(BQ) Part 2 book Vitiligo and other hypomelanoses of hair and skin presents the following contents: Hypomelanoses associated with nutritional and metabolic disorders, hypomelanosis associated with endocrine disorders, hypomelanosis secondary to irradiation and physical trauma, chemical hypomelanosis, miscellaneous hypomelanoses,....
SECTION DISORDERS AFFECTING HAIR PIGMENTATION WITHOUT AFFECTING SKIN PIGMENTATION PREMOLAR APLASIA, HYPERHIDROSIS, AND CANITIES PREMATURA In 1950, Book [1] described 18 patients with a new autosomal dominant syndrome with complete penetrance but somewhat variable expression and characterized by bicuspid aplasia, premature whitening of the hair, and hyperhidrosis Early whitening of the hair was found in all 18 cases Hair whitening began in 14 patients before or at the age of 14 years, but onset varied from six to 23 years The whitening was uniform and never patchy The progression of whitening was usually slow, and in the older patients was always complete The scalp hair was most constantly affected but in six of the 18 cases there was conspicuous whitening of axillary (five cases) and genital (six cases) hair and the eyebrows and cilia (two cases) In 16 cases, the original hair color was specified (seven were blond, four light brown, three dark brown, one red blond, and one black) The hair was otherwise completely normal No depigmentation of the skin was observed The author examined 63 members of this family and found premature graying of the hair in seven who lacked other features of the syndrome All 18 patients had blue irides, but this is such a common trait in Sweden that this observation may represent only coincidence Two-thirds of the patients had a definite functional palmoplantar hyperhidrosis The most striking feature was the involvement of the bicuspid teeth In nine patients, all eight bicuspids were missing and no anlage could be detected by x-ray The other patients were missing one to seven bicuspids In most cases, there was a posterior displacement of the canines Deciduous teeth were present in all cases General health is unimpaired The pathogenesis is unknown No treatment is available FANCONI SYNDROME Fanconi syndrome is vitamin-D-resistant rickets or osteomalacia with hypophosphatemia, glucosuria, generalized aminoaciduria and generally chronic acidosis, hypouricemia, and hypokalemia It may occur early (infantile form) or later (adult form) in life Fanconi syndrome may be idiopathic or associated with cystinosis, Lowe syndrome, or tyrosinemia In a series of 24 patients reported by Cowie [2], 19 patients had cystinosis, four had cirrhosis and no cystinosis, and one had neither Both groups of patients were found to have significantly fairer hair electrospectrophotometrically than their siblings or than age-matched controls Schneider and Seegmiller [3] noted that although these patients with increased intracellular cystine often have blond hair and are significantly fairer than their parents, they have much less tendency to sunburn than would be expected for their degree of pigmentary dilution 461 GENETIC AND CONGENITAL DISORDERS 462 CHAPTER The mechanism of hypopigmentation is unknown but may relate to cystine binding of sulfhydryl-requiring enzymes ROTHMUND-THOMSON SYNDROME Rothmund-Thomson syndrome is a rare, autosomal recessive disease which is characterized by acquired erythematous patches that develop atrophy, telangiectasia, hypo- and hyperpigmentation, and sometimes warty keratosis [4,5] Other features include alopecia, photosensitivity, bilateral cataracts, short stature, small skull, sometimes with birdlike features, and hypogonadism Life expectancy appears to be normal Premature canities is an inconstant feature of Rothmund-Thomson syndrome; it sometimes appears in adolescence and progresses rapidly DYSTROPHIA MYOTONICA Canities occurring in the second or third decade may be seen in dystrophia myotonica [6], an entity that was first described in 1909 by Steinert [7] This rare disorder, which is inherited as an autosomal dominant disease, usually appears in the second or third decade and is characterized by myotonia, severe muscle wasting, cataracts, premature frontal baldness, and characteristic lugubrious physiognomy Testicular atrophy, various disorders of ovarian function, and low basal metabolic rate are frequently observed Few of these patients survive beyond the sixth decade and death is often attributed to aspiration pneumonia or to cardiac conduction defects PREMATURE AGING SYNDROMES Two of the premature aging syndromes, Werner syndrome (pangeria) and Hutchinson-Gilford syndrome (progeria), are characterized by premature graying of hair Werner Syndrome (Pangeria) Werner syndrome, which is a rare autosomal recessive disorder, was first described in 1904 in the thesis "Uber Kataract in Verbindung mit Sklerodermie" (Cataract in Combination with Scleroderma) by Otto Werner [8] Werner gave a detailed description of four siblings with cataracts and sclerodermatous changes as well as a senile appearance and graying beginning at about the age of 20 Males and females are equally affected The nature of the fundamental defect responsible for the disease is unknown Pigmentary Disturbances Graying of hair is one of the earliest characteristic signs of the disease From a survey of 125 cases, Epstein et al [9] established that gray hair is first seen at about 20 years of age, while the mean age of onset is 25.3 years for alteration of the voice, 30 years for detection of cataract formation, 33 years for skin ulcers, and 34.2 years for diabetes mellitus Premature graying of hair is rarely present before eight years of age The graying generally first affects the temples and eyebrows, may require from five to 20 years for maximal loss of pigment, and often progresses to complete whiteness Baldness follows graying of the hair by several years Other Clinical Features Patients with Werner syndrome have a characteristic habitus with a beakshaped nose, stocky trunk with slender extremities, and short stature first apparent in adolescence A weak, high-pitched voice is characteristic The skin and subcutaneous tissues are atrophic with circumscribed hyperkeratosis Indolent ulcers often develop over malleoli of ankles, Achilles tendon, heels and toes Most of the patients develop juvenile cataracts Hypogonadism and diabetes mellitus are frequently observed Generalized arteriosclerosis, osteoporosis, calcifications of ligaments, tendons, and subcutaneous tissues may develop prematurely The incidence of malignancy is increased and the life expectancy is decreased Diagnosis The combination of the prematurely aged appearance, the other physical features, the scleroderma-like skin changes, and the cataracts establish the diagnosis [10] The other premature aging syndromes (metageria, acrogeria, total lipodystrophy, and progeria) have a different clinical picture [11] Sclerosis of the skin does not usually accompany Rothmund-Thomson syndrome Observation of early graying may alert the physician to other possible features Hutchinson-Gilford Syndrome (Progeria) This