Contents
18.1 Hyperpigmentation Associated
with Contact Dermatitis . . . 319
18.1.1 Classification . . . 319
18.1.2 Pigmented Contact Dermatitis . . . 320
18.1.2.1 History and Causative Agents . . . 320
18.1.2.2 Differential Diagnosis . . . 323
18.1.2.3 Prevention and Treatment . . . 323
18.1.3 Pigmented Cosmetic Dermatitis . . . 324
18.1.3.1 Signs . . . 324
18.1.3.2 Causative Allergens . . . 325
18.1.3.3 Treatment . . . 326
18.1.4 Purpuric Dermatitis . . . 328
18.1.5 “Dirty Neck” of Atopic Eczema . . . 329
18.2 Depigmentation from Contact with Chemicals . . . 330
18.2.1 Mechanism of Leukoderma due to Chemicals . . . 330
18.2.2 Contact Leukoderma Caused Mainly by Contact Sensitization . . . 332
References . . . 332
18.1 Hyperpigmentation Associated with Contact Dermatitis
18.1.1 Classification
Hyperpigmentation associated with contact derma- titis is classified into three categories: (1) hyperpig- mentation due to incontinentia pigmenti histologica;
(2) hyperpigmentation due to an increase in melanin in the basal layer cells of the epidermis, i.e., basal me- lanosis; and (3) hyperpigmentation due to slight hemorrhage around the vessels of the upper dermis, resulting in an accumulation of hemosiderin, such as in Majocchi–Schamberg dermatitis.
It is easy to understand that when the grade of contact dermatitis is more severe, or its duration longer, the secondary hyperpigmentation following dermatitis is more prominent. However, the first type mentioned above, incontinentia pigmenti histologi-
ca, often occurs without showing any positive mani- festations of dermatitis such as marked erythema, vesiculation, swelling, papules, rough skin or scaling.
Therefore, patients may complain only of a pigmen- tary disorder, even though the disease is entirely the result of allergic contact dermatitis. Hyperpigmenta- tion caused by incontinentia pigmenti histologica has often been called a lichenoid reaction, since the presence of basal liquefaction degeneration, the ac- cumulation of melanin pigment, and the mononucle- ar cell infiltrate in the upper dermis are very similar to the histopathological manifestations of lichen pla- nus. However, compared with typical lichen planus, hyperkeratosis is usually milder, hypergranulosis and saw-tooth-shape acanthosis are lacking, hyaline bodies are hardly seen, and the band-like massive in- filtration with lymphocytes and histiocytes is lack- ing.
A lichenoid reaction is considered to be a scaled- down type-IV allergic reaction of the lichen planus type, based on positive patch test 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 caused by hyperfunction of melanocytes, but the same phenomenon is also seen with irritant contact dermatitis.When sodium lauryl sulfate, a typical skin irritant, was repeatedly applied on the forearms of Caucasians, the number of epidermal melanocytes was observed to almost double, suggesting hyperpla- sia, hypertrophy, and increased function [1].
The pathological processes involved in the third form of hyperpigmentation with contact dermatitis, purpuric dermatitis, have not yet been clarified. Shii- take mushroom, very commonly eaten in Asia, has been known to produce a transient urticarial derma- titis with severe itching, which results in a purpuric scratch effect, when insufficiently cooked. This is thought to be due to toxic substances in the mush- room unstable to heat, and the pigmentation due to purpura is not caused by hypersensitivity [2].As with other forms of dermatitis, accompanying capillary fragility results in purpura. Some cases are associat-
Chapter 18
Pigmented Contact Dermatitis and Chemical Depigmentation
Hideo Nakayama
18
ed with contact hypersensitivity to rubber compo- nents or textile finishes, but in many cases the causes are not known.
18.1.2 Pigmented Contact Dermatitis 18.1.2.1 History and Causative Agents
쐽 Pigmented contact dermatitis on the covered area cannot be cured by the application of corticosteroid ointments, even though it is a result of contact
allergens from textiles, soaps or washing powders for textiles. Successive contact with small amounts of allergens destroys basal layer cells of the epidermis, resulting in melanin accumulation in the upper dermis for a long time. Treatment entails finding out the contact allergens, and avoiding them for a long time.
Pigmented contact dermatitis was first reported by Osmundsen in Denmark in 1969. In 8 months he had 120 patients, 7 of whom showed a pronounced and bizarre hyperpigmentation. In 4 of these 7 cases con- tact dermatitis preceded the hyperpigmentation,
18
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 cosmetics 1% pet.
lake red R
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.
Core Message
dehydrodiisoeugenol
while the other 3 did not notice any signs of derma- titis such as itching or erythema before the pigmen- tation appeared [3, 4].
