HISTOMORPHOLOGICAL STUDY OF PLANUS AND LICHENOID DRUG ERUPTIONS

Transcription

1 HISTOMORPHOLOGICAL STUDY OF LICHEN PLANUS AND LICHENOID DRUG ERUPTIONS Dissertation submitted in partial fulfillment of the requirements for the degree of M.D. (PATHOLOGY) Branch III APRIL Submitted to THE TAMILNADU DR.M.G.R.MEDICAL UNIVERSITY CHENNAI TAMILNADU

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5 ACKNOWLEDGEMENT I would like to express my gratitude to the Almighty who gave me the opportunity to take up and successfully complete this study. It s my privilege to have worked under the supervision of my respected Professor and Head, Dr.Elizabeth Chacko MD., Department of Pathology for the intense confidence, constant encouragement and valuable support for achieving my goal. I will be forever indebted to her for her understanding and guidance at every part of my postgraduate course. I am deeply grateful to my respected guide and mentor Dr.Sivasankaran.M,MD., Professor, for his valuable advice, constructive criticism and his readiness to help and guide and under whose supervision this dissertation work has been accomplished. Words will not suffice to thank Dr.Padmaprasad.M.K,MD, Professor, Department of Dermatology for his support and help he has given me throughout my study. I would like to express my heartfelt thanks to Dr.Jayasree Geothe, Dr.Santha Sadasivan, Professors for their kind encouragement and support during this dissertation work.

6 My deepest gratitude and respect to my beloved Chairman, Dr.C.K.Velayuthan Nair MS, and Director, Dr.Rema.V Nair MD, for providing the opportunity to pursue my post-graduate study in this institution and for the inspirative support. I would like to express my heartfelt thanks to Assistant professors of Pathology, Dr.Prathap Mohan, Dr.Evelyn Angel, Dr.Bindhuja and Dr.Donna for their support during the course of this study. I thank my colleagues Dr.Jem.K.Raj, Dr.Aswathy Jayachandran, Dr.C.Selin Sofiah, Dr.sreedevi and Dr.Megha for their untiring support and help in the preparation of my thesis work and their company has made these years brighter and cheerful. I wish to thank our lab technicians Mrs.Kunjumol, Mr.Prabhu, Mrs.Jemi, Miss.Nisha and our office staff Mrs.Vanajambika, Mrs.Sudha, Mrs.Glory for their help and cooperation in my study. I am as much thankful to those kind patients who formed the material for my work and who despite their pain and discomfort never extended to me anything but the best co-operation. Finally I wish to thank my Husband, Dr.Ganesh, M.T MS ORTHO, my dear Parents and Parents-in law for their kind and invaluable help, faith in me, and support in enabling my study to come to fruition. It would have been out of my reach to perform this task without their support.

7 TABLE OF CONTENTS Sl. No Contents Page No 1 INTRODUCTION 1 2 AIMS AND OBJECTIVES 3 3 REVIEW OF LITERATURE 4 4 MATERIALS AND METHODS 44 5 OBSERVATION AND RESULTS 51 6 DISCUSSION 72 7 SUMMARY 83 8 CONCLUSION 89 9 BIBLIOGRAPHY ANNEXURES ANNEXURE I PROFORMA ANNEXURE II MASTERCHART 11 ABBREVIATIONS

8 Introduction

9 INTRODUCTION Lichen planus is an idiopathic, chronic inflammatory disease of the skin, mucous membrane and nails. 1 Several hypotheses have been made regarding its aetiology, including genetic, infective, psychogenic and autoimmune factors. 1 The term lichen is of Greek origin meaning to lick. The term is altered to a noun in both Greek and Latin for a symbiotic form of plant life. Lichen planus (LP) was first described by Erasmus Wilson in A worldwide distribution is seen with 0.38% of the lesions prevalent in India. 3 The typical lesion of a classical LP is a polygonal, purple, pruritic, violaceous papule of a few millimeters in diameter with sharp borders, the surface of which has streaky or net-like pattern i.e. Wickham striae. The upper and lower limbs, mainly the flexor aspects of lower legs and volar aspect of the wrists and forearms and also on the trunk and lumbar region 4. The clinical variants comprise Atrophic Lichen planus, Hypertrophic Lichen planus, Annular Lichen planus, Ulcerative lichen planus, Bullous lichen planus, Lichen planus pemphigoides, pigmented lichen planus, Erythrodermic lichen planus, lichen planus inversus,linear lichen planus, Follicular Lichen planus, lichen planus follicularis decalvans and lichen planus actinicus 4.The characteristic histopathological findings of L.P are orthohyperkeratosis of epidermis, circumscribed wedge-shaped hypergranulosis respresenting the 1

10 histopathologic substrate of Wickham striae and sawtooth like acanthosis. Upper dermis shows a band-like infiltrate consisting mainly of lymphocytes. Dermoepidermal junction shows vacuolar degeneration with civatte bodies. 4 Lichenoid drug eruption has clinical similarity to Lichen planus. Erythematous to violaceous papules and plaques develop on the trunk and extremities in association with drug ingestion. Implicated agents most commonly include quinacrine, quinidine and gold but also include nonsteroidal anti-inflammatory drugs, anti-hypertensive medications (especially captopril), penicillamine, chloroquine, etanercept, imatinib, terazosin, infliximab and hepatitis B vaccine. 5 Malignant change of cutaneous Lichen planus occurs in fewer than 1% of cases. Features distinguishing Lichenoid Drug Eruptions (LDE) from Lichen Planus include the presence of focal parakeratosis, agranular layer, civatte bodies in basal and spinous layer, lymphocytic exocytosis on upper layer of epidermis and a deeper inflammatory infiltrate with numerous eosinophils. 6 Skin diseases demonstrated by interface dermatitis is common in our country. 7 Lichen planus constitutes about 1% of the patients in dermatology OPD. 8 Lichenoid Drug Eruption has clinical similarity to Lichen planus 5. As the lichenoid skin eruptions consists of heterogenous groups of diseases, clinical evaluation along with histopathological examination is needed for every case before the treatment is started. 7 2

11 Aims & Objectives

12 AIMS AND OBJECTIVES 1) To study the morphology and histopathology of clinically established cases of Lichen Planus (LP) and Lichenoid Drug Eruption (LDE). 2) To compare the clinical forms and histopathological criteria of different forms of Lichen Planus (LP) and Lichenoid Drug Eruption (LDE). 3

13 Review of Literature

14 REVIEW OF LITERATURE In 1869, Erasmus Wilson described the dermatosis, Lichen planus (LP) as a purple, polygonal, pruritic, papular eruption of the skin that can also involve the mucous membranes and the nails. It has unknown etiology. 2 In 1895, Louis Frederic Wickham described the term Wickham striae (WS) that corresponds to fine white or gray lines or dots seen on the top of papular rashes and oral mucosal lesions of lichen planus also called as Lichen Ruber planus. WS appears bilaterally in tree-like structures or in the form of a lacy pattern in the oral cavity, and are seen with higher frequency on the buccal mucosa, the lateral margins of tongue, gingiva and lips. 9 Darier et al. has proposed that the presence of WS is due to proliferation of the granular cell layer of epidermis. Summerly et al. gave an alternate proposal that appearance of striae is due to focal increase in epidermal activity. A third pathological factor suggested by Ryan for formation of WS is lack of dermal vessels in the area which acts as a contributing factor. Histological confirmation of WS can be done by India ink staining in which the ink is retained on the stratum corneum. 9 Existence of numerous civatte bodies in biopsies is a characteristic finding in skin lesions of patients with various dermatoses, particularly lichen 4

15 planus and discoid lupus erythematosus. These bodies are generated by damaged basal keratinocytes through apoptotic cell death and consist of keratin intermediate filaments, almost invariably covered with immunoglobulins, mainly IgM. CBs have been variously termed cytoid, hyaline, colloid, or keratin bodies. Their formation and transport were initially explained by Sabouraudin (1910). One of the groups in 1970s studied the origin of CBs and proved its derivation from degenerated epidermal keratinocytes. Some investigators have also described that CBs may be derived from melanocytes. 10 CLINICAL VARIANTS OF LICHEN PLANUS ARE BASED UPON 11 Configuration Annular Linear Morphology of Lesions Hypertrophic Atrophic Vesiculobullous Erosive and Ulcerative Follicular Actinic Lichen Planus Pigmentosus Site of Involvement Palms, Soles, Mucous Membrane, Nails, Scalp 5

16 Special Forms Drug Induced (Lichenoid drug eruptions) LP Lupus Erythematosis Overlap Syndrome LP Pemphigoides Keratosis Lichenoides Chronica Lichen Planus and Malignant Transformation Lichenoid Keratosis Lichenoid Dermatosis The terms lichen planus-like and lichenoid are used to describe the phenomenon in which skin eruptions identical to LP have been reported following drug administration. 12 In 1981, Janin Mercier et al reported lymphocytic satellites of injured Keratinocytes in lichenoid drug eruptions (LDE). Lichenoid drug Eruptions (LDE) are rarely seen in children. 13 Haute V.V, Antoine J.L, and Lacha Pelle J.M (1989) concluded that a relevant drug history is obtained when the certain histopathological signs (LDE related criteria) are present in more than 50% of lichenoid drug eruption (LDE). 13 DRUGS IMPLICATED IN LICHENOID DRUG ERUPTION 12 ANTIMICROBIALS Aminosalicylate sodium, Ethambutol, Griseofulvin, Ketoconazole, Streptomycin, Tetracyclines, Trovafloxacin. 6

17 ANTIHYPERTENSIVES Prazosin. Captopril, Enalapril, Labetalol, Propranolol, Doxazosin, Methyldopa, ANTIMALARIALS Chloroquine, Hyrodoxychloroquine, Quinacrine. ANTIDEPRESSANTS, ANTI-ANXIETY DRUGS, ANTI-PSYCHOTICS AND ANTICONVULSANTS Amitriptyline, Carbamazepine, Chlorpromazine, Imipramine, Levomepromazine, Lorazepam, Methopromazine, Phenytoin. DIURETIC AGENTS Hydrochlorothiazide, Furosemide, Spironolactone. HYPOGLYCEMIC AGENTS Chlorpropamide, Tolazamide, Tobutamide METALS Gold salts, Arsenic, Bismuth, Mercury, Palladium. NSAIDS Acetyl salicylic acid, Benoxaprofen, Diflunisal, Fenclofenac, Flurbiprofen, Ibuprofen, Indomethacin, Naproxen, Sulindac. 7

18 MISCELLANEOUS Allopurinol, Amiphenazole, Cinnarizine, Cyanamide, Dapsone, Gemifibrozil, Hydroxyurea, Interferon-α, Iodides, Levamisole, Lithium, Mercapto propionylglycine, Mesalamine, Methycran, Nifedipine, Omeprazole, Penicillamine, Procainamide, Pyrimethamine, Pyrithioxine, Simvastatin, Quinine, Quinidine, Sulfasalazine, Trihexyphenidyl. EPIDEMIOLOGY Lichen planus constitutes about 1% of patients in dermatology OPD. It is widespread all over the world with varying incidence. All races are affected with concentration in the age group between years. 8 Childhood lichen planus is comparatively rare with 2-3% of all lichen planus cases occurring below the 2 nd decade of life. 8 Age of onset in oral lichen planus is usually between 3 rd and 6 th decade of life and is common in Asian population. The prevalence of OLP is 1-2% in general population while its prevalence in Indian population is 2.6%. It is predominantly seen in females. 14 Oral lesions are seen in more than one-third of patients with lichen planus of the skin. Skin diseases develop in 15% of patients with OLP. 15 Women with oral lichen planus have associated expressions in the vaginal areas. 16 8

19 In women, LP may present as desquamative inflammatory vaginitis. Genital involvement is common in men with cutaneous lichen planus. 17 Lichen planus (LP) is very rare in infants. 17 In 2013, Asmita Parihar et al conducted a retrospective study of 145 cases of histologically diagnosed lichen planus samples. Most of the patients of lichen planus, lichen planus pigmentosus and lichen planopilaris were in yrs age group with a slight female preponderance. Mean age of males was a decade lower than that of females in LP and lichen planus pigmentosus 1. In 2014, Mohammad Ebrahimzadeh et al studied 132 patients diagnosed with lichen planus for oral and genital involvement. Mucosal lichen planus including oral and genital lichen planus are more frequent in the tropical areas like southern parts of Iran and India. 19 In a study conducted by Dilip Kachhawa et al in India in 1995, on 375 cases of lichen planus, association with hypertension (2.4%), polymorphic light eruption (2.1%), vitiligo (1.9%) and diabetes mellitus(1.6%) was seen. The incidence was higher during summer. 20 An LP-like eruption can occur with the ingestion of certain medications. The eruption is more eczematous or psoriasiform in appearance with no evidence of Wickham s striae or oral changes of LP. 21 9