autosomal recessive disease was first described in 1886 by Hutchinson [12] who reported a boy who had been bald since infancy and whose skin was atrophic and wrinkled This child and another patient were subsequently reported by Gilford [13], who first used the name "progeria." Progeria is a rare condition occurring equally in both sexes The primary defect responsible for the disease is unknown Pigmentary Disturbances In progeria, the hair is sparse and prematurely gray DeBusk [14] noted that sparse, downy blond or white fuzz was present even if the original hair was black Other Clinical Features Patients with this disease usually appear normal at birth During the first year of life there is a profound failure to meet normal growth markers and 463 GENETIC AND CONGENITAL DISORDERS 464 CHAPTER during the second year of life the characteristic facies (plucked-bird appearance with craniofacial disproportion, micronathia, and prominent eyes), alopecia, loss of subcutaneous fat, stiffness of joints and bones, skeletal abnormalities (pyriform thorax, coxa valga), cutaneous changes (diminution of subcutaneous fat and sclerodermatous skin), and abnormal dentition become apparent Motor and mental development is normal There is insulin resistance and increased basal metabolic rate Early death results from severe generalized arteriosclerosis Diagnosis Progeria with its remarkably constant phenotypic expression can easily be distinguished from other premature aging syndromes Graying of the hair, when present, appears sooner than in Werner syndrome Cockayne syndrome differs from progeria by the presence of light sensitivity, disproportionate dwarfism, and absence of alopecia No treatment is available FISCH SYNDROME Fisch [15] described a family with deafness and early, pronounced graying of the hair Among 21 members of this family, two of the 10 who had early graying also had deafness Two other young children had only deafness and two others partial heterochromia irides Fisch observed similar cases and believed this a genetically distinct syndrome Soussi Tsafir [16], arguing that none of the 13 affected members of this family had dystopia canthorum, drew the same conclusion and distinguished this condition from Waardenburg syndrome, which has a penetrance of 40% to 99% Other possible cases include those of Ballantyne [17] who noted that many of his patients with progressive high-tone deafness, among them a father and daughter and a brother and sister, had strikingly light blond hair and light blue eyes KAPPA CHAIN DEFICIENCY Bernier et al [18] reported a young girl with recurrent respiratory infections, diarrhea, white hair, extremely long white eyelashes, and very pale skin This was associated with a decreased concentration of immunoglobulins of one light chain type (kappa) Radiolabeled kappa and lamda type molecules survived equally well, suggesting that the synthesis of molecules bearing kappa chains was decreased HEREDITARY PREMATURE CANITIES Premature graying of hair in individuals who are otherwise normal has been reported as an hereditary autosomal dominant trait Among six generations in one family, nine individuals were involved In these cases, graying of scalp and body hair appeared during the second decade or earlier, but did not affect the eyebrows and eyelashes [19] BIRD· HEADED DWARFISM (SECKEL SYNDROME) Bird-headed dwarfism is a rare autosomal recessive form of dwarfism characterized by a bird-head profile, trident hands, skeletal defects, hypodontia, and pancytopenia with hypersplenism Brown pigmentation with white macules has been reported in one Japanese infant [20] and premature senility has been described in several patients with this disease [21] Fitch et al [21] reported premature graying of scalp hair that began at age 18 in one patient Though premature graying is most characteristic, hypo melanotic macules have also been described In 1974, Tay et al [22] reported such a recessive disorder in two Indian teen-aged sisters from West Malaysia The disease, probably inherited as a recessive autosomal trait, was characterized by microcephaly, triangular-shaped face, prominent eyes, hypoplastic alae nasi, small pinched nose, tiny mouth and large pegged-shaped incisors, abnormal limbs characterized by trident hands, hypoplastic transverse palmar creases, and large big toes and stubbed short toes One girl had a large number of cafe-au-Iait spots and depigmented lesions on the shins, knees, extensor surfaces of the arms, and upper chest wall that appeared at the age of nine At the same time, hairs of the scalp, eyebrows, eyelashes, and of the limbs turned prematurely gray The skin biopsy of the hypopigmented patches resembled vitiligo The second patient showed similar premature canities and depigmented macules, though fewer and less extensive In addition, these two girls had liver involvement with fatty infiltration and hepatic cirrhosis with hypersplenism, raised serum immunoglobulins, and hyperaminoaciduria, mainly of taurine, beta-aminoisoleutyric acid, and glycine As there is a striking similarity between these cases and patients with "birdheaded dwarfism," the authors suggest that these cases may represent a variant of the latter TREACHER COLLINS SYNDROME, PIERRE ROBIN SYNDROME, HALLERMAN-STREIFF SYNDROME, DOWN SYNDROME, CHROMOSOME FIVE P·SYNDROME Lopez et al [23] included Treacher Collins syndrome, Pierre Robin syndrome, and Hallerman-Streiff syndrome in the group of hereditary disorders associated with hypomelanosis of the skin and hair Porter and Lobitz [24] also mention fine, light-colored hair in Pierre Robin syndrome and light-colored hair in tyrosinemia and in Down syndrome (trisomy 21) However, these are only isolated reports Several adult patients with chromosome five p-syndrome (cri-du-chat syndrome) have prematurely gray hair [25] 465 GENETIC AND CONGENITAL DISORDERS 466 CHAPTER PROLIDASE DEFICIENCY Prolidase deficiency, a very rarely reported inborn error of metabolism, has important and severe dermatologic manifestations, especially ulcers of the lower extremities Poliosis or premature graying of hair has been found in several of these patients [26] REFERENCES Book JA: Clinical and genetical studies of hyperdontia I Premolar aplasia, hyperhidrosis and canities prematura A new hereditary syndrome in man Am J Hum Genet 2:240-263, 1950 Cowie V: Hair colour in the infantile Fanconi syndrome Ann Hum Genet 21: 170-176, 1956 Schneider JA, Seegmiller JE: Cystinosis and the Fanconi syndrome, in Metabolic Basis of Inherited Disease, 3rd ed Edited by JB Stanbury et al New York, McGraw-Hill, 1972, pp 1581-1604 Rook A, Wells RS: Genetics in dermatology, in Textbook of Dermatology Edited by A Rook et al London, Blackwell, 1969, pp 57-60 Tannhauser SJ: Werner's syndrome (progeria of the adult) and Rothmund's syndrome: two types of closely related heredofamilial atrophic dermatoses with juvenile cataracts and endocrine features A critical study of five new cases Ann Intern Med 23:559-626, 1945 Touraine A: (Progres Medical 73:47, 1945) Quoted in Ebling EJ, Rook A: Premature canities, in