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A STUDY ON THE CORRELATION OF SERUM CHOLECALCIFEROL LEVEL AND VITILIGO IN PATIENTS
ATTENDING GOVERNMENT RAJAJI HOSPITAL, MADURAI
Dissertation submitted in partial
fulfillment of the university regulations for
M.D. DEGREE in
DERMATOLOGY, VENEREOLOGY AND LEPROSY
(BRANCH XX)
APRIL 2018
THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY
CHENNAI TAMIL NADU
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CERTIFICATE FROM THE DEAN
This is to certify that this dissertation entitled " A STUDY ON THE
CORRELATION OF SERUM CHOLECALCIFEROL LEVEL AND
VITILIGO IN PATIENTS ATTENDING GOVERNMENT RAJAJI
HOSPITAL, MADURAI" submitted by Dr. Deepthi Vijayakumar to The Tamil
Nadu Dr. M.G.R. Medical University, Chennai is in partial fulfillment of the
requirement for the award of M.D.[DERMATOLOGY, VENEREOLOGY AND
LEPROSY] and is a bonafide research work carried out by her under direct
supervision and guidance. This work has not previously formed the basis for the
award of any degree or diploma.
Dr. MARUDHUPANDIYAN M.S. (GENERAL SURGERY)
THE DEAN,
Madurai Medical College,
Government Rajaji Hospital,
Madurai.
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CERTIFICATE FROM THE HOD
This is to certify that this dissertation entitled " A STUDY ON THE
CORRELATION OF SERUM CHOLECALCIFEROL LEVEL and VITILIGO
IN PATIENTS ATTENDING GOVERNMENT RAJAJI HOSPITAL,
MADURAI submitted by Dr. Deepthi Vijayakumar to The Tamil Nadu Dr.M.G.R.
Medical University, Chennai is in partial fulfillment of the requirement for the award
of M.D. [DERMATOLOGY, VENEREOLOGY AND LEPROSY] and is a bonafide
research work carried out by her under direct supervision and guidance. This work has
not previously formed the basis for the award of any degree or diploma.
Dr. G.GEETHARANI M.D., D.D.,
Professor and HOD.
Department of Dermatology,
Madurai Medical College and
Government Rajaji Hospital,
Madurai.
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CERTIFICATE FROM THE GUIDE
This is to certify that this dissertation entitled " A STUDY ON THE
CORRELATION OF SERUM CHOLECALCIFEROL LEVEL AND
VITILIGO IN PATIENTS ATTENDING GOVERNMENT RAJAJI
HOSPITAL, MADURAI submitted by Dr.Deepthi Vijayakumar to The Tamil
Nadu Dr.M.G.R. Medical University, Chennai is in partial fulfillment of the
requirement for the award of M.D.[DERMATOLOGY, VENEREOLOGY AND
LEPROSY] and is a bonafide research work carried out by her under my direct
supervision and guidance. This work has not previously formed the basis for the
award of any degree or diploma.
Dr. G.GEETHARANI M.D., D.D.,
Professor and HOD.
Department of Dermatology,
Madurai Medical College and
Government Rajaji Hospital,
Madurai.
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DECLARATION
I, Dr. DEEPTHI VIJAYAKUMAR, solemnly declare that the dissertation
titled A STUDY ON THE CORRELATION OF SERUM
CHOLECALCIFEROL LEVEL AND VITILIGO IN PATIENTS ATTENDING
GOVERNMENT RAJAJI HOSPITAL, MADURAI is a bonafide work done by
me at Government Rajaji Hospital during 2015 2018 under the guidance and
supervision of Prof. Dr. G. GEETHARANI M.D., D.D., Professor and Head of the
Department of Dermatology, Madurai Medical College, Madurai. I also declare that
this bonafide work or a part of this work was not submitted by me or any other for any
award, degree and diploma to any university, board either in India or abroad. The
dissertation is submitted to The Tamilnadu Dr.M.G.R. Medical University, towards
partial fulfilment of requirement for the award of M.D.Degree in Dermatology,
Venereology and Leprosy (BRANCH XX).
Place: Madurai.
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ACKNOWLEDGEMENT
I am extremely thankful to Dr. MARUDHUPANDIYAN, M.S, Dean, Madurai
Medical College, and Medical Superintendent, Government Rajaji Hospital,
Madurai for permitting me to use the college and hospital facilities for this study.
I express my sincere and heartfelt gratitude to Prof.Dr.G.Geetharani M.D., D.D.,
Professor and Head of the Department of Dermatology, Madurai medical college,
Madurai, for her excellent guidance and supervision for this dissertation work. Her
commitment, devotion and perfection in work gave me the drive for completing the
project successfully.
I would like to express my deep sense of gratitude to Dr.P.Mohan kumaresh ,
M.D., Professor and Head of the department of Biochemistry for his kindly help of
sharing his wisdom and experience without which this study would not have been
possible.
I profoundly thank Prof.Dr.R.Suganthy Rajakumari M.D., Professor and Head
of the Department of Venereology who has always guided me, by example and
valuable words of advice through the conduct of the study and also during my
postgraduate course. My heartful thanks to Dr. K. Dhanalakshmi M.D., D.V.L,
Associate Professor for her valuable support and guidance throughout the study. I
proudly thank Dr. K.P. Saradha M.D.D.V.L., Associate professor for her valuable
guidance.
I express my deep sense of gratitude and thanks to my teachers
Dr.R.Kothandaraman, Associate Professor, Dr.P.Sathesh and Dr.S.Deva Prabha
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Assistant Professors, for their valuable guidance, timely advice and constant
encouragement.
I would also like to acknowledge my thanks to Dr. S. Sumithra, Dr .R. Sudha,
Dr. S. Durgadevi, and Dr.M.Nithya Assitant Professors of STD for their constant
support during the period of my study.
I would like to convey my regards to fellow post graduates, seniors, juniors and
my family members who have always stood by me in my carrier.
I owe a lot of thanks to my patients without them this study would not have been
possible, and the authors, who have worked on this subject, from whose wisdom and
experience, I have been benefited immensely.
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CONTENTS
S.NO TITLES PAGE NO.
1. INTRODUCTION 10
2. AIM OF THE STUDY 14
3. REVIEW OF LITERATURE 16
4. MATERIALS AND METHODS 54
5. OBSERVATION AND RESULTS 58
6. DISCUSSION 75
7. SUMMARY 85
8. CONCLUSION 89
Annexures
BIBILIOGRAPHY 9 1
PROFORMA 110
CLINICAL PHOTOGRAPHS 123
MASTER CHART 138
ANTI PLAGIARISM CERTIFICATE 146
ETHICAL COMMITTEE APPROVAL FORM 1
49
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ABBRIEVATIONS
IL- Interleukin
IF ἀ- Interferon alpha
TNF ἀ- Tumour Necrosis Factor alpha
HLA- Human Leukocyte Antigen
NALP- NACHT Leucine rich repeat Protein
NLR- Nod Like Receptor
AIS- Autoimmune Susceptibility
PTPN- Lymphocyte Protein Tyrosine Phosphatase
CTLA4- Antigen 4 of Cytotoxic T Lymphocytes
MITF- Microphthalmia Associated Transcription Factor
ACE- Angiotensin Converting Enzyme
VDR- Vitamin D Receptor
AIRE- AutoImmune Regulator
COMT-Catechol O Methyl Transferase
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INTRODUCTION
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INTRODUCTION
Vitiligo is an autoimmune pigmentary disorder caused by destruction of
functional melanocytes in epidermis and infundibulum of hair, characterized by well
demarcated depigmented patches or macules. It affects both sexes and all races
equally. The inheritance is polygenic or autosomal dominant with variable
penetrance.
The following hypothesis have been postulated regarding its
etiopathogenesis:1,3,4,5
1. Autoimmune hypothesis: This theory is based on the clinical association of
vitiligo with other autoimmune disorders like Hashimoto's thyroiditis, pernicious
anemia, Addisons disease, diabetes mellitus, myasthenia gravis, alopecia areata. Also,
antibodies to human melanocytes have been detected using immunoprecipitant assay
in some patients.
2. Neurogenic hypothesis: This theory suggest that neuropeptide Y released from
peripheral nerve endings may inhibit melanogenesis. Electron microscopy shows
abnormalities in peripheral nerves.
3. Self destruct theory of Lerner: This theory suggest that melanocytes destroy
themselves due to a protective mechanism that removes toxic melanin precursors.
This is based on studies of cutaneous depigmentation caused by chemical compounds
that have selective lethal effects on functional melanocytes.
4. It is suggested that defective keratinocyte metabolism plays a major role and a new
hypothesis relating vitiligo with defective tetrahydrobiopterin and catecholamine
biosynthesis have been postulated.
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Role of vitamin D in melanogenesis:
Vitamin D is synthesized from 7 dehydrocholesterol present in skin which is
converted to 25(OH) cholecalciferol and then to its active metabolite 1,25(OH)2
cholecalciferol and has a role in skin pigmentation.
1.Vitamin D in addition to its regulatory effect in calcium and bone metabolism,
controls cell proliferation and differentiation, exerts immuno regulatory activities via
its nuclear receptor and increases melanogenesis. It increases the tyrosinase content
of cultured human melanocytes by its antiapoptotic effect.6
2.Topical vitamin D increased L-3,4 dihydroxyphenylalanine positive melanocytes6
and is used in combination with other modalities of treatment for vitiligo successfully.
