Sec 11 Disorders of Melanocytes Flashcards
1
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Ratio of melanocyte to keratinocytes
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1:5-6
2
Q
Pigmented polymer that is stored in cytosolic organelles
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Melanin
3
Q
Cytosolic organelles that are transferred to keratinocytes through melanocyte dendritic processes
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Melanosomes
4
Q
Describes a single epidermal melanocyte surrounded by several epidermal keratinocytes
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Epidermal melanin unit
5
Q
Major differentiated function of melanocytes
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To synthesize melanin in specialized organelles within the melanocytes, the melanosomes, and to transfer melanosomes to neighboring keratinocytes in order to provide protection from UV irradiation
6
Q
Are large (∼0.9 × 0.3 mm), elliptical in shape and contain a highly structured fibrillar glycoprotein matrix required for eumelanin synthesis.
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Eumelanosomes
7
Q
Are smaller (∼0.7 mm in diameter), spherical in shape and their glycoprotein matrix appears disorganized and loose
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Pheomelanosomes
8
Q
Dark, brown–black, and insoluble melanin
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Eumelanin
9
Q
Light, red–yellow sulfur-containing, and soluble melanin
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Pheomelanin
10
Q
Critical rate-limiting step in melanogenesis
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Conversion of tyrosine to DOPA
11
Q
The main function of melanin
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To provide protection against UV-induced DNA damage by absorbing and scattering UV radiation (280–400 nm).
12
Q
These proteins act as short cross-bridge structures connecting the organelle to the microtubules.
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Kinesins (centrifugal, anterograde)
Dyneins (centripetal)
13
Q
Potent stimulators of melanogenesis
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MSH and ACTH
14
Q
A diffusible free radical displaying pleiotropic bioregulatory effects in diverse cells and tissues which are produced by melanocytes and keratinocytes in response to inflammatory cytokines. Its production in keratinocytes is induced by UV irradiation increasing tyrosinase activity and melanogenesis
A
Nitric Oxide
15
Q
A group of signaling molecules, primarily functioning as neurotransmitters and as endocrine hormones
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Catecholamines
16
Q
Most common inherited disorder of generalized hypopigmentation, with an estimated frequency of 1 in 20,000 in most populations.
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Oculocutaneous albinism (OCA)
17
Q
Results from the dysfunction of a normal complement of pigment cells, which results in complete or partial loss of cutaneous pigmentation.
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Albinism
18
Q
Caused by loss of function of the melanocytic enzyme tyrosinase resulting from mutations of the TYR gene. Most common type in non-Hispanic Caucasian patients.
A
OCA1
19
Q
There is a complete inability to synthesize melanin in skin, hair, and eyes, resulting in the characteristic “albino” phenotype. They are born with white hair and skin and blue eyes, and there are no changes as they mature. The hair may develop a slight yellow tint due to denaturing of the hair protein due to sun exposure and/or shampoo use. The irides are translucent, appear pink early in life, and often turn a gray–blue color with time. No pigmented lesions develop in the skin.
A
OCA1A
20
Q
Can range from minimal hair pigment to skin and hair pigmentation approaching the normal pigmentary phenotype for the individual’s genetic composition and continental ancestry. Most have very little or no pigment at birth and develop varying amounts of melanin in the hair and skin in the first or second decade of life. The hair color changes to light yellow, light blond, or golden blond first, as a result of residual pheomelanin synthesis, and eventually can turn dark blond or brown in adolescents and adults. The irides can develop light-tan or brown pigment, sometimes limited to the inner third of the iris, and iris pigment can be present on globe transillumination. Many individuals will tan with sun exposure. Pigmented lesions (nevi, freckles, lentigines) develop in the skin of individuals who have developed pigmented hair and skin.
A
OCA1B
21
Q
Due to mutations of the P gene, which maps to chromosome arm 15q
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OCA2
22
Q
Hair is yellow at birth and remains so throughout life, although the color may turn darker. The skin is creamy white at birth and changes little with time. No generalized skin pigment is present, and no tan develops with sun exposure, but pigmented nevi, lentigines, and freckles often develop, since the cutaneous melanocytes in these individuals both remain susceptible to ultraviolet (UV)induced changes early in life and retain some ability to synthesize melanin later. The irides are blue–gray or light tan or brown.
A
OCA2
23
Q
Due to mutations in the TYRP1 gene
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OCA3
24
Q
Distinct OCA phenotype in which the skin color is a mahogany brown with a slight reddish hue, and the hair color varies from deep mahogany to sandy red.
