RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

PROFORMA FOR REGISTRATION OF SUBJECTS OF DISSERTATION

1. / Name of the Candidate & address / Dr. RAJANIKANTH. S
No.39,Prem Nivas, Dr AMC Road, Kavalbyrasandra,Bangalore-560032
2. / Name of the institution / Dr. B R Ambedkar Medical College
3. / Course of study & Subject / MD PATHOLOGY
4. / Date of admission to course / 19-06-2009
5. / Title of the topic / " A HISTOPATHOLOGICAL STUDY OF LICHENOID DERMATITIS AND ITS RELATION TO GLUCOSE TOLERANCE ”
6. / Brief Resume of the Intended work / 6.1 / Need of the Study / Annexure I
6.2 / Review of Literature / Annexure II
6.3 / Objectives of the study / Annexure III
7. / Materials & Methods / 7.1 / Source of Data / Annexure IV
7.2 / Method of collection / Annexure V
7.3 / Does the study require any investigations or interventions / YES Annexure VI
7.4 / Has Ethical clearances been obtained from your institution? / YES
Annexure VII
8. / List of References / Annexure VIII
9. / Signature of the candidate
10. / Remarks of the Guide / Histopathological study of Lichenoid Dermatitis helps to confirm the type of Lichenoid Dermatitis. Glucose Tolerance study in those patients helps to find out the relationship between Glucose Intolerance and the Lichenoid Dermatitis.
11.1 / Name & Designation of the Guide / Dr. H. T. Jayaprakash,
Associate Professor,
Department of Pathology
11.2 / Signature
11.3 / Co-Guide if any / Dr. Madan Mohan.N.T
Associate Professor,
Department of Dermatology
11.4 / Signature /
11.5 / Head of the Department / Dr. D. S. Vasudeva ,
Professor and Head of the Department,
Department of Pathology
12.1 / Signature
12.2 / Remarks by the Chairman & Principal
12.3 / Signature

6. BRIEF RESUME OF THE INTENDED WORK

Annexure I

6.1 NEED FOR STUDY

Lichenoid Dermatitis, an obstinate skin disorder has baffled not only the patients but also the practitioners equally. The cases of Lichen Planus have been observed all over the world, irrespective of the race, skin color and culture. The medical field today finds little help for this chronic disease.

It is a long standing (chronic), recurring, non-allergic, non-infectious, non-contagious disease of the skin, of which the exact cause is not yet fully understood.

It can affect skin, oral mucosa, tongue, scalp, genitals and nails. However, it is less likely that it affects all the areas as stated, at the same time. It has a tendency to relapse after some months or years. Females are more frequently affected as compared to the male counterpart. It is however, uncommon to find it in children. Over 1.9% of the total population is affected by Lichen Planus.

Sometimes the Lichen Planus eruptions, especially in early states, may resemble some other diseases like atopic dermatitis, psoriasis, candidiasis (in mouth), Leukoplakia (mouth), apthous ulcers (mouth).In case of doubt, or to confirm the diagnosis, a biopsy would help. Biopsy is more often indicated in cases of oral and scalp Lichen Planus. Also, Lichen Planus of nails alone could resemble psoriatic nails and fungus infection of nails.

The spectrum of Lichenoid Dermatitis include Lichen Planus and its variants like Lichen Planus Hypertrophicus, Lichen Planus Actinus, Lichen Nitidus,Lichen Sclerosus et Atrophics, Lichen Planus Linearis, Lichen Planus Annularis, Lichen Planus Follicularis, Lichen Planus Atrophicus, Bullous Lichen Planus, Lichen Planus Pigmentosa. Each of these has specific histologic picture and vary in distribution which needs to be studied.

The need for this study is to identify the histopathological appearance of the spectrum of lichenoid dermatitis and to define a relationship if any between any one of its components and glucose tolerance. Since many studies show that there is impaired glucose tolerance in many patients with lichen planus, the present study will be undertaken to see if there is any such relation with the spectrum of lichenoid lesions.

Annexure II

6.2 REVIEW OF LITERATURE:

This study aims to identify the histopathological picture, distribution pattern of spectrum of lichenoid dermatitis and to define a relationship if any between any one of its components and glucose tolerance. Plenty of literature is available to know the distribution pattern of spectrum of Lichenoid Dermatitis and also the relation between glucose metabolism and the components of spectrum of Lichenoid dermatitis.

