2. EL MODELO DE LAS INTELIGENCIAS MÚLTIPLES (IM) DE HOWARD
2.4. LA EVALUACIÓN DESDE EL MODELO DE LAS IM
2.4.2. El procedimiento de evaluación: El Portafolios
identifiable melanocytes. In India, the incidence of vitiligo is estimated to be between 3 and 4 %.
The term vitiligo is probably derived from the Latin word “vitium”(“blemish”). Many ancient terms are applied to this condition—
shwetakustha in the sacred Indian book, Atharva Veda (1400BC), and switra in Manusmriti (200 BC). In South India where the old Dravidian language of Tamil is spoken, the condition is known as ven kushtam—”white leprosy.”
Pathogenesis
The white macules of vitiligo are the result of a loss of melanocytes. The mechanism(s) by which the melanocytes are lost may be multiple but have not been identified unequivocally. Seven hypo-theses, not mutually exclusive, have been proposed to explain the causation of vitiligo:
• Autoimmune: Strengthened by the demonstration of specific autoantibodies to melanocyte cell surface antigens and the association of vitiligo with a variety of autoimmune disorders.
• Autocytotoxic: Also called the self-destruction theory, it proposes melanocyte destruction by intracellular retention of various precursors of melanin synthesis.
• Neural: Especially proposed to explain the segmental type of vitiligo.
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• Biochemical: Accumulation of pteridines (6-biopterin and 7-(6-biopterin) in the vitiliginous skin causes the depigmentation.
• Antioxidant deficiency theory: There is an increased level of norepinephrine and catecholamine derivatives in vitiligo skin which leads to tissue ischemia and increased activity of monoamine oxidase enzyme, which in turn causes excess production of stress related hydrogen peroxide. Reduced catalase activity in vitiligo skin leads to impaired degradation of H2O2 and accumulation of superoxide radicals causing depigmentation.
• Melanocyte growth factor reduction hypothesis:
In vitiligo, there is reduced melanocyte growth factors derived from keratinocytes, fibroblasts and other tissues.
• Intrinsic (genetic) theory: An underlying genetic/intrinsic factor predisposes some individuals to be more prone to develop vitiligo.
Clinical Features
• The diagnostic lesion of vitiligo is the typical vitiligo macule, which is of variable size, round/oval in shape, has a milky white color and scalloped margins (Fig. 15.1).
• May appear at any age, however, the peak age at onset has been reported to be five to thirty years.
• Prevalence is the same in both sexes.
• The natural course of the disease is of gradual progression, the lesions increasing both in number and size. In some cases there may be a rapid downhill course of vitiligo and this has been termed ‘galloping vitiligo’ or ‘vitiligo fulminans’.
• Segmental vitiligo and vitiligo in children have a better prognosis.
• Mucous membrane involvement is also noted in vitiligo and is commoner, or rather, easily detectable in dark-skinned races.
• Leukotrichia refers to depigmentation of the hair and may occur in some patients.
Classification of Vitiligo Localized
• Focal vitiligo: This consists of one or more macules in one area but not clearly in a segmental or zosteriform distribution .
• Segmental vitiligo: Number of macules involving a unilateral segment of the body.
The lesions stop abruptly at the midline of the affected segment (Fig. 15.1).
• Mucosal vitiligo: Vitiligo affecting mucous membranes of the lips, oral cavity or the genitalia (Fig. 15.2).
Fig. 15.1: Zosteriform vitiligo—milky white macules in a zosteriform distribution over the back.
Fig. 15.2: Vulval vitiligo—female genitalia involved by milky white lesions
Generalized
• Acrofacial vitiligo: Lesions on the acral areas (hands and feet) (Fig. 15.3) and on the face, very often the perioral areas.
• Vitiligo vulgaris: Multiple macules of variable sizes over widely scattered areas often tending to bilateral symmetry (Fig. 15.4).
• Lip-tip vitiligo: Lesions affecting the tips of the digits and the lips (Fig. 15.5)
• Mixed: Any combination- of vitiligo vulgaris and acrofacial vitiligo or of vitiligo vulgaris with segmental vitiligo.
• Universal Vitiligo: This is the term used to describe complete or near complete depig-mentation.
