norway). The discs were placed 5 cm apart on the subject's back. Lengths of hair sufficient to fill the aluminum disks (1 to 1.5 cm) were used and were held to the Finn Chambers with petrolatum (Fig. 1). The discs were left in place 48 hours, then removed and read 30 minutes later. A second reading was done at 7 days. Only reactions present at the 7-day reading were recorded as positive. Part B. Patch test subjects were six women aged 23 to 70 years. Two subjects had also participated in the first part of the study. Four had at least one marker for atopy, although none fit all the Hanifin criteria for atopy. *~Two were hairdressers and four were clients. All underwent patch testing as described above, except that the hair used for patch testing was human hair tresses, not samples from beauty shop clients. None of the subjects in either part had any significant degree of active dermatitis during patch testing. Hair samples permanent waved with solutions containing glyceryl monothioglycolate were tested for irritancy by including them with allergens on the standard tray used to evaluate patients with suspect allergic con-
Volume 19 Number 1, Part 1 July 1988
Hair
3 mo
--
samples
Antigen Io~
Allergen in hair after glyceryl monothioglycolate exposure 55
control
+
Virgin hair
-
GMTG
+
DDG
+
ATG
-
-
+
-
+
+
+
-
-t-
-
+
-
-
-
-k
-
+
-
-
- -
- -
- -
"Jl-
- -
- -
--
+
--
+
+
-
--
+
--
+
+
--
--
+
--
+
+
--
0
7
0
11
5
1
tact dermatitis in our clinics. Thirty-three patients were tested to hair obtained 6 weeks after a permanent containing glyceryl monothioglycolate. RESULTS The hair permanent waved with glyceryl monothioglycolate used for irritancy screening caused no irritant or allergic reactions in any of the 33 patients tested. The results of part A aa'e summarized in Table I and those of part B are listed in Table II. A total of 11 subjects positive to glyceryl monothioglycolate underwent patch testing with hair from beauty shop clients and six subjects were tested with hair tresses. In part A, 7 of 11 subjects and in part B all six subjects had at least one positive reaction to hair permanent waved with a glyceryl monothioglycolate solution. Excluding the antigen loss control, 4 of 11 subjects in part A and 3 of 6 subjects in part B reacted positively to hair collected from the five different clients or tresses, respectively (Fig. 2). The antigen loss control sample gave the highest number of positive reactions in both parts of the study. None of the subjects had positive reactions to either virgin hair,
2. Seven-day patch test results with permanentwaved hair tresses. The antigen loss control is labeled "control perm."
Fig.
beauty shop client hair that had not been waved, or hair tresses that had not received a permanent. All subjects were sensitive to glyceryl monothioglycolate. Five of the 11 in part A and 4 of the 6 in part B were positive to diglyceryldifhioglycolate. One subject who participated in both parts A and B was positive to ammonium thioglycolate. This result was confirmed 6 months after the end of the study by patch testing of the subject to ammonium thioglycolate alone. The donor's hair care practices and brand name of permanent wave they received were correlated with the number of subjects who had positive reactions to the hair from each of the five separate donors. Results are summarized in Table I[1. DISCUSSION We found 7 of 17 subjects to have positive reactions to permanent-waved hair collected from the various clients and tresses, but none had positive reactions to virgin hair or client hair and hair
56
Journal of the American Academy of Dermatology
M o r r i s o n and Storr.~
T a b l e II. Part B: Patch test results with permanent-waved hair tresses (lab-washed hair) Atopie history
Hair samples
Subject No.
Age (yr)
1
41
None
None
2
64
None
None
3 4 5* 6*
-56 23 70
Hay fever Hay fever Hay fever Nummular dermatitis, hay fever
? Asthma Hay fever Hay fever
Personal
Family
Other positive reactions
Cinnamic aldehyde, cinnamic alcohol, formaldehyde, PPD, quaternium- 15 Thiuram mix, fragrance mix, nickel, frullania Thimerosal PPD Balsam Peru, nickel, EED Formaldehyde
Total positive patients
Before permanent
Same day
2 wk
-
+
+
-
+ + -
+ + -
0
3
3
6 wk
ATG, Ammoniumthioglycolate;DDG, diglyceryldithioglycolate;EED, ethylenediaminehydrochloride;GMTG, glyceryl rnonothioglycolate; PPD, p = phenylenediamine.