3.Vitamin D exerts immunomodulatory effect by inhibiting the expression of
cytokines IL6, IL8, IL10, IL12, IFἀ, TNFἀ 7,8,9 which are pro inflammatory and
proapoptotic in vitiligo.
4.Another study revealed Apa-I polymorphism9 of vitamin D receptor gene is
associated with vitiligo.
Normal serum vitamin D is 30-70ng/ml (75- 250 nmol/L). Low levels of vitamin
D has been observed in vitiligo and other autoimmune disorders.6-9 The improvement
of serum vitamin D deficiency after UV exposure correlates with clinical
improvement13 as assessed by VASI score.16
Thus, vitamin D and its receptor play a role in etiopathogenesis of skin
pigmentation. But, the exact association of low vitamin D levels and vitiligo needs to
be further evaluated. Hence, It is decided to study on this association among vitiligo
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patients attending the Department of Dermatology, Government Rajaji Hospital,
Madurai.
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AIM OF THE STUDY
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AIM OF THE STUDY
To study the relationship between serum cholecalciferol levels and vitiligo with
respect to type, duration and severity among patients attending dermatology OP (out
patient) at Government Rajaji hospital, Madurai.
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REVIEW OF
LITERATURE
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REVIEW OF LITERATURE
NOMENCLATURE
As to the origin of the term "vitiligo", there are different views. The word may
have evolved from the Latin word "vitium", meaning a blemish17 or "vitelius"
signifying a calf's white patches.18
Leider and Rasenblum19 ascribe the term to the Latin word "vitium" which means a
blemish or a fault.
Bateman20 believed that the glistening white appearance of the vitiligenous patches
bear a striking resemblance to the flesh of calves (vituli).
The term vitiligo was first used by the Roman physician Celsus in the second
centaury AD.21
Documentation of the use of the word vitiligo occurred in the first century AD
when the Roman physician Celsus wrote De Medicina.22
HISTORICAL PERSPECTIVE
Vitiligo is a disease of great antiquity. Vitiligo is cited in many ancient writings.
The earliest authentic reference to vitiligo was made in the ancient Indian sacred book
'Atharva Veda'23 which dates back to 1400 BC.
Indian literature dating to 1500 to 1000 BC refers to the words Kilas ("Kil" means
white, "as" means to cast or throw away) and palita ("pal" implies gray, old and aged)
referring to white patches on the skin.
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In the sacred book of Buddhism "Vinay Pitak" (624-544 BC), persons suffering
from kilas were unable to be ordained.24
In the Indian scripture Manusmriti (200 BC), those members of society suffering
from "Svitra" (spreading whiteness) were not respected.
In the Koran, the word "Baras", meaning white skin, is used to describe a condition
that Jesus cured.25
In the Bible, the white spots were grouped, under the Hebrew word "Zora' at" and
have been described in Leviticus chapter 13 in the Old Testament.
The confusion between vitiligo and leprosy prevailed in ancient times also, as the
term "Zora' at" has been translated as lepra in the Greek as well as the English
translation of Bible. This confusion of leprosy with vitiligo in the Old Testament is an
important cause for the social stigma attached to the white spots on the skin.26
Graphic descriptions are given in other ancient Indian medical treatises like Charak
Samhita (800 BC) and Manu Smriti (200 BC). It was described as "Shweta Kushta"
which probably meant vitiligo21.
Vasuchika, which was identified with the plant called Psoralia corylifolia, the oil
from bouchi seeds contains active furocoumarin27 was given for leukoderma until
1950s. In ancient Chinese literature, similar drug, ‘pu-ku-c’ was given for treating
leukoderma. In the thirteenth century, Ibn Eb Bitar in Egypt mentioned the cure of
leukoderma by an Egyptian herb known as Ammi majus, from the fruit extract of
which important furocoumarins were eventually identified in the twentieth century.28
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EPIDEMIOLOGY
Incidence and prevalence
Vitiligo affects all the races and both the sexes all over the world.
The prevalence of vitiligo worldwide varies from 0.1% to 8.0%29 and in India is
0.46-8.8%,30of which stable vitiligo accounted for 65.21%. Lips are the common site
affected in India (75%). The incidence of vitiligo in India was 0.25%- 2.5%.31 Gujarat
and Rajasthan have the highest prevalence.31
Host factors
Age of onset
Vitiligo can occur at any age. Nearly 50% of all vitiligo cases occur below 20
years of age and 70-80% below the age of 30 years.
Some other studies suggest that the lowest age of onset of vitiligo to be at birth32
and the highest age incidence to be 97 years.33
Halder et al34 reviewed their experience with childhood vitiligo. They found it to
be a distinct subset, showing increased segmental presentation, strong autoimmune or
endocrine background and a high incidence of premature graying of hair in the
families and poor response to PUVA therapy.
Sex incidence
Though vitiligo affects both sexes equally, some series based on out patients
attendance show female preponderance5.
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Skin types
Skin types III and IV 5 are commonly associated with vitiligo.
Dietary factors
Prolonged intake of diet poor in protein and cuprominerals35 for prolonged
period was thought to be contributory and cysteine poor diet was associated with
lower incidence of vitiligo.36 There is no significant association between high vitamin
C ingestion and vitiligo.37
Heredofamilial aspects
Familial incidence in India and abroad vary between 7.5% and 41%.38
Inheritance was thought to be autosomal dominant with variable expression and
incomplete penetrance39-41. Few human leukocyte antigen (HLA) associations like
HLA-DR4 in blacks, HLA-B13 in Moroccan Jews, and HLA- BW35 in Yemenite
Jews with vitiligo have been reported. An association with catalase have been
reported42. VIT1 gene found on chromosome 2p16 has been associated with vitiligo.
Recently, variants of a gene NALP1 found on chromosome 17p13 were associated
with vitiligo, and other autoimmune diseases like thyroiditis. NALP1 is a member of
NLR super family of proteins which is involved in the pathogenesis of vitiligo43.
Precipitating factors
These factors include emotional stress, sunburn, major illness, surgery,
pregnancy, parturition and physical trauma44-46.
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AETIOLOGY AND PATHOGENESIS
Various theories have been proposed regarding the pathogenesis of vitiligo. These
concentrate in the following hypothesis:
Autoimmune
Autocytotoxic
Neural
Genetic
AUTOIMMUNE THEORY
The basis of the autoimmune theory initially developed from studies that
demonstrated an association between vitiligo and autoimmune diseases. The primary
disturbance in the immune system results from the formation of auto antibodies
against some antigens of the melanocytes. As a result melanogenesis may be inhibited
or melanocytes may be destroyed47.
Alternatively, some injury to melanocytes may result in the release of an antigenic
substance so that antibody formation occurs either against the melanogenic process or
the antibodies become cytotoxic to melanocytes47.
Several studies have documented that incidence of vitiligo is higher in patients with
autoimmune diseases as compared to its incidence in the general population44,48-52.
A recent study by Naughten et al53 has demonstrated unequivocally in the serum of
vitiligo patients, the presence of antibodies to surface antigens of melanocytes grown
in cell culture according to the method of Eisinger et al.54
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Antityrosinase antibodies have also been found in patients with both local and
generalized vitiligo55,56.
Aronson et al (1987)57 demonstrated a sensitive and specific Ig A immunoassay
against human melanoma cells in patients with active disease, although other
investigators found that antipigment Ig G 1,2, and 3 are present in the serum of
vitiligo patients58.
Mozzanica et al(1990)59 found different CD4+ and CD8+ concentrations,
depending on the stability of the disease. Patients with active vitiligo demonstrated
more marked changes and decreased helper and suppressor T cell levels. The use of T
cell antibodies in active vitiligo biopsy specimens showed a decreased CD4+/CD8+
ratio at the active periphery of the vitiligenous lesions.60
Zaman et al61 (1992) demonstrated that leukocyte migration inhibition factor
levels Ig G immunoglobulin, a marker of T lymphocyte function and circulating
immunocomplex levels are markedly elevated in patients with active vitiligo.
An Ig G antibody to melanocytes, naevus cells and melanoma cells have been
reported in the serum of two patients of vitiligo associated with multiple endocrine
insufficiency.52
Linear deposits of Ig G in the basement membrane zone in 70% and 80% of
cases of vitiligo vulgaris and halo naevus respectively have been reported21.
However, natural killer cell and lymphokine activated killed cell cytotoxicity
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have been shown to be normal in patients with progressive vitiligo according to
Durham Pierre et al(1995).62
Depigmentation possibly occurs secondary to gene expression regulation, as
demonstrated by induction of vitiligo in susceptible chickens with the cytosine
analogue5-azacytidine63. Halder et al64 reported natural killer (NK) cells to be
increased in the peripheral blood of patients with vitiligo.
AUTOCYTOTOXIC THEORY
The autocytotoxic theory stems from the belief that increased melanocyte activity
leads to its own demise.65
Electron microscope examination of interface between vitiligenous and normal
skin in patients with vitiligo demonstrated accumulation of extracellular granular
material and basilar vacuolation of pigmented skin in patients with rapidly
progressing disease. Some studies have demonstrated little, if any, lymphocytic
infiltrate contiguous to melanocytes, substantiating the autocytotoxic theory.66
A second mechanism by which autocytotoxicity may occur is through inhibition
of thioredoxin reductase, a free radical scavenger located on membrane of
melanocytes64. This enzyme is inhibited by calcium which has been shown to be
membrane bound in higher concentrations on vitiligenous keratinocytes relative to
controls. Higher extracellular calcium levels cause increased superoxide radicals that
lead to inhibition of tyrosinase by upsetting the equilibrium of oxidized and reduced
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thioredoxin in the epidermis later causing vacuolization and eventually cell death.68
Levels of catalase, an enzyme that reduces superoxides to water, have also been
shown to be reduced in involved and uninvolved skin in patients with vitiligo causing
cell death.69,70
Certain tyrosinase analogues and intermediates in melanin synthesis are toxic to
melanocytes. The autocytotoxic theory postulates that an intermediate or metabolite in
melanin synthesis is toxic to melanocytes.45
The melanocytes have an inherent protective mechanism that leads to successful
elimination of toxic melanin precursors (dopa, dopachrome, 5,6-dihydroxyindole).
