Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka s33

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

SYNOPSIS OF DISSERTATION

"A CLINICOEPIDEMIOLOGICAL SURVEY OF DEGREE COLLEGE STUDENTS IN THE FIELD PRACTICE AREA OF AIMS, B.G.NAGARA FOR PREMATURE CANITIES"

Submitted by DR. BHRAMARAMBA T.S M.B.B.S. POST GRADUATE STUDENT IN DVL (M.D)

DEPARTMENT OF DERMATOLOGY, VENEROLOGY & LEPROSY ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES, B. G. NAGARA - 571448 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA ANNEXURE II PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 NAME OF THE CANDIDATE Dr. BHRAMARAMBA T.S AND ADDRESS P.G IN DVL, (in block letters) ADICHUNCHUNAGIRI INSTITUTE OF MEDICAL SCIENCES, B.G NAGARA, MANDYA DISTRICT -571448 ADICHUNCHANAGIRI INSTITUTE OF 2. NAME OF THE INSTITUTION MEDICAL SCIENCES, B.G.NAGARA.

3. COURSE OF STUDY AND SUBJECT M.D. IN DVL

4. DATE OF ADMISSION TO COURSE 2nd NOVEMBER 2011 "A CLINICOEPIDEMIOLOGICAL 5. TITLE OF THE TOPIC SURVEY OF DEGREE COLLEGE STUDENTS IN THE FIELD PRACTICE AREA OF AIMS, B.G.NAGARA FOR PREMATURE CANITIES" 6. BRIEF RESUME OF INTENDED WORK APPENDIX - I 6.1 NEED FOR THE STUDY APPENDIX - IA 6.2 REVIEW OF LITERATURE APPENDIX - IB 6.3 OBJECTIVES OF THE STUDY APPENDIX - IC 7 MATERIALS AND METHODS APPENDIX - II

7.1 SOURCE OF DATA APPENDIX - IIA

7.2 METHOD OF COLLECTION OF DATA : (INCLUDING SAMPLING APPENDIX - IIB PROCEDURE IF ANY)

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS YES TO BE CONDUCTED ON PATIENTS OR APPENDIX - IIC OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY.

7.4 HAS ETHICAL CLEARENCE BEEN YES OBTAINED FROM YOUR INSTITUTION APPENDIX – IID IN CASE OF 7.3

8. LIST OF REFERENCES APPENDIX – III

9. SIGNATURE OF THE CANDIDATE

2 Graying of hair has been associated with aging 10. REMARKS OF THE GUIDE and premature canities has long been looked as unaesthetic. The reasons for premature canities is hypothetical and there is paucity of literature on its clinicoepidemiological data. Hence this study is taken for better understanding of the condition. NAME AND DESIGNATION 11 (in Block Letters)

11.1 GUIDE Dr. B. D. SATHYANARAYANA MD , DVD PROFESSOR AND HEAD, DEPARTMENT OF DERMATOLOGY, AIMS, B.G. NAGARA-571448

11.2 SIGNATURE OF THE GUIDE

11.3 HEAD OF DEPARTMENT Dr. B. D. SATHYANARAYANA MD , DVD PROFESSOR AND HEAD, DEPARTMENT OF DERMATOLOGY, AIMS, B.G. NAGARA-571448

11.4 SIGNATURE

12 12.1 REMARKS OF THE CHAIRMAN Dr. M.G. SHIVRAMU AND PRINCIPAL MBBS,MD Professor and HOD, Department of Forensic Medicine, A.I.M.S., B.G. Nagara-571448

12.2 SIGNATURE

3 APPENDIX-I

6.0 BRIEF RESUME OF THE INTENDED WORK:

APPENDIX –I A

6.1 NEED FOR THE STUDY:

Premature graying of hair, also called as ‘premature canities’ refers to diffuse loss of hair color, especially of scalp hair, at an age earlier than that generally accepted as physiologic, before the age of 20 years in whites and 30 years in Blacks.1 Usually, beard hair is often the first to gray and scalp hair graying usually commences in the temporal areas, subsequently spreading toward the crown and occiput.2 This occurs due to reduction in the activity of melanocytes in the hair follicles (poor sustenance of melanocyte stem cell).1 Premature graying of hair probably has a genetic basis and occasionally occurs as an isolated autosomal dominant condition.3 Premature graying has been associated with various autoimmune diseases, genodermatoses, hormonal dysfunction and metabolic disorders. But occasionally, premature graying may occur in the apparent absence of any dermatologic or systemic disease.1

