Dermatology lec

1. Disorders of pigmentation

2. Normal skin colour
 The colour of normal skin comes from a mixture of
pigments
1. pink by oxyhaemoglobin in the blood within the
dermis.
2. brown of melanin
3. yellow from carotene mainly in subcutaneous fat
and in the horny layer of the epidermis.
 There is no natural blue pigment
 Hair colour is determined by the relative amounts of
the different types of melanin. Eumelanin
predominates in black hair and phaeomelanin in red.

3. Melanogenesis
 Melanin is formed from the essential aminoacid
phenylalanine through a series of enzymatic steps in
the liver and skin.
 Melanin is made within melanosomes
 fully melanized melanosomes pass into the dendritic
processes of the melanocyte to be injected into
neighbouring keratinocytes and distributed
throughout the cytoplasm.
 Skin color depend on nummber and size of
melanosomes
 Melanins protect against UVR damage by absorbing
and scattering the rays, and by scavenging free
radicals.

4. Control of melanogenesis
 Melanogenesis can be increased by several stimuli:
1. UVR is the most important
2. Melanocytestimulating hormone (MSH) peptides
from the pituitary and other areas of the brain
3. Oestrogens and progestogens (and possibly
testosterone too) may stimulate melanogenesis,
either directly (by acting on oestrogen and
progestogen receptors in the melanocyte) or by
increasing the release of MSH peptides from the
pituitary

5. Tanning
 involves two distinct reactions.
A-Immediate pigment darkening (IPD) following
exposure to longwave ultraviolet (UVA 320–400 nm).
 This pigment darkening occurs over minutes to days
 responsible for the well-known phenomenon of a ‘false
tan’.
 It is not brought about by melanin synthesis but oxidation
of preformed melanin and redistribution of melanin from
perinuclear melanosomes to peripheral dendrites.
B-Delayed tanning (DT): the production of new pigment
occurs some 3–4 days after exposure to medium-wave
ultraviolet (UVB: 290–320 nm) and UVA and is maximal
at 7 days

6. Genetics and skin pigmentation
 Genetic differences determine the pigmentation of
the different races
 A black person living in Britain and a white person
living in Africa will remain black and white,
respectively

7. Abnormal skin colours
 These may be caused by:
1. Imbalance of the normal pigments
2. Presence of abnormal pigments

8. Some abnormal pigments
Endogenous
Haemoglobin-derived
 Methaemoglobin,
Sulphaemoglobin - Blue colour in
vessels, cyanosis
 Carboxyhaemoglobin -Pink
 Bilirubin, Biliverdin -Yellow–green
 Haemosiderin- Brown
Drugs
 Gold- Blue-grey (chrysiasis)
 Silver -Blue-grey (argyria)
 Amiodarone- Blue-grey
 Bismuth -Grey
 Mepacrine- Yellow
 Clofazamine- Red
 Phenothiazines- Slate-grey
Diet
 Carotene Orange
Exogenous
Tattoo pigments
Local medications
• Silver nitrate- Black
• Magenta paint- Magenta
• Gentian violet- Violet
• Eosin- Pink
• Potassium permanganate-
Brown
• Dithranol (anthralin)-
Purple
• Tar- Brown
• Iodine- Yellow

9. Decreased melanin pigmentation

10. Some causes of hypopigmentation.
Genetic
 Albinism
 Piebaldism
 Phenylketonuria
 Waardenburg’s syndrome
 Chediak–Higashi syndrome
 Tuberous sclerosis
Endocrine
 Hypopituitarism
Chemical
 Contact with substituted
phenols (in rubber industry)
Chloroquine and
hydroxychloroquine
Post-inflammatory
• Eczema
• Pityriasis alba
• Psoriasis
• Sarcoidosis
• Lupus erythematosus
• Lichen sclerosus et atrophicus
• Cryotherapy
Infections
• Leprosy
• Pityriasis versicolor
• Syphilis, yaws and pinta
Tumours
• Halo naevus
• Malignant melanoma
Miscellaneous
• Vitiligo
• Idiopathic guttate
hypomelanosis

11. Oculocutaneous albinism
 genetic conditions in which there is a defect in the
synthesis of melanin in the melanocyte, or a defective
transfer of melanosomes to surrounding keratinocytes
Types
1. skin and eyes (oculocutaneous albinism)
2. eyes alone (ocular albinis)
Cause
 oculocutaneous albinism of two main types:
1. tyrosinase negative, lies on chromosome 11q14- q21
2. tyrosinase positive, mapped to chromosome 15q11-
q13
 both being inherited as autosomal recessive traits. This
explains how children with two albino parents can
sometimes themselves be normally pigmented, the
genes being complementary in the double heterozygote

12. Presentation and course
 The whole epidermis is white
 Albinos have poor sight, photophobia and a rotatory
Nystagmus as pigment is also lacking in the hair, iris
and retina
 As they grow older, tyrosinasepositive albinos gain a
little pigment in their skin, iris and hair, also develop
freckles.
 Sunburn is common on unprotected skin.
 As melanocytes are present, albinos have non-
pigmented melanocytic naevi and may develop
amelanotic malignant melanomas.