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Rufous OCA
25
Due to dysfunction in trafficking cell type-specific products in cells containing lysosome-related organelles (LROs), including melanosomes in melanocytes.
Hermansky-Pudlak Syndrome (HPS)
26
These patients have OCA, with variable hypopigmentation of the skin, hair, and irides, and ocular abnormalities. They also lack platelet dense bodies and demonstrate a prolonged bleeding time, mucous membrane bleeding, a predisposition to epistaxis, easy bruising, and metromenorrhagia.
Hermansky-Pudlak Syndrome
27
Common and severe manifestation of HPS1 and HPS4.
Pulmonary fibrosis
28
A complex lipid-protein material said to accumulate in the cells of HPS patients, predominantly those with HPS1.
Ceroid lipofuscin
29
A rare autosomal recessive disorder characterized by severe immunologic defects, hypopigmentation, bleeding tendency due to absent or reduced platelet dense bodies, progressive neurologic dysfunction, and the presence of giant peroxidase-positive lysosomal granules in peripheral blood granulocytes. Mutations in the LYST (lysosomal regulator trafficking) gene have been associated with this.
Chediak-Higashi Syndrome (CHS)
30
Asyndrome combining pigmentary defects of the hair (poliosis or white forelock) and iris, congenital deafness, and developmental craniofacial abnormalities.
Waardenburg Syndrome (WS)
31
AD, usually heterozygous for mutations in PAX3; Individuals with have pigmentation abnormalities associated with craniofacial abnormalities. Dystopia canthorum, is seen virtually all cases. A broadening of the nasal root, the presence of hypoplastic alae nasi, and synophrys are other craniofacial abnormalities. Poliosis, such as the presence of a white forelock, is the most common pigmentation abnormality. Depigmented white spots on the skin occur less commonly, but are often located at the ventral midline reflecting the compromised migration of dysfunctional melanocyte precursors from their origin in the dorsal neural crest. Pigmentary abnormalities of the iris, including complete heterochromia irides (differently colored irises), partial heterochromia irides (variations of color within an iris), or hypoplastic blue irides, can also be seen as well as premature praying. Congenital deafness is present in 57% of cases.
WS1
32
This lateral displacement of the medial canthi of the eyes is the hallmark craniofacial defect found in virtually all cases of WS1.
Dystopia canthorum
33
MITF locus (15%) as a candidate locus for the disease gene. Notable for featuring only auditory-pigmentary symptoms.
WS2
34
Diagnostic criteria for WS2
Individuals fulfilling two of the following four criteria, in the absence of dystopia canthorum, limb deformity, or Hirschsprung disease, should be counted as affected:
1. Congenital sensorineural hearing loss
2. Pigmentary disturbance of iris
a. Complete heterochromia irides (two eyes of different color)
b. Partial or segmental heterochromia (segments of blue or brown pigmentation in one or both eyes)
c. Hypoplastic blue irides (characteristic brilliant blue, with thin iris stroma, in both eyes)
3. Pigmentary disturbance of the hair
a. White forelock from birth or in teens
b. Premature graying before age 30 years
4. A first- or second-degree relative with two or more of criteria 1–3
35
Also known as Klein–Waardenburg syndrome; heterozygous for a mutation in PAX3; patients have musculoskeletal abnormalities, manifested as limb contractures and hypoplasia of the limb musculature (in addition to features of WS1)
WS3
36
Also known as Shah–Waardenburg syndrome, is caused by heterozygous mutations in the transcription factor gene SOX10, or by homozygous mutations in the gene encoding the peptide ligand endothelin-3, EDN3, or its receptor, EDNRB. Associated with Hirschsprung’s disease or congenital aganglionosis of the colon.
WS4
37
A hypopigmentation–deafness syndrome resulting, like WS2, from mutations in MITF. These individuals exhibit generalized cutaneous hypopigmentation similar to that found in OCA2, rather than distinct depigmented patches. Reduced melanosomes in keratinocytes found in one affected individual 132 may account for the generalized hypopigmentation that is observed. Affected individuals invariably exhibit profound hearing loss.
Tietz Syndrome
38
Caused by mutations in the KIT proto-oncogene. Have depigmented patches on the ventral or lateral trunk and/ or the mid-extremities, sparing the hands and feet. Poliosis is a common feature. The depigmented patches tend to be larger than those observed in WS. Typically, not associated with deafness.
