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,
3. Introduction
ā¢ Vitiligo is an acquired & progressive pigmentary
disorder of the skin and mucous membranes
ā¢ Characterized by loss of melanocytes within the epidermis,
and possibly in other organs as well.
ā¢ Resulting in depigmented macules and patches.
ā¢ It is a common cutaneous disorder that has severe
psychological and significant social consequences.
4. Epidemiology
ā¢ Vitiligo affects ~0.1-2% of the general population worldwide.
ā¢ US - estimated incidence is 1%.
ā¢ It can occur at any age
ā¢ With peak onset of 10-30 yrs, (50% - develops before the age of
20yrs)
ā¢ All races are affected
ā¢ Both sexes are equally affected
5. Epidemiology
ā¢ ~30-40% of Pts have at least one first-degree relative with
vitiligo.
ā¢ The relative risk for first-degree relatives of vitiligo pts is
increased by 7-10 fold.
ā¢ Most pts attribute the onset to specific life events (physical
injury, sunburn, emotional stress, illness or pregnancy)
ā¢ Most common sites are - periorificial, face, genitals, extensor
surfaces, hands, and feet.
7. Epidemiology in Tigray,Ethiopia
ā¢ 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.
ā¢ Males 22(57.9%) were affected more than females 16(42.1%) giving
a male to female ratio of 1.4:1.
ā¢ 50.9% of the Respondents were aged between 14-24 years.
ā¢ 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
ā¢ Vitiligo is a multifactorial disorder with a complex pathogenesis.
ā¢ The precise cause remains unknown.
ā¢ 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
ā¢ Vitiligo is characterized by
Incomplete penetrance,
Multiple susceptibility loci, and
Genetic heterogeneity
ā¢ A recent study on pts and families identified at least ten different
loci that contribute to GV risk
ā¢ 7 of these GV susceptibility loci have also been associated with
other AI diseases
ā¢ HLA class I, HLA class II, PTPN22, LPP, IL2RA, UBASH3A, and
C1QTNF6
10. Autoimmune Hypothesis
ā¢ The autoimmune theory proposes that alterations in humoral or
cellular immunity result in the destruction of melanocytes.
ā¢ Dysfunction of the humoral components is supported by the
association of vitiligo with autoimmune disease
12. Autoimmune Hypothesis
ā¢ This group of disorders is accompanied by circulating anti-organ
antibodies.
ā¢ These autoantibodies are directed against several melanocyte
antigens such as:
ā¢ Tyrosinase-related proteins 1 and 2 (TYRP1 and TYRP2)
ā¢ More recently, two transcription factors (SOX9 and SOX10) and
the melanin-concentrating hormone receptor-1
13. Autoimmune Hypothesis
ā¢ Cellular Immune Mechanisms
ā¢ Destruction of melanocytes may be directly mediated by
autoreactive cytotoxic T cells.
ā¢ An increased number of circulating CD8+ cytotoxic lymphocytes
ā¢ Specific cytotoxic responses against MART-l, tyrosinase and
gp100.
14. Oxidant-Antioxidant hypothesis
ā¢ Suggests that accumulation of free radicals toxic to melanocytes
leads to their destruction.
ā¢ 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
ā¢ Proposes certain chemical mediators (neural peptides)
released from nerve endings cause decreased melanin
production and could have a toxic effect on
melanocytes.
ā¢ Segmental vitiligo/dermatomal pattern
Intrinsic defect of melanocytes:
ā¢ Melanocytes have an inherent abnormality that
impedes their growth and differentiation in conditions
that support normal melanocytes.
16. Convergence Theory
ā¢ 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
ā¢ All contribute to the phenomenon of vitiligo
ā¢ Experts concur that vitiligo may be a syndrome rather than a
single disease.
18. Clinical Features
ā¢ Most Pts present with one to several amelanotic macule/patch,
that appear chalk- or milk-white in color.
ā¢ The lesions are usually well-demarcated, round, oval or linear in
shape.
ā¢ Range from millimeters to centimeters in size.
ā¢ The borders are usually convex and enlarge centrifugally at an
unpredictable rate.
19. Clinical Features
ā¢ Usually asymptomatic, but occasionally, may be pruritic.
ā¢ Can occur anywhere on the body
ā¢ Most frequently:
ā¢ 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)
21. Clinical Features
ā¢ Body hair in vitiliginous macules may be
depigmented(leukotrichia)
ā¢ Pts can also have a localized patch of white or
gray hair (poliosis)
ā¢ Palmoplantar, lip and oral mucosa
involvement in lightly pigmented individuals
is difficult to visualize
23. Trichrome vitiligo
ā¢ Is characterized by both
depigmented and hypopigmented
macules in addition to normally
pigmented skin.
