This document provides an overview of vitiligo, including: - Vitiligo is a pigmentation disorder characterized by loss of skin pigment cells called melanocytes, resulting in white patches of skin. - It affects around 0.1-2% of the general population worldwide. Onset is usually between 10-30 years of age. - The cause is unknown but theories include genetic factors, autoimmunity, oxidative stress, and neural mechanisms. - Clinically, vitiligo appears as well-demarcated white patches that develop in areas of skin. - Treatments aim to induce repigmentation or stabilize the disease, and include topical corticosteroids, phototherapy,

1. VITILIGO
Dr.Tesfamariam (R2)
Feb,2019

2. Presentation outline
• INTRODUCTION
• EPIDEMOLOGY
• ETIOPATHOGENESIS
• CLINICAL PRESENTATION
• DIFFERENTIAL DIAGNOSIS
• DIAGNOSIS
• PROGNOSIS AND CLINICAL COURSE
• TREATMENT
• REFERENCES

3. Introduction
• Vitiligo is an acquired & progressive pigmentary
disorder of the skin and mucous membranes
• Characterized by loss of melanocytes within the epidermis,
and possibly in other organs as well.
• Resulting in depigmented macules and patches.
• It is a common cutaneous disorder that has severe
psychological and significant social consequences.

4. Epidemiology
• Vitiligo affects ~0.1-2% of the general population worldwide.
• US - estimated incidence is 1%.
• It can occur at any age
• With peak onset of 10-30 yrs, (50% - develops before the age of
20yrs)
• All races are affected
• Both sexes are equally affected

5. Epidemiology
• ~30-40% of Pts have at least one first-degree relative with
vitiligo.
• The relative risk for first-degree relatives of vitiligo pts is
increased by 7-10 fold.
• Most pts attribute the onset to specific life events (physical
injury, sunburn, emotional stress, illness or pregnancy)
• Most common sites are - periorificial, face, genitals, extensor
surfaces, hands, and feet.

6. Epidemiology in Tigray,Ethiopia

7. Epidemiology in Tigray,Ethiopia
• Of the 405 patients, who attended the dermatology outpatient
department of the study center over a period of 3 months, 38(9.4%)
had vitiligo.
• Males 22(57.9%) were affected more than females 16(42.1%) giving
a male to female ratio of 1.4:1.
• 50.9% of the Respondents were aged between 14-24 years.
• Family history was found in 11(28.9 %) of the patients, in first-
degree relatives was 54.5% and in second degree relatives 45.5%.
Journal of Health, Medicine and Nursing
ISSN 2422-8419 An International Peer-reviewed Journal
Vol.52, 2018

8. Etiology and Pathogenesis
• Vitiligo is a multifactorial disorder with a complex pathogenesis.
• The precise cause remains unknown.
• Several theories have been proposed to explain the loss of
epidermal melanocytes in vitiligo:
Genetic hypothesis
Autoimmune hypothesis
Neural hypothesis
Oxidant-Antioxidant hypothesis
Convergence theory

9. Genetic Hypothesis
• Vitiligo is characterized by
Incomplete penetrance,
Multiple susceptibility loci, and
Genetic heterogeneity
• A recent study on pts and families identified at least ten different
loci that contribute to GV risk
• 7 of these GV susceptibility loci have also been associated with
other AI diseases
• HLA class I, HLA class II, PTPN22, LPP, IL2RA, UBASH3A, and
C1QTNF6

10. Autoimmune Hypothesis
• The autoimmune theory proposes that alterations in humoral or
cellular immunity result in the destruction of melanocytes.
• Dysfunction of the humoral components is supported by the
association of vitiligo with autoimmune disease

11. Autoimmune Hypothesis

12. Autoimmune Hypothesis
• This group of disorders is accompanied by circulating anti-organ
antibodies.
• These autoantibodies are directed against several melanocyte
antigens such as:
• Tyrosinase-related proteins 1 and 2 (TYRP1 and TYRP2)
• More recently, two transcription factors (SOX9 and SOX10) and
the melanin-concentrating hormone receptor-1

13. Autoimmune Hypothesis
• Cellular Immune Mechanisms
• Destruction of melanocytes may be directly mediated by
autoreactive cytotoxic T cells.
• An increased number of circulating CD8+ cytotoxic lymphocytes
• Specific cytotoxic responses against MART-l, tyrosinase and
gp100.

