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What Kind of Rash Is It? A Tutorial About a Skin Rash Associated with Epidermal Growth Factor Receptor Inhibitors used

What Kind of Rash Is It? A Tutorial About a Skin Rash Associated with Epidermal Growth Factor Receptor Inhibitors used in Cancer Treatment. Denise Portz RN, BSN, OCN Alverno College MSN 621 Spring 2009 portzda@alverno.edu. Welcome. Target Audience Oncology Nurses who want to learn

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What Kind of Rash Is It? A Tutorial About a Skin Rash Associated with Epidermal Growth Factor Receptor Inhibitors used

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  1. What Kind of Rash Is It?A Tutorial About a Skin Rash Associated with Epidermal Growth Factor Receptor Inhibitors used in Cancer Treatment Denise Portz RN, BSN, OCN Alverno College MSN 621 Spring 2009 portzda@alverno.edu

  2. Welcome Target Audience Oncology Nurses who want to learn more about the skin rash associated with Epidermal Growth Factor Receptor Inhibitors used in cancer treatment

  3. Objectives At the end of this program the learner will be able to: • Define Epidermal Growth Factor and Inhibitor treatments used in cancer treatment. • Describe the function and structure of skin. • Describe the mechanism of the EGFR rash and inflammatory response involved. • Explore if there is a genetic relationship. • Review assessment and treatment approaches.

  4. Navigating through this tutorial To advance to the next slide click on To review the previous slide click on Roll mouse over underlined words to get a definition To return to the home screen to review a different section click on

  5. Content of the TutorialAt any time during the tutorial you may click on to come to this screen and advance through the topics. Let’s start first by clicking on the first link. Epidermal Growth Factor and Inhibitor Treatments Common Side Effects and Incidence of EGFR Treatments Skin Function and Structure Mechanism of EGFR Inhibitor Rash and Inflammatory Response Genetic Relationship Nursing Sensitive Patient Outcomes Assessment and Treatment Approaches Patient Teaching Case Study

  6. Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation and differentiation by binding to it’s receptor EGFR (epidermal growth factor receptor). What is Epidermal Growth Factor? Illustration of EGF Wikipedia.org

  7. What is Epidermal Growth Factor Receptor (EGFR)? EGFR is a receptor essential for proper growth and function of epidermis and hair. EGFR at the cellular level Used with permission. Mario Lacouture MD Lacouture M, 2006

  8. What are EGFR inhibitors? When Epidermal Growth Factor is over expressed there is an increase in cell growth, proliferation and differentiation which can lead to cancer growth. Blocking or “inhibiting” EGFR results in apoptosis of cells ultimately causing cancer cell death. Cancerous Cell Destruction http://nanotechie.blogspot.com/

  9. What cancers are treated with EGFR Inhibitors? EGFR-Inhibitors are cancer treatments used in: Breast cancer Colorectal cancer Hepatocellular cancer Non-small cell lung cancer Pancreatic cancer Renal Cell cancer All Illustrations retrieved from Microsoft Clip Art March 23, 2009 unless otherwise noted http://office.microsoft.com/en-us/clipart.com

  10. What are EGFR inhibitor agents? Panitumumab (Vectibix) Cetuximab (Erbitux) Gefitinib (Erlotinib) Lapatinib (Tykerb) Erlotinib (Tarceva) Sorafanib (Nexavar) Sunitinib (Sutent) More EGFR Inhibitor treatments are on the horizon

  11. Test your knowledge EGFR is essential in epidermis and hair True False

  12. Test your knowledge EGFR-Inhibitor treatments have shown effectiveness in which types of cancer? A. Lung B. Pancreatic C. Melanoma D. A & B

  13. What are the common side effects from EGFR inhibitor treatments? Fatigue Diarrhea Headaches Hypersensitivity Reactions Skin toxicities including rash Nursing Drug Handbook, 2009

  14. What is the incidence of skin rash? Rash is the most common reported side effect to EGFR Inhibitor treatments Rash occurs in 45-100% of patients Oishi, K., 2008

  15. Test your knowledge The most common side effect of EGFR inhibitors is skin rash • True • False

  16. Function of Skin The skin is the largest organ of the body The skin serves several distinct functions simultaneously Protection Sensation Thermoregulation Communication Skin is also self-repairingafter injury Click on one of the Functions of the Skin to learn more Porth, C., 2005

  17. Structure of the Skin The skin’s structure is composed of 3 layers Epidermis Dermis Hypodermis Wikipedia.org Porth, C., 2005

  18. Epidermis Illustration of Epidermis on the cellular level • Outermost layer of skin that is avascular • Made of 4 to 5 layers of cellsvariable thickness depending on location • Responsible for protection properties of skin Porth, C., 2005

  19. Epidermal cells Keratinocytes • Make up 90% of epidermal layers • Communicate and regulate cells of the immune response by secreting cytokines and inflammatory mediators including Epidermal Growth Factor Lacouture, M., 2006

  20. Scattered among the keratinocytesare a few other cell types Melanocytes Langerhans cells Merkel cells Drag mouse over cell type for definition Wikipedia.org Porth, C., 2005