ā¢ Results 3 shades of color ā tan
zone, normal and totally
depigmented skin
ā¢ The natural evolution of the
hypopigmented areas is
progression to full depigmentation
24. Quadrichrome vitiligo
ā¢ Refers to the additional presence of
marginal or perifollicular
hyperpigmentation.
ā¢ Presence of a fourth color (dark brown)
at sites of perifollicular repigmentation.
ā¢ This variant is recognized more
frequently in darker skin types,
particularly in areas of repigmentation
25. Pentachrome vitiligo
ā¢ Additional blue-gray hyperpigmented macules with 5 shades
of color has been described (black, dark brown, medium
brown [unaffected skin], tan and white)
ā¢ Representing areas of melanin incontinence (dermal
melanin).
ā¢ Observed in a pts with post inflammatory hyperpigmentatio
who then developed vitiligo.
26. Marginal Inflammatory vitiligo
ā¢ Characterized clinically by raised
border erythema at the margins of
vitiligo.
ā¢ In 5% of pts, a pruritic, inflammatory
border is associated with edema, and
erythema is visible.
27. Vitiligo ponctue (Confetti type)
ā¢ Unusual variant
ā¢ 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)
ā¢ Development of vitiligo in
sites of specific trauma,
such as a cut, burn, or
abrasionā¦...
ā¢ Minimum injury is required
for Koebner phenomenon to
occur
ā¢ Observed in both bilateral &
unilateral forms of vitiligo
29. Occupational vitiligo
ā¢ Thiols, phenolic compounds,
catechols, mercaptoamines,
and several quinines
(including chloroquine) can
produce depigmentation.
30. Clinical classification of vitiligo
ā¢ According to the extent of involvement, severity and distribution
of the depigmentation, vitiligo has been classified in different
clinical classes.
ā¢ This classification is very useful to evaluate different therapeutics
regimens.
Based on severity vitiligo can be divided into 4 stages
Limited (10%) involvement
Moderate (10ā25%)
Moderately severe (26ā50%)
Severe disease (50%) depigmentation
31. ā¢ 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
ā« A. Segmental
ā« B. Non-segmental
32. Localized vitiligo
ā¢ Restricted to one general area of distribution
ā¢ Further subtyped into focal, segmental, and mucosal
Focal vitiligo
ā¢ Usually a solitary macule or a few scattered macules in one area
ā¢ But not clearly in a segmental or zosteriform distribution
ā¢ The neck and trunk are also commonly involved
Mucosal vitiligo:
ā¢ Mucous membranes alone are affected.
33. Localized vitiligo
Segmental (unilateral) vitiligo
ā¢ One or more macules involving a unilateral segment (dermatomal)
distribution
ā¢ The lesions stop abruptly at the midline
ā¢ Tends to have an early age of onset
ā¢ The trigeminal dermatome, with poliosis (> 50%) and tend to be
stable
ā¢ Not associated with autoimmune diseases.
ā¢ Bad prognosis
34. Generalized vitiligo (bilateral vitiligo)
ā¢ More than one general area of involvement either symmetrically
or asymmetrically arrayed
ā¢ Is the commonest (>90% of vitiligo pts)
ā¢ Begin later in life
ā¢ Sites sensitive to pressure, friction, trauma and mucous mms
involvement is frequently observed
ā¢ Typically progressive with flare-ups
ā¢ Hair is affected in later stages.
ā¢ Associated with personal or family Hx of autoimmune diseases.
ā¢ Has 3 subtypes
35. Generalized vitiligo (bilateral vitiligo)
Vulgaris
ā¢ Most common subtype
ā¢ Scattered patches that are
widely distributed
Acrofacial
ā¢ Depigmentation occurs on
the Distal extremities (distal
fingers, periungual ) & face
(periorificial, lip ) areas.
Mixed
ā¢ Various combinations
ā¢ Acrofacial & vulgaris vitiligo,
or segmental & Acrofacial
vitiligo &/or vulgaris vitiligo
present together.
36. Universal vitiligo
ā¢ Depigmented macules and patches over most of the body
ā¢ Complete or nearly complete depigmentation
ā¢ It involves more than 80% of the skin
ā¢ The worst QOL is seen in these pts
ā¢ Associated with multiple autoimmune diseases and +ve family Hx
37. Associated Disorders
Ocular finding
ā¢ Patients with vitiligo can have several ocular findings like:
ā¢ Uveitis (the most significant ocular abnormality associated with
vitiligo)
ā¢ Pigmentary abnormalities of the iris and retina
ā¢ Choroidal abnormalities (~30%)
ā¢ Iritis (~5%)
ā¢ Visual acuity is generally not affected.