Hyperpigmentation, with or without dermatitis, was located mostly in covered areas, such as the chest, back, waist, arms, neck, and thighs. After a pa- tient wanted to conceal the pigmentation by wearing long sleeves and a high-neck sweater, which she washed with a washing powder every day, the hyper- pigmentation extended from the neck and axillae to all over the neck, chest, and arms. The hyperpigmen- tation was brown, slate-colored, grayish-brown, red- dish-brown, bluish-brown, etc., according to the case, and often had a reticulate pattern. The histopatholo- gy of the pigmentation showed incontinentia pig- menti histologica.
Patch tests with the standard series current at that time gave no information as to the causative aller- gens. However, Osmundsen noticed that the patients had used washing powders that contained a new op-
tical whitener, Tinopal or CH3566 (Table 1). This was one of numerous optical whiteners which became available at that time to make textiles “whiter than white.” Patch tests with CH3566 1% pet. finally ex- plained the pigmentary disorder, as they showed strong positive reactions in the patients and negative results in the controls. The pigmentation was persis- tent, but the dermatitis that often preceded hyperpig- mentation was observed to disappear following the elimination of washing powders that contained CH3566. Fortunately, the identification of the causa- tive chemical was made rapidly, and the widespread usage of CH3566 was avoided in time.
Pigmented contact dermatitis is rare in Cauca- sians but not uncommon in Mongoloids. The next pigmented contact dermatitis was reported by Anco- na-Alayón et al. in Mexico [5]. Among 53 workers handling azo dyes in a textile factory, 12 developed a spotted hyperpigmentation without pruritus, and 18 suffered from hyperpigmentation to a lesser extent.
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.
Table 1.Continued
Name Chemical structure Purpose Patch test concentration
and base
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 spongiosis, irregular acanthosis, edema of the dermis, pericapillary lymphocytic infil- tration, basal liquefaction degeneration, and inconti- nentia pigmenti histologica. Melanocyte prolifera- tion at the affected sites was also noted.
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 neck. The factory was said to have improved the washing process and the materials quickly, but the presence of such cases indicates that whenever the textile industry uses Naphthol AS, and at the same 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- akawa et al. [7] the amount of Naphthol AS detected in the patients’ nightwear was 4,900–8,700 ppm, a considerable amount. A case due to Naphthol AS in a pillow case was later reported [8].
In 1984, the city of Tokyo decided to investigate new textile finishes which seemed to have produced contact dermatitis of the covered skin areas, includ- ing pigmented contact dermatitis (Fig. 1). Based on information about the textile finishes which actually came into contact with the patients’ skin or were very commonly used, 115 chemicals were finally chosen and patch tested. The test materials included 50 dyes of all colors, 13 whiteners, 5 fungicides, 32 resin com- ponents, 13 softening agents, and 15 other miscellane- ous textile finishes which were widely used at that
time by the textile industry in Japan. They were cho- sen from approximately 1,200 textile finishes, either imported or produced in Japan. They were checked as to solubility in water, ethanol, acetone, etc., diluted to 5% (except bactericides, fungicides, and other pes- ticides for textiles which were diluted to 1%), and then applied to dry paper discs 8 mm in diameter, to make dry allergen-containing discs named “instant patch test allergens.” They were peeled off silicon- treated covering paper before use.
The results obtained from five hospitals in and around Tokyo revealed that several new contact sen- sitizers were responsible for producing textile der- matitis and secondary hyperpigmentation. These textile finishes included Biochek 60, a very toxic fun- gicide which seemed also to have acted as a sensitiz-
18
Fig. 1a, b.Pigmented contact dermatitis (a) in a 67-year-old man who was sensitized by several textile finishes, including commercial grade red and brown dyes and fungicides (b)
a
b
er, a phosphite polymer of pentaerythritol and hy- drogenated bisphenol A (PPP-HB), impurities in a dye CI Blue 19 (or Brilliant Blue R), and mercury compounds [9].
The research on these 115 chemicals was per- formed in the 5 hospitals on 80–101 persons, among whom 51–62 were patients suffering from textile con- tact dermatitis, and the rest, 29–39, were controls with atopic dermatitis and dermatitis due to causes other than textiles. Among those with textile contact dermatitis, 27–33 had pigmented contact dermatitis.
Such cases had been deliberately chosen for patch testing because the investigators hoped to find out the causative contact sensitizers producing such hy- perpigmentation. Of these pigmented contact der- matitis patients, 9 showed positive reactions sugges- tive of an allergy to Biochek 60, and 1 to several tex- tile finishes. The results were rather disappointing, but they did show that it is not easy to discover the contact sensitizers producing pigmented contact dermatitis from contact with textile finishes. The dis- coveries of CH3566 and Naphthol AS can be regarded as having been important and valuable. Pigmented contact dermatitis due to blue dyes, Blue 106 and 124 was reported by Kovacevic et al. in 2001 [10].