These are synthesized by melanocytes but are also toxic to them. Disruption of the
labile destructive process could permit accumulation of indoles and free radicals,
destructive to melanocytes.45
A phenolic derivative may emerge as a degradation product of melanogenesis and a
cause for tyrosinase inhibition and cell death.21
It has been postulated that faulty enzymatic protective mechanism is an inherited
genetic defect in vitiligo patients.21
NEURAL THEORY
In the genesis of vitiligo, 'neural concept' was postulated first by Lerner.44 His
hypothesis was based on the following:
Clinical evidence of segmental/ dermatomal vitiligo.
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Increased sweating and vasoconstriction in vitiligenous areas implying
increased adrenergic activity.
Depigmentation in animal models with severed nerve fibers.
According to neural theory, certain compounds released at the peripheral nerve
endings inhibit melanogenesis and have toxic effect on melanocytes.71
Chanco turner et al in their studies demonstrated increased cholinergic activity as seen
by surface temperature and sweat production and prolonged bleeding time in the
depigmented macules.72
Breathnach et al demonstrated degenerative changes in the terminal portions of
peripheral nerves in vitiligenous areas.73
As melanocytes originate from the neural crest, their activity may be under neural
control, and degeneration of nerves and nerve endings may be an important link in the
pathogenesis of vitiligo.74
Ultra structural studies have indicated anatomic contact between nerve fibers and
melanocytes.75
Biochemical support for neural hypothesis arises from the observation that
acetylcholine may cause depigmentation , by virtue of its inhibitory effect on dopa
oxidase activity in marginal melanocytes in vitiligo,76 and acetylcholine esterase
activity has been shown to be absent in depigmenting skin.
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Lerner et al77 observed a patient with transverse myelitis of the spinal cord who
developed vitiligo confined to the face and trunk areas above the level of the cord
injury.
Gokhale and co-workers78 in their skin conductivity study found that perspiration
was decreased in patients with generalized vitiligo.
GENETICS IN VITILIGO
Genetic associations of vitiligo with alleles of MHC loci are strongest in patients
and families with various vitiligo-associated autoimmune diseases versus in patients
and families with only generalized vitiligo. In the first genome-wide linkage analysis
of vitiligo, a susceptibility gene, NALP1, on chromosome 17p13, was identified in
families with vitiligo-related systemic lupus erythematosus.
Later analyses identified highly significant linkage to chromosome 1p31.3–p32.2,
the AIS1 locus, as well as linkage to chromosomes 7q and 8p (AIS2 and AIS3,
respectively).
While linkage to the AIS1, AIS2 and NALP1 loci was observed primarily in
autoimmunity-associated families, the evidence for the AIS3 locus was primarily
from non-autoimmunity-associated families, suggesting that generalized vitiligo
might be divided into two distinct phenotypic subcategories. Other genes involved are
PTPN22, CTLA4, MITF, ACE, VDR, AIRE, and COMT.86-89
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FREE RADICAL THEORY
Overproduction of 6- and 7-tetrahydrobiopterins pointed to a metabolic defect in
tetrahydrobiopterin homeostasis in patients with vitiligo.
Such a defect would result in hydrogen peroxide (H2O2) overproduction, and high
levels of epidermal H2O2 have been confirmed in vitiligo skin. Thus there is oxidative
degradation of the porphyrin active site of catalase and deficiency of catalase in
vitiligo patients.90
CLINICAL FEATURES
Vitiligo is characterized by depigmented macules of different shapes and sizes,
which gradually spread peripherally.
Hypomelanotic macules are usually first noted on sun exposed areas of skin, on
the face or dorsa of hands.65 No part of the skin is immune to vitiligo.44
The extent of involvement is extremely variable. There may be one, several, or
upto hundreds of macules that may be small to large in size even in a single patient.
As vitiligo naturally evolves over time, the macules enlarge, coalesce and impart a
scalloped appearance to the interface of the normal and vitiligo skin. When vitiligo
becomes very extensive so that little normal pigment remains, the remaining islands
of normal pigmentation have concave borders, which is a diagnostic clue that
distinguishes this process from hyper pigmented macule on normal extremely fair
skin.45
Spontaneously repigmentation has been observed in 6 to 44%.46
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OCULAR ABNORMALITIES
The pigment epithelium of the retina is derieved from the cephalic neural crest
although the choroid consists of melanocytes from the spinal neural crest.79
Although the colour of the irides do not change in patients with even extensive
vitiligo, depigmented areas in the pigment epithelium and choroid occur in upto 4% of
patients.80-82
The incidence of uveitis in patients with vitiligo is elevated.83
Cowan et al81 and Norlund et al84 have shown a high percentage of ocular
abnormalities in the fundus. There is a report of coexistence of vitiligo and idiopathic
uveitis.85
OTIC ABNORMALITIES
The membranous labyrinth of the inner ear contains melanocytes and the
heaviest pigmentation is present in scala vestibuli.91 Because vitiligo affects all active
melanocytes auditory problems can result in patients with vitiligo.
In a study of patients with vitiligo who were less than 40 years of age, 16% had
hyperacusis in the 2 to8 KHZ range, which was of minimal disturbance to those
affected.92
In addition, two studies described familial vitiligo associated with auditory
anomalies.93,94
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KOEBNERISATION
This is the appearance of new vitiligo lesion on sites of trauma. The common sites
involved are waist band, saree, lungi, shoulder strap, slippers etc.32
LEUKOTRICHIA
Depigmented hair is commonly associated with vitiligo in about 9 to 45% of
patients.46 Extensive white hair may be a poor prognostic marker.46 Apart from
leukotrichia, premature greying occurs in upto 37% of vitiligo patients.
STABILITY OF VITILIGO
Vitiligo is considered as stable vitiligo if
no new lesions occur
no enlargement of older lesions
koebnerisation is negative
for a period of atleast 6 months to 2 years. These patients are ideal for vitiligo
surgeries.
PUNSHI'S SIGN:
White vitiligo macules turn red-pink during menstruation in females.
CLASSIFICATION OF VITILIGO
Vitiligo is classified based on the distribution pattern as below:3
LOCALISED
a) FOCAL: It is a depigmented macule in a localized non dermatomal distribution.
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b) SEGMENTAL: Occurs in a dermatomal, asymmetric distribution. It is considered
as a special type of vitiligo, because of its earlier onset, recalcitrant course and
decreased association with autoimmune diseases. It affects males and females equally.
Most patients (90%) with this form of vitiligo develop depigmentation before the age
of 20 years compared to only 50% of those with generalized variety.
In a study conducted by Han et al (1996) the mean age of onset of segmental
vitiligo was 15.6 years. He further noted that face was the most common site of
involvement, regardless of sex and 11.5% had a family history of segmental vitiligo.
c) MUCOSAL VITILIGO: Involves only the mucosal surface i.e. oral or genital or
both.
GENERALISED:
a) ACROFACIAL VITILIGO: Encompasses depigmentation of the distal
extremities and facial orifices, the latter in a circumferential pattern.
LIP TIP VITILIGO: Involves lips and all tips i.e. fingers, nipples, penis.
b) VITILIGO VULGARIS: It is the most common presentation with bilateral,
symmetric depigmentation of the face, neck, torso, extensor surfaces or bony
prominences of the hands, wrists and legs, axillae, orifices or mucosal surfaces. Legs
are the most common initial sites of involvement.
c) VITILIGO UNIVERSALIS: Encompasses those cases where the depigmentation
involves the entire or nearly entire body surface area with specks of normally
pigmented areas.
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MIXED TYPE: This consists of more than one type of vitiligo.
The following are the clinical variants of vitiligo:4
TRICHROME VITILIGO: refers to an uniform tan colour between the normally
pigmented skin and the typically depigmented vitiligo macule.
QUADRICHROME VITILIGO: refers to the fourth colour i.e. a perifollicular
hyperpigmentation.
PENTACHROME VITILIGO: refers to vitiligo with five shades of color (black,
dark brown, medium brown [unaffected skin], tan and white).