20 In 1929, Lichenoid drug eruptions (LDEs) was considered a variant of lichen planus (LP). 23 In 1990, West et al did a study in which mean age of patients with Lichenoid drug eruptions (LDE) was 57 years. In 1993, Halvey S did a study of 17 patients with lichenoid drug eruptions (LDE) and reported 66 years as the mean age for LDE. 24 Ongoing alarm is that malignant transformation in LP has been reported which is <1% in cutaneous LP. 3 Previous investigations have reported that oral lichen planus is a precancerous lesion. Squamous cell carcinoma is seen in % cases of oral lichen planus. The estimated range of malignancy in genital lichen planus is low to 2.4%. 16 AETIOPATHOGENESIS The etiology and pathogenesis of LP is unclear. An autoimmune process in which CD8+ T-lymphocytes attack the basal keratinocytes leading to apoptosis of cells is favoured. Autoimmune process is initiated by various potential triggers, such as viral or bacterial antigens, metal ions, drugs or physical factors. 3 Lichen planus is likely to denote an abnormal delayed hypersensitivity reaction to an undetermined epidermal neoantigen, which could be a blend of an external antigen together with an internal self-antigen

21 A viral etiology is frequently involved when the etiology is unknown but there has been no evidence by microscopic or cultural isolation studies to justify a belief that LP is caused by a virus. 23 The disease is more common in patients with hepatic dysfunction. After the discovery of hepatitis C virus in 1989, and tests for anti HCV antibodies in 1991, an increased prevalence of LP was found with HCV infection. LP also coexists with HBV and chronic active hepatitis. 27 GENETICS There may be a genetic susceptibility to idiopathic LP. Familial incidence is 10.7%. LP has also been reported in monozygotic twins. 3 Lichen planus is strongly associated with HLA-DR1 and HLA-DQ1. 26 Association with HLA-DR1 is seen in non-familial cases. In Italian patients, an increased rate of HLA-DR6 with HCV-associated oral lichen planus is seen 25. An association with HLA DR1 is found in non familial cases 26. A strong link between HLA Bw35 and cutaneous lichen Planus is seen. 11 Lichen planus is also found associated with HLA-3, HLA-5, HLA-B7 and HLA In a study conducted in 1994 on 50 Arab patients with cutaneous lichen planus, HLA typing was done and universal association of the disease with HLA DR1 and HLA-DR10 was observed

22 HLA-A3, A11, A26, A28, B3, B5, B7, B8, DR1, and DRW9 are also found related to Lichen planus. In Chinese patients, HLA-DR9 and Te 22 antigens have been found to be increased. 30 In a study by Hatez M. Saafan F.A. and Sharta L in 1984 comprising of 71 Families of probands with lichen planus, the incidence of LP among relatives of patients was significantly higher than that in general population. 29 ASSOCIATIONS Association with immunodeficiency states, internal malignancy, including thymoma, primary biliary cirrhosis, peptic ulcer, chronic hepatitis C infection, hepatitis B vaccination, herpes virus type 7 replication, simultaneous MMR and diphtheria-tetanus-pertussis-polio vaccinations, stress, vitiligo, pemphigus, porphyria cutanea tarda, radiotherapy, ulcerative colitis, chronic giardiasis, a Becker s nevus, and lichen sclerosus et atrophicus with coexisting morphea have been noted. 26 Lichen planus and alopecia areata may coexist. 27 Lichen planus is associated with aberrant liver function tests and serology. 26 PATHOGENESIS Both CD4+ and CD8+ cells are found in lesions of lichen planus. Progression of disease leads to preferential accumulation of CD8+ cells. Most of the lymphocytes in infiltrates of lichen planus are CD8+ and CD45RO (memory) positive cells and express α-β T-cell receptor (TCR) and γ-δ receptor. Majority of T cells, in the epithelial infiltrates of lichen planus are 12

23 activated CD8+ cytotoxic lymphocytes, leading to development of the lichenoid reaction that is the hallmark of lichen planus. 11 Cell-mediated immune reactions are precipitated by alteration in the antigenicity of epidermal keratinocytes, caused by a virus or drug or allogeneic cell. 28 Keratinocytes express HLA-DR on their surface which may have an inductive role. They also express fetal cytokeratins (CK13 and CK8/18) but their role in triggering T cell response is unknown. 28 CYTOKINES T-cells and keratinocytes express IFN-γ and interleukin-6, lymphocyte function associated antigen-1 (LFA-1) and secrete IFN-γ in vitro. 3 Keratinocytes produce interleukins (IL) IL-Iβ, IL-4, IL-6, granulocyte macrophage colony stimulating factor, and tumour necrosis factor α. These cytokines activate tissue macrophages and peripheral blood mononuclear cells and upregulate expression of specific keratin genes. 11 Interferons have a main role in cytotoxic skin inflammation by expression of chemokines including IP10/exCL10 by epidermal keratinocytes which recruit cytotoxic effector lymphocytes into the inflammatory milieu of LP. Plasmacytoid dendritic cells are the major source of type I IFNs in LP

24 NATURAL KILLER CELLS AND MAST CELLS- Increase in number of mast cells is consistent in OLP. Degranulated mast cells release preformed and newly synthesized cytokines and chemokines. They release chymase (a mast cell protease) that damages the epithelial basement membrane directly or indirectly by activating matrix metalloproteinase-9 secreted by T cells. 33 In a study conducted in 1989, decrease in NK response was noted in LP patients with extensive erosive oral mucosal involvement compared to nonerosive LP. 34 INFECTIONS HCV induces extrahepatic manifestations including lichen planus and porphyria cutanea tarda. LP is related to the pattern of immune dysregulation induced by HCV, the mechanism of which is related to the viral replication in lymphocytes. 35 In a study conducted by Devrajani et al in 2009, it was found that patients with lichen planus are predisposed to obtain helicobacter pylori infection. 17 Lichen planus is reported to be associated with syphilis, herpes simplex virus 2, HIV, amoebiasis, and chronic bladder infections

25 Association of lichen planus with chronic hepatitis C virus (HCV) has also been widely reported. 35 IMMUNOLOGY Biochemical epithelial alterations along with genetic factors associated with MHC profiles render persons susceptible to LP or a spectrum of benign LP-like reactions. 37 AUTOIMMUNE DISEASES LP is found to be associated with several different autoimmune diseases which mainly include Lymphocytic thyroiditis, Alopecia areata, Rheumatoid Arthritis, Idiopathic inflammatory myopathy, Dermatitis herpetiformis, Keratoconjuctivitis sicca, Xerostomia, Morphea, Myasthenia gravis, Pemphigus foliaceus, Pemphigus vulgaris, Pernicious anemia, Systemic sclerosis, Thymoma and Vitiligo etc. 36 ASSOCIATIONS WITH DIABETES MELLITUS AND HYPERTENSION Upto 5.7% of patients with DM may develop OLP. 1.6% to 38.9% of patients with OLP may develop DM. 39 A triad of diabetes mellitus, lichen planus and hypertension were described by Grinspan and termed as Grinspans' Syndrome of Grupper who confirmed these findings. Christensen et al, reported higher arterial blood pressure values in lichen planus patients with diabetes mellitus when compared 15

26 to a general section of adult population. A pathogenesis based on an autoimmune response has been proposed. 40 PSYCHOLOGICAL STRESS planus. 38 High stress and anxiety levels are found to be associated with lichen CLINICAL FEATURES LP is characterized by small, smooth, shiny, flat-topped polygonal papules measuring several millimeters to 1 cm in diameter with a violaceous color. Delicate white lines known as Wickham s striae cross the slightly scaly surface. The lesions are seen most commonly on the flexor aspect of the wrists, forearms, extensor aspect of hands and ankles, lumbar area and the glans penis. 17 Lichen planus presents with pruritic papules. Degree of pruritis is related to the extent of involvement, with more intense pruritis in generalized cases. An exception is hypertrophic Lichen planus, which is localized but extremely pruritic. Erosive oral lichen planus is very painful. In the acute stages of the disease, scratching, injury or trauma may induce an isomorphic (Koebner) response. Lichen planus heals with hyperpigmentation, which is more prominent among patients with darker skin colour. Hypopigmentation uncommonly develops after resolution of lesions

27 As a rarity, LP can develop at intertriginous sites, where it completely loses its classical morphology. 20 Lichen planus has clinical variants which are distinguished from the classical form based on the clinical presentation and dissemination of the lesions. The classical primary lesions of lichen planus may be replaced by patches, hyperkeratoses, ulcerations, or bullous lesions. Histologic findings remain distinctive with few additional features. 3 Clinical variants of lichen planus 25 Annular lichen planus Lichen planus verrucosus Erosive lichen planus Ulcerative lichen planus Bullous lichen planus Lichen planus pemphigoides Pigmented lichen planus Erythrodermic lichen planus Lichen planus inversus Linear lichen planus Follicular lichen planus Lichen planus follicularis decalvans Actinic lichen planus ANNULAR LICHEN PLANUS Annular lichen planus (ALP) is a rare long-recognized clinical variant of lichen planus commonly involving the male genital parts, axilla and groin 17

28 folds. Classic lesions of lichen planus presenting with pruritus are typically absent in ALP. If central atrophy is seen, it is called annular atrophic lichen planus. 41 HYPERTROPHIC LICHEN PLANUS Hypertrophic lichen planus/lichen planus verrucosus/lichen planus hyperkeratosis is mostly seen on the shins. It clinically presents as red or yellow-gray, extremely pruritic papules and plaques that coalesce and possess a papular, verrucous or hyperkeratotic surface. Long term lesions carry an elevated risk of development of squamous cell carcinoma due to carcinogenic cofactors. 25 ATROPHIC LICHEN PLANUS Atrophic lichen planus is a rare variant seen on the legs presenting as round to oval, centrally atrophic depressed, brown or violet papules and plaques. 25 A rare form of atrophic lichen planus is composed of annular lesions. 42 ULCERATIVE LICHEN PLANUS Ulcerative lichen planus is a rare variant presenting with chronic, painful bullae and ulcerations of the feet. This variant is usually associated with lesions of the nail, mucosal surfaces and skin which often aids in establishing the diagnosis. Permanent loss of toe nails and cicatricial alopecia are common

29 BULLOUS LICHEN PLANUS This variant presents with blistering of typical LP lesions. The blisters erupt during an acute flair. The intact bullae contain clear or pale yellow fluid. Sometimes, the blisters are multilocular. 43 LICHEN PLANUS PEMPHIGOIDES Lichen planus pemphigoides is a rare condition characterized by the presence of bullae and lichen planus. It has been reported to be induced by medications such as cinnarizine, Captopril, ramipril, psoralen & Ultraviolet A therapy. 44 Lichen planus pemphigoides is different from bullous lichen planus in which vesicles or bullae develop only in the lichenoid papules, probably as a result of unusually severe basal damage and accompanying dermal edema. 45 Recent studies suggest that although LPP antigen and bullous pemphigoid antigen have similar ultrastructural localization, they have different properties and LPP is a distinct entity. 67 LICHEN PLANUS PIGMENTOSUS Lichen planus pigmentosus follows the lines of Blaschko and present with pigmented macular or papular lesions. 25 A case has been found to be associated with a head and neck cancer

30 ERYTHRODERMIC LICHEN PLANUS Erythrodermic lichen planus is extremely rare. 47 Typical LP lesions, blisters, pruritic papules or erosions appear in a localized fashion. 25 INVERSE LICHEN PLANUS Inverse lichen planus presents with pigmented lesions involving the axillae, inguinal creases, limb flexures and submammary region. 48 LINEAR LICHEN PLANUS Less than 0.2% of lesions are distributed along the lines of Blaschko and are called linear lichen planus. It is more common in children than in adults. 49 Papules of Lichen planus may develop a linear pattern secondary to any trauma(koebnerization) or, as a spontaneous, isolated eruption on the extremities. Rarely, the face may develop linear lichen planus. 11 KOEBNER S PHENOMENON Heinrich Koebner ( ), a well-known dermatologist of the 19th century, first described the Koebner phenomenon. It is the occurrence of isomorphic pathologic lesions in the injured uninvolved skin of patients who have cutaneous diseases. 54 True Koebner s phenomenon occurs in lichen planus and other conditions also

31 FOLLICULAR LICHEN PLANUS The synonyms for follicular lichen planus include lichen planopilaris, lichen planus follicularis, peripilaris and acuminatus. 11 Common sites of occurrence include the scalp, axilla, inguinal creases, sacrum and flexures of the limbs. 25 LPP is one of the main causes of primary cicatrical alopecias. 63 Graham Little-Piccardi-Lassueur syndrome is a type of lichen planopilaris characterized by the triad of patchy cicatrical alopecia of the scalp, noncicatrical alopecia of the axilla and groin, and a follicular spinous papule on the body, scalp, or both. It is common in women of years. 50 It is associated with human leukocyte antigen-dr1 in familial cases of LP. 64 In a study conducted by Kossard et al. frontal fibrosing alopecia is considered as a variant of lichen planopilaris which is mostly seen in postmenopausal women as progressive frontotemporal hair loss. 51 In 2001, Sehgal V.N. and Bajaj P., reported a case of lichen planopilaris in a child. The child had classic lesions of lichen planus on glabrous skin. Skin examination showed presence of discolored acuminate papules dispersed singly or in groups, afflicting hair follicles and causing scarring alopecia of the scalp

