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Istomorphological Study of Lichen Lanus and Lichenoid Drug Eruptions

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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- 2017 Submitted to THE TAMILNADU DR.M.G.R.MEDICAL UNIVERSITY CHENNAI – TAMILNADU 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. 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. TABLE OF CONTENTS Sl. Contents Page No 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 91 10 ANNEXURES ANNEXURE – I PROFORMA ANNEXURE – II MASTERCHART 11 ABBREVIATIONS Introduction 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 1869. 2 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 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 Aims & Objectives 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 Review of Literature 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 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 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 ANTIHYPERTENSIVES Captopril, Enalapril, Labetalol, Propranolol, Doxazosin, Methyldopa, Prazosin. ANTIMALARIALS Chloroquine, Hyrodoxychloroquine, Quinacrine. ANTIDEPRESSANTS, ANTI-ANXIETY DRUGS,
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