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
1
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.
2
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.
3
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.
4
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 149
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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
9
INTRODUCTION
10
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.
11
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
12 patients attending the Department of Dermatology, Government Rajaji Hospital,
Madurai.
13
AIM OF THE STUDY
14
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.
15
REVIEW OF
LITERATURE
16
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.
17
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
18
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.
19
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.
20
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
21
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
22 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
23 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.
24
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.
25
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
26
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
27
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
28
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.
29 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.
30
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
31
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
32
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
33
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
34
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
35 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.
36
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:
37
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
38
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
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
39
hilar lymphadenopathy, jaundice, leukemic gingivitis,
pseudomembranous sloughing of buccal mucosa
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
40
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
41
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
42
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 rosea
Psoriasis
Lichen stiatus
Lichen striatus et atrophicans
Discoid lupus erythematosis
Morphea
Sarcoidosis
Bullous dermatitis
Cutaneous lymphoma
43
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
44
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.
45
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.
46
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.
47
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.
48
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 <12 ng/mL was seen in a vitiligo patient.136
Another study showed that the Apa-I polymorphism of the VDR gene is associated with vitiligo.137 Thereby it is found that vitamin D or its receptor plays a role in the etiopathogenesis of pigmentation of skin.
The occurrence of hyperpigmentation in psoriatic lesions treated with calcipotriol led to the discovery of a new therapeutic modality in vitiligo.138
Calcipotriol is found to be effective on immunomodulation by inhibiting the
49 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.
50
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.
51
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
52
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
53
MATERIALS and
METHODS
54
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
55 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%
56
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
<5 Very severe deficiency
5-10 Severe deficiency
10-20 Deficiency
20-30 Sub optimal
30-50 Normal
50-70 Upper normal
70-150 Above normal
>150 Intoxication
57
OBSERVATIONS and RESULTS
58
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.
59
AGE DISTIBUTION OF THE STUDY: The study included 26 cases and 13 controls in the age <20 years, 43 cases and 23 controls in 21-40 years, 43 cases and 21 controls in 41-60 years, 8 cases and3 controls in >60 years thus matching the age of cases and controls.
Group Age (in years) 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
Age Distribution 38.3 Case 40.0 35.8 35.835.0 Control 35.0 30.0 21.721.7 25.0 20.0 15.0 6.7
(in percentage) (in 10.0 5.0 5.0 0.0 ≤ 20 21 - 40 41 - 60 >=61 Age group (in yrs)
60
SEX DISTRIBUTION OF THE STUDY: This study included 59 males and 61 females among cases and 29 males and 31 females in controls.
Group Gender 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
SEX DISTRIBUTION
70 59 61 60 Cases Control 50
40 29 31 30
20
10
0 Male Female
61
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.
Sex Type of Vitiligo 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
SEX DISTRIBUTION IN THE TYPE OF VITILIGO 30 28 26 Male 25 Female 20
15 10 10 10 9 10 7 5 4 4 5 5 2 0 Focal Mucosal Segmental acrofacial Vulgaris universalis
62
SEX DISTRIBUTION IN THE DURATION OF VITILIGO: This study included
49 males and 48 females in <5 years, 6 males and 9 females in 6-10 years, 1 male and
3 females in 11-15 years, 2 males and 0 females in 16- 20 years, 1 male and 1 female in ≥21 years duration.
Duration Sex (in years) Male n (%) Female n (%)
< 5 49 (83.1) 48 (78.7)
6 – 10 6 (10.2) 9 (14.8)
11 – 15 1 (1.7) 3 (4.9)
16 – 20 2 (3.4) -
≥ 21 1 (1.7) 1 (1.6)
Total 59 (100.0) 61 (100.0)
p value 0.466 – Not Significant
SEX DISTRIBUTION IN VITILIGO DURATION 60 49 Male 50 48 Female
40
30
20 9 10 6 3 1 2 0 1 1 0 < 5 6 - 10 11 - 15 16 - 20 > 20
63
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.
Group Serum VIT D3(ng/ml) 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 COMPARISON OF SERUM VIT D3 (CASES VS 50 CONTROLS) 39 Case 40 Control 30 28 22 20 17 17 17 12 9 9 10 4 4 1 1 0 0 < 5 5.1 - 10 10.1 - 20 20.1 - 30 30.1 - 50 50.1 - 70 > 70 SERUM VIT D3
64
CHOLECALCIFEROL IMPLICATION IN CASES vs CONTROLS: In order to avoid confusion, those people with very severe and severe deficiency of cholecalciferol levels <10ng/dl were clubbed together as severe deficiency which includes 31 cases and 4 controls. Those with deficiency and suboptimal levels of serum cholecalciferol 10-30ng/dl were clubbed together as deficiency whih includes
67 cases and 30 controls and those with serum cholecalciferol >30ng/dl were clubbed together as normal with 22 cases and 26 controls.