Besides the above-mentioned textile finishes, rub- ber components can also produce dermatitis result- ing in hyperpigmentation, mainly around the waist.
Sometimes in such cases the pigmentation is not due to incontinentia pigmenti histologica but to purpura (see Sect. 18.1.4, Purpuric Dermatitis). Thus far, only cases of pigmented contact dermatitis in which caus- ative allergens were found have been reported. Caus- es other than contact sensitivity have not yet been well investigated, except for friction melanosis which is described in Sect. 18.1.2.2, Differential Diagnosis.
18.1.2.2 Differential Diagnosis
Differential diagnosis of pigmented contact derma- titis due to washing powder or textile components in- cludes Addison’s disease, friction melanosis, amyloi- dosis cutis, drug eruption, atopic dermatitis with pig- mentation and dermatitis and secondary hyperpig- mentation due to dental metal sensitivity (dental metal eruption).
Friction melanosis was frequently seen in Japan in the 1970s and 1980s, the disease consisting of dark brown or black hyperpigmentation unaccompanied by dermatitis or itching [11]. Friction melanosis oc- curred predominantly on the skin over or along bones, such as the clavicles, ribs, scapulae, spine, knees, and elbows. The color and distribution of fric- tion melanosis sometimes leads to confusion with
pigmented contact dermatitis. The disease, however, is produced by patients vigorously rubbing the skin with a hard nylon towel or nylon brush every day when bathing. Patch testing with various contact al- lergens failed to demonstrate allergens that seemed to be correlated with the disease. It was Tanigaki et al.
[12] in 1983 who pointed out the causative association of rubbing with a nylon towel or brush, and the dis- ease has gradually decreased since this hazard has become known to the public.
The use of nylon towels or brushes for washing the skin should therefore be checked before the diagno- sis of pigmented contact dermatitis due to textiles is made. If the dark hyperpigmentation of the skin over bones gradually fades and disappears after use of ny- lon towels or brushes is discontinued and patients change their mode of washing to a milder technique, the diagnosis of friction melanosis should be consid- ered. Curiously, the histopathology of friction melan- osis shows incontinentia pigmenti histologica, which is a characteristic feature of pigmented contact der- matitis. However, liquefaction degeneration of basal layer cells of the epidermis is not present [11].
Another skin disorder to be distinguished is skin amyloidosis, especially lichen amyloidosus or papu- lar amyloidosis. It is possible that a small amount of amyloid, which can be demonstrated by Dylon stain- ing, is found in lichenoid tissue reactions, probably because amyloid in the upper dermis is considered to be derived from degenerate epidermal cells pro- duced by epidermal inflammation. Special staining with Congo red or thioflavine T and electron-micro- scopic study of the skin specimen are also helpful in the differential diagnosis.
18.1.2.3 Prevention and Treatment
It is essential to avoid the use of textiles and washing powders containing strong contact sensitizers, in or- der to prevent contact dermatitis and pigmented contact dermatitis of the skin areas that come into contact with the fabric and washing powders or sof- tening agents that remain on them even after rinsing.
There are, however, many textile finishes available to-
day, with more than 1,200 commercial finishes being
sold to the textile industry, and unfortunately their
components are mainly secret. The purity of dyes is,
in general, very low and some of the many impurities
are allergenic. For example, the very commonly used
CI Blue 19 (or Brilliant Blue R) turned out to be aller-
genic and caused some patch-test-positive cases of
pigmented contact dermatitis in 1985 [9]. Purified CI
Blue 19, in contrast, never produced positive patch
test reactions at the same 5% concentration.
The experiences accumulated in the past show that, when entirely new textile finishes are intro- duced to the textile industry, the minimum safety evaluation tests such as LD50, Ames test, and skin ir- ritation test should be performed, and their sensiti- zation potential should be investigated by a research team including dermatologists. Strong contact sensi- tizers can be detected by several experimental proce- dures using animals. Although animal experiments are now the subject of ethical scrutiny in connection with such investigations, they remain indicated if the irritability and allergenicity of textile finishes are to be adequately investigated.
The textile industry should cooperate with derma- tologists when pigmented contact dermatitis has once occurred, by immediately informing them of the components of the chemical finishes of the textile suspected to have caused the disease, and a precise study of impurities and quality control in the factory should also be performed. Shortening of the washing process should be strictly refrained, otherwise sur- plus dyes, their impurities, and other chemical finish- es may remain and produce a problem.