Textbook of Dermatology Edited by A Rook et al London, Blackwell, 1969, pp 1413-1414 Steinert H: Myopathologische Beitrage I Dber das klinische und anatomische Bild des Muskelschwunds der myotaniker Dtsch Z Nervenh 37:58-104, 1909 Werner 0: Dber Katarakt in Verbindung mit Sclerodermie Doctoral Dissertation, Kiel University Kiel, Schmidt and Klaunig, 1904 Epstein DJ et al: Werner's syndrome Medicine (Baltimore) 45:177-221, 1966 10 Rook A: Disorders of connective tissues, in Textbook of Dermatology Edited by A Rook et al London, Blackwell, 1969, pp 1287-1288 11 Gilkes JJH et al: The premature aging syndromes Br J Dermatol 91:243-262, 1974 12 Hutchinson J: Congenital absence of hair and mammary glands Medico-Chirurg Trans 69:473, 1886 Quoted by Gilkes JJH et al: The premature aging syndromes Br J Dermatol 91:243-262, 1974 13 Gilford H: Progeria: a form of senilism Practitioner 73:188-217,1904 14 DeBusk FL: The Hutchinson-Gilford progeria syndrome J Pediatr 80:697-724, 1972 15 Fisch L: Deafness as part of an hereditary syndrome J Laryngol Otol 73:355-382, 1959 16 Soussi Tsafir J: Light-Eyed Negroes and the Klein-Waardenburg Syndrome London, MacMillan, 1974 17 Ballantyne JC: Deafness London, Churchill, 1960 18 Bernier GM et al: Kappa chain deficiency Blood 40:795-805, 1972 19 Hare HJH: Premature whitening of hair J Hered 20:31-32, 1929 20 Seckel HPG: Bird-Headed Dwarfs Basel, S Karger, 1960 21 Fitch N et al: A form of bird-headed dwarfism with features of premature senility Am J Dis Child 120:260-264, 1970 22 Tay CH et al: A recessive disorder with growth and mental retardation, peculiar facies, abnormal pigmentation, hepatic cirrhosis and aminoaciduria Acta Paediatr Scand 63:777-782, 1974 23 Lopez B et al: Trastornos de la pigmentaci6n, in Actas Del VI Congresso Ibero-Latino Americano de Dermatologia (Barcelona, Spain, 1967) Barcelona, Editorial Cientifico Medica, 1970, pp 157-179 24 Porter PS, Lobitz WC: Human hair: a genetic marker Br J Dermatol 83:225-241, 1970 25 Breg WR: Abnormalities of chromosomes and 5, Endocrine and Genetic Diseases of Childhood and Adolescence Edited by 11 Gardner Philadelphia, Saunders, 1975, pp 1505-1515 26 Der Kaloustian VM et al: Prolidase deficiency: an inborn error of metabolism with major dermatological manifestations Dermatologica 164:293-304, 1982 Hypomelanoses Associated with Nutritional and Metabolic Disorders KWASHIORKOR Kwashiorkor is a result of dietary deficiency of protein in the weaning and early postweaning stage of childhood In underdeveloped nations it remains a significant cause of death among children from one to four years of age Credit for the first description of kwashiorkor is generally given to Williams [1], who, in 1953, reported five "Gold Coast children," four of whom died The origin of the term "kwashiorkor" is not precisely known Kwashiorkor has been reported in every part of Africa, and also in China, India, Malaya, Indonesia, Fiji, the Philippines, Caribbean Islands, Hungary, Italy, and various parts of South America Henington et al [2], in 1958, reported four cases from Louisiana The general prevalence of kwashiorkor is 0.5% to 1.5% in various community surveys [3] It is said to be much higher in primitive cultures Depigmentation in Kwashiorkor Clinical Description Depigmentation, according to Williams [1] may precede by weeks other dermatologic features of kwashiorkor It may present in the early stages of the disease-before the rash is well circumscribed The hypopigmentation of kwashiorkor usually first involves the face and, after the appearance of a shiny epidermis, resembles a background of fair skin on a red baby As the eruption evolves over one to two days, except on the face, red raised plaques gradually darken until they take on a shiny black appearance Exfoliation is followed by depigmentation Enamel-plaque areas or ulcerations develop to suggest the de pigmented skin is readily predisposed to destructive processes These depigmented macules later repigment, often with hyperpigmentation Lesions most typically occur on pressure points 467 468 CHAPTER Banerjee and Dutta [4] noted that there may be generalized pallor with extensive hypo- and hyperpigmentation, the latter mostly in the diaper area, buttocks, back, thighs, and elbows-as opposed to the sun-exposed areas of pellagra Dyschromic hair is a common feature of kwashiorkor Mukherjee and Jelliffe [5] found the changes minimal in India compared to those seen in Africa, where hypochromotrichia is pronounced Others [6] reported only 13% with hair discoloration, yet Jelliffe [7] reported as high as 82% among African infants in Jamaica In the latter, curled jet black hair is replaced by sparse dry hair varying from red-brown to gray in color Henington et al [2] noted golden to reddish coloration at the ends of normally black hair in their four black patients There is often such minimal dilution of color-a fringe effect-and the color may be brown, red, golden, gray, or white The "signe de bandera" or "flag sign"-which is striped hairmay represent a recurrence Thinning of eyebrows or loss of the outer thirds may occur The hair also becomes dry, thin, and brittle and may be removed painlessly with little effort [8] Partial or total alopecia may result Hair production is 59 /-Lm per follicle in kwashiorkor vs 514 /-Lm for controls [9] Cystine levels are also reduced but return to normal after therapy Histology of Depigmentation Sims [9] compared the epidermis of 10 Zulu infants with kwashiorkor to five unaffected infants He reported decreased thickness of the epidermis and normal cell volumes and concluded there were changes in the kinetics of cell migration Desmosomes were found to be shorter than controls, and this may explain the epidermal fragility Pathogenesis of Depigmentation Protein deficiency in hair, infection, and multiple nutritional deficiencies have been invoked to explain the pigmentary abnormality Rao and Gopalan [10] found no correlation between hair color and amino acid content Nor could hair color or cystine content be correlated with severity of clinical disease Bradfield and Jelliffe [11] emphasized that tuberculosis and malnutrition may coexist in underprivileged populations and that the two together cause greater loss of skin and hair pigment than does either alone Partial de polymerization of melanin has also been suggested Riboflavin or pantothenic acid deficiency and deficiency of sulfur or of sulfur-containing amino acids have been implicated [10]; this fits with the observation that cystine and glutathione as well as other reducing enzymes affect the conversion of tyrosine to melanin by inhibiting tyrosinase and by regulating the oxidation reduction potential of melanocytes [12] That the pigment in the discolored hair behaves chromatographically like oxidized melanin [13], coupled with the above observation, supports the theory that lowering the SH concentration in melanocytes accelerates the conversion of tyrosine to melanin; further oxidation of melanin to a brown or colorless product results TABLE 111 Kwashiorkor: Associated Findings Skin "Crazy-pavement" dermatitis