32 ACTINIC LICHEN PLANUS Actinic LP, also called lichen planus subtropicus or lichen planus actinicus, is a rare variant that affects sun-exposed areas of the skin. Eruptions occur more during spring and summer, with improvement or remission during the winter months. Sun exposure is a major precipitating factor. Clinically, actinic LP presents in three forms: annular, pigmented, and dyschromic. Annular actinic LP is the most common form characterized by erythematous brownish plaques in an annular configuration with or without atrophy. Pigmented forms present as hypermelanotic patches with a melasmalike appearance. Dyschromic-type actinic LP lesions are the rarest and are characterized by whitish pinhead and coalescent papules. Frequently affected sites include the face, upper chest, extensor surface of distal forearms; and dorsal surface of the hands. Actinic lesions are commonly asymptomatic and may resemble actinic keratosis. Diagnosis is made based on distribution in sunexposed areas in combination with histological findings consistent with those of classic LP. 53 LICHEN PLANUS OF THE NAILS Nail involvement is a common manifestation of disseminated LP, affecting up to 10% of patients with LP involving other sites. It appears during the fifth or sixth decades of life and affects genders equally. Nail LP involves the fingernails more than toenails. Biopsy of involved tissue shows classic histopathological features of LP

33 CLINICAL FINDINGS OF LP IN THE NAILS 25 Thinning of nail plates Longitudinal ridging Pterygium unguis Trachyonychia Onycholysis Onychorrhexis Koilonychias Subungual hyperkeratoses Chromonychia Onychomadesis Dorsal pterygium is one of the characteristic findings and may be present in the classic form. Rarely, localized distal subungual hyperkeratosis with multinucleated cells can arise (onychopapilloma). In the toenails, remarkable thickening may be seen and can be mistaken with yellow nail syndrome. Erosive nail LP may occur with painful erosions and consequent scarring. Another rare variant, idiopathic atrophy of the nails, can cause rapid diffuse nail atrophy and pterygium of the nails and ultimately lead to permanent anonychia. 56 In 2000, Tosti A.et al did a retrospective study of 15 children with nail LP and found that LP of nails in children has three different presentations. The first presentation is like the typical NLP of adults caused by strong lichenoid infiltration of nail matrix. The second presentation is twenty nail dystrophy (trachyonychia). The third variety is idiopathic atrophy of the nails

34 TWENTY-NAIL DYSTROPHY It is characterized by coarseness affecting all the fingernails and toenails due to extreme longitudinal ridging (trachyonychia). This clinical presentation is observed in LP, alopecia areata, psoriasis, eczema, and pemphigus vulgaris. 56 TRUE LEUKONYCHIA A defect in nail matrix giving rise to white discolouration of nail plate has been seen in lichen planopilaris which arises due to disorganization of the keratin fibrils and diffraction of light, hence the white opaque appearance. 58 BLACK CHROMONYCHIA- (MELANONYCHIA) Melanonychia, the black- brown discoloration of nails due to the deposition of melanin is also been seen in lichen planus (inflammatory nail disorders). 58 ESOPHAGEAL LP It is a rare presentation of the disease which is underdiagnosed and underreported with a sexual predilection in women. It is seen concomitant with cutaneous manifestations. The proximal esophagus is affected in 90% of cases. There is a significant delay between the onset of symptoms and detection of esophageal involvement. Thyroid dysfunction is the most common associated disorder

35 In a study, superficial gastritis was significantly more common in LP patients than healthy controls. Hence, it is important to consider upper GI endoscopy in LP patients with complaints of dysphagia, odynophagia, weight loss, or other esophageal symptoms and those with involvement of other mucosal surfaces. 57 OCULAR LP LP maybe accompanied by a decrease in tear production. More than one third of LP patients have blepharitis. Şanli and coworkers noted a lower number of goblet cells in the conjunctival epithelium of LP patients, when compared to controls. Ocular involvement may also cause mild to moderate xerophthalmia and occasionally cicatricial conjunctivitis. 60 In a case series of 9 LP patients with ophthalmological signs, 7 cases had vulvovaginal-gingival syndrome and all patients developed subepithelial fibrosis and lacrimal duct stenosis. 61 Other ophthalmologic signs include eyelid lesions, keratouveitis, keratoconjunctivitis sicca, punctate epithelial erosions, corneal ulceration/ scarring, and dysplastic conjunctival lesions resembling ocular surface squamous neoplasia

36 MUCOSAL LP Lichen planus affects the mucosal surfaces of mouth, vagina, esophagus, conjunctiva, urethra, anus, nose and larynx. 11 Vulvovaginal-gingival syndrome is a suset of mucosal lichen planus presenting with erosions and desquamation of the vulva, vagina and gingiva. 62 LICHEN PLANUS PIGMENTOSUS INVERSUS It is a rare variant of LP which is mildy pruritic, hypersegmented macules and patches involving the skin folds in light-skinned people. Nail, scalp and oral lesions are absent. 65 PALMO-PLANTAR LICHEN PLANUS Palmoplantar LP is a rare limited variant presenting with pruritic, erythematous, scaly plaques with or without hyperkeratosis, located on the internal plantar arch. 66 LICHEN PLANUS- LUPUS ERYTHEMATOSUS OVERLAP SYNDROME The lichen planus/ lupus erythematosus overlap syndrome refers to a heterogeneous group of patients bearing at the same time, skin lesions with clinical, histologic, and / or immunologic features typical of both diseases. 69 In 1977, Romero R.W., Nesbitt L.T. and Reed R.J reported eleven cases with skin disorders in which histomorphological and immunofluorescent findings showed features of both lupus enythematosus (LE) and LP. Long 26

37 duration of Clinical lesions were seen which consisted of furious red to violaceous atrophic patches and plaques on the acral aspects of the extremities. 70 KERATOSIS LICHENOIDES CHRONICA Kaposi named the disease in a patient in 1886 who presented with extensive papules, nodules, and keloid-like streaks on the extremities, lower part of the abdomen and the neck as lichen ruber monoliformis as it resembled lichen planus.in 1895, He renamed the same as lichen ruber acuminatus verrucosus et reticularis. In 1872, The term keratosis lichenoides chronica was introduced by Margolis. 71 There is an extensive, symmetrically distributed eruption predominantly on the dorsal aspects of extremities and trunk consisting of red to violaceous papulonodules covered with thick, adherent scales and arranged in a characteristic linear/reticular pattern. There is associated seborrheic dermatitislike eruption on the face, palmoplantar hyperkeratosis and nail changes with warty hypertrophy of the periungual tissues. 6 LICHEN PLANUS AND MALIGNANT TRANSFORMATION The risk of malignant change is relatively low. Risk factors that increase the chance of developing oral cancer are progressive disease, erosive or atrophic types, and tobacco use

38 In hypertrophic lichen planus of leg, development of squamous cell carcinoma, verrucous carcinoma, or keratoacanthoma is an exceptional occurrence. There is a risk of developing squamous cell carcinoma in long standing lesions of lichen planus located on the mucous membranes or vermilion border. 6 The risk of malignant change occurs when there is epithelial atypia in the lesion. 38 LICHENOID DRUG ERUPTION Lichen planus like or lichenoid eruptions describe a group of cutaneous reactions identical to or similar to lichen planus. Lichenoid drug eruptions have been reported after ingestion, contact or inhalation of certain chemicals. Lichenoid drug eruptions manifests as post-inflammatory hyperpigmentation and alopecia, and do not exhibit classic Wickham striae. 11 Lichenoid drug eruption (LDE) has a different distribution from lichen planus (LP). It spares the flexural aspects of the wrist, genitalia, and mucous membranes. 72 A few clinical features suggestive of oral lichenoid drug eruption (OLE) include unusual sites for oral lichen planus (OLP) such as the unilateral palate erosions

39 Table I: Clinical differences between idiopathic lichen planus (ILP) and Lichenoid drug eruptions (LDE) 11 Clinical features ILP LDE Lesions Small Large and scaly Wickham s striae Present Absent Residual hyperpigmentation Possible Common Predilection Flexural/ extremities Sun exposed areas Alopecia Uncommon Common Mucous membrane Involvement Anhydrosis Very common Uncommon Common Common due to sweat gland atrophy. Resolution of the eruptions (on discontinuation of causative drugs/ avoidance of causative chemicals) occurs in 3 to 4 months. For many inciting drugs, the severity and extent of the eruption influences the rate of clearance 11 HISTOPATHOLOGY Typical papules of lichen planus show: Compact orthokeratosis Wedge shaped hypergranulosis Irregular acanthosis Damage to basal cell layer Band like dermal lymphocytic infiltrate hugging the epidermis This constellation of findings is sufficient to make a histological diagnosis of Lichen Planus rendered in more than 90% of the cases. 6 29

40 HYPERKERATOSIS The cornified layer shows solid orthokeratosis with minimal parakeratotic cells, a finding which can help exclude lichenoid drug eruptions from lichen planus. 6 HYPERGRANULOSIS There is wedge shaped, unevenly thickened granular layer. There is increase in size of granular cells with coarse, abundant keratohyaline granules. Wickham s striae is considered to be the clinical presentation of hypergranulosis. 74 ACANTHOSIS There is irregular epidermal hyperplasia which affects the spinous layer and suprapapillary plates. Keratinocytes of spinous layer appear eosinophillic because of advanced keratinization. Rete-ridges appear elongated and are pointed at their lower ends, hence called saw- toothed rete ridges. The adjacent dermal papillae are dome shaped. 6 BASAL VACUOLAR ALTERATION Cells of the basal layer are not clearly visible in early lesions because the dense dermal infiltrate obscures the dermal epidermal junction with vacuolar alteration and necrosis of these cells. In fully developed lesions the basal layer has the appearance of flattened squamous cells. 6 30

41 BAND LIKE INFLAMMATORY INFILTRATE IN THE DERMIS In active Lichen planus (LP), a band like infiltrate of lymphocytes and rarely histocytes admixed with plasma cells are seen in the dermoepidermal junction (DEJ). 3 In some instances, the dermal lymphocytic infiltrate is seen in juxtaposition to the acrosyringeal basal cell layer, which is a prominent finding in (acrosyringeal lichen planus). 6 APOPTOTIC BODIES Colloid bodies are also calledas cytoid/civatte bodies ranging upto 20µm in diameter with a homogeneous eosinophilic appearance. In lichen planus, the number of civatte bodies are so big and are seen as clusters in the superficial dermis. Their aggregation may result in the perforation of epidermis with subsequent transepidermal elimination. 6 Keratinocytes contain tonofilaments which act as a strait jacket within the cell, and therefore budding and fragmentation are less complete in the skin than other cells in the body undergoing death by apoptosis. 25 Colloid bodies denote injured basal keratinocytes that have endured amyloid degeneration. 78 MAX JOSEPH SPACES Ellis F.A described max joseph spaces in These are small areas of separation between dermis and epidermis. Basal vacuolar degeneration and extracellular fluid accumulation around the individual basal cells is suggestive of mild irritation. These edematous changes are responsible for the ragged 31

42 appearance of lower rete ridges. More advanced accumulation of fluid results in Max Joseph spaces found in the areas of the basal vacuolar degeneration. This separationis believed to precede bullous lichen planus clinically. They may seen in up to 17% of the specimens. 75 MELANIN INCONTINENCE Due to basal cell damage, there is variable melanin pigmentary incontinence due to interposition with melanin transfer from melanocytes to keratinocytes and death of cells in the basal layer. 25 In 1967, Ellis F.A. did a histopathological study of 100 biopsy specimens from clinically accepted cases of lichen planus. He summarized the following histopathological features 75 Stratum corneum does not show parakeratosis Beading of granular layer Atrophic, normal or moderate lyhypertrophic epidermis Some liquefactive degeneration at the basal layer at times which results information of vesicles (Max Joseph spaces) at the dermal- epidermal borders. Characteristic well defined band like infiltrate composed principally of small mononuclear cells (lymphocytes), variable numbers of epitheloid cells, occasionally plasma cells and fibroblasts below the basal layer, slightly extending into the epidermis

43 In 1977, Pinkus H. did a study and summarised the following histopathological features of LP. 76 Epidermal hypertrophy with relatively few large prickle cells. Orthokeratotic dense hyperkeratosis. Multiple granular layers. Liquefaction/hyalinization of basal cells. Short saw tooth rete- ridges. Invasion of lower epidermal strata by round cells. Sub-epidermal cleft formation. Hugging band like sub epidermal infiltrate of lymphocytes and other inflammatory cells. Few epidermal mitosis. Incontinentia pigmenti: loss of melanin out of the epidermis and accumulation in dermal macrophages. 76 In 1986, Rivers J.K., Jackson R and Orizanga M. reported a patient of LP having papules. Beneath the Wickham striae there was a focal hypergranulosis and uneven epidermal hyperplasia. 74 In 2000, Chu C.Y., et al reported xanthomatous change in lichen planus with primary biliary cirrhosis. Skin biopsy from the lichen planus lesion revealed orthokeratosis, saw toothed acanthosis, colloid bodies and a band like foamy histiocytic infiltrate admixed with some lymphocytes in the upper dermis