When a causative allergen is discovered, the solu- tion of pigmented contact dermatitis is not difficult [4, 5, 7]. However, when causative allergens are not identified, the solution of the pigmentary disorder is usually very difficult. In 1985, in Japan, a new strategy for the treatment of both recurrent textile dermatitis and pigmented contact dermatitis was introduced.
Based on the research project for finding out contact sensitizers and irritants in textiles [9], underwear with only four or five kinds of textile finishes which showed no evidence of positive reactions in patients with contact dermatitis, pigmented contact derma- titis, atopic dermatitis, and healthy controls was put into mass production and became available. This is a measure to prevent the patients coming into contact with the responsible allergen in ordinary underwear again, and keeps the patients out of range of the re- sponsible allergens.
Such allergen-free underwear for patients is called allergen-controlled wearing apparel (ACW) and has successfully counteracted pigmented contact derma- titis. The idea was inspired by the success of allergen- controlled cosmetics in 1970, which is discussed later (see Sect. 18.1.3, Pigmented Cosmetic Dermatitis). It is not surprising that persistent secondary hyperpig- mentation disappears only very slowly when the causative contact allergens are completely eliminated from the patient’s environment for a long period, as the hyperpigmentation is considered to be brought about by frequent and repeated contact with a very small amount of contact sensitizer in the textile or washing material. Patients were requested to use al- lergen-free soaps and allergen-eliminated washing
materials for their clothing at the same time, so that their skin was not contaminated by the responsible allergens in ordinary soaps and washing materials.
Matsuo et al. reported several cases in which this treatment was successful [13, 14].
Even though cases are very rare, pigmented con- tact dermatitis can also occur following systemic contact dermatitis. In a 50-year-old man, for exam- ple, recurrent and persistent dermatitis accompanied diffuse secondary hyperpigmentation. The use of corticosteroid ointments, oral antihistamines, and al- lergen-free soaps did not improve the condition at all. A patch test with nickel sulfate 5% aq. showed a strong positive reaction, with a focal flare of most of the original skin lesion. This implied not only that the patient was sensitive to nickel, but also that only a few hundred parts per million of nickel ions ab- sorbed from the patch test site into the bloodstream were enough to provoke an allergic reaction over a wide area of the site of the original skin lesions. This observation led to a search for a source of nickel ions in the patient, and five nickel alloys were subsequent- ly found in the patient’s oral cavity. He agreed to eliminate these nickel crowns, as they turned out to have been acting as cathodes, attracting an electric current of 1–3 mA at 100–200 mV. According to Faraday’s law of electrolysis, cations elute from the cathode in proportion to the amount of electric cur- rent passing into the cathode.
The complete elimination of nickel-containing al- loys from his oral cavity and their substitution with gold alloys, which did not contain any nickel at all, re- sulted in complete cure of the dermatitis and secon- dary hyperpigmentation in 3 months, and there has never been any recrudescence of the disease. The patient’s pigmented contact dermatitis had been kept going for a long period by metal allergens continu- ously supplied from his own oral cavity [15].
18.1.3 Pigmented Cosmetic Dermatitis 18.1.3.1 Signs
쐽 Pigmented cosmetic dermatitis is caused by the same mechanism as pigmented contact dermatitis of the covered area;
however, the causative allergens are quite different, and they are a number of cosmet- ic allergens. Patch test of cosmetic series allergens is recommended, and continual and exclusive usage of allergen-controlled cosmetics and soaps cures the disease.
18
Core Message
The most commonly seen hyperpigmentation due to contact dermatitis in the history of dermatology must be the pigmented cosmetic dermatitis which af- fected the faces of Oriental women [16]. Innumerable patients with this pigmentary disorder presented in the 1960s and 1970s in Japan, and similar patients were also seen in Korea, India, Taiwan, China, and the USA.
The signs of pigmented cosmetic dermatitis are diffuse or reticular, black or dark brown hyperpig- mentation of the face, which cannot be cured by the use of corticosteroid ointments or the continuous in- gestion of vitamin C. The border of pigmented cos- metic dermatitis is not sharp, as in lichen planus or melasma, and it is not spot-like as in nevus of Ota tardus bilateralis.
Slight dermatitis is occasionally seen with hyper- pigmentation, or dermatitis may precede hyperpig- mentation. In contrast to Addison’s disease, pigment- ed cosmetic dermatitis does not show any systemic symptoms such as weakness, fatigue, and emaciation.
Laboratory findings such as full blood count, liver function tests, daily urinary excretion of 17-ketoster- oid and 17-hydroxy corticosteroid, and serum immu- noglobulins and electrolytes are normal in the ma- jority of patients with pigmented cosmetic derma- titis [16].
