Disorders of Pigmentation

1. Disorders of Pigmentation

2. Skin colour • Determined by - melanin - haemoglobin - carotenoids • Melanin - major determinant • Melanin is synthesized by melanocytes within melanosomes and transferred to keratinocytes • Constitutive skin colour - genetically determined • Facultative skin colour - induced by sun and hormones

3. Melanocyte • Dendritic cells • Derived from neutral crest • Migrate to epidermis • Epidermal melanin unit - one melanocyte connected to about 36 keratinocytes by dendrites • Synthesize melanin in organelles called melanosomes • Melanosomes are then transferred to keratinocytes through dendrites

4. Melanin • Two types - eumelanin (black or brown) - pheomelanin (reddish) • Derived from tyrosine Tyrosine Tyrosinase DOPA[3,4 dihydroxy phenylalanine] Dopaquinone Dopachrome 5, 6 dihydroxindole Eumelanin Cysteinyldopa pheomelanin

5. Disorders of pigmentation - An Overview • Skin pigmentation has far-reaching social and psychological implications • White people strive for tanning which while brown and black people strive for a lighter skin • Melanin pigmentation disorders are important for medical and cosmetic reasons

6. Classification • Hypomelanosis: reduced or absent pigment eg. Vitiligo, Pityriasis alba • Brown hypermelanosis: increased pigment in epidermis. eg. Freckles • Slate gray or blue hypermelanosis: pigment in dermis. eg. Mongolian spots

7. Approach to a patient: History • Onset : birth, infancy or later • Cause: sun exposure, drugs, occupation • Systemic complaints • Family history: neurofibromatosis, tuberous sclerosis, vitiligo

8. Approach to a patient: Examination: • Type of lesion: brown, blue, hypopigmented (check sensation), depigmented • Shape: Ash leaf macules (tuberous slerosis) Koebner phenomenon(vitiligo) • Distribution pattern : linear/segmental (nevus depigmentosus), symmetric (vitiligo), specific sites (melasma, Addison’s disease)

9. Approach to a patient: Examination aids: • Hand lens • Oblique lighting for elevation or depression • Dermatoscopy • Wood’s lamp - 360 nm. Epidermal pigmentary anomalies made more prominent • Histology- H and E for presence or absence of melanin Dopa reaction - melanocytes stain dark Silver stains - melanin stains black

10. Disorders of decreased pigmentation • Hypopigmentation • Depigmentation The pigment may be absent from birth or lost later in life. It may be diffuse or cicumscribed.

11. Classification: Hypogimented / depigmented lesions • Genetic and Developmental: Albinism, Nevus depigmentosus, Nevus anaemicus, Halo nevus, Tuberous sclerosis (ash leaf macule) • Endocrine: Addison’s disease, Hypothyroidism, Hypopituitarism • Nutritional: Vit.B12 deficiency, Kwashiorkor, Malabsorption

12. Classification: Hypogimented / depigmented lesions • Post-inflammatory: Pityriasis alba, Eczema, Psoriasis, Pityriasisrosea, Lupus erythematosus, Morphea, Scleroderma, Bullousdermatoses • Infection: Leprosy, Tineaversicolor, Candidiasis, Post kalaazar dermal leishmaniasis • Chemicals and Drugs: Phenols, Arsenicals, Hydroquinone, Steroids

13. Classification: Hypogimented / depigmented lesions • Physical: Burns, Trauma, Post dermabrasion, Post laser • Miscellaneous: Idiopathic guttatehypomelanosis, Vitiligo, Mycosis fungoides

14. Albinism • Oculocutaneous albinism involves skin, hair and eyes • Mostly autosomal recessive • Absence of pigmentation from birth • Photophobia, reduced visual activity • Sunburns, skin cancers common • Protection of eyes and skin by sunglasses, sunscreens SPF > 20, clothing

15. Waardenburg’s syndrome • Rare, autosomal dominant disorder • White forelock • Hypertelorism • Congenital deafness • Hypomelanoticmacules • Heterochromicirides • Incomplete forms may occur

16. Tuberous sclerosis • Autosominal dominant, neurocutaneous syndrome with skin lesions, mental retardation and epilepsy • Skin lesions are ash-leaf macules, angiofibromas and shagreen patches • Ash-leaf macules - present at birth in>90% cases, so important in early diagnosis Oval or ash-leaf shaped, hypopigmentedmacules, made prominent in Wood’s lamp • Long axis is axial on limbs and transverse on trunk