Piebaldism
39
Piebaldism with deafness
Woolf syndrome
40
AD condition, was recently shown to be caused by mutations in ADAR1. Patients exhibit speckled hypopigmentation, which is limited to the dorsa of the hands and feet.
Dyschromatosis symmetrica hereditaria
41
A multifactorial, polygenic disorder, with a complex pathogenesis, considered as most frequent depigmenting disorder (0.3-0.5%)
Vitiligo
42
May occur in individuals who encounter large doses of phenolic compounds, usually 4-tertiary butyl phenol (4-TBP) and other phenolic compounds that may be contained in cleaning solutions; usually initially involves the hands and forearms. It may appear at sites of skin trauma (Koebner’s phenomenon).
Occupational vitiligo
43
Principal clinical manifestation is the appearance of acquired milk-white macules with fairly homogeneous depigmentation and well-defined borders often demonstrates a predilection for sunexposed regions, body folds, and periorificial areas.
Vitiligo
44
Multiple scattered lesions distributed in a more or less symmetrical pattern; the most common presentation of GV
Vitiligo vulgaris
45
Affects the distal end of fingers and facial orifices in a circumferential pattern; a subtype of GV
Acrofacial vitiligo
46
Combination of acrofacial and vulgaris, or segmental and acrofacial types.
Mixed vitiligo
47
Complete or nearly complete depigmentation of the whole body; the most severe form of GV.
Vitiligo universalis
48
Characterized by the presence of one/few macule(s) in one area but not distributed in a segmental pattern; considered a precursor form of GV.
Focal vitiligo
49
A term reserved for depigmentation of mucous membrane alone.
Mucosal vitiligo
50
Characterized by macules having unilateral dermatomal distribution that do not cross the midline. It generally affects young children and typically remains localized, the depigmented lesions persisting unchanged for many years. The occurrence of concomitant other autoimmune diseases is uncommon, compared with GV.
Segmental vitiligo
51
Depigmentation of hair within vitiligo macules, can be quite variable (10%–60%), and is considered to indicate destruction of the melanocyte reservoir within the hair follicle, therefore, predicting a poor therapeutic response.
Leukotrichia
52
Characterized by the presence of patches of intermediate hue (hypopigmentation) between the normal skin and the completely depigmented skin.
Trichome vitiligo
53
Characterized by the presence of a fourth color (dark brown) at sites of perifollicular repigmentation. It is more often encountered in patients with darker skin phototypes.
Quadrichrome vitiligo
54
The occurrence of five shades of color: (1) white, (2) tan, (3) medium brown, (4) dark brown, and (5) black.
Pentachrome vitiligo
55
Tiny punctate-like depigmented macules on a hyperpigmented macule or on normal skin.
Confetti vitiligo or vitiligo ponctué
56
The depigmented lesions have a raised erythematous border.
Red vitiligo
57
A blue–gray appearance of the skin, which corresponds histologically with the absence of epidermal melanocytes and presence of numerous dermal melanophages.
Blue vitiligo
58
Most prevalent associated autoimmune disease with Vitiligo
Autoimmune thyroid dysfunction, either hypothyroidism (Hashimoto’s thyroiditis) or hyperthyroidism (Grave’s disease)
59
A multiorgan disorder that affects pigmented structures, such as the eye, inner ear, meninges, and skin; pointing to a role of cell-mediated immunity, particularly involving CD4 + T cells and Th1 cytokines.
Vogt–KoyanagiHarada (VKH) syndrome
60
Another very rare multiorgan disorder associates facial skin depigmentation, poliosis, deafness, and unilateral tapetoretinal degeneration of the eye.
Alezzandrini syndrome
61
Histopathology: shows an epidermis devoid of melanocytes in lesional areas, and sometimes sparse dermal, perivascular, and perifollicular lymphocytic infiltrates at the margins of early and active lesions, consistent with cell-mediated immune processes destroying melanocytes in situ.
Vitiligo
62
Considered the most effective and safest current therapy for vitiligo, and thus is currently the treatment of choice for patients with moderateto-severe GV.
Narrowband UV (NB-UVB) at 311 nm
63
Most responsive sites to NB-UVB in Vitiligo
Face, trunk, and limbs
64
Least responsive sites to NB-UVB in Vitiligo
Hands and feet
65
Represent the first-line therapy for localized vitiligo, and are highly recommended for facial or small lesions and for use in children.
