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Epidermolysis Bullosa and Chronic Wounds:A Model for Wound Bed Preparation ofFragile Skin
C M E1 AMA PRACategory 1 Credit TM
ANCC3.3 Contact Hours
Elena Pope, MD, MSc, FRCPC & Head Section of Dermatology & The Hospital for Sick Children & Toronto, Ontario, CanadaIrene Lara-Corrales, MD, FRCPC (Derm) & Assistant Professor of Pediatrics & University of Toronto & Toronto, Ontario,Canada & Pediatric Dermatologist & Interdisciplinary Clinic, The Hospital for Sick Children & Toronto, Ontario, CanadaJemima E. Mellerio, BSc, MD, FRCP & Consultant Dermatologist and Lead for the Adult Epidermolysis Bullosa Service &St John’s Institute of Dermatology, Guy’s & St. Thomas’ NHS Foundation Trust, and Great Ormond Street Hospital for ChildrenNHS Foundation Trust & London, United KingdomAnnaE.Martinez,MBBS,MRCP,MRCPCH &Consultant Pediatrician andClinical Lead for thePediatric Epidermolysis BullosaService & Great Ormond Street Hospital & London, United KingdomCathryn Sibbald, RPh, BScPhm, ACPR & MD Candidate 2013 & University of Toronto & Toronto, Ontario, CanadaR. Gary Sibbald, BSc, MD, MEd, FRCPC (Med) (Derm), FACP, FAAD, MAPWCA, for the EB International ConsensusPanel & Professor of Public Health and Medicine & University of Toronto & Toronto, Ontario, Canada & Director & InternationalInterprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care) & Dalla LanaSchool of Public Health & University of Toronto & Past President & World Union of Wound Healing Societies & Clinical Editor &Advances in Skin & Wound Care & Ambler, Pennsylvania
Acknowledgments: This article is dedicated to all persons suffering from epidermolysis bullosa in an attempt to improve their quality of life. The authors thank the late Alex Melkic andDeanna Molinaro from whom we have learned so much and Molnlycke for their unrestrictive educational grant support.
Dr Pope has disclosed that her institution received an unrestricted educational grant from Molnlycke Health Care to host the EB International Consensus Panel. Dr Lara-Corrales hasdisclosed that The Hospital for Sick Children is a recipient of grant/research funding from the Canadian Dermatology Foundation Society of Pediatric Dermatology. Dr Mellerio, Dr Martinez,and Dr C. Sibbald have disclosed that they have no financial relationships related to this article. Dr R.G. Sibbald has disclosed that he is a board member of Coloplast, Covidien, J & J(Systagenix), Molnlycke, Registered Nurses’ Association of Ontario, Hollister; and was a board member of 3M, BSN Medical, Gaymar, KCI, and Healthpoint Biotherapeutics; he was amember of the speaker’s bureau for 3M, BSN Medical, Gaymar, KCI, Coloplast, Covidien, J & J (Systagenix), and Molnlycke; is a member of the speaker’s bureau for Galderma; was arecipient of grant/research funding from 3M, BSN Medical, Canadian International Development Agency, Coloplast, Covidien, Government of Ontario, KCI, J & J (Systagenix), Molnlycke,and the Registered Nurses’ Association of Ontario; and is a recipient of grant/research funding from Exciton, J & J (Systagenix), Hollister, and Healthpoint Biotherapeutics.
All staff and planners, including spouses/partners (if any), in any position to control the content of this CME activity have disclosed that they have no financial relationships with, or financialinterests in, any commercial companies pertaining to this educational activity.
Lippincott CME Institute has identified and resolved all conflicts of interest concerning this educational activity.
To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least 13 of the 18 questions correctly.
This continuing educational activity will expire for physicians on April 30, 2014.
PURPOSE:
To enhance the learner’s competence with information about a wound bed preparation model of fragile skin for
patients with epidermolysis bullosa (EB).
TARGET AUDIENCE:
This continuing education activity is intended for physicians and nurses with an interest in skin and wound care.
APRIL 2013
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OBJECTIVES:
After participating in this educational activity, the participant should be better able to:
1. Differentiate between the types and subtypes of EB.
2. Apply EB assessment and treatment strategies to patient care scenarios.
ABSTRACT
Epidermolysis bullosa (EB) is a group of inherited diseases with4 subtypes. This disorder is amodel for fragile skin,with some affectedindividuals having chronic, difficult-to-heal wounds. The care ofwounds in people with EB can be guided by the Wound BedPreparation paradigm. The treatment of chronic EB wounds is outlinedwith a quick reference guide of 12 consensus recommendationscreated by a panel of 11 experts. These recommendations werereviewed by a computer-facilitated modified Delphi process where15 external reviewers (68.8% of whom reported having 11 or moreyears’ experience with EB care). Inclusion of recommendations wascontingent on 80% agreement from reviewers.KEYWORDS: epidermolysis bullosa (EB), skin diseases, EB simplex,junctional EB, dystrophic EB, Kindler syndrome
ADV SKIN WOUND CARE 2013;26:177-88; quiz 189-90.