  21. Dermis • Inner layer of skin • Links epidermis to hypodermis • Sweat glands, sebaceous glands and hair follicles reside mostly in this layer • Roughly two layers • Variable thickness over different regions of the body • Provides support and tensile strength Wikipedia.org Porth, C., 2005

  22. Hypodermis • not a true layer of the skin but subcutaneous tissue • links skin to body proper • variable thickness in different regions of the body • allows for movement of skin over body Wikipedia.org Porth, C., 2005

  23. Test your knowledge The largest organ of the body is • Liver • Brain • Skin

  24. Test your knowledge The skin serves the following distinct functions: • Protection • Sensation • Thermoregulation • Communication • All of the above

  25. Test your knowledge Keratinocytes are found in the epidermis and are responsible for communicating and regulating the immune response secreting cytokines and inflammatory mediators including epidermal growth factor. TRUEFALSE

  26. Mechanism of EGFR Inhibitor Rash Although the exact pathophysiology of an EGFR inhibitor rash remains largely unknown; there are hypotheses about the mechanism. Lacouture, M., 2006

  27. We do know that…. EGFR is highly expressed in keratinocytes Lacouture, M., 2006

  28. and when… EGFR is inhibited, keratinocytes are damaged Stimulating an inflammatory response Lacouture, M., 2006

  29. The Inflammatory Response Inflammation is an attempt by the body to restore and maintain homeostasis after injury and is an integral part of body defense. Porth, C., 2005

  30. Inflammatory Response The Inflammatory Response is initiated by: Tissue damage and/or Bacterial invasion Porth, C., 2005

  31. Stages of Inflammation 1. Inflammatory mediators are recruited 2. Vascular response occurs 3. Cellular response occurs Porth, C., 2005

  32. Inflammatory Mediators • Inflammation is produced by chemical mediators such as: (click on word for definition) Histamine Plasma proteases Arachidonic acid metabolites Platelet activating factor Cytokines Porth, C., 2005

  33. Vascular Stage of Inflammation • After recruitment of chemical mediators, there is dilation of vessels resulting in: • Redness, heat and swelling of tissues • Cells are then recruited to the area Porth, C., 2005

  34. Cellular Stage of Inflammation White Blood Cells are recruited including: • Neutrophils • Lymphocytes • Monocytes Drag mouse over cell type for definition Neutrophils migrate from blood vessels to the inflamed tissue Wikipedia.org/inflammatory_response, 2009 Porth, C., 2005

  35. The inflammatory response causes keratinocyte damage in the epidermal cells….. Causing a Skin Rash The following slide is a representation of this response

  36. Inflammatory Response EGFR Inhibition Chemical Mediator Expression Inflammatory Cell Recruitment More chemicals and neutrophils expressed Keratinocyte damage Rash Develops Adapted from Lacouture, M., 2006

  37. The next slide is another representation explaining how rash develops when EGFR is inhibited…..

  38. a.Shows normal expression of EGFR before treatment with inhibitor b.Shows that during treatment, EGFR is abolished in all epidermal cells leading to differentiation and cell death c. Shows the release of chemical mediators and recruitment of neutrophils causing apoptosis and cell death d. Shows the decrease in epidermal thickness indicating abnormal cell differentiation

  39. Test your knowledge When EGFR in inhibited, an inflammatory response occurs which causes damage to keratinocytes leading to skin rash: TRUEFALSE

  40. You’re Right ! The inhibition of EGFR produces an inflammatory response where chemical mediators and inflammatory cells are recruited, causing damage to the keratinocytes leading to skin rash.

  41. Actually…. the answer is true. The inhibition of EGFR produces an inflammatory response where chemical mediators and inflammatory cells are recruited, causing damage to the keratinocytes leading to skin rash. Try again

  42. Is There a Genetic Link? Recent research identifies a strong correlation between genetics and the effectiveness of EGFR Inhibitors… Wong, R., 2008

  43. EGFR mutationshave been discovered… Wong, R., 2008

  44. The mutation is found in the K RAS gene of the tumor. • Patients are unlikely to benefit from EGFR Inhibitor treatment if they have this mutation. Wong, R., 2008

  45. Is there a Genetic Linkto the skin rash? • There is no specific genetic indication behind the incidence of rash. • With more research it is possible that we may identify a connection for those who develop rash more than others.

  46. Test your knowledge All patients who receive EGFR inhibitors respond to therapy TRUEFALSE

  47. NOPE!! There is a genetic mutation that has been found on the KRAS gene of the tumor. Patients who have this mutation are unlikely to respond well to treatment with an EGFR inhibitor.

  48. Oncology Nursing Impact How do oncology nurses make a difference?

  49. Oncology Nursing Impact Oncology nurses can affect the lives of oncology patients through the development of nursing sensitive patient outcomes.

  50. Nursing Sensitive Patient Outcomes In 2003, the Oncology Nursing Society committed to develop ways to define, measure and educate nurses about nursing sensitive patient outcomes. ONS, 2003

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