*Also includedin partA. T a b l e IlI. Donor's hair care practices
donor
Brand of permanent
I Shmpoon frequency
Day Into Night (Redken)
Daily
2
Synerfusion (Matrix)
Daily
3
One Better (Helene Curtis)
Once
Heated hair care appliances
Blow dry daily Curling iron every other day None
weekly 4
Apple Pectin (La Maur)
Daily
5
One Better (Helene Curtis)
3 times weekly
Blow dry daily Blow dry 3 times weekly
Other hair care products
Positive subjeets*/total subjeets testedt
None
1/3
None
1/3
Setting lotion and hair spray None
0/1 0/1
None
2/3
*Number of subjectshavingpositive patch test reactions. tTotal numberof subjectstestedto each donor'shair. tresses that had not received a permanent. This indicates that the reactions we saw were not directed against the hair itself, but rather to an allergen in the hair. Because this allergen was detected only in permanent-waved hair, it is probably a product related to the permanent solution containing glyceryl monothioglycolate. To help eliminate the possibility that the reactions might have resulted from a retained extraneous hair care prod-
uct (such as shampoo or conditioners) used by any of the five clients, we carried out part B of the study, in which we completely controlled the care of the hair tresses receiving a permanent. Under these conditions, in which the only potential allergens would be those contained in either the shampoo or the permanent wave solutions, three subjects had positive reactions to the permanent-waved tresses. Glyceryl monothiogly-
V o l u m e 19 N u m b e r 1, P a r t 1 J u l y 1988
Hair
3 mo --
Allergen in hair after glyceryl monothioglycolate exposure 57
samples
Antigen loss control
Virgin hair
GMTG
DDG
ATG
+
--
+
+
--
+
+
+
+
--
+
+
--
+
--
+
+
--
+
--
+ +
---
+ +
+ +
+ --
2
6
0
6
5
1
--
colate was the only allergen common to all three subjects, and only one was positive to any potentially allergenic ingredient of the shampoo or other ingredient of the permanent wave solution (e.g., fragrance). It therefore seems unlikely that the positive reactions are caused by the shampoo or preservative or sequestering agents in the permanent wave solution; it is most probable that the positive reactions result from a glyceryl rnonothioglycolate-derived product bound to the hair. The data indicate that the allergen can persist up to 3 months. Thirty-three percent of the subjects in part B reacted to hair that had been permanent waved 3 months earlier. This persistence of the allergen in hair for weeks to months correlates with the long-lasting dermatitis occurring in our sensitive patients after receiving a permanent containing glyceryl monothioglycolate and it provides a possible explanation for the phenomenon. Patch test subjects 2 and 7 had positive reactions to hair samples obtained 2 to 6 weeks after the permanent but no reaction to permanented hair that had been collected earlier--an unexpected finding. This may be due to false-negative responses. Subject 7 had a questionably positive reaction to sameday and 2-week samples, so for the purposes of this study she was considered to have no reaction. Subject 2 had a questionably positive reaction to the same-day sample at 48 hours. If these do represent false-negative responses, they may result
from a combination of high subject threshold, variable concentration of allergen within the hair, and minor variations in test site or degree of occlusion. It is interesting that the antigen loss control consistently gave the greatest number of positive resuits. The reason for this is not clear because the hair was treated in the same fashion as the other five same-day samples. It is possible that, because of a difference in the technique of giving the permanent wave (such as a brief rinse of waving solution), there was a greater amount of retained allergen. In a report of 121 patients, Schulz found that 29% o f those allergic to the glycolic ester of thioglycolic acid and 35% of those allergic to the hydrazide were also sensitive to ammonium thioglycolate, suggesting cross-reactivity.* We had one subject react positively to both glyceryl monothioglycolate and ammonium thioglycolate. Given the rarity of allergic contact dermatitis to ammonium thioglycolate, the coexistence of glyceryl monothioglycolate and ammonium thioglycolate sensitivity suggests that development of a glyceryl monothioglycolate allergy may "unlock" sensitization to ammonium thioglycolate. 11 Therefore, patients suspected or known to be allergic to glyceryl monothioglycolate should also undergo patch testing with ammonium thioglycolate. The identity of the antigen is not yet precisely known. We do not suspect that it is diglyceryldithioglycolate, because there was no correlation between sensitivity to diglyceryldithioglycolate and positive reactions to permanent-waved hair. In fact, three subjects who were not sensitive to diglyceryldithioglycolate had positive reactions to permanent-waved hair. Diglyceryldithioglycolate may cross-react with the antigen, but it is doubtful that it itself is the retained antigen. We have preliminary data suggesting that the allergen may be a mixed disulfide, which is an intermediate compound formed in the process of disulfide bond reduction and consists of glyceryl monothioglycolate covalently linked to keratin. Samples of hair from one of our clients were submitred to Redken Research Laboratories for amino *Schultz KH. Durch Thioglykolsaurederivate ausgeloste kontaktekzeme im friseurberuf. Berufsdermatosen 1961;9:244-57.
