A study on the correlation of serum cholecalciferol level and vitiligo in patients attending Government Rajaji Hospital, Madurai

150  Download (0)

Full text

(1)

1

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

(2)

2

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,

(3)

3

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.

(4)

4

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.

(5)

5

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 Headof the Department of Dermatology, Madurai Medical College, Madurai. I also declare that this bonafide work or a part of this work was notsubmitted 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).

(6)

6

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 hospitalfacilities 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

(7)

7

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.

(8)

8

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

(9)

9

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

(10)

10

(11)

11

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.

(12)

12

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

(13)

13

(14)

14

(15)

15

AIM OF THE STUDY

(16)

16

REVIEW OF

(17)

17

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.

(18)

18

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

(19)

19

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

(20)

20

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

(21)

21

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.

(22)

22

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.

(23)

23

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

(24)

24

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:

(25)

25

 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

(26)

26

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).

(27)

27

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

(28)

28

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

(29)

29

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

(30)

30

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.

(31)

31

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

(32)

32

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

(33)

33

Histopathologic findings101 have been used to support various theories concerning the development of vitiligo. Perilesional melanocytes express major histocompatibility class II antigens and substantially higher intercellular adhesion molecule 1relative to normal skin controls. These have been found in follicular epithelium in auto immune thyroiditis and in pancreatic beta cells in type 1 diabetes, upholding the autoimmune hypothesis.

The phenomenon of direct nerve contact with melanocytes along the dermoepidermal junction in depigmented skin of patients with vitiligo75 and a complete or partial degeneration of the nerves73,74 support the neural hypothesis of vitiligo.

ASSOCIATED DISORDERS

A) Skin diseases

Premature canities has been reported in about 37% of vitiligo cases.102 Vitiligo is frequently seen in association with atopic eczema.103

Coexistence of psoriasis and vitiligo and occurence of psoriasis on vitiligo macules have been documented.104,105

(34)

34

There have been reports of association of vitiligo with alopecia areata and DLE,108 pemphigus vulgaris,109,110 lichen planus111 and squamous cell carcinoma112 on

a patch of mucosal vitiligo.

Halo naevi have been estimated to occur in about 50% of cases of vitiligo.113

Alopecia areata has been reported in up to 16% of vitiligo patients.114

Jopling W.H.115 has been found an association of vitiligo with lepromatous leprosy. In his study conducted among 114 lepromatous leprosy, 8 patients developed vitiligo after varying years of treatment accounting for incidence of 7%. The association of vitiligo with lepromatous leprosy has supported the hypothesis that vitiligo has an autoimmune basis, for a wide variety of autoantibodies have been described in lepromatous leprosy.

Vitiligo and melanoma frequently occur together. Vitiligo associated with melanoma carry a poor prognosis.100

Saiham et al (1979) reported vitiligo in association with morphoea.116

B) Systemic disorders

There is ample documentation of the association of vitiligo with autoimmune disoders.

The increased incidence of hyperthyroidism and Hashimoto's thyroiditis in vitiligo patients is well recorded.117,118

(35)

35

Vitiligo has been reported to develop in 7% of patients with Graves' disease.51

Pernicious anemia is recorded 30 times more frequent among vitiligo patients than in general population.119

Fifteen percent of Addison's disease patients have been reported to have vitiligo.120

The prevalence of diabetes mellitus in vitiligo patients is reported to vary from 1% to 7.1%.117

According to Dawber (1968), diabetes mellitus should be excluded in every patient with late onset vitiligo.121

Bhargava et al reported a case of congenital leopard vitiligo associated with multiple sclerosis.122

Satish et al reported a case of vitiligo with oesophageal carcinoma.123

There are reports of vitiligo with ulcerative colitis, myasthenia gravis,124 primary ovarian failure and juvenile rheumatoid arthritis.125 Some other studies have reported the association of vitiligo with multiple myeloma, pernicious anemia126 and dysgammaglobulinemia A.127

SYNDROMES ASSOCIATED WITH VITILIGO

Vogt Koyanagi Harada syndrome128,129 is an apparently rare, multisystem disease

(36)

36

was first described by Vogt in 1906. Harada in 1926, described five cases with bilateral posterior uveitis with retinal detachment. Koyanagi completed the description of the syndrome in 1929. It affects both sexes equally and the peak frequency is in the third decade.