17. Nevus depigmentosus • A hypopigmented birthmark which is congenital and stable • Irregular, geographic margins and quasidermatomal distribution • Block in transfer of melanosomes from melanocytes to keratinocytes • Sporadic occurrence, no medical significance and no treatment required

18. Kwashiorkor • Protein deficiency in post weaning years • Reddish patches which turn into dark plaques which turn white after exfoliation (crazy pavement dermatosis) • Disruption of melanogenesis is due to multiple deficiencies • Pigment changes and dyschromic hair are reversible with proper diet

19. Tineaversicolor • Common, superficial fungal infection • Overgrowth of Malasezziafurfur - a normal resident • Common after puberty; face, neck, upper trunk affected • Nonpruritic or mildly pruritic, hypo or hyperpigmented lesions with fine scales • Common in tropics; during summers

20. Leprosy • Both hypopigmented and erythematous lesions common • Hypopigmentedmacules common in tuberculoid type of disease • Each hypopigmented lesions in leprosy endemic areas should be examined for sensations of touch, pain, temperature • Treatment according to type of leprosy

21. Pityriasis alba • A common disorder in children • Hypopigmented lesions with powdery scaling; chiefly affecting face • Etiology not known but may be a feature of atopy or malnutrition • To be differentiated from indeterminate leprosy and early vitiligo • Treatment with emollients

22. Other causes • Chemical, thermal burns, trauma • Postinflammatory: after healing of lesions of eczema, psoriasis, discoid lupus erythematosus, lichen striatus etc. • Endocrine: hypopitutarism and hypogonadism - diffuse hypomelanosis • Idiopathic guttatehypomelanosis: tiny depigmentedmacules an extremities due to ageing

23. Disorders of hyperpigmentation • May be epidermal or dermal • Epidermal hyperpigmentation due to - Increased melanin with normal number of melanocytes - Increased number of melanocytes • Dermal hyperpigmentation due to - Melanin from epidermis transferred to dermis - Melanin formed in dermal melanocytes - Melanin pigments appears blue-gray due to Tyndall effect

24. Classification: Epidermal hyperpigmentation • Physiologic: Pigmentary demarcation lines, suntanning • Genetic and Developmental: Lentigines, Freckles, Peutz-Jeghers syndrome, Melanocytic nevus, Café-au-lait spots, Xerodermapigmentosum, Becker’s nevus, Nevus spilus, Acanthosisnigricans

25. Classification: Epidermal hyperpigmentation • Post-inflammatory: Eczema, Psoriasis, Lichen planus, Lupus erythematosus, Scleroderma, Morphoea, Vagabond’s disease • Infection: Tineaversicolor, Tineanigra • Nutritional: Kwashiorkor, Pellagra, Vit.B12, Vit.C, Folic acid deficiency

26. Classification: Epidermal hyperpigmentation • Physical: Trauma, Radiation dermatitis • Endocrine: Melasma, Addison’s disease, Cushing’s syndrome, Phaeochromocytoma, Acromegaly, Hyperthyroidism • Neoplastic: Malignant melanoma, Seborrhoeickeratosis, Pigmented basal cell carcinoma

27. Classification: Dermal hyperpigmentation • Genetic and Developmental: Mongolian spots, Nevus of Ota/Ito, Incontinentiapigmenti • Inflammatory: Stasis dermatitis, Post inflammatory to eczema and fixed drug eruption • Chemicals and Drugs: Anti-malarials, OC Pills, Minocycline, Clofazimine, Topical hydroquinone, Tattoos

28. Classification: Dermal hyperpigmentation • Endocrine: Melasma • Physical: Thermal burns, Post traumatic • Infection: Syphilis, Yaws, Pinta • Neoplastic: Metastasis of melanoma

29. Classification: Dermal hyperpigmentation • Nutritional: Chronic nutritional deficiency • Metabolic: Hemochromatosis, Alkaptonuria, Macular/Lichen amyloidosis • Miscellaneous: Pigmented purpuricdermatosis, Purpura

30. Melanocytic nevi • Benign proliferations of melanocytic nevus cells at the dermo-epidermal junction • May be congenital or acquired • Acquired nevi are more common • Appear in infancy or childhood, slowly grow and mature and then regress in older life • Important for cosmetic reasons and as precursors for melanoma (esp in white)

31. Acquired nevi • Round or oval, uniformly coloured and sharply bordered lesions • Appear after birth • Increase in frequency during childhood and adolescence and plateaus during middle age • Most of them start as junctional nevi which are flat and histologically confined to dermal-epidermal junction