44 ELECTRON MICROSCOPY On electron microscopy, the basal keratinocytes in lichen planus, their desmosomes and hemidesmosomes, show degenerative changes. The tonofilaments in the basal cells are decreased in early lesions but are increased in later lesions. The dermal infiltrate, extending to the epidermis causes damage to the lamina densa. The dermal infiltrate contains lymphocytes and macrophages. Some lymphocytes have hyperconvoluted nuclei and appear indistinguishable from Sezary cells. Necrotic keratinocytes or colloid bodies are located largely in the papillary dermis. They develop from damaged keratinocytes through filamentous degeneration. This is followed by their discharge into the dermis. Necrotic keratinocytes consist of aggregates of filament bundles, each filament measuring approximately 10 nm in diameter. Use of antikeratin immune sera has resulted in their intense staining. Necrotic keratinocytes often contain cell organelles, such as melanosomes and mitochondria, but rarely contain nuclear material. Fibrin deposits in the upper dermis are a common finding in election microscopy studies. 6 IMMUNOFLUORESCENCE In lichen planus, fibrinogen deposition is demonstrated by direct immunofluorescence as shaggy deposits at the dermal-epidermal junction. Occasionally there are granular deposits of IgM or linear deposits of C3 in the basement membrane zone. Necrotic keratinocytes are demonstrable in lichen 34

45 planus by direct immunoflorescence staining in about 87% of the cases. They stain mainly for IgM but also for IgG, IgA, C3 and fibrin. In lichen planopilaris, direct immunofluorescence show deposition of IgM and/or IgA, IgG, and rarely C3 at the level of infundibulum and isthmus. There is deposition of fibrinogen in a shaggy pattern surrounding the affected follicles. The dermis at epidermal junction is virtually always negative for deposition of immunoreactants. In lichen planus pemphigoides, direct immunofluorescence of perilesional skin shows the presence of IgG and C3 in a linear arrangement along the basement membrane zone. In the Overlap syndrome lichen planus/ Lupus erythematosus, some patients show immunofluorescence testing consistent with lichen planus; yet another group demonstrates deposition of immunoglobulins and C3 at the dermal- epidermal junction in linear granular pattern as in cutaneous Lupus erythematosus. 6 IMMUNOHISTOCHEMISTRY The infiltrating cells in lichen planus are predominantly T lymphocytes and a few B-lymphocytes. In older lesionsof oral lichen planus, the suppressor T lymphocytes predominate. Immunophenotyping studies on T lymphocytes extracted from specimens of lichen planus have shown that majority of clones were CD8+T lymphocytes, displayed suppressor activity, and expressed αβtcell receptor or a distinctive γδt-cell receptor. Clonal expansion of α2β3t 35

46 cell receptor of V-gene family has been reported. Recent studies have shown that lesional type I interferons produced by plasmacytoid dendritic cells play an important role in chronic inflammation of lichen planus. 6 HISTOCHEMICAL STUDIES In 1972, enzyme histochemical studies on 18 cases of lichen planus was done by Black M.M. and Wilson Jones E. Common finding was a apparent depression of respiratory enzyme activity in the epidermis. 79 HISTOPATHOLOGY OF VARIANTS OF LICHEN PLANUS ATROPHIC LICHEN PLANUS The epidermis is thinned out with loss of normal rete -ridge pattern and less dense dermal infiltrate. 25 HYPERTROPHIC LICHEN PLANUS The epidermis shows prominent hyperplasia and overlying orthokeratosis. Vertically oriented collagen is present in the superficial dermis in association with the changes of lichen simplex chronicus. Basal cell damage is limited to the tips of rete-ridges. The infiltrate is not as dense as in the classical lichen planus. Xanthoma cells have been found in dermis, localized to a plaque of hypertrophic lichen planus, in a patient with secondary hyperlipidemia

47 LICHEN PLANUS PEMPHIGOIDES A typical lesion of lichen planus pemphigoides consists of a subepidermal bulla which is cell poor, with only a mild, perivascular infiltrate of lymphocytes, neutrophils and eosinophils. The presence of neutrophils and eosinophils has not been mentioned in all reports. Sometimes a lichenoid infiltrate is present at the margins of the blister with occasional degenerated kerationocytes in the epidermis overlying the blister. Lesions which arise in papules show predominant features of lichen planus, a few eosinophils and neutrophils are usually present, in contrast to bullous lichen planus in which they are absent. On Electron microscopy in lichen planus pemphigoides the split occurs in the lamina lucida as it does in bullous pemphigoides. 25 In 1989, Lotem M., et al reported a case of a patient suffering from a rare variant of lichen planus pemphigoides, having the histopathologic features of both lichen planus and pemphigus vulgaris confirmed by immunofluorescence. 80 BULLOUS LICHEN PLANUS Histologically, the typical changes of lichen planus are seen in conjunction with sub- epidermal separation. 25 LICHEN PLANOPILARIS Most early lesions of lichen planopilaris show a focally dense, band like perifollicular lymphocytic infiltrate at the level of the infundibulum and 37

48 the isthmus where the hair bulge is located. Initially, the inferior segment of hair follicle is spared. Vacuolar changes of the basal layer of the outer root sheath and necrotic keratinocytes are often seen. In addition, orthokeratosis, follicular plugging and wedge- shaped hypergranulosis of the infundibulum are observed. In more developed lesions, perifollicular fibrosis and epithelial atrophy are seen which give rise to an hour glass configuration. Damage to the hair bulge, where the stem cells of the hair follicle reside results in permanent scarring. This end stage scarring alopecia with no visible hair follicles is called pseudopelade of Brocq. 6 In 2001, Sehgal V.N., Bajaj P. reported a case of lichen planopilaris in a child. H & E sections prepared from classical lichen planus (LP) lesions over the trunk and lichen planopilaris (LPP) of the scalp were concurrently studied. Classical features of lichen planus along with atrophy of epidermis and vacuolization of basal cells is seen. Dilated hair follicles with plugging is seen. Pigment laden macrophages and lymphohistiocytic infiltrate was prominent. Erector piloris and sweat glands were preserved. 52 ULCERATIVE LICHEN PLANUS Epidermal ulceration with more typical changes of lichen planus at the margins of the ulcer are seen. Plasma cells are invariably present in cases involving mucosal surfaces

49 LICHEN PLANUS ACTINICUS The histologic picture of lichen planus actinicus is similar to that of the typical lichen planus but with a tendency towards thinning of the epidermis at the center of the lesion and more evident pigmentary incontinence in the upper dermis. The inflammatory cell infiltrate in lichen planus actinicus is not always as heavy as it is in typical lesions of lichen planus. 6 In 1988, Salman S.M., Kibbi A.G and Zaynouna S. reviewed the histopathological features of lichen planus actinicus in 16 patients, the lesions of whom consisted of regular lichen planus features, parakeratosis, follicular intercellular edema, papillary and mid-dermal perivascular inflammation. 81 LICHEN PLANUS PIGMENTOSUS Histologically, thinned out epidermis, vacuolar basal cell alteration with a scanty lymphohistocytic lichenoid infiltrate, and melanin incontinence are seen. 11 LICHEN PLANUS-LUPUS ERYTHEMATOSUS OVERLAP SYNDROME Histological features of classical lichen planus and lupus erythematosus are present in the same biopsy. By direct immunofluorescence, the most common findings is the presence of colloid bodies staining with IgG, IgM and C3 intraepidermally or at dermal-epidermal junction, as seen in classic lichen planus. Linear to granular deposition of IgM and C3 (as seen inlupus 39

50 erythematosus, but not in lichen planus) has been observed occasionally. Shaggy deposition of fibrinogen at the basement membrane zone, typical of lichen planus, is sometimes found. 11 ORAL LICHEN PLANUS Light microscopic feature of oral lichen planus consist of Hyperorthokeratosis Parakeratosis Liquefactive basal degeneration A sub-epithelial band of chronic inflammatory cells, consisting predominantly of lymphocytes. The saw tooth rete ridges frequently seen in skin biopsies of lichen planus, are rarely seen in samples of oral lesions. 82 Erosive and atrophic oral forms may show thin epithelium and very little hyperkeratosis, basal cell degeneration or civatte bodies. Plaque form shows some acanthosis, hyperkeratosis, and often no basal cell degeneration

51 LICHENOID DRUG ERUPTION TABLE II: COMPARISON OF HISTOPATHOLOGICAL FINDINGS OF ILP AND LDE Microscopy ILP LDE 1) Cytoids in granular layer Very common 2) Parakeratosis Not seen Common 3) Plasma cell in infiltrates Occasional Abundant 4) Lymphocytic infiltration Dense band like Common (situated higher in granular & cornified Less dense (deeper perivascular) 5) Eosinophils in infiltrates Uncommon Abundant 6) Hypogranulosis Uncommon Common 7) Lymphoid Epidermotropism Uncommon 8) Atrophy of epidermis Uncommon Common. Exocytosis of lymphoid cells in the upper into epidermis In 1977, Pinkus H, Reported that lichenoid drug eruption seems to exemplify a reaction to secondary basal change on the basis of dermal inflammation. They have some parakeratosis and a more spotty affection of the basal layer. 77 In 1985, Miyagowa S. et al reported a case lichen planus pemphigoides like eruption induced by cinnarizine. Biopsy showed the classical features of LP. A biopsy from bullous lesion on normal skin showed sub-epidermal blister containing many eosinophils and fibrin

52 In 1989, Haute V.V., Antonie J.L and Lachapelle J.M, studied histopathological features of idiopathic lichen planus (ILP) in 15 patients and compared them with histopathological features in 15 clinically relevant cases of lichenoid drug eruption (LDE). A statistical analysis of the results showed that no totally discriminant criteria existed between LP and ILP. However, it was confirmed that some histopathological lesions were sometimes present in LDE, whereas they never occurred in ILP. On the other hand, all the histopathological lesions encountered in ILP can also be present in LDE. 13 In 1990, West A.J, Berger T.G. and Leboit P.E in a comparative histopathological study of photodistributed and non photodistributed LDEs, concluded that photodistributed lichenoid eruptions were indistinguishable from those of ILP while non photodistributed differed from ILP, in that they can involve the deep and the superficial plexus with eosinophilsand parakeratosis. 85 In 1993, Halevy S. and Shai A reported that no significant difference in immunostaining patterns were found between LDE and idiopathic LP which suggests that common mechanisms are involved. 86 In 2000, Goldman B.D. reported a case of LDE due to sildenafil and concluded that classic findings indicative of LDE s include eosinophils in the inflammatory infiltrate, focal parakeratosis, and an infiltrate around the deep vessels

53 Deposits of fibrinogen and IgM along the epidermal basement membrane zone, IgG, Clq and C3 in the civatte bodies are found in drug induced lichen planus like lesions

54 Materials & Methods

55 MATERIALS AND METHODS a) Study design : Descriptive Study. b) Study setting (Exact place where the study is conducted): Department of Dermatology&Department of Pathology, SMIMS, Kulasekharam. c) Approximate total duration of the study : One year d) No of groups to be studied : One group e) Detailed description of the groups:males and females of any age group attending the Dermatology OPD of SMIMS Kulasekharam, during the period of June 2015 to May 2016,considering with inclusion and exclusion criteria. f) Sample Size : 72 g) Total sample size of the study : 72 h) Scientific basis of sample size used in the study: Sample size was calculated according to the prevalence of Lichen planus(79 cases out of %) and Lichenoid Drug eruption(10 cases out of 125-8%) of totally 71.2% as reported in a study done by Hegde VK et al in Kerala. (7) Sample size was calculated using the formula N = 4pq/d 2 P = prevalence ie, P = 71.2% 44

56 q = 100-p = = 28.8 d = allowable error (5-20%p) With Relative precision d=15% of p so d=10.68 N = 4 x 71.2 x 28.8/ = = Required sample size rounded to = 72 Estimated sample size for this study = 72 i)sampling Technique: convenient sampling j) Inclusion Criteria : Males and females of any age group. Males and Females attending to Dermatology out-patient department with any of the below conditions: Purplish coloured raised or flat topped lesions, anywhere in the body (most commonly on the wrist,inner forearm and ankle) Lesions that develop and spread over the course of two weeks to a few months. Flat-topped, purple, pruritic, erythematous or violaceous papules and plaques on the trunk and extremities with a significant drug history. Itching at the region of rash. Rashes showing Koebner s phenomenon. k) Exclusion Criteria : Those who are not willing to participate. Patients who are already on treatment for lichen planus. 45