Clinical Features:

Classical Vogt Koyanagi Harada syndrome has 3 phases.

I. Meningoencephalitic phase: manifested by headache, malaise, nausea, vomiting, confusion, psychosis, paraplegia, and generalised weakness.

II. Ophthalmic auditory phase: characterised by decreased visual acuity, photophobia, and eye pain. Dysacousia is seen in 50% of patients.

III. Convalescent phase: starts as uveitis begins to abate and is characterised by alopecia, poliosis and vitiligo.

Criteria for diagnosis for Vogt Koyanagi Harada syndrome are as follows:1  No history of ocular trauma or surgery preceding the initial onset of uveitis.  No clinical or laboratory evidence suggestive of ocular disease entities.  Bilateral ocular involvement

 diffuse choroiditis- early sign  ocular depigmentation- late sign

 Neurological and auditory findings: meningismus, tinnitus, cerebrospinal fluid

pleocytosis.

(37)

37

Alezzandrini's syndrome130 is charcterised by a unilateral degenerative retinitis

followed after several months by ipsilateral vitiligo on the face and ipsilateral poliosis. Deafness may also be present.

SCORING SYSTEMS IN VITILIGO:16

Vitiligo area and severity index (VASI Score):

Percentage of vitiligo involvement is calculated in terms of hand units. One hand unit (encompass palm and volar surface of all digits) is approximately equivalent to 1% of total body surface area. The degree of depigmentation is estimated to the nearest of the following percentages:

 100%- complete depigmentation

 90%- specks of normal pigmentation present  75%- depigmented area exceeds pigmented area  50%- pigmented and depigmented area are equal

 25%- normally pigmented area exceeds depigmented area  10%- only specks of depigmentation present

Vitiligo disease activity score (VIDA):

The VIDA is a six-point scale for assessing vitiligo activity.

(38)

38

 VIDA Score 4+ - Activity of 6 weeks or less duration  3+ - Activity of 6 weeks to 3 months

 2+ - Activity of 3 - 6 months  1+ - Activity of 6 - 12 months  0 - Stable for 1 year or more

 -1 - Stable with spontaneous repigmentation since 1 year or more.

A low VIDA score indicates less activity.

DIFFERENTIAL DIAGNOSIS:1,3,4,5

Congenital normal variant:

 Nevus achromicus- Solitary hypopigmented macule well circumscribed with irregular borders, stable in size, solitary, most often present at birth

 Nevus anaemicus- Hypochromic pale lesion with well-defined borders and irregular margins which are usually solitary and they are located on the trunk. Histology and electron microscopic examination reveal no abnormality in melanocytes or melanization

Genetic disorders:

 Oculo cutaneous albinism-

 Type -1: TYR mutation- 1a- total lack of tyrosinase

(39)

39

 Type -3: TYRP1 mutation- defective oxidation of dihydroxy indole 2 carboxylic acid

 Type -4: SLC45A2 mutation- defective melasome transfer

 Type -6: SLC24A5 mutation- defective maturation of melanosomes

 Oculo cutaneous albinoidism- mild form of tyrosinase positive oculocutaneous albinism.

 Piebaldism- defect in c-kit protooncogene  poliosis

 depigmented macules

 Hermansky Pudlak syndrome  oculocutaneous albinism  haemmorrhagic diasthesis

 pulmonary fibrosis, granulomatous colitis, lupus nephritis  nystagmus, photophobia, visual disturbances

 Chediak Higashi syndrome- LYST mutation

 squint, photophobia, decreased retinal pigmentation  increased susceptibility to infection

 pancytopenia

(40)

40

 hilar lymphadenopathy, jaundice, leukemic gingivitis, pseudomembranous sloughing of buccal mucosa

 Waardenburg syndrome

 Type 1- classical- dystopia canthorum, prominent nasal root and

medial eyebrows, congenital sensoryneural hearing loss, heterochromia irides, white forelock, premature canites.