38. Associated Disorders
Auditory Findings
ā¢ Abnormal sensory hearing loss (suggesting an impairment of
cochlear melanocytes)
VOGT-KOYANAGI-HARADA SYNDROME (VKH)
ā¢ VKH syndrome consists of vitiligo in association with uveitis,
aseptic meningitis, dysacusis, tinnitus, poliosis, and alopecia.
ā¢ It is a rare, systemic, T-cell-mediated autoimmune disorder.
ā¢ Associated with other autoimmune disorders - autoimmune
polyglandular syndrome, hypothyroidism, Hashimoto thyroiditis,
and diabetes mellitus.
39. Associated Disorders
ALEZZANDRINI SYNDROME
ā¢ Facial vitiligo, poliosis, deafness, and unilateral retinitis
(decreased visual acuity and an atrophic iris)
ā¢ Etiology - poorly understood, ???autoimmune processes
Melanoma
ā¢ Vitiligo like depigmentation can occur in patients with malignant
melanoma
ā¢ Believed to result from a T-cellāmediated reaction to antigenic
melanoma cells and cross-reactivity to healthy melanocytes.
40. PROGNOSIS AND CLINICAL COURSE
ā¢ Unpredictable
ā¢ Initial clinical sub-type of vitiligo does not predict future
anatomical sites of involvement or activity of disease
ā¢ Complete and stable repigmentation is rare.
ā¢ Spontaneous repigmentation - 10ā20% of Pts, most frequently in
sun-exposed areas and in younger pts.
ā¢ Spontaneous repigmentation poliosis does not occur.
41. PROGNOSIS AND CLINICAL COURSE
Poor prognostic sign
ā¢ Early age of onset
ā¢ Presence of associated autoimmune disorders
ā¢ Acrofacial Vitiligo.
ā¢ Segmental Vitiligo
ā¢ A family history of vitiligo,
ā¢ Mucosal involvement,
ā¢ A positive Koebner response
ā¢ Leucotrichia
43. Diagnosis
ā¢ Dx is primarily based on clinical examination
ā¢ Hx/careful examination (ophthalmologic and audiologic)
ā¢ Pts should be questioned about symptoms for common related
autoimmune disorders.
44. Workup
Woodās lamp examination
ā¢ light is strongly absorbed by melanin
ā¢ yellow/green or bluish fluorescence with sharp margins
ā¢ Palmoplantar, lip and oral mucosa involvement in lightly
pigmented individuals.
ā¢ Determine true extent of involvement and activity of vitiligo
ā¢ Monitoring response to therapy
46. Workup
Biopsy
ā¢ Marked absence of melanocytes
and melanin in the epidermis,
which appear to be replaced by
Langerhansā cells.
ā¢ There is increased cellularity of the
dermis.
ā¢ Melanocytes on the pigmented
edge of vitiliginous skin are larger,
often vacuolated, and with long
dendritic processes filled with
melanin granules.
ā¢ special Immunohistochemical
staining that can maximize yield
by detecting both active and
dormant melanocyes
47. Management
The aims of treatments are:
ā¢ Attain repigmentation
ā¢ Minimize disease progression (stabilization of the depigmentation
process)
ā¢ Achieve cosmetically pleasing results
ā¢ Improvement in quality of life
ā¢ Treatment efficacy varies with duration and type of
vitiligo.
50. MEDICAL TREATMENTS
Topical treatment
ā¢ First-line vitiligo treatment includes moderate-to-high strength
topical corticosteroids and calcineurin inhibitors.
ā¢ Both of which dampen the cellular immune response.
ā¢ 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
ā¢ 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): 15ā28.
Published online 2017 Jan 1.
51. MEDICAL TREATMENTS
Systemic medications
Systemic corticosteroids
ā¢ Are generally employed in rapidly progressive cases to help with
disease stabilization.
ā¢ 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 13.2Ā±3.1 weeks.
ā¢ Some degree of repigmentation was observed in all lesions at a
mean of 16.1Ā±5.9 weeks.
ā¢ Relapse occurred in 12.3 percent of patients at an average of
55.7Ā±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
ā¢ 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.
ā¢ 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): 15ā28.
Published online 2017 Jan 1.
53. MEDICAL TREATMENTS
Methotrexate
ā¢ 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.
ā¢ 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): 15ā28.