Topical corticosteroids
66
Used in pulse therapy and for short periods to halt rapid spread of depigmentation in some cases of GV.
Systemic corticosteroids
67
Can be effective in vitiligo therapy because of their capacity to restore the altered cytokine network.
Calcineurin inhibitors
68
Generally preferred for treating localized vitiligo lesions of the face and neck, and more effective in combination with UV radiation delivered by high-fluency UVB devices.
Tacrolimus ointment 0.03%–0.1%
| Pimecrolimus ointment 1%
69
Restore pigmentation in vitiligo by inducing skin immunosuppression, which halts the local autoimmune process, and via direct activation of melanocytic precursors and melanogenic pathways.
Vitamin D analogs - Calcipotriol ointment (0.005%)
70
Has been used to reconstitute deficient activity of catalase in vitiligo epidermis, degrading excessive H2O2 and allowing recovery of enzyme activities in vitiligo skin.
Pseudocatalase
71
For repigmentation only in patients with stable vitiligo that is refractory or only partially responsive to medical treatment, and in general limited in extent (<3% BSA)
Autologous skin grafts
72
This technique is performed by grafting noncultured suspensions containing both keratinocytes and melanocytes; obtained by 0.25% trypsin digestion of a thin piece of donor skin and are injected into blisters raised by liquid nitrogen freezing or seeded on recipient sites denuded by superficial dermabrasion. An advantage of this method is lack of scarring if recipient and donor sites are carefully manipulated.
Noncultured epidermal suspensions
73
Grafts are harvested at a depth of 0.1-0.3 mm, placed directly on recipient abraded areas next to each other, and are secured with surgical dressings under mild pressure for 1 week. Repigmentation occurs during the following weeks. Good results have been reported on dorsal hands and fingers.
Thin Dermal-Epidermal Grafts
74
Represents the most commonly used current surgical method for vitiligo repigmentation. Multiple perforations are made on recipient sites using 1.0-1.2-mm punches 3-4 mm apart from each other. Then minigrafts are harvested from the donor site using a similar punch and are transferred to recipient sites with fine forceps or a hypodermic needle. Repigmentation occurs around each minigraft up to 2-5 mm by coalescence of spreading pigment. An advantage of this method is its simplicity.
Minigrafting
75
Grafts are harvested at negative pressure using different custom-made suction devices, the preferred donor sites being the inner aspect of the thigh and the flexor aspect of the forearm. Recipient sites are prepared by removing the epidermis using liquid nitrogen freezing or superficial dermabrasion or laser ablation. The main advantage is the absence of scarring in donor and recipient sites.
Epidermal Grafting
76
Useful for vitiligo lesions on mucous and mucocutaneous areas. It is accomplished by tattooing inert pigment granules into the dermis within collagen bundles and extracellularly at a depth of 1–2 mm, delivered by multiple electrically driven needles.
Micropigmentation
77
Achieved using 20% monobenzyl ether of hydroquinone (MBEH; monobenzone), which induces melanocyte loss via necrotic death without activating the caspase cascade or DNA fragmentation.
Depigmentation
78
Genetic disorders with reduced skin and hair pigmentation are caused by impaired melanocyte migration/differentiation
Piebaldism
Waardenburg syndrome
Tietze syndrome
79
Genetic disorders with reduced skin and hair pigmentation are caused by melanosome abnormalities
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Oculocutaneous albinism (OCA)
Griscelli syndrome (GS)
Elejalde syndrome (ES)
Chédiak–Higashi syndrome (CHS)
Hermansky–Pudlak syndrome (HPS)
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80
“Silvery hair syndromes” because hair of these patients has a particular silver–gray hue
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Griscelli syndrome (GS)
Elejalde syndrome (ES)
Chédiak–Higashi syndrome (CHS)
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81
Various degrees of skin hypopigmentation and hair with a silvery shine, usually lighter than in unaffected family members. Neurological signs and symptoms and/or immunologic impairment with “accelerated phases” of uncontrolled lymphocyte and macrophage activation with lymphohistiocytic infiltration of the central nervous system (CNS) are associated. They usually die in the first or second decade of their life if accelerated phases are not treated adequately.
Griscelli syndrome
82
Characterized by primary and severe neurological symptoms occurring early in life or even at birth without signs of an accelerated phase. These symptoms can include seizures, spasticity, psychomotor retardation, peripheral facial palsy, hemiparesis, encephalopathy, and hypotonia. CNS disorder is pertinent and never regresses with time.