57 l) Whether placebo used in study : No m) whether drugs/medical devices used in the study : No n) if drugs/medical devices used : No o) if research proposal is a clinical trial : No p) Parameters to be studied : Gross morphology of cutaneous lesions of patients presenting to the skin OPD. Formalin fixed Skin biopsy specimens, processed by routine paraffinsection technique and stained with Hematoxylin and eosin. Microscopic features of Dermal and Epidermal changes (hyper orthokeratosis, hypergranulosis, acanthosis, atrophy, basal vacuolar alteration, ulceration, and a bandlike dermal lymphocytic infiltrate hugging the epidermis) Microscopic features of Dermal and epidermal changes (focal parakeratosis with absence of granular layer, necrotic keratinocytes in basal and spinous layer, exocytosis of lymphocytes on upper layer of epidermis) Inflammatory infiltrate. q) Method(s)/Technique(s)/Reagent(s) used to measure the quantitative parameters along with their manufacturing source details: Tissue sampling skin biopsy Light microscope (LABOMED VISION 2000) 46

58 r) Procedure in detail :Protocol was submitted to Human Ethical Committee (HEC) for its approval. After getting approval from IHEC, written informed consent was obtained from the patient before enrolling them in the study. Males and females of any age group attending to Dermatology outpatient department with any of the below conditions were included in the study: Purplish coloured raised or flat topped lesions, anywhere in the body (most commonly on the wrist,inner forearm and ankle) Lesions that developed and spread over the course of two weeks to a few months. Flat-topped,erythematous or violaceous papules and plaques on the trunk and extremities with a significant drug history. Itching at the site of rash. Rashes showing Koebner s phenomenon. Clinically suspected cases of Lichen planus and Lichenoid drug eruption were subjected to skin biopsy. Patients clinical data were collected from the medical records. The gross morphology of the lesions were recorded as photographs. Skin biopsy was performed at the Department of Dermatology,SMIMS by the Dermatologist on duty. After getting consent from the patient, the target lesion where biopsy was to be performed was prepared with a cotton swab to assure hygienic conditions. Area was anesthetized with a local anesthetic. 47

59 Using a sterile blade, the epidermis of the skin was pierced and removed from the rest of the skin Once the biopsy was removed, the site of biopsy was fortified with sterile gauze. Tissue bits were processed in LIECA automatic tissue processor paraffin blocks were prepared. Tissue sections (4-6µ) were cut and stained with hematoxylin and eosin stain (H&E) following which microscopic examination was done. Preparation of smears: The skin biopsy specimens were fixed in 10% neutral buffered formalin, and subjected to thorough gross examination. Representative bits taken and processed routinely to obtain multiple 4-6µ thin paraffin sections and stained with Haemotoxylin Eosin (H & E). TECHNIQUE PROCEDURE- Haematoxylin and Eosin stain REAGENTS: 1) HARRIS HAEMATOXYLIN Haematoxylin 5 gm Aluminium potassium sulphate 100gms Absolute Alcohol 50ml Mercuric oxide 2.5gms Distilled water 1000ml Glacial acetic acid ml 48

60 2) 1%ACID ALCOHOL (differentiation) 70% alcohol -99m Concentrated HCL -1ml 3) 2% SODIUM BICARBONATE (Bluing) Sodium bicarbonate -2gms Distilled water -100ml 4) 0.5% Eosin (Stock) Eosin y(water soluble) -5gms Distilled water -50ml Absolute alcohol -950ml Glacial acetic acid -5ml Add eosin powder in distilled water and add absolute alcohol 5)0.5% Eosin (working) Eosin stock -100ml 80% alcohol -400ml Procedure : 1) Xylene 2 changes each 5 minutes. 2) Absolute alcohol followed by graded alcohol (90% & 70%), each for one minute. 3) Rinse in running tap water for 3 minutes. 4) Distilled water 2 dips. 5) Hematoxylin for 5 minutes. 6) Rinse in running tap water for 3 minutes. 49

61 7) 2% sodium bicarbonate for 2 minutes. 8) Rinse in tap water for 2 minutes. 10) Distilled water 2 dips. 11) 0.5% Eosin seconds. 12) Absolute alcohol 3 changes. 13) Xylene 3 changes. 14) Mount with DPX. 50

62 Observation & Results

63 OBSERVATION AND RESULTS My present study includes 72 skin biopsies out of which 65(90.28%) were diagnosed as Lichen planus and the rest 7(9.72%) were diagnosed as Lichenoid Drug Eruptions (LDE) on histopathological examination. 9.72% LP/LDE % Lichen planus (LP) Lichenoid Drug Eruptions (LDE) Further microscopic and clinical analysis of 65 skin biopsies, diagnosed as Lichen Planus (including its variants) and 7 skin biospies, diagnosed as Lichenoid drug eruption is as follows:- 51

64 AGE OF DISTRIBUTION Lichen planus The age of the patients ranged from 12 years to 60 years with 4 patients from the 1 st decade of life (6.15%), 10 patients being in 2 nd decade(15.38%), 18 patients (27.69%) in 3rd decade, 8 patients (12.31%) in 4 th decade, 12 patients (18.46%) in 5th decade and 13 patients (20%) above the 5 th decade. INCIDENCE 80.00% 70.00% 71.43% 60.00% 50.00% 40.00% 30.00% 27.69% 28.57% 20.00% 15.38% 12.31% 18.46% 20% 10.00% 6.15% 0.00% 1 decade 2 decade 3 decade 4 decade 5 decade >50 LP LDE INCIDENCE Lichenoid drug eruption Out of the 7 patients with lichenoid drug eruption, 5 patients (71.43%) belonged to the 4 th decade of life. 2 patients (28.57%) were over 60 years of age. 52

65 SEX INCIDENCE Lichen planus Out of the 65 diagnosed cases of lichen planus, 35 (53.85%) were females and 30(46.15%) were males. SEX INCIDENCE 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% LP LDE Male Female Lichenoid drug eruption 5 patients (71.43%) were males and 2 patients (28.57%) were females. EDUCATIONAL STATUS Lichen planus Of the 65 cases diagnosed as Lichen planus, 19 (29.2%) patients were illiterates and 46 (70.8%) patients were literates. The level of education was 53

66 varying from primary school education to degree course. Among the 46 (70.8%) literate patients, 12(26.1%)patients were educated up to degree level and above. EDUCATIONAL STATUS 80.00% 70.00% 60.00% 50.00% 70.80% 71.43% 40.00% 30.00% 20.00% 10.00% 29.20% 28.57% 0.00% LP LDE literates illiterates Lichenoid drug eruption 5 patients (71.43%) were literates and 2 patient(28.57% %) were illiterates in the group studied. OCCUPATION Lichen planus Patients belonged to a wide range of occupations ranging from being sedentary e.g businessman, shopkeeper and students to those doing heavy 54

67 physical labour e.g labourer, coolie etc.18(27.7%) patients were housewives, 18 (27.7%) patients were businessmen, 12 (18.5%) patients were students and the remaining patients were employed in various jobs- labourers, coolies, shopkeepers, as shown in graph below. OCCUPATION 30.00% 27.70% 27.70% 25.00% 20.00% 18.50% 15.00% 10.00% 5.00% 10.77% 6.15% 9.23% 0.00% sedentary heavy labour businessmann shopkeeper students housewives coolie labourer Lichenoid drug eruption Out of the 7 patients, 2 patients (28.57%) were housewives, 4(57.14%) were coolie workers and 1 patient (14.29%) was a businessmen. 55

68 MARITAL STATUS Lichen planus Out of the 61 adult patients included in the study, 54 patients (88.5%) were married and 7 patients (11.5%) were single. Lichenoid drug eruption All the seven patients were married. DRUG HISTORY Lichen planus Out of the 65 diagnosed patients of Lichen planus, 19 patients (29.23%) were known cases of Hypertension and 16 of these patients (84.21%) were on regular antihypertensive drugs. 23 patients (35.38%) were known patients of Diabetes mellitus and all of them were on drugs. Patients who had both Hypertension & diabetes were 17(26.15%) and all patients were on regular treatment. 2 patients (3.08%) had been diagnosed with Hypothyroidism and were on regular medications. LATENT PERIOD FROM DRUG INGESTION IN LICHENOID DRUG ERUPTION Out of the 7 patients, lichenoid drug eruptions were noted in 3 patients(42.86%) following ingestion of Non-steroidal Anti-inflammatory drugs, 1 patient(14.29%) developed eruptions after ingestion of betablockers(nifedipine), 1 patients(14.29%) developed eruptions after intake of diuretics (furosemide), 1 patient(14.29%) had eruptions following intake of chloroquine, 1 patient(14.29%) developed drug reactions after intake of propranolol. 56

69 Number of Patients Drugs Latent Period % NSAIDs months Nifedipine months Diuretics months Chloroquine 1 3 Months Propranolol Months CLINICAL FEATURES Lichen planus The duration of illness in all diagnosed patients of Lichen planus in study group ranged from 1 month to 6 years. In 14(21.5%) patients duration of symptoms less than 3 months, 28 patients (43.1%) had duration of months, 9 patients (13.9%) had duration of months and 14 patients (21.5%) had the lesions for more than a year. DURATION OF ILLNESS 60.00% 57.14% 50.00% 43.10% 42.86% 40.00% 30.00% 21.50% 21.50% 20.00% 13.90% 10.00% 0.00% <3 months 4-6 months 7-12 months LP 57 LDE >1yr

70 Lichenoid drug eruption The duration of illness varied from 1 month to one year. In 4 patients (57.14%) duration was 1-6 months, 1 patient (14.29%) had duration of 7-9 months and 2 patients (28.57%) had duration of 9-12 months. SYMPTOMS Lichen planus All these patients presented with small flat topped, violaceous, erythematous, papules and plaques on the skin. These lesions developed and spread over a period of few weeks to months. Wickham s striae was appreciated in 26 patients (40%). Koebner phenomenon was observed in 34 patients (52.3%). Patients also presented with pruritus. Pruritis ranged from being mild to severe pruritis. 57(87.7%) patients complained of pruritis. Among these, pruritis was mild in 24 patients (36.9%), moderate in 27 patients (41.6%) and severe in 6 patients (9.2%).Remaining 8(12.3%) patients did not complain of pruritis. 24 patients (36.9%) also complained of irritation of the lesions. 58

71 60% 52.30% 50% 40% 40% 41.60% 36.90% 36.90% 30% 20% 10% 9.20% 0% Wickham s striae Koebner phenomenon Pruritis Irritation Column1 mild moderate severe SYMPTOMS Lichenoid drug eruption All patients presented with erythematous to violaceous papules and plaques, hyperpigmentation. Koebner s phenomenon was seen in all cases. Wickham s striae were not seen. Pruritus of varying severity was noted in all cases. 3(42.86%) patients had mild pruritis, 2(28.57%) patients had moderate pruritis and 2(28.57% %) patients had severe pruritis. MORPHOLOGY LOCATION Lichen planus In all 65 patients, skin lesions were seen. Along with skin lesions, 12 patients (18.5%) had mucous membrane involvement also. 13 patients (20%) had lesions in oral cavity also. 59

72 DISTRIBUTION OF LESIONS Lichen planus Lesions confined to skin and those associated with mucous membrane lesions in these patients were multiple and variably distributed from the scalp to lower extremities. (64.62%) skin lesions were on upper limbs, (89.23%) skin lesions were on lower limbs, (35.38%) skin lesions were on trunk, (4.62%) skin lesions were on face & neck, (6.15%) skin lesions were on scalp, Remaining lesions were generalized. Oral lesions were usually associated with genital lesions but patients did not disclose that complaint. Oral lesions were being treated in the Department of Dental sciences. Distribution of Lesions in Lichen Planus Lesions Number of patients Percentage SCALP FACE AND NECK TRUNK UPPER LIMB LOWER LIMB PALM/SOLE GENERALIZED ORAL CAVITY GENITALIA

73 Lichenoid drug eruption Skin involvement was seen in all 7 cases, with mucous membrane involvement also noted in 2(28.57%) cases. Generalised skin lesions were seen in all patients involving the trunk, face, neck and limbs. MORPHOLOGY OF LESIONS Lichen planus Out of 65 diagnosed patients of Lichen planus, 42(64.62%) had flat topped violaceous, shiny polygonal papules and plaques, varying in size from few millimeters to greater than 1 cm in diameter involving both upper limbs and lower limbs. Hyperpigmented lesions were seen in 7(10.77%) of patients. Ulceration was noted in the lesions of 5(7.69%) patients. Lichenoid drug eruption All seven patients of lichenoid drug eruptions presented with extensive eczematous rashes over the trunks and limbs. Wickham striae was absent. HISTOPATHOLOGY OF 65 CASES OF CUTANEOUS LICHEN PLANUS CHANGES IN EPIDERMIS Epidermis showed hyperkeratosis in 65(100%) biopsies, atrophy in 6(9.23%), hypergranulosis in 60(92.31%) and irregular acanthosis in 58 (89.23%), epidermal hyperplasia was noted in 7(10.77%). Saw-toothing of rete ridges was observed in 48(73.85%), basal cell vacuolar degeneration in 50(76.92%), Max Joseph space in 9(13.85%) biopsies. Civatte bodies were observed in 25(38.46%) biopsies. 61

