Disorders of pigmentation

Dermatology lec

1. Disorders of pigmentation

2. Normal skin colour The colour of normal skin comes from a mixture of pigments pink by oxyhaemoglobin in the blood within the dermis. brown of melanin 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: UVR is the most important Melanocytestimulating hormone (MSH) peptides from the pituitary and other areas of the brain 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: Imbalance of the normal pigments 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 skin and eyes ( oculocutaneous albinism) eyes alone (ocular albinis ) Cause oculocutaneous albinism of two main types: tyrosinase negative, lies on chromosome 11q14- q21 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.

13. 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.

14. 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.

15. 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: Generalized Segmental, rare Trauma and sunburn can precipitate both types.

16. 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.

17. 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

18. 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

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

20. 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

21. Recent patches 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. Alternatively, calcineurin inhibitors , such as 0.1% tacrolimus ointment 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 Narrow-band (311 nm) UVB may also be effective New lesions seem to respond best. Less reliable treatments include excimer laser and antioxidant therapy A utologous skin grafts if pigment is absent in hair follicles or skin without hair follicles

22. 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

23. Post-inflammatory depigmentation Eczema Psoriasis Sarcoidosis Lupus erythematosus lichen planus 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.

24. Disorders with increased pigmentation ( hypermelanosis )

25. 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

26. 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.

27. 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

28. Histology of a freckle and lentigo

29. Conditions associated with multiple lentigines 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 . Cronkhite –Canada syndrome LEOPARD syndrome

30. 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: Sunlight pregnancy ‘the mask of pregnancy ’ oestrogens and oral contraceptives thyroid dysfunction photosensitizing drugs The placenta may secrete sex hormones that stimulate melanocytes .

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

32. 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.

33. 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 ,

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

35. The end