GS1
83
Immunological and hematological manifestations are only observed and include: anemia, neutropenia, and lack of natural killer cell function, with development of an accelerated phase of the disease with fever, jaundice, hepatosplenomegaly, lymphadenopathy, pancytopenia, and generalized lymphohistiocytic infiltrates of various organs, including the CNS.
GS2
84
Also referred to as neuroectodermal melanolysosomal disease, is another autosomal recessive pigment mutation with silvery hair, pigment abnormalities, and severe CNS dysfunction. Do not manifest the hemophagocytic syndrome or immunological impairment.
Elejalde syndrome (ES)
85
Characterized by slightly scaling macules that can either be hypopigmented, pink or salmon-colored, or hyperpigmented variants with red and black macules have also been described caused by Malassezia species of which M. globosa, M. sympodialis, and M. Furfur are most frequently identified in lesional scales.
Pityriasis versicolor
86
A line present on upper and lower extremities corresponding to a border of transition between the more deeply pigmented skin of the outer (dorsal) surfaces and the lighter inner (ventral) surfaces.
Pigmentary Demarcation Line (Futcher line)
87
Pigmentary Demarcation Line (Futcher line)
A: upper anterolateral arms, across pectoral area
B: posteromedial portion of lower limb
C: vertical hypopigmented line in pre- and parasternal area
D: posteromedial area of spine
E: bilateral aspect of chest, marking from midthird of clavicle to periareolar skin
88
A common benign condition mainly affecting the head and neck region of preadolescent children; widely understood to represent mild atopic dermatitis. May present as a pink patch with an elevated border, fading after several weeks into a paler spot covered with powdery white scale.
Pityriasis alba
89
Variant associating classic PA with a superficial dermatophyte infection, almost always affecting the face. It is clinically characterized by a bluish hyperpigmentation, attributed to melanin deposits in the dermis surrounded by a hypopigmented scaly area.
Pigmenting Pityriasis alba
90
Hypopigmentation is a rare manifestation. Hypopigmented macular lesions scattered over the trunk and extremities but also papular or nodular lesions may be present. The presence of noncaseating dermal granulomas, usually most evident in biopsies of indurated lesions, reinforce the diagnosis.
Sarcoidosis
91
Localized hypopigmentation and/or hyperpigmentation are seen in areas of localized sclerosis. Focal depigmentation with perifollicular hyperpigmentation (“salt and pepper pigmentation”) especially on upper trunk and extremities, mimicking vitiligo, is reported in up to 30% of patients.
Scleroderma
92
Hypopigmented patches result from interface dermatitis with destruction of the epidermal basal layer containing melanocytes. “Burned out” lesions are atrophic and depigmented and may be surrounded by hyperpigmentation. Cutaneous depigmentation is also reported, usually localized to inflammatory skin lesions.
Lupus erythematous
93
It mainly develops before the fourth decade, predominantly in juvenile-onset cases and in dark-skinned individuals, without sex predilection. Irregular hypopigmented patches with variably distinct borders are preferentially located on trunk and extremities. Erythema, scaling, and infiltration may be present. A central area of normal pigmentation may be observed. The hypopigmentation develops without preceding skin changes and occasionally complete depigmentation is observed. Histopathologically, it is characterized by minimal dermal involvement, lack of epidermal atrophy, and moderate to marked exocytosis. Pigment incontinence and decrease or absence of melanin may be observed. Infiltrating lymphocytes often have a T-suppressor cell CD8 + phenotype, but a CD4 + phenotype has also been reported.
Hypopigmented Mycosis Fungoides
94
Rarely associated with itch. Hypopigmented patches with perifollicular spots of normally pigmented skin, typically occur symmetrically on the pretibial area of older people in endemic areas.
Onchocercal depigmentation or “leopard skin”
95
Develops in insufficiently treated kala-azar or visceral leishmaniasis, which is caused by L. donovani. Skin manifestations are nodules and plaques, facial erythema, and hypopigmented macules. Nodules and plaques typically develop around the mouth and spread to the face, arms and chest, but the macules may occur more generalized over the whole body.
Post-kala-azar dermal leishmaniasis
96
The presence of a hypopigmented lesion with reduced sensation is its hallmark and is one of the diagnostic criteria.