A study of clinico-histopathological features of lichen planus in 75 patients was done by Kumar V etal. The male to female ratio was 1:1.3. The largest number of patients (30.6 percent) fell into the 31-40 year age group. There was no history of lichen planus in the family.The most common type seen was classical lichen planus (73.3 percent), followed by lichen planus hypertrophicus (17.3 percent). Lichen planopilaris and oral lichen planus were uncommon.Lower limbs were involved in 38 percent of cases. Mucosal involvement was seen in 24 percent in addition to skin involvement and nail involvement was seen in 9.33 percent.1

A study done by Tag-El -Din Anbar et al on 50 LP (Lichen Planus) patients at al-Minya University Hospital, al-Minya , Egypt over 1-year period has shown the incidence of various types of Lichenoid Dermatitis as follows : actinic LP (36 %), classic LP (30 %), hypertrophic LP (12 %), guttate LP (6 %), atrophic LP (4 %), follicular LP (4 %), and isolated oral LP (8 %). Pruritus was the chief complaint of 50 percent of these patients. In 56 percent of patients, limbs were the initial site of onset. The sex incidence was 44% females and 56% males. 2

Several studies done all over the world has shown that Lichen Planus is an uncommonly encountered dermatosis in children. However in sub-Saharan Africa there is paucity of data on Lichen planus among children. A study was undertaken in South East Nigeria from 1998 to 2001 to document the clinical types of Lichen planus and to highlight any differences and similarities with the adult disease. In all, 13 patients (eight boys and five girls) aged between 3 and 15years were diagnosed with Lichen planus. The limbs were the most common sites of involvement in nine (69.2%) children. Classic Lichen planus was the commonest clinical variant in eight (61.5%), while extensive hypertrophic plaques were observed in three (23.1%), linear lesions in two (15.4%) and eruptive generalized Lichen planus in two (15.4%). Koebner phenomenon was documented in five (38.5%); mucosal involvement, which is very uncommon in children affected by this disease, occurred in three (23.1%). Only one child had pterygium formation in all 20 nails (total nail dystrophy).No child had scalp or palmoplantar involvement.3

The histopathologic features of Lichen Planus include the presence of irregular acanthosis and colloid bodies in the epidermis with destruction of the basal layer. The upper dermis has a bandlike infiltrate of lymphocytes and histiocytes.The epidermis is hyperkeratotic with irregular acanthosis and focal thickening in the granular layer. Degenerative keratinocytes, known as colloid or Civatte bodies, are found in the lower epidermis. In addition to degenerative keratinocytes, colloid bodies are composed of globular deposits of IgM (occasionally immunoglobulin G [IgG] or immunoglobulin A [IgA]) and complement. Linear or shaggy deposits of fibrin and fibrinogen are noted in the basement membrane zone.4

The upper dermis has a bandlike infiltrate of lymphocytic (primarily helper T) and histiocytic cells with many Langerhans cells. The infiltrate is very close to the epidermis and often disrupts the dermal-epidermal junction.5

A study by Eisen D et al showed that the typical clinical features of oral lichen planus are usually sufficient for the diagnosis of the condition but a biopsy for histopathology is recommended to confirm the clinical diagnosis and mainly to exclude epithelial atypia and signs of malignancy.6

K R Jain et al investigated twenty patients with lichen planus and 5 healthy controls were investigated for their glucose tolerance. Using steroid- primed glucose tolerance test, 60% of patients showed abnormal glucose tolerance as compared to none in control. Glucose intolerance was found to be more commonly associated with recent onset of disease but no relationship with the extent of involvement was observed.7

A study of glucose tolerance and insulin response to oral glucose was carried out in 56 consecutive histologically confirmed cases of lichen planus by Nigam P K et al. 30.3% patients showed abnormal glucose tolerance. The pattern of insulin response was similar to that seen in type II diabetes. Insulin/glucose ratio showed the same relationship as seen in type II diabetes. These results reinforce the possibility of glucose intolerance in lichen planus patients. However, no correlation between glucose tolerance abnormalities and duration and distribution of lesions was observed.8

