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Home , Contact dermatitis, Depigmentation, Hypopigmentation, Incontinentia pigmenti, Lentigo, Melanosis

18_319_334* 05.11.2005 10:30 Uhr Seite 319

Chapter 18 Pigmented Contact 18 and Chemical

Hideo Nakayama

Contents ca, often occurs without showing any positive mani- 18.1 Associated festations of dermatitis such as marked , with ...... 319 vesiculation, swelling, , rough skin or scaling. 18.1.1 Classification ...... 319 Therefore, patients may complain only of a pigmen- 18.1.2 Pigmented Contact Dermatitis ...... 320 tary disorder, even though the disease is entirely the 18.1.2.1 History and Causative Agents ...... 320 result of allergic contact dermatitis. Hyperpigmenta- 18.1.2.2 Differential Diagnosis ...... 323 tion caused by histologica 18.1.2.3 Prevention and Treatment ...... 323 has often been called a lichenoid reaction, since the 18.1.3 Pigmented Cosmetic Dermatitis ...... 324 presence of basal liquefaction degeneration, the ac- 18.1.3.1 Signs ...... 324 cumulation of pigment, and the mononucle- 18.1.3.2 Causative ...... 325 ar cell infiltrate in the upper dermis are very similar 18.1.3.3 Treatment ...... 326 to the histopathological manifestations of lichen pla- 18.1.4 Purpuric Dermatitis ...... 328 nus. However, compared with typical , 18.1.5 “Dirty Neck” of Atopic Eczema ...... 329 is usually milder, 18.2 Depigmentation from Contact and saw-tooth-shape acanthosis are lacking, hyaline with Chemicals ...... 330 bodies are hardly seen, and the band-like massive in- 18.2.1 Mechanism of Leukoderma filtration with lymphocytes and histiocytes is lack- due to Chemicals ...... 330 ing. 18.2.2 Contact Leukoderma Caused Mainly by Contact Sensitization ...... 332 A lichenoid reaction is considered to be a scaled- down type-IV allergic reaction of the lichen planus References ...... 332 type, based on positive reactions in pa- tients and negative reactions in controls, as in ordi- nary allergic contact dermatitis. An increase in melanin pigment in keratinocytes is noted after allergic contact dermatitis, presumably 18.1 Hyperpigmentation Associated caused by hyperfunction of , but the with Contact Dermatitis same phenomenon is also seen with irritant contact dermatitis.When sodium lauryl sulfate,a typical skin 18.1.1 Classification irritant, was repeatedly applied on the forearms of Caucasians, the number of epidermal melanocytes Hyperpigmentation associated with contact derma- was observed to almost double, suggesting hyperpla- titis is classified into three categories: (1) hyperpig- sia, hypertrophy, and increased function [1]. mentation due to incontinentia pigmenti histologica; The pathological processes involved in the third (2) hyperpigmentation due to an increase in melanin form of hyperpigmentation with contact dermatitis, in the basal layer cells of the , i.e., basal me- purpuric dermatitis, have not yet been clarified. Shii- lanosis; and (3) hyperpigmentation due to slight take mushroom, very commonly eaten in Asia, has hemorrhage around the vessels of the upper dermis, been known to produce a transient urticarial derma- resulting in an accumulation of hemosiderin, such as titis with severe itching, which results in a purpuric in Majocchi–Schamberg dermatitis. scratch effect, when insufficiently cooked. This is It is easy to understand that when the grade of thought to be due to toxic substances in the mush- contact dermatitis is more severe, or its duration room unstable to heat, and the pigmentation due to longer, the secondary hyperpigmentation following purpura is not caused by [2].As with dermatitis is more prominent. However, the first type other forms of dermatitis, accompanying capillary mentioned above, incontinentia pigmenti histologi- fragility results in purpura. Some cases are associat- 18_319_334* 05.11.2005 10:30 Uhr Seite 320

320 Hideo Nakayama

ed with contact hypersensitivity to rubber compo- allergens from textiles, soaps or washing nents or textile finishes, but in many cases the causes powders for textiles. Successive contact are not known. with small amounts of allergens destroys basal layer cells of the epidermis, resulting in melanin accumulation in the upper 18.1.2 Pigmented Contact Dermatitis dermis for a long time. Treatment entails finding out the contact allergens, and 18.1.2.1 History and Causative Agents avoiding them for a long time.

Core Message Pigmented contact dermatitis was first reported by í Pigmented contact dermatitis on the Osmundsen in Denmark in 1969. In 8 months he had covered area cannot be cured by the 120 patients, 7 of whom showed a pronounced and application of ointments, bizarre hyperpigmentation. In 4 of these 7 cases con- even though it is a result of contact tact dermatitis preceded the hyperpigmentation,

Table 1. The main contact sensitizers producing secondary hyperpigmentation

Name Chemical structure Purpose Patch test concentration and base

Tinopal CH3566 Optical whitener in 1% pet. washing powder

Naphthol AS Dye for textile 1% pet.

Benzyl salicylate Fragrance 5–1% pet.

Hydroxycitronellal Fragrance 5–1% pet.

D &C Red 3 and brilliant Pigment for 1% pet. lake red R

18 Phenyl-azo-2-naphthol Impurity 0.1% pet. (PAN)

D & C Yellow 11 Pigment for cosmetics 0.1% pet.

Ylang-ylang oil Fragrance, incense 5% pet.

dehydrodiisoeugenol 18_319_334* 05.11.2005 10:30 Uhr Seite 321

Contact Dermatitis and Chemical Depigmentation Chapter 18 321

Table 1. Continued

Name Chemical structure Purpose Patch test concentration and base

Jasmine absolute Main sensitizer not yet identified Fragrance 10–5% pet.

Synthetic sandalwood Main sensitizer not yet identified Fragrance 10% pet.

Cinnamic alcohol Fragrance 1% pet.

Musk ambrette Fragrance, incense 5% pet.

Biocheck 60 Pesticide for textiles 0.2% aq.

PPP-HB Textile finish 5% eth.

Impurity of commercial Main sensitizers not yet identified Dye 5% eth. CI Blue 19 (Brilliant Blue)

Mercury compounds Hg2+ Bactericides 0.1–0.05% aq. or pet. (not with aluminum chamber)

Nickel (sulfate) Ni2+ Metal product 5% aq. or pet.