INTRODUCTIONEpidermolysis bullosa (EB) is a rare group of genetic blistering
skin diseases with skin fragility leading to bulla formation.1 There
is a wide spectrum of severity in EB: the mildest form is localized
EB simplex, where blistering predominantly affects the feet and
hands, but other forms, notably recessive dystrophic EB (RDEB)
and junctional EB, are characterized by more extensive skin and
mucosal involvement, systemic complications, disfigurement,
and often severely limited life expectancy. It is persons with these
more severe forms of EB who have a tendency to develop lifelong
chronic wounds and infections. In 2012, a best practice con-
sensus was created examining the issue of wound bed prep-
aration (WBP) that was literally ‘‘born on the back’’ of Alex, a
person with RDEB.2 This WBP knowledge can be applied not
only to all patients with EB, but also as a model for fragile skin
and chronic ulcers (Figure 1).
The consensus project united EB experts with wound healers
(basic scientists, physicians, and nurse clinicians) with a pioneer
in bone marrow transplantation (Table 1). The aim was to facil-
itate knowledge of the 4 different subtypes of EB so that affected
individuals are recognized early and receive appropriate symp-
tomatic treatment, including optimal local wound care to pre-
vent life-threatening infections and failure to thrive. Another
objective was to increase awareness of complications such as car-
diomyopathy and squamous cell carcinomas (persistent inflam-
mation leads to malignant transformation) that may rarely occur
even in childhood. By reading this continuing education article, cli-
nicians will be better able to identify and treat EB and its subtypes.
Attempts to optimize wound care in EB patients began many
years ago. In January 1997, Canada was the first country in the world
to approve an artificial skin substitute grown in vitro (Graftskin
[Apligraf; Organogenesis, Canton, Massachusetts]: a bovine type
1 collagen with human fibroblasts and an epidermal cell layer). In
February 1997, Alex (Figure 1) had 2 pieces of Graftskin placed on
the upper part of his extensive back ulceration (covering 50% of
his back for 3 years). One week after application, the skin sub-
stitutes (with fluid release slits to maintain contact) under the silver
and foam dressing were intact. In contrast, the other skin substi-
tute piece without the bacterial balancing silver was destroyed
by the local collagenase, partly produced by the Pseudomonas or-
ganisms. Subsequent applications of both Vicryl skin substitute
populated with human fibroblasts (Dermagraft; Shire Regen-
erative Medicine, San Diego, California) and Graftskin resulted
in complete wound healing of Alex’s back. These results were
subsequently reproduced on wounds of other EB patients.3,4
Although Alex has since died as a result of infection and car-
diomyopathy, his contribution to the better understanding of
local wound care has shaped what clinicians know today.
The authors have published a model for WBP.5–7 This model
includes treating the whole patient, patient-centered concerns,
and local wound care. In EB patients, ideal treatment of the cause
involves replacing type VII collagen for RDEB patients through
bone marrow transplants or other gene-modifying therapies.8
Treating the cause also includes optimizing other cofactors in-
volved in healing, including nutrition (such as supplements and
early insertion of feeding tubes) and the correction of anemia.
The components of local wound care are as follows: DIM before
DIME: debridement, infection/inflammation control, and moisture
balance before the edge effect for advanced therapies (eg, skin
substitutes for stalled but healable wounds). Trauma and pain
associated with local wound care have been improved with
local silicone mesh products, soft silicone foam coatings, and
silicone tape.
Wagner et al9 published a seminal article in 2010 reporting
on the first 7 patients with RDEB undergoing immunoablative
chemotherapy and allogeneic stem cell transplant. Of the 7 pa-
tients, 1 died of cardiomyopathy before transplantation and a
second patient died of infection and transplant rejection 183 days
after transplantation. All recipients had a reduction in new blister
formation between days 30 and 130 after transplantation. Five of
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the 6 recipients had an increase in type VII collagen expression,
but without formation of normal anchoring fibrils.
There are 2 key concerns surrounding transplantation pro-
cedures. First, the small number of individuals eligible for trans-
plant may develop human leukocyte antigens from the allogeneic
cells in the skin transplant, increasing the potential for rejection of
a bone marrow transplant. Second, older individuals with RDEB
(especially after age 20 years) are very susceptible to aggressive
squamous cell carcinomas, and the immunosuppression associ-
ated with allogeneic stem cell transplantation may increase this.
The authors have currently completed the full circle to apply the
principles of wound bed preparation, specifically for people with
EB, not only to optimize healing but also to prevent infections and
other complications before and after bone marrow transplanta-
tion (Figure 2). In addition, the authors are suggesting strategies
for persons with EB and their circle of care (parents and healthcare
providers) in resource-poor areas where links to EB experts will
help improve diagnosis and treatment.
Epidermolysis bullosa also represents a model for fragile skin
found in older adults, Skin Changes at Life’s End,10 and other
patients suffering from chronic disease or immunosuppression.
Therefore, the principles discussed in this article can be applied
to other patient populations with skin fragility.