14. Complications
 sun-induced skin cancers even when they are young,
confirming the protective role of melanin
Differential diagnosis
 Piebaldism and vitiligo
Investigations
 Prenatal diagnosis of albinism is now possible
 The hair bulb test to distinguishes tyrosinase-positive
from tyrosinase-negative types.
Treatment
 Avoidance of sun exposure and protection with opaque
clothing, wide-brimmed hats and sunscreen creams are
essential and allow albinos in temperate climates to live a
relatively normal life.
 Early diagnosis and treatment of skin tumours is critical.

15. Piebaldism
 a white forelock of hair
 patches of depigmentation lying symmetrically on the
limbs, trunk and central part of the face, especially
the chin.
 present at birth
 inherited as an autosomal dominant
 Melanocytes are absent from the hypopigmented
areas.
 The depigmentation, often mistaken for vitiligo, may
improve with age.
 There is no effective treatment.

16. Vitiligo
 The word vitiligo comes from the Latin word vitellus
meaning ‘veal’ (pale, pink flesh).
 It is an acquired circumscribed depigmentation, found in
all races
 its inheritance is polygenic.
Cause and types
 There is a complete loss of melanocytes from affected
areas.
 There are two main patterns:
1. Generalized
2. Segmental, rare
 Trauma and sunburn can precipitate both types.

18. Generalized vitiligo
 including the acrofacial variant
 Is a common type
 usually starts after the second decade
 positive family history in 30% of patients
associated with autoimmune diseases such as
diabetes, thyroid disorders and pernicious anaemia.
 in this type, melanocytes are the target of a cell-
mediated autoimmune attack or self-destruct
because of an inability to remove toxic melanin
precursors.

19. Segmental vitiligo
 is restricted to one part of the body, but not
necessarily to a dermatome.
 It occurs earlier than generalized vitiligo
 not associated with autoimmune diseases

20. Clinical course
Generalized type
 sharply defined, usually symmetrical white patches are
especially common on the backs of the hands, wrists, fronts of
knees, neck and around body orifices.
 The hair of the scalp and beard may depigment too. In
 Caucasoids, the surrounding skin is sometimes partially
depigmented or hyperpigmented (trichrome vitiligo).
 The course is unpredictable: lesions may remain static or
spread, sometimes following minor trauma (Köbner
phenomenon)
 they repigment spontaneously from the hair follicles.
Segmental type
 look like the generalized type but their segmental distribution
is striking.
 Spontaneous repigmentation occurs more often in this type
than in generalized vitiligo

21. Differential diagnosis
1. Contact with depigmenting chemicals, such as
hydroquinones and substituted phenols in the
rubber industry
2. Pityriasis versicolor
3. Post-inflammatory depigmentation
4. patches of piebaldism
5. Leprosy must be excluded
6. leishmaniasis and pinta.

22. Treatment
 Treatment is unsatisfactory
 The cosmetic disfigurement from vitiligo can be
devastating to affected paients..
 In the white patches pigment cells are only present
deep in the hair follicles and treatments mostly try to
get melanocytes to divide and migrate into affected
skin.
 Repigmentation is thus often heralded by freckling at
follicles within patches

24. Recent patches
1. Potent or very potent topical corticosteroid, applied
for 1–2 months. After this, the strength should be
gradually tapered to a mildly potent steroid for
maintenance treatment.
2. Alternatively, calcineurin inhibitors, such as 0.1%
tacrolimus ointment
3. Psoralens (trimethylpsoralen or 8-methoxypsoralen, in
a dosage of 0.4–0.6 mg/kg body weight), taken 1–2 h
before graduated exposure to natural sunshine or to
artificial UVA
4. Narrow-band (311 nm) UVB may also be effective
 New lesions seem to respond best.
1. Less reliable treatments include excimer laser and
antioxidant therapy
2. Autologous skin grafts if pigment is absent in hair
follicles or skin without hair follicles

25. Established vitiligo
 As a general rule,it is best left untreated in most
white people
 Advice about suitable camouflage preparations
 Sun avoidance and screening preparations are
needed to avoid sunburn of the affected areas and a
heightened contrast between the pale and dark
areas.
 Black patients with extensive vitiligo can be
completely and irreversibly depigmented

26. Post-inflammatory depigmentation
1. Eczema
2. Psoriasis
3. Sarcoidosis
4. Lupus erythematosus
5. lichen planus
6. cryotherapy or a burn
 In general, the more severe the inflammation, the more likely
pigment is to decrease rather than increase
Pityriasis alba
 is common on the faces of children.
 The initial lesion is probably a variant of eczema (pinkish with
fine scaling), which fades leaving one or more pale, slightly
scaly, areas.
 Exposure to the sun makes the patches more obvious.