Leprosy
97
Typically presents as a pruritic erythematous patch in the early stage, evolving to a depigmented atrophic plaque with porcelain white appearance. Mechanisms include decreased melanin production, blocked transfer of melanosomes to keratinocytes, and loss of melanocytes.
Lichen sclerosus
98
Hypo- or depigmentation that can occur around the primary melanoma or metastases or at distant sites.
Leukoderma acquisitum centrifugum,
99
An acquired leukoderma, characterized by discrete, round, or oval porcelain-white macules of approximately 2–5-mm diameter, which increase in number with aging. Any associated hairs often remain pigmented. Lesions are found in a photodistribution and tend to occur in chronically sun-damaged skin.
Histologically, these are characterized by slight basket-weave hyperkeratosis with epidermal atrophy and flattening of the rete pegs. Lesions show a decrease in melanocytes and melanin content of the affected epidermis and pigment granules are irregularly distributed.
Idiopathic guttate hypomelanosis
100
Multiple punctiform hypopigmented and achromic spots after several months of PUVA treatment. Later, similar cases were described after UVB therapy for psoriasis and after topical PUVA in one case of segmental vitiligo. Lesions are predominantly present on the extremities, upper back and chest. They are round or oval, sharply demarcated, and small (0.5–1.5 mm), without follicular distribution. Spontaneous reduction of the leukodermic lesions has been observed.
Leukoderma punctata
101
A process of chronological aging that occurs regardless of gender or race. The age of onset, which appears to be hereditary, is usually in the fourth decade. Usually appears at the temples first, then the vertex, and, finally, the occiput. Beard and body hair are affected later.
Hair graying or canities
102
An entity that affects the trunk with nummular, hypopigmented nonscaly macules. It affects young adults, mainly women. It affects young adults, mainly women.
Progressive macular hypomelanosis
103
Are small, irregular apparently hypopigmented areas, usually on arms and legs in young adults, resulting in a reticulated appearance. The surrounding skin is erythematous and blanches with pressure causing the “hypopigmented” macules to disappear.
Bier spots
104
Represents a blanched halo surrounding a psoriatic lesion. It is observed after UV treatment or topical steroid treatment, but may also occur in untreated psoriasis.
Woronoff’s ring
105
Produces an appearance of leukoderma that is not true hypomelanosis. Decreased absorption of light, reduced capillary blood flow, and increased dermal thickness may contribute to the pale appearance of the skin.
Cutaneous edema
106
Characterized by hyperpigmented macules in streaky configuration along the lines of Blaschko without preceding inflammation or atrophy.
Linear and whorled nevoid hypermelanosis (LWNH)
107
An X-linked, dominantly inherited disorder, reported primarily in females, and believed to be embryonic lethal in the majority of males due to a mutation in the gene NEMO. A significant percentage of patients have ocular, dental, skeletal, and CNS anomalies. The hyperpigmentation appears in streaks and whorls along the lines of Blaschko and is usually most pronounced on the trunk, but can also appear on the extremities. The degree of hyperpigmentation varies among individuals.
Incontinentia Pigmenti or Bloch-Sulzberger syndrome
108
Four stages of Incontinentia Pigmenti
(1) vesicular stage (from birth or shortly thereafter)
(2) verrucous stage (between 2 and 8 weeks of age)
(3) hyperpigmented stage (several months of age into adulthood)
(4) hypopigmentation stage (from infancy through adulthood)
109
Characterized by reticulate skin pigmentation, nail atrophy, leukoplakia, and bone marrow failure. Bone marrow failure and malignancy develop in the second and third decades. In all characterized cases, the causative mutations are present in components of the telomerase complex.
Dyskeratosis congenita (DKC) or Zinnser–Engmann–Cole syndrome
110
Characterized by the presence of melanin-producing dendritic melanocytes in the dermis. They include the nevus of Ito, nevus of Ota, and Mongolian spot and dermal melanocyte hamartoma.
Dermal melanocytoses
111
It is characterized by blue–black or gray–brown dermal melanocytic pigmentation and typically occurs in areas innervated by the first and second branches of the trigeminal nerve. Mucosal pigmentation may occur involving conjunctiva, sclera, and tympanic membrane (oculodermal melanocytosis), or other sites. It is most frequently seen in the Asian population, has a female predominance, and is usually congenital, although appearance in early childhood or at puberty has been described.
Nevus of Ota
112
A congenital dermal melanocytosis first described as nevus fuscocaeruleus acromiodeltoideus. It can be considered as a variant of nevus of Ota but with involvement of the acromioclavicular and deltoideal region.