Chromate (K dichromate) Cr6+ Leather, soap 0.5% aq. or pet.

while the other 3 did not notice any signs of derma- tical whitener, Tinopal or CH3566 (Table 1). This was titis such as itching or erythema before the pigmen- one of numerous optical whiteners which became tation appeared [3, 4]. available at that time to make textiles “whiter than Hyperpigmentation, with or without dermatitis, white.” Patch tests with CH3566 1% pet. finally ex- was located mostly in covered areas, such as the plained the pigmentary disorder, as they showed chest, back, waist, arms, neck, and thighs. After a pa- strong positive reactions in the patients and negative tient wanted to conceal the pigmentation by wearing results in the controls. The pigmentation was persis- long sleeves and a high-neck sweater, which she tent, but the dermatitis that often preceded hyperpig- washed with a washing powder every day, the hyper- mentation was observed to disappear following the pigmentation extended from the neck and axillae to elimination of washing powders that contained all over the neck, chest, and arms. The hyperpigmen- CH3566. Fortunately, the identification of the causa- tation was brown, slate-colored, grayish-brown, red- tive chemical was made rapidly, and the widespread dish-brown, bluish-brown, etc., according to the case, usage of CH3566 was avoided in time. and often had a reticulate pattern. The histopatholo- Pigmented contact dermatitis is rare in Cauca- gy of the pigmentation showed incontinentia pig- sians but not uncommon in Mongoloids. The next menti histologica. pigmented contact dermatitis was reported by Anco- Patch tests with the standard series current at that na-Alayón et al. in Mexico [5]. Among 53 workers time gave no information as to the causative aller- handling azo dyes in a textile factory, 12 developed a gens. However, Osmundsen noticed that the patients spotted hyperpigmentation without pruritus, and 18 had used washing powders that contained a new op- suffered from hyperpigmentation to a lesser extent. 18_319_334* 05.11.2005 10:30 Uhr Seite 322

322 Hideo Nakayama

This new occupational skin disorder appeared 4 months after the introduction of a new dyeing pro- cess of azo-coupling on textiles, and most of the pa- tients had contact with azo dyes on weaving ma- chines. Hyperpigmentation varied from a bizarre dark pigmentation to a streaky milder pigmentation of the neck, arms, face, and, in exceptional cases, cov- ered areas. Histopathological examination of the pigmentary disorder showed , irregular acanthosis, of the dermis, pericapillary lymphocytic infil- tration, basal liquefaction degeneration, and inconti- nentia pigmenti histologica. prolifera- tion at the affected sites was also noted. a Patch tests showed that 24 of the 53 workers were positive to Naphthol AS 5% in water, while the other 29, as well as 10 controls, were negative to Naphthol AS. The dermatoses disappeared after the dyeing process was changed so that the workers did not di- rectly touch Naphthol AS, an azo dye coupling agent. In the early 1980s, pigmented contact dermatitis due to Naphthol AS appeared in central Japan, but this time it was not occupational. A textile factory manufacturing flannel nightwear, a traditional Japa- nese garment called yukata, economized on water for washing the products after the process of azo- coupling using Naphthol AS. This modification of production resulted in the appearance of pigmented contact dermatitis of the covered areas of skin of people living in the districts where the products were distributed and worn. Kawachi et al. [6] and Hay- akawa et al. [7] reported such cases, and the hyper- pigmentation was mainly located on the back and b neck. The factory was said to have improved the washing process and the materials quickly, but the Fig. 1a, b. Pigmented contact dermatitis (a) in a 67-year-old presence of such cases indicates that whenever the man who was sensitized by several textile finishes, including textile industry uses Naphthol AS, and at the same commercial grade red and brown dyes and fungicides (b) time economizes on water for washing the products, there must be a risk of producing pigmented contact dermatitis of the covered areas. According to Hay- time by the textile industry in Japan. They were cho- akawa et al. [7] the amount of Naphthol AS detected sen from approximately 1,200 textile finishes, either in the patients’ nightwear was 4,900–8,700 ppm, a imported or produced in Japan. They were checked considerable amount. A case due to Naphthol AS in a as to solubility in water, ethanol, , etc., diluted 18 pillow case was later reported [8]. to 5% (except bactericides, fungicides, and other pes- In 1984, the city of Tokyo decided to investigate ticides for textiles which were diluted to 1%), and new textile finishes which seemed to have produced then applied to dry paper discs 8 mm in diameter, to contact dermatitis of the covered skin areas, includ- make dry -containing discs named “instant ing pigmented contact dermatitis (Fig. 1). Based on patch test allergens.” They were peeled off silicon- information about the textile finishes which actually treated covering paper before use. came into contact with the patients’ skin or were very The results obtained from five hospitals in and commonly used, 115 chemicals were finally chosen around Tokyo revealed that several new contact sen- and patch tested. The test materials included 50 dyes sitizers were responsible for producing textile der- of all colors, 13 whiteners, 5 fungicides, 32 resin com- matitis and secondary hyperpigmentation. These ponents, 13 softening agents, and 15 other miscellane- textile finishes included Biochek 60, a very toxic fun- ous textile finishes which were widely used at that gicide which seemed also to have acted as a sensitiz- 18_319_334* 05.11.2005 10:30 Uhr Seite 323

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er, a phosphite polymer of pentaerythritol and hy- pigmented contact dermatitis. The disease, however, drogenated bisphenol A (PPP-HB), impurities in a is produced by patients vigorously rubbing the skin dye CI Blue 19 (or Brilliant Blue R), and mercury with a hard nylon towel or nylon brush every day compounds [9]. when bathing. Patch testing with various contact al- The research on these 115 chemicals was per- lergens failed to demonstrate allergens that seemed formed in the 5 hospitals on 80–101 persons, among to be correlated with the disease.It was Tanigaki et al. whom 51–62 were patients suffering from textile con- [12] in 1983 who pointed out the causative association tact dermatitis, and the rest, 29–39, were controls of rubbing with a nylon towel or brush, and the dis- with and dermatitis due to causes ease has gradually decreased since this hazard has other than textiles. Among those with textile contact become known to the public. dermatitis, 27–33 had pigmented contact dermatitis. The use of nylon towels or brushes for washing the Such cases had been deliberately chosen for patch skin should therefore be checked before the diagno- testing because the investigators hoped to find out sis of pigmented contact dermatitis due to textiles is the causative contact sensitizers producing such hy- made. If the dark hyperpigmentation of the skin over perpigmentation. Of these pigmented contact der- gradually fades and disappears after use of ny- matitis patients, 9 showed positive reactions sugges- lon towels or brushes is discontinued and patients tive of an to Biochek 60, and 1 to several tex- change their mode of washing to a milder technique, tile finishes. The results were rather disappointing, the diagnosis of friction should be consid- but they did show that it is not easy to discover the ered. Curiously,the histopathology of friction melan- contact sensitizers producing pigmented contact osis shows incontinentia pigmenti histologica, which dermatitis from contact with textile finishes. The dis- is a characteristic feature of pigmented contact der- coveries of CH3566 and Naphthol AS can be regarded matitis. However, liquefaction degeneration of basal as having been important and valuable. Pigmented layer cells of the epidermis is not present [11]. contact dermatitis due to blue dyes, Blue 106 and 124 Another skin disorder to be distinguished is skin was reported by Kovacevic et al. in 2001 [10]. amyloidosis, especially lichen amyloidosus or papu- Besides the above-mentioned textile finishes, rub- lar amyloidosis. It is possible that a small amount of ber components can also produce dermatitis result- amyloid, which can be demonstrated by Dylon stain- ing in hyperpigmentation, mainly around the waist. ing, is found in lichenoid tissue reactions, probably Sometimes in such cases the pigmentation is not due because amyloid in the upper dermis is considered to to incontinentia pigmenti histologica but to purpura be derived from degenerate epidermal cells pro- (see Sect. 18.1.4, Purpuric Dermatitis). Thus far, only duced by epidermal inflammation. Special staining cases of pigmented contact dermatitis in which caus- with Congo red or thioflavine T and electron-micro- ative allergens were found have been reported. Caus- scopic study of the skin specimen are also helpful in es other than contact sensitivity have not yet been the differential diagnosis. well investigated, except for friction melanosis which is described in Sect. 18.1.2.2, Differential Diagnosis. 18.1.2.3 Prevention and Treatment