VITILIGO PONCTUE: An unusual clinical presentation of vitiligo, is characterized
by small confetti-like or tiny, discrete, amelanotic macules occurring either on
otherwise normal skin or on a hyperpigmented macule.4
INFLAMMATORY VITILIGO: when there is erythema of the margin of a vitiligo
macule.4
BLUE VITILIGO: when vitiligo develops over post inflammatory
hyperpigmentation.4
VALECEO TYPE OF VITILIGO: Emotional trauma and repression have been
noted to be responsible for a very sudden onset, rapid extension and spread of
lesions.21
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HISTOPATHOLOGY
Routine histopathology shows marked absence of melanin granules in vitiligenous
areas. This is best seen in sections stained with silver stains. The dopa reaction also
shows absence of melanocytes.95
Early lesions and peripheral zone of enlarging lesions that are hypopigmented
show a few dopa positive melanocytes and some melanin granules in the basal layer.96
Narayanan et al in his study found that in addition to the absence of melanocytes
there was vacuolated degeneration of langerhans cells and degenerative changes in
keratinocytes suggesting that all the three types of epidermal cells may be involved in
some way in vitiligo.97
At the border of the patches of vitiligo the melanocytes appear large and possess
long dendritic processes filled with melanin granules and the dermis shows
lymphocytic infiltration.84
Basal layer of epidermis show focal areas of vacuolar degeneration in association
with a mild mononuclear cell infiltrate seen in the normal appearing skin adjacent to
vitiliginous areas.66
The melanoytes undergo fibrillar degeneration. As they degenerate, fibrils
accumulate within the cytoplasm.98 These masses of cytoplasmic fibrillar material
form the colloid like masses observed in the basal layer.99 Keratinocytes in pigmented
skin also show degenerative changes.100
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33
Histopathologic findings101 have been used to support various theories concerning
the development of vitiligo. Perilesional melanocytes express major
histocompatibility class II antigens and substantially higher intercellular adhesion
molecule 1relative to normal skin controls. These have been found in follicular
epithelium in auto immune thyroiditis and in pancreatic beta cells in type 1 diabetes,
upholding the autoimmune hypothesis.
The phenomenon of direct nerve contact with melanocytes along the
dermoepidermal junction in depigmented skin of patients with vitiligo75 and a
complete or partial degeneration of the nerves73,74 support the neural hypothesis of
vitiligo.
ASSOCIATED DISORDERS
A) Skin diseases
Premature canities has been reported in about 37% of vitiligo cases.102 Vitiligo is
frequently seen in association with atopic eczema.103
Coexistence of psoriasis and vitiligo and occurence of psoriasis on vitiligo
macules have been documented.104,105
There are reports of association of neurofibromatosis with vitiligo.106
Palmoplantar hyperhidrosis has been reported in 10.5% of vitiligo cases in contrast to
3.5% in the control group.107
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34
There have been reports of association of vitiligo with alopecia areata and
DLE,108 pemphigus vulgaris,109,110 lichen planus111 and squamous cell carcinoma112 on
a patch of mucosal vitiligo.
Halo naevi have been estimated to occur in about 50% of cases of vitiligo.113
Alopecia areata has been reported in up to 16% of vitiligo patients.114
Jopling W.H.115 has been found an association of vitiligo with lepromatous
leprosy. In his study conducted among 114 lepromatous leprosy, 8 patients developed
vitiligo after varying years of treatment accounting for incidence of 7%. The
association of vitiligo with lepromatous leprosy has supported the hypothesis that
vitiligo has an autoimmune basis, for a wide variety of autoantibodies have been
described in lepromatous leprosy.
Vitiligo and melanoma frequently occur together. Vitiligo associated with
melanoma carry a poor prognosis.100
Saiham et al (1979) reported vitiligo in association with morphoea.116
B) Systemic disorders
There is ample documentation of the association of vitiligo with autoimmune
disoders.
The increased incidence of hyperthyroidism and Hashimoto's thyroiditis in
vitiligo patients is well recorded.117,118
Higher incidence of vitiligo in elderly women patients of Graves disease,
hyperthyroidism, toxic goitre and thyroditis have been reported.21
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35
Vitiligo has been reported to develop in 7% of patients with Graves' disease.51
Pernicious anemia is recorded 30 times more frequent among vitiligo patients
than in general population.119
Fifteen percent of Addison's disease patients have been reported to have
vitiligo.120
The prevalence of diabetes mellitus in vitiligo patients is reported to vary from
1% to 7.1%.117
According to Dawber (1968), diabetes mellitus should be excluded in every
patient with late onset vitiligo.121
Bhargava et al reported a case of congenital leopard vitiligo associated with
multiple sclerosis.122
Satish et al reported a case of vitiligo with oesophageal carcinoma.123
There are reports of vitiligo with ulcerative colitis, myasthenia gravis,124 primary
ovarian failure and juvenile rheumatoid arthritis.125 Some other studies have reported
the association of vitiligo with multiple myeloma, pernicious anemia126 and
dysgammaglobulinemia A.127
SYNDROMES ASSOCIATED WITH VITILIGO
Vogt Koyanagi Harada syndrome128,129 is an apparently rare, multisystem disease
characterised by uveitis, dysacousia, alopecia, poliosis and vitiligo. This syndrome
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36
was first described by Vogt in 1906. Harada in 1926, described five cases with
bilateral posterior uveitis with retinal detachment. Koyanagi completed the
description of the syndrome in 1929. It affects both sexes equally and the peak
frequency is in the third decade.
Clinical Features:
Classical Vogt Koyanagi Harada syndrome has 3 phases.
I. Meningoencephalitic phase: manifested by headache, malaise, nausea, vomiting,
confusion, psychosis, paraplegia, and generalised weakness.
II. Ophthalmic auditory phase: characterised by decreased visual acuity,
photophobia, and eye pain. Dysacousia is seen in 50% of patients.
III. Convalescent phase: starts as uveitis begins to abate and is characterised by
alopecia, poliosis and vitiligo.
Criteria for diagnosis for Vogt Koyanagi Harada syndrome are as follows:1
No history of ocular trauma or surgery preceding the initial onset of uveitis.
No clinical or laboratory evidence suggestive of ocular disease entities.
Bilateral ocular involvement
diffuse choroiditis- early sign
ocular depigmentation- late sign
Neurological and auditory findings: meningismus, tinnitus, cerebrospinal fluid
pleocytosis.
Skin and hair changes: alopecia, vitiligo, poliosis.
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37
Alezzandrini's syndrome130 is charcterised by a unilateral degenerative retinitis
followed after several months by ipsilateral vitiligo on the face and ipsilateral
poliosis. Deafness may also be present.
SCORING SYSTEMS IN VITILIGO:16
Vitiligo area and severity index (VASI Score):
Percentage of vitiligo involvement is calculated in terms of hand units. One hand
unit (encompass palm and volar surface of all digits) is approximately equivalent to
1% of total body surface area. The degree of depigmentation is estimated to the
nearest of the following percentages:
100%- complete depigmentation
90%- specks of normal pigmentation present
75%- depigmented area exceeds pigmented area
50%- pigmented and depigmented area are equal
25%- normally pigmented area exceeds depigmented area
10%- only specks of depigmentation present
Vitiligo disease activity score (VIDA):
The VIDA is a six-point scale for assessing vitiligo activity.
Scoring is based on the individual's own opinion of the present disease activity
over time. Active vitiligo involves either expansion of existing lesions or appearance
of new lesions. Grading is as follows:
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38
VIDA Score 4+ - Activity of 6 weeks or less duration
3+ - Activity of 6 weeks to 3 months
2+ - Activity of 3 - 6 months
1+ - Activity of 6 - 12 months
0 - Stable for 1 year or more
-1 - Stable with spontaneous repigmentation since 1 year or more.
A low VIDA score indicates less activity.
DIFFERENTIAL DIAGNOSIS:1,3,4,5
Congenital normal variant:
Nevus achromicus- Solitary hypopigmented macule well circumscribed with
irregular borders, stable in size, solitary, most often present at birth
Nevus anaemicus- Hypochromic pale lesion with well-defined borders and
irregular margins which are usually solitary and they are located on the trunk.
Histology and electron microscopic examination reveal no abnormality in
melanocytes or melanization
Genetic disorders:
Oculo cutaneous albinism-
Type -1: TYR mutation- 1a- total lack of tyrosinase
1b- partial tyrosinase activity present
Type -2: OCA2 mutation- defective transport of tyrosinase
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39
Type -3: TYRP1 mutation- defective oxidation of dihydroxy indole 2
carboxylic acid
Type -4: SLC45A2 mutation- defective melasome transfer
Type -6: SLC24A5 mutation- defective maturation of melanosomes
Oculo cutaneous albinoidism- mild form of tyrosinase positive oculocutaneous
albinism.
Piebaldism- defect in c-kit protooncogene
poliosis
depigmented macules
Hermansky Pudlak syndrome
oculocutaneous albinism
haemmorrhagic diasthesis
pulmonary fibrosis, granulomatous colitis, lupus nephritis
nystagmus, photophobia, visual disturbances
Chediak Higashi syndrome- LYST mutation
squint, photophobia, decreased retinal pigmentation
increased susceptibility to infection
pancytopenia
convulsions, neuropathy
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40
hilar lymphadenopathy, jaundice, leukemic gingivitis,
pseudomembranous sloughing of buccal mucosa
Waardenburg syndrome
Type 1- classical- dystopia canthorum, prominent nasal root and
medial eyebrows, congenital sensoryneural hearing loss, heterochromia
irides, white forelock, premature canites.
Type 2- No dystopia canthorum and facial dysmorphism. higher
incidence of deafness and heterochromia
Type 3- associated with musculoskeletal abnormalities
Type 4- associated with Hirschsprung disease
Cross syndrome- geeralised hypopigmentation, mental retardation, spastic
tetraplegia, athetosis, microphthalmos
Griscelli Prunieras syndrome
Type 1- primary CNS dysfunction
Type 2- haemophagocytic lymphohistiocytosis
Type 3- partial albinism
Woolf's syndrome- piebaldism, deafness, mental retardation
Tietz's syndrome
depigmented skin and hair
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41
normal eyes
deaf mutism
hypoplasia of eyebrows
Ataxia telangectasia
premature greying of hair
cerebellar ataxia, choreoathetosis
oculocutaneous telangiectasia
bronchiectasis
Tuberous sclerosis- TSC 1 and 2 mutation- ash leaf macules
Hypomelanosis of Ito- hypopigmented linear streaks along blaschko lines,
neurological, ophthalmological, and skeletal defects.