Nevus of Ito
113
Are congenital, benign hyperpigmentations preferentially occurring in the African, Asian, and Hispanic population and only rarely seen in Caucasians. They occur in both sexes but with a slight male predominance, usually in the sacral area. They can also be found in the gluteal and lumbar region and on the thorax, abdomen, arms, legs, and shoulders. In most cases they spontaneously regress during childhood.
Mongolian spot
114
A distinctive form of congenital dermal melanocytosis. Gray–blue pigmentation, caused by melanocytes residing in the dermis, occurs in a dermatomal pattern.
Dermal melanocyte hamartoma
115
Characterized by the presence of lentigine-circumscribed brown macules (usually < 5 mm in diameter), which display an increased number of melanocytes in the epidermis (epidermal melanocytic hypermelanosis) and an increased incidence of cardiovascular, endocrine, or gastrointestinal neoplasias.
Familial lentiginosis syndrome
116
An autosomal dominant cancer predisposition syndrome with mucocutaneous pigmentation and intestinal hamartomatous polyposis are hallmarks of the disease. The pigmentary lesions resemble those of Carney complex, with small hyperpigmented macules typically appearing in childhood (not present at birth) on the lips and buccal mucosa, but they may also involve the eyelids, hands, and feet.
Peutz–Jeghers Syndrome
117
An autosomal dominant genodermatosis with characteristic lentigines that usually develop during childhood and in the first months of life. Clinical diagnosis is primarily based on the typical facial features and the presence of hypertrophic cardiomyopathy and/or café-au-lait macules (CALMs). The disorder is caused by mutations in the PTPN11 gene, coding for the protein tyrosine phosphatase SHP-2 and situated on chromosome 12.
LEOPARD Syndrome
118
Consist of sharply bordered hyperpigmented patches of skin, varying in size from 0.5 cm to more than 20.0 cm. They are often present at birth or appear in the early months of life. Histologically, show a normal number of melanocytes but increased epidermal melanin (epidermal melanotic hypermelanosis).
Cafe Au Lait Macules
119
An autosomal dominant disease caused by a mutation in the NF1 gene, situated on chromosome 17q11.2 and encoding the neurofibromin protein. The most important neurofibromin function involves downregulation of the Ras signal transduction pathway and it is, therefore, considered a tumor-suppressor gene. It has been considered as a neurocristopathy and is characterized by a number of cutaneous and noncutaneous pigment cell-related manifestations such as CALMs, intertriginous freckling, and iris Lisch nodules.
Neurofibromatosis Type 1
120
A triad of poly/ monostotic fibrous dysplasia, CALMs, and hyperfunctioning endocrinopathies, including precocious puberty, hyperthyroidism, hypercortisolism, hypersomatotropism, and hypophosphatemic rickets. The CALMs are fewer in number and have more irregular borders than those seen in NF1.
McCuneAlbright syndrome
121
Describedas acquired, bilateral nevus of Ota-like macules termed ABNOM. It consists of blue–brown to slate-gray mottled hyperpigmentation on the face with predilection for the malar regions. Similar to nevus of Ota, it typically affects the Asian population and has a female predominance. Histologically, melanocytes with stage III or IV melanosomes reside in the upper and middle layers of the dermis.
Nevus of Hori
122
Preferentially occurs in the scapular region, although it has been described in any area of the body, and classically after an intense sun exposure. The lesion is androgen-dependent and becomes more prominent in adolescence, especially in the male population. Hypertrichosis in the lesion is often associated.
Becker's nevus
123
Small light brown macules appearing in sun-exposed skin of fairskinned individuals, often those with red or blond hair and Celtic ancestry. They are more pronounced during spring and summer and fade during the winter period.
Ephelides
124
A common condition caused by numerous preceding cutaneous insults such as drug and phototoxic reactions, infections, physical injury or trauma, allergic reactions, and inflammatory diseases. Consists of a macular hyperpigmentation at the site of inflammation. It is more common and persistent in darker skin types (Fitzpatrick types III–VI) and can be characterized by epidermal as well as dermal melanotic hypermelanosis.
Postinflammatory hyperpigmentation
125
An autosomal recessive disorder associated with increased intestinal absorption of iron and deposition of excessive amounts of iron in the liver, pancreas, and other organs, including the skin.
Hereditary hemochromatosis