Journal of the American Academy of Dermatology
58 Morrison and Storrs
acid analysis. Results show that a significant amount of cysteine in this client's hair was coupled with glyceryl monothioglycolate in the same-day, 2-week, 6-week, and 3-month samples. No mixed disulfide was found in the hair sample that had not been permanent waved. These findings will require further investigation but implicate the mixed disulfide as the retained product in hair permanent waved with solutions containing glyceryl monothioglycolate. We found no relationship between the hair care practices of the clients or the brand of permanent wave solution and the number o f positive reactions obtained with the hair samples. Although these data are from a small number o f clients, they suggest that there is no routine hair care practice that is important in helping to remove the bound allergen. It is hoped that further study of this allergen will provide methods for efficiently removing it from permanent-waved hair. Presently the available options include trimming off the hair exposed to the waving solution or, as has been suggested by the hair care industry, rinsing or washing the permanent-waved hair in an alkaline solution, which causes instability o f the mixed disulfide and may help remove this substance. We thank Constance Strawn for her valuable assistance with this study. REFERENCES 1. Foussereau J, Benezra C, Maibach H. Hairdressers and barbers. In: Occupational contact dermatitis. Clinical and chemical aspects. Philadelphia: WB Saunders, 1982:31323. 2. James J, Calnan CDE. Dermatitis of the hands in ladies' hairdressers. Trans St Johns Hosp Dermatol Soc 1959; 42:19-42. 3. Wilkinson JB, Moore RJ, eds. Permanent waving and hair strengtheners. In: Harry's cosmeticology. 7th ed. New York: Chemical Publishing, 1982:555-80. 4. Cronin E. Contact dermatitis. New York: Churchill Livingstone, 1980:93-170. 5. Ishihara M. The composition of hair preparations and their skin hazards. In: Kobori T, Montagna W, eds. Biology and disease of the hair. Tokyo: University of Tokyo, 1976:603-29. 6. Storrs FJ. Permanent wave contact dermatitis: Contact allergy to glyceryl monothioglycolate. J AM ACADDERMATOL1984;11:74-85. 7. Voss JG. Skin sensitization by mercaptans of low molecular weight. J Invest Dermatol 1958;31:273-9.