Published online 2017 Jan 1.
55. Phototherapy
MOA
ā¢ Act as a skin immunomodulator, regulating the activity of
inflammatory cytokines & polarizing the immune response toward
the Th2 profile.
ā¢ 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)
ā¢ It is a treatment of choice than BB-UVB
ā¢ NB UVB - is the first choice for
Adults and children (>6yrs) - generalized vitiligo
Localized vitiligo associated with a significant impact on
patientās quality of life (QoL).
ā¢ Administered 2-3x per week, but never on two consecutive days.
ā¢ Monitored with serial photographs every 2-3 months.
57. Phototherapy
Photochemotherapy (PUVA)
ā¢ Topical or oral 8-methoxypsoralen followed by exposure to either
artificial UV (320 to 400 nm) light or natural sunlight (PUVASOL)
ā¢ In general, vitiligo on the trunk, proximal extremities, and face
respond well to PUVA, but lesions on the distal extremities respond
poorly.
ā¢ The total number of PUVA Tx required is b/n 50 and 300.
58. NB-UVB is preferred than PUVA
ā¢ Shorter Tx times with greater efficacy (67% VS 46%)
ā¢ No drug costs
ā¢ No GI side effects (such as nausea..)
ā¢ Reduced photo toxic reactions
ā¢ No need for post-treatment photoprotection
ā¢ Can be used in children, pregnant or lactating women, and
in individuals with hepatic or kidney dysfunction.
59. Phototherapy
Excimer laser
ā¢ The excimer laser produces monochromatic rays at 308 nm to
treat limited, stable patches of vitiligo.
ā¢ Efficacy is close to NB-UVB
ā¢ Has advantage of delivering high doses of light to the vitiligo
lesions.
ā¢ 3x weekly, with Tx periods of >12 weeks (average of 24 - 48
sessions)
ā¢ Best treatment results on the face
ā¢ Erythema is a possible side effect
60. Surgical treatments
ā¢ Transfer of melanocytes or full-thickness skin from normally
pigmented areas to hypomelanotic patches.
ā¢ For pts who fail to respond with significant repigmentation,
autologous transplantation can be performed.
The general selection criteria for autologous
transplantation are:
ā¢ Small areas of vitiligo with stable activity (No progression for at
least 2 yrs)
ā¢ Absence of new koebnerization
ā¢ No tendency for scar or keloid formation
ā¢ Age above 12 years
61. Surgical treatments
Several methods are used for surgical repigmentation
CELLULAR GRAFTING
ā¢ Non-cultured epidermal
suspensions
ā¢ Melanocyte culture
transplantation
TISSUE GRAFTING
ā¢ Suction blister grafting
ā¢ Split thickness grafting
ā¢ Mini-Punch grafting
ā¢ Follicular unit grafting
ā¢ Smash grafting
62. Depigmentation
ā¢ Pts who have extensive vitiligo with only a few areas of residual
normal pigmented skin.
ā¢ Monobenzyl ether of hydroquinone (Monobenzone) is the agent
used for depigmentation
ā¢ It is a phenolic toxin that destroys epidermal melanocytes resulting
uniform depigmented state
ā¢ Available as a 20% cream and can be formulated at concentrations
up to 40%.
63. Depigmentation
ā¢ Most commonly used is 20% , applied 1-2x daily for 9-12mo or
longer.
ā¢ Response start 1-3 mo
ā¢ Avoid direct contact with others for 1hr after application.
64. Camouflage
ā¢ Make-up, self-tanning products, or other topical dyes
ā¢ A valuable Tx option:
Focal vitiligo
Lesions on exposed skin (face, neck, or hands)
ā¢ Exact color match to the patient's normal skin.
66. Psychological treatments
ā¢ The impact of this disorder on psychological and
quality of life is very severe in many patients.
ā¢ The use of support groups and psychological counseling
are important supplementary therapies.
ā¢ May actually improve clinical outcomes.
67. REFERNCES
ā¢ Fitzpatrickās 8th
ā¢ Bologna 3rd
ā¢ Rookās 8th
ā¢ Medscape
ā¢ Uptodate 21.2
ā¢ 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
ā¢ 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 )
ā¢ 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):E1āE13. [PMC free article] [PubMed]
ā¢ Silverberg JI, Silverberg NB. Association between vitiligo extent and distribution and
quality-of-life impairment. JAMA Dermatol. 2013;149:159ā64. [PubMed]
ā¢ Kanwar AJ1, Mahajan R, Parsad D. Low-dose oral mini-pulse dexamethasone
therapy in progressive unstable vitiligo.