Discolorations of the skin, such as vitiligo, were recognized thousands of years ago. White spots caused by vitiligo and other disorders have caused significant social opprobrium to those disfigured by these pigmentary disorders, throughout history and still in the present day. Treatments have been desperately sought with only partial success. Recent advances suggest that vitiligo and other pigmentary disorders might soon be curable.
Key points
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Vitiligo and other disorders causing white spots on the skin have been recognized for thousands of years.
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Vitiligo carries a heavy social burden resulting in banishment, inability to marry, and embarrassment.
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Investigators have sought treatments that range from burning to blistering to tattooing to relieve the suffering of those affected.
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Phototherapy, especially psoralens and exposure to ultraviolet A, have had a modicum of success in treating vitiligo.
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Many other oral and topical agents are used to minimize the scourge of vitiligo.
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Results of new research promise the possibility of a cure that would stop the progression of depigmentation and permit repigmentation in those affected.
You are not just white, but a rainbow of colors. You are not just black, but golden. You are not just a nationality, but a citizen of the world.
The color of human skin is remarkable for its breadth of color and fascinating for its science and biology. It ranges from white, to yellow, to brown and even a dark, almost black. Humans have used skin color to distinguish their nation, tribe, and even their family from other peoples, skin color often a designation of friend or foe. The science and biology of skin color remained a mystery until the early twentieth century when melanocytes were described and the chemistry of formation of melanin within the epidermis was worked out.
History of leukoderma, white spots, and vitiligo
Perfect, flawless skin color is desired by everyone for its beauty and attractiveness. However, like all biologic systems, pigmentation can be abnormal. There can be dark spots or light spots, both of which are disfiguring. These problems have caused distress to people for millennia. Already in 1500 to 1000 bce , Indian writers described “kilas” and “palita,” translated as white or yellowish white spots. The Ebers Papyrus describes people with white spots. In these early writings, the precise condition being described is not known, although leprosy and vitiligo are just two of many possible candidates. There are numerous references to white spots in the Old Testament. Typically these were considered leprosy but it is plausible that much of what was considered to be leprosy was vitiligo or other disorders of skin color. In the Far East prayers known as Makatominoharai dating from 1200 bce recognized white skin, possibly vitiligo.
In the sixteenth century, Hieronymus Mercurialis published his book on diseases of the skin. In it he devotes an entire chapter, entitled “On Leuce and Alphos,” to disorders of abnormal skin color. He cites early Arabic, Greek, and Latin scholars about white spots and notes that the word “…‘vitiligo’ is a Latin word derived from either ‘vitium’ (blemish) or ‘vitulum’ (small blemish)…” The word vitiligo might have been first used by Celsus. Mercurialis suggests that phlegm accumulating under the skin was the source of leukoderma, a theory that he confirms from the writings of “…divine Plato…that white phlegm has two effects in the body….if it begins to vent through the exterior of the body, it will cause …vitiligo.” Herodotus in Greece noted white spots on foreigners and suggested they be banished immediately, their having sinned against the sun.
In China and Korea, writers discussed white spots and white skin. In Korea vitiligo and other pigmentary disorders, such as nevus depigmentosus or tinea versicolor, were described in Doney Bogam, published in the seventeenth century. A portrait of Chang-Myeong Song, a high ranking official of the Yi dynasty of Korea, was painted about this time that shows the typical depigmentation of vitiligo.
In the seventeenth century, William Byrd described “An Account of a Negro-Boy that is, dappel’d in several places of his Body with White Spots.” The depigmentation began at age 3 years and continued to spread. Byrd conjectures that in time the boy would become all white. The leukoderma was obviously mysterious in origin.
Brito in the nineteenth century discussed vitiligo. He emphasized the social stigma of white spots and their capacity to disfigure. “The appearance of the unfortunate victims of vitiligo is striking, and scarcely fails to evoke a feeling of horror and pity for the afflicted,…The picture of otherwise dark person,…marked with spots perfectly white,…to even eyes familiarized to the sight, appears repugnant.”