Acquired reversible diffuse hypopigmentation results from various nutritional deficiencies like vitaminB12, copper, iron, protein energy malnutrition.4

PATHOPHYSIOLOGY: Follicular melanogenesis is linked to follicular cycling with melanin synthesis occurring only in the anagen phase. This pigmentary unit recycling occurs effectively only upto first 40 hair cycles, which scale upto 40 years of age in an individual. The hairbulb tyrosinase activity gradually peaks at middle age. With progressing age, reduced melanocyte activity occurs, which leads to graying of hair. Premature graying of hair is due to poor sustenance of melanocyte stem cells. Genes for melanocyte stem cell maintenance and differentiation are Pax3 and MITF (microphthalmia-transcription factor).3

4 Light microscopy of gray hair reveals loss of pigment in the matrix of hair, uneveness of the surface of the hair and appearance of air bubbles in rapidly developing canities.5 Electron microscopy showed normal number of melanocytes with incompletely melanized melanosomes in gray hair and reduced or absent melanocytes in white hair.

Since there is paucity of medical literature on clinico-epidemiological aspects of premature graying of hair and to study the effect of malnutrition in rural set up, where anaemia and undernutrition plays a major role in India, we have taken up this study.

APPENDIX –I B

6.2 REVIEW OF LITERATURE

Premature canities is a common condition with very few epidemiological studies.

Following are some related data in world literature.

Choi et al in their study found that key molecules in melanogenesis namely, microphthalmia-associated transcription factor-M (MITF-M), Sox10, Pax3, tyrosine related protein-1 (TRP-1), and tyrosinase, were absent or greatly reduced in the bulbs of white hair compared to black hair. They also observed that melanocyte stem cells (MSCs) or melanocytes express markers for neural crest cells, Sox10, Pax3, and MITF-M. combining both above facts, they hypothesized that hair graying is caused by defective migration of MSCs into the bulb area of hair.6

Diaz de Leon A et al found that asymptomatic persons with mutations in gene coding protein component of telomerase (TERT) had significant association with premature canities.7

Nishimura EK et al have demonstrated that hair graying may be caused by defective self maintenance of melanocyte stem cells rather than differentiated melanocytes. This process

5 was dramatically accelerated with Bcl-2 deficiency, which causes selective apoptosis of melanocytes stem cells.8

Arck et al introduced the concept of “Free radical theory of graying” and have demonstrated that oxidative stress is high in follicular melanocytes and leads to premature aging and apoptosis.9

Wood et al have recently demonstrated for the first time that human white scalp hair shafts accumulate hydrogen peroxide in milimolar concentrations consequent to absence of catalase, MSR (methionine sulfoxide reductase) and functional loss of methionine sulfoxide repair in the entire gray hair follicle. Thus supporting the long held claim of hydrogen peroxide induced oxidative stress.10

Pavithran K studied 37 patients with premature graying of hair and found most of them to be of 10 -15 years of age (59.09%).11

Halder A in his survey of people of Jajjal village, Punjab found 4.7% of study group to have premature canities with male preponderance. There was spontaneous repigmentation of gray hairs after migrating to different place. He also found accelerated aging and increased incidence of cancer and attributed these findings to “derailed genomic integrity following exogenous insult”.12

Fatami Nainei F, Ebrahimi B et al in their study of relationship between serum iron, zinc and copper concentration in premature graying of hair in 66 patients, found mean age of onset of canities to be 15.5 ± 3.2 years with no much difference between males and females.

Among copper, zinc and iron, statistically a low serum copper concentration was found in patients in comparison to controls.13

6 Glasser demonstrated on autopsy that there is no association between systemic diseases like myocardial infarction, congestive heart failure, cancer, stroke etc. and premature graying of hair.14

Morton et al in his study on 1207 subjects, found no association between premature graying of hairs and low bone mineral density, thus refuting earlier studies which had alternate observation.15

Mosley and Gibbs in their clinical trial with 606 patients showed a significant relation between premature graying of hairs and smoking (p<0.0001), which was consistent for all age groups in both sexes.16

Van Neste D has demonstrated that, gray hairs had enlarged and collapsed medulla giving rise to central cavity in the hair shaft.17

APPENDIX –IC

6.2 AIMS AND OBJECTIVES OF STUDY

1. To study the clinico-epidemiological aspects of premature canities

2. To correlate height, weight, body mass index with premature canities

3. To correlate serum hemoglobin with premature canities

7 APPENDIX-II

7.0 MATERIALS AND METHODS

APPENDIX-II A

7.1 SOURCE OF DATA

This study will be conducted in degree colleges coming under the field practice area of

Sri Adichunchanagiri Hospital and Research Centre, B.G. Nagara, in those students, meeting the mentioned inclusion and exclusion criteria.