Group Implication Case n (%) Control n (%)
Severe Deficiency (<10 ) 31 (25.8) 4 (6.7)
Deficiency (10-30) 67 (55.8) 30 (50.0)
Normal (>30) 22 (18.3) 26 (43.3)
Total 120 (100.0) 60 (100.0)
p value <0.001 - Significant
Comparison of Serum cholecalciferol (cases vs controls) 80 70 67 Case 60 Control 50 40 31 29 26 30 22 20 10 5 0 Severe Deficiency Deficiency Normal (>30) (<10 ) (10.1-30)
65
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.
Implication Type of Vitiligo Severe Deficiency Deficiency Normal n (%) n (%) 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
Type of Vitiligo Vs Implication Severe Deficiency
60 54.8 Deficiency 45.5 50 40.3 Normal 40 30 patients under 17.9 22.7 16.1 16.1 phototherapy 20 14.9 13.6 14.913.6 9 & natural 6.5 4.5 6.5 (in percentage) (in 3 10 sunlight 0 exposure
66
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 <5 years duration, most of them (80) had deficiency and severe deficiency while only 17 had normal cholecalciferol values.
Implication of cholecalciferol Duration (in years) Severe Deficiency Deficiency Normal n (%) n (%) n (%) < 5 19 (61.3) 61 (91.0) 17 (77.3)
6 - 10 8 (25.8) 6 (9.0) 1 (4.5)
11 - 15 3 (9.7) - 1 (4.5)
16 - 20 1 (3.2) - 1 (4.5)
≥ 21 - - 2 (9.1)
Total 31 (100.0) 67 (100.0) 22 (100.0)
p value 0.001 – Significant
Duration Vs Implication Severe Deficiency
100 91 Deficiency 77.3 Normal 80 61.3 60 patients under 40 25.8 phototherapy
(in percentage) (in 20 9 9.7 9.1 4.5 4.5 3.2 4.5 0 < 5 6 - 10 11 - 15 16 - 20 ≥ 21 (in yrs)
67
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.
Implication of s.cholecalciferol Severe VASI Deficiency Normal Deficiency n (%) n (%) 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 <0.001 – Significant
VASI Score Vs Implication
77.3 80 Severe Deficiency
70 64.2 Deficiency
60 Normal
50
40 32.3 29.9
30 25.8 25.8 (in percentage) (in 16.1 20 13.6 9.1 10 3 3 patients under 0 phototherapy < 10 % 11 - 25 26 - 50 51 - 75% > 75% % %
68
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.
Implication of s.cholecalciferol Age (in years) Severe Deficiency Deficiency Normal n (%) n (%) 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
Age Vs Implication ( Among Cases)
50 45.5 40.9 45 38.7 Severe Deficiency 35.5 37.3 40 32.8 Deficiency 35 25.8 Normal 30 22.4 25 20 13.6 15 7.5 (in percentage) (in 10 5 0 ≤ 20 21 - 40 41 - 60 ≥ 61 Age (in yrs)
69
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.
Implication of s.cholecalciferol Age (in years) Severe Deficiency Deficiency Normal n (%) n (%) 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
Age Vs Implication (Among Controls) 100 Severe 100 Deficiency Deficiency 80 57.7 60 40 33.3 34.6 40
20 (in percentage) (in 20 3.8 6.7 3.8
0 ≤ 20 21 - 40 41 - 60 ≥ 61 Age (in yrs)
70
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.
Implication of s.cholecalciferol Sex Severe Deficiency Deficiency Normal n (%) n (%) 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
Gender Vs Implication (Among Cases) Male 64.5 70 Female 55.2 60 50 50 44.8 50
35.5 40
30 (in percentage) (in 20
10
0 Severe Deficiency Deficiency Normal
71
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.
Implication of s.cholecalciferol Sex Severe Deficiency Deficiency Normal n (%) n (%) 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
Gender Vs Implication (Among Controls) 100 Male 100
90 Female
80
70 53.3 60 50 50 46.7 50
40 (in percentage) (in 30
20
10
0 Severe Deficiency Deficiency Normal
72
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.
Implication of s. cholecalciferol UV Exposure Severe Deficiency Deficiency Normal n (%) n (%) n (%) Exposed to UV 6 (19.4) 15 (22.4) 21 (95.5) rays Not Exposed to 25 (80.6) 52 (77.6) 1 (4.5) UV rays Total 31 (100.0) 67 (100.0) 22 (100.0)
p value <0.001 – Significant
Implication with UV exposure (Among Cases) 95.5 100 80.6 Exposed to Sunlight 90 77.6 80 Not Exposed to 70 Sunlight 60 50 40 19.4 22.4 (in percentage) (in 30
20 4.5 10 0 Severe Deficiency Normal Deficiency
73
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)
Implication of s.cholecalciferol UV Exposure Severe Deficiency Deficiency Normal n (%) n (%) n (%) Exposed to UV - 2 (6.7) 7 (26.9) rays Not Exposed to 4 (100.0) 28 (93.3) 19 (73.1) UV rays Total 4 (100.0) 30 (100.0) 26 (100.0)
p value 0.073 - Not Significant
Implication with uv exposure (Among Controls) 100 Exposed to Sunlight 93.3 100 90 Not Exposed to 73.1 80 Sunlight 70 60 50 40 26.9
(in percentage) (in 30 20 6.7 10 0 Severe Deficiency Normal Deficiency
74
DISCUSSION
75
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 <20 years, 43 cases and 23 controls in 21-40 years, 43 cases and 21 controls in 41-60 years, 8 cases and 3 controls in >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.