14. Oxidant-Antioxidant hypothesis
• Suggests that accumulation of free radicals toxic to melanocytes
leads to their destruction.
• Oxidative stress plus the accumulation of melanocytotoxic (nitric
oxide) compounds and an inhibition of the natural detoxifying
processes may contribute to the destruction of melanocytes.

15. Neural hypothesis
• Proposes certain chemical mediators (neural peptides)
released from nerve endings cause decreased melanin
production and could have a toxic effect on
melanocytes.
• Segmental vitiligo/dermatomal pattern
Intrinsic defect of melanocytes:
• Melanocytes have an inherent abnormality that
impedes their growth and differentiation in conditions
that support normal melanocytes.

16. Convergence Theory
• Vitiligo is multifactorial and may be the end result of several
different pathologic pathways like:
genetic factors
stress
accumulation of toxic compounds
infection
autoimmunity
altered cellular environment, and impaired
melanocyte migration and proliferation
• All contribute to the phenomenon of vitiligo
• Experts concur that vitiligo may be a syndrome rather than a
single disease.

17. •Clinical Features ,variants
and classification

18. Clinical Features
• Most Pts present with one to several amelanotic macule/patch,
that appear chalk- or milk-white in color.
• The lesions are usually well-demarcated, round, oval or linear in
shape.
• Range from millimeters to centimeters in size.
• The borders are usually convex and enlarge centrifugally at an
unpredictable rate.

19. Clinical Features
• Usually asymptomatic, but occasionally, may be pruritic.
• Can occur anywhere on the body
• Most frequently:
• To areas subjected to repeated trauma or contact with clothing ---
(face, dorsal aspect of the hands, nipples, axillae, umbilicus, bony
prominences, and inguinal and anogenital regions)

20. Clinical Features

21. Clinical Features
• Body hair in vitiliginous macules may be
depigmented(leukotrichia)
• Pts can also have a localized patch of white or
gray hair (poliosis)
• Palmoplantar, lip and oral mucosa
involvement in lightly pigmented individuals
is difficult to visualize

22. Clinical Variants
• Trichrome vitiligo
• Quadrichrome vitiligo
• Pentachrome vitiligo
• Marginal Inflammatory vitiligo
• Vitiligo ponctue (Confetti type)
• Isomorphic Koebner phenomenon (IKP)
• Occupational vitiligo

23. Trichrome vitiligo
• Is characterized by both
depigmented and hypopigmented
macules in addition to normally
pigmented skin.
• Results 3 shades of color → tan
zone, normal and totally
depigmented skin
• The natural evolution of the
hypopigmented areas is
progression to full depigmentation

24. Quadrichrome vitiligo
• Refers to the additional presence of
marginal or perifollicular
hyperpigmentation.
• Presence of a fourth color (dark brown)
at sites of perifollicular repigmentation.
• This variant is recognized more
frequently in darker skin types,
particularly in areas of repigmentation

25. Pentachrome vitiligo
• Additional blue-gray hyperpigmented macules with 5 shades
of color has been described (black, dark brown, medium
brown [unaffected skin], tan and white)
• Representing areas of melanin incontinence (dermal
melanin).
• Observed in a pts with post inflammatory hyperpigmentatio
who then developed vitiligo.

26. Marginal Inflammatory vitiligo
• Characterized clinically by raised
border erythema at the margins of
vitiligo.
• In 5% of pts, a pruritic, inflammatory
border is associated with edema, and
erythema is visible.