Bullae, ulceration Purpura Mucous membrane Angular stomatitis Cheilosis Nails Thinning, softening, ridging Eyes Xerophthalmia Bitot's spots Blepharitis, conjunctivitis, photophobia Systemic changes Growth retardation Psychic disturbances and mental retardation Muscle wasting Edema Gastrointestinal disorders (anorexia, diarrhea) Hepatomegaly Laboratory findings Hypoalbuminemia Anemia Hypovitaminosis Associated Clinical Findings See Table 111 Diagnosis Leukoderma is not a primary or essential feature of kwashiorkor, the diagnosis of which is based on the history of malnutrition in an infant from an endemic area plus the presence of the many clinical features noted Bands of de pigmented or dyschromic hair may correspond to relapses and those of repigmentation to treatment Other nutritional deficiency syndromes may also be present Treatment Kwashiorkor responds to dietary protein and the skin is said to repigment slowly [4] GENERALIZED DYSCHROMIA IN A MALNOURISHED INFANT Petrozzi [14] reported a 20-month-old black girl who presented several months after birth with multiple episodes of infectious diarrhea associated with febrile seizures At the age of two months, she developed asymptomatic, small, 469 HYPOMELANOSES ASSOCIATED WITH NUTRITIONAL AND METABOLIC DISORDERS 470 CHAPTER hypopigmented macules in the diaper area, upper legs, and lower abdomen During the next two months, similar lesions continued to appear on the trunk and spread to the distal extremities No inflammation preceded the hypopigmented eruption but the father and an older sister had a history of infantile eczema Examination revealed a generalized mottling of the skin which had irregularly scattered hyperpigmented and hypopigmented macules As poor dietary intake and recurrent diarrhea had been present in the first months of life, the author suggested that the dyschromia may result from malnutrition However, amino acid, copper, and vitamin B12 studies were not done PIGMENTARY CHANGES IN THE HAIR OF PATIENTS WITH NEPHROSIS, ULCERATIVE COLITIS, OR EXTENSIVE RESECTION OF THE GUT As in kwashiorkor, chronic protein loss may result in pigmentary changes of the hair [15] This can be observed in nephrosis [16] and also in malabsorption syndromes [16] Mellinkoff [17] reported a 26-year-old Caucasian with ulcerative colitis whose hair turned red with malnutrition and returned to its normal dark brown color after he had gained weight Silverblatt and Brown [16] observed a kwashiorkor-like syndrome with change of the hair from black to red associated with "burning feet" in a 45-year-old black male in whom, 10 years after a gastrectomy for intractable duodenal ulcer, progressively severe diarrhea and pronounced malnutrition developed SEVERE IRON DEFICIENCY Tasker and Polunin [18] reported a 10-year-old aboriginal Malayan male with extremely severe iron deficiency anemia (hemoglobin level of 0.7 g per 100 ml) This boy had light brown hair, a very unusual feature among the usually dark brown-haired peoples of Malaya As the plasma protein values were grossly normal, the authors attributed the pigmentary disturbance to severe iron deficiency Treatment with intravenous iron oxide did not alter the hair color Clinical features of copper deficiency were not present in this patient but blood copper levels were not obtained COPPER DEFICIENCY Acquired copper deficiency is discussed with Menkes kinky hair syndrome (see "Copper Deficiency" in Chapter 1) 94 Yoshida E: Experimental studies in pathogenesis of idiopathic uveitis (uveo-encephalitis) II Acta Soc Ophthalmol Jpn 61:1211-1220, 1957 95 Friedenwald JS, MacKee CM: Filter passing agent as a cause of endophthalmitis, Am J Ophthalmol 21:723-738, 1938 96 Erbakan S: Harada's disease The first case reported in Turkey Am J OphthalmoI53:368-371, 1962 97 Sugiura S et al: The viral nature of Harada's and Vogt-Koyanagi syndrome (abstr) Acta Soc Ophthalmol Jpn 57:117,1953 98 Bruno MG, McPherson SO Jr: Harada's disease Am J Ophthalmol 32:513-522, 1949 99 Pusey B: Cytotoxins and sympathetic ophthalmia Arch Ophthalmol (old series) 32:334-338, 1903 100 Elschnig A: Studien zur sympathischen Ophthalmie Die autigene Wirkung des Augenpigmentes Arch Ophthalmol 76:509, 1910 Quoted in Fine BS, Gilligan JH: The Vogt-Koyanagi syndrome Am J Ophthalmol 43:433-440, 1957 101 Donaldson RC et al: Uveitis and vitiligo associated with BCG treatment for malignant melanoma Surgery 76:771-778, 1974 102 Riehm W: Die neue Theorie von J Meller liber die tuberkulose Aetiologie der sympathischen Ophthalmie und die Schiecksche Eigenblutinjektion in die vordere Augenkammer Klin Monatsbl Augenheilkd 90:477-485, 1933 103 Fine BS, Gilligan JH: The Vogt-Koyanagi syndrome Am J Ophthalmol 43: 433-440, 1957 104 McPherson SO, Wood AC: The significance of the intracutaneous test for hypersensitivity to uveal pigment Am J Ophthalmol 31:35-45, 1948 105 Kahan A et al: Pigment Autoagression in der Pathogenese es Vogt-Koyanagi-Harada syndroms Albrecht von Graefes Arch Klin OphthalmoI167:246-264, 1964 106 Hammer H: Lymphocytic transformation in sympathetic ophthalmitis and the Vogt-Koyanagi-Harada syndrome Br J Ophthalmol 55:850-852, 1977 107 Tagawa Y: Lymphocyte-mediated cytotoxicity against melanocyte antigens in Vogt-Koyanagi-Harada disease Jpn J Ophthalmol 22:36-39, 1978 ALEZZANDRINI SYNDROME 108 Cremona AC et al: Vitiligo, poliosis and unilateral macular degeneration Arch Oftalmol Buenos Aires 36:102-106, 1961 109 Alezzandrini AA: Manifestations unilaterales de degenerescence tapeto-retinienne de vitiligo, de poliose, des cheveux blancs et d'hypoacousie Ophthalmologica 147:409-419, 1964 SENILE GRAYING OF HAIR 110 Hollingsworth JW et al: Correlations between tests of aging in Hiroshima subjects-an attempt to define "physiologic age." Yale J BioI Med 38:11-26, 1965 111 Fitzpatrick TB et al: Age changes in the human melanocyte system, Advances in Biology of Skin Edited by W Montagna New York, Pergamon, 1965, vol VI, pp 35-50 112 Keogh EV, Walsh RJ: Rate of greying of human hair Nature 207:877-878, 1965 113 Burch PRJ et al: The age-prevalence of arcus senilis, greying of hair and baldness Etiological consideJ:'ations J Gerontol 26:364-372, 1971 114 Boas F, Michelson N: The graying of hair Am J Phys AnthropoI17:213-228, 1932 115 Straile WE: A study of the hair follicle and its melanocytes Dev BioI 10:45-70, 1964 116 Wade WG et al: A study of two families with multiple autoimmune disease Irish J Med Sci 3:463-473, 1970 117 Conrad RA: An attempt to quantify some clinical criteria of aging J GerontoI15:358-365, 1960 118 Ebling FJ, Rook A: Hair, in Textbook of Dermatology, 2nd ed Edited by A Rook et a1 Oxford, Blackwell, 1972, p 1628 669 MISCELLANEOUS HYPOMELANOSES 670 CHAPTER 119 Ronchese F: A comment on even whitening of senile hair Int J Dermatol11:84-85, 1972 120 Comaish S: White scalp hairs turning black-an unusual reversal of the aging process Br J Dermatol 86:513-514, 1972 121 Bloch B: Uber die Entwicklung des Haut- und Haarpigmentes beim menschlichen Embryo und liber das Erliischen der Pigmentbildung im ergrauenden Haar (Ursache der