28. Disorders with increased pigmentation
(hypermelanosis)

29. Some causes of hyperpigmentation.
Genetic
 Freckles
 Lentigines
 Café au lait macules
 Peutz–Jeghers syndrome
 Xeroderma pigmentosum
Endocrine
 Addison’s disease
 Cushing’s syndrome
 Pregnancy
 Renal failure
Metabolic
 Biliary cirrhosis
 Haemochromatosis
 Porphyria
Nutritional
 Malabsorption
 Carcinomatosis
 Kwashiorkor
 Pellagra
Drugs
• Photosensitizing drugs
• ACTH and synthetic analogues
• Oestrogens and progestogens
• Psoralens
• Arsenic
• Busulfan
• Minocycline
Post inflammatory
• Lichen planus
• Eczema
• Secondary syphilis
• Systemic sclerosis
• Lichen and macular amyloidosis
• Cryotherapy
• Poikiloderma
Tumours
• Acanthosis nigricans
• Pigmented naevi
• Malignant melanoma
• Mastocytosis

30. Freckles (ephelides)
 so common that to describe them seems
unnecessary
 They are seen most often in the redhaired or blond
person as sharply demarcated, light brown–ginger
macules, usually less than 5 mm in diameter.
 They multiply and become darker with sun exposure.
 Increased melanin is seen in the basal layer of the
epidermis without any increase in the number of
melanocytes, and without elongation of the rete
ridges
 No treatment is necessary.

31. Lentigo
 Simple and senile lentigines look alike.
 They are light or dark brown macules, ranging from 1 mm to 1 cm across.
 Are usually discrete, and may have an irregular outline.
 Simple lentigines arise most often in childhood as a few scattered lesions,
often on areas not exposed to sun, including the mucous membranes.
 Senile or solar lentigines are common after middle age on the backs of the
hands (‘age spots’, ‘liver spots’and on the face
 lentigines have increased numbers of melanocytes.
 They should be distinguished from a lentigo maligna
 Treatment is usually unnecessary and prevention, by sun avoidance and the
use of sunscreens is the best approach.
 cryotherapy
 laser
 daily application of 0.1% tretinoin cream or 2–4% hydroquinone or a
combination

32. Histology of a freckle and lentigo

36. Conditions associated with multiple
lentigines
1. Peutz–Jeghers syndrome
 autosomal dominant condition
 Scattered lentigines also occur on the buccal
mucosa, gums, hard palate, hands and feet.
 association with polyposis of the small intestine
 10 % of affected women have ovarian tumours.
2. Cronkhite–Canada syndrome
3. LEOPARD syndrome

38. Melasma (chloasma)
 acquired, symmetrical hypermelanosis occurring on sun-
exposed skin, especially the face.
 The areas of increased pigmentation are well defined and their
edges may be scalloped.
 more common in women, affects all races but is most
prevalent in dark-skinnned individuals with skin types IV–VI
 hypermelanosis becomes darker after exposure to the sun.
 There are many causes including:
1. Sunlight
2. pregnancy ‘the mask of pregnancy’
3. oestrogens and oral contraceptives
4. thyroid dysfunction
5. photosensitizing drugs
 The placenta may secrete sex hormones that stimulate
melanocytes.

40. Melasma Treatment
 This is unsatisfactory
 sunscreen
 bleaching agents that contain 2–5% hydroquinone,
applied for 6–10 weeks.
 Chemical peels

41. Endocrine hyperpigmentation
Addison’s disease
 caused by the overproduction of ACTH
 generalized or limited to the skin folds, creases of the
palms, scars and the buccal mucosa.
Cushing’s syndrome
 Increased ACTH production may cause a picture like that
of Addison’s disease.
Pregnancy
 There is a generalized increase in pigmentation during
pregnancy, especially of the nipples and areolae, and of
the linea alba. Melasma
 The nipples and areolae may remain pigmented for a
while after parturition.

42. Chronic renal failure
 The hyperpigmentation is caused by an increase in levels
of pituitary melanotrophic peptides, normally cleared by
the kidney.
Porphyria
 Formed porphyrins, especially uroporphyrins is
endogenous photosensitizers induce hyperpigmentation
on exposed areas
Nutritional hyperpigmentation
 Any severe wasting disease, such as malabsorption,
AIDS, tuberculosis or cancer, may be accompanied by
diffuse hyperpigmentation.
 Kwashiorkor presents a mixed picture of generalized
hypopigmentation and patchy post-inflammatory
hyperpigmentation,

43. Post-inflammatory
hyperpigmentation
 common after lichen planus
 systemic sclerosis
 some types of cutaneous amyloidosis
 cryotherapy

44. The end