27. Vitiligo ponctue (Confetti type)
• Unusual variant
• Characterized by small confetti-like or several tiny, discrete,
amelanotic macules occurring either on normal skin or on a
hyperpigmented macule

28. Isomorphic Koebner phenomenon (IKP)
• Development of vitiligo in
sites of specific trauma,
such as a cut, burn, or
abrasion…...
• Minimum injury is required
for Koebner phenomenon to
occur
• Observed in both bilateral &
unilateral forms of vitiligo

29. Occupational vitiligo
• Thiols, phenolic compounds,
catechols, mercaptoamines,
and several quinines
(including chloroquine) can
produce depigmentation.

30. Clinical classification of vitiligo
• According to the extent of involvement, severity and distribution
of the depigmentation, vitiligo has been classified in different
clinical classes.
• This classification is very useful to evaluate different therapeutics
regimens.
Based on severity vitiligo can be divided into 4 stages
Limited (10%) involvement
Moderate (10–25%)
Moderately severe (26–50%)
Severe disease (50%) depigmentation

31. • Based on distribution vitiligo is divided into 3 types:
1. Localized vitiligo
A. Focal
B. Segmental
C. Mucosal
2. Generalized vitiligo
A. Vulgaris
B. Acrofacial
C. Mixed
3. Universal vitiligo
Based on progression, prognosis
▫ A. Segmental
▫ B. Non-segmental

32. Localized vitiligo
• Restricted to one general area of distribution
• Further subtyped into focal, segmental, and mucosal
Focal vitiligo
• Usually a solitary macule or a few scattered macules in one area
• But not clearly in a segmental or zosteriform distribution
• The neck and trunk are also commonly involved
Mucosal vitiligo:
• Mucous membranes alone are affected.

33. Localized vitiligo
Segmental (unilateral) vitiligo
• One or more macules involving a unilateral segment (dermatomal)
distribution
• The lesions stop abruptly at the midline
• Tends to have an early age of onset
• The trigeminal dermatome, with poliosis (> 50%) and tend to be
stable
• Not associated with autoimmune diseases.
• Bad prognosis

34. Generalized vitiligo (bilateral vitiligo)
• More than one general area of involvement either symmetrically
or asymmetrically arrayed
• Is the commonest (>90% of vitiligo pts)
• Begin later in life
• Sites sensitive to pressure, friction, trauma and mucous mms
involvement is frequently observed
• Typically progressive with flare-ups
• Hair is affected in later stages.
• Associated with personal or family Hx of autoimmune diseases.
• Has 3 subtypes

35. Generalized vitiligo (bilateral vitiligo)
Vulgaris
• Most common subtype
• Scattered patches that are
widely distributed
Acrofacial
• Depigmentation occurs on
the Distal extremities (distal
fingers, periungual ) & face
(periorificial, lip ) areas.
Mixed
• Various combinations
• Acrofacial & vulgaris vitiligo,
or segmental & Acrofacial
vitiligo &/or vulgaris vitiligo
present together.

36. Universal vitiligo
• Depigmented macules and patches over most of the body
• Complete or nearly complete depigmentation
• It involves more than 80% of the skin
• The worst QOL is seen in these pts
• Associated with multiple autoimmune diseases and +ve family Hx

37. Associated Disorders
Ocular finding
• Patients with vitiligo can have several ocular findings like:
• Uveitis (the most significant ocular abnormality associated with
vitiligo)
• Pigmentary abnormalities of the iris and retina
• Choroidal abnormalities (~30%)
• Iritis (~5%)
• Visual acuity is generally not affected.

38. Associated Disorders
Auditory Findings
• Abnormal sensory hearing loss (suggesting an impairment of
cochlear melanocytes)
VOGT-KOYANAGI-HARADA SYNDROME (VKH)
• VKH syndrome consists of vitiligo in association with uveitis,
aseptic meningitis, dysacusis, tinnitus, poliosis, and alopecia.
• It is a rare, systemic, T-cell-mediated autoimmune disorder.
• Associated with other autoimmune disorders - autoimmune
polyglandular syndrome, hypothyroidism, Hashimoto thyroiditis,
and diabetes mellitus.