76
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.
77
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 <5 years duration, 6 males and 9 females in 6-10 years duration, 1 male and 3 females in 11-15 years duration, 2 males and 0 females in 16- 20 years duration, 1 male and 1 female in ≥21 years duration.
Majority (80.83%) of the patients included in this study are affected by vitiligo for <5 years duration.
This is in accordance with other study done by Prakash D et al,159 where
75.55% cases had vitiligo for <5 years.
SERUM CHOLECALCIFEROL 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, 21 cases and 26 controls with normal levels of serum cholecaciferol. One patient had above normal value of cholecalciferol.
All the patients with normal values and above normal value had been treated with phototherapy and the values were attributed to the same. They showed clinical improvement also. Thus, Serum cholecalciferol is low in cases (81.6%) compared to
78 controls (56.7%). Thus significant correlation exists between vitiligo and cholecalciferol. (P value<0.001 )
But, in the study done by Prakash D et al,159 there were no difference in serum cholecalciferol levels between cases and controls. In the Iranian study,160 cholecalciferol levels were lower in cases (Mean+S.D. 10.24+1.72) than controls
(Mean+S.D. 18.31+7.39). In the study by Karagun E.,161 the patients’ serum vitamin
D levels ranged from 6 to 42 ng/ml (mean: 12.04 ±8.84 ng/ml); in the control group they ranged from 8 to 39 ng/ml (mean: 12.91 ±6.08 ng/ml). The patients had lower circulating vitamin D levels than controls, but this difference was not significant (p =
0.570). In the study by Takci Z., 162 72.73% of the cases and 30.2% controls had deficiency. Thus, our study is in accordance with the study done by Tackci Z.
CORRELATION OF S. CHOLECALCIFEROL WITH TYPE OF VITILIGO:
In focal vitiligo, 2 patients had severe deficiency, 12 had deficiency and 1 had normal value. In mucosal vitiligo, 2 patients had severe deficiency, 10 had deficiency and 5 had normal values. In segmental vitiligo, 5 patients had severe deficiency, 6 had deficiency and 3 had normal values. In acrofacial vitiligo, none had severe deficiency,
10 had deficiency and 3 had normal values. In vitiligo vulgaris, 17 patients had severe deficiency, 27 had deficiency and 10 had normal values. In vitiligo universalis, 5 had severe deficiency, 2 had deficiency and none had normal values.
Though all the patients of all the vitiligo types with severe deficiency and deficiency outnumbers those having normal values of cholecalciferol, this study showed exclusively deficiency and severe deficiency with vitiligo vulgaris and
79 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
<5 years duration, majority (80) had deficiency and severe deficiency while only 17 had normal cholecalciferol values.
But, in the study done by Prakash D et al,159 there is no change in cholecalciferol levels with the duration of vitiligo.
80
CORRELATION OF S.CHOLECALCIFEROL WITH SEVERITY (VASI
Score):
In VASI <10% group, 10 patients had severe deficiency, 43 had deficiency and
17 had normal values. In VASI 11-25%, 8 patients had severe deficiency, 20 had deficiency and 3 had normal values. In VASI 26-50%, 8 had severe deficiency, 2 had deficiency and none had normal values. In VASI >75%, 5 patients had severe deficiency, 2 had deficiency and none had normal values.
This study shows significant correlation (P value<0.001) with the severity of vitiligo. In VASI score >26%, 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 <20years, none showed normal values. In age group of
>60years, none of them showed severe deficiency. This indirectly shows the minimal
81 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 group<40 years, those with severe deficiency and deficiency, outnumbers those with normal values while in age group>40 years, those with normal values are greater than those with deficiency. None of the studies compared age of the controls with cholecalciferol.
82
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.
83
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<0.001) with UV exposure either due to phototherapy or due to natural sunlight exposure.
There is no case control study that assessed cholecalciferol levels with UV exposure.
But, this study is in accordance with the study done by Sehrawat et al8 and the study done by Danilo et al.15
CORRELATION OF S.CHOLECALCIFEROL WITH UV EXPOSURE IN
CONTROLS: Among the controls who are exposed to UV rays by natural sun exposure, there is none with severe deficiency, 2 with deficiency and 7 with normal values. In those who are not exposed to UV rays, there are 4 with severe deficiency,
28 with deficiency and 19 with normal values. But, the correlation of cholecalciferol is not significant (P value-0.073) with UV exposure. None of the other studies compared UV exposure of controls with cholecalciferol.
84
SUMMARY
85
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 <20 years, 43 cases and
23 controls in 21-40 years, 43 cases and 21 controls in 41-60 years, 8 cases
and 3 controls in >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.
86
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
value<0.001).
In both cases and controls, serum cholecalciferol show some improvement
with age since severe deficiency is less common in >40 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
87 exposed. Significant correlation is seen in cases with P value of <0.001 and the association is not significant in control group with P value-0.073. The fact that the patients under phototherapy showed clinical improvement following phototherapy supports the role of vitamin D in the pathogenesis of vitiligo.
