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Mucocutaneous Manifestations in Patients Receiving Cancer

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Mucocutaneous Manifestations in Patients Receiving Cancer MUCOCUTANEOUS MANIFESTATIONS IN PATIENTS RECEIVING CANCER CHEMOTHERAPY IN REGIONAL CANCER CENTRE OF TIRUNELVELI MEDICAL COLLEGE Dissertation Submitted to THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY IN PARTIAL FULFILMENT FOR THE AWARD OF THE DEGREE OF DOCTOR OF MEDICINE IN DERMATOLOGY, VENEREOLOGY & LEPROSY BRANCH XII-A APRIL 2019 DEPARTMENT OF DERMATOLOGY VENEREOLOGY & LEPROSY TIRUNELVELI MEDICAL COLLEGE TIRUNELVELI -11 BONAFIDE CERTIFICATE This is to certify that the dissertation titled as “MUCOCUTANEOUS MANIFESTATIONS IN PATIENTS RECEIVING CANCER CHEMOTHERAPY IN REGIONAL CANCER CENTRE OF TIRUNELVELI MEDICAL COLLEGE” submitted by DR. P. SULOCHANA to the Tamil Nadu Dr. M.G.R Medical University, Chennai, in partial fulfilment of the requirement for the award of the Degree of DOCTOR OF MEDICINE in DERMATOLOGY, VENEREOLOGY & LEPROSY during the academic period 2016-2019 is a bonafide research work carried out by her under direct supervision & guidance. PROFESSOR & HEAD DEAN Department of Dermatology, Venereology & Leprosy Tirunelveli Medical college Tirunelveli Medical college Tirunelveli Tirunelveli. CERTIFICATE This is to certify that the dissertation titled as “MUCOCUTANEOUS MANIFESTATIONS IN PATIENTS RECEIVING CANCER CHEMOTHERAPY IN REGIONAL CANCER CENTRE OF TIRUNELVELI MEDICAL COLLEGE” submitted by DR. P. SULOCHANA is an original work done by her in the Department of Dermatology Venereology & Leprosy, Tirunelveli Medical college, Tirunelveli for the award of the Degree of DOCTOR OF MEDICINE in DERMATOLOGY, VENEREOLOGY & LEPROSY during the academic period 2016-2019. Place: Tirunelveli GUIDE Date: PROFESSOR & HEAD Department of Dermatology, Venereology & Leprosy, Tirunelveli Medical college, Tirunelveli. DECLARATION I solemnly declare that the dissertation titled “MUCOCUTANEOUS MANIFESTATIONS IN PATIENTS RECEIVING CANCER CHEMOTHERAPY IN REGIONAL CANCER CENTRE OF TIRUNELVELI MEDICAL COLLEGE” is done by me in the Department of Dermatology, Venereology & Leprosy, Tirunelveli Medical College, Tirunelveli. The dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University in partial fulfilment for the award of the Degree of Doctor of Medicine in Dermatology Venereology & Leprosy. Place: Tirunelveli DR.P.SULOCHANA Post Graduate Student Date: M.D. Dermatology Venereology & Leprosy Dept. of Dermatology Venereology & Leprosy Tirunelveli Medical college Tirunelveli -627011 Acknowledgement It gives me great pleasure in presenting my dissertation. At first, I must bow down with reverence to almighty God, my parents and my teachers for giving me the opportunity to pursue my aim. I express my gratitude to Dean, Tirunelveli Medical College Hospital and Medical Superintendent of Tirunelveli Medical College Hospital for permitting me to carry out this research work. “It is the supreme art of the teacher to awaken joy in creative expression and knowledge.” These words of Albert Einstein, I dedicate to my esteemed teacher and guide Dr. P.Nirmaladevi MD, Professor and Head, Dept of DVL, Tirunelveli Medical College Hospital, whose presence and expert guidance helped in bringing out the best in me. It would not have been possible without her support and guidance. I am very fortunate to have such a kind and outstanding person as my guide, my guru. I express my deep sense of gratitude to Dr. K.Punithavathi MD, Associate Professor Dept of DVL, for her valuable guidance. I also want to express my gratitude to Dr.M.Selvakumar MD, Associate Professor, Dept of Venereology for his guidance and valuable suggestions. I sincerely thank Dr. R. Deivanayagam M.D. D.M., Professor and HOD, Department of Medical Oncology and Dr. V. Arumugam M.D. D.M., Assistant Professor, Department of Medical Oncology for their support. With deep sense of gratitude, I thank all the faculty member of the Department of Medical Oncology for sharing their implicit knowledge, support and encouragement during the course of this research work. I have learnt a lot of things and also got immeasurable guidance from my teachers. I sincerely thank Dr.Judith Joy MD., (Late) Dr.R.Karthikeyan MD., Dr.A.N.M. Maalikbabu MD., Dr.P.Kalyanakumar DDVL., Dr.S.Seeniammal MD., for their constant support and encouragement. I am obliged to all my teachers from other departments who encouraged, supported and guided me throughout my endeavor. Kind words of affection have to be mentioned about all my all colleagues Dr.B.Arun kumar, Dr.M.Aravind Baskar, Dr. P.Karthik raja, Dr.R.Monisha, Dr.S.Soundarya, Dr.Vijay kumar, Dr.P.Jemi singh, Dr.A.Rupan, Dr.Ramasubramanium, Dr.S.Vidhya, Dr.S.Yogeswari for their support at various stages of my research work. I am thankful to my patients for participating in this study, for their cooperation and for allowing me to learn the skills of Dermatology Venereology & Leprosy. I am really grateful to my husband Dr.B.Rajesh Kumar and my parents & family members who are the pillar of my strength, providing me emotional support and all the help during my research work. I express my apologies and gratitude to those wittingly or unwittingly remained unsung during my research work. Date: . 