8. Lynde CW, Mitchell JC. Patch test results in 66 hairdressers. Contact Dermatitis 1982;8:302-7. 9. Warshawshki L, Mitchell JC, Storrs FJ. Allergic contact dermatitis from glyceryl monothioglycolate in hairdressers. Contact Dermatitis 1982;7:351-2. 10. Hanifin JM, Lobitz WC Jr. Newer concepts of atopie dermatitis. Arch Dermatol 1977;113:663-70. 11. Dupuis G, Benezra C. Allergic contact dermatitis to simple chemicals: A molecular approach. New York: Marcel Dekker, 1982. APPENDIX I. NORTH AMERICAN CONTACT DERMATITIS GROUP'S PATCH TEST TRAYS
Standard tray Benzocaine 5% in petrolatum Mercaptobenzothiazole 1% in petrolatum Colophony 20% in petrolatum Diazolidinyl urea 1% in petrolatum p-Phenylenediamine 1% in petrolatum Imidazolidinyl urea 2% in aqueous solution Cinnamic aldehyde 1% in petrolatum Wool (lanolin) alcohols 30% in petrolatum Carba mix 3% in petrolatum Neomycin sulfate 20% in petrolatum Thiuram mix 1% in petrolatum Formaldehyde 2% in aqueous solution Ethylenediamine dihydrochloride 1% in petrolatum Epoxy resin 1% in petrolatum Quatemium-15 2% in petrolatum p-tertiary-butylphenol formaldehyde resin 1% in petrolatum Mercapto mix 1% in petrolatum Diazolidinyl urea 1% in aqueous solution Black rubber mix (PPD mix) 0.6% in petrolatum Thimerosal 0.1% in petrolatum Imidazolidinyl urea 2% in petrolatum Potassium dichromate 0.25% in petrolatum Balsam Peru 25% in petrolatum Diaminodiphenyl methane 0.5% in petrolatum Cinnamic alcohol 5% in petrolatum d/-a-Tocopherol acetate 4% in petrolatum Colophony mix 60% in petrolatum Nickel sulfate 2.5% in petrolatum Vehicle and preservative tray Benzophenone 1% in petrolatum 2-Bromo-2-nitropropane-l,3-diol (Bronopol) 0.5% in petrolatum p-Chloro-m-cresol 1% in petrolatum Dichlorophene 1% in petrolatum Polyethylene glycol 400 (as is) Sorbic acid 2% in petrolatum DMDM hydantoin 1% in petrolatum
Volume 19 Number 1, Part 1 July 1988
Allergen in hair after glyceryl monothioglycolate exposure
Propylene glycol 10% in aqueous solution Ortho-phenylphenol 1% in petrolatum 5-Chloro-2-methyl-4-isothiasolin-3-one and 2methyl-4-isothiazolin-3-one (Kathon CG) 0.1% in petrolatum Captan 0.25% in petrolatum Chloroxylenol (para-chloro-meta-xylenol) 1% in petrolatum
I
5-Chloro-2-methyl-4-isothiazolin-3-one and 2methyl-4-isothiazotin-3-one (Kathon CG) 0.01% in aqueous solution DMDM hydantoin 1% in aqueous solution Chloroacetamide 0.1% in petrolatum Paraben mix 12% in petrolatum Ammoniated mercury 1% in petrolatum Tween 85 2.5% in petrolatum
1 I
The duration of local control of classic (non-AIDS-associated) Kaposi's sarcoma by radiotherapy Jay S. Cooper, M.D., John Sacco, M.D., and Joseph Newall, M.D. New York, NY We report the short- and long-term responses to radiotherapy of 82 classic Kaposi's sarcomas. Doses were prescribed ab initio and no attempt was made to discontinue treatment as soon as shrinkage was observed, as has been recommended by others. More than 50% of the lesions regressed completely and nearly all underwent some regression. Almost all recurrences were detected within 2 years of treatment and virtually all occurred in lesions that had not regressed completely within 2 weeks of radiotherapy. We conclude that classic Kaposi's sarcoma should be treated with sufficient radiotherapy from the beginning to provide long-term control. (J AM ACADDERMATOL 1988;19:59-66.)
Classic Kaposi's sarcoma is an incurable, multicentric disease that generally occurs in elderly patients of Mediterranean origin who have no k n o w n immunologic suppression. Typically the disease progresses slowly and confines itself to the l o w e r extremities. Local treatment by radiation allows patients to coexist with and often outlive the disease. Because of the relative rarity of classic Kaposi's From the New York University Medical Center. Accepted for publication Dec. 17, 1987. Reprint requests to: Dr. Jay S, Cooper, 560 First Ave., New York, NY 10016.
sarcoma in the United States, literature describing the results of treatment of large numbers of patients is uncommon, Published reports tend to describe the results of radiotherapy in terms of response, analogous to response of lesions to chemotherapy. What is rarely, if ever, discussed is the duration of control. We herein describe the duration of local control after radiotherapy and its relationship to initial tumor response. MATERIALS AND METHODS
From 1972 to 1986 we irradiated 82 Kaposi's sarcomas that occurred in patients who did not have acquired immunodeficiency disease, an organ transplant, 59