Canities) Arch Dermatol Syphilol (Berlin) 135:77-108, 1921 122 Fitzpatrick TB et al: The nature of hair pigment, The Biology of Hair Growth Edited by W Montagna, RA Ellis New York, Academic, 1958, pp 255-303 123 Orlanos C et al: Das weisse Haar alterer Menschen Arch Klin Exp Dermatol 236:395 405, 1970 124 Herzberg Gusek W: Das Ergrauen des Kopfhaares Arch Klin Exp Dermatol 236:368-384, 1970 125 Kukita A et al: The electron microscopic study on dendritic cells in the hair matrix of human white and gray hair Jpn J Dermatol [BJ 81:326-334, 1971 126 Metchnikoff E: Sur Ie blanchissement des cheveux et des pails Ann Inst Pasteur Lille 15:215, 1901 127 Yosikawa H: Studies in biochemistry of copper; copper in keratinous appendages of skin Jpn J Med Sci II Biochem 3:267-272, 1937 128 Kirby GC: Greying with age: a coat-color variant in wild Australian populations of mice J Hered 65:126-128, 1974 129 Burch PRJ, Jackson D: The greying of hair and the loss of permanent teeth considered in relation to an autoimmune theory of aging J Gerontol 21:522-528, 1966 SUDDEN WHITENING OF HAIR 130 Smiley ER: Blanched hair from sudden emotions Boston Med Surg J 44: 438 440, 1851 131 Jelinek JE: Sudden whitening of the hair Bull NY Acad Med 48:1003-1013, 1972 132 Menninger-Lerchenthal E: Pliitzliches Ergrauen der Haare durch Schreck Wien Klin Wochenschr 60:295-296, 1948 133 MacLeod JMH: A case of leucodermia and leucotrichia following motor accident Br J Dermatol 49:437 438, 1937 134 Baelz (1908): Quoted by Ephraim AJ: On sudden or rapid whitening of the hair Arch Dermatol 79:228-236, 1959 135 Ephraim AJ: On sudden or rapid whitening of the hair Arch Dermatol 79: 228-236, 1959 136 Perry BC: A treatise on the Human Hair and Its Diseases New Bedford, Tauber, 1859, pp 54-67 137 Holzgraefe A: Alopecie als Symptom neurohormonaler Erkrankungen Nervenarzt 18:134-138, 1947 138 Ornsteen (1930): Quoted by Ephraim AJ: On sudden or rapid whitening of the hair Arch Dermatol 79:228-236, 1959 139 Canuto F: Quoted by Vignolo-Lutati C: Canizie precoce e psicopatie di guerra Policlinico 25:680-685, 1918 140 Landois L: Das pliitzliche Ergrauener Haupthaare Arch Pathol Anat Physiol 35:575-599, 1866 141 Raymond (1882): Quoted by Ephraim AJ: On sudden or rapid whicening of the hair Arch Dermatol 79:228-236, 1959 142 Hoff F: Akuter totaler Pigmentverlust Dtsch Med Wochenschr 79:284-287, 1954 143 Gowers WR: A letter on metallic poisoning Lancet 2:1173-1176, 1901 144 von Stieda L: 1st Pliitzliches Ergrauen des Haupthaares miiglich? Wien Med Wochenschr 36:1484-1487, 1910 145 Hebra Kaposi: Quoted by Ephraim AJ: On sudden or rapid whitening of the hair Arch Dermatol 79:228-236, 1959 146 Brown-Sequard M: Experience demontrent que les poils pouvent passer rapidement du noir au blanc chez l'hamme Arch Physiol 2:442 443, 1869 147 Editorial: Sudden whitening of hair Br Med J 1:504, 1973 148 Klingmuller G: Sudden graying of hair Hautarzt 24:44 45, 1973 149 Ronchese F: A comment on uneven whitening of senile hair Int J DermatolI3:84-85, 1974 150 Vauquelin: Quoted in Ephraim AJ: On sudden or rapid whitening of the hair Arch Dermatol 79:228-236, 1959 151 Metchnikoff E: On the process of hair turning white Proc R Soc Lond 69:156, 1901-1902 152 Helm F, Milgrom H: Can scalp hair suddenly turn white? Arch Dermatoll02:102-103, 1970 153 Burton JL: Canities of rapid onset due to diffuse alopecia Practitioner 205:655 656, 1970 154 Damste TJ: A case of alopecia with acute pigment loss Dermatologica 136:440, 1968 155 Klingmiiller G: Dber "plotzliches Weisswerden" und psychische Traumen bei der Alopecia areata Dermatologica 117:84-92, 1958 156 Lehnert W: Beitrag zur Frage des "plotzlichen Weisswerdens" von Korperhaaren Dtsch Gesund 26:740-743, 1971 157 Montgomery PR: White overnight? (letter) Br Med J 1:300,1967 158 Lerner AB: Vitiligo Prog Dermatol 6:1 6, 1972 158a Guin JD et al: Immunofluorescence findings in rapid whitening of scalp hair Arch Dermatol 117:576-578, 1981 ALOPECIA AREATA 159 Demis J, Weiner MA: Alopecia universalis, onychodystrophy, and total vitiligo Arch Dermatol 8:195-201, 1963 160 Van Scott EJ: Morphologic changes in pilosebaceous units and anagen hairs in alopecia areata J Invest Dermato! 31:35-38, 1958 161 Ortonne J-p, Jeune R: Hair color and alopecia areata Arch Dermatol114:1716, 1978 162 Lubowe II: Pigmentation in alopecia totalis Arch Dermato! 77:593-594, 1958 VAGABOND'S LEUKOMELANODERMA 163 Bondet M: Melanodermic parasitaire Lyon Med 70:262-264, 1892 164 Habermann R: Paratypishe Pigmentanomalien, in Toxicodermien Edited by E Guttmann et a1 Handbuch der Haut- und Geschlechtskrankheiten, IV Berlin, Springer-Verlag, 1933, pp 854-856 165 Pautrier LM, Levy G: Maladie des vagabonds et melanodermie generalisee Bull Soc Fr Dermatol Syphiligr 32:172-175, 1925 166 Pautrier LM et al: Maladie des vagabonds et melanodermie generalisee (contribution a I'etude des melanodermies) Bull Soc Fr Dermatol Syphiligr 34:249-253, 1927 167 Jeghers H: Pigmentation of the skin N Eng! J Med 231:122-136, 1944 168 Greenhow EH: A case of vagabond's discoloration simulating the bronzed skin of Addison's disease Trans Clin Soc Lond 9:44-47, 1876 169 Lanzerberg MP: Maladie des vagabonds, avec pigmentation de la mugueuse buceale Opposition avec un autre malade atteint de phtiriase et d'un autre type de melanodermie Bull Soc Fr Dermatol Syphiligr 39:293-295, 1932 170 Becker SW, Obermayer M: Modern Dermatology and Syphilology Philadelphia, Lippincott, 1940, pp 3-7 171 Marie P, Guillain G: Melanodermie de cause incertaine (maladie d'Addison ou maladie des vagabonds) Bull Mem Soc Med Hop Paris 19:198-203, 1902 172 Thiers H et al: Deux cas de melanodermie des vagabonds Etude des epreuves de fonctionnement surrena1 Bull Soc Fr Dermatol Syphiligr 72:82-83, 1965 173 Grosshans E et al: La leucomelanodermie des vagabonds Etude anatomopathologique et ultrastructurale Ann Dermatol Syphiligr (Paris) 99:141-166, 1972 HETEROCHROMIA IRIDES AND HORNER SYNDROME 174 Gladstone RM: Development and significance of heterochromia of the iris Arch Neurol 21:184-192, 1969 671 MISCELLANEOUS HYPOMELANOSES 672 CHAPTER 175 Grimson BS, Thompson HS: Drug testing in Horner's syndrome, in Neuroophthalmology 176 Calhoun FP: Causes of heterochromia irides with special reference to paralysis of the cervical sympathetic Am J Ophthalmol 2:255-269, 1919 177 Durham DG: Congenital hereditary Horner's syndrome Arch Ophthalmol 60: 939-940, 1958 178 Angelucci A: Sulle alterazioni trofiche dell'occhio che nei manniferi seguono Ie estirpazione del gangl ganglio cervicale superiore de sympatico Arch Ottalm 1:1-100, 1893 179 Mayou MS: Heterachromia iridis associated with paralysis of the sympathetic in early life Trans Ophthalmol Soc UK 30:196-197,1910 180 Bistis J: Etude clinique et experimentale sur Ie r61e du sympathique dans l'etiologie de l'heterochromie Arch Ophtalmol 45:569-595, 1928 181 Duke Elder S (Ed): System of Ophthalmology, Vol London, Harry Kimpton, 1964 182 Lazarescu D, Lazarescu E: Heterochromia neurogene de l'iris et syndrome de Claude Bernard-Horner: observation clinique et recherches experimentales Ann