88
CONCLUSION
89
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.
90
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109
PROFORMA
110
PROFORMA FOR VITILIGO CASES
Name: O.P. No.:
Age/ sex: Occupation:
Address:
Contact no: c/o: Depigmented patch
Area Size Age of onset duration Repigmentation Stable unstable involved Spont/treatment
h/o mucosa involvement h/o scalp and hair involvement h/o other dermatological conditions associated: psoriasis Alopecia areata atopic eczema
Scleroderma/ SLE lichen planus lichen sclerosis discoid lupus erythematosus halo naevus icthyosis vulgaris
111 h/o other associated systemic conditions
pernicious anemia Addison's disease Myasthenia gravis
nephrotic syndrome hyperthyroidism/ hypoparathyroidism hypothyroidism/
Diabetes mellitus malignancythyroiditis Liver disease
h/o scaling h/o photo sensitivity h/o asthma/ atopy h/o progression of lesion on trauma/friction h/o topical application h/o itching/ burning h/o diminished sensation h/o cosmetic procedures like bleaching h/s/o Herpes simplex/ zoster h/o chemical contact
monobenzyl antiseptic deodorants
ether of soap,
hydroquinoneinsecticides detergentscondom usage slippers gloves alta/ bindhi
112 h/o fever, malaise, weakness h/o premature greying of hair h/o visual disturbance, squint, photophobia h/o headache, confusion, convulsions, ataxia h/o RRTI h/o gingivitis
PAST HISTORY: k/c/o DM/ HT/ BA/ TB/ epilepsy/ CAD h/o previous surgery
PERSONAL HISTORY:
Diet
Smoker
Alcoholic
IVDA
FAMILY HISTORY: h/o similar illness in the family members h/o BA / atopy
TREATMENT HISTORY:
113
Topical application
PUVA
LASER
Surgery
GENERAL EXAMINATION:
Built and Afebrile anemia icterus nourishment Clubbing cyanosis lymphadenopathy Pedal edema
Thyroid:
VITALS:
Pulse rate:
BP:
SYSTEMIC EXAMINATION:
CVS: S1S2+, no murmurs
RS: NVBS+, no added sounds
P/A: soft, BS+
CNS: NFND
114
Dermatological examination:
Configuration and distribution of lesions:
RIGHT LEFT
FACE
NECK
CHEST
ABDOMEN
BACK
UL
LL
Palms
Soles
Oral mucosa:
Genital mucosa:
Scalp and Hair:
Nails:
Diagnosis: Vitiligo- type
VASI Score:
115
INVESTIGATIONS:
COMPLETE HEMOGRAM:
Hb-
TC-
DC- P L E M
ESR-
PLATELET COUNT-
RBC-
PERIPHERAL SMEAR-
LIVER FUNCTION TEST:
TOTAL BILIRUBIN-
DIRECT-
INDIRECT-
SGOT-
SGPT-
TOTAL PROTEIN-
ALBUMIN-
GLOBULIN-
116
RANDOM BLOOD SUGAR-
RENAL FUNCTION TEST:
UREA-
CREATININE-
LIPID PROFILE:
CHOLESTEROL-
TGL-
LDL-
HDL-
VLDL-
ANA PROFILE:
SERUM CHOLECALCIFEROL:
ASSOCIATION-
117
PROFORMA FOR CONTROL
Name:
Age/ sex:
Address:
Contact no:
Occupation:
Lifestyle: clothing-
sunscreen-
food habits- h/o diabetes h/o hypertension h/o liver disease h/o kidney disease h/o cancer h/o heart diseaseh/o neurodegenerative disease- Alzeihmer's disease/ Huntington disease/ Parkinsonism h/o altered bowel habits h/o bone disease
118 h/o thyroid disease h/o parathyroid disease h/o acne h/s/o psoriasis h/s/o alopecia areata h/s/o atopic dermatitis h/o easy fatiguability on eye blinking (Myasthenia gravis) h/o any pigmentation of face and nails (Addisons disease) h/s/o bullous disorder h/s/o DLE h/s/o lichen planus h/s/o lichen sclerosis/ scleroderma
GENERAL EXAMINATION:
Built and Afebrile anemia icterus
nourishment
clubbing cyanosis lymphadenopathy Pedal edema
Thyroid:
119
VITALS:
Pulse rate:
BP:
SYSTEMIC EXAMINATION:
CVS: S1S2+, no murmurs
RS: NVBS+, no added sounds
P/A: soft, BS+
CNS: NFND
DERMATOLOGICAL EXAMINATION:
Skin- mucosa- hair and scalp- palms and soles- nails-
INVESTIGATIONS:
Hb-
TC-
DC- P L E M
120
ESR-
PLATELET COUNT-
RBC-
PERIPHERAL SMEAR-
LFT:TOTAL BILIRUBIN- SGOT-
DIRECT- SGPT-
INDIRECT-
TOTAL PROTEIN-
ALBUMIN- GLOBULIN-
RANDOM BLOOD SUGAR-
RFT:UREA-
CREATININE-
LIPID PROFILE:CHOLESTEROL-
TGL- LDL-
HDL- VLDL-
ANA PROFILE:
SERUM CHOLECALCIFEROL:
ASSOCIATION-
121
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பபயர்: தததி:
வய鏁: உள் த ாயாளி எண்:
பால்: ஆராய்ச்சி தசர்க்லை எண்:
இந்த ஆராய்ச்சியின் விவரங்ை쿁ம் அதன் த ாக்ைங்ை쿁ம் 믁폁லையாை எனக்埁 விளக்ைபட்ட鏁.