39. Associated Disorders
ALEZZANDRINI SYNDROME
• Facial vitiligo, poliosis, deafness, and unilateral retinitis
(decreased visual acuity and an atrophic iris)
• Etiology - poorly understood, ???autoimmune processes
Melanoma
• Vitiligo like depigmentation can occur in patients with malignant
melanoma
• Believed to result from a T-cell–mediated reaction to antigenic
melanoma cells and cross-reactivity to healthy melanocytes.

40. PROGNOSIS AND CLINICAL COURSE
• Unpredictable
• Initial clinical sub-type of vitiligo does not predict future
anatomical sites of involvement or activity of disease
• Complete and stable repigmentation is rare.
• Spontaneous repigmentation - 10–20% of Pts, most frequently in
sun-exposed areas and in younger pts.
• Spontaneous repigmentation poliosis does not occur.

41. PROGNOSIS AND CLINICAL COURSE
Poor prognostic sign
• Early age of onset
• Presence of associated autoimmune disorders
• Acrofacial Vitiligo.
• Segmental Vitiligo
• A family history of vitiligo,
• Mucosal involvement,
• A positive Koebner response
• Leucotrichia

42. Differential Diagnosis
• Face
– Tinea versicolor
– Pityriasis alba
– Post-inflammatory
hypopigmentation
– Chemical
leukoderma
– Sarcoidosis
• Anogenital area
– Lichen sclerosus et
atrophicus
• Hands
– Chemical
leukoderma
Infections
• Leishmaniasis
• Leprosy (anaesthetic)
• Onchocerciasis
• Tinea versicolor
• Syphilis
Genetic syndromes
• Hypomelanosis of Ito
• Piebaldism
• Tuberous sclerosis
• Vogt-Koyanagi-Harada
syndrome
Inflammatory disorders
• Dermatitis
• Phototherapy/radiotherapy-induced
hypopigmentation
• Pityriasis alba
• Psoriasis
• SLE
• Sarcoidosis
• Topical or systemic drug-induced
Idiopathic disorders
• Idiopathic guttate hypomelanosis
• Lichen sclerosus et atrophicus
• Lichen striatuselike leukoderma
• Progressive (or acquired) macular
hypomelanosis
Neoplastic
• Amelanotic melanoma
• Halo nevus
• Melanoma-associated leukoderma
• Mycosis fungoides
Malformations
• Nevus anemicus
• Nevus depigmentosus/
hypopigmentosus

43. Diagnosis
• Dx is primarily based on clinical examination
• Hx/careful examination (ophthalmologic and audiologic)
• Pts should be questioned about symptoms for common related
autoimmune disorders.

44. Workup
Wood’s lamp examination
• light is strongly absorbed by melanin
• yellow/green or bluish fluorescence with sharp margins
• Palmoplantar, lip and oral mucosa involvement in lightly
pigmented individuals.
• Determine true extent of involvement and activity of vitiligo
• Monitoring response to therapy

45. Workup
Laboratory Tests
• CBC
• FBS
• LFT
• RFT
• ANA
• TSH level ,T3 & T4

46. Workup
Biopsy
• Marked absence of melanocytes
and melanin in the epidermis,
which appear to be replaced by
Langerhans’ cells.
• There is increased cellularity of the
dermis.
• Melanocytes on the pigmented
edge of vitiliginous skin are larger,
often vacuolated, and with long
dendritic processes filled with
melanin granules.
• special Immunohistochemical
staining that can maximize yield
by detecting both active and
dormant melanocyes

47. Management
The aims of treatments are:
• Attain repigmentation
• Minimize disease progression (stabilization of the depigmentation
process)
• Achieve cosmetically pleasing results
• Improvement in quality of life
• Treatment efficacy varies with duration and type of
vitiligo.