 Type 2- No dystopia canthorum and facial dysmorphism. higher incidence of deafness and heterochromia

 Type 3- associated with musculoskeletal abnormalities  Type 4- associated with Hirschsprung disease

 Cross syndrome- geeralised hypopigmentation, mental retardation, spastic tetraplegia, athetosis, microphthalmos

 Griscelli Prunieras syndrome

 Type 1- primary CNS dysfunction

 Type 2- haemophagocytic lymphohistiocytosis  Type 3- partial albinism

 Woolf's syndrome- piebaldism, deafness, mental retardation

 Tietz's syndrome

(41)

41  normal eyes

 deaf mutism

 hypoplasia of eyebrows

 Ataxia telangectasia

 premature greying of hair

 cerebellar ataxia, choreoathetosis  oculocutaneous telangiectasia  bronchiectasis

 Tuberous sclerosis- TSC 1 and 2 mutation- ash leaf macules

 Hypomelanosis of Ito- hypopigmented linear streaks along blaschko lines, neurological, ophthalmological, and skeletal defects.

 Inborn errors of metabolism:

 Phenylketonuria- depigmented skin, hair, eyes, photophobia.  Menke kinky syndrome- ATP7A mutation- hair changes-

monelethrix, pili torti, trichorrhexis nodosa, neurological deterioration.

 Homocystinuria- marfanoid features, mental retardation, ectopia lentis, depigmented macules, hypopigmented hair.

Endocrinopathy:

(42)

42

 Hyperthyroidism

 Hypogonadism

Nutritional:

 Kwashiorkar

 Malabsorption

Chemical contact:

 Monobenzyl ether of hydroquinone and Hydroquinone

 Phenol

 Thiouracil

 Thiol

 Butylated hydroxytoluine

 Steroids

 Retinoids

 Topical imiquimod

Systemic drugs:

 chloroquine

 fluphenazine

 physostigmine

(43)

43

Post inflammatory:

 Mechanical trauma

 Thermal injury

 Ionizing radiation

 Infections:

 Bacterial- Leprosy, Syphilis

 Viral- Herpes simplex, Herpes zoster  Fungal- Tinea versicolor, Candidiasis  Parasitic- Onchocerciasis

Other dermatological disorders with hypo pigmentation:

 Pityriasis alba

 Pityriasis rosea

 Psoriasis

 Lichen stiatus

 Lichen planus

 Lichen striatus et atrophicans

 Discoid lupus erythematosis

 Morphea

 Sarcoidosis

 Bullous dermatitis

(44)

44

Others:

 Idiopathic guttate hypomelanosis

 Progressive macular hypomelanosis

 Halo nevus

MANAGEMENT1

First line

Potent topical corticosteroid (e.g. 0.1% betamethasone valerate or 0.05% clobetasol propionate) is effective at inducing repigmentation of areas of vitiligo.

It is preferable to use an intermittent regimen (e.g. 15 days per month for 6 months) to avoid local side effects (skin atrophy, telangiectasia, striae, hypertrichosis and acneform eruptions).

Topical calcineurin inhibitors (pimecrolimus, tacrolimus) has been

reported to be successful, mainly for lesions on the face and neck twice daily applications are recommended, initially for 6 months.

Topical Vitamin D analogscalcipotriol ointment (0.005%) and tacalcitol

(45)

45

probably because of stimulation of both melanocyte growth (with corticosteroids or UV) and differentiation (with a vitamin D analog).

Vitamin D derivatives are indicated for use in localized disease They lack adverse effects of skin atrophy. However, their role in vitiligo treatment remains controversial

Second line

Systemic psoralen photochemotherapy (PUVA) is effective in a proportion of cases. The use of topical applications of psoralens is more hazardous and may result in untoward blistering of the skin.

Photosensitizers including khellin have been advocated but there are concerns over hepatotoxicity and it has not been widely adopted.

UVB therapy can also be used selectively.

 Localized targeted phototherapy devices (excimer lamp or lasers with a

peak at 308 nm). There is no consensus as to the optimum treatment duration of phototherapy. Most often irradiation will be stopped if no repigmentation occurs within the first 3 months of treatment.

Third line

Grafting techniques

(46)

46

Different surgical techniques for repigmenting vitiligo have been gradually devised and include

Tissue grafts

 full thickness punch grafts  split thickness grafts  suction blister grafts

Cellular grafts

 cultured melanocytes

 cultured epithelial sheet grafts

 non cultured epidermal cellular grafts

Lately, the use of hair follicle outer root sheath cells has been introduced. The three tissue grafting methods (full thickness punch grafts, split thickness grafts, suction blister grafts) seem to have comparable success rates in inducing repigmentation.