32. Acquired nevi • Gradually mature to compound nevi which have nests and columns of nevus cells in dermis along with the junctional component. These are raised, rounded, brown or black • Intradermal nevi : Compound nevi mature to intradermal nevi with nevus cells only in dermis having neuron like appearance. These are dome shaped, nonpigmented and may have one or more coarse hairs

33. Treatment Elliptical excision and biopsy • Indications of excision: • Cosmetic reasons • Irritation due to clothing, belts, straps • Atypical appearance: sudden increase in size, varied pigmentation, irregular borders, bleeding. Destructive methods (cautery, cryotherapy) not recommended as recurrence with atypical appearance may occur

34. Congenital melanocytic nevi • Small < 1.5 • Intermediate: 1.5 to 20 cms • Giant > 20 cms • Malignant potential for giant nevi is 4-6% • Excision justified for cosmetic reasons and risk of malignancy

35. Café au lait macules (CALM) • Circumscribed, brown macules with irregular margins, 2-5 cm in size • Present at birth • Isolated CALM may occur in 10-20% of normal population • No increase in the number of melanocytes • Five or more CALM of size >0.5 cm in prepubertal age group and >1.5 cm in an adult are strongly suggestive of neurofibromatosis

36. Becker’snevus • Acquired, pigmented, hairy plaque common on trunk, more common in males • Appears in first or second decade • Common sites: shoulder, chest, back • May become verrucous with hair growth and then remains stable • No treatment needed

37. Ephelides (Freckles) • Tiny (<0.5 cm), discrete brown macules • Common in fair skinned • Appear in childhood on sun exposed parts; lighten in absence of sun exposure • Melanocytes are not increased in number but are hyperactive • May be part of some syndromes

38. Melasma • A common macular brown coloured lesion seen on face in males and females • Common in pregnancy: Mask of pregnancy • Etiology: hormones (OC Pills) and sunlight • May disappear or remain after delivery • Forehead, nose, cheeks affected • Exacerbation on sun exposure • Histologically may be epidermal, dermal or mixed

39. Treatment of melasma • Sunscreens and bleaching agents • Physical sunscreens to be used daily • Bleaching agents : Hydroquinone 2-4%, Kojic acid 2-3%, Tretinoin 0.025-0.05%, Arbutin • About two months needed to see a response and six months for complete resolution • Recurrence common after sun exposure • Dermal melasma does not respond

40. Diffuse hyperpigmentation • Addison’s disease • Haemochromatosis • HIV infection and AIDS • Drugs: Clofazimine Chlorpromazine Amiodarone Anticancer agents

41. Post-inflammatory hyperpigmentation • After resolution of specific eruptions • Common after lichen planus, atopic dermatitis, acne vulgaris, contact dermatitis, psoriasis, pyodermas etc. • Discrete macules exactly on the sites previously affected by eruptions • May persist for months

42. Fixed Drug Eruption (FDE) • NSAIDs, antibiotics, barbiturates etc. • Reddish brown macule → edematous → desquamation → pigmentation • Recurs at same site on rechallenge • May become generalised or blistering • Melanin is increased in epidermis and dermis (melanophages)

43. Mongolian spots • Common in asian newborns on buttocks or lower back • Due to arrest of migrating melanocytes in the dermis • No treatment is needed as they spontaneously disappear by 2 to 10 yrs of age

44. Nevus of Ota and Ito • Nevus of Ota (around eyes) and nevus of Ito (shoulder area) are other examples of dermal pigmentation

45. Management

46. Drugs Hydroquinone (2 - 4%) • Inhibits tyrosinase activity by 90% • Affects DNA, RNA synthesis • Safety concerns like irritation, exogenous ochronosis • May be combined with topical steroids, tretinoin, kojic acid Tretinoin • Adjuvant • Inhibits tyrosinase in cells cultures • Exact mechanism of action unknown

47. Drugs Kojic acid • Fungal metabolite • Food additive - Japan • Suppresses tyrosinase by chelating copper • Stability • Sensitization A.H.A • Natural saturated dicarboxylic acid • Diminished corneocyte cohesion • Faster desquamation due to increased turnover • Side effects: irritation, hyperpigmentation • Glycolic, lactic, mandelic acid

48. Drugs Azelaic acid • Antiproliferative, cytotoxic • Inhibits tyrosinase • As effective as hydroquinone • Azelaic acid 20% + Glycolic acid 15-20% is an effective combination Vit. C Problems with penetration and stability

49. Physical modalities • Chemical peels with increasing concentrations of glycolic acid, trichloroacetic acid, salicylic acid • Lasers : • Q switched Nd: YAG laser • Alexandrite laser • Pulse dye laser • Intense pulse dye laser

50. Thank you