Special Signs in Vitiligo
• Trichrome vitiligo: The trichrome sign, also termed ‘vitiligo gradata’ describes a tan colored zone (intermediate colour) between the normal skin and the depigmented macules (Fig. 15.2). ‘Quadrichrome vitiligo’ implies the presence of a fourth color – dark brown – at the sites of perifollicular repigmentation.
• Pentachrome vitiligo: Has five colors—white, tan, brown hyperpigmented, blue-grey hyper-pigmented, and normal skin color.
• Inflammatory vitiligo: Here skin lesions of vitiligo have erythematous raised margin. This should be differentiated from the erythema of vitiligo macule following exposure to sunlight.
• Koebner’s sign: This phenomenon, a common feature of vitiligo, is defined as the development of lesions along the lines of specific trauma such as a cut, burn or abrasion.
It may be a marker of disease activity.
Fig. 15.3: Acral vitiligo—vitiligo involving hands and feet
Fig. 15.4: Vitiligo vulgaris—multiple depigmented and hypopigmented macules over the chest and abdomen (Trichrome vitiligo)
Fig. 15.5: Lip tip vitiligo-lesions affecting the tips of the digits and the lips
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Association of Vitiligo with Other Diseases
Vitiligo has been shown to be associated with autoimmune thyroid disease, Addison’s disease, pernicious anemia, diabetes mellitus and various dermatological disorders like alopecia areata, scleroderma, psoriasis and collagen vascular disorders. The Vogt Koyanagi Harada syndrome is an apparently rare, multisystem disease characterized by vitiligo, poliosis, uveitis, dysacousia, and alopecia.
Differential Diagnosis of Localized Vitiligo Includes
Naevus depigmentosus (localized hypo-melanosis present since birth), naevus anemicus (pale area due to vasoconsconstriction), leprosy (suspect in an endemic area, shows hypo-anesthetic or hypo-anesthetic hypopigmented patch/
es), pityriasis alba (hypopigmented macular lesions have ill defined margins with fine scaling, self limiting course), postinflammatory hypo-melanosis (such cases have preceding history of dermatoses, and the skin lesions are ill defined), tinea versicolor (typical localization to upper trunk, pigmented macular lesions have fine powdery scales, KOH +vity conclusive), ash-leaf macules and confetti depigmentation of tuberous sclerosis, and idiopathic guttate hypomelanosis (tiny porcelain white macules, 2-6 mm with distinct margins, localized to limbs in older individuals).
Differential Diagnosis of Generalized Vitiligo Includes
Chemical leukoderma (there is history of exposure to phenolic germicides; confetti macules; localized to the site of contact), leprosy (suspect in an endemic area, has anesthetic hypopigmented patch/es), mycosis fungoides (unpatterned lesions, diagnosis confirmed by biopsy), postinflammatory hypomelanosis
(hypopig-mented macules with ill defined border, history of preceding dermatoses like psoriasis, eczema, pityriasis rosea, etc. in same areas with pattern mimicking it), tinea versicolor (has fine powdery scales over the lesions, in doubt do KOH examination of skin scrapings), Waardenburg’s syndrome, albinism and piebaldism (see next page for last three).
Treatment
Treatment of vitiligo can be broadly divided into medical and surgical modalities.
Medical management Topical therapy
1. Photoprotection: It prevents sunburn and Koebner phenomenon, prevents tanning of uninvolved skin and therefore lessens contrast between normal and depigmented skin.
2. Topical potent corticosteroids.
3. Intralesional corticosteroids: (Triamcinolone acetonide) especially for leukotrichia on scalp.
4. Human placental extract.
5. Topical immunomodulators: Such as tacrolimus (0.1%, 0.03%), pimecrolimus or tacrolimus (0.1%) combined with narrow band UVB three times a week.
6. Calcipotriol: Can be used as monotherapy or combined therapy (sunlight, PUVA, or narrow band UVB, clobetasol).
7. Topical pseudocatalase + calcium + UVB 8. Vitix®: Formulation containing superoxide
dismutase and catalase. It removes hydrogen peroxide from skin, thereby helps in repigmentation.
9. Phenytoin local application: It inhibits release of norepinephrine and activity of monoamine oxidase, inhibits the production of superoxide anion and suppresses cytotoxic T- lymphocyte activity and induces type 2 like cytokine profile.