18.1.2.2 Differential Diagnosis It is essential to avoid the use of textiles and washing powders containing strong contact sensitizers, in or- Differential diagnosis of pigmented contact derma- der to prevent contact dermatitis and pigmented titis due to washing powder or textile components in- contact dermatitis of the skin areas that come into cludes Addison’s disease, friction melanosis, amyloi- contact with the fabric and washing powders or sof- dosis cutis,,atopic dermatitis with pig- tening agents that remain on them even after rinsing. mentation and dermatitis and secondary hyperpig- There are, however, many textile finishes available to- mentation due to dental metal sensitivity (dental day, with more than 1,200 commercial finishes being metal eruption). sold to the textile industry, and unfortunately their Friction melanosis was frequently seen in Japan in components are mainly secret. The purity of dyes is, the 1970s and 1980s, the disease consisting of dark in general, very low and some of the many impurities brown or black hyperpigmentation unaccompanied are allergenic. For example, the very commonly used by dermatitis or itching [11]. Friction melanosis oc- CI Blue 19 (or Brilliant Blue R) turned out to be aller- curred predominantly on the skin over or along genic and caused some patch-test-positive cases of bones, such as the clavicles, ribs, scapulae, spine, pigmented contact dermatitis in 1985 [9]. Purified CI knees, and elbows. The color and distribution of fric- Blue 19, in contrast, never produced positive patch tion melanosis sometimes leads to confusion with test reactions at the same 5% concentration. 18_319_334* 05.11.2005 10:30 Uhr Seite 324

324 Hideo Nakayama

The experiences accumulated in the past show materials for their clothing at the same time, so that that, when entirely new textile finishes are intro- their skin was not contaminated by the responsible duced to the textile industry, the minimum safety allergens in ordinary soaps and washing materials. evaluation tests such as LD50, Ames test, and skin ir- Matsuo et al. reported several cases in which this ritation test should be performed, and their sensiti- treatment was successful [13, 14]. zation potential should be investigated by a research Even though cases are very rare, pigmented con- team including dermatologists. Strong contact sensi- tact dermatitis can also occur following systemic tizers can be detected by several experimental proce- contact dermatitis. In a 50-year-old man, for exam- dures using animals. Although animal experiments ple, recurrent and persistent dermatitis accompanied are now the subject of ethical scrutiny in connection diffuse secondary hyperpigmentation. The use of with such investigations, they remain indicated if the corticosteroid ointments,oral ,and al- irritability and allergenicity of textile finishes are to lergen-free soaps did not improve the condition at be adequately investigated. all. A patch test with sulfate 5% aq. showed a The textile industry should cooperate with derma- strong positive reaction, with a focal flare of most of tologists when pigmented contact dermatitis has the original skin lesion. This implied not only that once occurred, by immediately informing them of the patient was sensitive to nickel, but also that only a the components of the chemical finishes of the textile few hundred parts per million of nickel ions ab- suspected to have caused the disease, and a precise sorbed from the patch test site into the bloodstream study of impurities and quality control in the factory were enough to provoke an allergic reaction over a should also be performed. Shortening of the washing wide area of the site of the original skin lesions. This process should be strictly refrained, otherwise sur- observation led to a search for a source of nickel ions plus dyes,their impurities,and other chemical finish- in the patient, and five nickel alloys were subsequent- es may remain and produce a problem. ly found in the patient’s oral cavity. He agreed to When a causative allergen is discovered, the solu- eliminate these nickel crowns, as they turned out to tion of pigmented contact dermatitis is not difficult have been acting as cathodes, attracting an electric [4, 5, 7]. However, when causative allergens are not current of 1–3 mA at 100–200 mV. According to identified, the solution of the pigmentary disorder is Faraday’s law of electrolysis, cations elute from the usually very difficult. In 1985, in Japan, a new strategy cathode in proportion to the amount of electric cur- for the treatment of both recurrent textile dermatitis rent passing into the cathode. and pigmented contact dermatitis was introduced. The complete elimination of nickel-containing al- Based on the research project for finding out contact loys from his oral cavity and their substitution with sensitizers and irritants in textiles [9], underwear gold alloys, which did not contain any nickel at all, re- with only four or five kinds of textile finishes which sulted in complete cure of the dermatitis and secon- showed no evidence of positive reactions in patients dary hyperpigmentation in 3 months, and there has with contact dermatitis, pigmented contact derma- never been any recrudescence of the disease. The titis, atopic dermatitis, and healthy controls was put patient’s pigmented contact dermatitis had been kept into mass production and became available. This is a going for a long period by metal allergens continu- measure to prevent the patients coming into contact ously supplied from his own oral cavity [15]. with the responsible allergen in ordinary underwear again, and keeps the patients out of range of the re- sponsible allergens. 18.1.3 Pigmented Cosmetic Dermatitis Such allergen-free underwear for patients is called allergen-controlled wearing apparel (ACW) and has 18.1.3.1 Signs 18 successfully counteracted pigmented contact derma- titis. The idea was inspired by the success of allergen- controlled cosmetics in 1970, which is discussed later Core Message (see Sect. 18.1.3, Pigmented Cosmetic Dermatitis). It is not surprising that persistent secondary hyperpig- í Pigmented cosmetic dermatitis is caused mentation disappears only very slowly when the by the same mechanism as pigmented causative contact allergens are completely eliminated contact dermatitis of the covered area; from the patient’s environment for a long period, as however, the causative allergens are quite the hyperpigmentation is considered to be brought different, and they are a number of cosmet- about by frequent and repeated contact with a very ic allergens. Patch test of cosmetic series small amount of contact sensitizer in the textile or allergens is recommended, and continual washing material. Patients were requested to use al- and exclusive usage of allergen-controlled lergen-free soaps and allergen-eliminated washing cosmetics and soaps cures the disease. 18_319_334* 05.11.2005 10:30 Uhr Seite 325

