به نام خدا وند بخشنده و مهربان

1. به نام خدا وند بخشنده و مهربان

2. Hyperpigmentation disorders Dr Gita Faghihi Dermatology ASSOc.Professor Isf.Univ.Med.Sci

3. Skin color Depends on: Amount of : Melanin , Chromophores such as :hemoglobin, carotenoids…

4. Causes of skin hyperpigmentation • Increase in amount of melanin or number of active melanocytes • deposition of exogenous pigments,…

5. Classifications of skin hyperpigmentation (morphologic): Circumscribed Reticular Linear diffuse

6. Reticular • Reticulate acropigmentation of Kitamura & Dohi • Naegeli–Franceschetti–Jadassohnsyndrome • Dyskeratosiscongenita , .…

7. Diffuse/Circumscribed • Lentigo/Lentiginosis • Melasma • Erythema dyschromicumperstans • Lichen planuspigmentosus • Café au laitspot • Poikiloderma (Poikiloderma of Civatte),,(Poikilodermavasculareatrophicans) • Riehlmelanosis • PIP • Acanthosisnigricans • Periorbital hyperpigmentation • Photoleukomelanodermatitis of Kobori • Transient neonatal pustularmelanosis

8. Linear • Incontinentiapigmenti • Scratch dermatitis(flagellate bleomycin induced) • Shiitake mushroom dermatitis linearity of the lesions is probably related to Blaschko’s lines, which suggests that the predisposition to develop ,,determined during embryogenesis

9. Others/unclassified(due to drugs, ,exogenous..) • pigments iron: Hemochromatosis • Iron metallic discoloration • Pigmented purpuricdermatosis (Schamberg disease, Majocchi's disease, Gougerot–Blum syndrome, Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis, Lichen aureus, Angiomaserpiginosum) • Hemosiderin hyperpigmentation • other metals: Argyria • Chrysiasis • Arsenic poisoning • Lead poisoning • Titanium metallic discoloration • Carotenosis , Tattoo,Tarmelanosis

10. One of the common Diffuse or circumscribed disorders….

11. Post inflammatory hyperpigmentationPIH

12. Postinflammatory hyperpigmentation (PIH) acquired hypermelanosis…… after cutaneous inflammation or injury ….can arise in all skin types, But, more frequently affects darker patients, including : African Americans, Hispanics/Latinos, Asians

13. PostinflammatoryhyperpigmentationPIHin Fitzpatrick skin type 4 vs. 6Note the greater intensity of pigmentation in darker skin

14. A wide range of etiologies for PIH: • Acne • Infect.(Dermatophytoses, viral exanthemsbacterials.., • allergic reactions ( insect bites or a contact dermatitis, medication-induced PIH from(.. hypersensitivity reactions, • papulosquamousdiseases (psoriasis or lichen planus, PR • cutaneous injury from irritants, burns, or cosmetic procedures

15. Postinflammatoryhyperpigmentation after electrodessication for dermatosispapulosanigra

16. Acne-induced PIH in a patient with Fitzpatrick skin type V

17. Pathophysiology of PIH

18. In PIH:melanocyte activity ….to be stimulated by: • LTC4, • prostaglandins E2 and D2, thromboxane-2, interleukin (IL)-1, IL-6, • tumor necrosis factor (TNF)-α, • epidermal growth factor, and • reactive oxygen species .

19. First-line therapy (PIH) typically consists of : Photoprotection(a sunscreen) + topical depigmenting Topical tyrosinase inhibitors, such as: hydroquinone, azelaicacid, kojicacid, arbutin, and certain licorice extracts, can effectively lighten areas of hypermelanosis.

20. Recent clinical studies have shown that: • topical 5% methimazole, • Topical2% dioic acid can successfully treat hyperpigmentation secondary to a variety of etiologies../(PIH).

21. One of the most common…CIRCUMSCRIBED DISORDERS…

22. Melasma is an acquired symmetrical pigmentary disorder where confluent grey-brown patches typically appear on the face. %90 of individuals are women It is A disease with considerable psychological impacts The management of melasma is challenging and requires a long-term treatment plan.

23. factors implicated in the etiopathogenesis of melasma • One of the most important factors in the development of melasma is ultraviolet exposure from sunlight or other sources • photosensitizing and anticonvulsant medication • mild ovarian or thyroid dysfunction • certain cosmetics.

24. The centrofacial pattern is the most common and involves: • the cheeks, • nose, • forehead, • upper lip, and • chin.

25. Wood's lamp examination is of benefit classifiyingmelasma(epidermal,dermal,mixed/..)

26. Treatment of melasma, remains a challenge • Kligman and Willis : hydroquinone(5%) with tretinoin (0.1%) And dexamethasone (0.1%).