74 Changes in Epidermis in Lichen Planus Epidermal Changes Number of patients Percentage (%) Hyperkeratosis Atrophy Hypergranulosis Acanthosis LymphoidEpidermotropism - - Saw Toothing of Rete-Ridges Basal cell vacuolar degeneration Max Joseph Spaces Civatte Bodies Changes in the Dermis A band like inflammatory cell infiltrates closely hugging the epidermis was observed in 60(92.31%) biopsies. Melanin incontinence was observed in 33(50.77%) biopsies, perifollicular infiltrate and perivascular infiltrates were seen in 2(3.08%) and 3 (4.62%) biopsies each. Subepidermal clefting is seen in 1(1.54%) biopsy. Dermal Changes in Lichen Planus Dermal Changes Number of patients Percentage (%) Band like infiltration Melanin Incontinence Perifollicular Infiltrate Perivascular lymphocytic infiltrate Subepidermal clefting % 62

75 Composition of inflammatory infiltrate in dermis Inflammatory infiltrate consisted of lymphocytes in 65( (100%) biopsies, Histiocytes were observed in 29(44.62%) of biopsies. Plasmaa cells were seen in 2(3.08%) biopsies. Melanophages were observed in15(23.08%) biopsies. Composition of Inflammatory Infiltrate in Lichen Planus Composition of Inflammatory infiltrates Lymphocytes Histiocytes Plasma Cells Melanophages Variants of Lichen planus Numbers Percentage Out of 65 cases of Lichen planus, 50 (76.92%) casess were Classical/ Idiopathic Lichen Planus (ILP). The other microscopic/clinical variants detected were Actinic LP in 3 (4.62%)cases, Hypertrophic LP in 4 (6.15%) cases, Pigmented LP in 3(4.62%) cases, Follicular LP in 2 (3.08%) cases, Overlap LP in 2 (3.08%) cases and bullous LP in 1 (1.54%) % 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% Idiopathic Lichen Planus(ILP) Actinic LP Hypertrophic LP Follicular LP Overlap LP Bullous LP LP 63

76 AGE VARIATION IN VARIANTS OF LICHEN PLANUS Age in Years ILP Actinic LP Hypertr ophic LP Overla p LP Follicu lar LP LP pigmento sus Bullous LP 1 st Decade 2 nd Decade 3 rd Decade 4 th Decade 4 (8%) 5 (10%) 15 (30%) 6 (12%) (33.33%) 1 (33.33%) 1 (33.33%) 2 (50%) (100%) 2 (66.67%) (100%) > 50 Yrs 20 (40%) - 2(50%) 2 100%) - 1 (33.33%) - Total 50 (100% ) 3 (100%) 4 (100%) 2 (100%) 2 (100%) 3 (100%) 1 (100%) In our present study, more number of cases were of the lichen planus classical type. Similar results have also been obtained in the study conducted by Asmita Parihar et al. 13 SEX DISTRIBUTION IN VARIANTS OF LICHEN PLANUS Sex ILP Actinic LP Hypertroph ic LP Overlap LP Follicular LP LP pigmentosus Bullous LP Male 23 (46%) 3 (100%) - 2 (100%) - 1 (33.33%) 1 (100%) Female 27 (54%) - 4 (100%) - 2 (100%) 2 (66.67%) - Total 50 (100%) 3 (100%) 4 (100%) 2 (100%) 2 (100%) 3 (100%) 1 (100%) 64

77 Pruritus in variants of lichen planus All the patients except 8 patients of Idiopathic lichen planus presented with varying severity of pruritus. HISTOPATHOLOGICAL EXAMINATION OF VARIANTS OF LICHEN PLANUS EPIDERMAL CHANGES In lichen planus classical type, epidermal changes seen were Hyperkeratosis in 50(100%) biopsies, hypergranulosis in 50(100%) biopsies, acanthosis in 42(84%) biopsies, saw-toothing of rete ridges in 39(78%) biopsies, liquefactive degeneration in 41(82%) biopsies, Civatte bodies in 46 biopsies(92%) and Max Joseph space in 29(58%) biopsies. In Actinic Lichen planus, microscopic epidermal features observed were-hyperkeratosis in 3(100%) biopsies, atrophy in 3(100%) biopsies, hypergranulosis in 2(66.67%) biopsies, acanthosis in 1(33.33%) biopsies, liquefaction degeneration in 2(66.67%) cases, colloid bodies in 1(33.33%) biopsy. Microscopic features of hypertrophic lichen planus observed were hyperkeratosis in 4(100%) biopsies, Hypergranulosis in 4(100%) biopsies, acanthosis in 1(25%)biopsy, hyperplasia in 4 (100%) biopsies, saw toothing of rete- ridges in 3(75%) of biopsies. 65

78 Microscopic features seen in lichen planus pigmentosus were - Hyperkeratosis in 3(100%) biopsies, hypergranulosis in 3(100%) biopsies, atrophy in 3(100%), saw-toothing of rete ridges and liquefaction degeneration in 3(100%) biopsies. Microscopic features of overlap LP were- hyperkeratosis in 2(100%) biopsies, hypergranulosis in 2(100%) biopsies, acanthosis in 2(100%) biopsies, saw toothing of rete- ridges in 1(50%) biopsy, basal cell degeneration in 2(100%) biopsies. In follicular lichen planus microscopic features seen were- Hyperkeratosis in 2(100%) biopsies, hypergranulosis in 1(50%) biopsies, hyperplasia in 2(100%) biopsies, follicular plugging in 2(100%) biopsies, saw toothing of rete ridges in 1(50%) biopsy, basal cell degeneration in 2(100%) of biopsies. In bullous lichen planus, epidermal changes were- Hyperkeratosis in 1(100%) case, acanthosis, hypergranulosis, elongated rete ridges in 1(100%) case. 66

79 DERMAL CHANGES- Dermal changes ILP Actinic LP Hypertrophic LP Overlap LP LP pigmentosus Follicular LP Bullous LP Band like Infiltration 50 (100%) 3 (100%) 4 (100%) 2 (100%) 3 (100%) 2 (100%) 1 (100%) Melanin Incontinence 27 (54%) - 2 (50%) 2 (100%) 2 (66.67%) - - Perifollicular Infiltrate Perivascular Infiltrate (100%) 2 (100%) - Subepidermal clefting 1 (100%) INFLAMMATORY INFILTRATES IN VARIANTS OF LICHEN PLANUS Dermal inflammatory infiltrates were composed of lymphocytes in 50 (100%) cases of Idiopathic Lichen Planus (ILP), 3(100%) cases of Actinic Lichen Planus, 2(100%) cases of Overlap Lichen Planus. Histocytes were observed in 11(22%) cases of ILP, 1 (33.33%) case of Actinic Lichen Planus, 2(50%) cases of Hypertrophic Lichen Planus, 2 (50%) cases of Pigmented Lichen Planus. Melanophages were observed in 7 cases (14%) of ILP, 3 cases (100%) of Actinic lichen planus and 3 cases (100%) of Pigmented lichen planus. 67

80 Dermal changes Idiopathic LP Actinic LP Hypertrophic LP Overlap LP LP pigmentosus Follicular LP Bullous LP Lymphocytes 50 (100%) 3 (100%) 4 (100%) 2 (100%) 3 (100%) 2 (100%) 1 (100%) Histiocytes 11 (22%) 1 (33.33%) 2 (50%) 2 (100%) 3 (100%) 1(50%) - Plasma Cells 1 (2%) (50%) - - Eosinophils Melanophages 7 (14%) 3 (100%) 2 (50%) - 3 (100%) - HISTOPATHOLOGY OF LICHENOID DRUG ERUPTIONS Epidermis showed hyperkeratosis in 7(100%) biopsies, parakeratosis in 5(71.43%),atrophy in 4(57.14%) biopsies, hypergranulosis in 4(57.14%) and acanthosis in 3(42.86%) biopsies. Lymphoid epidermotropism was observed in 7(100%) biopsies. Liquefactive degeneration was seen in 4(57.14%) of cases. Saw -toothing of rete ridges was seen in 3(42.86%) and civatte bodies in 5(71.43%) biopsies were seen. 68

81 Epidermal Changes Number of Patients Percentage Hyperkeratosis 7 100% Atrophy % Parakeratosis % Hypergranulosis % Acanthosis % Hyperplasia - - Lymphoid Epidermotropism 7 100% Saw Toothing of the Rete- ridges % Liquefactive Degeneration % Max Joseph Space - - Civatte Bodies % DERMAL CHANGES IN LICHENOID DRUG ERUPTIONS Band-like inflammatory cell infiltration close to the epidermis was noted in all the cases(100%), melanin incontinence was noted in 2(28.57%) cases, perivascular inflammatory infiltrate was noted in 5(71.43%) of cases. The inflammatory infiltrates composed of eosinophils in 6(85.71%) cases, lymphocytes in 4(57.14%) of biopsies, histiocytes, plasma cells and melanophages in 1(14.29%) case each. 69

82 COMPARISON OF CLINICAL PRESENTATION OF LICHEN PLANUS AND LICHENOID DRUG ERUPTIONS Clinical features LP LDE Erythematous papules + + Pruritus + + Photo-distribution _ + Wickham striae + _ Koebner phenomenon + _ Irritation + + COMPARISON OF HISTOPATHOLOGICAL FEATURES OF LICHEN PLANUS AND LICHENOID DRUG ERUPTIONS EPIDERMAL CHANGES Epidermal Changes Lichen Planus Lichenoid Drug Eruption Hyperkeratosis 65(100%) 7(100%) Parakeratosis - 5(71.43%) Atrophy 6(9.23%) 4(57.14%) Hypergranulosis 60 (92.3%) 4(57.14%) Acanthosis 55(84.62%) 3(42.86%) Hyperplasia 7 (10.8%) - Lymphoid Epidermotropism - 7(100%) Saw Toothing of the Rete- Ridges 45 (69.2%) 3 (42.86%) Liquefactive Degeneration 50 (76.9%) 4(57.14%) Max Joseph Space 9 (13.9%) - Civatte Bodies 25 (38.5%) 5(71.43%) 70

83 DERMAL CHANGES Dermal changes Lichen Planus Lichenoid Drug Eruption Band Like Infiltration 65 (100%) 7(100%) Melanin Incontinence 33(50.8%) 2(28.57%) Perifollicular Infiltrate 2 (3.08%) - Perivascular Infiltrate 3(4.62%) 5(71.43%) Subepidermal clefting 1(1.5%) - INFLAMMATORY CELL INFILTRATES IN DERMIS Cells in Infiltrates Lichen Planus Lichenoid Drug Eruptions Lymphocytes 65 (100%) 4(57.14%) Histiocytes 29 (44.6%) 1 (14.29%) Plasma Cells 4 (6.2%) 1 (14.29%) Melanophages 18 (27.7%) 1 (14.29%) Eosinophils - 6(85.71%) 71

84 CLASSICAL LICHEN PLANUS HYPERKERATOSIS SAW TOOTHED RETE RIDGES, BAND LIKE INFILTRATES MELANIN INCONTINENCE

85 MAX JOSEPH SPACES CLASSICAL LICHEN PLANUS IRREGULAR ACANTHOSIS

86 LICHEN PLANUS PIGMENTOSUS ATROPHIC EPIDERMIS

87 HYPERTROPHIC LICHEN PLANUS DENSE HYPERKERATOSIS

88 HYPERTROPHIC LICHEN PLANUS IRREGULAR ACANTHOSIS

89 BULLOUS LICHEN PLANUS SUBEPIDERMAL BULLA FOLLICULAR LICHEN PLANUS PERIFOLLICULAR INFILTRATES

90 LICHENOID DRUG ERUPTION EOSINOPHILIC INFILTRATES AND MELANIN INCONTINENCE

91 LICHENOID DRUG ERUPTIONS PERIVASCULAR INFILTRATES

92 Discussion

93 DISCUSSION My study was conducted to study the histopathological features of Lichen planus and its variants along with Lichenoid drug eruptions and the clinical presentation of the same and to compare the findings in both the lesions. Lichen planus is an idiopathic subacute or chronic inflammatory disease of the skin, mucous membranes and nails. Cutaneous LP has worldwide distribution with incidence varying from 0.22% to 1% depending upon the geographic location. No racial predilection has been observed. 9 The incidence of Lichen planus is concentrated in the age group of years. Childhood lichen planus is rare involving 2-3% of all lichen planus cases occurring below the age of 20 years. 14 In the present study, 4 patients (6.15%) were in the first decade of life, 10 patients being in 2 nd decade(15.38%), 18 patients(27.69%) in 3rd decade, 8 patients (12.31%) in 4 th decade, 12 patients (18.46%) in 5th decade and 13 patients (20%) above the 5 th decade. Similar to our present study, more number of cases were seen in the 3 rd decade in a study conducted by Devrajani et al