Contact Dermatitis and Chemical Depigmentation Chapter 18 325

The most commonly seen hyperpigmentation due to lular infiltrates of lymphocytes and histiocytes are contact dermatitis in the history of seen perivascularly, as are often seen in ordinary al- must be the pigmented cosmetic dermatitis which af- lergic contact dermatitis (Fig. 2). fected the faces of Oriental women [16]. Innumerable In some cases, the dark brown or black hyperpig- patients with this pigmentary disorder presented in mentation is also seen on skin other than on the face. the 1960s and 1970s in Japan, and similar patients The neck, chest, and back can be involved and, in a were also seen in Korea, India, Taiwan, China, and the few exceptional cases, hyperpigmentation may ex- USA. tend to the whole body. In these cases, the allergens The signs of pigmented cosmetic dermatitis are cinnamic alcohol and its derivatives sensitize the pa- diffuse or reticular, black or dark brown hyperpig- tients first to cosmetics and then provoke allergic re- mentation of the face, which cannot be cured by the actions to soaps, domestic fabric softeners, and food, use of corticosteroid ointments or the continuous in- all of which sometimes contain cinnamic derivatives. gestion of vitamin C. The border of pigmented cos- The ingestion of 1 g cinnamon sugar from a cup of metic dermatitis is not sharp, as in lichen planus or tea in a supermarket was enough to provoke a mild , and it is not spot-like as in of Ota focal flare of dermatitis at the sites of diffuse reticu- tardus bilateralis. lar black hyperpigmentation of the whole body in Slight dermatitis is occasionally seen with hyper- one reported case [17].When one of the common po- pigmentation, or dermatitis may precede hyperpig- tent sensitizers producing pigmented cosmetic der- mentation. In contrast to Addison’s disease, pigment- matitis, D & C Red 31 (Japanese name R-219), was dis- ed cosmetic dermatitis does not show any systemic covered, a focal flare of dermatitis at the site of facial symptoms such as weakness,fatigue,and emaciation. hyperpigmentation was occasionally noted by patch Laboratory findings such as full blood count, liver testing 5% R-219 in petrolatum. These findings show function tests, daily urinary excretion of 17-ketoster- that the allergen could provoke the dermatitis not oid and 17-hydroxy corticosteroid, and serum immu- only by contact with the skin surface but also from noglobulins and electrolytes are normal in the ma- within the skin, by allergens transported via blood jority of patients with pigmented cosmetic derma- vessels, just as allergic contact dermatitis can be pro- titis [16]. voked by the administration of small amounts of Histopathological examination of pigmented cos- nickel or drugs. metic dermatitis shows basal liquefaction degenera- tion of the epidermis and incontinentia pigmenti histologica. The epidermis maybe mildly acanthotic, 18.1.3.2 Causative Allergens however it is sometimes atrophic, presumably the ef- fect of frequently applied corticosteroid ointments The term “pigmented cosmetic dermatitis” was in- for the treatment of itchy dermatitis of the face. Cel- troduced in 1973 for what had previously been known

Fig. 2. Histopathology of a typical lichenoid reaction, with in- continentia pigmenti histo- logica of pigmented cosmet- ic dermatitis. The epidermis shows mild acanthosis, and occasional liquefaction de- generation in the basal layer of the epidermis has dropped melanin pigments into the upper dermis. Note that the cellular infiltration in the upper dermis is not as dense as in lichen planus 18_319_334* 05.11.2005 10:30 Uhr Seite 326

326 Hideo Nakayama

as melanosis faciei feminae when the mechanism than 1,000) for their allergenicity to be evaluated. (type IV allergy), most of the causative allergens, and Finally, in 1969, a research project was set up to successful treatment with allergen control for this identify the causative allergens from 477 cosmetic in- miserable pigmentary disorder were clarified for the gredients by patch and photopatch testing. It was a first time [18, 19]. The name was adopted by modify- new idea, because melanosis faciei feminae had been ing Osmundsen’s designation pigmented contact regarded as a rather than a type dermatitis, for the disease caused by CH3566 on the of contact dermatitis. This was 7 years before Finn trunk. chambers became available; therefore, small patch Historically, the first description of the disease test plasters of 10× 2 cm with six discs 7 mm in diam- goes back to 1948, when Japanese dermatologists en- eter (Miniplaster) were put into production to enable countered this peculiar pigmentary disorder for the 48–96 samples to be patch tested at one time on the first time, and were greatly embarrassed as to diag- backs of volunteer control subjects and patients. nosis. Bibliographical surveys showed that Riehl’s Many cosmetic ingredients, adjusted to nonirritant melanosis, described in 1917 [20], seemed probable, concentrations with the cooperation of 30–40 volun- because World War II had ended just 3 years before teers, were subsequently patch and photopatch tested the investigation. Subsequently, the disease was erro- in the patients. Results for each ingredient were ob- neously called Riehl’s melanosis for almost 30 years tained from 172–348 patients, including 79–121 with in Asian countries. Riehl’s melanosis, however, was a melanosis faciei feminae. Statistical evaluation dark brown hyperpigmentation observed during brought to light a number of newly discovered con- World War I in Caucasian men, women and children, tact sensitizers amongst the cosmetic ingredients, when food was extremely scarce and the patients had mainly fragrance materials and pigments, including to eat decayed corn and weed crops instead of the jasmine absolute, ylang-ylang oil, cananga oil, benzyl normal food of peacetime. Besides hyperpigmenta- salicylate, hydroxycitronellal, sandalwood oil, artifi- tion of the face, ears and scalp, there were nodules cial sandalwood, geraniol, geranium oil, D & C Red and, histopathologically, dense cellular infiltration 31, and Yellow No. 11 [16, 18, 19, 22]. was present in the dermis. Cosmetics could be ex- cluded as a cause, because it was during World War I, and it was not possible for all these people, especially 18.1.3.3 Treatment the men and children, to have used cosmetics before they had the disease. Riehl could not discover the The above-mentioned research project at the same true cause of this pigmentary disorder, but suspected time included a plan to produce soaps (acylgluta- the role of the abnormal wartime diet [20]. Riehl’s mate) and cosmetics for the patients from whom the melanosis disappeared when World War I ended, causative allergens had been completely eliminated, when people obtained normal food again, to reap- as even those who suffered from severe and bizarre pear for a short period in France during the German hyperpigmentation usually could not accept aban- occupation in World War II,when food again became doning their use of cosmetics to remove this pigmen- scarce. tary disorder. Patch testing with a series of 30 stan- Consequently, Riehl’s melanosis, a wartime me- dard cosmetic ingredients to find the allergens caus- lanosis having no relationship to cosmetic allergy, ing the disease [23], followed by the exclusive use of should not be confused with pigmented cosmetic soaps and cosmetics that were completely allergen- dermatitis, which involved many Asian women in free for such patients, designated the allergen control peacetime for many years. In 1950, Minami and No- system, produced dramatic effects. Around 1970, ma [21] designated the disease melanosis faciei femi- most textbooks of dermatology in Japan said that 18 nae, and recognized the disease as a new entity. The melanosis faciei feminae was very difficult to cure causation was not known for many years. However, and that the causation was unknown. However, after Japanese dermatologists gradually became aware of allergen control was introduced, the disease became the role of cosmetics in this hyperpigmentation. completely curable. Table 2 shows the effect of aller- First, it occurred only on those women, and very ex- gen control in 165 cases reported to the American ceptionally men, who used cosmetics and, secondly, Academy of Dermatology in 1977, and also the long- even though the bizarre brown hyperpigmentation term follow-up results of allergen control obtained was so conspicuous, the presence of slight, recurrent, by Watanabe after 3–11 years (mean, 5 years). In 50 or preceding dermatitis was observed. The problem cases of pigmented cosmetic dermatitis cured by al- for the dermatologists at that time was that the com- lergen control (i.e., patch test with 30 cosmetic series ponents of cosmetics were completely secret, and the patch test allergens [25] followed by the exclusive use kinds of cosmetic ingredients were too many (more of allergen-free soaps and cosmetics, Acseine® in Ja- 18_319_334* 05.11.2005 10:30 Uhr Seite 327

