Vitiligo

Basic information on Vitiligo including management principles

1. VITILIGO Facilitator- Dr S.Kiprono Presenter-Richard Rotich

2. Background $ definition of terms Basis of skin colour Pigments & Blood flow in the skin Pigments may be Those normally present Those not normally present

3. Pigments normally present Depends on presence of various chromophores-color producing molecule. Melanin synthesized by melanocyte is the most important

4. Melanocytes -present in the basal layer of epidermis ;their dendrites interdigitate with keratinocytes Melanocyte with associated keratinocytes ( abt 36) forms an epidermal melanin unit Melanocytes contain organelles called melanosome s - synthesize melanin

5. Epidermal melanin unit

6. There are two types of melanin; Eumelanin – brown-black, present in spherical melanosomes Pheomelanin - Red –brown or yellow present in ovoid melanosomes Once the pigment is formed, the melanosomes are injected into the keratinocytes by dendrites of melanocytes

7. Hypermelanosis - Increase of melanin in the epidermis Can occur in two ways; melanocytotic hypermelanosis - An increase in the number of melanocytes in the epidermis producing increased levels of melanin e.g lentigo . melanotic hypermelanosis - No increase of melanocytes but an increase in the production of melanin only e.g melasma .

8. Hypomelanosis -decrease of melanin in the epidermis . This reflects mainly two types of changes : Melanopenic hypomelanosis - No decrease in no of melanocytes but a decrease in the production of melanin only e.g albinism. Melanocytopenic hypomelanosis -A decrease in the number or absence of melanocytes in the epidermis producing no or decreased levels of melanin e.g vitiligo.

9. Melanogenesis

10. Control of melanogenesis Constitutional skin colour - blacks have same no of melanocytes as caucasians but with different activity (production of melanosomes)blacks-they’re large and broken down less rapidly. Hormones –melanosome stimulating hormone by pit. gland ( MSH)

11. 3. UV radiation(UVR )-most important stimuli (tanning) occurs in 2 phases; Immediate –exposure to UVA and is due to photo-oxidation of preformed melanin and rearrangement of melanosomes Delayed –exposure to both UVA & UVB and is due to proliferation of melanocytes , Increased tyrosinase activity , Increased melanosome production, Increased transfer of newly formed melanosomes from melanocytes to keratinocytes.

12. Pathogenesis of Hypopigmentation Hypopigmentation of skin is of two types Melanopenic hypopigmentation -decrease in number of melanosomes and can be due to Anatomical defect of melanocytes -Absent/damaged melanocytes e.g Vitiligo, Piebaldism , Chemicals like rubber, Postinflammatory Functional defect of melanocytes- Defective tyrosine metabolism e.g Pityriasis versicolor, Endocrine disorders, Albinism

13. Nonmelanopenic hypopigmentation : Due to abnormalities of vasculature, e.g ., nevus anemicus .

14. Definition Vitiligo -an acquired de-pigmenting disorder of unknown etiology. It is a chronic skin disease, characterized by the appearance of white depigmented macules and patches due to loss of melanocytes .

15. Etiology Exact mechanism not known; 1. Genetic -Genetic factors definitely important, since 20% of patients have a positive family history. Inheritance may be polygenic

16. 2. Autoimmune hypothesis- evidence pointing to autoimmune etiology includes; Frequent association with other autoimmune disorders like alopecia areata and thyroid disorders . Presence of antibodies to melanocytes. Presence of lymphocytes in early lesions.

17. 3. Neurogenic hypothesis- Segmental vitiligo is present along a dermatome in distribution of nerves , suggesting a neurogenic origin. It has been hypothesized that a toxin, which destroys melanocytes , is released at the nerve endings.

18. immediate mechanism for the evolving white macules involves progressive destruction of selected melanocytes by cytotoxic T cells. Vitiligo may follow cytokine dermatitis. Because of differences in the extent and course of segmental and generalized vitiligo, the pathogenesis of these two types is probably different

19. Epidemiology Incidence : affects 1-2% of the world’s population. Affects all races. Gender: No gender predilection. Age : Affects all ages; peak incidence between 10 and 30 years

20. In a study to determine clinical and epidemiological xtics of pts with vitiligo in Tanzania 122 pts were identified and results showed; Mean age of onset-26.2yrs Types observed; Vitiligo vulgaris-50.8% Focal and non-segmental-41.8% Acrofacial-12.3%

21. Positive family hx -10% Commonest sites of initial onset Head and neck-41.8% Lower limbs-18% Autoimmune dse were noticed in 17.8% with atopic dermatitis commonest (9.8%)

22. Clinical presentation Morphology D epigmented macules, which are chalky or milky white. Sometimes , pigment loss is partial and occasionally, three shades (trichrome) are seen in the same lesion—depigmented center, surrounded by a hypopigmented rim, which in turn has normal pigmented skin around it- represents different stages in the evolution.

23. trichrome

24. Macules have a scalloped(wavy) outline and form geo-graphical patterns on fusion with neighboring lesions. Hairs in the lesions may remain pigmented , ( leucotrichia ) though in the older lesions the hairs may lose their pigment.