Oculist 170:767-771, 1933 183 Makley TA, Abbott K: Neurogenic heterochromia; report of an interesting case Am JOphthalmol 59:927-928, 1965 184 Waardenburg PJ: Over ongelijke iristeleur bij verlamming van den nevus sympathicus Ned Tijdschr Geneeskd 64:1929-1941, 1920 Quoted in Gladstone RM: Development and significance of heterochromia of the iris Arch Neurol 21:184-192, 1969 185 Weber E: Ober einen feltenen Fall von heterochromia Iridis Klin Monatabl Augenheilkd 106:719, 1941 186 Laties AM, Lerner AB: Iris colour and relationship of tyrosinase activity to adrenergic innervation Nature 255:152-153, 1975 SCLERODERMA 187 Jablonska S: Cutaneous lesions in systemic scleroderma (progressive systemic sclerosis), in Scleroderma and Pseudoscleroderma Edited by S Jablonska Warsaw, Polish Medical Publishers, 1975 pp 243-276 188 Jablonska S: Localized scleroderma, in Scleroderma and Pseudoscleroderma Edited by S Jablonska Warsaw, Polish Medical Publishers, 1975, pp 277-303 189 Szczepanski A: Studies of rheobase and sensory chromaxy in an appraisal of the role of the nervous system in cases of the coexistence of circumscribed scleroderma with vitiligo Przegl Dermatol 60:219-222, 1973 190 Szczepanski A: Clinical and etiopathological appraisal of diffuse scleroderma with skin depigmentation Przegl Dermatol 60:323-326, 1973 191 Ortonne J-p, Perrot H: Scleroderma: ultrastructural study of the melanin pigmentary disturbances of the skin Clin Exp Dermatol 5:13-25, 1980 192 Guillaum A et al: A propos de deux cas de sclerodermie generalisee chez l'Africain Bordeaux Medical 11:101-105, 1978 IV Leukodermas without Hypomelanosis NEVUS ANEMICUS Nevus anemicus, first described by Vomer [1] in 1906, is a congenital malformation characterized by macules of varying size and shape which appear distinctly pallid compared to the surrounding skin Clinical Features Nevus anemicus is rare Piorkowski [2] observed only seven cases in 19 years However, as the disease is asymptomatic and causes no cosmetic disfigurement, it is likely that few affected patients seek medical counseling It is more frequent in women [3] The lesion is present at birth Most patients are generally in good health, but nevus anemicus has been reported in patients with von Recklinghausen disease [3,4] and with multiple vascular malformations [5] But there is no data supporting an increased incidence; the incidence in the general population is unknown Clinical Description Usually, nevus anemicus appears as a large area of pale skin with sharply outlined irregular borders surrounded by satellite macules (Fig 285) Sometimes it appears as a number of grouped small macules "arranged like the fronds of a maidenhair fern" [6] (Fig 286) Nevus anemicus is usually located on the trunk, most commonly on the chest However, involvement of the face and extremities has been reported [4,7,8] A patient with a linear nevus anemicus on an arm has been described [2] The epidermis appears otherwise normal and the condition is usually asymptomatic There are no local sensory abnormalities Several simple tests facilitate the diagnosis: Under the Wood's light, nevus anemicus seems to disappear This clearly establishes that the decreased color of the involved skin is not secondary to decreased melanin content Pressure on the border of the lesion with a glass slide renders the area of the nevus 673 674 PART IV FIGURE 285 Large area of pale skin surrounded by small satellite macules Even with suninduced pigmentation, in the right part of the picture the nevus anemicus is still apparent indistinguishable from that of the blanched surrounding skin [21 Vigorous rubbing or prolonged application of heat or cold to the affected area fails to induce erythema in the nevus area in contrast to normal surrounding skin which reacts with intense vasodilatation Histology The histology is normal [9] In the affected areas, hematoxylin-eosin-saffran stains reveal normal papillary and subpapillary vasculature Alkalinephosphatase histochemical preparations show intact vasculature indistinguishable from uninvolved skin [3] Electron Microscopy Electron microscopy of involved skin is normal [10] 675 LEUKODERMAS WITHOUT HYPOMELANOSIS FIGURE 286 a, b: Grouped small macules of pale skin with sharply outlined borders "arranged like the fronds of a maidenhair fern " 676 PARTlY Pathogenesis Nevus anemic us is a vascular phenomenon Since no anatomic abnormalities have been identified in the vasculature of the involved skin, nevus anemicus must result from a physiologic vascular abnormality Nevus anemicus is fascinating because it is a purely functional congenital disorder Greaves et al [10] suggested that nevus anemicus may justifiably be called "pharmacological nevus." Inquiry into the nature of the vascular reaction pattern anomaly has provoked some observations and studies Vomer [1] noted that it was difficult to produce urticaria factitia within a nevus anemicus Piorkowski [2] concluded, from physiologic studies of nevus anemicus, that "the cause of the disease is a permanent tonic constriction" of the vasculature Butterworth and Walters [11) hypothesized that the underlying defect is in the effector cells of the arterioles Fleisher and Zeligman [3) noted that intralesional injection of acetylcholine, pilocarpine, histamine, or serotonin failed to produce vasodilatation in the affected areas and concluded that the defect may be "at the motor endplate or at the smooth muscle effector cells of the blood vessels, perhaps associated with an increased stimulation of the vasoconstrictor fibers or of inhibition of the vasodilator fibers of the arterioles." Greaves et al [10] concluded that the immediate cutaneous abnormality is sustained adrenergic vasoconstriction Abolition of visible evidence of the nevus by a sympathetic block suggested sympathetic vasoconstriction produced the nevoid pallor The lowered threshold of the nevus vessels to the blanching effect of levarterenol suggested increased sensitivity of cutaneous blood vessels to catecholamines as important to the production of the nevoid pallor However the possibility of increased adrenergic sympathetic tone due to increased local catecholamine concentration in nevus anemic us could not be excluded Transplant studies demonstrated donor dominance [9) Transplanted skin biopsies retained their original characteristics and did not assume those of the receptor site The defect seems to be an increased sensitivity of blood vessels to catecholamines and not increased adrenergic stimulation Diagnosis and Differential Diagnosis (Table 135) The diagnosis of nevus anemicus is easily established clinically Wood's light examination, local reactivity after vigorous stroking, heat, or cold exposure clearly distinguish nevus anemic us from leukoderma related to melanin abnormalities Histologic and ultrastructural studies are not helpful Treatment Fortunately, nevus anemicus induces only a slight cosmetic disfigurement, because no effective treatment is available TABLE 135 Clinical Features in Nevus Anemicus Frequency Age of onset Sex Shape and size Borders Color Distribution