48. Management
options:
• Medical
• Physical
• Surgical
• Depigmentation
• Camouflage
• Psychological support

49. Management
General measures
• Patient education about the disease course , treatment options & outcome
• Psychological support
• Use of sun screens

50. MEDICAL TREATMENTS
Topical treatment
• First-line vitiligo treatment includes moderate-to-high strength
topical corticosteroids and calcineurin inhibitors.
• Both of which dampen the cellular immune response.
• Several recent studies comparing the use of topical steroids to
calcineurin inhibitors have found topical steroids (mometasone
0.1% or clobetasol 0.05% daily) similar in efficacy to calcineurin
inhibitors (tacrolimus 0.1% or pimecrolimus 1.0% BID
• A study by Kose et al showed mean repigmentation rates of 65
percent with mometasone and 42 percent with pimecrolimus after
three months of daily treatment .
J Clin Aesthet Dermatol. 2017 Jan; 10(1): 15–28.
Published online 2017 Jan 1.

51. MEDICAL TREATMENTS
Systemic medications
Systemic corticosteroids
• Are generally employed in rapidly progressive cases to help with
disease stabilization.
• In a large, retrospective study, Kanwar et al found that low-dose
oral dexamethasone mini pulse therapy (2.5mg/day on 2
consecutive days/week) halted progressive vitiligo in 91.8 percent
of subjects at a mean of 13.2±3.1 weeks.
• Some degree of repigmentation was observed in all lesions at a
mean of 16.1±5.9 weeks.
• Relapse occurred in 12.3 percent of patients at an average of
55.7±26.7 weeks post-treatment.
Kanwar AJ1, Mahajan R, Parsad D. Low-dose oral mini-pulse
dexamethasone therapy in progressive unstable vitiligo.

52. MEDICAL TREATMENTS
Minocycline
• Has also shown promising outcome in the treatment of vitiligo
due to its anti-inflammatory & free-radical scavenging properties
that confer a protective effect on melanocytes against H2O2-
induced apoptosis.
• A preliminary study assessing the efficacy of oral minocycline
(100mg daily) in progressive, slowly spreading vitiligo showed
initial arrest of disease progression in 91 percent (29/32) of
patients and arrest of re-progression in 10 patients after one
month.
J Clin Aesthet Dermatol. 2017 Jan; 10(1): 15–28.
Published online 2017 Jan 1.

53. MEDICAL TREATMENTS
Methotrexate
• Singh et al recently conducted a randomized, open-label trial of
methotrexate (10mg weekly) compared with oral mini-pulse
steroid therapy in 52 patients with unstable vitiligo.
• And found no difference in effectiveness between the two
treatment modalities in halting the spread of depigmentation.
Statins
J Clin Aesthet Dermatol. 2017 Jan; 10(1): 15–28.
Published online 2017 Jan 1.

54. Phototherapy
• Narrowband UVB (311 nm)
• Broadband UVB (BB-UVB—290–320 nm),
• Photochemotherapy
PUVA
• Excimer laser

55. Phototherapy
MOA
• Act as a skin immunomodulator, regulating the activity of
inflammatory cytokines & polarizing the immune response toward
the Th2 profile.
• Induction of local immunosuppression and stimulation of the
proliferation of melanocytes in the skin and the outer root sheath
of hair follicles

56. Phototherapy
Phototherapy (NB-UVB)
• It is a treatment of choice than BB-UVB
• NB UVB - is the first choice for
Adults and children (>6yrs) - generalized vitiligo
Localized vitiligo associated with a significant impact on
patient’s quality of life (QoL).
• Administered 2-3x per week, but never on two consecutive days.
• Monitored with serial photographs every 2-3 months.

57. Phototherapy
Photochemotherapy (PUVA)
• Topical or oral 8-methoxypsoralen followed by exposure to either
artificial UV (320 to 400 nm) light or natural sunlight (PUVASOL)
• In general, vitiligo on the trunk, proximal extremities, and face
respond well to PUVA, but lesions on the distal extremities respond
poorly.
• The total number of PUVA Tx required is b/n 50 and 300.