2018 Place: Tirunelveli Medical College Hospital Dr. P. Sulochana CERTIFICATE – II This is to certify that this dissertation work titled “MUCOCUTANEOUS MANIFESTATIONS IN PATIENTS RECEIVING CANCER CHEMOTHERAPY IN REGIONAL CANCER CENTRE OF TIRUNELVELI MEDICAL COLLEGE” of the candidate DR. P. SULOCHANA with registration Number 201630251 for the award of M.D. in the branch of Dermatology, Venereology & Leprosy. I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion page and result shows 1 percentage of plagiarism in the dissertation. Guide & Supervisor sign with Seal. CONTENTS SL NO TITLE PAGE NO 1 INTRODUCTION 1 2 REVIEW OF LITERATURE 3 3 AIMS &OBJECTIVES 48 4 MATERIALS AND METHODOLOGY 49 5 OBSERVATION & RESULTS 51 6 DISCUSSION 71 7 SUMMARY 89 8 CONCLUSION 93 9 LIMITATION OF THE STUDY 95 10 BIBLIOGRAPHY ANNEXURES PROFORMA CLINICAL PHOTOGRAPHS MASTER CHART CONSENT FORM LIST OF ABBREVIATIONS USED WHO – World Health Organisation ADR – Adverse Drug Reaction CADRs – Cutaneous Adverse Drug Reactions CA - Carcinoma AICAR – Aminoimidazole – Carboxamide –Ribonucleotide Transformylase 5FU – 5 Fluorouracil 6MP – 6 Mercaptopurine 6 TG – 6 Thioguanine ABVD – Adriamycin/ Bleomycin/ Vinblastine/ Dacarbazine FOLFOX – Folinic acid/ Leucovorin/ Oxaliplatin TPMT – ThioPurine S Methyl Transferase AHS – Azathioprine Hypersenstivity Syndrome DNA – Deoxy Ribonucleic Acid RNA – Ribonucleic acid PATEO – Periarticular Thenar Erythema with Onycholysis HL – Hodgkin’s Lymphoma NHL- Non Hodgkin’s Lymphoma CML- Chronic Myeloid Leukemia CLL- Chronic lymphocytic Leukemia ALL – Acute Lymphoblastic Leukemia GIST – Gastro Intestinal Stromal Tumour NSCLC – Non Small Cell Lung Carcinoma EGFR – Epidemal Growth Factor Receptor VEGFR – Vascular Endothelial Growth Factor Receptor PDGFR – Platelet Derived Growth Factor Receptor SJS – Stevens – Johnson syndrome TEN – Toxic epidermal Necrolysis AGEP – Acute Generalised Exanthematous Pustulosis DRESS – Drug Rash with Eosinophilia and Systemic Symptoms HFS – Hand – foot syndrome PPES – PalmoPlantar Erythrodysesthesia PRIDE syndrome - Papulopustules, paronychia, Regulatory abnormalities of hair growth, Itching and Dryness due to EGFR inhibitor. GIT – Gastro Intestinal Tract INTRODUCTION Chemotherapy is a common, widely used treatment for cancer. We started to use Cancer chemotherapy since 1940. First FDA approved drug is Mechlorethamine and it is being used for non small cell lung cancer since 1949(1). Cutaneous adverse reactions (CARs) are the most commonly associated adverse effects with chemotherapy next to haematological toxicity. They range from mild reactions to severe fatal reactions. Mechanism of drug reaction: Chemotherapeutic drugs act on tumour by interfering with DNA replication process that affects normal healthy tissues containing rapidly dividing cells such as hair, nails, skin and mucosa(2).Cutaneous complications following chemotherapeutic agents administration are generally due to accidental extravasation of drugs, while systemic toxicity may be caused by i) A direct toxic effect, ii) Hypersensitivity reactions and iii) Dissemination of inflammatory response mediators by necrotic cells. Nowadays newer chemotherapeutic agents are introduced to improve the clinical outcome such as targeted therapies which contain small molecule drugs and monoclonal antibodies. Oldest drugs represent 1 cytotoxic agents. Single agent or combination of multiple drugs can be given to target many types of tumour cells. These agents may be cell cycle specific or cell cycle non specific. Cell cycle specific agents target one specific phase of cell cycle and can be given more frequently or as continuous infusion. Cell cycle non specific agents act against all proliferating cells regardless of cell cycle and are usually given as a single dose(3). Most commonly observed adverse effects like xerosis, alopecia, rash, pruritus, mucositis, hand-foot syndrome, dyspigmentation, acneiform eruption, nail changes, and hair changes lead to decreased compliance to the drug and increased morbidity. These adverse effects are common with both cytotoxic drugs and targeted therapies. Newer anticancer drugs are replacing the older traditional chemotherapy agents. Pattern of adverse cutaneous reactions to chemotherapeutic drugs is changing every year. Hence this study was conducted to study the pattern
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