எனக்埁 விளக்ைபட்ட விஷயங்ைலள ான் ꯁ쎿ந்鏁 பைாண்翁 என鏁 믁폁 ைன鏁டன் சம்ைதிக்ைிதேன்.
இந்த ஆராய்ச்சியில் பிே쎿ன் ிர்பந்தைின்ேி என் பசாந்த வி쏁ப்பத்தின்தப쎿ல் தான் பங்埁 பப쟁ைிதேன் ைற்쟁ம் ான் இந்த ஆராய்ச்சியில் இ쏁ந்鏁 எந்த த ர믁ம்
122
பின்வாங்ைைாம் என்쟁ம் அதனால் எந்த பாதிப்ꯁம் எனக்埁 ஏற்படா鏁 என்பலத뿁ம் ꯁ쎿ந்鏁 பைாண்தடன்.
ான் என்ꟁலடய 毁ய ிலனퟁடன் ைற்쟁ம் 믁폁毁தந்திரத்鏁டன் இந்த ை쏁த்鏁வ ஆராய்ச்சியில் பங்埁 பைாள்ள சம்ைதிக்ைிதேன்.
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CLINICAL PHOTOGRAPHS
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ACRAL VITILIGO
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LIP VITILIGO
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GENITAL VITILIGO
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ACRAL VITILIGO
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HALO NEVUS
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SEGMENTAL VITILIGO
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POLIOSIS
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INFLAMMATORY TYPE OF SEGMENTAL VITILIGO
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SEGMENTAL VITILIGO
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TRICHROME VITILIGO WITH REPIGMENTATION
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QUADRICHROME VITILIGO
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INFLAMMATORY VITILIGO
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VITILIGO VULGARIS
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EURO IMMUNE ELISA KIT FOR SERUM CHOLECALCIFEROL
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MASTER CHART
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CASES SERUM S. AGE/ TYPE OF NAME OCCUPATION DURATION VASI VITD3 CORRELATION REASON No SEX VITILIGO (ng/ml) Vitiligo 1 Vaishnav 13/M student 2 years 10% 5.6 Severe deficiency vulgaris Mucosal 2 Muthupechi 39/F sweeper 2years 1% 6.4 Severe deficiency vitiligo
Vitiligo 3 Srimathi 6/F student 1 year 10% 17.9 Deficiency vulgaris
Vitiligo 4 Padmanaban 31/M lawyer 8 years 50% 24.6 Sub optimal vulgaris Segmental 5 Madhushri 14/F student 1 year 10% 9.1 Severe deficiency vitiligo Vitiligo MANUAL 6 Vellathai 60/F coolie 1 year 10% 34.9 normal vulgaris LABOUR Mucosal 7 Balamurugan 14/M student 1 year 1% 11.9 deficiency vitiligo Segmental 8 Kaaleswari 15/M student 2 years 10% 9.1 Severe deficiency vitiligo focal 9 Karuppayee 53/F vegetable vendor 1 year 10% 9 Severe deficiency vitiligo Ranjith Vitiligo 10 20/M student 6 months 25% 27.7 Sub optimal kumar vulgaris Vitiligo HOUSEW 11 Latha 31/F housewife 1 year 10% 31.4 normal vulgaris IFE B/L SHEPHER 12 Muthuraja 65/M shepherd 10 years 10% 50.2 Upper normal segmental D B/L MANUAL 13 Rasu 60/M manual labour 4 years 10% 41.7 normal segmental LABOUR Krishnamoor acro facial 14 40/M coolie 30 years 10% 43.9 normal PUVA thy vitiligo Thirumalaina pharmacovigilanc Universal 15 46/M 10 years 90% 14.6 deficiency mbi e vitiligo Segmental 16 Rajkumar 31/M buisness 10 years 10% 13.8 deficiency vitiligo acro facial 17 Santhi 46/F teacher 3 years 10% 15.7 deficiency vitiligo Vitiligo 18 Andiyappan 35/M agriculture worker 5 years 10% 17.8 Deficiency vulgaris B/L focal 19 Praveena 12/F student 1year 10% 20.3 Sub optimal vitiligo TEXTILE 20 Alagarsamy 65/M textile labour acrofacial 1 year 10% 64.6 Upper normal LABOUR Sikkandar Vitiligo 21 57/F housewife 2 years 25% 12.2 Deficiency beevi vulgaris Vitiligo 22 Vasu 22/M clerk 1 year 25% 23.4 Sub optimal vulgaris Mucosal 23 Jalaludeen 33/M teacher 2 years 1% 13.3 Deficiency vitiligo focal 24 Pandikumari 54/F housewife vitiligo 3 years 10% 13.5 Deficiency vitiligo Ramachandr Mucosal 25 25/M courier boy 1 year 1% 16.2 Deficiency an vitiligo acro facial 26 Muniyandi 42/M coolie 2 years 10% 18 Deficiency vitiligo Mucosal 27 Muniyammal 41/F housewife 6 months 1% 18.7 Deficiency vitiligo Mucosal MANUAL 28 Boominathan 23/M manual labour 1 month 1% 54.8 Upper normal vitiligo LABOUR Vitiligo 29 Bose 36/M Driver 3 years 10% 41.9 Normal DRIVER vulgaris