Histopathological examination of pigmented cos- metic dermatitis shows basal liquefaction degenera- tion of the epidermis and incontinentia pigmenti histologica. The epidermis maybe mildly acanthotic, however it is sometimes atrophic, presumably the ef- fect of frequently applied corticosteroid ointments for the treatment of itchy dermatitis of the face. Cel-
lular infiltrates of lymphocytes and histiocytes are seen perivascularly, as are often seen in ordinary al- lergic contact dermatitis (Fig. 2).
In some cases, the dark brown or black hyperpig- mentation is also seen on skin other than on the face.
The neck, chest, and back can be involved and, in a few exceptional cases, hyperpigmentation may ex- tend to the whole body. In these cases, the allergens cinnamic alcohol and its derivatives sensitize the pa- tients first to cosmetics and then provoke allergic re- actions to soaps, domestic fabric softeners, and food, all of which sometimes contain cinnamic derivatives.
The ingestion of 1 g cinnamon sugar from a cup of tea in a supermarket was enough to provoke a mild focal flare of dermatitis at the sites of diffuse reticu- lar black hyperpigmentation of the whole body in one reported case [17]. When one of the common po- tent sensitizers producing pigmented cosmetic der- matitis, D & C Red 31 (Japanese name R-219), was dis- covered, a focal flare of dermatitis at the site of facial hyperpigmentation was occasionally noted by patch testing 5% R-219 in petrolatum. These findings show that the allergen could provoke the dermatitis not only by contact with the skin surface but also from within the skin, by allergens transported via blood vessels, just as allergic contact dermatitis can be pro- voked by the administration of small amounts of nickel or drugs.
18.1.3.2 Causative Allergens
The term “pigmented cosmetic dermatitis” was in- 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
as melanosis faciei feminae when the mechanism (type IV allergy), most of the causative allergens, and successful treatment with allergen control for this miserable pigmentary disorder were clarified for the first time [18, 19]. The name was adopted by modify- ing Osmundsen’s designation pigmented contact dermatitis, for the disease caused by CH3566 on the trunk.
Historically, the first description of the disease goes back to 1948, when Japanese dermatologists en- countered this peculiar pigmentary disorder for the first time, and were greatly embarrassed as to diag- nosis. Bibliographical surveys showed that Riehl’s melanosis, described in 1917 [20], seemed probable, because World War II had ended just 3 years before the investigation. Subsequently, the disease was erro- neously called Riehl’s melanosis for almost 30 years in Asian countries. Riehl’s melanosis, however, was a dark brown hyperpigmentation observed during World War I in Caucasian men, women and children, when food was extremely scarce and the patients had to eat decayed corn and weed crops instead of the normal food of peacetime. Besides hyperpigmenta- tion of the face, ears and scalp, there were nodules and, histopathologically, dense cellular infiltration 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 the men and children, to have used cosmetics before they had the disease. Riehl could not discover the true cause of this pigmentary disorder, but suspected the role of the abnormal wartime diet [20]. Riehl’s melanosis disappeared when World War I ended, when people obtained normal food again, to reap- pear for a short period in France during the German occupation in World War II, when food again became scarce.
Consequently, Riehl’s melanosis, a wartime me- lanosis having no relationship to cosmetic allergy, should not be confused with pigmented cosmetic dermatitis, which involved many Asian women in peacetime for many years. In 1950, Minami and No- ma [21] designated the disease melanosis faciei femi- nae, and recognized the disease as a new entity. The causation was not known for many years. However, Japanese dermatologists gradually became aware of the role of cosmetics in this hyperpigmentation.
First, it occurred only on those women, and very ex- ceptionally men, who used cosmetics and, secondly, even though the bizarre brown hyperpigmentation was so conspicuous, the presence of slight, recurrent, or preceding dermatitis was observed. The problem for the dermatologists at that time was that the com- ponents of cosmetics were completely secret, and the kinds of cosmetic ingredients were too many (more
than 1,000) for their allergenicity to be evaluated.
Finally, in 1969, a research project was set up to identify the causative allergens from 477 cosmetic in- gredients by patch and photopatch testing. It was a new idea, because melanosis faciei feminae had been regarded as a metabolic disorder rather than a type of contact dermatitis. This was 7 years before Finn chambers became available; therefore, small patch test plasters of 10 × 2 cm with six discs 7 mm in diam- eter (Miniplaster) were put into production to enable 48–96 samples to be patch tested at one time on the backs of volunteer control subjects and patients.
Many cosmetic ingredients, adjusted to nonirritant concentrations with the cooperation of 30–40 volun- teers, were subsequently patch and photopatch tested in the patients. Results for each ingredient were ob- tained from 172–348 patients, including 79–121 with melanosis faciei feminae. Statistical evaluation brought to light a number of newly discovered con- tact sensitizers amongst the cosmetic ingredients, mainly fragrance materials and pigments, including jasmine absolute, ylang-ylang oil, cananga oil, benzyl salicylate, hydroxycitronellal, sandalwood oil, artifi- cial sandalwood, geraniol, geranium oil, D & C Red 31, and Yellow No. 11 [16, 18, 19, 22].
