In 1997 the U.S. Food and Drug Administration granted an indication for the use of the Thin-layer Rapid Use Epicutaneous (T.R.U.E.) test panels 1.1 and 2.1 as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis (ACD). Many dermatologists utilize this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen.
Specifically, the T.R.U.E. test screens for 46 distinct allergens and the Balsam of Peru mixture. The test is thought to adequately identify an allergen in approximately 24.5% of patients with allergic contact dermatitis.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious Allergens of the Year and the North American Contact Dermatitis Group (NACDG) standard allergens.
“Allergen Focus” is a column designed to concentrate on common allergens and is intended to answer some of the most frequently asked questions relating to their origin and most common uses. This month, we focus on glyceryl monothioglycolate (GTG), a reducing agent in permanent wave solutions frequently applied by hairdressers, who are most at risk for sensitivity to this potential allergen.
The contact dermatides include irritant contact dermatitis, contact urticaria, and allergic contact dermatitis (ACD).
Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-occupational based dermatoses.
Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis, the foremost example of this would be latex protein hypersensitivity. While this is beyond the scope of this section, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.2,3
Allergic contact dermatitis is an important disease with high impact both in terms of patient morbidity and economics. Allergic contact dermatitis represents a T-helper cell, Type 1 (Th1)-dependent, delayed-type (Type IV) hypersensitivity reaction. The instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. On direct antigen exposure to the skin or mucosa, an immunologic cascade is initiated that includes cytokines, i.e., interleukin 2 (IL-2) and interferon gamma (IFN-gamma), T cells and Langerhan cells. This complex interaction leads to the clinical picture of ACD.
A hairdresser presented to the University of Miami Contact Dermatitis Referral Clinic for evaluation of hand dermatitis. She related improvement after avoiding her work place for some time, and she attributed her hand dermatitis to a chemical she was exposed to occupationally.
The History of Hairdressing
Worrying about personal appearance has been a relevant feature of human behavior in all kinds of societies. The way people dress, choose their adornments or hairstyles not only serves for romantic purposes but also defines social status and may even intimidate enemies in a battlefield.4,5
The history of hairdressing as a profession began with barbers in ancient Egypt, a time during which these professionals belonged to a very respected and prosperous class.4,6 Barbers were also noted to exist in Greek, Roman and ancient Jewish societies, among others, serving both men and women.
Not until the 18th century did hairdressers become distinct professionals helping to cultivate social structure. This was a prestigious occupation for men, and many had formal training as wigmakers. Legros de Rumigny, a former baker, became a court hairdresser and later published the Art de la Coiffure des Dames (1765), and opened the Academy of Coiffure in 1769.4
Even until the end of the 19th century, a person’s hairstyle was defined by strict social rules (and the practice of “dressing the hair” was restricted to the higher social classes), as it was an indicator of their social class, religion, occupation and marital status. It also reflected each region’s cultural and fashion preferences.4
By the 20th century (which coincided with the development of the fashion industry), dressing the hair became popular among the “lower” classes.4
The multi-million dollar fashion industry was seen to trigger the amount of influence hairstyling had, people’s way of dressing and behaving, and the demand for more specialized professionals in hairstyling.
With this came regulations and schools, and the chemical industry was looked to for support of these new emerging hairstyles.4 The advances in chemical research allowed development of a great number of new substances that increased the efficiency and the quality of hairdressing procedures. Although this progress helped hairdressers develop their art, it also exposed them to new and potentially dangerous substances.
Early History of the Permanent Wave
Curly hair has been a favorite among both men and women for centuries. In the beginning, hairdressers applied caustic chemicals on wigs to form curls, but those products were known to be too harsh to risk application and processing near human skin. The desire to have fashionably curly or wavy hair led to the search for treatments that promoted long-lasting and wash-resistant curls.
By the 1870s, the French hairdresser Marcel Grateau had invented the heated iron in order to make curls. However, the first chemical treatment for curling hair was conceived by Karl Nessler, a German hairdresser, in 1906. Nessler’s method consisted of wrapping hair in a spiral around rods connected to an electric heating machine. While the device heated the hair (212o F, 100o C or more), sodium hydroxide, a strong alkali, was applied for an extended period of time. Notably, his first two attempts resulted in burning the subjects’ hair and scalp. Undeterred, the method was eventually improved to allow for consistent results and led to the patenting of the permanent wave machine in London in 1909. This machine and method were very popular in Europe and United States until the beginning of the 20th Century.7
Creating a Permanent Wave Process for Short Hair
Short hair became fashionable after the World War I, and because Nessler’s method was only useful for long hair, alternative systems needed to be developed.