Study Design : Cross-sectional observational study

Study Period : 18 months

Sample size : 1350

APPENDIX-II B

7.2 METHOD OF COLLECTION OF DATA

INCLUSION CRITERIA

1. All students willing to participate in the study

2. All students less than 30 years of age

EXCLUSION CRITERIA

1. Students not willing for the study

2. Students who are pregnant or lactating mothers

3. Those on any topical or systemic treatments (allopathic, ayurvedic, home remedies,

homeopathic or unani) for any hair concern

4. Students on immunosuppressants

5. Students with immunocompromised status

8 PILOT STUDY

In view of the paucity of literature on clinicepidemiological data, we conducted a Pilot

Study involving three degree colleges. 350 students were randomly screened. All students satisfying the aforementioned inclusion and exclusion criterias were recruited in the study after informed consent. A detailed history was taken as per the prepared questionnaire. An elaborate general examination was done to look for any signs of systemic or genetic or dermatological diseases or disorders. Scalp was examined for any dermatoses, hair pigmentation and hair loss.

Of them, 86 had premature canities. Thus the pilot study revealed a prevalence of 24%. Based on this data, we calculated the sample size for the study using the formula (n) = 4pq/l 2 where n

= sample size, p = prevalence rate of premature graying of hair based on pilot study, q = (100- prevalence rate), l = allowable error (10% of prevalence) .

Step 1: Based on the WHO estimate of premature canities of p is taken up as 24% and q is (100-24) and allowable error 10% of p, the expected sample size is

n =4 p q /l2 n = sample size

q = 100 – 24 = 76

l = 10% of p =2.4

n = 4× 24× 76 2.4 × 2.4

= 1262

Step 2 : To compensate sample attrition, 5% ( 5% of 1262 ) is added to calculated sample size for arriving to final sample size.

Final sample size n = 1262 + 5% of 1262

= 1326

Finally, we have taken 1350 as our total sample size.

9 PROCEDURE OF THE STUDY

All degree college students of BG Nagara, satisfying the aforementioned inclusion and exclusion criterias will be recruited in the study after informed consent from patient. A detailed history will be taken as per the prepared questionnaire. An elaborate general examination will be done to look for any signs of systemic or genetic or dermatological diseases or disorders.

Scalp will be examined for any dermatoses, hair pigmentation and hair loss. Hairs will be examined for pigmentation, texture and any shaft defects. Hair mount of prematurely grayed hairs will be done and findings noted in the prepared proforma. Various clinicoepidemiological aspects of premature graying of hairs will be analyzed using appropriate statistical methods.

APPENDIX-II C

7.3 Does the study require any investigation or intervention to be conducted on the patients or animals, if so please describe briefly

1. Hair mount of prematurely grayed hairs

2. Serum haemoglobin (Hb%)

3. Peripheral smear

10 APPENDIX-IID

PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL

SECTION A "A CLINICOEPIDEMIOLOGICAL SURVEY OF DEGREE COLLEGE STUDENTS IN THE a Title of the study FIELD PRACTICE AREA OF AIMS, B.G.NAGARA FOR PREMATURE CANITIES"

Dr. BHRAMARAMBA T.S Principle investigator P.G IN DVL, b (Name and Designation) ADICHUNCHUNAGIRI INSTITUTE OF MEDICAL SCIENCES, B.G NAGARA, MANDYA DISTRICT -571448

Dr. B. D. SATHYANARAYANA MD , DVD Co-investigator PROFESSOR AND HEAD, c (Name and Designation) DEPARTMENT OF DERMATOLOGY, AIMS, B.G. NAGARA-571448

Name of the Collaborating d NIL Department/Institutions

Whether permission has been obtained from e the heads of the collaborating departments & NA Institution Section – B Summary of the Project APPENDIX – I Section – C Objectives of the study Section – D APPENDIX – II B Methodology FIELD PRACTICE AREA OF AIMS, A Where the proposed study will be undertaken B. G. NAGARA B Duration of the Project 18 MONTHS C Nature of the subjects: Does the study involve adult patients? YES Does the study involve Children? NO Does the study involve normal volunteers? NO Does the study involve Psychiatric patients? NO Does the study involve pregnant women? NO

11 D If the study involves health volunteers I. Will they be institute students? YES II. Will they be institute employees? NO III. Will they be Paid? NO IV. If they are to be paid, how much per NA session?