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Table 2. Effect of allergen-controlled cosmetics on pigmented pan and Hong Kong), there were, on average, 2.5 al- cosmetic dermatitis patients lergens for each patient. It usually required 1–2 years Nakayama Watanabe for a patient to regain normal nonhyperpigmented et al. [22] [24] facial skin (Fig. 3). Contamination with ordinary soaps and cosmetics was the most influential and de- Total 165 53 cisive factor inhibiting therapy, because such ordi- Complete cure 52 40 nary daily necessities contained the allergens that Almost complete cure 21 0 were producing the disease. The patients were there- Remarkable improvement 51 13 fore requested to visit the dermatologist once a Improvement 22 0 month to be checked for improvement, and were per- Not effective 19 0 suaded every time to avoid such contamination, in- Follow-up 3 months 3–11 years cluding products used in beauty parlors [16, 24]. to 5 years (mean 5 years) In 1979, Kozuka [25] discovered a new contact sen- sitizer, phenylazo-2-naphthol (PAN), as an impurity

a b

Fig. 3a–c. Pigmented cosmetic derma- titis in a 43-year-old woman, caused by contact hypersen- sitivity to jasmine absolute (a). Jasmine absolute 10% in petrolatum produced reac- tions (site 1) which were still positive even on the eighth day of the patch test (b). The exclusive use of soaps and cosmetics that did not con- tain common and rare cos- metic sensitizers cleared the persistent dermatitis with pigmentation completely af- ter 1 year and 8 months of use (c) c 18_319_334* 05.11.2005 10:30 Uhr Seite 328

328 Hideo Nakayama

in commercial supplies of D & C Red 31. Its sensitiz- dermatologists to recognize the importance of cos- ing ability and ability to produce secondary hyper- metic allergens in producing hyperpigmentation. pigmentation were as great as those of Yellow No. 11, and therefore many industries began to eliminate or considerably decrease the amount of PAN and Yellow 18.1.4 Purpuric Dermatitis No. 11 in their products. The legal partial restriction of Red No. 31 and Yellow No. 11 by the Japanese gov- In 1886 Majocchi described purpura annularis telan- ernment and the voluntary restriction by cosmetic giectodes and, 4 years later, Schamberg described a companies of the use of allergenic fragrances, bacte- progressive pigmentary dermatitis which is now well ricides, and pigments resulted in a remarkable de- known as Schamberg’s disease. The pigmentation in crease in pigmented cosmetic dermatitis after 1980. this dermatitis is due to the intradermal accumula- One of the reasons for the proposal to change the tion of hemosiderin, the predominant sites being the name from “melanosis faciei feminae” to “pigmented legs and thighs. Later, Gougerot and Blum described cosmetic dermatitis” [18] was that the latter name a similar dermatosis as pigmented purpuric lichen- makes it easier for the patients to understand the oid dermatitis. causation of the disease and, at the same time, for in- The disease was rare but most often occurred in dustry to recognize the danger of cosmetics in pro- middle-aged or elderly men.However,when a similar ducing such disastrous pigmentary disorders disease occurred in many British soldiers during through contact sensitization. The disease was still World War II, especially in those who sweated freely present in the 1990s [26, 27], and it is necessary for or experienced friction when wearing khaki shirts or

b

18

a

Fig. 4a, b. Reticular brown hyperpigmentation of pigmented Exposure to the contact allergen was considered to have been purpuric lichenoid dermatitis on an 80-year-old male (a). Bi- from the textile finishes of his socks. The exclusive usage of opsy showed marked hemorrhage around capillaries of the well-washed white cotton socks gradually improved the der- upper dermis, along with the cellular infiltrates composed of matitis. Complete blood count (CBC) and liver function test lymphocytes and histiocytes. Patch test revealed strong con- results were normal. This case indicates the importance of tact hypersensitivity to paratertiarybutyl phenolformaldehyde patch test of textile finishes if possible,for the treatment of this resin at 1% petrolatum (b). It had been (H) positive from D2 to pigmentary disorder D14 and confirmative patch test was again strongly positive. 18_319_334* 05.11.2005 10:30 Uhr Seite 329

