What Kind of Rash Is It A Tutorial

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 more about the skin rash associated with Epidermal Growth Factor Receptor Inhibitors used in cancer treatment

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.

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

Content of the Tutorial At 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

What is Epidermal Growth Factor? 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). Illustration of EGF Wikipedia. org

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

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. blog spot. com/

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/enus/clipart. com

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

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

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

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

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

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

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

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

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

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

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

Dermis n n n Inner layer of skin Links epidermis to hypodermis Wikipedia. org 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 Porth, C. , 2005

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

Test your knowledge The largest organ of the body is A. Liver B. Brain C. Skin

Test your knowledge The skin serves the following distinct functions: A. Protection B. Sensation C. Thermoregulation D. Communication E. All of the above

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. TRUE FALSE

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

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

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

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

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

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

Inflammatory Mediators n 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

Vascular Stage of Inflammation n 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

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

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

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

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

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

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

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.

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

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

EGFR mutations have been discovered… Wong, R. , 2008

– 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

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

Test your knowledge All patients who receive EGFR inhibitors respond to therapy TRUE FALSE

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.

Oncology Nursing Impact How do oncology nurses make a difference?

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

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

Nursing Sensitive Patient Outcomes Definition: Nursing sensitive patient outcomes (NSPOs) are outcomes that are attained through or are significantly impacted by nursing interventions. ONS, 2003

Nursing Sensitive Patient Outcomes The interventions must be within the scope of nursing practice and integral to the processes of nursing care. ONS, 2003

Nursing Sensitive Patient Outcomes NSPOs represent the consequences or effects of nursing interventions and result in changes in patient symptom experience, functional status, safety, psychological distress, and/or costs. ONS, 2003

What are the NSPOs for EGFR Inhibitor rash? NSPOs for EGFR inhibitor rash focus on: 1. Symptom management – Promoting skin integrity – Decreasing skin pain, burning, and itching 2. Psychological Distress – Improving self image

Early Assessment and Intervention is key n Oncology nurses need to know: – How to describe the rash – When the rash develops – Where the rash develops

Terms related to skin rash Erythema n Papule n Pustule n Crusting n Xerosis n Drag mouse over word for definition Porth, C. , 2005

When does rash develop? After treatment with EGFR inhibitor: Week 0 -1: skin erythema and edema occurs Week 1 -3: Papular- pustular eruption occurs Week 3 -5: Crusting of skin occurs Week 5 -8: Dry skin occurs Rash usually resolves completely within 2 -3 weeks of discontinuing treatment Lynch, T. , 2007

An example of the course of rash: from erythema to papulopustules Used with permission from Lacouture, M. , 2006

Where does rash develop? EGFR-Inhibitor Rash occurs most frequently on the Face, Chest, and Back

How do we assess or grade skin rash? Oncology nurses need to go beyond just identifying if a patient has a rash or not. n Grading the rash can be subjective and needs to be consistent amongst the care team. n

Grading Tools The National Cancer Institute (2006) Common Toxicity Criteria (NCI-CTC) grading tool is often used but it can be very unspecific for grading an EGFR inhibitor rash. Eaby, B. , 2008

Grading Tools A tool developed by Lynch et. al. , describing the rash as Mild Moderate Or Severe is a more simple and specific way to grade EGFR inhibitor rash. Eaby, B. , 2008

Lynch’s grading scale n Mild Rash is: – Generally localized – Minimally symptomatic – No impact on ADLs – No signs of superinfection Lynch, T. , 2007

Lynch’s grading scale n Moderate Rash is: – Generalized – Mildly symptomatic (pruritis, tenderness) – Minimal impact on ADLs – No signs of superinfection Lynch, T. , 2007

Lynch’s grading scale n Severe Rash is: – Generalized – Severely symptomatic n Pain, pruritis, tenderness – Significant impact on ADLs – Potential for superinfection Lynch, T. , 2007

Other associated skin toxicities EGFR inhibitors can also cause: n Hair changes – Hair thinning/hair loss n Nail changes – Cracks and fissures n n Eyelash elongation and inversion Itchy, dry skin Used with permission. Mario Lacouture MD Lacouture M. , 2006

What can make rash worse? Temperature changes to skin – Burns (eg. sunburn, radiation burn) – Freezing Friction on skin – bed shearing, turning Pressure on skin – bedridden patients Skin damage – Tape stripping (eg. tegaderm) – Surgical Incisions

Symptom Management The following treatment algorithm should be used as a guideline for EGFR inhibitor induced rash…. Oishi, K. , 2008

Treatment algorithm For a MILD Grade rash: n No treatment OR topical hydrocortisone 1% or 2. 5% cream and or Clindamycin 1% gel n Reassess after 2 weeks – If no improvement proceed to next step Lynch, T. , 2007

Treatment algorithm For a MODERATE Grade rash: n Continue EGFR-I treatment at current dose and: – Hydrocortisone 2. 5% cream or Clindamycin gel or Pimecrolimus 1% cream PLUS – Doxycycline 100 mg BID or Minocycline 100 mg BID Reassess after 2 weeks if If no improvement proceed to next step Lynch, T. , 2007

Treatment algorithm For a SEVERE Grade rash: – Reduce EGFR-I dose per label and: – Hydrocortisone 2. 5% cream or Clindamycin gel or Pimecrolimus 1% cream PLUS – Doxycycline 100 mg BID or Minocycline 100 mg BID PLUS – MEDROL dose pack Reassess after 2 weeks; if reactions worsen, dose interruption or discontinuation may be necessary Lynch, T. , 2007

Key Points for Patient teaching…. Oncology nurses need to teach patients to: – Remain hydrated – Use mild soap such as dove or use oil – Use lukewarm water when bathing – Use alcohol free emollient twice daily (eg. Aveeno®, Eucerin®, Cetaphil®, Aquaphor®) (con’t…. . ) Eaby, B. , 2008 Oishi, K. , 2008

Key Points for Patient teaching (con’t) n n n Use dye-free, alcohol-free, and perfume-free products (eg. lotions, soaps, shampoos, laundry detergents) DO NOT USE over the counter acne medications that contain benzoyl peroxide (drying) Use only hypoallergenic makeup (Dermablend®)can be used to conceal the rash, but remove daily with mild cleanser (Cetaphil®, Neutrogena®) Eaby, B. , 2008 Oishi, K. , 2008

Key Points for Patient teaching (con’t) n n Avoid sun exposure Use sunscreen SPF 30 or higher (titanium dioxide or zinc oxide formulations) Use protective clothing and brimmed hat outside Use of saline nasal spray followed by petroleum jelly on nasal skin breakdown Eaby, B. , 2008 Oishi, K. , 2008

Key Points for Patient teaching (con’t) Keep finger and toe nails clean and trimmed. Avoid biting nails, using artificial nails, or wearing tight fitting shoes or socks n Moisturize hands and feet frequently using petroleum jelly n Use of skin sealant for finger or toe fissures (eg. New Skin®, Liquid Band-Aid®) n Eaby, B. , 2008 Oishi, K. , 2008

Psychological Distress n Nursing Sensitive Patient Outcome: Improved Self Image – Rash may: n be a reminder of cancer n provoke negative self image

Key Points Patient teaching… n Tell patients rash is an expected side effect: n Make sure they know the time frame of when to expect the rash n That the rash is not an allergic reaction n The rash is an indication of positive treatment response n Treatment continuation is important for best response

Key Points Patient teaching…. Offer Support n Make Referrals n n Dermatologist if symptoms continue/worsen n Psychologist/counselor n Integrative Medicine n Massage n American Cancer Society-look good, feel better program

Case Study JK is a 55 y/o male diagnosed in Dec 2008 with colon cancer. He started treatment with FOLFOX regimen. The tumor was sent for gene testing. He received his first dose of Cetuximab (Erbitux) Feb 20. He returns to the clinic a week later for his second dose of Erbitux. His face is reddened and slightly edematous. He denies any pain or tenderness. He has a few macular papular eruptions on his face.

Case Study Question #1 JK’s rash would be graded as: A. Mild B. Moderate C. Severe

Case Study Question #2 Recommended treatments for Mild Grade include: A. Hydrocortisone 2. 5% cream or Clindamycin gel or Pimecrolimus 1% cream B. Doxycycline & Medrol dose pack C. No treatment OR topical hydrocortisone 1% or 2. 5% cream and or Clindamycin 1% gel

Case Study Question #3 As the nurse treating JK, you would emphasize the importance of the following: A. Drinking fluids B. Applying lotion BID C. Avoiding the sun D. All of the above

Case Study Question #4 During JK’s 2 nd visit for Cetuximab, he is worried and reports, “maybe the treatment isn’t working for me since I haven’t gotten a bad rash yet”. Your best response would be:

Case Study Question #4 A. You’re right, let me talk to the doctor. B. Rash may begin in 1 -3 weeks. After this dose, you may have some raised areas that are tender. C. Rash usually appears a good month after you receive the Cetuximab.

Correct!! Rash does generally begin during the first 3 weeks After treatment with an EGFR inhibitor

There’s a better answer Although a rash is a predictor marker of a positive response to treatment, it is too early to tell if there will be a rash or not. Rash can begin in the first 3 weeks after receiving treatment. Try Again

There’s a better answer Rash generally begins during the first 3 weeks After treatment with an EGFR inhibitor Try Again

Case Study Question #5 JK returns to the clinic for week 3 of Cetuximab treatment. He seems down and reports that he is “embarrassed to go to work. I feel like a teenager again, I think I’m going to use Clean and Clear ®, that usually worked on my zits” You would reply:

Case Study Question #5 A. Try it, we’ll see if it works for you. B. Clean and Clear® is not the best acne treatment, there are better ones out there. C. This rash is not acne, and applying Clean and Clear ® will only increase the dryness.

Congratulations!!! You have successfully completed the case studies. Nice Job!

Future Direction As the use of EGFR inhibitors grows for many types of cancers, continued research is necessary to develop evidenced based guidelines to provide the best nursing sensitive patient outcomes for patients with EGFR inhibitor rash.

References n n n Eaby, B. , Culkin, A. , & Lacouture, M. (2008). An interdisciplinary consensus on managing skin reactions associated with human epidermal growth factor receptor inhibitors. Clinical Journal of Oncology Nursing. 12, 283 -290. Esper, P. , Gale, D. , & Muehlbauer, P. (2007). What kind of rash is it? Deciphering the dermatologic toxicities of biologic and targeted therapies. Clinical Journal of Oncology Nursing, 11. 659 -666. Lacouture, M. , Basti, S. , Patel, J. & Benson, A. (2006). The SERIES Clinis: An Interdisciplinary Approach to the Management of Toxicities of EGFR Inhibitors. The Journal of Supportive Oncology. 4(5). Lacouture, M. , Cotliar, J. , & Mitchell, E. (2007). Clinical management of EGFRI associated dermatologic toxicities: US perspective. Oncology, 21, 10 -16. Lacouture, M. (2006). Mechanisms of cutaneous toxicities to EGFR inhibitors. Nature Reviews Cancer, 6, 10.

References n n n Lynch, T. , Kim, E. , Eaby, B. , Garey, J. , West, D. & Lacouture, M. (2007). Epidermal Growth Factor Receptor Inhibitor-Associated Cutaneous Toxicities: An Evolving Paradigm in Clinical Management. The Oncologist. 12. 610 -621. Oishi, K. (2008). Clinical approaches to minimize rash associated with EGFR inhibitors. Oncology Nursing Forum, 35, 103 -111. Microsoft Clip Art images. Retrieved March 23, 2009 from http: //office. microsoft. com/en-us/clipart. com Mosby (2009). Nursing Drug Handbook. Lippincott, Williams and Wilkens. Oishi, K. (2008). Clinical approaches to minimize rash associated with EGFR inhibitors. Oncology Nursing Forum. 35. 103 -111. Oncology Nursing Society (2003). Nursing Sensitive Patient Outcomes. Retrieved March 23, 2009 from http: //www. ons. org/outcomes/measures/.

References n n n Perez-Soler, R. , Delord, J. , Halpern, A. , Kelly, K. , & Krueger, J. (2005). HER 1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER 1/EGFR inhibitor rash forum. Oncologist, 10, 245 -356. Purdom, K. , & Aki, O. (2007). Clinical management of EGFRI associated dermatologic toxicities: The nursing perspective. Oncology, 21, 29 -33 Porth, C. M. (2005) Pathophysiology: Concepts of altered health status (7 th ed). Philadelphia, PA: Lippincott & Wilkins. Southern Illinois University School of Medicine (2005) Skin Histology. Retrieved March 3, 2009 from http: //www. siumed. edu/~dking 2/index. htm Wong, R. & Cunningham, D. (2008). Using predictive biomarkers to select patients with advanced colorectal cancer for treatemnt with epidermal growth factor receptor antibodies. Journal of Clinical Oncology. 26 (35). 5668 -5670.

Thank you to my preceptor, Mary Pat Johnston RN, MS, AOCN for her guidance. n Thank you to my coworkers and family for their support. n Questions, comments or suggestions n I invite you to contact me: portzda@alverno. edu