(47)

47

Depigmenting treatment: In those patients with extensive vitiligo and only a few residual areas of pigmentation, skin bleaching with

 laser therapy (e.g. Q switched alexandrite 755 nm, Q switched ruby 694 nm),  cryotherapy

 creams(e.g. 20% monobenzylether of hydroquinone), may be used.

Camouflage and psychological support:

Camouflage:131

Temporary camouflage:

Liquid dyes:

Potassium permanganate, indigo carmine, Bismarck brown and henna pastes are commonly used. But, they may get washed away easily.

Indigenous preparations (Traditional Indian Preparations)

Iron fillings (Loha Bhasma) and Suvarna Karini (clay mixed with henna and oils) are used. But, colour matching is difficult.

Foundation-based cosmetic camouflage

Oil-based, water-based, oil-free and water-free forms are available with matte, semi-matte, moist semi-matte and shiny finishes. Liquid foundations are also available.

Self-tanning products:

(48)

48

Permanent camouflage:

It is achieved mainly by micropigmentation/medical tattooing. Iron oxide is the most

common pigment used. Various other chemicals used and the respective colors produced are as follows:

 black, camel yellow, light and dark brown (iron oxide)  white (titanium dioxide)

 yellow (cadmium sulfide)

 red (mercuric sulfide/cinnabar with cadmium sulfide added to make the red shade brighter).

Complications include colour fading, allergic contact dermatitis, reactivation of herpes, transmission of HIV and hepatitis B.

Psychological support:

(49)

49

Role of vitamin D in vitiligo:

Parsad et al.132 first reported the use of vitamin D analogues in combination with PUVAsol and topical calcipotriol for the treatment of vitiligo. Many studies have been reported about the use of vitamin D analogues alone or in combination with ultraviolet light or corticosteroids to enhance repigmentation in vitiligo.133

Birlea et al., concluded that vitamin D3 analogues are effective in combination with PUVA, NBUVB, or an excimer laser after reviewing 22 studies published on calcipotriol/tacalcitol used alone or in combination with other agents.134

Oh et al., reported that high concentration of tacalcitol was applied topically with 308 nm xenon chloride excimer laser to lower the energy threshold to treat non segmental vitiligo.135

In a recently published case report, it was found low levels of vitamin D <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.

(50)

50

inflammatory mediators139 and stimulate melanin production by activating melanocytes and keratinocytes.140

Melanocytes in the epidermis become swollen with elongated dendrites after UV exposure. On long term UV exposure, the tyrosinase activity in these melanocytes is increased by microphthalmia transcription factor (MITF),141 and results in the deposition of the melanin in the epidermis.

Tomita et al., studied that increased cell size, number of dendrites, and tyrosinase activity was induced by both vitamin D3 and UV radiation individually.142

Ermis et al., reported that the combination of calcipotriol and PUVA was safe and more effective in initiating and achieving complete repigmentation than a placebo with PUVA.143

A marginal type of repigmentation pattern is seen and the onset of repigmentation induced by calcipotriol was slow.144 In a few cases, treatment failure or no added response was observed at the end of 3 months with combination therapy with these vitamin D analogues.133

(51)

51

It has been shown that defective calcium (Ca2+) transport is found in keratinocytes and melanocytes of vitiliginous skin samples.146 Both plasma membrane

associated and cytosolic thioredoxin reductase is controlled by calcium. Decreased intracellular Ca2+ inhibits melanin synthesis due to high levels of reduced thioredoxin which inhibits tyrosinase activity. Moreover, melanocytes express 1,25-dihydroxyvitamin D3 receptors and regulates melanin synthesis.147,148

Thus, calcipotriol plays a role in Ca2+ regulation through 1,25-dihydroxyvitamin D3 receptors on melanocytes and/or by the regulation of defective Ca2+ homeostasis.143

Proinflammatory and proapoptotic cytokines, such as IL-6, IL-8, IL-10, IL-12, INF-ᵧ, and TNF-ἀ, play a role in the pathogenesis of vitiligo.149,150 The expression of IL-6, IL-8, TNF-ἀ, and TNF-ἀ is inhibited by vitamin D.151 Dendritic cell maturation, differentiation, and activation in both human and murine culture systems,152 are modulated by vitamin D probably by VDR-dependent pathway.153