10. Dead sea climatotherapy in combination with pseudocatalase: Here patients take bath in dead sea for 15 minutes twice daily followed by a shower to wash off salt followed by application of pseudocatalase cream prior to sun exposure.
11. Topical prostaglandin analogues (PGE2).
12. Cosmetic camouflage where nothing works or when on treatment.
Systemic Therapy
1. Low dose oral corticosteroids-prednisolone 0.3 mg/kg body weight daily.
2. Oral dexamethasone or betamethasone pulse therapy- 0.5 mg/ every 5 kg body weight for two consecutive days in a week.
3. High dose methylprednisolone pulse therapy-8 mg/kg/day IV over 30 minutes for three consecutive days every 4-8 weeks.
4. Multivitamin therapy (folic acid/vitamin B12/ vitamin C).
5. Antioxidants (β-carotene, α-tocopherol, methionine, ubiquinone, vitamin C).
6. Immunomodulators- Levamisole 150 mg on two consecutive days every week; cyclo-phosphamide 50 mg twice daily; cyclosporine 6 mg/kg/day; dapsone 100 mg/day; azathi-oprine.
7. Quinoline compounds- chloroquine 250 mg/
day and hydroxychloroquine 400 mg/day.
They can be combined with psoralen therapy.
Phototherapy
• Psoralen (stimulates melanogenesis in presence of ultra violet radiation)with ultraviolet A therapy (PUVA)- topical and systemic
• Khellin + UVA (KUVA). Khellin is extracted from seeds of the plant Ammi visnaga. It can be given either topically or systemically.
Khellin is given orally 50-100 mg/day, 2.5 hours prior to sun or UVA exposure up to 15 J/cm2. But due to systemic toxicity, topical preparation of khellin is recommended.
• Phenylalanine + UVA (PAUVA). Pheny-alanine both topically and systemically can be used in combination with UVA. Pheny-alanine can be used at a dose of 50-100 mg/
kg body weight 45 minutes prior to UVA exposure.
• UVB radiation especially narrow band UVB
• Targeted light therapy and Excimer laser (308 nm).
Surgical Management Indications
• Stable vitiligo (i.e. no new lesions for last two years)
• Refractory to medical management.
Modalities
• Punch grafting
• Split skin thickness graft
• Blister grafting
• Melanocyte culture and transplantation
• Tattooing
• Therapeutic spot and regional dermabrasion
• Trypsinized autograft injection
• Topical 5- fluorouracil combined with epidermal abrasion.
For universal vitiligo options for depigmentation are:
• Depigmentation with 20% monobenzyl ether of hydroquinone (for islands of residual repigmentation in extensive vitiligo).
• Imatinib mesilate 400 mg/day for 15 days, then 300 mg once a day for 30 days has caused vitiligo-like depigmentation. It is a selective inhibitor of several tyrosine kinases.
ALBINISM
• Autosomal recessive inherited disorder.
• It is characterized by reduced melanin synthesis in the melanocytes of the skin, hair, and eyes, termed oculocutaneous albinism
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(OCA), and hypopigmentation primarily involving the retinal pigment epithelium of the eyes termed ocular albinism (OA).
• Due to genetic abnormalities of melanin synthesis associated with normal number and structure of melanocytes (differentiate it from vitiligo where melanocytes are reduced or absent).
• Tyrosinase-related OCA, the most common type of albinism is produced by loss of function of the melanocytic enzyme tyrosinase resulting from mutations of the tyrosinase gene.
• Affected individuals are born with white or blond hair and skin and blue eyes (Fig. 15.6).
PIEBALDISM
• Piebaldism is an uncommon, autosomal dominant, congenital, stable leukoderma characterized by a white forelock and vitiligo-like amelanotic macules, usually containing a few normally pigmented or hyper-pigmented macules (Fig. 15.7).
• Hyperpigmented macules within the amelanotic macules and on normally pigmented skin are characteristic of piebaldism.
WAARDENBURG’S SYNDROME
WS (Waardenburg syndrome–Hirschsprung’s disease or Shab-Waardenburg syndrome) is a rare autosomal dominant disorder that is characterized by:
• Lateral displacement of the inner canthi and of lacrimal puncta
• Prominence of the nasal root and of the medial eyebrows
• Congenital deafness
• Heterochromic irides
• White forelock
• Hypomelanotic macules.