In 1924, a Czech hairdresser named Josef Mayer invented the croquignole method, in which hair was wrapped straight up the rod from the ends to the scalp. Because this method was applicable to all different lengths of hair, it soon became popular. Around this time, another method debuted, which consisted of applying pre-heated clamps over the wrapped rods (without the need for connection to a device), but a strong alkali solution was still used.7
In 1931, Ralph I. Evans and Everett G. McDonough showed a heatless system at Midwest Beauty Show in Chicago for the first time. Their method used a bi-sulphite solution that was applied in the salon and conveniently removed by the client the next day. Even so, all of these methods still used very strong alkali solutions, tight wrapping and long exposure time, which often led to hair damage and scalp burns.7
Arnold F. Willatt revolutionized the whole process in 1938 when he invented the cold wave, which needed neither machines nor heat. Hair was wrapped on rods and a reduction lotion was applied. This lotion contained ammonium thioglycolate that broke the disulphide linkages between the polypeptide bonds in the keratin in the hair.
Hydrogen peroxide, a neutralizer acid, was then applied to close the disulphide bridges again, giving the hair the shape of the rod. The process was carried out at room temperature, but it took hours to complete.7 His method maintained a stronghold until the invention of the acid permanent in the 1970s.
Modern-Day Permanent Wave — and Straightening — Solutions
The acid permanent method employed glycerol monothioglycolate and was ammonia-free. While it was slower, it was less aggressive to the hair. The reaction was endothermic, so it needed additional heat, which was supplied by a drier. The heat was necessary to increase the pH from 6.9 to 7.2.7
The process has been further improved, and today’s traditional style perms use sodium thioglycolate rather than ammonium thioglycolate, at a pH of 8 to 9.5. The current process takes 15 to 30 minutes until the neutralizer solution is applied.
It is important to note that there are other types of modern perms that include exothermic, neutral, or low pH, thioglycolate-free perms, and perms for gray hair or children’s hair. Although some home permanent kits are still available, nowaday their use to create curly hair has decreased since perms are currently not as popular as they were in the 1980s. Dermatologists need to be cognizant that curly hair can be straightened by a permanent wave in reverse (and straightening practices are on the rise in some cultures).7
The hair is composed of keratin, a protein that contains a lot of cysteine amino acid. Cysteine can form disulphide bonds between protein chains. Disulphide bonds are bridges between two sulphur atoms (protein-S-protein), and these protein strand cross-links cause the hair to hold its shape. They give hair elasticity and can be reformed with chemicals.8
A perm consists of two parts: the physical action of wrapping the hair and the chemical phase.7
Chemical Phase. The chemical phase has three steps.
1. The first consists of breaking the cysteine disulphide linkages in the hair keratin filament with a reducing agent. This enables the rearrangement of the keratin filament by winding.
2. In the second stage, the hair is shaped into the desired configuration, usually with curlers. The size of the curler determines the tightness of resulting curl.
3. In the final part, the disulphide bonds are reformed into the new positions by an oxidizing agent.9
Many kinds of perm waving solutions can be used, depending on the hair characteristics and desired results: acid cold wave, acid heat activated, self regulated, exothermic, alkaline or buffered alkaline sulphite.9 The basic concepts of softening (reduction), rearrangement (winding) and fixing (oxidation) are supplemented with other treatments to obtain a better result.9
The typical list of ingredients that you would find in a permanent wave solution today would include the following:
Reducing agents: ammonium thioglycolate, diammonium thioglycolate, glyceryl thioglycolate (monothioglycolate), thiolactic acid, cysteamin, potassium sulphite.
Oxidation agents: hydrogen peroxide, sodium bromate.9
Buffering and alkaline agents: ammonium hydroxide, triethanolamine, ethanolamine, ammonium carbonate.9
Others: wetting agents, conditioners, opacifiers, chelating agents, stabilizers, preservatives and perfumes.9
K-S-S-K + 2R- SH 2K-SH + R-S-S-R
2K-SH + 1/2 O2 K-S-S-K + H2O
Glyceryl monothioglycolate (GTG) is a reducing agent in perm solution, with a pH 5-6, and it’s used in hot permanent waves.10-12 It is applied in beauty salons, and it is not available over the counter but may be obtained through wholesale outlets.10 This agent contains a sulphydryl: SH group, and its side chain (see Figure 1) appears to enhance allergenicity.11
An allergen on the NACDG screening tray, GTG is tested in 1% in petrolatum.9,13 It occasionally sensitizes consumers, but it is usually an occupational hazard for hairdressers.9 Therefore, because of a high incidence of cases of occupational sensitization to GTG, products containing this compound were withdrawn from the German market in the mid-nineties.
After this compound was removed from permanent wave solutions, the proportion of hairdressers who reacted positively to GTG initially fell from 48% in 1992 to less than 20% in 1997 and 1998.14 This decrease was confirmed in 2005.15
References published after 2000 showed the following: in Italy a group of 209 hairdressers presented 11.9% of sensitization to glyceryl monothioglycolate. According to recent studies, in the United States the frequency of the GTG allergy has been keeping the same within this country.16
The results of patch testing by NACDG from January 2001 to December 2002 did not show differences in the frequency of positive reactions among the studies of 1994 to 1996, 1996 to 1998 and 1998 to 2000.13 In Spain 300 hairdressers had a similar frequency of sensitization to GTG in the periods between 1994 and 2003 and between 1990 to 1993, 2.7% and 4%, respectively.17
In contrast, ammonium thioglycolate (ATG) has been used since 1943 in cold alkaline permanent waves both in homes and salons, and it has been associated with a rare incidence of allergic contact dermatitis in hairdressers or clients.