Vitamin D compounds also induce the inhibition of antigen presentation.152,153

Vitamin D protects the epidermal melanin unit and restores melanocyte integrity by the following mechanisms:

(52)

52

 Immunomodulatory action of VDR on immune cells lead to coordination of T cell activation mainly by the inhibition of T cell transition from the early to the late G1 phase and by the inhibition of several cytokine genes encoding TNF-ἀ and IFN-ᵧ.154

The mechanism through which vitamin D exerts its effects on melanocytes is not yet fully understood. Vitamin D helps in coordinating melanogenic cytokines like endothelin-3 and the activity of the SCF/c-Kit system, which regulates melanocyte maturation.154

There is also an antioxidant role of vitamin D in vitiligo by regulating reative

oxygen species.

The active form of vitamin D produces IL-6 and reduces the apoptotic activity of keratinocytes155 and melanocytes 156 induced by UVB.

In another study, melanocytes protected from apoptosis through the formation of sphingosine-1-phosphate by vitamin D,also opposes apoptotic action in diverse melanoma cell lines.157

 Vitamin D-It acts on specific T cell by inhibiting the expression of several proinflammatory cytokines genes (TNFἀ, IFᵧ)

(53)

53

 1,25-Dihydroxyvitamin D3- It has anti apoptotic effects and decreased cyclobutane pyrimidine dimers damage by up to 60%

 Tacalcitol- a vitamin D analogue plays a role in Ca2+ regulation by vitamin D receptor (VDR) on melanocytes

(54)

54

MATERIALS and

(55)

55

MATERIALS AND METHODS

This is a hospital based case control study with a sample size of 180 including 120 cases and 60 controls.

The study was done for 6 months from December 2016 to May 2017 in dermatology out patient department, Government Rajaji hospital.

Clinically diagnosed cases of vitiligo attending dermatology department constitute the cases. Age matched and sex matched healthy volunteers comprised the control group. Ethical committee approval was obtained.

Informed consent were obtained from all those who were included in this study. All were interrogated for a detailed history and a meticulous examination of each case was carried out and recorded in a special proforma separately for cases and controls.

History of precipitating factors such as trauma, chemicals, stress, associations were specifically asked for and noted. History suggestive of thyroid disease, atopy, diabetes was noted.

A complete general physical examination was done in all those who were included in the study. A thorough systemic examination was also made for associated disorders and the findings were noted. Detailed dermatological examination including the mucosa was carried out to classify the disease, to know the extent of vitiligo and to study the specific features such as trichrome, quadrichrome, and leukotrichia.

(56)

56

test, serum fasting lipid profile, serum proteins, antinuclear antibody, and serum 25 hydroxy cholecalciferol.

The patients were categorized based on the type, duration, and severity of vitiligo.

The patients were classified based on the following clinical types:

 Focal  segmental  mucosal  acrofacial  vitiligo vulgaris  vitiligo universalis

The patients were categorized on the basis of duration as follows:

 0-5 years  6-10 years  11-15 years  16-20 years  >21 years

Severity of vitiligo was assessed using VASI score.16

The patients are categorized based on VASI score as follows:

(57)

57  26-50%

 51-75%  76-100%

Serum 25-OH cholecalciferol levels were calculated using Euro immune ELISA kit. The cases and controls were categorized based on serum 25-OH cholecalciferol levels as follows:158

Serum 25-OH cholecalciferol level (ng/ml) Implication

<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

(58)

58

(59)

59

OBSERVATION and RESULTS:

(60)

60

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.

Age (in years)

Group

Case n (%) Control n (%)

≤ 20 26 (21.7) 13 (21.7) 21 - 40 43 (35.8) 23 (38.3) 41 - 60 43 (35.8) 21 (35.0) >=61 8 (6.7) 3 (5.0) Total 120 (100.0) 60 (100.0) Mean±SD 37.6±17.2 36.2±15.8

Min, Max 4, 68 6,68

p value 0.968 - Not Significant

0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0

≤ 20 21 - 40 41 - 60 >=61

21.7 35.8 35.8 6.7 21.7 38.3 35.0 5.0 (in pe rc entag e)

Age group (in yrs)

Age Distribution

(61)

61

SEX DISTRIBUTION OF THE STUDY: This study included 59 males and 61

females among cases and 29 males and 31 females in controls.