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woolen socks, with severe pruritus, dermatitis and cases, and also shows an aspect of contact hypersen- pigmentation due to purpura, dermatologists be- sitivity to house dust mites [34–36], metals [37], and came aware that some textile finishes must have been other environmental substances. responsible for the disease [28, 29]. Patch tests and The elevation of serum IgE in patients with mod- use tests revealed that a blend of vegetable oils and erate or severe atopic dermatitis up to 2,000 or even oleic acid seemed to have been responsible. to 20,000 IU/ml is peculiar, since with bronchial In 1968, Batschvarov and Minkov [30] reported asthma, , conjunctivitis, and urticaria, only that rubber components such as N-phenyl-N´-iso- rarely does the level of IgE exceed 1,000 IU/ml [38]. propyl-p-phenylenediamine (IPPD), N-phenyl-β- However, it is certain that some 20–30% of moderate naphthylamine (PNA), 2-mercaptobenzothiazole or severe atopic dermatitis patients do not show any (MBT) and dibenzothiazole disulfide (DBD), i.e., de- rise in serum IgE levels; therefore, one explanation rivatives of p-phenylenediamine, naphthylamine, for this controversy is that atopic dermatitis has two and benzothiazoles, were the allergens responsible aspects of immunity for the production of eczema: for a purpuric dermatitis around the waist under- first, IgE-mediated allergy resulting in spongiosis neath the elastic of underwear. A similar pigmented [39], and, second, cell-mediated allergic contact der- dermatitis was recognized in the shoulders, breasts, matitis [40, 41]. groins, and thighs. The capillary resistance (Rumpel- So-called dirty neck is, histologically, a moderate Leede) test was positive in all 23 cases studied. Simi- dermatitis composed of slight acanthosis, lympho- lar test results were obtained in a smaller proportion cyte and histiocyte infiltration around the vessels in of patients with the khaki dermatitis mentioned the upper dermis, and incontinentia pigmenti histo- above. In Bulgaria, over 600 patients were recorded, logica. The reticular pattern of “dirty neck” resem- and the necessity for dermatologists to investigate bles macular amyloidosis; however, amyloid is usual- contact allergens in textiles to solve the problem of ly negative according to Congo red stain, and only a purpuric dermatitis of covered areas of skin was small amount of amyloid was detected by electron stressed [30]. A dye, blue 85, was reported as a causa- microscopy [32]. The pigmentation and configura- tion in 1988 [31].A case due to a textile finish of socks tion are also similar to pigmented cosmetic derma- is demonstrated (Fig. 4). titis morphologically; however, the most commonly detected contact allergens with severe atopic derma- titis including “dirty neck” were not previously de- 18.1.5 “Dirty Neck” of Atopic Eczema scribed cosmetic allergens, but frequently house dust mite components [34, 35]. Today, a test to demon- strate mite contact hypersensitivity is possible using Core Message a commercially sold patch test reagent Dermatopha- goides Mix® (Chemotechnique, Sweden) in a Finn í Today, there is much evidence that house chamber. House dust mite proteins such as Der 1 to 7 dust mites are one of the most important have been known as sensitizers, and recently α-aca- causations of severe atopic dermatitis. ridial, a component of a house dust mite Tyrophagus Suffering from this dermatitis for many putrescentiae, turned out to be a primary sensitizer years often leads to reticular dark brown [42]. Active sensitization was observed by the patch hyperpigmentation of the neck, i.e., the test of α-acaridial at 5–0.5% in petrolatum, and the dirty neck. Using the patch test and RAST positive reactions were maintained for 1–11 months. to identify exacerbating factors and then It is amazing that such a strong contact sensitizer is actively removing them is recommended, present in house dust mites. as is measuring mite fauna levels in The treatment of “dirty neck”is not easy.When the patients’ homes. mite fauna were investigated by a new methylene blue agar method in the homes of atopic dermatitis patients, and environmental improvements were made to decrease the mite numbers to fewer than Atopic dermatitis has been increasing in incidence in 20/m2 at 20 second aspiration using a 320-W cleaner, many countries, and approximately 1.7–2% of mod- 88% of severe atopic dermatitis patients showed con- erate or severe atopic dermatitis patients suffer from siderable improvement in their severe dermatitis reticular dark brown or dark purple pigmentation of when they were followed up for 1–2 years [43]. The the neck. It has been called “dirty neck” [32, 33].Atop- statistically significant effect of house dust mite elim- ic dermatitis is a multifactorial disease with in- ination with controls in atopic dermatitis was also re- creased serum IgE in 70–80% of moderate or severe ported by Tan et al. [44]. The “dirty neck,” however, 18_319_334* 05.11.2005 10:30 Uhr Seite 330

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a b

Fig. 5a, b. A severe case of atopic dermatitis of a 28-year-old stannic (tin) derivatives; therefore, dental metals containing woman had resulted in “dirty neck”for almost 10 years (a).The stannic were all eliminated and replaced by other metals to generalized severe eczema could not be sufficiently controlled which she was not hypersensitive. Tacrolimus ointment has by corticosteroid ointments; therefore, among her multiple al- been used as an antisymptomatic treatment recently. General- lergens, mite and metal were selected for elimination to obtain ized severe eczema disappeared after the above-mentioned al- improvement. First, mite fauna was investigated in her home lergen elimination, then “dirty neck” slowly disappeared in followed by environmental improvement to efficiently de- 4 years, as the last symptom of this case (b) crease Dermatophagoides. Second, she was hypersensitive to

was difficult to cure even with this method,and it can which is almost impossible to differentiate from id- be regarded as the last symptom to improve for atop- iopathic . The incidence is low, except for cer- ic dermatitis (Fig. 5). tain phenol derivatives and catechols, which produce a much higher incidence in workers who frequently come into contact with them (Table 3). 18.2 Depigmentation from Contact Monobenzyl ether of (MBEH) has with Chemicals been known to be a cause of occupational vitiligo since the 1930s [45], the main source of contact hav- 18.2.1 Mechanism of Leukoderma ing been rubber, in which it is used as an antioxidant due to Chemicals to prevent degeneration. The use of MBEH in the rubber industry today is rare, as it had a long history There are at least three kinds of mechanism produc- of causing occupational leukoderma by destroying 18 ing leukoderma from contact with chemicals: melanocytes. Instead, MBEH came to be used as a bleaching agent for melanotic skin, being used to treat diseases such as melasma and solar and í Leukoderma due to selective destruction of by dark-skinned people for cosmetic purposes. How- melanocytes ever, as its toxic effect on melanocytes was too í Leukomelanoderma or photoleukomelanoder- strong, the treatment often resulted in a mottled pat- ma due to pigment blockade tern of leukoderma (confetti-like depigmentation), í due to reduction of mela- which was worse than simple hyperpigmentation, nin synthesis and produced problems [46]. Historically, the next chemical to produce leuko- Allergic contact dermatitis and irritant contact der- derma by contact was 4-tert-butylcatechol (PTBC), matitis can both produce a secondary leukoderma known since the 1970s [47,48]. Approximately half of 18_319_334* 05.11.2005 10:30 Uhr Seite 331