27. Prolonged HQ usage may lead to untoward effects like exogenous ochronosis.

28. In 2006, (FDA) released a statement proposing a ban on all OTC HQ agents based on rodent studies, which suggested that oral HQ may be a carcinogen so,

29. Many agents used in the treatment of hyperpigmentation act as tyrosinase inhibitors.

30. Therapeutic effects: azelaic acid inhibit the energy production and/or DNA synthesis of hyperactive melanocytes, azelaicacidantityrosinaseactivity. azelaicacid This may also account for the beneficial effect on postinflammatoryhyperpigmentation. azelaic acid 20% cream twice daily over a period of 12 weeks

31. Melasma & new treatment modalities: • Tranexamic acid tabletswere prescribed at a dosage of 250 mg twice daily for a therapeutic period of 6 months. 75% good to excellent response No side effects except hypomenorrhea and mild GI upset in <10%

32. Other Melasma drugs: • Arbutin ,(3-5 %) a herbal agent ,, higher concentrations of arbutin can lead to a paradoxical hyperpigmentation. Synthetic forms of arbutin, alpha-arbutin and deoxyarbutin, exhibit greater ability to inhibit tyrosinase Adding kojicacid, betulinic acid and niacinamide To arbutin gives better inhibition of Tyrosinase and higher efficacy

33. Cont… Melasma treatment combination of • Tretinoin , and • kojic acid, and • azelaic acid improve the melasma very effectively .

34. Other… melasma Therapeutics/ : • There is a lot of documented evidence about efficacy of adapalene gel 0.1% in melasma

35. Oral treatments • Dioic acid • Resveratrol

36. Procedures for melasmainclude: • chemical peel (such as glycolic acid,SA.. …etc..) • microdermabrasion • Laser (fractional ,ruby ,low fluence Q-switch nd:YAG …) • intense pulsed light (IPL)

37. One of diffuse hyperpig….

38. ERYTHEMA DYSCHROMICUM PERSTANS(ashy dermatosis)

39. ERYTHEMA DYSCHROMICUM PERSTANS Most common in individuals with skin phototypesIII–IV(women are more commonly affected) Ashy, gray–brown to blue–gray macules and patches in a symmetric distribution Lesions favor the neck, trunk and proximal extremities Causes: ■ Genetic susceptibility ■Toxic effects of chemicals such as ammonium nitrate or barium sulphate ■ worm infestation ■ Viral infections ■ Adverse effect of drugs and medications

40. Pigmentary incontinence vacuolar degeneration (ashy dermatosis)

41. Erythema dyschromicumperstans(also known as "Ashy dermatosis," ) • is a skin condition with age of onset almost always before 40 years old • characterized by skin lesions that are usually symmetrical and generalized

42. A consistently effective treatment is not currently available But some case series responded to oral corticosteroids

43. Treatment/ ashy dermatosis ... • The use of narrow-band UVB phototherapy has shown success in a few patients • A low-potency topical steroid applied twice a day to the affected areas may be used, with or without a 4% hydroquinone cream for the hyperpigmentation • A patient from Turkey was described to have responded remarkably well to treatment with dapsone

44. Diff. diagnosis , for ashy dermatosis Lichen planuspigmentosus

45. LICHEN PLANUS PIGMENTOSUS Lichen planuspigmentosus (LPP) is an uncommon variant of lichen planus that favors individuals with skin phototypes III–V, including those from India Latin America and the Middle East. LPP usually has its onset during the third or fourth decade of life; it presents as oval or round, brown, gray–brown or dark brown macules and patches in either sun-exposed areas (especially the forehead, temples and neck) or intertriginouszones. There may be no associated symptoms versus mild pruritus or burning, and, in contrast to some cases of EDP, early lesions do not have an erythematous border

46. Gray–brown to dark brown macules and patches in either a photodistribution or an inverse (intertriginous) pattern

47. Tacrolimus (protopic ) ointment is effective in LPP

48. One common Cicumscribed,,retic/ hyperpig/

49. Amyloidosis a spectrum of disorders characterized by the deposition of amyloid within the skin and other tissues . • Primary (localized) cutaneous amyloidosis is subdivided into three major forms– macular, lichenoid and nodular the first two are associated with hyperpigmentation. The most common locations are the upper back (macular amyloidosis) and the extensor surface of the lower extremities (lichen amyloidosis). Areas of involvement are often pruritic, and because rubbing plays a key role in the production of lesions, there is a characteristic rippled pattern with parallel bands or ridges of hyperpigmentation. Histologically, melanophages as well as amyloid deposits that stain positively with antikeratin antibodies are seen within the upper dermis.

50. chronic pruritic hyperpigmented patches on upper back esp/. in adult women