The worldwide distribution of these reports dating back thousands of years attests that vitiligo was and is ubiquitous. The comments of some of the previously quoted authors confirm its deleterious effects on those who suffer from it. It is often said that vitiligo is only a cosmetic problem. It is not entirely true that vitiligo does not affect the physical functioning of the body in any detrimental way. There are pigment cells in organs and tissues other than skin, such as the eye, inner ear, and leptomeninges. Vitiligo can affect choroidal melanocytes and retinal pigment epithelium causing iritis and chorioretinitis. Vogt-Koyanagi syndrome is characterized by unilateral vitiligo, poliosis, meningitis, and dysacusia, probable manifestations of melanocyte destruction in each of these organs and tissues. These extracutaneous manifestations of vitiligo rarely cause loss of visual acuity or hearing. Regardless vitiligo like albinism causes immense social, emotional, and personal pain and disability. Even today in the middle east, young people with vitiligo find it an impediment to finding a marriageable partner. The plethora of treatments ( Table 1 ) proposed and tried for thousands of years attest to its significance in all cultures and societies. Its detrimental effects on quality of life have now been thoroughly studied and are well characterized.
| ACTH Agaric, turpeth, and colocynth Anapsos Anthralin Arsenic Aspirin Bergamot Bavachee seeds Bitter almonds in vinegar Byzantine syrup Cantharidin Carmustine (BCNU) Clofazimine Chloroquine Copper Corrosive sublimate Cosmetics Crude coal tar Cryotherapy Cyclophosphamide Cyclosporine Dapsone Dermabrasion Dopa oral and topical Escharotics Finsen lamp Fluorouracil Fluphenazine enanthate Folic acid Hydrochloric acid Hydrogen peroxide Injections of silver nitrate Iron Isoprinosine Khellin oral and topical | Levamisole Mefloquin Melaginina Methotrexate Minigrafting autografts Minoxidil Monoamine oxidase inhibitors Monobenzyl ether of hydroquinone Mustard Oxymel Pimecrolimus Phenylalanine-ultraviolet A Psoralens + sunlight Psoralens + ultraviolet A Pseudocatalase Quinacrine Resorcin paste Rose-flavored honey Selective diets Steroids oral or topical Surgical excision Syrup of betony Tacrolimus Tattooing Thermal and caustic blistering Tincture of nux vomica Tretinoin Ultraviolet B narrow band Vesicants Vibrapuncture Vitamin B 6 Vitamin B 12 Vitamin C Vitamin D Vitamin E |
History of leukoderma, white spots, and vitiligo
Perfect, flawless skin color is desired by everyone for its beauty and attractiveness. However, like all biologic systems, pigmentation can be abnormal. There can be dark spots or light spots, both of which are disfiguring. These problems have caused distress to people for millennia. Already in 1500 to 1000 bce , Indian writers described “kilas” and “palita,” translated as white or yellowish white spots. The Ebers Papyrus describes people with white spots. In these early writings, the precise condition being described is not known, although leprosy and vitiligo are just two of many possible candidates. There are numerous references to white spots in the Old Testament. Typically these were considered leprosy but it is plausible that much of what was considered to be leprosy was vitiligo or other disorders of skin color. In the Far East prayers known as Makatominoharai dating from 1200 bce recognized white skin, possibly vitiligo.
In the sixteenth century, Hieronymus Mercurialis published his book on diseases of the skin. In it he devotes an entire chapter, entitled “On Leuce and Alphos,” to disorders of abnormal skin color. He cites early Arabic, Greek, and Latin scholars about white spots and notes that the word “…‘vitiligo’ is a Latin word derived from either ‘vitium’ (blemish) or ‘vitulum’ (small blemish)…” The word vitiligo might have been first used by Celsus. Mercurialis suggests that phlegm accumulating under the skin was the source of leukoderma, a theory that he confirms from the writings of “…divine Plato…that white phlegm has two effects in the body….if it begins to vent through the exterior of the body, it will cause …vitiligo.” Herodotus in Greece noted white spots on foreigners and suggested they be banished immediately, their having sinned against the sun.