Extent Local symptomatology Wood's light examination Stroking, heat, or cold exposure Associated findings Rare Birth More frequent in females Variable: large area with small satellite spots; grouped small spots Irregular, sharply outlined Slightly paler than normal skin Trunk, face, extremities Localized None No contrast with normal skin Absence of vasodilatation Usually none EDEMA OF THE SKIN Cutaneous edema renders the skin more pallid than normal This may result from altered transmission through and reflection from the affected tissues [12) Separation of the structural elements of the skin from each other because of the presence of edema fluid results in decreased absorption of light Possibly intra- or extracellular edema also disturbs melanosome transfer ANEMIA Decreased levels of circulating oxyhemoglobin in anemic states induce a pallor which is most readily detected in areas where there is physiologically less melanin (palms and soles, mucous membranes) The degree of pallor in the skin is inversely proportional to the hemoglobin content of the blood Pallor also results from decreased cutaneous blood perfusion, as in Raynaud phenomenon However, nevus anemicus is the only focal leukoderma secondary to decreased oxyhemoglobin content of the skin that can be confused with melanin disturbances REFERENCES Vomer H: Uber Naevus anaemicus Arch Dermatol Syphilol (Berlin) 82:391-398, 1906 Piorkowski FO: Naevus anaemicus (Vomer) Arch Dermatol Syphilol 50:374-377, 1944 Fleisher TL, Zeligman I: Nevus anemicus Arch Dermatol100:750-755, 1969 Naegeli 0: Naevi anaemici und Recklinghausensche Krankheit Arch Dermatol Syphilol (Berlin) 121:742-745, 1915 Weber FP: Case of nevus anemicus Br J Dermatol 41:119-120, 1929 Little EGG: Case of nevus anemicus Br J Dermatol 33:25-26, 1921 Lane J: Naevus anaemicus J Cutan Dis 34:602-604, 1916 MacKee GM: Case report presented before the Manhattan Dermatologic Society J Cutan Dis 36:200-201, 1918 677 LEUKODERMAS WITHOUT HYPOMELANOSIS 678 PART IV Daniel RH et al: Nevus anemicus Arch Dermotol 113:53-56, 1977 10 Greaves MW et al: Nevus anemicus: a unique catecholamine-dependent nevus Arch Dermotol 102:172-176, 1970 11 Butterworth T, Walters JD: Observations and pharmacologic responses of Vomer's nevus anemicus Arch Dermotol Syphilol 66:333-339, 1952 12 Jeghers H, Edelstein LM: Pigmentation of the skin, Signs ond Symptoms, 5th ed Edited by eM MacBryde, RS Blacklow Philadelphia, Lippincott, 1970 Index Achromic guttate parapsoriasis, 512 Addison disease and vitiligo, 191 Albinism with hemorrhagic diathesis, 75 and immunodeficiency, 87 ocular, 89 optic pathway abnormalities, 92 Albinism, oculocutaneous, 59 classification, 61 incidence, 63 tyrosinase-negative, 65 tyrosinase-positive, 69 yellow-mutant, 74 Albino, 61 Alezzandrini syndrome, 641 Alopecia areata, 656 Alpha-dendritic cells, see Indeterminate cells Amelanosis, 37 Arsenic, 499 Ascorbic acid in vitiligo, 237 Ataxia-telangiectasia, 433 other cutaneous features, 433 systemic abnormalities, 434 Basement membrane in vitiligo, 233 Benoquin, therapeutic use in vitiligo, 284 Bird-headed dwarfism, 465 Bleeding times in vitiligo, 241 Bloch-Sulzberger syndrome, 422, 427 Butyrophenone, 500 Canities, 37 Chediak-Higashi syndrome, 79; see also Depigmentation, chemically indiced Chemical hypomelanosis, 479 mechanism of action, 489 Chloroquine diphosphate, 501 Clofazimine, therapeutic use in vitiligo, 284 Copper, in vitiligo, 235 Copper deficiency, 102, 470 hereditary, 103 in infants, 103 nutritional, 102 Corticosteroids, therapeutic use in vitiligo, 282 Cross-McKusick-Breen syndrome, 88 Cushing syndrome and hypomelanosis, 473 Cutaneous blood flow in vitiligo, 239 Cystathionine synthetase deficiency, 119 Darier-White disease, 452 Delayed tanning, 27 Dendritic cells in vitiligo, 227 Depigmentation, 37 chemically induced, 479 diagnosis, 492 mechanism of action, 489 treatment, 492 and corticosteroids, 499 in vitiligo, 284 Dinitrochlorobenzene, 498 Dopa melanin precursor, therapeutic use in vitiligo, 283 Down syndrome, 465 Dyschromatosis symmetrica, 440 clinical features, 440 diagnosis, 443 incidence, 440 Dyschromatosis universalis hereditaria, 440 clinical features, 440 diagnosis, 443 incidence, 440 Dyschromia, 469 Dyschromic hair, 468 Dystrophia myotonica, 462 Endocrine disorders and hypomelanosis, 473 Epidermal dendritic cells, 679 680 INDEX Epidermal melanin unit, Epinephrine and depigmentation, 502 Eserine, 502 Eumelanin, Fanconi syndrome, 461 Fisch syndrome, 464 Focal dermal hypoplasia syndrome, 456 Furocoumarins, 261 Gastric function abnormalities and vitiligo, 195 Gastroenteropathies, 219 Guanonitrofuracin and depigmentation, 497 Hair, pigmentary changes in Kwashiorkor, 467 in malabsorption syndromes, 470 in nephrosis, 470 in ulcerative colitis, 470 Hair pigmentation disorders, 461 Hallerman-Streiff syndrome, 465 Halo nevus, 567 clinical features, 572 electron microscopy, 586 histology, 583 incidence, 570 pathogenesis, 599 and vitiligo, 581 Halo phenomena, 595 Harada disease, 627 Hematologic disorders in vitiligo, 217 Hereditary premature canities, 464 Hermansky-Pudlak syndrome, 75 Herpes zoster, 544 Heterochromia irides, 662 Histidinemia, 107 Homocystinuria, 119 Horner syndrome, 662 Hydroquinone, therapeutic use, 284, 492 Hyperthyroidism and premature graying of hair, 473 Hypogonadism and hypomelanosis, 474 Hypomelanoses, 467 and copper deficiency, 470 and endocrine disorders, 473 and iron deficiency, 470 and metabolic disorders, 470 and nutritional disorders, 467 in possible ectodermal dysplasia syndromes, 460 and Vitamin B'2 deficiency, 471 Hypomelanosis; see also Leukoderma associated with neoplasms, 567 cellular and subcellular basis for, 53 chemical, 479 circumscribed, 129 classification, 38, 60 Hypomelanosis (cont.) and endocrine disorders, 52, 473 hereditary, 42, 60 infectious, 523 and inflammation, 509 following irradiation, 475 of Ito, 423, 425 and neurocutaneous disorders, 52 with oculocutaneous albinism, 59 parasitic, 523 pathogenesis, 54 following physical trauma, 475 of scalp hair, 39 theoretical mechanisms, 55 Wood's light examination, 49 Hypomelanotic disorders, 57 with circumscribed hypomelanosis, 129 with generalized decreased pigmentation, 102 genetic and congenital, 59 Hypopigmentation and microphthalmia, 88 with punctate kerotosis of the palms and soles, 458 Hypopituitarism and hypomelanosis, 473 Hutchinson-Gifford syndrome, 463 Idiopathic guttate hypomelanosis, 619 Immediate pigment darkening, 27 Incontinentia pigmenti, 422 development anomalies in, 432 diagnosis, 430 hypopigmentation in, 427 nervous system abnormalities in, 431 ocular anomalies in, 431 Incontinentia pigmenti achromians, 411 clinical findings, 412 diagnosis, 425 familial, 412 histology and electron microscopy, 420 incidence, 412 systemic findings, 418 pathogenesis, 421 Indeterminate cells, 7, 232 Inflammation and hypomelanosis, 509 Kappa chain deficiency, 464 Keratinocytes, in vitiligo, 233 Koebner phenomenon, 163 Kwashirokor, 467 associated findings, 469 depigmentation in, 467 diagnosis, 469 histology, 468 pathogenesis, 468 Langerhans