E Is the study a part of multi central trial? NO

F If yes, who is the coordinator? (Name and Designation) NA

Has the trail been approved by the ethics NA Committee of the other centers?

If the study involves the use of drugs please NA indicate whether.

I. The drug is marketed in India for the NA indication in which it will be used in the study.

II. The drug is marketed in India but not for the indication in which it will be used in the NA study

III. The drug is only used for experimental use in humans. NA

IV. Clearance of the drugs controller of India NA has been obtained for:

 Use of the drug in healthy volunteers  Use of the drug in-patients for a new indication. NA  Phase one and two clinical trials  Experimental use in-patients and healthy volunteers.

12 G How do you propose to obtain the drug to be used in the study? - Gift from a drug company NA - Hospital supplies - Patients will be asked to purchase - Other sources (Explain) H Funding (If any) for the project please state - None - Amount NIL - Source - To whom payable

Does any agency have a vested interest in the I NO out come of the Project?

Will data relating to subjects /controls be stored J YES in a computer? Will the data analysis be done by K - The researcher? YES - The funding agent NO L Will technical / nursing help be required form YES the staff of hospital.

If yes, will it interfere with their duties? NO

Will you recruit other staff for the duration of NO the study?

If Yes give details of I. Designation II. Qualification NA III. Number IV. Duration of Employment

13 M Will informed consent be taken? If yes YES Will it be written informed consent: YES Will it be oral consent? NO Will it be taken from the subject themselves? YES Will it be from the legal guardian? If no, give NA reason:

N Describe design, Methodology and techniques APPENDIX - II

Ethical clearance has been accorded.

Chairman, P.G Training Cum-Research Institute, A.I.M.S., B.G.Nagara. Date:

PS: NA – Not Applicable

14 APPENDIX-III

8. LIST OF REFERENCES

1. Anitha B, Raghunatha S. Disorders of Hair.In: Imamdar C, Sachidananda S, Aparna P,

Raghunatha S. Textbook of paediatric dermatology. India: Jaypee ; 2009. p. 303-304.

2. Arthur P. Bertolino and Irwin M. Freedberg. Disorders of Epidermal appendages and

related disorders. In Fitzpatric TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF.

Textbook of Dermatology in general medicine. 3rd edn. USA: Mc Grow publishers;1987.

p.627-629.

3. Wadhwa SL, Uday Khopkar, KC Nischal. Hair and scalp disorders. In: RG Valia, ARValia,

editors. IADVL Textbook of Dermatology. 3rd edn. India: BHALANI; 2008. p. 929-948.

4. de Berker DAR. Disorders of Hair. In: Burns T, Breathnach S, Neilcox, Christopher

Griffiths. Rook’s Textbook of Dermatology. 7th edn. UK: Blackwell Publishing; 2004. p.

63.1 - 63.120.

5. Behl P N, Aggarwal A, Srivastava G. Diseases of the Hair and scalp.In: Behl PN, Aggarwal

A,Srivastava G. Practice of Dermatology. 10th edn. India: CBS; 2007. p.424-425.

6. Choi YJ, Yoon TJ, Lee YH. Changing expression of the genes related to human hair

graying. Eur J Derm 2008;18:397-399.

7. Diaz de Leon A, Cronkhite JT, Katzenstein AL, Godwin JD, Raghu G, Glazer CS, et al.

Telomere lengths, pulmonary fibrosis and Telomerase (TERT) mutations. PLoS One

2010;5:e10680.

8. Nishimura EK, Granter SR, Fisher DE. Mechanism of hair graying: incomplete

melanocytes stem cell maintenance in the niche. Science 2005;307:720-4.

9. Arck PC, Overall R, Spatz K, Liezman C, Handjiski B, Hard B, et al. Towards a “free

radical theory of graying”: melanocytes apoptosis in the aging human hair follicle is an

indicator of oxidative stress induced tissue damage. FASEB J 2006;20:1567-1569.