MELASMA (CHLOASMA)
• Melasma is a common acquired hyper-melanosis that occurs exclusively in sun-exposed areas; it is exacerbated by sun exposure, pregnancy, oral contraceptives, and certain anti-epilepsy drugs.
• Melasma presents in one of three usually symmetric facial patterns. The most common Fig. 15.6: Albinism—Blond hair and white skin with
actinic keratosis.
Fig. 15.7: Piebaldism—typical white forelock
is a centrofacial pattern involving the cheeks (Fig. 15.8), forehead, upper lip, nose, and chin.
Less common are the malar pattern, involving the cheeks and nose, and the mandibular pattern.
• Successful treatment of melasma involves the triad of sunblocks, bleach and time.
FRECKLE (EPHELIDES)
It is an area of pale brown pigmentation usually less than 3 mm with poorly defined lateral margins
• Freckle appears as result of functionally overactive melanocytes (though they are normal in number )
• They are seen only in fair skinned people
• They are stimulated by ultra violet radiation and fade away during winter
• Histology reveals excess of melanin pigment in the basal layer.
LENTIGO (PLURAL: LENTIGINES)
It is a sharply demarcated brown pigmented macule usually circular or polycyclic in shape.
• Lentigo appears as a result of increased number of melanocytes in the basal layer
• They do not show seasonal colour variations ( not affected by ultra violet radiation).
• Histology reveals linear increase of melanocytes in the basal layer
Syndromes Associated with Lentigines
• LEOPARD syndrome:
Lentigines (multiple), ECG abnormalities,
Ocular abnormalities (hypertelorism), Pulmonary stenosis,
Abnormalities of genitalia, Retardation of growth and Deafness (sensorineural).
• NAME syndrome:
Nevi,
Atrial myxoma,
Myxoid neurofibromas and Ephelides.
• LAMB syndrome:
Lentigines, Atrial myxoma,
Mucocutaneous myxomas and Blue nevi.
PEUTZ JEGHERS SYNDROME
• Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by pig-mented macules (lentigines) of the buccal mucosa, lips, fingers, and toes and by gastrointestinal polyps.
• It is caused by mutations in a novel serine threonine kinase, and its gene has recently been mapped to chromosome 19p.
• The pigmented macules (dark brown or blue-brown) are most common on the buccal mucosa and lips, but also seen over palate and tongue. The macules on the skin are usually found on the face (around the mouth and eyes), dorsa of the hands and feet and perium-bilically.
• The diagnosis is particularly important because of the presence of gastrointestinal polyps, which are most frequent in the small bowel, particularly the jejunum, which may manifest with gastrointestinal bleeding.
Malignant change may occur in these polyps.
Fig. 15.8: Melasma—hyperpigmented light brown macules over the cheeks
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• Any child with recurrent, unexplained abdominal pain should be examined for the typical mucosal, and periorificial pigmented lesions of Peutz-Jeghers syndrome.
DRUGS CAUSING HYPERPIGMENTATION
• Generalized–Addisonian-like occurs with ACTH and generalized diffuse due to clofa-zimine, cyclophosphamide, minocycline, etc.
• Localized:
– Melasma- like- estrogen, progesterone, phenytoin
– Knuckle pigmentation- bleomycin – Palmoplantar- cyclophosphamide,
doxo-rubicin
– Linear – bleomycin (flagellate), zido-vudine.
ICHTHYOSIS
Ichthyosis (from Greek ichthys “fish”) denotes a group of hereditary and acquired disorders of keratinization characterized by the development of dry rectangular scales.
Hereditary (Inherited) Ichthyoses Ichthyosis Vulgaris
It is a common autosomal dominant disorder characterized by mild scaling on extensor aspect of the limbs (Fig. 16.1), more than trunk and spares the flexures. Increased palmar markings or frank palmoplantar keratoderma may be associated features. Onset is after 3 months of age.
Scaling gets worse in winter.
Differential diagnosis: Atopic xerosis, eczema craquele, acquired ichthyosis, and Refsum’s disease.
X-linked Recessive Ichthyosis
It appears in infancy and occurs in males. Females may be heterozygotes and female carriers are either totally spared or only mildly affected. Large dirty brown scales characterize it. Extensor and flexor aspects of the limbs are involved but spare rhomboidal spaces in body folds (Figs. 16.2 and 16.3). Palms and soles are spared but the neck,