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Ramakrishna Vitiligo 30 60/M agriculture worker 20 years 25% 36.3 Normal PUVA n vulgaris acro facial 31 Angammal 60/F Housewife 2 years 10% 16.4 Deficiency vitiligo Vitiligo 32 Sudha 32/F Housewife 6 years 25% 10.4 Deficiency vulgaris Vitiligo 33 Prabha 30/F Housewife 15 years 25% 5.2 Severe deficiency vulgaris Vitiligo Very severe 34 Palanimuthu 40/M auto driver 3 years 10% 3.4 vulgaris deficiency Vitiligo 35 Mariyappan 58/F Housewife 6 years 25% 22.6 Sub optimal vulgaris Vitiligo 36 Rajendran 60/M Broker 6 months 25% 54.5 Upper normal BROKER vulgaris Mucosal 37 Mukila 11/F Student 3 years 1% 19.9 Deficiency vitiligo Mucosal 38 Balamurugan 58/M tea master 3 months 1% 28.4 Sub optimal vitiligo Vitiligo 39 Jagadeeswari 56/F Housewife 10 years 50% 9.5 Severe deficiency vulgaris Vitiligo 40 Maheswari 37/F Housewife 1 month 10% 22.8 Sub optimal vulgaris Vitiligo 41 Mookan 65/M agriculture worker 2 months 25% 44.7 Normal PUVA vulgaris Vitiligo 42 Durairaj 55/M retd. Clerk 4 months 25% 29.8 Sub optimal vulgaris Universal 43 Selvi 52/F Housewife 10 years 90% 11.8 Deficiency vitiligo Kavyadharsh Vitiligo 44 15/F Student 1 year 25% 13.7 Deficiency ini vulgaris Vitiligo 45 Punitha 51/F Teacher 15 years 75% 31.1 Normal PUVA vulgaris Mucosal 46 Santhi 52/F Tailor 1 year 1% 14 Deficiency vitiligo Vitiligo SHEPHER 47 Chellamuthu 55/F Shepherd 4 years 10% 34.7 Normal vulgaris D Vitiligo 48 Manoharan 64/M 2 years 50% 12.8 Deficiency vulgaris Vitiligo 49 Meena 48/F Dhoby 3 years 10% 14.5 Deficiency vulgaris Acrofacial 50 Prema 21/F sales girl 3 years 10% 10.2 Deficiency vitiligo Bhuvaneswa B/L focal 51 13/M Student 2 years 1% 22.4 Sub optimal ran vitiligo Vitiligo 52 Kalaiselvi 40/F Housewife 6 months 2% 20.1 Sub optimal vulgaris Vitiligo SHEPHER 53 Pichaimani 56/M Shepherd 3 months 1% 82 Above normal vulgaris D Dhanasekara Mucosal 54 20/M Student 5 years 1% 17 Deficiency n vitiligo Vitiligo 55 Poopandi 38/M load man 3 months 10% 25.3 Sub optimal vulgaris Vitiligo 56 Thangammal 44/F Housewife 22 years 75% 30.9 Normal NBUVB vulgaris Segmental 57 Ashok kumar 16/M Cleaner 4 years 10% 21.7 Sub optimal vitiligo Vitiligo 58 Raghupathy 35/M Driver 2 years 10% 20.3 Sub optimal vulgaris Mucosal 59 Indhumathi 30/F housewife 3 years 1% 14.7 Deficiency vitiligo B/L 60 Muniselvi 21/F student 4 years 10% 24 Sub optimal segmental focal 61 Rahul 15/M student 2 months 1% 16.2 deficiency vitiligo Rogeshwara Segmental 62 7/M student 1 year 10% 10.8 deficiency n vitiligo