25. geo-graphical patterns

26. leucotrichia

27. Sites Can occur in any part of the body. Areas subjected to repeated friction and trauma are frequently affected, e.g., the dorsal aspect of hands and feet, elbows, and knees

28. Patterns Vitiligo vulgaris Commonest type. Occurs after second decade. May be slowly or rapidly progressive. Family history is frequently present.

29. 2. Segmental vitiligo Occurs in children . Not associated with an autoimmune disease . Depigmentation is dermatomal or quasi-dermatomal . Most frequently (50%) seen in distribution of trigeminal nerve (mandibular division ). Has a stable course, i.e., lesions increase initially ( 6–12 months) and then remain static. Leucotrichia on the depigmented areas as well as away from vitiliginous areas frequently seen. Margins are feathery. Distant lesions uncommon . Poor response to rx .

30. 3. Generalized vitiligo Extensive lesions. Variants of generalized vitiligo are: Acrofacial vitiligo vitiligo predominantly seen periorificially (around eyes and on lips on the face) and acral parts ( periungual area i.e fingernails or toenails, palms, and soles). This type of vitiligo is more resistant to therapy due to absence of hair in the affected parts .

31. Lip-tip vitiligo When lips, tip of penis, the vulva and nipples are involved. Vitiligo universalis Widespread vitiligo with only few areas of normal pigmentation; this type of vitiligo is often associated with multiple endocrinopathies .

32. Associations Cutaneous disorders: Alopecia areata , halo nevus, atopic dermatitis, malignant melanoma , and morphea . Endocrine disorders: Diabetes mellitus, pernicious anemia, Addison’s disease, hypoparathyroidism, hypothyroidism, and hyperthyroidism.

33. Course and prognosis Onset usually before age of 20 years. Usually slowly progressive, but sometimes can progress rapidly. Segmental vitiligo progresses initially but stabilizes in about 6 months Spontaneous repigmentation is seen in 30% of patients, especially in the sun-exposed parts . Acrofacial vitiligo is more resistant to treatment .

34. Prognostic factors Following factors indicate poor response to treatment: Long-standing disease. Leucotrichia . Acrofacial lesions. Lesions on resistant areas, i.e ., bony prominences , non-fleshy areas, non-hairy areas and mucosae , and on ankles, wrists, elbows, periungual areas, nipples and areolae lips, and genitalia .

35. ddx Albinism Piebaldism Nevus achromicus - distribution is also fairly stable and are nonprogressive hypopigmented patches Leucoderma -an acquired condition with localized loss of pigmentation of the skin that may occur after any number of inflammatory skin conditions, burns, intralesional steroid injections, postdermabrasion, etc.

36. Investigations Wood lamp examination Dermatopathology - Skin biopsy-show normal skin except for absent melanocytes. Special stain is used to identify melanocyte Electron microscopy-absence of melanocytes and melanosome in keratinocytes Lab studies-T 4, TSH, Fasting blood glucose, CBC with indices(pernicious anemia),ACTH stimulation test(Addison dse suspected)

37. management Rx depends on Age of patient. Extent of disease. Pattern of disease. Cosmetic disability. Effect on quality of life

38. General measures Reassurance and psychological support to the patient and family. Explanation about prognosis.

39. Physical modalities of treatment 1.Photochemotherapy Photo-chemotherapy is use of psoralens in combination with UVA exposure (PUVA). It forms the mainstay of therapy in vitiligo. Repigmetation is slow. M ost frequently used psoralens is 8-methoxypsoralen ( 8-MOP) . Depending on the extent of disease, either topical (for localized disease) or systemic ( for extensive disease) therapy is used.

40. 2.Phototherapy Broadband UVB: Is no longer used. Narrow band UVB (311 nm): Indications: in extensive disease (>10%). Especially indicated in children and in pregnant women and in patients in whom psoralens are contraindicated. Regimen : in gradually increasing doses of UVB, given from specialized chambers. Side effects: generally safe . Excimer laser (308 nm) This is effective but, as for PUVA, repigmentation is also slow. Produces best results in the face

41. Medical treatment 1. Steroids Topical steroids: Are used for: Single lesions, (sometimes a few localized lesions ) especially of recent origin. As adjuvant to other forms of therapy . Systemic steroids: Are used: When the patient cannot be given photo-therapy/ photochemotherapy . In rapidly progressive vitiligo, along with PUVA/PUVA sol. In vitiligo, unresponsive to psoralens . Side effects to steroids limit their use, though the recently devised weekly schedule (oral mini pulse6) probably causes fewer side effects than daily doses.

42. 2. Topical calcineurin inhibitors- Tacrolimus and pimecrolimus . effective in repigmenting vitiligo but only in sun-exposed areas . reported to be most effective when combined with UVB or excimer laser therapy

43. 3. Depigmenting agents: Like monobenzyl ether of hydroquinone . Used to depigment the few normally pigmented areas in patients with extensive vitiligo. Depigmented skin of photo-exposed areas aggressively protected with sunscreens to prevent spotty repigmentation

44. Surgical measures Indications : At sites poorly responsive to conventional therapy (ankles and knuckles), in a patient with stable disease (for at least 6months ). Techniques: Melanocyte transfer . Blister grafting . Punch grafting . Split thickness skin grafting.

45. The end