cells, 7, 228 Leprosy, 523 diagnosis, 533 histology, 529 Leukoderma; see also Hypomelanosis diagnosis, 37 chemically induced, 479 eye examination, 51 histology and electron microscopy, 51 without hypomelanosis, 673 physical examination, 41 Wood's light examination, 49 Leukoderma acquisitum centrifigum, 567; see also Halo nevus Leukoderma lenticular disseminata, 619 Leukomelanoderma, 37 Leukopigmentary nevus, 567 Lupus erythematosus, 213, 509 Macular tropical hypochromia, 627 MBEH, see Hydroquinone Melanin formation, Melanin metabolites in vitiligo, 238 Melanin pigmentary system, Melanin pigmentation, biologic basis of, 11 Melanin synthesis, inhibitors of, in vitiligo, 237 Melanization of melanosomes, 14 Melanocyte function, 24 Melanocytes melanosome formation in, 11 origin of, racial differences, 23 variation in, 20 Melanogenesis, regulation and variables, 20 Melanoprotein, 14 Melanosome formation in melanocytes, 11 Melanosome organization, 13 Melanosome-stimulating hormone, 16, 25 Melanosomes degradation of, 19 movement within melanocytes, 15 transfer of, 16 Melatonin, 26 Menkes Kinky Hair syndrome, 103 Mephenesin carbamate, 498 Metabolic disorders and hypomelanosis, 467 Methionine malabsorption syndrome, 123 Methionine metabolism disorders, 119 MSH, see Melanosome-stimulating hormone Neoplasms and hypomelanoses, 567 Neural crest, Neurofibromatosis, 438 Neuromelanin, Nevus anemicus, 37,40,673 Nevus depigmentosus, 424 clinical features, 398 diagnosis, 409 histology and electron microscopy, 406 treatment, 410 Nitrogen mustard, 499 Nutritional disorders and hypomelanoses, 467 Oasthouse urine disease, 123 Occupational leukoderma, 483 Ocular albinism, 89 Oculocerebral-hypopigmentation syndrome, 88 Oculocutaneous albinism, 59 Oculocutaneous albinoidism, 89 Onchocerciasis, 555 Pangeria, 462 Parapsoriasis, 512 Paratertiary amyl phenol and hypomelanosis, 485 Paratertiary butyl phenol and hypomelanosis, 485 Parkinson disease, 215 Perinevoid leukoderma, 567 Perinevoid vitiligo, 567 Pernicious anemia, 471 Phaeomelanin, Phenolic compounds, 480, 482 Phenolic de pigmenting agents, therapeutic use, 492 Phenylketonuria, 109 enzymatic defect in, 116 pathogenesis of melanin in, 117 pigmentary dilution in, 110 Phototoxic drugs, 503 Piebaldism, 310 with deafness (Woolf syndrome), 326, 369 diagnosis, 321, 333 distinguished from vitiligo, 321, 333 heredity, 317 histology and electron microscopy, 328 incidence, 313 pedigrees, 314 systemic findings, 324 Pierre Robin syndrome, 465 Pigmentary demarcation line, 444 Pigmentation, genetic control of, 22 hormonal factors, 25 human, 23 mouse models, 22 neural control, 26' nutritional and metabolic factors, 26 tissue factors in control of, 24 Pinta, 536 Pityriasis alba, 516 Poliosis, 37 681 INDEX 682 INDEX Porphyria, 213 Post-kala-azar dermatosis, 559 Premature aging syndromes, 462 Premature graying of scalp hair, 40 and vitiligo, 207 with Waardenburg syndrom, 344 Premolar aplasia, hyperhidrosis and canities prematura, 461 Progeria, 463 Protein deficiency, 467 Psoralens, 260 absorption spectra, 261 pharmacology, 262 photosensitization, 263 therapeutic use, 267 side effects, 279 Psoriasis, 513 Quinacrine, therapeutic use in vitiligo, 283 Rothmund-Thomson syndrome, 462 Rozycki syndrome, 452 Sarcoidosis, 613 Scleroderma, 663 Seckel syndrome, 465 Senile graying of hair, 641; see also Canities Sensory function of skin, in vitiligo, 238 Skin temperature in vitiligo, 239 Sudden whitening of hair, 651 Sulfhydryl compounds and depigmentation, 496 Sutton's nevus, see Halo nevus Sweat secretion in vitiligo, 240 Syphilis endemic, 542 secondary, 543 Thiambutosine, therapeutic use in vitiligo, 284 Thiamine in vitiligo, 237 Thyroid disease and vitiligo, 182 Tietz syndrome, 123 Tinea versicolor, 545 diagnosis, 555 electron microscopy, 551 histology, 547 treatment, 555 Treacher-Collins syndrome, 465 Trichochrome, Trichopoliodystrophy, 103 Triparanol 498 Tuberculosis, 562 Tuberous sclerosis, 375 clinical features, 376 diagnosis, 392 histology and electron microscopy, 386 systemic manifestations, 391 Tyrosinase, in vitiligo, 234 Tyrosinase inhibitors, 27 Tyrosine-melanin pathway, Ultraviolet radiation, control of pigmentation by, 27 Vagabond's leukomelanoderma, 657 Vesicoglobular bodies, 14 Vitamin BI2 deficiency, 471 Vitiligo and Addison disease, 191 and alopecia areata, 205 animal models, 241 and associated disorders, 182 and atopic dermatitis, 211 auditory changes, 177 and autosomal recessive deafness, 452 biochemical studies, 234 and blood groups, 178 classification, 165 clinical features, 132, 145 composite hypothesis, 257 confusion with leprosy, 129 and diabetes mellitus, 198 diagnosis, 258 distribution of depigmented macules, 153 and dysglobulinemia, 216 familial 135 functional abnormalities of skin, 238 and gastric function abnormalities, 195 and gastroenteropathies, 219 and hematologic disorders, 217 hepatobiliary disease, 216 histologic findings, 225 history, 129 and hypogonadism, 214 and hypoparathyroidism, 204 and hypopituitarism, 214 and idiopathic heart block, 220 immune hypothesis, 243 incidence, 132 involvement of hair in, 161 isomorphic phenomenon, 163 and lichen planus, 211 and lichen sclerosus et atrophicus, 213 and lupus erythematosus, 213 and malignancies, 217 and multiglandular insufficiency syndromes, 200 and myasthenia gravis, 220 neural hypothesis, 250 and Parkinson disease, 215 and pernicious anemia, 194 and porphyria, 213 precipitating factors, 140 pregnancy, 144 Vitiligo (cont.) psoralen and ultraviolet radiation therapy, 260 and psoriasis, 207 psychologic factors, 141 repigmentation, 260, 265 and rheumatoid arthritis, 215 self-destruct hypothesis, 256 and thyroid disease, 182 trauma, 143, 163 treatment, 258 Vitiligo-like leukoderma and melanoma, 208 Vogt-Koyanagi-Harada syndrome, 627 clinical features, 630 diagnosis, 640 etiology, 638 pathologic findings, 635 Waardenburg syndrome, 337 abnormalities in, 341 animal models, 339 deafness in, 356 "deficient neural crest" theory, 357 Waardenburg syndrome (cont.) diagnosis, 363 dystopia canthorum in, 354 as First Arch syndrome, 359 histopathology and electron microscopy, 348 incidence, 340 "Intrauterine necrosis" theory, 361 ocular pigmentary abnormalities, 350 and status dysraphicus, 360 Werner syndrome, 462 White forelock in piebaldism, 318 Woolf syndrome, see Piebaldism, with deafness Woronoff's ring, 513 Xeroderma pigmentosum, 435 X-ray depigmentation, 475 Yaws, 534 Ziprkowski-Margolis syndrome, 373 683 INDEX ... [22 ], generalized lentigines [22 ], senile lentigines [22 ], seborrheic keratoses [22 ], berloque dermatitis [22 ], hyperpigmented scars [21 ], and normally melanized skin in vitiligo patients [22 ]... [18 -22 ], postinflammatory hyperpigmentation [22 ], benign acanthosis nigricans [22 ], idiopathic melanoderma [22 ], congenital eyelid melanosis [22 ], pigmented nevi [22 ,23 ], Riehl melanosis [24 ],... anemia, 14 (11 .2% ) had graying of the hair before the age of 20 , compared to only three out of 1 32 controls (2. 2%) Furthermore, early graying of the hair (between 20 and 50 years of age) was more