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focal 63 Rajamani 60/F retd. Palwadi ayah 1.5 years 10% 18.1 deficiency vitiligo focal 64 Palanikumar 9/M student 1 year 1% 12.3 deficiency vitiligo Vitiligo 65 Latha 31/F tailor 2 years 25% 5.1 Severe deficiency vulgaris acro facial 66 Chandran 65/M farmer 1 year 25% 13.2 deficiency vitiligo Vitiligo 67 Muniasamy 55/M merchant 2 years 25% 9.8 Severe deficiency vulgaris Vitiligo 68 Pandi 55/M mason 2 years 25% 8.6 Severe deficiency vulgaris focal 69 Malliga 54/F housewife 1 year 1% 21.2 Sub optimal vitiligo Vitiligo Very severe 70 Malayammal 34/F buisness 3 years 50% 4.6 vulgaris deficiency Mucosal agriculture 71 Selvi 42/F agriculture worker 1 year 1% 44.2 Normal vitiligo worker Vitiligo 72 Ajithkumar 17/M mason 6 months 25% 22.2 Sub optimal vulgaris Universal Very severe 73 Balakrishnan 55/M tailor 17 years 90% 3.2 vitiligo deficiency Mucosal 74 Seethai 40/F coolie 1 month 1% 34.6 Normal coolie vitiligo Segmental 75 Sangili 60/M dhoby 3 years 10% 21.2 Sub optimal vitiligo Dhanalaksh Mucosal 76 49/F housewife 5 months 1% 32.6 Normal mi vitiligo Acrofacial 77 Neelakandan 37/M blacksmith 1 year 25% 17.2 Deficiency vitiligo Universal Very severe 78 Nagarathnam 27/F tailor 5 years 90% 4.1 vitiligo deficiency Acrofacial 79 Pangu 45/F dhoby 1 year 25% 13.1 Deficiency vitiligo Segmental 80 Reshma 10/F student 1 year 10% 6.1 Severe deficiency vitiligo Universal Very severe 81 Chandra 45/F dairy farm owner 3 months 90% 3.2 vitiligo deficiency focal 82 Nagarajan 33/M rice mill owner 6 months 10% 22.6 Sub optimal vitiligo Rengagurusa Mucosal 83 8/M student 3 months 1% 11.9 Deficiency stha vitiligo Vitiligo Very severe 84 Sneha 12/F student 10 years 50% 4 vulgaris deficiency focal 85 Uma 50/F housewife 4 months 10% 28.1 Sub optimal vitiligo Vitiligo 86 Rajapandi 4/M student 2 years 10% 9.8 Severe deficiency vulgaris Vitiligo 87 Santhi 35/F agriculture worker 1 year 25% 19.7 Deficiency vulgaris Acrofacial 88 Subramanian 55/M mechanic 2 years 25% 29.6 Sub optimal vitiligo Acrofacial 89 Senthilkumar 20/M student 6 months 25% 26.8 Sub optimal vitiligo Segmental 90 thangamari 21/M student 1.5 years 10% 17.1 Deficiency vitiligo Vitiligo Very severe 91 Poomayil 30/F coolie 6 years 50% 4.8 vulgaris deficiency papad industry focal 92 Rani 45/F 1 year 1% 20.6 Sub optimal worker vitiligo panchavarna Universal Very severe 93 50/F housewife 8 years 90% 2.1 m vitiligo deficiency Pandiyamma Vitiligo 94 37/F housewife 2 years 25% 16.1 Deficiency l vulgaris Vitiligo 95 Velpandi 17/F student 3 years 50% 7.4 Severe deficiency vulgaris
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Vitiligo 96 Mariammal 55/F housemaid 1.5 years 25% 14.6 Deficiency vulgaris focal 97 Ranjitham 56/F tailor 1 year 1% 25.1 Sub optimal vitiligo focal 98 Imran 18/M student 6 years 1% 7.8 Severe deficiency vitiligo acro facial topical 99 Prabhu 27/M clerk 6 months 10% 31.7 Normal vitiligo PUVA 10 Segmental topical Chellammal 36/F tailor 7 months 10% 30.7 Normal 0 vitiligo PUVA 10 focal Vijayarani 40/F housewife 2 months 1% 44.3 Normal 1 vitiligo 10 Segmental Raman 13/M student 1 year 25% 7.4 Severe deficiency 2 vitiligo 10 Muthuselva Segmental Very severe 12/M student 7 years 25% 4.1 3 m vitiligo deficiency 10 focal Saranya 24/F housewife 3 years 1% 29.1 Sub optimal 4 vitiligo 10 Vitiligo Amudha 35/F mason asst 1 year 10% 26.7 Sub optimal 5 vulgaris 10 Radhakrishn Vitiligo 61/M watchman 2.5 years 25% 16.3 Deficiency 6 an vulgaris 10 Universal Soorya 40/F housemaid 9 months 90% 9.1 Severe deficiency 7 vitiligo 10 Vitiligo Thangam 30/F rice mill owner 11 years 25% 6.1 Severe deficiency 8 vulgaris 10 Mucosal Abi 15/F coolie 2.5 years 1% 9.2 Severe deficiency 9 vitiligo 11 Vitiligo Muthusamy 60/M buisness 12 years 50% 6.2 Severe deficiency 0 vulgaris 11 acro facial Ibrahim 27/M coolie 1 year 25% 22.4 Sub optimal 1 vitiligo 11 Vitiligo Jothi 47/M cook 1.5 years 10% 26.1 Sub optimal 2 vulgaris 11 Mucosal topical Selvarani 32/F housewife 4 months 1% 30.1 Normal 3 