94 In our study, 35 (53.85%) were females and 30(46.15%) were males. Similarly a higher proportion of female patients have been seen in studies conducted by Prabhu et al and Jyothi et al. 89,90 In our study, out of the 65 cases of Lichen planus, 19 patients (29.23%) were known cases of hypertension and 23(35.38%) had diabetes mellitus. Similar association with these diseases were also noted in the study conducted by Kachhawa et al in Lichen planus begins as faint erythematous macules ranging from purplish papules ranging over several weeks. Disseminated multiple lesions may develop rapidly over a short time. In generalized Lichen planus, the eruption often spreads within 1 to 4 months from onset. The onset in most cases is insidious and it is some weeks or months before the patients seek advice. In our study, the duration of illness was less than a year in 51 patients (78.46%) which was similar to that seen in the study conducted by Bhattacharya M, Kaur I and Kumar B (2000) and Prabhu S, Pavithran K, Shobhnadevi (2002). 21,89 All our patients presented with small flat topped, violaceous, erythematous, papules, plaques on the skin.wickham s striae was appreciated in 26 patients (40%). 73

95 Lichen planus tends to be quite pruritic, although some patients are completely asymptomatic. The degree of pruritis is generally related to extent of involvement with more intense pruritis in generalized cases. Pruritis ranges from occasional mild irritation to move or less severe itching which interferes with sleep. 11 In our study, 57 patients (87.69%) complained of pruritus and high incidence of pruritus have also been seen in a study conducted by Bhattacharya M, Kaur I and Kumar B (2000). 21 LP can affect any part of the body surface, but most often seen in the volar aspect of the wrists, the lumbar region and around the ankles. Mucous membrane lesions are very common, occurring in 30-70% of cases and may be present without evidence of skin lesion. 3 In our study, all 65 patients presented with skin lesions. 12 patients (18.46%) also had mucous membrane involvement along with the skin lesions. Lichen planus involves the flexural areas of wrists, forearms and legs. The thighs, lower back, trunk and neck may also be affected. The face is usually spared in typical cases. 11 In our study, the most common sites of involvement were lower limbs, upper limbs, trunk, face and neck and scalp. Similar sites of involvement were seen in the study conducted by Kanwar A.J and De.D. 91 Typical papules of Lichen planus show hyperkeratosis, wedge shaped hypergranulosis, irregular acanthosis, vacuolar degeneration of the basal layer, 74

96 and band like dermal lymphocytic infiltrate in close approximation to the epidermis. This constellation of findings is sufficiently diagnostic that in Lichen planus, a histological diagnosis can be rendered in more than 90% of the cases. 6 Epidermis showed hyperkeratosis in 65(100%) biopsies, atrophy in 4(6.15%), hypergranulosis in 60(92.31%) and irregular acanthosis in 58 (89.23%). Saw-toothing of rete ridges was observed in 48(73.25%), basal cell vacuolar degeneration in 50(76.92%), Max Joseph space in 9(13.85%) biopsies. Civatte bodies were observed in 25(38.46%) biopsies. All these findings were similar to that seen in studies conducted by various authors. A band like inflammatory cell infiltrate closely hugging the epidermis was observed in 65(100%) biopsies and the cells were predominantly lymphocytes. The dermal infiltrate in the Lichen planus, is composed entirely of lymphocytes intermingled with a few histiocytes.mast cells are also present whereas eosinophils are absent. Melanophages are seen in the upper dermis, often in considerable number, as a result of basal cell damage with subsequent pigment incontinence. 6 Melanin incontinence was observed in 33(50.77%) biopsies. In 1967, Ellis observed lymphocytes as the dominant infiltrate in all the biopsies (100%) he studied

97 Plasma cells were seen in 2 patients (3.08%). In 1967, the results of study conducted by Ellis is also similar to our study, in which only 3% biopies showed plasma cells. 76 Rarely, plasma cells are prominent in cutaneous lesions. They are present in lesions adjacent to or on mucous membranes. 26 The variants of lichen planus are generally categorized according to the configuration of the lesions, morphologic appearance, histopathological differences, varying clinical symptoms and the site of involvement. IDIOPATHIC/CLASSICAL LICHEN PLANUS Out of the total 65 cases of Lichen planus, Majority of cases were Classical / Idiopathic Lichen Planus (ILP) including 50(76.92%) cases. The other microscopic/clinical variants detected were Hypertrophic LP in 4 (6.15%) cases, Actinic LP in 3 (4.62%)cases, Pigmented LP in 3 (4.62%) cases, Follicular LP in 2 (3.08%) cases, Overlap LP in 2 (3.08%) cases and bullous LP in 1 (1.54%). In 1995, Kachhawa et al did a study on the clinic-aetiological profile of 375 cases of Lichen planus and found a similarly increased number of classical lichen planus. 20 Bhattacharya M. Kaur I and Kumar B in 2000 detected a similar high number of cases of idiopathic lichen planus

98 LICHEN PLANUS ACTINICUS Lichen planus actinicus is a distinct clinical variant of lichen planus with lesions limited to sun-limited areas of the body. Various terms include lichen planus tropicus, lichen planus subtropicus, lichenoid melanodermatitis and summertime actinic lichenoid eruption (SALE). 25 Features that differentiate Lichen planus actinicus from Idiopathic Lichen planus- ILP appears mostly in 3 rd decade of life, seen invariably during spring and summer and eruption involves mainly the exposed skin. Itching is generally absent. 81 In our study, lichen planus actinicus is seen in 3(4.62%). All the patients were males and presented with varying degrees of pruritus. The lesions mainly included sun exposed areas. The histopathological features included hyperkeratosis and thinning of epidermis in 3(100%) biopsies, presence of melanophages (100%) in the dermis. Similar findings have been reported in previous studies also. 81 HYPERTROPHIC LICHEN PLANUS This variant of LP, also known as lichen planus verrucosus or lichen planus hyperkeratosis, is mostly seen in the shins, less often in arms or trunk. After years or decades of existence, the risk of development of squamous cell carcinoma appears elevated, possibly due to carcinogenic cofactors

99 In our study group, 4 patients (6.15%) had Hypertrophic lichen planus. Lesions were confined to the lower limbs in all the cases with moderate grades of pruritus. The microscopic features seen were hyperkeratosis in 4(100%) biopsies, Hypergranulosis in 4(100%) biopsies, acanthosis in 1(25%)biopsy, hyperplasia in 4(100%) biopsies, saw toothing of rete- ridges in 3(75%) of biopsies and band like inflammatory cell infiltration in all the cases. Similar features have been described by various authors. 25,6 FOLLICULAR LICHEN PLANUS Lichen planopilaris (follicular lichen planus) is a clinically heterogenous variant of lichen planus. It is characterized by scarring, erythematous alopecia of the scalp. 25 Our study included 2 cases(3.08%) of follicular lichen planus. Both the patients were in the 3 rd decade of life. Both presented with lesions on the scalp. Microscopic features were acanthosis, with follicular plugging and hyperkeratosis. Perifollicular lymphohistiocytic infiltration was also seen. In the studies conducted by Sehgal and Poblet et al, features seen included inflammatory lymphocytic infiltrate involving the hair follicles, presence of apoptotic cell debris in the external root sheath which was similar to that seen in our study. 52,92 78

100 LUPUS ERYTHEMATOSUS-LICHEN PLANUS OVERLAP SYNDROME It is a heterogeneous entity in which one or more of the clinical, histological, and immunopathological features of both diseases are present. 25 Two cases (3.02%) of overlap LP were diagnosed in which hyperkeratosis, hypergranulosis and acanthosis were seen in 2(100%) biopsies, saw toothing of rete- ridges in 1(50%) biopsy, basal cell degeneration in 2(100%) biopsies. Band like inflammatory cell infiltration and melanin incontinence was also noted. LICHEN PLANUS PIGMENTOSUS The term lichen planus pigmentosus inversus has been used for cases with predominant localization of the disease in inter-triginous areas. LPP has been reported in association with a head and neck cancer and with concurrent acrokeratosis paraneoplastica. Both conditions cleared after treatment of the cancer. 25 In our study, two cases of lichen planus pigmentosus were diagnosed. Both of the cases showed atrophic epidermis, basal cell vacuolar alteration, band like inflammatory cell infiltration and melanin incontinence. Similar features have been described by Pittelkow et al. 11 BULLOUS LICHEN PLANUS Bullous LP and LP pemphigoides were in the past differentiated solely on clinical and histological criteria but can now be differentiated using IMF 79

101 procedures and immunoelectron microscopy. In bullous LP, there is subepidermal bulla formation with typical changes of LP. The eruption is usually of short duration. 3 In our study, one patient had Bullous LP with the typical histomorphological picture already described. LICHENOID DRUG ERUPTION A lichenoid eruption which occurs following ingestion of a wide range of chemical substances and drugs may mimic lichen planus clinically. Discontinuation of the drug usually leads to clearing of the rash over a period of several weeks. 25 eruptions. In our study, 7 cases (9.72%) were diagnosed with lichenoid drug All the patients were over 4 th decade of life and majority were males. The latent period between ingestion of drugs and occurrence of lesion varied between 1 month to 1 year. The latency period for development of a Lichenoid drug eruption by these agents varies from months to a year or more based upon the dosage, host response, previous exposure and concomitant drug administration. 11 The most common epidermal changes in our study were hyperkeratosis, parakeratosis, atrophy, hypergranulosis and acanthosi. Lymphoid epidermotropism was observed in all the biopsies. Liquefactive degeneration, Saw -toothing of rete ridges and civatte bodies were also seen. Dermal 80

102 changes included inflammatory infiltrates composed predominantly of eosinophils with perivascular inflammatory cell infiltration. Presence of eosinophils in the dermal infiltrates has been reported by Powell et al in his study. 93 DIFFERENTIATING FEATURES BETWEEN LP AND LDE Photodistribution of lesions was a common feature of LDE when compared to LP. Wickham striae and koebner s phenomenon were constantly seen in LP than in LDE. Inspite of similar clinical presentation, a relevant drug history prompted a appropriate clinical diagnosis in most of the cases. DIFFERENCES IN EPIDERMAL CHANGES BETWEEN LP AND LDE Parakeratosis and lymphoid epidermotropism were prominent features in Lichenoid Drug Eruptions which were absent in Lichen Planus. Acanthosis, max joseph spaces and saw toothing of rete ridges were classical features of LP. Civatte bodies were more frequently found in lichenoid drug eruptions. DIFFERENCES IN DERMAL CHANGES BETWEEN LP AND LDE Deep perivascular inflammatory cell infiltration was commonly seen in lichenoid drug eruptions. Both lichen planus and lichenoid drug eruptions presented with band like inflammatory cell infiltration. Lymphocytes were the predominant cells seen in lichen planus, in contrast to eosinophils which were seen numerously in lichenoid drug eruptions. 81

103 In 1998, Keough G.C., Richardson T.T and Grabski W.J did a comparative study and postulated that changes in lichenoid drug eruptions were similar to lichen planus with varying degree of dermal infiltration by eosinophils and plasma cells with focal parakeratosis

104 Summary

105 SUMMARY My study was conducted to evaluate the morphological and histopathological features of Lichen Planus and Lichenoid Drug Eruptions at the Department of Pathology, Sree Mookambika Institute of Medical Sciences, over a period of 1 year (from June 2015 to May 2016). In the present study on 72 patients who fulfilled the inclusion criteria, 65 (90.28%) were diagnosed as Lichen planus and the rest 7(9.72%) were diagnosed as Lichenoid DrugEruptions (LDE) on histopathological examination. The minimum age was 12 years and the maximum was 60 years. Lichen planus affected both the sexes, Females ranging a slightly higher number than males. Occupation of patients ranged from coolies, labourers performing heavy physical work to businessmen with a sedentary life style. The duration of illness ranged from 1 month to 6 years with 21.5% having duration of symptoms less than 3 months, 23.1% had a duration of 4-6 months, 13.9% had a duration of 7-12 months and 21.5% had the lesions for more than a year. 83

106 Out of the all the subjects, 29.23% were known cases of Hypertension and 84.21% were on regular antihypertensive drugs % were known patients of Diabetes mellitus and all of them were on drugs % had both hypertension and diabetes mellitus and all patients were on regular treatment. 3.08% were on medications for Hypothyroidism. All patients presented with small flat topped, violaceous, erythematous, papules, plaques on the skin. 87.7% of Patients also presented with pruritus with 36.9% also complaining of irritation. The lesions were limited to skin in all patients and in 18.5% both skin and mucous membrane were involved. Oral lesions were seen in 20% of patients. The lesions were distributed mainly on the extremities involving the lower limbs in 89.23% of patients and upper limbs in 64.62% of patients followed by trunk in 35.38% of the patients. In the epidermis, hyperkeratosis was the most common finding seen in 65(100%) biopsies. Other changes seen were hypergranulosis in 60(92.31%), irregular acanthosis in 58(89.23%), Saw-toothing of rete ridges in 48(73.85%), basal cell vacuolar degeneration in 50(76.92%), atrophy in 6(9.23%), epidermal hyperplasia in 7(10.8%) and Max 84