Inborn errors of metabolism:
Phenylketonuria- depigmented skin, hair, eyes, photophobia.
Menke kinky syndrome- ATP7A mutation- hair changes-
monelethrix, pili torti, trichorrhexis nodosa, neurological
deterioration.
Homocystinuria- marfanoid features, mental retardation,
ectopia lentis, depigmented macules, hypopigmented hair.
Endocrinopathy:
Hypopituitarism
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42
Hyperthyroidism
Hypogonadism
Nutritional:
Kwashiorkar
Malabsorption
Chemical contact:
Monobenzyl ether of hydroquinone and Hydroquinone
Phenol
Thiouracil
Thiol
Butylated hydroxytoluine
Steroids
Retinoids
Topical imiquimod
Systemic drugs:
chloroquine
fluphenazine
physostigmine
imatinib
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43
Post inflammatory:
Mechanical trauma
Thermal injury
Ionizing radiation
Infections:
Bacterial- Leprosy, Syphilis
Viral- Herpes simplex, Herpes zoster
Fungal- Tinea versicolor, Candidiasis
Parasitic- Onchocerciasis
Other dermatological disorders with hypo pigmentation:
Pityriasis alba
Pityriasis rosea
Psoriasis
Lichen stiatus
Lichen planus
Lichen striatus et atrophicans
Discoid lupus erythematosis
Morphea
Sarcoidosis
Bullous dermatitis
Cutaneous lymphoma
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44
Others:
Idiopathic guttate hypomelanosis
Progressive macular hypomelanosis
Halo nevus
MANAGEMENT1
First line
Potent topical corticosteroid (e.g. 0.1% betamethasone valerate or 0.05%
clobetasol propionate) is effective at inducing repigmentation of areas of
vitiligo.
It is preferable to use an intermittent regimen (e.g. 15 days per month for 6
months) to avoid local side effects (skin atrophy, telangiectasia, striae, hypertrichosis
and acneform eruptions).
Topical calcineurin inhibitors (pimecrolimus, tacrolimus) has been
reported to be successful, mainly for lesions on the face and neck twice daily
applications are recommended, initially for 6 months.
Topical Vitamin D analogs—calcipotriol ointment (0.005%) and tacalcitol
ointment (20 μg/g) restore pigmentation in vitiligo by inducing skin
immunosuppression, which halts the local autoimmune process, and via direct
activation of melanocytic precursors and melanogenic pathways. When
vitamin D analogs are used in combination therapy, it is more effective
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45
probably because of stimulation of both melanocyte growth (with
corticosteroids or UV) and differentiation (with a vitamin D analog).
Vitamin D derivatives are indicated for use in localized disease They lack
adverse effects of skin atrophy. However, their role in vitiligo treatment
remains controversial
Second line
Systemic psoralen photochemotherapy (PUVA) is effective in a proportion
of cases. The use of topical applications of psoralens is more hazardous and
may result in untoward blistering of the skin.
Photosensitizers including khellin have been advocated but there are
concerns over hepatotoxicity and it has not been widely adopted.
UVB therapy can also be used selectively.
Localized targeted phototherapy devices (excimer lamp or lasers with a
peak at 308 nm). There is no consensus as to the optimum treatment duration
of phototherapy. Most often irradiation will be stopped if no repigmentation
occurs within the first 3 months of treatment.
Third line
Grafting techniques
Surgical methods have been proposed as a therapeutic option in patients with stable
vitiligo (e.g. segmental vitiligo). These surgical techniques are based on a common
basic principle: to transplant autologous melanocytes from a normal pigmented area
to the affected depigmented skin.
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46
Different surgical techniques for repigmenting vitiligo have been gradually devised
and include
Tissue grafts
full thickness punch grafts
split thickness grafts
suction blister grafts
Cellular grafts
cultured melanocytes
cultured epithelial sheet grafts
non cultured epidermal cellular grafts
Lately, the use of hair follicle outer root sheath cells has been introduced. The
three tissue grafting methods (full thickness punch grafts, split thickness grafts,
suction blister grafts) seem to have comparable success rates in inducing
repigmentation.
Cellular grafting techniques were in general found to be nearly as effective,
although the percentages of patients in whom repigmentation was achieved were
slightly lower than with the tissue grafting techniques. However, cellular grafting can
be used to treat larger areas and has in general better cosmetic results compared to
tissue grafts. Furthermore, adverse events seem to be less frequent with cellular grafts
than with punch or split skin grafts.
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47
Depigmenting treatment: In those patients with extensive vitiligo and only a few
residual areas of pigmentation, skin bleaching with
laser therapy (e.g. Q switched alexandrite 755 nm, Q switched ruby 694 nm),
cryotherapy
creams (e.g. 20% monobenzylether of hydroquinone), may be used.
Camouflage and psychological support:
Camouflage:131
Temporary camouflage:
Liquid dyes:
Potassium permanganate, indigo carmine, Bismarck brown and henna pastes are
commonly used. But, they may get washed away easily.
Indigenous preparations (Traditional Indian Preparations)
Iron fillings (Loha Bhasma) and Suvarna Karini (clay mixed with henna and oils) are
used. But, colour matching is difficult.
Foundation-based cosmetic camouflage
Oil-based, water-based, oil-free and water-free forms are available with matte, semi-
matte, moist semi-matte and shiny finishes. Liquid foundations are also available.
Self-tanning products:
Dihydroxyacetone is commonly used self tanning agent but has a mutagenic property
and cause allergic contact dermatitis. colour matching is also difficult.
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48
Permanent camouflage:
It is achieved mainly by micropigmentation/medical tattooing. Iron oxide is the most
common pigment used. Various other chemicals used and the respective colors
produced are as follows:
black, camel yellow, light and dark brown (iron oxide)
white (titanium dioxide)
yellow (cadmium sulfide)
red (mercuric sulfide/cinnabar with cadmium sulfide added to make the red
shade brighter).
Complications include colour fading, allergic contact dermatitis, reactivation of
herpes, transmission of HIV and hepatitis B.
Psychological support:
Since vitiligo is associated with social stigma, these patients are more prone for
depression. Psychiatric counselling and family support is necessary in such patients.
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49
Role of vitamin D in vitiligo:
Parsad et al.132 first reported the use of vitamin D analogues in combination with
PUVAsol and topical calcipotriol for the treatment of vitiligo. Many studies have
been reported about the use of vitamin D analogues alone or in combination with
ultraviolet light or corticosteroids to enhance repigmentation in vitiligo.133
Birlea et al., concluded that vitamin D3 analogues are effective in combination
with PUVA, NBUVB, or an excimer laser after reviewing 22 studies published on
calcipotriol/tacalcitol used alone or in combination with other agents.134
Oh et al., reported that high concentration of tacalcitol was applied topically
with 308 nm xenon chloride excimer laser to lower the energy threshold to treat non
segmental vitiligo.135
In a recently published case report, it was found low levels of vitamin D
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50
inflammatory mediators139 and stimulate melanin production by activating
melanocytes and keratinocytes.140
Melanocytes in the epidermis become swollen with elongated dendrites after UV
exposure. On long term UV exposure, the tyrosinase activity in these melanocytes is
increased by microphthalmia transcription factor (MITF),141 and results in the
deposition of the melanin in the epidermis.
Tomita et al., studied that increased cell size, number of dendrites, and tyrosinase
activity was induced by both vitamin D3 and UV radiation individually.142
Ermis et al., reported that the combination of calcipotriol and PUVA was safe and
more effective in initiating and achieving complete repigmentation than a placebo
with PUVA.143
A marginal type of repigmentation pattern is seen and the onset of repigmentation
induced by calcipotriol was slow.144 In a few cases, treatment failure or no added
response was observed at the end of 3 months with combination therapy with these
vitamin D analogues.133
A recent study on the influence of low-dose narrowband UVB phototherapy on
serum levels of vitamin D145 revealed that UVB phototherapy increased vitamin D
levels in patients with low initial levels of 25-hydroxyvitamin D (25(OH) D) (the
serum marker for vitamin D status), thus indicating the beneficial effect of UVB
depends partially on vitamin D.
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51
It has been shown that defective calcium (Ca2+) transport is found in
keratinocytes and melanocytes of vitiliginous skin samples.146 Both plasma membrane
associated and cytosolic thioredoxin reductase is controlled by calcium. Decreased
intracellular Ca2+ inhibits melanin synthesis due to high levels of reduced
thioredoxin which inhibits tyrosinase activity. Moreover, melanocytes express 1,25-
dihydroxyvitamin D3 receptors and regulates melanin synthesis.147,148
Thus, calcipotriol plays a role in Ca2+ regulation through 1,25-dihydroxyvitamin
D3 receptors on melanocytes and/or by the regulation of defective Ca2+
homeostasis.143
Proinflammatory and proapoptotic cytokines, such as IL-6, IL-8, IL-10, IL-12,
INF-ᵧ, and TNF-ἀ, play a role in the pathogenesis of vitiligo.149,150 The expression of
IL-6, IL-8, TNF-ἀ, and TNF-ἀ is inhibited by vitamin D.151 Dendritic cell maturation,
differentiation, and activation in both human and murine culture systems,152 are
modulated by vitamin D probably by VDR-dependent pathway.153
Vitamin D compounds also induce the inhibition of antigen presentation.152,153
Vitamin D protects the epidermal melanin unit and restores melanocyte integrity
by the following mechanisms:
By controlling the activation, proliferation, migration of melanocytes and
pigmentation pathways by modulating T cell activation, which is apparently
related to disappearance of melanocytes in vitiligo.