In China and Korea, writers discussed white spots and white skin. In Korea vitiligo and other pigmentary disorders, such as nevus depigmentosus or tinea versicolor, were described in Doney Bogam, published in the seventeenth century. A portrait of Chang-Myeong Song, a high ranking official of the Yi dynasty of Korea, was painted about this time that shows the typical depigmentation of vitiligo.
In the seventeenth century, William Byrd described “An Account of a Negro-Boy that is, dappel’d in several places of his Body with White Spots.” The depigmentation began at age 3 years and continued to spread. Byrd conjectures that in time the boy would become all white. The leukoderma was obviously mysterious in origin.
Brito in the nineteenth century discussed vitiligo. He emphasized the social stigma of white spots and their capacity to disfigure. “The appearance of the unfortunate victims of vitiligo is striking, and scarcely fails to evoke a feeling of horror and pity for the afflicted,…The picture of otherwise dark person,…marked with spots perfectly white,…to even eyes familiarized to the sight, appears repugnant.”
The worldwide distribution of these reports dating back thousands of years attests that vitiligo was and is ubiquitous. The comments of some of the previously quoted authors confirm its deleterious effects on those who suffer from it. It is often said that vitiligo is only a cosmetic problem. It is not entirely true that vitiligo does not affect the physical functioning of the body in any detrimental way. There are pigment cells in organs and tissues other than skin, such as the eye, inner ear, and leptomeninges. Vitiligo can affect choroidal melanocytes and retinal pigment epithelium causing iritis and chorioretinitis. Vogt-Koyanagi syndrome is characterized by unilateral vitiligo, poliosis, meningitis, and dysacusia, probable manifestations of melanocyte destruction in each of these organs and tissues. These extracutaneous manifestations of vitiligo rarely cause loss of visual acuity or hearing. Regardless vitiligo like albinism causes immense social, emotional, and personal pain and disability. Even today in the middle east, young people with vitiligo find it an impediment to finding a marriageable partner. The plethora of treatments ( Table 1 ) proposed and tried for thousands of years attest to its significance in all cultures and societies. Its detrimental effects on quality of life have now been thoroughly studied and are well characterized.
| ACTH Agaric, turpeth, and colocynth Anapsos Anthralin Arsenic Aspirin Bergamot Bavachee seeds Bitter almonds in vinegar Byzantine syrup Cantharidin Carmustine (BCNU) Clofazimine Chloroquine Copper Corrosive sublimate Cosmetics Crude coal tar Cryotherapy Cyclophosphamide Cyclosporine Dapsone Dermabrasion Dopa oral and topical Escharotics Finsen lamp Fluorouracil Fluphenazine enanthate Folic acid Hydrochloric acid Hydrogen peroxide Injections of silver nitrate Iron Isoprinosine Khellin oral and topical | Levamisole Mefloquin Melaginina Methotrexate Minigrafting autografts Minoxidil Monoamine oxidase inhibitors Monobenzyl ether of hydroquinone Mustard Oxymel Pimecrolimus Phenylalanine-ultraviolet A Psoralens + sunlight Psoralens + ultraviolet A Pseudocatalase Quinacrine Resorcin paste Rose-flavored honey Selective diets Steroids oral or topical Surgical excision Syrup of betony Tacrolimus Tattooing Thermal and caustic blistering Tincture of nux vomica Tretinoin Ultraviolet B narrow band Vesicants Vibrapuncture Vitamin B 6 Vitamin B 12 Vitamin C Vitamin D Vitamin E |
Study of skin color and white spots
Skin color was a mystery until modern times after the invention of the microscope, the techniques of biopsy, and the discovery of histochemical stains. Before the seventeenth century, the origin of skin color was based on myths, folklore, and religious theories. Explanations attempted to explain the origin of dark skin color, not why some skin was very light. Jean Roland in 1618 separated the epidermis from the dermis of a black individual. He was able to observe the upper layer of skin (epidermis) was pigmented, the lower dermal layer not pigmented. He proposed that sunlight and heat caused dark skin, a theory that might explain dark skin at the equator but not why Europeans remained white when traveling to southern climes. Another scientist, Thomas Browne, noted this discrepancy and decided skin color was a genetic trait carried within the sperm.