18.1.3.3 Treatment
The above-mentioned research project at the same time included a plan to produce soaps (acylgluta- mate) and cosmetics for the patients from whom the causative allergens had been completely eliminated, as even those who suffered from severe and bizarre hyperpigmentation usually could not accept aban- doning their use of cosmetics to remove this pigmen- tary disorder. Patch testing with a series of 30 stan- dard cosmetic ingredients to find the allergens caus- ing the disease [23], followed by the exclusive use of soaps and cosmetics that were completely allergen- free for such patients, designated the allergen control system, produced dramatic effects. Around 1970, most textbooks of dermatology in Japan said that melanosis faciei feminae was very difficult to cure and that the causation was unknown. However, after allergen control was introduced, the disease became completely curable. Table 2 shows the effect of aller- gen control in 165 cases reported to the American Academy of Dermatology in 1977, and also the long- term follow-up results of allergen control obtained by Watanabe after 3–11 years (mean, 5 years). In 50 cases of pigmented cosmetic dermatitis cured by al- lergen control (i.e., patch test with 30 cosmetic series patch test allergens [25] followed by the exclusive use of allergen-free soaps and cosmetics, Acseine® in Ja-
18
pan and Hong Kong), there were, on average, 2.5 al- lergens for each patient. It usually required 1–2 years for a patient to regain normal nonhyperpigmented facial skin (Fig. 3). Contamination with ordinary soaps and cosmetics was the most influential and de- cisive factor inhibiting therapy, because such ordi- nary daily necessities contained the allergens that were producing the disease. The patients were there- fore requested to visit the dermatologist once a month to be checked for improvement, and were per- suaded every time to avoid such contamination, in- cluding products used in beauty parlors [16, 24].
In 1979, Kozuka [25] discovered a new contact sen- sitizer, phenylazo-2-naphthol (PAN), as an impurity
Table 2.Effect of allergen-controlled cosmetics on pigmented cosmetic dermatitis patients
Nakayama Watanabe et al. [22] [24]
Total 165 53
Complete cure 52 40
Almost complete cure 21 0
Remarkable improvement 51 13
Improvement 22 0
Not effective 19 0
Follow-up 3 months 3–11 years
to 5 years (mean 5 years)
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)
b a
c
in commercial supplies of D & C Red 31. Its sensitiz- ing ability and ability to produce secondary hyper- 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 No. 11 in their products. The legal partial restriction of Red No. 31 and Yellow No. 11 by the Japanese gov- ernment and the voluntary restriction by cosmetic companies of the use of allergenic fragrances, bacte- ricides, and pigments resulted in a remarkable de- crease in pigmented cosmetic dermatitis after 1980.
One of the reasons for the proposal to change the name from “melanosis faciei feminae” to “pigmented cosmetic dermatitis” [18] was that the latter name makes it easier for the patients to understand the causation of the disease and, at the same time, for in- dustry to recognize the danger of cosmetics in pro- ducing such disastrous pigmentary disorders through contact sensitization. The disease was still present in the 1990s [26, 27], and it is necessary for
dermatologists to recognize the importance of cos- metic allergens in producing hyperpigmentation.
18.1.4 Purpuric Dermatitis
In 1886 Majocchi described purpura annularis telan- giectodes and, 4 years later, Schamberg described a progressive pigmentary dermatitis which is now well known as Schamberg’s disease. The pigmentation in this dermatitis is due to the intradermal accumula- tion of hemosiderin, the predominant sites being the legs and thighs. Later, Gougerot and Blum described a similar dermatosis as pigmented purpuric lichen- oid dermatitis.
The disease was rare but most often occurred in middle-aged or elderly men. However, when a similar disease occurred in many British soldiers during World War II, especially in those who sweated freely or experienced friction when wearing khaki shirts or
18
Fig. 4a, b.Reticular brown hyperpigmentation of pigmented purpuric lichenoid dermatitis on an 80-year-old male (a). Bi- opsy showed marked hemorrhage around capillaries of the upper dermis, along with the cellular infiltrates composed of lymphocytes and histiocytes. Patch test revealed strong con- tact hypersensitivity to paratertiarybutyl phenolformaldehyde resin at 1% petrolatum (b). It had been (H) positive from D2 to D14 and confirmative patch test was again strongly positive.