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52
Immunomodulatory action of VDR on immune cells lead to coordination of T
cell activation mainly by the inhibition of T cell transition from the early to the
late G1 phase and by the inhibition of several cytokine genes encoding TNF-ἀ
and IFN-ᵧ.154
The mechanism through which vitamin D exerts its effects on melanocytes is not
yet fully understood. Vitamin D helps in coordinating melanogenic cytokines like
endothelin-3 and the activity of the SCF/c-Kit system, which regulates melanocyte
maturation.154
There is also an antioxidant role of vitamin D in vitiligo by regulating reative
oxygen species.
The active form of vitamin D produces IL-6 and reduces the apoptotic activity of
keratinocytes155 and melanocytes 156 induced by UVB.
In another study, melanocytes protected from apoptosis through the formation of
sphingosine-1-phosphate by vitamin D,also opposes apoptotic action in diverse
melanoma cell lines.157
Vitamin D-It acts on specific T cell by inhibiting the expression of several
proinflammatory cytokines genes (TNFἀ, IFᵧ)
1, 25-Dihydroxyvitamin D3- It protects human melanocytes from apoptosis by
formation of sphingosine-1-phosphate
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53
1,25-Dihydroxyvitamin D3- It has anti apoptotic effects and decreased
cyclobutane pyrimidine dimers damage by up to 60%
Tacalcitol- a vitamin D analogue plays a role in Ca2+ regulation by vitamin D
receptor (VDR) on melanocytes
Vitamin D receptor- is the nuclear receptor that mediates the effects of vitamin
D through regulating the transcription of other genes
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54
MATERIALS and
METHODS
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55
MATERIALS AND METHODS
This is a hospital based case control study with a sample size of 180 including
120 cases and 60 controls.
The study was done for 6 months from December 2016 to May 2017 in
dermatology out patient department, Government Rajaji hospital.
Clinically diagnosed cases of vitiligo attending dermatology department
constitute the cases. Age matched and sex matched healthy volunteers comprised the
control group. Ethical committee approval was obtained.
Informed consent were obtained from all those who were included in this study.
All were interrogated for a detailed history and a meticulous examination of each case
was carried out and recorded in a special proforma separately for cases and controls.
History of precipitating factors such as trauma, chemicals, stress, associations
were specifically asked for and noted. History suggestive of thyroid disease, atopy,
diabetes was noted.
A complete general physical examination was done in all those who were
included in the study. A thorough systemic examination was also made for associated
disorders and the findings were noted. Detailed dermatological examination including
the mucosa was carried out to classify the disease, to know the extent of vitiligo and
to study the specific features such as trichrome, quadrichrome, and leukotrichia.
All those who were included in this study were subjected to the following
investigations: complete hemogram, blood sugar, renal function test, liver function
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56
test, serum fasting lipid profile, serum proteins, antinuclear antibody, and serum 25
hydroxy cholecalciferol.
The patients were categorized based on the type, duration, and severity of vitiligo.
The patients were classified based on the following clinical types:
Focal
segmental
mucosal
acrofacial
vitiligo vulgaris
vitiligo universalis
The patients were categorized on the basis of duration as follows:
0-5 years
6-10 years
11-15 years
16-20 years
>21 years
Severity of vitiligo was assessed using VASI score.16
The patients are categorized based on VASI score as follows:
0-10%
11-25%
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57
26-50%
51-75%
76-100%
Serum 25-OH cholecalciferol levels were calculated using Euro immune ELISA
kit. The cases and controls were categorized based on serum 25-OH cholecalciferol
levels as follows:158
Serum 25-OH cholecalciferol level (ng/ml) Implication
150 Intoxication
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58
OBSERVATIONS
and RESULTS
-
59
OBSERVATION and RESULTS:
In this study comprising of 120 cases and 60 controls done in the dermatology OP,
Government Rajaji hospital, Madurai, the following observations are found.
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60
AGE DISTIBUTION OF THE STUDY: The study included 26 cases and 13
controls in the age 60 years thus matching the age of
cases and controls.
Age (in years) Group
Case n (%) Control n (%)
≤ 20 26 (21.7) 13 (21.7)
21 - 40 43 (35.8) 23 (38.3)
41 - 60 43 (35.8) 21 (35.0)
>=61 8 (6.7) 3 (5.0)
Total 120 (100.0) 60 (100.0)
Mean±SD 37.6±17.2 36.2±15.8
Min, Max 4, 68 6,68
p value 0.968 - Not Significant
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
≤ 20 21 - 40 41 - 60 >=61
21.7
35.8 35.8
6.7
21.7
38.335.0
5.0(in p
erce
nta
ge)
Age group (in yrs)
Age Distribution
Case
Control
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61
SEX DISTRIBUTION OF THE STUDY: This study included 59 males and 61
females among cases and 29 males and 31 females in controls.
Gender Group
Case n (%) Control n (%)
Male 59 (49.2) 29 (48.3)
Female 61 (50.8) 31 (51.7)
Total 120 (100.0) 60 (100.0)
p value 0.916 - Not Significant
59 61
29 31
0
10
20
30
40
50
60
70
Male Female
SEX DISTRIBUTION
Cases
Control
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62
SEX DISTRIBUTION IN THE TYPE OF VITIIGO: This study included 5 males
and10 females in focal vitiligo, 7 males and 10 females in mucosal vitiligo, 10 males
and 4 females in segmental vitiligo, 9 males and 4 females in acrofacial vitiligo, 26
males and 28 females in vitiligo vulgaris, 2 males and 5 females in vitiligo
universalis.
Type of Vitiligo Sex
Male n (%) Female n (%)
Focal 5 (8.5) 10 (16.4)
Mucosal 7 (11.9) 10 (16.4)
Segmental 10 (16.9) 4 (6.6)
Acrofacial 9 (15.3) 4 (6.6)
Vulgaris 26 (44.1) 28 (45.9)
Universalis 2 (3.4) 5 (8.2)
Total 59 (100.0) 61 (100.0)
p value 0.155 – Not Significant
57
10 9
26
2
10 10
4 4
28
5
0
5
10
15
20
25
30
Focal Mucosal Segmental acrofacial Vulgaris universalis
SEX DISTRIBUTION IN THE TYPE OF VITILIGO
Male
Female
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63
SEX DISTRIBUTION IN THE DURATION OF VITILIGO: This study included
49 males and 48 females in 20
SEX DISTRIBUTION IN VITILIGO DURATION
Male
Female
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64
S. CHOLECALCIFEROL LEVELS IN CASES vs CONTROLS : There were 9
cases and 1 control with very severe deficiency, 22 cases and 4 controls with severe
deficiency, 39 cases and 17 controls with deficiency, 28 cases and 12 controls with
suboptimal levels, 22 cases and 26 controls with normal levels and 1 patient had
above normal value.
Serum VIT D3(ng/ml) Group
Case n (%) Control n (%)
Very severe deficiency(< 5) 9 (7.5) 1 (1.7)
Severe deficiency(5.1 - 10) 22 (18.3) 4 (6.7)
Deficiency (10.1 - 20) 39 (32.5) 17 (28.3)
Sub optimal(20.1 - 30) 28 (23.3) 12 (20.0)
Normal (30.1 - 50) 17 (14.2) 17 (28.3)
Upper normal (50.1 - 70) 4 (3.3) 9 (15.0)
Above normal (> 70) 1 (0.8) -
Total 120 (100.0) 60 (100.0)
Mean±SD 19.8±13.6 29.5±17.1
Min, Max 2.1, 82.0 4.7, 69.4
p value < 0.004 Sig
9
22
39
28
17
411
4
1712
17
9
00
10
20
30
40
50
< 5 5.1 - 10 10.1 - 20 20.1 - 30 30.1 - 50 50.1 - 70 > 70
SERUM VIT D3
COMPARISON OF SERUM VIT D3 (CASES VS
CONTROLS)
Case
Control
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65
CHOLECALCIFEROL IMPLICATION IN CASES vs CONTROLS: In order to
avoid confusion, those people with very severe and severe deficiency of
cholecalciferol levels 30ng/dl were clubbed
together as normal with 22 cases and 26 controls.
Implication Group
Case n (%) Control n (%)
Severe Deficiency (30) 22 (18.3) 26 (43.3)
Total 120 (100.0) 60 (100.0)
p value
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66
CORRELATION OF S. CHOLECALCIFEROL WITH TYPE OF VITILIGO:
The study showed deficiency and severe deficiency of serum cholecalciferol in
patients with vitiligo vulgaris and universalis thus suggesting significant correlation
with the type of vitiligo. Ten vitiligo vulgaris patients with normal values could be
explained by the fact that they were on phototherapy and are clinically improving.