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the 75 workers in a tappet assembly plant in the Unit- Table 3. Chemicals producing leukoderma or hypopigmenta- ed States were reported to have various grades of leu- tion on contact koderma from daily occupational contact with Hydroquinone PTBC. Four severe cases reported in 1970 by Gellin et al. [47] initially had itchy erythematous reactions at the sites of contact, then developed sharply outlined or confluent leukoderma on the face, scalp, hands, fingers,forearms,etc.The patients were all Caucasians. Patch tests revealed that 0.1% PTBC in acetone Monobenzyl ether produced positive reactions in three of these four of hydroquinone cases, one of whom later developed leukoderma at the site of the patch test. However, an exposure test with 1% PTBC in the assembly oil, carried out with occlusion of the forearms in six volunteers, failed to produce leukoderma artificially. Animal tests re- vealed that PTBC was an irritant, producing erythe- ma and necrosis in albino rabbits, and a bleaching p-tert-Butylcatechol test with 10% PTBC in black guinea pigs resulted in (PTBC) depigmentation of the black skin, both macroscopi- cally and histologically, from the loss of pigment in the epidermis and hair follicles. At almost the same time, at the beginning of the 1970s, occupational contact leukoderma due to p- p-tert-Butylphenol tert-butylphenol (PTBP) began to be recognized. The (PTBP) incidence of vitiligo vulgaris in the general popula- tion was considered to be less than 1%. Therefore, the presence of several cases of vitiligo, located mainly on exposed areas of skin, in the same factory of 20–30 workers alerted dermatologists to the fact that Kojic acid (hypopigmentation the depigmentation was an occupational dermatosis only) [49]. PTBP is contained in cobblers’ glues, shoes ce- mented with rubber glues, resins, industrial oils, paints, adhesives, bactericides, plasticizers for cellu- lose acetate, and printing inks [49–52]. Catechol The changes produced by PTBP are similar to those caused by p-tert-butylcatechol, and can occur with or without sensitization. Kahn [50] and Roma- guera et al.[53] reported patients who were apparent- Monomethyl ether of ly sensitized to PTBP with positive reactions on a hydroquinone (MMEH) closed patch test with 1% PTBP. Hydroquinone is an excellent depigmenting agent for clinical treatment of various pigmentations [54]. However, it may rarely produce leukoderma that is similar to vitiligo vulgaris [55, 56]. The mechanism of Alstroemeria components the hypopigmentation caused by hydroquinone is (tulipalin A) thought to be decreased formation of and destruction of the membranous organelles in the melanocytes, thus causing degeneration of melanoc- Squaric acid dibutylester ytes [57]. These historically accumulated cases of contact leukoderma caused by phenol derivatives indicate that selective toxicity of these chemicals to melanoc- ytes is the main cause of leukoderma, judging from the degeneration of melanocytes, the often Cerium oxide CeO2 noted, and the fact that sensitization is not always demonstrated. 18_319_334* 05.11.2005 10:30 Uhr Seite 332

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Another hazard of using hydroquinone as a 11. Takayama N, Suzuki T, Sakurai Y et al (1984) Friction bleaching agent is ochronosis, especially when it is melanosis (in Japanese). Nishinihon Hifuka (West Japan Dermatol) 46 : 1340–1345 used at high concentrations (e.g., 3.5–7.5%) [58].Och- 12. Tanigaki T, Hata S, Kitano M et al (1983) On peculiar me- ronosis means “yellow disease,” and black Africans lanosis occuring on the trunk and extremities (in Japa- suffer from hyperpigmentation of the face due to the nese). Rinsho Hifuka 37 : 347–351 degeneration of elastic fibers caused by this topical 13. Matsuo S, Nakayama H, Suzuki A (1989) Successful treat- agent [59]. Therefore, the use of hydroquinone as a ment with allergen controlled wearing apparel of textile dermatitis patients (in Japanese). Hifu 31 [Suppl 6] : bleaching agent by blacks should be advised careful- 178–185 ly, and high concentrations are not recommended. 14. Nakayama H (1989) Allergen control, an indispensable treatment for allergic contact dermatitis. Dermat Clin 8 : 197–204 18.2.2 Contact Leukoderma Caused Mainly 15. Nakayama H (1987) Dental metal and allergy (in Japa- by Contact Sensitization nese). Jpn J Dent Assoc 40 : 893–903 16. Nakayama H, Matsuo S, Hayakawa K et al (1984) Pigment- ed cosmetic dermatitis. Int J Dermatol 23 : 299–305 Very rarely, allergic contact dermatitis produces a 17. Matsuo S, Nakayama H (1984) A case of pigmented derma- titis induced by cinnamic derivatives (in Japanese). Hifu secondary depigmentation similar to vitiligo. A gar- 26 : 573–579 dener was reported to have developed secondary leu- 18. Nakayama H (1974) Perfume allergy and cosmetic derma- koderma after allergic contact dermatitis due to Al- titis (in Japanese). Jpn J Dermatol 84 : 659–667 stroemeria [60], and when squaric acid dibutylester 19. Nakayama H, Hanaoka H, Ohshiro A (1974) Allergen con- was used for immunotherapy in a 26-year-old male trolled system. Kanehara Shuppan, Tokyo, pp 1–42 20. Von Riehl G (1917) Über eine eigenartige Melanose. Wien with , depigmentation over the whole Klin Wochenschr 30 : 780–781 scalp was reported after repeated contact dermatitis 21. Minami S, Noma Y (1950) Melanosis faciei feminae (in Jap- produced by nine courses of treatment. Regrowth of anese). Dermatol Urol 12 : 73–77 hair was also noted [61]. A herbicide, Carbyne R, and 22. Nakayama H, Harada R, Toda M (1981) Pigmented cosmet- cerium oxide have also been reported to produce ic dermatitis. Int J Dermatol 15 : 673–675 23. Nakayama H (1983) Cosmetic series patch test allergens, contact hypersensitivity and secondary leukoderma types 19 to 20 (in Japanese, with English abstract). Fra- [62, 63]. grance Journal Publications, Tokyo, pp 1–121 24. Watanabe N (1989) Long term follow-up of allergen con- trol system on patients with cosmetic dermatitis (in Japa- nese). Nishinihon Hifuka 51 : 113–130 References 25. Kozuka T, Tashiro M, Sano S et al (1979) Brilliant Lake Red R as a cause of pigmented contact dermatitis.Contact Der- 1. Papa CM, Kligman AM (1965) The behavior of melanocy- matitis 5 : 294–304 tes in inflammation. J Invest Dermatol 45 : 465–474 26. Gonçalo S, Sil J, Gonçalo M, Polares Batista A (1991) Pig- 2. Nakamura T (1977) Toxicoderma caused by “Shiitake”,len- mented photoallergic contact dermatitis from musk am- tinus edodos (in Japanese). Rinsho-Hifuka 31 : 65–68 brette. Contact Dermatitis 24 : 229–231 3. Osmundsen PE (1969) Contact dermatitis due to an opti- 27. Trattner A, Hodak E, David M (1999) Screening Patch tests cal whitener in washing powders. Br J Dermatol 81 : for pigmented contact dermatitis in Israel. Contact Der- 799–803 matitis 40 : 155–157 4. Osmundsen PE (1970) Pigmented contact dermatitis. Br J 28. Greenwood K (1960) Dermatitis with capillary fragility. Dermatol 83 : 296–301 Arch Dermatol 81 : 947–952 5. Ancona-Alayón A, Escobar-Márques R, González-Mendo- 29. Twiston Davies JH, Neish Barker A (1944) Textile derma- za A et al (1976) Occupational pigmented contact derma- titis. Br J Dermatol 56 : 33–43 titis from Naphthol AS. Contact Dermatitis 2 : 129–134 30. Batschvarov B, Minkov DM (1968) Dermatitis and purpu- 6. Kawachi S, Kawashima T,Akiyama J et al (1985) Pigmented ra from rubber in clothing. Trans St John’s Hosp Dermatol contact dermatitis due to dyes from nightgown (in Japa- Soc 54 : 178–182 18 nese). Hifuka No Rinsho 27 : 91–92, 181–187 31. Van der Veen, JPW, Neering H, DeHaan P et al (1988) Pig- 7. Hayakawa R, Matsunaga K, Kojima S et al (1985) Naphthol mented purpuric clothing dermatitis due to Disperse Blue AS as a cause of pigmented contact dermatitis. Contact 85. Contact Dermatitis 19 : 222–223 Dermatitis 13 : 20–25 32. Humphreys F,Spencer J, McLaren K, Tidman MJ (1996) An 8. Osawa J, Takekawa K, Onuma S, Kitamura K, Ikezawa Z histological and ultrastructural study of the dirty neck ap- (1997) Pigmented contact dermatitis due to Naphthol AS pearance in atopic eczema. Clin Exp Dermatol 21 : 17–19 in a pillow case. Contact Dermatitis 37 : 37–38 33. Manabe T, Inagaki Y, Nakagawa S et al (1987) Ripple pig- 9. Nakayama H, Suzuki A (1985) Investigation of skin distur- mentation of the neck in atopic dermatitis. Am J Derma- bances caused by the chemicals contained in daily neces- topathol 9 : 301–307 sities, part 1. On the ability of textile finishes to produce 34. Nakayama H (1995) The role of the house dust mite in dermatitis (in Japanese). Tokyo-To Living Division Report atopic eczema. Practical contact dermatitis. McGraw-Hill, 1–27 New York, pp 623–630 10. Kovacevic Z, Kränke B (2001) Pigmented purpuric contact 35. Vincenti C, Trevisi P, Guerra L, Lorenzi S, Tosti A (1994) dermatitis from Disperse Blue 106 and 124 dyes. J Am Acad Patch testing with whole dust mite bodies in atopic derma- Dermatol 45 : 456–458 titis. Am J Contact Dermatitis 5 : 213–215 18_319_334* 05.11.2005 10:30 Uhr Seite 333