Gender

Group

Case n (%) Control n (%)

Male 59 (49.2) 29 (48.3) Female 61 (50.8) 31 (51.7) Total 120 (100.0) 60 (100.0) p value 0.916 - Not Significant

59

61

29

31

0

10

20

30

40

50

60

70

Male Female

SEX DISTRIBUTION

(62)

62

SEX DISTRIBUTION IN THE TYPE OF VITIIGO: This study included 5 males

and10 females in focal vitiligo, 7 males and 10 females in mucosal vitiligo, 10 males and 4 females in segmental vitiligo, 9 males and 4 females in acrofacial vitiligo, 26 males and 28 females in vitiligo vulgaris, 2 males and 5 females in vitiligo universalis.

Type of Vitiligo

Sex

Male n (%) Female n (%)

Focal 5 (8.5) 10 (16.4)

Mucosal 7 (11.9) 10 (16.4) Segmental 10 (16.9) 4 (6.6) Acrofacial 9 (15.3) 4 (6.6) Vulgaris 26 (44.1) 28 (45.9) Universalis 2 (3.4) 5 (8.2)

Total 59 (100.0) 61 (100.0) p value 0.155 – Not Significant

5

7

10

9

26

2

10

10

4

4

28

5

0

5

10

15

20

25

30

Focal Mucosal Segmental acrofacial Vulgaris universalis

SEX DISTRIBUTION IN THE TYPE OF VITILIGO

(63)

63

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 (in years)

Sex

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

49

6

1

2

1

48

9

3

0

1

0 10 20 30 40 50 60

< 5 6 - 10 11 - 15 16 - 20 > 20

SEX DISTRIBUTION IN VITILIGO DURATION

(64)

64

S. CHOLECALCIFEROL LEVELS IN CASES vs CONTROLS : There were 9

cases and 1 control with very severe deficiency, 22 cases and 4 controls with severe deficiency, 39 cases and 17 controls with deficiency, 28 cases and 12 controls with suboptimal levels, 22 cases and 26 controls with normal levels and 1 patient had above normal value.

Serum VIT D3(ng/ml) Group

Case n (%) Control n (%)

Very severe deficiency(< 5) 9 (7.5) 1 (1.7) Severe deficiency(5.1 - 10) 22 (18.3) 4 (6.7) Deficiency (10.1 - 20) 39 (32.5) 17 (28.3) Sub optimal(20.1 - 30) 28 (23.3) 12 (20.0)

Normal (30.1 - 50) 17 (14.2) 17 (28.3)

Upper normal (50.1 - 70) 4 (3.3) 9 (15.0)

Above normal (> 70) 1 (0.8) -

Total 120 (100.0) 60 (100.0)

Mean±SD 19.8±13.6 29.5±17.1

Min, Max 2.1, 82.0 4.7, 69.4

p value < 0.004 Sig

9 22 39 28 17 4 1 1 4 17 12 17 9 0 0 10 20 30 40 50

< 5 5.1 - 10 10.1 - 20 20.1 - 30 30.1 - 50 50.1 - 70 > 70

SERUM VIT D3

COMPARISON OF SERUM VIT D3 (CASES VS CONTROLS)

(65)

65

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.

Implication

Group

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

31

67

22

5

29

26

0 10 20 30 40 50 60 70 80

Severe Deficiency

(<10 )

Deficiency

(10.1-30)

Normal (>30)

Comparison of Serum cholecalciferol (cases vs controls)

(66)

66

CORRELATION OF S. CHOLECALCIFEROL WITH TYPE OF VITILIGO:

The study showed deficiency and severe deficiency of serum cholecalciferol in patients with vitiligo vulgaris and universalis thus suggesting significant correlation with the type of vitiligo. Ten vitiligo vulgaris patients with normal values could be explained by the fact that they were on phototherapy and are clinically improving.