Type of Vitiligo
Implication
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
Focal 2 (6.5) 12 (17.9) 1 (4.5)
Mucosal 2 (6.5) 10 (14.9) 5 (22.7)
Segmental 5 (16.1) 6 (9.0) 3 (13.6)
Acrofacial - 10 (14.9) 3 (13.6)
Vulgaris 17 (54.8) 27 (40.3) 10 (45.5)
Universalis 5 (16.1) 2 (3.0) -
Total 31 (100.0) 67 (100.0) 22 (100.0)
p value 0.025 – Significant
0
10
20
30
40
50
60
6.5 6.5
16.1
54.8
16.117.9
14.99
14.9
40.3
34.5
22.7
13.6 13.6
45.5
(in p
erce
nta
ge)
Type of Vitiligo Vs ImplicationSevere Deficiency
Deficiency
Normal
patients under
phototherapy
& natural
sunlight
exposure
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67
CORRELATION OF S. CHOLECALCIFEROL WITH DURATION: This study
shows significant correlation (P value-0.001) with duration of vitiligo. Among
patients with vitiligo for > 5 years duration, only 5 show normal values and all these
patients were under phototherapy and showed clinical improvement. Majority of the
patients were suffering from vitiligo for
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68
CORRELATION OF S.CHOLECALCIFEROL WITH SEVERITY (VASI
Score): This study shows significant correlation with the severity of vitiligo. Among
patients with VASI score >26%, 2 out of 19 patients had normal value which could
probably be explained by previous phototherapy. They also showed clinical
improvement.
VASI
Implication of s.cholecalciferol
Severe
Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
< 10 % 10 (32.3) 43 (64.2) 17 (77.3)
11 - 25 % 8 (25.8) 20 (29.9) 3 (13.6)
26 - 50 % 8 (25.8) 2 (3.0) -
51 - 75% - - 2 (9.1)
> 75% 5 (16.1) 2 (3.0) -
Total 31 (100.0) 67 (100.0) 22 (100.0)
p value 75%
32.3
25.8 25.8
16.1
64.2
29.9
3 3
77.3
13.69.1
(in p
erce
nta
ge)
VASI Score Vs Implication
Severe Deficiency
Deficiency
Normal
patients under
phototherapy
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69
VARIATION OF S. CHOLECALCIFEROL WITH AGE AMONG CASES: In
age ≤20 years, 11 have severe deficiency, 15 have deficiency. In 21-40 years, 12 have
severe deficiency, 22 have deficiency and 9 have normal values. In 41-60 years, 8
have severe deficiency, 25 have deficiency, and 10 have normal values. In ≥ 61 years,
5 have deficiency and 3 have normal values while none show severe deficiency.
Age (in years)
Implication of s.cholecalciferol
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
≤ 20 11 (35.5) 15 (22.4) -
21 - 40 12 (38.7) 22 (32.8) 9 (40.9)
41 - 60 8 (25.8) 25 (37.3) 10 (45.5)
≥ 61 - 5 (7.5) 3 (13.6)
Total 31 (100.0) 67 (100.0) 22 (100.0)
p value 0.041 – Significant
0
5
10
15
20
25
30
35
40
45
50
≤ 20 21 - 40 41 - 60 ≥ 61
35.538.7
25.822.4
32.8
37.3
7.5
40.945.5
13.6
(in p
erce
nta
ge)
Age (in yrs)
Age Vs Implication ( Among Cases)
Severe Deficiency
Deficiency
Normal
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70
VARIATION OF S. CHOLECALCIFEROL WITH AGE AMONG
CONTROLS: In age ≤20 years, 12 have deficiency, 1 has normal value. In 21-40
years, 4 have severe deficiency, 10 have deficiency and 9 have normal values. In 41-
60 years, 6 have deficiency and 15 have normal values. In ≥ 61 years, 2 have
deficiency and 1 has normal value.
Age (in years)
Implication of s.cholecalciferol
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
≤ 20 - 12 (40.0) 1 (3.8)
21 - 40 4 (100.0) 10 (33.3) 9 (34.6)
41 - 60 - 6 (20.0) 15 (57.7)
≥ 61 - 2 (6.7) 1 (3.8)
Total 4 (100.0) 30 (100.0) 26 (100.0)
p value 0.002 – Significant
0
20
40
60
80
100
≤ 20 21 - 40 41 - 60 ≥ 61
100
4033.3
20
6.73.8
34.6
57.7
3.8
(in p
erce
nta
ge)
Age (in yrs)
Age Vs Implication (Among Controls)
Severe
Deficiency
Deficiency
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71
VARIATION OF S. CHOLECALCIFEROL WITH SEX AMONG CASES:
There are 11 males and20 females with severe deficiency, 37 males and30 females
with deficiency and 11 males and 11 females with normal values. Thus, there was no
significant variation with sex among cases in deficient and normal groups. But severe
deficiency was commonly seen in females.
Sex
Implication of s.cholecalciferol
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
Male 11 (35.5) 37 (55.2) 11 (50.0)
Female 20 (64.5) 30 (44.8) 11 (50.0)
Total 31 (100.0) 67 (100.0) 22 (100.0)
p value 0.191 - Not Significant
0
10
20
30
40
50
60
70
Severe Deficiency Deficiency Normal
35.5
55.2
50
64.5
44.8
50
(in p
erce
nta
ge)
Gender Vs Implication (Among Cases)Male
Female
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72
VARIATION OF S. CHOLECALCIFEROL WITH SEX AMONG
CONTROLS: Among controls, there are 0 males and 4 females with severe
deficiency, 16 males and 14 females with deficiency and 13 males and 13 females
with normal values. Thus, here also severe deficiency is more with females.
Sex
Implication of s.cholecalciferol
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
Male - 16 (53.3) 13 (50.0)
Female 4 (100.0) 14 (46.7) 13 (50.0)
Total 4 (100.0) 30 (100.0) 26 (100.0)
p value 0.131 - Not Significant
0
10
20
30
40
50
60
70
80
90
100
Severe Deficiency Deficiency Normal
53.350
100
46.750
(in p
erce
nta
ge)
Gender Vs Implication (Among Controls)
Male
Female
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73
CORRELATION OF S.CHOLECALCIFEROL WITH UV EXPOSURE IN
CASES: Among those exposed to UV rays, there are 6 cases with severe deficiency,
15 cases with deficiency and 21 with normal values. In comparison, in those who are
not exposed to UV rays, there are 25 had severe deficiency, 52 had deficiency and
only 1 had normal value thus suggesting significant correlation with UV exposure
either due to phototherapy or due to natural sunlight exposure.
UV Exposure
Implication of s. cholecalciferol
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
Exposed to UV
rays 6 (19.4) 15 (22.4) 21 (95.5)
Not Exposed to
UV rays 25 (80.6) 52 (77.6) 1 (4.5)
Total 31 (100.0) 67 (100.0) 22 (100.0)
p value
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74
CORRELATION OF S.CHOLECALCIFEROL WITH UV EXPOSURE IN
CONTROLS: Among the controls of those who were exposed to UV rays, none had
severe deficiency, 2 had deficiency and 7 had normal values. In those controls who
were not exposed to UV rays, 4 had severe deficiency, 28 had deficiency and 19 had
normal values. Though those who show deficiency and severe deficiency of
cholecalciferol levels are more in non UV rays exposed group, the association is not
significant (P value-0.073)
UV Exposure
Implication of s.cholecalciferol
Severe Deficiency
n (%)
Deficiency
n (%)
Normal
n (%)
Exposed to UV
rays - 2 (6.7) 7 (26.9)
Not Exposed to
UV rays 4 (100.0) 28 (93.3) 19 (73.1)
Total 4 (100.0) 30 (100.0) 26 (100.0)
p value 0.073 - Not Significant
0
10
20
30
40
50
60
70
80
90
100
Severe
Deficiency
Deficiency Normal
6.7
26.9
10093.3
73.1
(in p
erce
nta
ge)
Implication with uv exposure (Among Controls)
Exposed to Sunlight
Not Exposed to
Sunlight
-
75
DISCUSSION
-
76
DISCUSSION:
Out of the total 180 people included in this study, 120 were vitiligo cases and 60 were
age and sex matched controls.
Indian case control study done by Prakash D et al,159 45 cases and 45 age and sex
matched controls were compared. In another Iranian study,160 30 cases were compared
with 30 age and sex matched controls. In a Turkish study by Karagun E.,161 50 vitiligo
patients and 47 controls were compared. In another Turkish study by Takci Z., 162 44
vitiligo vulgaris patients were compared with 43 controls. Thus, this study included
more number of cases and controls when compared with other studies.
AGE DISTRIBUTION:
The study included 26 cases and 13 controls in the age 60 years. Thus, the age of cases and controls were matched with a p value
of 0.968. The mean age of cases is 37.6 + 17.2 and that of controls is 36.2±15.8.
In the Indian case control study done by Prakash D et al,159 mean age of patients was
43.78 ± 14.70 SD. In the Iranian study,160 the mean age was 30.2 + 0.91 in cases and
34.76 + 1.07 in controls. In the study by Karagun E.,161 the mean ages of the patient
and control groups were 30.96 ±10.57 and 31.45 ±8.33 years, respectively. In the
study by Takci Z., 162 a total of 44 patients with mean age of 34.5 + 16.1 years
(range: 16–60 years) and 43 controls with mean age of 33.0 + 12.6 years (range: 17 –
60 years) were included in the study.
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77
SEX DISTRIBUTION:
In this study, out of the 120 cases, 59 were males and 61 were females and out of
the 60 controls included 29 were males and 31 were females. Thus, the sex of cases
and controls are matched with a p value of 0.916.
In the study done by Prakash D et al,159 out of 45 cases, 26 were male and 19 were
female, with a male: female sex ratio of 1.5:1. In the Iranian study,160 60 cases
comprised of 32 males (53%) and 28 females (47%). In the study by Karagun
E.,16128 (56%) males and 22 (44%) females were included in the study group. The
control group consisted of 30 (63%) males and 17 (37%) females. In the study by
Takci Z., 162 44 cases included 20 females and 24 males while 43 controls included
33 females and 10 males. Thus the genders in this study are matched equally like that
of the other studies.