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36. Sakurai M (1996) Results of patch tests with mite compo- 49. Malten KE,Sutter E,Hara I,Nakajima T (1971) Occupation- nents in atopic dermatitis patients (in Japanese with Eng- al vitiligo due to paratertiary butylphenol and homo- lish abstract). Allergy 45 : 398–408 logues. Trans St John’s Hosp Dermatol Soc 57 : 115–134 37. Shanon J (1965) Pseudoatopic dermatitis, contact derma- 50. Kahn G (1970) Depigmentation caused by phenolic deter- titis due to chrome sensitivity simulating atopic derma- gent germicides. Arch Dermatol 102 : 177–187 titis. Dermatologica 131 : 118–190 51. Malten KE (1967) Contact sensitization caused by p-tert- 38. Okudaira H (1997) Atopic diseases and house dust mite al- butylphenol and certain phenolformaldehyde-containing lergens (in Japanese with English abstract). Hifu 39 [Suppl glues. Dermatologica 135 : 54–59 19] : 45–51 52. Malten KE (1975) Paratertiary butylphenol depigmenta- 39. Bruynzeel-Koomen, C VanWichen DF, Toonstra J et al tion in a consumer. Contact Dermatitis 1 : 180–192 (1986) The presence of IgE molecules on epidermal Lange- 52. Romaguera C, Grimalt F (1981) Occupational leukoderma rhans cells in patients with atopic dermatitis.Arch Derma- and contact dermatitis from paratertiary-butylphenol. tol Res 278 : 199–205 Contact Dermatitis 7 : 159–160 40. Imayama S, Hashizume T, Miyahara H et al (1992) Combi- 54. Arndt KA, Fitzpatrick TB (1965) Topical use of hydroqui- nation of patch test and IgE for dust mite antigens differ- none as a depigmenting agent. J Am Med Assoc 194 : ences 130 patients with atopic dermatitis into four groups. 965–967 J Am Acad Dermatol 27 : 531–538 55. Frenk E, Loi-Zedda P (1980) Occupational depigmentation 41. Rawle FC, Mitchell EB, Platts-Mills TAE (1984) re- due to a hydroquinone-containing photographic develop- sponses to major allergen from the house dust mite Der- er. Contact Dermatitis 6 : 238-239 matophagoides pteronyssinus antigen P1: comparison of 56. Kersey P,Stevenson CJ (1981) Vitiligo and occupational ex- patients with asthma, atopic dermatitis, and perennial posure to hydroquinone from servicing self-photograph- rhinitis. J Immunol 44 : 195–201 ing machines. Contact Dermatitis 7 : 285–287 42. Nakayama H,Kumei A (2003) House dust mite – an impor- 57. Jimbow K, Obata H, Pathak M, Fitzpatrick TB (1974) Mech- tant causation of atopic dermatitis. SP World 31 : 13–20 anism of depigmentation by hydroquinone. J Invest Der- 43. Kumei A (1995) Investigation of mites in the house of atop- matol 62 : 436–449 ic dermatitis (AD) patients, and clinical improvements by 58. Findlay GH (1982) Ochronosis following skin bleaching mite elimination (in Japanese with English abstract). with hydroquinone. J Am Acad Dermatol 6 : 1092–1093 Allergy 44 : 116–127 59. Hoshaw RA, Zimmerman KG, Menter A (1985) Ochrono- 44. Tan BB, Weald D, Strickland I, Friedmann PS (1996) Dou- sis-like pigmentation from hydroquinone bleaching ble-blind controlled trial of effect of housedust-mite aller- creams in American Blacks. Arch Dermatol 121 : 105–108 gen avoidance on atopic dermatitis. Lancet 347 : 15–18 60. Björkner BE (1982) Contact allergy and depigmentation 45. Oliver EA, Schwartz L, Warren LH (1939) Occupational from alstromeria. Contact Dermatitis 8 : 178–184 leukoderma: preliminary report. J Am Med Assoc 113 : 61. Valsecchi R, Cainelli T (1984) Depigmentation from squar- 927–928 ic acid dibutyl ester. Contact Dermatitis 10 : 108 46. Yoshida Y,Usuba M (1958) Monobenzyl ether of hydroqui- 62. Brancaccio RR, Chamales MH (1977) Contact dermatitis none leukomelanodermia (in Japanese). Rinsho Hifuka and depigmentation produced by the herbicide carbyne. Hinyokika 12 : 333–338 Contact Dermatitis 3 : 108–109 47. Gellin GA, Possik PA,Davis IH (1970) Occupational depig- 63. Rapaport MJ (1982) Depigmentation with cerium oxide. mentation due to 4-tertiarybutyl catechol (TBC). J Occup Contact Dermatitis 8 : 282–283 Med 12 : 386–389 48. Gellin GA, Maibach HI, Mislazek MH, Ring M (1979) De- tection of environmental depigmenting substances. Con- tact Dermatitis 5 : 201–213