Type of Vitiligo

Implication Severe Deficiency n (%) Deficiency n (%) Normal n (%)

Focal 2 (6.5) 12 (17.9) 1 (4.5)

Mucosal 2 (6.5) 10 (14.9) 5 (22.7)

Segmental 5 (16.1) 6 (9.0) 3 (13.6)

Acrofacial - 10 (14.9) 3 (13.6)

Vulgaris 17 (54.8) 27 (40.3) 10 (45.5)

Universalis 5 (16.1) 2 (3.0) -

Total 31 (100.0) 67 (100.0) 22 (100.0)

p value 0.025 – Significant

0 10 20 30 40 50 60 6.5 6.5 16.1 54.8 16.1 17.9 14.9 9 14.9 40.3 3 4.5 22.7 13.6 13.6 45.5 (in pe rc entag e)

Type of Vitiligo Vs Implication Severe Deficiency

(67)

67

CORRELATION OF S. CHOLECALCIFEROL WITH DURATION: This study

shows significant correlation (P value-0.001) with duration of vitiligo. Among patients with vitiligo for > 5 years duration, only 5 show normal values and all these patients were under phototherapy and showed clinical improvement. Majority of the patients were suffering from vitiligo for <5 years duration, most of them (80) had deficiency and severe deficiency while only 17 had normal cholecalciferol values.

Duration (in years)

Implication of cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal 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

0 20 40 60 80 100

< 5 6 - 10 11 - 15 16 - 20 ≥ 21

61.3 25.8 9.7 3.2 91 9 77.3

4.5 4.5 4.5 9.1

(in pe rc enta g e) (in yrs)

Duration Vs Implication Severe Deficiency

Deficiency Normal

patients under

(68)

68

CORRELATION OF S.CHOLECALCIFEROL WITH SEVERITY (VASI

Score): This study shows significant correlation with the severity of vitiligo. Among patients with VASI score >26%, 2 out of 19 patients had normal value which could probably be explained by previous phototherapy. They also showed clinical improvement.

VASI

Implication of s.cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

< 10 % 10 (32.3) 43 (64.2) 17 (77.3) 11 - 25 % 8 (25.8) 20 (29.9) 3 (13.6)

26 - 50 % 8 (25.8) 2 (3.0) -

51 - 75% - - 2 (9.1)

> 75% 5 (16.1) 2 (3.0) -

Total 31 (100.0) 67 (100.0) 22 (100.0) p value <0.001 – Significant

0 10 20 30 40 50 60 70 80

< 10 % 11 - 25 %

26 - 50 %

51 - 75% > 75%

32.3 25.8 25.8 16.1 64.2 29.9 3 3 77.3 13.6 9.1 (in pe rc enta g e)

VASI Score Vs Implication

Severe Deficiency Deficiency

Normal

(69)

69

VARIATION OF S. CHOLECALCIFEROL WITH AGE AMONG CASES: In

age ≤20 years, 11 have severe deficiency, 15 have deficiency. In 21-40 years, 12 have severe deficiency, 22 have deficiency and 9 have normal values. In 41-60 years, 8 have severe deficiency, 25 have deficiency, and 10 have normal values. In ≥ 61 years, 5 have deficiency and 3 have normal values while none show severe deficiency.

Age (in years)

Implication of s.cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

≤ 20 11 (35.5) 15 (22.4) -

21 - 40 12 (38.7) 22 (32.8) 9 (40.9) 41 - 60 8 (25.8) 25 (37.3) 10 (45.5)

≥ 61 - 5 (7.5) 3 (13.6)

Total 31 (100.0) 67 (100.0) 22 (100.0)

p value 0.041 – Significant

0 5 10 15 20 25 30 35 40 45 50

≤ 20 21 - 40 41 - 60 ≥ 61

35.5 38.7 25.8 22.4 32.8 37.3 7.5 40.9 45.5 13.6 (in pe rc entag e)

Age (in yrs)

Age Vs Implication ( Among Cases)

Severe Deficiency Deficiency

(70)

70

VARIATION OF S. CHOLECALCIFEROL WITH AGE AMONG

CONTROLS: In age ≤20 years, 12 have deficiency, 1 has normal value. In 21-40 years, 4 have severe deficiency, 10 have deficiency and 9 have normal values. In 41-60 years, 6 have deficiency and 15 have normal values. In ≥ 61 years, 2 have deficiency and 1 has normal value.