vitiligo PUVA 11 Vitiligo Panju 28/F housewife 3 years 50% 8 Severe deficiency 4 vulgaris 11 Vitiligo Vijaya 36/F coolie 10 years 25% 6.1 Severe deficiency 5 vulgaris 11 Vitiligo Alagu 62/M agriculture worker 5 years 10% 21.6 Sub optimal 6 vulgaris 11 Vitiligo Santhanam 68/M buisness 3 years 10% 10.2 Deficiency 7 vulgaris 11 Vitiligo Raju 45/M mason 5 years 25% 11.9 Deficiency 8 vulgaris 11 Vitiligo Anandhi 38/F housewife 6 years 50% 9.8 Severe deficiency 9 vulgaris 12 Vitiligo Manokaran 60/M barber 5 years 25% 20 Deficiency 0 vulgaris CONTROLS S. NAME AGE/SEX OCCUPATION S.VITD3 CORRELATION No 1 Subashini 25/F DOCTOR 10.2 Deficiency
2 Haameem 24/F DOCTOR 6.1 Severe deficiency
3 Gowthami 25/F DOCTOR 7.8 Severe deficiency
4 Suganya 30/F DOCTOR 11.3 Deficiency
5 Deepthi 30/F DOCTOR 8.9 Severe deficiency
6 Thameema 35/F DOCTOR 4.7 Very severe deficiency
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7 Mohammed amir khan 23/M DOCTOR 19.7 Deficiency
8 Sam arul 23/M DOCTOR 13.4 Deficiency
9 Tamil selvi 18/F STAFF NURSE 13.6 Deficiency
10 Swetha 18/F STAFF NURSE 12.5 Deficiency
11 Surya gandhi 54/F STAFF NURSE 43.7 Normal
12 Mariya 53/F STAFF NURSE 44.8 Normal
13 Kothandaramasamy 42/M DOCTOR 14.3 Deficiency
14 Geetha rani 53/F DOCTOR 41.3 Normal
15 Kamal 37/M mason 22.5 Sub optimal
16 Shakila 49/F STAFF NURSE 30.8 Normal
17 Rajeswari 53/F STAFF NURSE 21.3 Sub optimal
18 Vasanth 23/M DOCTOR 15.3 Deficiency
19 Kasthuri 50/F STAFF NURSE 16.8 Deficiency
20 Sivamani 68/M CLERK 16.5 Deficiency
21 Kannan 51/M mmc lab worker 34.2 Normal
22 Chandrakumar 48/M DOCTOR 13.3 Deficiency retd. 23 Vijayakumar Dhanasekar 62/M 39.4 Normal Admn.officer 24 Dorothy 61/F HOUSEWIFE 15.4 Deficiency
25 Zakir hussain 48/M mmc lab worker 29.4 Sub optimal
26 Maheswaran 18/M student 26.3 Sub optimal
27 Rajkumar 18/M student 32.3 Normal
28 Dhinakar 16/M student 25 Sub optimal
29 Mohammed yousif 16/M student 26.7 Sub optimal
30 Sathesh 40/M DOCTOR 57.2 Upper normal
31 Ilango 51/M xray technician 69.4 Normal
32 Saravanakumar 45/M pharmacist 50.2 Normal
33 Sharmila 29/F STAFF NURSE 26.5 Sub optimal
34 Rajalakshmi 38/F STAFF NURSE 49.6 Normal
35 Backiyalakshmi 30/F STAFF NURSE 36.2 Normal
36 Anitha 32/F DOCTOR 25.9 Sub optimal
37 Karthikeyan 32/M DOCTOR 40.1 Normal
38 Rakesh sharma 32/M DOCTOR 42.9 Normal
39 Keerthana 26/F DOCTOR 30.1 Normal
40 Latha rani 28/F DOCTOR 36.2 Normal
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41 Kavitha 40/F DOCTOR 32.7 Normal
42 Deepa 39/F DOCTOR 30.1 Normal
43 Suba 26/F DOCTOR 18.1 Deficiency
44 Hema 25/F DOCTOR 11.7 Deficiency
45 Shanmugaperumal 50/M DOCTOR 52.8 Normal Block health 46 Dhanasekaran 51/M 65.1 Normal supervisor 47 Murali 59/M office supdt 55.2 Normal
48 Rajendran 52/M health inspector 65 Normal
49 Saleem 55/M buisness 67.6 Normal village health 50 Thangammal 60/F 56.1 Normal nurse village health 51 Angayarkanni 60/F 48.6 Normal nurse 52 Dhivya 18/F student 20 Sub optimal
53 Saranya 15/F student 22.1 Sub optimal village health 54 Avudayammal 55/F 38.6 Normal nurse village health 55 Fathima 46/F 16.1 Deficiency nurse 56 Dhanush 6/M student 10 Deficiency
57 Priyan 15/M student 20.2 Sub optimal
58 Arun kumar 18/M student 26.1 Sub optimal
59 Suresh 20/M student 21.2 Sub optimal
60 Kumar 10/M student 11.1 Deficiency
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ANTI PLAGIARISM CERTIFICATE
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ETHICAL COMMITTEE APPROVAL CERTIFICATE
149
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