A study was conducted on 52 patients with lichen planus by Halevy S and Feuerman E J. Abnormal oral glucose tolerance was found in 19 (36%), including 5 with overt diabetes. The criteria for abnormality were based on an age-related score method. A family history of diabetes was found to be present in 14 (26%). The most common abnormality observed in the glucose tolerance test was an elevation of the blood glucose level 2 hours after administration of the glucose. These results further support the supposition of a disorder in carbohydrate metabolism associated with lichen planus.9

Glucose tolerance was investigated in twenty-one patients with lichen planus by Sheila M Powell et al. 62% of these patients have shown abnormal results, suggesting impaired tolerance.10

A study of 123 patients with oral lichen planus by E. Christensen et al revealed that two were known diabetics. The remainder were tested for fasting glucosuria, 113 for fasting blood glucose and 103 also with an oral glucose tolerance test. According to WHO criteria, 18 of the 123 patients were diabetics. In most of these patients the oral glucose tolerance test was only slightly abnormal. No decrease of the glucose tolerance with increasing duration of lichen planus was demonstrable.11

A study of 30 patients with LP by M. Sehyan et al showed that eight (26.7%) had Diabetes Mellitus (four newly diagnosed), however, only one (3.33%) was diagnosed as DM in control group (p=0.007). Six patients (20.0%) with LP and four healthy persons (13.3%) had Impaired Glucose Tolerance (p>0.05). Glucose metabolism disturbance (Diabetes Mellitus + Impaired Glucose Tolerance) was detected in 14 (46.7%) of the patients and in 5 (16.7%) of the controls (p=0.026).Their finding documented that approximately one half of the patients with LP had glucose metabolism disturbance, and one fourth had DM.12

Annexure III

6.3 OBJECTIVES OF THE STUDY:

1. To study the histopathological appearance of the spectrum of the lichenoid dermatitis.

2. To study the distribution pattern of spectrum of Lichenoid Dermatitis.

3. To study steroid primed oral glucose tolerance in patients with lichenoid dermatitis and to identify if there is any abnormality, and also to study whether there is any correlation with the onset of the lesions and also with the extent of involvement.

7. MATERIALS AND METHODS:

Annexure IV

7.1 Source of Data:

Inclusion criteria: Patients attending the Dermatology Out Patient Department in Dr.B.R. Ambedkar Medical College, K.G. Halli, Bangalore would be the source of study. The patients who would be clinically diagnosed as having lichen planus or one of its variants would be considered for this study. Details regarding age , sex ,duration of lesion ,onset ,initial site ,pattern of spread ,itching , family history of lesion and of diabetes ,drug intake and other associated illness would be obtained from each patient .Then he/she would be taken for general physical examination and also examined from head to toe for the sites of involvement including the oral cavity and external genetalia. A note would be made on sites of involvement, presence of koebnerization, configuration and morphology of lesion.

Exclusion criteria: Patients with established history of diabetes and patients above 50 years of age would be excluded from the study.

Annexure V

7.2 Method of Collection of data:

After selecting the patient, he/she would be subjected to steroid primed glucose tolerance test .For this the patient is asked to return to the clinic the following day ,instructing him to take 10 mg of tablet Betamethasone on the same night and another tablet the next day at 6 AM and then the glucose tolerance test would be done at 9AM.The patient will be fasting on the day of the test.

The purpose of priming the patient with steroid is to discover any latent diabetes.

Fasting samples of blood and urine are taken and then the patient would be asked to take 1.25 g/kg body weight (maximum of 75g) of glucose dissolved in 300 ml of water. After this blood and urine samples are taken every half hourly for a minimum of four times.

The patient is also subjected to punch biopsy from representative area of the eruption using 4 mm punch. A well developed lesion would be selected, neither too early nor too late in the stage of regression. The skin surface would be cleaned with spirit sponge. Local anesthesia would be obtained by infiltration under the lesion with 2% lignocaine solution with 2 ml / 5ml syringe with number 26 needle. The biopsy would be taken using a 4 mm punch to include the entire thickness of the corium and part of the subcutaneous fat tissue. The punch would be pressed into the skin with a rotary motion. On withdrawal of the instrument, the plug of skin pops out of the wound. It is lifted up gently with forceps without exerting pressure and its base is snipped through with scissors. The specimen is then put in a bottle containing 10 % buffered formalin and labeled. After adequate fixation, the entire skin tissue would be processed routinely and 4 to 5 µ thickness sections would be taken from paraffin blocks, stained with H & E and studied under the microscope.