107 Joseph space in 9(13.9%) biopsies. Civatte bodies were observed in 25(38.5%) biopsies. A band like inflammatory cell infiltrates close to the dermo-epidermal junction was observed in all the cases. Lymphocytes were the predominant cells seen. Melanin incontinence was observed in 33(50.8%) biopsies, perifollicular infiltrate and perivascular infiltrates were seen in 2(3.08%) and 3(4.62%) biopsies each. Subepidermal clefting is seen in 1(1.54%) biopsy. Majority of cases were idiopathic/classical lichen planus involving 50 cases (76.92%). Other variants seen include Actinic LP in 3 (4.62%)cases, Hypertrophic LP in 4 (6.15%) cases, Pigmented LP in 3 (4.62%) cases, Follicular LP in 2 (3.08%) cases, Overlap LP in 2 (3.08%) cases and bullous LP in 1 (1.54%). Actinic lichen planus was diagnosed in 3(4.62%) biopsies. The patients were in the 4 th decade of life, with lesions mostly in sun exposed areas. Histopathological findings included a thinned out epidermis, irregular acanthosis, basal cell degeneration and band like dermal infiltration which consisted predominantly oflymphocytes. 85

108 Hypertrophic lichen planus was diagnosed in 4(6.15%) patients with lesions involving mostly the lower limbs. Microscopic features seen were hypergranulosis, acanthosis, hyperplasia, saw toothing of reteridges, band like lymphocytic infiltration and Melanin incontinence. Follicular lichen planus was diagnosed in 2(3.08%) biopsies in our present study. Both the patients presented with itchy lesions on the scalp. Microscopic findings included Hyperkeratosis, hypergranulosis, follicular plugging, saw toothing of rete ridges, basal cell degeneration, band-like lymphocytic infiltration, perifollicular lymphocytic infiltration and melanin incontinence. Two(3.08%) cases of overlap LP were diagnosed in which microscopic features of hypergranulosis, acanthosis, saw toothing of rete ridges, basal cell degeneration, band like lymphohistiocytic infiltration and melanin incontinence were found. Pigmented lichen planus was seen in 3(4.62%) patients. Microscopic features included hyperkeratosis, hypergranulosis, acanthosis, saw toothing of rete ridges, liquefactive degeneration, band like lymphohistiocytic infiltration. Mild perivascular inflammatory cell infiltration was also seen. Bullous lichen planus was seen in 1(1.54%) patient who presented with lesions involving both upper and lower limbs. Microscopic features 86

109 included hyperkeratosis, acanthosis, hypergranulosis, elongated rete ridges with band like lymphocytic infiltration. Lichenoid drug eruption was diagnosed in 7(9.72%) patients out of which 5 were males and 2 were females. The period between ingestion of drugs and onset of symptoms varied from 1 month to 1 year. Drugs causing Lichenoid drug eruptions were NSAIDs, captopril, furosemide, chloroquine and propranolol. In LDE, the common microscopic features included showed hyperkeratosis in all the cases. Other cases showed parakeratosis, atrophy, hypergranulosis, acanthosis, liquefactive degeneration, sawtoothing of rete ridges and civatte bodies. Lymphoid epidermotropism was observed in all biopsies. The band-like inflammatory infiltration in the upper dermis showed eosinophils in high number of cases. Other cells included lymphocytes, plasma cells, histiocytes and melanophages. Atrophy of epidermis is more prominent in Lichenoid drug eruptions (57.14%) than in Lichen Planus (9.23%). Acanthosis (84.62%) was a more characteristic feature in Lichen planus than in Lichenoid drug eruptions (42.86%). 87

110 Civatte bodies were increased in number in cases of Lichenoid drug eruptions (71.43%) when compared to that seen in Lichen planus (38.5%). Parakeratosis was not seen in any case of lichen planus while 71.43% of lichenoid drug eruptions showed this feature. Saw-toothing of rete ridges were more prominently seen in Lichen planus (69.2%) and it was slightly lower in Lichenoid drug eruptions (32.86%). Lymphoid epidermotropism was only seen in cases of Lichenoid drup eruptions. It was not seen in lichen planus. Band like inflammatory cell infiltration was seen in all cases of lichen planus and Lichenoid drup eruptions. Lymphocyte was the most prominent inflammatory cell in Lichen planus (100%). Eosinophils are increased in number in Lichenoid drug eruptions (85.71%) while it was not seen in any case of lichen planus. 88

111 Conclusion

112 CONCLUSION The present study was conducted to study the dissimilarities in histopathological and morphological patterns of Lichen planus and its variants and Lichenoid drug eruption. It also helps to confirm the diagnosis and differentiate between the two entities. This helps the clinician to give correct therapeutic treatment, that would provide maximum benefit to the patient. The histomorphological study also aids a pathologist to categorize lichen planus lesions into various clinic-pathological subcategories by taking both histomorphological features and clinical presentations into account. These further help for specific therapeutic treatment and prognosis of the lesion. Lichen planus is a common, chronic idiopathic inflammatory dermatosis prevalent in India. Lichen planus is prevalent all over the world with varying incidence. It affects all races and is concentrated in the age group between years. Lichenoid drug eruptions can closely imitate classic lichen planus. A complete patient s history including his recent drug history and clinical examination and histopathological examination will assist in the differentiation between the two lesions. A detailed history of medications taken in the preceding year, along with drugs taken only briefly may help to identify the cause of lesion. 89

113 The results obtained from the study has shown that some morphological features like photodistribution seen more with lichenoid drug eruptions than with lichen planus and absence of wickham striae in lichenoid drug eruptions and histopathological features like eosinophils in inflammatory infiltrate, lymphoid epidermotropism, seen in Lichenoid Drug Eruptions can be used in differentiating between Lichen Planus and Lichenoid Drug Eruptions, however the basic drug etiology has to be taken into account. Use of electron microscopy, Immunofluorescence and Histopathology has added objectivity, specificity, and reproducibility to the diagnosis of Lichen Planus and Lichenoid Drug eruptions. Histopathological study and relationship with clinical presentation remains the simplest, easily accessible, quick, reliable and cost effective diagnostic tool. Various clinicopathological variants of Lichen planus exist. The changes in Histopathology of Lichen planus may be of viral origin or may represent early and abnormal keratinization or degeneration, which needs further investigation. Though associations of LP and neoplasia are uncommon, there are reported cases of malignant change in long standing lichen planus cases and clinicians should be aware of this association, especially in patients with refractory cases of LP. Awareness of Lichenoid drug eruptions and characteristic histopathological features is pivotal to the diagnosis and management of afflicted patients. 90

114 Bibliography

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126 Annexures

127 SREE MOOKAMBIKA INSTITUTE OF MEDICAL SCIENCES KULASEKHARAM Case Record Sheet DEPARTMENT OF PATHOLOGY STUDY TITLE : HISTOMORPHOLOGICAL STUDY OF LICHEN PLANUS AND LICHENOID DRUG ERUPTION PROFORMA NAME : DATE : AGE (in years) : (1-20)---(20-30)---(30-40)---(40-50)--- (>50 YRS) OCCUPATION : SEX : Male/Female MARITAL STATUS : Married/single/divorced DRUG HISTORY : Y/N IF YES, DETAILS OF DRUG HISTORY : MEDICAL/SURGICAL HISTORY : Hypertension Y/N Diabetes Convulsive Disorders Other Chronic conditions. COMPLAINTS Y/N Y/N : History of present illness: Onset of disease: Sudden / Insidious Duration of Illness : Day()/Week()/Months()/years() History of itching: Mild / Moderate / Intense /Asymptomatic

128 Associated Factors : Drug intake/ingestion or contact with Chemicals Emotional stress / Hair loss/tobacco chewing / Pain or burning sensation in the mouth. History of nail deformity : Yes/No Aggravation on exposure to heat/ sunlight or new lesions : Any seasonal variation : Yes/No Constitutional Symptoms : Headache / Chills / Fever / Weakness / Anorexia / Malaise / fatigue / Any other symptoms PAST HISTORY : Any previous treatment/ chronic disease/similar illness/other illness PERSONAL HISTORY : Diet : Vegetarian / Mixed Sleep : Good / Disturbed Appetite : Good/Loss of appetite Bowel and bladder : Normal / Disturbed Habits : Smoking / Tobacco / Betelnut chewing / Alcohol / Drugs Menstrual history: General Physical examination : Build and nourishment : Poor/ Moderate/Well built/ Pallor/ Cyanosis/ Clubbing/ Jaundice/ Pedal edema/ Lymphadenopathy/Pulse/BP/ Conjuctiva/ Sclera Oral cavity : Ulcer /Erosion/ Net like lacy pattern/ Papule/ Plaque

129 Mucosal involvement : Lips/Palate/Buccal mucosa/teeth/gums/tongue Nails : Toenails/Fingernails/Thinning of nail plate/ridging/linear depression/pterygium/anonychia/ Longitudinal Melanoychia/ Hyperpigmentation/ Oncholysis / Subungual hyperkeratosis. Scalp : Hair- Alopecia/ Scarring/ Lesion Genitalia: Lesions /Site Distribution of lesions : Generalized / Localized / Asymmetrical / Extremities / oriented lesions Grouped / Discrete / Linear/ Symmetrical / Flexors / Annular sun exposed area/follicular oriented lesions. CUTANEOUS EXAMINATION: Morphology of the lesion : Papules/ Plaques / Vesicles / Bullae / Erosions / Ulcers / Atrophic / Hypertrophic Primary Lesions : Macules / Papules / Plaques / Vesicles / Papulosquamous / Pustules / Maculopopular Secondary Lesions : Erosions / Ulcers / Atrophy / Scars / Scales / Crust / Excoriation /Induration / lichenification No. of lesions : Few/More/Numerous Size of lesions : Large / Small Colour of lesions : Violaceous/Brown/Hyperpigmented/Black Yellow/ Erythematous Surface : Flat / Elevated /Scarring / Shiny / Wickham's striae Estimation of Depth of Lesions : Epidermal / Dermo-epidermal / Dermal / Subcutaneous / Skin thickness : Thinned / Thickened Tenderness : Present / Absent

130 Systemicexamination: CVS/CNS/RS/P/A Routine Laboratory Investigations : Dermatopathological Examinations: Skin Biopsy: Gross: Size: Surface: Colour: C.S: HISTOPATHOLOGICAL REPORT OF CUTANEOUS L.P AND LDE Epidermis : Hyperkeratosis / Atrophy /Parakeratosis / Hypergranulosis / Acanthosis / Hyperplasia / Lymphoid and LDE epidermotropism / Saw toothing of rete- ridges / Liquefaction degeneration of basal cells / Max Joseph space / Colloid bodies. Dermis : Band like infiltration: Lymphocytes / Histiocytes / Plasma cells / Melanophages / Polymorphs / Giant cells / Eosinophils / Melanin incontinence /. Perifollicular infiltrate / Perivascular lymphocytic infiltrate / Dysplasia of papillary dermis LICHENOID DRUG ERUPTION *Age ofthepatient *Drug *Dosage *Latent period HISTOPATHOLOGICAL DIAGNOSIS DR.R.AJITHA (MD)

131 ABBREVIATIONS LP - LICHEN PLANUS LDE - LICHENOID DRUG ERUPTION ILP - IDIOPATHIC LICHEN PLANUS LTR/IFD - LICHENOID TISSUE REACTION/INTERFACE DERMATITIS OLP - ORAL LICHEN PLANUS TCR - T CELL RECEPTOR HIV - HUMAN IMMUNODEFICIENCY VIRUS NLP - NAIL LICHEN PLANUS IL - INTERLEUKIN ANA - ANTINUCLEAR ANTIBODY HCV - HEPATITIS C VIRUS SES-ANAS - ANTI NUCLEAR ANTIBODIES NUCLEI OF STRATIFIED EPITHELIUM LP/LE - LICHEN PLANUS/LUPUS ERYTHEMATOSUS OVERLAP DEJ - DERMO-EPIDERMAL JUNCTION G-CSF - GRANULOCYTE- COLONY STIMULATING FACTOR IMF - IMMUNOFLUORESCENCE BMZ - BASEMENT MEMBRANE ZONE LPP - LICHEN PLANUS PIGMENTOSUS

132 OPD - OUT PATIENT DEPARTMENT UL - UPPER LIMBS LL - LOWER LIMBS HLA - HUMAN LEUCOCYTE ANTIGEN NSAID - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS TNF - TUMOR NECROSIS FACTOR

133

134