Exposure to the contact allergen was considered to have been from the textile finishes of his socks. The exclusive usage of well-washed white cotton socks gradually improved the der- matitis. Complete blood count (CBC) and liver function test results were normal. This case indicates the importance of patch test of textile finishes if possible, for the treatment of this pigmentary disorder
a
b
woolen socks, with severe pruritus, dermatitis and pigmentation due to purpura, dermatologists be- came aware that some textile finishes must have been responsible for the disease [28, 29]. Patch tests and use tests revealed that a blend of vegetable oils and oleic acid seemed to have been responsible.
In 1968, Batschvarov and Minkov [30] reported that rubber components such as N-phenyl-N´-iso- propyl- p-phenylenediamine (IPPD), N-phenyl-β- naphthylamine (PNA), 2-mercaptobenzothiazole (MBT) and dibenzothiazole disulfide (DBD), i.e., de- rivatives of p-phenylenediamine, naphthylamine, and benzothiazoles, were the allergens responsible for a purpuric dermatitis around the waist under- neath the elastic of underwear. A similar pigmented dermatitis was recognized in the shoulders, breasts, groins, and thighs. The capillary resistance (Rumpel- Leede) test was positive in all 23 cases studied. Simi- lar test results were obtained in a smaller proportion of patients with the khaki dermatitis mentioned above. In Bulgaria, over 600 patients were recorded, and the necessity for dermatologists to investigate contact allergens in textiles to solve the problem of purpuric dermatitis of covered areas of skin was stressed [30]. A dye, blue 85, was reported as a causa- tion in 1988 [31]. A case due to a textile finish of socks is demonstrated (Fig. 4).
18.1.5 “Dirty Neck” of Atopic Eczema
쐽 Today, there is much evidence that house dust mites are one of the most important causations of severe atopic dermatitis.
Suffering from this dermatitis for many years often leads to reticular dark brown hyperpigmentation of the neck, i.e., the dirty neck. Using the patch test and RAST to identify exacerbating factors and then actively removing them is recommended, as is measuring mite fauna levels in patients’ homes.
Atopic dermatitis has been increasing in incidence in many countries, and approximately 1.7–2% of mod- erate or severe atopic dermatitis patients suffer from reticular dark brown or dark purple pigmentation of the neck. It has been called “dirty neck” [32, 33]. Atop- ic dermatitis is a multifactorial disease with in- creased serum IgE in 70–80% of moderate or severe
cases, and also shows an aspect of contact hypersen- sitivity to house dust mites [34–36], metals [37], and other environmental substances.
The elevation of serum IgE in patients with mod- erate or severe atopic dermatitis up to 2,000 or even to 20,000 IU/ml is peculiar, since with bronchial asthma, rhinitis, conjunctivitis, and urticaria, only rarely does the level of IgE exceed 1,000 IU/ml [38].
However, it is certain that some 20–30% of moderate or severe atopic dermatitis patients do not show any rise in serum IgE levels; therefore, one explanation for this controversy is that atopic dermatitis has two aspects of immunity for the production of eczema:
first, IgE-mediated allergy resulting in spongiosis [39], and, second, cell-mediated allergic contact der- matitis [40, 41].
So-called dirty neck is, histologically, a moderate dermatitis composed of slight acanthosis, lympho- cyte and histiocyte infiltration around the vessels in the upper dermis, and incontinentia pigmenti histo- logica. The reticular pattern of “dirty neck” resem- bles macular amyloidosis; however, amyloid is usual- ly negative according to Congo red stain, and only a small amount of amyloid was detected by electron microscopy [32]. The pigmentation and configura- tion are also similar to pigmented cosmetic derma- titis morphologically; however, the most commonly detected contact allergens with severe atopic derma- titis including “dirty neck” were not previously de- scribed cosmetic allergens, but frequently house dust mite components [34, 35]. Today, a test to demon- strate mite contact hypersensitivity is possible using a commercially sold patch test reagent Dermatopha- goides Mix
®(Chemotechnique, Sweden) in a Finn chamber. House dust mite proteins such as Der 1 to 7 have been known as sensitizers, and recently α-aca- ridial, a component of a house dust mite Tyrophagus putrescentiae, turned out to be a primary sensitizer [42]. Active sensitization was observed by the patch test of α-acaridial at 5–0.5% in petrolatum, and the positive reactions were maintained for 1–11 months.
It is amazing that such a strong contact sensitizer is present in house dust mites.
The treatment of “dirty neck” is not easy.When the 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 20/m
2at 20 second aspiration using a 320-W cleaner, 88% of severe atopic dermatitis patients showed con- siderable improvement in their severe dermatitis when they were followed up for 1–2 years [43]. The statistically significant effect of house dust mite elim- ination with controls in atopic dermatitis was also re- ported by Tan et al. [44]. The “dirty neck,” however,
Core Message
was difficult to cure even with this method, and it can be regarded as the last symptom to improve for atop- ic dermatitis (Fig. 5).