Theories about the mechanism for production of skin color came and went. Many famous investigators, such as van Leeuwenhoek, John Hunter, Immanuel Kant, and Marcello Malpighi, all studied skin color usually in deeply pigmented Ethiopians, often on cadavers but occasionally in living subjects. However, without proper instruments and techniques, the origins of pigmentation remained a mystery. More mysterious back then were the mechanisms for loss of skin color. Benjamin Rush suggested that black skin of Negroes was a form of leprosy and that vitiligo was an indication of spontaneous cure.
History of treatment of vitiligo
The treatment of white spots or vitiligo has been tried for as long as white spots and/or vitiligo have been recognized. A partial list of therapies tried over the centuries is presented in Table 1 . Detailed descriptions of methods, mostly ineffective, are found in ancient texts. The stigma of white spots in ancient times was frightening. In the Old Testament, those with white spots/vitiligo were considered unclean from leprosy or sinful, the spots a punishment from God. They were rejected from society. Herodotus noted that those affected had sinned against the sun and were to be driven from Greece. In the sixteenth century Mercurialis acknowledged that the appearance of those with white spots was objectionable. He stated white spots were so offensive that if blistering medications applied topically were not helpful, then fire itself (the actual cautery) was to be applied on the parts involved with care taken to avoid scarring if possible. Even in the nineteenth century, the mechanism for skin color, for white spots, and their treatment were unknown. Brito made a list of therapeutic possibilities for treatment that included escharotics; surgical excision; grafts; injections of dark substances, such as silver nitrate into the dermis; tattooing, or administration of silver salts by mouth.
Early phototherapy was recorded in the Atharva Veda. Black colored seeds combined with other herbs were prepared in an attempt to make the skin an even color as described in this poem.
Born by night art thou, O plant,
Dark, black, sable, do thou,
That art rich in color,
Stain this leprosy and white gray spots.
Even color is the name of thy mother,
Even color is the name of thy father,
Thou O plant produces even color
Render this even color.
The black seeds probably were from the plant Bavachee , which contained psoralens and probably had some success following exposure to sunlight. Other references to use of plants containing psoralens, such as Psoralea corylifolia , are found in Buddhist, Chinese, and Egyptian writings. In the early twentieth century the Finsen light seemed to be the first treatment offering some hope to those with vitiligo. The Finsen light was a source of short ultraviolet waves produced by a carbon or mercury arc. These observations were confirmed by Menon who exposed patients to ultraviolet light with visible perifollicular repigmentation occurring after a series of treatments.
Psoralens and exposure to ultraviolet light A (PUVA) was started by an Egyptian physician, Abdel Moneim El-Mofty. He cited Bloch’s observations that dopa stains for melanocytes were negative in vitiliginous skin. He described the early use of crude extracts from plants containing psoralen followed by exposure to sunlight until inflammation and vesiculation occurred. After the blisters ruptured and the patch healed pigmentation was often restored. Early forms of PUVA using crude extracts were associated with severe gastrointestinal distress and rarely coma followed by death.
El-Mofty isolated from the Ammi majus Linn plant a purified form of psoralen that was safer and more tolerable than the original plant extracts. He tested a topical and oral form of the psoralen and found that together they produced the best repigmentation, although alone they were partially successful. He later purified and identified 8-methoxypsoralen (also termed xanthotoxin) and 4,5,8-trimethylpsoralen. Subsequent studies confirmed his earlier observations that psoralens were capable of producing repigmentation in patches of vitiligo, sometimes totally repigmenting white skin, sometimes inducing only partial repigmentation. Typically repigmentation begins as freckling, a manifestation of melanocyte proliferation within hair follicles and migration to the interfollicular skin ( Figs. 1 and 2 ). The pigmentation spreads to produce almost total repigmentation, although the PUVA treatments take a year or more ( Figs. 3 and 4 ).
Related posts:
Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients
Skin Cancer Risk (Nonmelanoma Skin Cancers/Melanoma) in Vitiligo Patients
Presentations, Signs of Activity, and Differential Diagnosis of Vitiligo
Surgical Therapies for Vitiligo
Depigmentation Therapies for Vitiligo
Vitiligo Pathogenesis and Emerging Treatments
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