58. NB-UVB is preferred than PUVA
• Shorter Tx times with greater efficacy (67% VS 46%)
• No drug costs
• No GI side effects (such as nausea..)
• Reduced photo toxic reactions
• No need for post-treatment photoprotection
• Can be used in children, pregnant or lactating women, and
in individuals with hepatic or kidney dysfunction.

59. Phototherapy
Excimer laser
• The excimer laser produces monochromatic rays at 308 nm to
treat limited, stable patches of vitiligo.
• Efficacy is close to NB-UVB
• Has advantage of delivering high doses of light to the vitiligo
lesions.
• 3x weekly, with Tx periods of >12 weeks (average of 24 - 48
sessions)
• Best treatment results on the face
• Erythema is a possible side effect

60. Surgical treatments
• Transfer of melanocytes or full-thickness skin from normally
pigmented areas to hypomelanotic patches.
• For pts who fail to respond with significant repigmentation,
autologous transplantation can be performed.
The general selection criteria for autologous
transplantation are:
• Small areas of vitiligo with stable activity (No progression for at
least 2 yrs)
• Absence of new koebnerization
• No tendency for scar or keloid formation
• Age above 12 years

61. Surgical treatments
Several methods are used for surgical repigmentation
CELLULAR GRAFTING
• Non-cultured epidermal
suspensions
• Melanocyte culture
transplantation
TISSUE GRAFTING
• Suction blister grafting
• Split thickness grafting
• Mini-Punch grafting
• Follicular unit grafting
• Smash grafting

62. Depigmentation
• Pts who have extensive vitiligo with only a few areas of residual
normal pigmented skin.
• Monobenzyl ether of hydroquinone (Monobenzone) is the agent
used for depigmentation
• It is a phenolic toxin that destroys epidermal melanocytes resulting
uniform depigmented state
• Available as a 20% cream and can be formulated at concentrations
up to 40%.

63. Depigmentation
• Most commonly used is 20% , applied 1-2x daily for 9-12mo or
longer.
• Response start 1-3 mo
• Avoid direct contact with others for 1hr after application.

64. Camouflage
• Make-up, self-tanning products, or other topical dyes
• A valuable Tx option:
Focal vitiligo
Lesions on exposed skin (face, neck, or hands)
• Exact color match to the patient's normal skin.

65. Camouflage

66. Psychological treatments
• The impact of this disorder on psychological and
quality of life is very severe in many patients.
• The use of support groups and psychological counseling
are important supplementary therapies.
• May actually improve clinical outcomes.

67. REFERNCES
• Fitzpatrick’s 8th
• Bologna 3rd
• Rook’s 8th
• Medscape
• Uptodate 21.2
• Alexander B. Dillon, MD, Andrew Sideris, MSC, Ali Hadi, BA, and Nada Elbuluk,
MD, MSC Advances in Vitiligo: An Update on Medical and Surgical Treatments
• Prevalence of Vitiligo and Associated Factors AmongAdult Patients Attending Ayder
Referral Teaching Hospital Dermatology Clinic in Mekelle Town, Tigray Region-
Northern Ethiopia (journal of Health, Medicine and Nursing )
• Ezzedine K, Lim HW, Suzuki T, et al. Revised classification/nomenclature of vitiligo
and related issues: the Vitiligo Global Issues Consensus Conference. Pigment Cell
Melanoma Res. 2012;25(3):E1–E13. [PMC free article] [PubMed]
• Silverberg JI, Silverberg NB. Association between vitiligo extent and distribution and
quality-of-life impairment. JAMA Dermatol. 2013;149:159–64. [PubMed]
• Kanwar AJ1, Mahajan R, Parsad D. Low-dose oral mini-pulse dexamethasone
therapy in progressive unstable vitiligo.