DISTRIBUTION OF VITILIGO TYPE:
This study included 5 males and 10 females in focal vitiligo, 7 males and 10
females in mucosal vitiligo, 10 males and 4 females in segmental vitiligo, 9 males and
4 females in acrofacial vitiligo, 26 males and 28 females in vitiligo vulgaris, 2 males
and 5 females in vitiligo universalis. This study shows preponderance of vitiligo
vulgaris (45%) which is in accordance with other studies.
Focal, mucosal and universal vitiligo were commonly seen in females (41%)
while segmental and acrofacial vitiligo were commonly seen in males (32.2%) in this
study.
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78
In the study done by Prakash D et al,159 there were 53% patients with vitiligo vulgaris
type. In the study by Karagun E.,161 all the patients belonged to generalised vitiligo. In
the study by Takci Z., 162 6.8% had localized vitiligo and 93.2% had the generalized.
DISTRIBUTION OF VITILIGO DURATION:
This study included 49 males and 48 females in
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79
controls (56.7%). Thus significant correlation exists between vitiligo and
cholecalciferol. (P value
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80
universalis which implies a significant correlation (P value- 0.025) with the type of
vitiligo. Ten persons (18.5%) with normal values in vitiligo vulgaris were under
phototherapy and are clinically improving.
But, in the study done by Prakash D et al,159 there is no change in cholecalciferol
levels with the type of vitiligo.
CORRELATION OF S. CHOLECALCIFEROL WITH DURATION:
In < 5 years duration, 19(61.3%) patients had severe deficiency, 61(91%) had
deficiency and 17(77.3%) had normal values. In 6-10 years duration, 8(25.8%)
patients had severe deficiency, 6(9%) had deficiency and 1(4.5%) had normal value.
In 11-15 years duration, 3(9.7%) patients had severe deficiency, none had deficiency
and 1(4.5%) patient on phototherapy had normal value. In 16-20 years duration,
1(3.2%) had severe deficiency and 1(4.5%) patient on phototherapy had normal value.
In >21 years duration, 2(9.1%) patients on phototherapy had normal values and none
had deficiency or severe deficiency. This study shows significant correlation (P value-
0.001) with duration of vitiligo. Among patients with vitiligo for > 5 years duration,
only 5 show normal values and all these patients were under phototherapy and
showed clinical improvement. Majority of the patients were suffering from vitiligo for
-
81
CORRELATION OF S.CHOLECALCIFEROL WITH SEVERITY (VASI
Score):
In VASI 75%, 5 patients had severe
deficiency, 2 had deficiency and none had normal values.
This study shows significant correlation (P value26%, none of them show normal values, except 2 (9.1%)
who were under phototherapy were clinically improving.
But, in the study by Takci Z., 162 there was no change in cholecalciferol levels with
the severity of vitiligo patients.
VARIATION OF S. CHOLECALCIFEROL WITH AGE AMONG CASES:
In age ≤20 years, 11 have severe deficiency, 15 have deficiency and none had
normal values. In 21-40 years, 12 have severe deficiency, 22 have deficiency and 9
have normal values. In 41-60 years, 8 have severe deficiency, 25 have deficiency, and
10 have normal values. In ≥ 61 years, 5 have deficiency and 3 have normal values
while none showed severe deficiency.
Thus, in the age group of 60years, none of them showed severe deficiency. This indirectly shows the minimal
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82
sun exposure among younger age groups and higher outdoor activities in older age
group. Moreover, phototherapy is started in comparatively older age group.
In the study done by Prakash D et al,159 there is no change in cholecalciferol levels
with the age of vitiligo patients. In the study by Karagun E.,161 there is no change in
cholecalciferol levels with the age of vitiligo patients. In the study by Takci Z., 162
there is no change in cholecalciferol levels with the age of vitiligo patients.
VARIATION OF S. CHOLECALCIFEROL WITH AGE AMONG
CONTROLS:
In age ≤20 years, none had severe deficiency, 12 had deficiency, 1 had normal
value. In 21-40 years, 4 had severe deficiency, 10 had deficiency and 9 had normal
values. In 41-60 years, none had severe deficiency, 6 had deficiency and 15 had
normal values. In ≥ 61 years, none had severe deficiency, 2 had deficiency and 1 had
normal value.
Thus, in age group40 years, those with normal values are
greater than those with deficiency. None of the studies compared age of the controls
with cholecalciferol.
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83
VARIATION OF S. CHOLECALCIFEROL WITH SEX AMONG CASES:
There are 11 males and 20 females with severe deficiency, 37 males and 30 females
with deficiency and 11 males and 11 females with normal values.
In the study done by Prakash D et al,159 there is no change in cholecalciferol
levels with the sex of vitiligo patients. In the Iranian study,160 Male patients had lower
levels of vitamin D compared to controls (7.25 ng/ mL vs. 13.31ng/mL, P=0.03) while
no significant difference was observed between female patients and controls (14.12
ng/mL vs. 16.25 ng/mL, P=0.51). In the study by Karagun E.,161 there is no change in
cholecalciferol levels with the sex of vitiligo patients. In the study by Takci Z., 162
there is no change in cholecalciferol levels with the sex of vitiligo patients.
In this study, in both cases and controls, there is no sex prediliction (P value- 0.191)
for serum cholecalciferol in normal and deficient groups which was consistent with
other studies, though females show a greater preponderance to severe deficiency.
VARIATION OF S. CHOLECALCIFEROL WITH SEX AMONG
CONTROLS:
Among controls, there are 0 males and 4 females with severe deficiency, 16 males
and 14 females with deficiency and 13 males and 13 females with normal values.
Thus, here also severe deficiency is more commonly seen with females. Otherwise,
there was no significant correlation of cholecalciferol with sex . None of the other
studies compared cholecalciferol variation in sex of control group.
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84
CORRELATION OF S.CHOLECALCIFEROL WITH UV EXPOSURE IN
CASES:
Among those exposed to UV rays by phototherapy or natural sun exposure, there are
6 cases with severe deficiency, 15 cases with deficiency and 21 with normal values. In
comparison, in those who are not exposed to UV rays, there are 25 with severe
deficiency, 52 with deficiency and 1 with normal value thus suggesting significant
correlation of serum cholecalciferol (P value
-
85
SUMMARY
-
86
SUMMARY
Of the total 180 people included in this study, 120 were vitiligo cases and 60
were age and sex matched controls.
The study included 26 cases and 13 controls in the age 60 years. Thus, the age of cases and controls are matched
with a p value of 0.968.
This study included 59 cases, 29 controls in male gender and 61 cases, 31
controls in female gender. Thus, the sex of cases and controls are matched
with a p value of 0.916.
This study shows higher preponderance of vitiligo vulgaris (45%).
Focal, mucosal and universal vitiligo were commonly seen in females (41%)
while segmental and acrofacial vitiligo were commonly seen in males
(32.2%).
Majority (80.83%) of the patients included in this study are affected by vitiligo
for less than 5 years duration. Thus it implies the early health seeking
behaviour due to the social stigma of the disease.
Serum cholecalciferol is low in cases (81.6%) compared to controls (56.7%).
Normal cholecalciferol values among the remaining vitiligo patients could be
attributed to UV radiation either in the form of phototherapy and regular
exposure of sun due to their occupation. The patients under phototherapy
showed clinical improvement following phototherapy.
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87
Serum cholecalciferol deficiency is more commonly associated with vitiligo
vulgaris (36.66%) and universal vitiligo (5.83%). Ten patients of vitiligo
vulgaris having normal values are under phototherapy and show clinical
improvement. Thus, there is significant correlation of serum cholecalciferol
with the type of vitiligo (P value- 0.025).
Serum cholecalciferol deficiency is noted in patients irrespective of the
duration of vitiligo. But, in patients with disease duration of >5 years, all the 5
who had normal values are under phototherapy and show clinical
improvement and others have either deficiency or severe deficiency. Thus
there is significant correlation (P value-0.001) of serum cholecalciferol with
the duration of vitiligo.
In patients with VASI > 26%, almost all had deficiency, except 2 patients
under phototherapy and they show clinical improvement. Thus, significant
correlation exist between serum cholecalciferol level and vitiligo severity (P
value40 years of age
suggesting significant correlation with age. (P value-0.041 for cases and 0.002
for controls)
In both cases and controls, there is no sex prediliction (P value- 0.191 for
cases and 0.131 for controls) for serum cholecalciferol in normal and deficient
groups, though females show a greater preponderance to severe deficiency.
In both cases and controls, normal serum cholecalciferol levels were seen
more commonly in those exposed to UV rays compared to those who are not
-
88
exposed. Significant correlation is seen in cases with P value of
-
89
CONCLUSION
-
90
CONCLUSION
In this study, there is a significant correlation between serum cholecalciferol and
vitiligo. There is also significant correlation of cholecalciferol with the clinical type,
duration and severity of vitiligo. The study showed deficient cholecalciferol levels in
certain clinical types like vitiligo vulgaris and universalis, with vitiligo of longer
duration and of VASI score >26%. Those patients receiving phototherapy showed
normal cholecalciferol and were improving clinically. The observation made in this
study favours the role of low vitamin D level in the pathogenesis of vitiligo and the
role of vitamin D supplementation in the management of vitiligo.
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91