18.2 Depigmentation from Contact with Chemicals
18.2.1 Mechanism of Leukoderma due to Chemicals
There are at least three kinds of mechanism produc- ing leukoderma from contact with chemicals:
쐽
Leukoderma due to selective destruction of melanocytes
쐽
Leukomelanoderma or photoleukomelanoder- ma due to pigment blockade
쐽
Hypopigmentation due to reduction of mela- nin synthesis
Allergic contact dermatitis and irritant contact der- matitis can both produce a secondary leukoderma
which is almost impossible to differentiate from id- iopathic vitiligo. The incidence is low, except for cer- tain phenol derivatives and catechols, which produce a much higher incidence in workers who frequently come into contact with them (Table 3).
Monobenzyl ether of hydroquinone (MBEH) has been known to be a cause of occupational vitiligo since the 1930s [45], the main source of contact hav- ing been rubber, in which it is used as an antioxidant to prevent degeneration. The use of MBEH in the rubber industry today is rare, as it had a long history of causing occupational leukoderma by destroying melanocytes. Instead, MBEH came to be used as a bleaching agent for melanotic skin, being used to treat diseases such as melasma and solar lentigo and by dark-skinned people for cosmetic purposes. How- ever, as its toxic effect on melanocytes was too strong, the treatment often resulted in a mottled pat- tern of leukoderma (confetti-like depigmentation), which was worse than simple hyperpigmentation, and produced problems [46].
Historically, the next chemical to produce leuko- derma by contact was 4- tert-butylcatechol (PTBC), known since the 1970s [47, 48]. Approximately half of
18
Fig. 5a, b.A severe case of atopic dermatitis of a 28-year-old woman had resulted in “dirty neck” for almost 10 years (a). The generalized severe eczema could not be sufficiently controlled by corticosteroid ointments; therefore, among her multiple al- lergens, mite and metal were selected for elimination to obtain improvement. First, mite fauna was investigated in her home followed by environmental improvement to efficiently de- crease Dermatophagoides. Second, she was hypersensitive to
stannic (tin) derivatives; therefore, dental metals containing stannic were all eliminated and replaced by other metals to which she was not hypersensitive. Tacrolimus ointment has been used as an antisymptomatic treatment recently. General- ized severe eczema disappeared after the above-mentioned al- lergen elimination, then “dirty neck” slowly disappeared in 4 years, as the last symptom of this case (b)
a b
the 75 workers in a tappet assembly plant in the Unit- ed States were reported to have various grades of leu- koderma from daily occupational contact with 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 produced positive reactions in three of these four 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 test with 10% PTBC in black guinea pigs resulted in 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- tert-butylphenol (PTBP) began to be recognized. The 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 the depigmentation was an occupational dermatosis [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].
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- ly sensitized to PTBP with positive reactions on a 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 the hypopigmentation caused by hydroquinone is thought to be decreased formation of melanosomes and destruction of the membranous organelles in the melanocytes, thus causing degeneration of melanoc- 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 irritation often noted, and the fact that sensitization is not always demonstrated.
Table 3.Chemicals producing leukoderma or hypopigmenta- tion on contact
Hydroquinone
Monobenzyl ether of hydroquinone
p-tert-Butylcatechol (PTBC)
p-tert-Butylphenol (PTBP)
Kojic acid (hypopigmentation only)
Catechol
Monomethyl ether of hydroquinone (MMEH)
Alstroemeria components (tulipalin A)
Squaric acid dibutylester
Cerium oxide CeO2
Another hazard of using hydroquinone as a bleaching agent is ochronosis, especially when it is used at high concentrations (e.g., 3.5–7.5%) [58]. Och- ronosis means “yellow disease,” and black Africans suffer from hyperpigmentation of the face due to the degeneration of elastic fibers caused by this topical agent [59]. Therefore, the use of hydroquinone as a bleaching agent by blacks should be advised careful- ly, and high concentrations are not recommended.
18.2.2 Contact Leukoderma Caused Mainly by Contact Sensitization
Very rarely, allergic contact dermatitis produces a secondary depigmentation similar to vitiligo. A gar- dener was reported to have developed secondary leu- koderma after allergic contact dermatitis due to Al- stroemeria [60], and when squaric acid dibutylester was used for immunotherapy in a 26-year-old male with alopecia areata, depigmentation over the whole scalp was reported after repeated contact dermatitis produced by nine courses of treatment. Regrowth of hair was also noted [61]. A herbicide, Carbyne R, and cerium oxide have also been reported to produce contact hypersensitivity and secondary leukoderma [62, 63].
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