It is important to note that ATG reactions are blocked by vinyl gloves. The possibility of association between ATG and GTG is low. Storrs mentioned no awareness of GTG-ATG co-sensitivity, thus far, in the United States.11
Importantly, GTG and paraphenylenediamine are among the most common sensitizers in hairdressers, therefore co-reactions between them are not rare.18
Clinical Aspects of GTG-Induced Reactions
Glyceryl monothioglycolate has the tendency to cause a strong ACD, which easily spreads to the arms, neck and face.9 Hairdressers in general manifest their allergy as a hand dermatitis, whereas the clients with reactions have dermatitis on the scalp, face, ears and neck.11,19 The hairdresser’s hand dermatitis shows a predilection for the fingertips, although dorsal surfaces of the distal aspects of the fingers can also be affected.
A especially interesting pattern of dermatitis is noticed involving the radial and ulnar sides of the second and third fingers. It corresponds to skin exposed to test curl before the neutralization process. The back of the hands and arm involvement can correspond to spatters of curling solution.10,19
In the clients, the neck and ears are commonly involved with acute dermatitis, but the scalp can also be extensively affected.10,19
Two cases of Type 1 allergy to GTG were reported, but it is speculated that it could be more common. In the first case, the patient suffered an accident and had the face, arms and chest sprayed with an 80% solution of GTG, which caused chemical burns on the patient’s eyes.
After 4 days, generalized urticaria broke out, and recurred whenever the patient went to the beauty salon. Patch tests were negative, but a scratch test was positive. The second case presented both Type 1 and Type 4 sensitivity to GTG. She had a subacute dermatitis on the tops of some fingers. Several hours after the patch test, an erythematous streak developed at the site of the GTG patch test, on the right side of her back and spread to the right elbow. It disappeared hours later. At the day 4 reading, GTG 1% pet was applied open on her left hand, above the areas of dermatitis, and urticarial lesions were seen at that site within 10 minutes.20
Characteristics of the Allergen: GTG
An unusual feature observed in several patients is that their GTG-associated dermatitis lasted months after exposure to the permanent wave solution. In addition to this, hairdressers who are allergic to this compound have reported that touching hair that has recently undergone processing with a permanent wave solution makes their hands itch.7 Based on these observations; a study suggested that a GTG-related allergen is retained in hair for up to 3 months after the permanent is applied.10
Another study by Storrs proved that some GTG allergic patients could react through various glove materials. The household-weight neoprene glove and the 4-hour glove blocked penetration of the allergen. The occurrence of allergens penetrating protective gloves is well known, and GTG is listed among others such as acrylate monomers, hair dyes, neomycin, paraben, nickel and nitrogen mustard.11, 21
Glyceryl thioglycolate permanent-waving solution is supplied in two separate bottles or in one bottle with two separate compartments. The contents of these bottles is mixed before application. During mixing and application to the rollers, the solution can spill onto hands, worktables and instruments and can contaminate the salon with GTG. That would explain why some hairdressers experience flare-ups even after they stop applying GTG or handling permed hair.
Thiol groups can be detected with a chemical spot test using sodium nitroprusside. The test easily traces contamination with GTG, but does not differentiate between different chemicals with thiol groups, for example GTG and ATG.12
Preventing This Allergy
In order to prevent this allergy, it is worthwhile for hairdressers to wear adequate protective gloves when shampooing or handling hair that has been treated with GTG within the last 3 months. For clients who are allergic to GTG, avoidance of the compound is stressed, and cold permanent wave solutions containing ATG can be used instead of acid perms.11 In addition to these tactics, the sink, the taps and tools in the salon should be carefully rinsed with water after every perm is applied.9
Although the frequency of GTG allergy is not increasing, it is advisable to be aware of some points such as clinical aspects, persistence of the allergen in hair, penetrance through some protective gloves, and contamination of the salons with it.
Value of the Case
The hairdresser we treated was found to have positive reactions to GTG and para-phenylenediamine (PPD). On post patch-test review, it was determined that she was using thioglycolic acid to do perms, not GTG.
When reviewing our patient’s history, we found a positive correlation with a past occupational exposure (and sensitization) to GTG. However, the current positive patch reaction was determined to be of past clinical relevance. The PPD, on the other hand, was found to be of definite clinical relevance.
This case demonstrates the importance of recognizing the ability of the immune system to recall past sensitization and the need to assign proper clinical relevance. In Brazil, cases of sensitization to GTG have not been reported, and this allergen is not routinely screened for on our standard tray.