15 10. Wood JM, Decker H, Hartmann H, Chanan B, Rokos H, Spencer JD, et al. Senile hair

graying: Hydrogen peroxide-mediated oxidative stress affects human hair color by blunting

methionine sulfoxide repair. FASEB J 2009;23:2065-2075.

11. Pavithran K. Puvasol therapy in premature greying of Hair. Indian J Dermatol Venerol

Leprol 1986;52:74-75.

12. Halder A. Premature graying of hairs, premature aging and predisposition to cancer in

Jajjal, Punjab: a preliminary observation. J Clinical and Diagnostic Research 2007;6:577-

13. Fatemi Naieni F, Ebrahimi B, Vakilian HR, Shahmoradi Z. Serum iron, zinc and copper

concentration in premature graying of hair. Biol Trace Elem Res 2011 Oct 7. [Epub ahead

of print].

14. lasser M. Is early onset of gray hair is a risk factor? Med Hypotheses 1991;36:404-411.

15. Mortan DJ, Kritz-Silverstein-D, Riley DJ, Barrett-connor EL, Wingard DL. Premature

graying, balding and low bone mineral density in older women and men: The Rancho

Bernado study. J Aging Health 2007;19:275-285.

16. Mosley JG, Gibbs ACC. Premature gray hair and hair loss among smokers; a new

opportunity for health education? BMJ 1996;313:1616.

17. Van Neste D. Thickness, medullation and growth rate of female scalp hair are subject to

significant variation according to pigmentation and scalp location during aging. Eur J

Dermatol 2004;14:28-32.

16 PROFORMA Case No…………

Name : Date :

Age : Contact number :

Sex : Male / Female Clinical Image : Yes / No

Name & Address : Degree course & : of the Institute Year

CHIEF COMPLAINTS Onset : Sudden / Insidious Duration of Premature Graying : (canities) Distribution Scalp: Temples / Vertex / Occipital / Frontal / Diffuse : Beard / Moustache / Body Hairs / Eyebrows / Eye lashes / Axillary / Pubic No. of gray hairs : ≤ 20 / 20 – 50 / >50 H/o exacerbating factors Change of place / Change of water (hard / soft; river / : lake / well) / Stress / Disturbed or lack of 6-8hrs sleep Hair Care Practice Frequency of washing hairs Daily / Alternate days / twice weekly / weekly / : Otherwise ______Hair wash done with Plain water / Soap / Shampoo / Soapnut powder / Gram : flour H/o Conditioner use Yes / No. If yes, is it with every wash or otherwise : ______H/o hair care parlor activities Yes / No. If yes, then Head massage / Head wash / Straightening / Curling / : Streaking / Coloring Duration: Frequency: H/o hair care procedures done Hair Ironing / Hair Coloring (Mehendi / Black Mehendi / at home Color) : Duration: Frequency:

Hair Products Used : Hair gel / Hair setting foam / Hair Serum

17 Anaemia / Hypothyroidism / Hyperthyroidism / Polycystic Ovarian Disease / Diabetes mellitus / Medical History : Hypertension / Chronic Renal failure / Hepatitis Please specify if any other: ______Antioxidants / Others, specify Drug history : ______Father / Mother / Brother / Sister Family history of premature : Yes / No, If yes, then, canities Age of onset: ______Diet: Vegetarian / Mixed / Crash diet Personal history : If on crash diet, was Dietician consulted: Yes / No

GENERAL EXAMINATION

Height (in cm): Weight (in Kg):

BMI: Pulse: BP:

Pallor / Icterus / Koilonychia / Cyanosis / Clubbing / Lymphadenopathy / Pedal edema /

Xerosis / Ichthyosis

Seborrhea: Yes / No

Seborrehic dermatitis: Yes / No

If yes,

Scalp / Eyebrows / Eyelashes / External auditory meatus / Retroauricular / Chest / Back / Axilla

/ Groins / Generalized / Erythroderma

Pityriasis versicolor: Yes / No

Pityrosporum folliculitis: Yes / No

SCALP EXAMINATION Scalp: Temples / Vertex / Occipital / Frontal / Diffuse Site of premature : Beard / Moustache / Body Hairs / Eyebrows / Eye lashes / Axillary / graying of hairs Pubic Smooth / Rough Hair quality : Split ends: Yes / No Cosmetic : Straightening / Curling / Streaking / Coloring

18 procedures for hair

INVESTIGATIONS TEST OBSERVED VALUE Hb% : Peripheral smear : Hair mount :

DIAGNOSIS: