Transcript Denise Portz, 2009. What Kind of Rash Is It?

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
[email protected]
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/en
-us/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
False
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
Made of 4 to 5 layers of cells
variable thickness depending on
location
Responsible for protection properties
of skin
Porth, C., 2005
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
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






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




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
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

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

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:
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
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.
With more research it is possible that
we may identify a connection for those
who develop rash more than others.
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

Oncology nurses need to know:
– How to describe the rash
– When the rash develops
– Where the rash develops
Terms related to
skin rash





Erythema
Papule
Pustule
Crusting
Xerosis
Drag mouse over word for
definition
Porth, C., 2005
When does rash develop?
After treatment with EGFR inhibitor:
Week
Week
Week
Week
0-1:
1-3:
3-5:
5-8:
skin erythema and edema occurs
Papular- pustular eruption occurs
Crusting of skin occurs
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.
Grading the rash can be subjective
and needs to be consistent amongst
the care team.
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

Mild Rash is:
– Generally localized
– Minimally
symptomatic
– No impact on ADLs
– No signs of
superinfection
Lynch, T., 2007
Lynch’s grading scale

Moderate Rash is:
– Generalized
– Mildly symptomatic
(pruritis, tenderness)
– Minimal impact on
ADLs
– No signs of
superinfection
Lynch, T., 2007
Lynch’s grading scale

Severe Rash is:
– Generalized
– Severely
symptomatic

Pain, pruritis,
tenderness
– Significant impact
on ADLs
– Potential for
superinfection
Lynch, T., 2007
Other associated
skin toxicities
EGFR inhibitors can also
cause:

Hair changes
– Hair thinning/hair loss

Nail changes
– Cracks and fissures


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:
 No treatment OR topical
hydrocortisone 1% or 2.5% cream and
or Clindamycin 1% gel
 Reassess after 2 weeks
– If no improvement proceed to next step
Lynch, T., 2007
Treatment algorithm
For a MODERATE Grade rash:

Continue EGFR-I treatment at current dose and:
– Hydrocortisone 2.5% cream or Clindamycin gel
or Pimecrolimus 1% cream
PLUS
– Doxycycline 100mg BID or Minocycline 100mg
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 100mg BID or Minocycline 100mg
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)



Use dye-free, alcohol-free, and perfumefree 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)




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
 Moisturize hands and feet frequently using
petroleum jelly
 Use of skin sealant for finger or toe fissures
(eg. New Skin®, Liquid Band-Aid®)

Eaby, B., 2008 Oishi, K., 2008
Psychological Distress

Nursing Sensitive Patient Outcome:
Improved Self Image
– Rash may:
 be a reminder of cancer
 provoke negative self image
Key Points
Patient teaching…

Tell patients rash is an expected side
effect:
Make sure they know the time frame of when
to expect the rash
 That the rash is not an allergic reaction
 The rash is an indication of positive treatment
response
 Treatment continuation is important for best
response

Key Points
Patient teaching….


Offer Support
Make Referrals
Dermatologist if symptoms continue/worsen
 Psychologist/counselor
 Integrative Medicine
 Massage
 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.
C.
Doxycycline & Medrol dose pack
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 2nd 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



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
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





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





Perez-Soler, R., Delord, J., Halpern, A., Kelly, K., & Krueger, J.
(2005). HER1/EGFR inhibitor-associated rash: future directions for
management and investigation outcomes from the HER1/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 (7th ed). Philadelphia, PA: Lippincott & Wilkins.
Southern Illinois University School of Medicine (2005) Skin Histology.
Retrieved March 3, 2009 from
http://www.siumed.edu/~dking2/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.
Thank you to my coworkers and family
for their support.
Questions, comments or suggestions
I invite you to contact me:
[email protected]