Age (in years)

Implication of s.cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

≤ 20 - 12 (40.0) 1 (3.8)

21 - 40 4 (100.0) 10 (33.3) 9 (34.6)

41 - 60 - 6 (20.0) 15 (57.7)

≥ 61 - 2 (6.7) 1 (3.8)

Total 4 (100.0) 30 (100.0) 26 (100.0)

p value 0.002 – Significant

0 20 40 60 80 100

≤ 20 21 - 40 41 - 60 ≥ 61

100 40 33.3 20 6.7 3.8 34.6 57.7 3.8 (in pe rc entag e)

Age (in yrs)

Age Vs Implication (Among Controls)

(71)

71

VARIATION OF S. CHOLECALCIFEROL WITH SEX AMONG CASES:

There are 11 males and20 females with severe deficiency, 37 males and30 females with deficiency and 11 males and 11 females with normal values. Thus, there was no significant variation with sex among cases in deficient and normal groups. But severe deficiency was commonly seen in females.

Sex

Implication of s.cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

Male 11 (35.5) 37 (55.2) 11 (50.0) Female 20 (64.5) 30 (44.8) 11 (50.0) Total 31 (100.0) 67 (100.0) 22 (100.0) p value 0.191 - Not Significant

0 10 20 30 40 50 60 70

Severe Deficiency Deficiency Normal 35.5 55.2 50 64.5 44.8 50 (in pe rc entag e)

Gender Vs Implication (Among Cases)

Male

(72)

72

VARIATION OF S. CHOLECALCIFEROL WITH SEX AMONG

CONTROLS: Among controls, there are 0 males and 4 females with severe deficiency, 16 males and 14 females with deficiency and 13 males and 13 females with normal values. Thus, here also severe deficiency is more with females.

Sex

Implication of s.cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

Male - 16 (53.3) 13 (50.0)

Female 4 (100.0) 14 (46.7) 13 (50.0) Total 4 (100.0) 30 (100.0) 26 (100.0) p value 0.131 - Not Significant

0 10 20 30 40 50 60 70 80 90 100

Severe Deficiency Deficiency Normal 53.3 50 100 46.7 50 (in pe rc entag e)

Gender Vs Implication (Among Controls)

Male

(73)

73

CORRELATION OF S.CHOLECALCIFEROL WITH UV EXPOSURE IN

CASES: Among those exposed to UV rays, there are 6 cases with severe deficiency, 15 cases with deficiency and 21 with normal values. In comparison, in those who are not exposed to UV rays, there are 25 had severe deficiency, 52 had deficiency and only 1 had normal value thus suggesting significant correlation with UV exposure either due to phototherapy or due to natural sunlight exposure.

UV Exposure

Implication of s. cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

Exposed to UV

rays 6 (19.4) 15 (22.4) 21 (95.5)

Not Exposed to

UV rays 25 (80.6) 52 (77.6) 1 (4.5) Total 31 (100.0) 67 (100.0) 22 (100.0) p value <0.001 – Significant

0 10 20 30 40 50 60 70 80 90 100 Severe Deficiency Deficiency Normal 19.4 22.4 95.5 80.6 77.6 4.5 (in pe rc entag e)

Implication with UV exposure (Among Cases)

Exposed to Sunlight

(74)

74

CORRELATION OF S.CHOLECALCIFEROL WITH UV EXPOSURE IN

CONTROLS: Among the controls of those who were exposed to UV rays, none had

severe deficiency, 2 had deficiency and 7 had normal values. In those controls who were not exposed to UV rays, 4 had severe deficiency, 28 had deficiency and 19 had normal values. Though those who show deficiency and severe deficiency of cholecalciferol levels are more in non UV rays exposed group, the association is not significant (P value-0.073)

UV Exposure

Implication of s.cholecalciferol Severe Deficiency n (%) Deficiency n (%) Normal n (%)

Exposed to UV

rays - 2 (6.7) 7 (26.9)

Not Exposed to

UV rays 4 (100.0) 28 (93.3) 19 (73.1) Total 4 (100.0) 30 (100.0) 26 (100.0) p value 0.073 - Not Significant

0 10 20 30 40 50 60 70 80 90 100 Severe Deficiency Deficiency Normal 6.7 26.9 100 93.3 73.1 (in pe rc entag e)

Implication with uv exposure (Among Controls)

(75)

75

Figure

Updating...

References

Updating...