METHODSThe process of consensus building with a full discussion of the
dermatological and general medical components of the care
of individuals with EB has been published elsewhere.2 Briefly,
the recommendations were generated by a diverse panel of 11
experts and reviewed by 15 external reviewers (Tables 1 and 2).
Inclusion of recommendations was contingent on 80% agree-
ment from responders.
This article summarizes the EB recommendations with a special
emphasis on the wound healing component as outlined with the
WBP paradigm and utilizes EB as a model for fragile skin.
TREAT THE CAUSE
1. Assess the patient’s ability to heal.
2. Develop an individualized goal of care.Epidermolysis bullosa is caused by mutations in structural proteins
with resultant fragile skin. There are currently 4 main subtypes
Figure 1.
WOUND BED PREPARATION ADAPTED TO THE PERSON WITH EPIDERMOLYSIS BULLOSA
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described, based on the specific genetic defect and the level at
which blisters form in the skin in response to trauma (Figure 3).1,11
Epidermolysis Bullosa Simplex: The most common type of
EB simplex is localized EB simplex with skin cleavage within the
basal layer of the epidermis. The blisters are usually on the palms
and soles, aggravated by heat and friction. The inheritance is au-
tosomal dominant with mild disease. Mutations are present in
keratins 5 or 14. A less common but also autosomal dominant
type, Dowling-Meara, features clustered distal blisters with a string
of pearl-like arrangement. Although painful keratoderma is noted
with time, patients tend to be less severe with increasing age.
Junctional EB: Skin and mucosal cleavage occurs at the
lamina lucida level of the basement membrane zone, including
periorificial areas of skin, ocular, tracheolaryngeal, gastrointestinal,
genitourinary, and renal systems. The mode of inheritance is
usually autosomal recessive, with mutations in the genes encoding
collagen XVII, !6"4 integrin, or laminin 332. The Herlitz form
is the most severe (exuberant granulation in the perioral area,
around the nails, and denuded diaper area), with death in most
cases in the first 1 to 2 years of life. The non-Herlitz form is often
severe in infancy, but life expectancy is considerably longer.
Dystrophic EB: This type of EB involves cleavage beneath the
lamina densa, within the dermis at the level of the anchoring fibrils
due to mutations in the type VII collagen gene.l The autosomal
dominant form is the second most common EB type, and pa-
tients present with blisters in areas prone to bumps or knocks
such as the toes, knees, fingers, and elbows. The autosomal reces-
sive form is usually more debilitating, with blisters from birth
and pseudosyndactyly, where toes and fingers become fused. This
form is associated with lifelong chronic wounds and with the de-
velopment of aggressive squamous cell carcinomas in the 30s to
40s. If they reach their mid-50s, 90% of individuals will have had
a squamous cell carcinoma.
Kindler Syndrome: This rare form of EB may result in cleav-
age at any of the 3 levels outlined above. Blisters in early childhood
are gradually replaced by scarring, keratoderma (thickened palms
and soles), poikiloderma (hypopigmentation and hyperpigmen-
tation, telangiectasia, and atrophy), and photosensitivity. It is
caused by mutations in the gene encoding kindlin 1, which is in-
volved in basal layer keratinocyte adhesion at focal contacts.
Genetic EngineeringUntil recently, care of patients with EB has consisted of trying to
minimize trauma-induced blistering of the skin and supportive care
of resulting wounds. However, there are some new and exciting
therapies being proposed to target the cause of the skin fragility
in these patients, including replacement of the abnormal protein
(eg, collagen VII in RDEB) and bone marrow transplantation.
Recent studies have suggested that delivery of allogeneic fi-
broblasts to the skin of patients with RDEB may be beneficial
in improving skin adhesion and increasing type VII collagen
deposition at the dermal-epidermal junction.12 There are promis-
ing data from patients with RDEBtreated with immunomyeloablative
chemotherapy and allogeneic stem cell transplantation, resulting
in improved wound healing, decreased blister formation, and
increased collagen VII deposition at the dermal-epidermal junc-
tion. Although encouraging, further study is needed to deter-
mine long-term safety and efficacy of this modality.9 Until then,
treatment goals are aimed at optimizing wound healing and min-
imizing disability from blistering.
Nutrition and HemoglobinThere are many different ways in which nutrition may be compro-
mised in patients with EB; both poor dietary intake and increased
metabolic demands can impair wound healing.13 Adequate pro-
tein is a prerequisite to good wound healing through its integral
role in the production of granulation tissue, and albumin levels
Table 1.
CONSENSUS PANEL AND EXTERNAL REVIEWERS
Panel Members
Elena Pope, co-chair Pediatrics, Dermatology (Canada)
Irene Lara-Corrales MD, Pediatrics, Dermatology
(Canada)
Jemima Mellerio MD, Dermatology, Adult and
Pediatric EB (United Kingdom)
Anna Martinez MD, Pediatrics, Pediatric EB
(United Kingdom)
Greg Schultz PhD, Scientist (United States)
Rob Burrell PhD, Scientist (Canada)
Laurie Goodman Nurse (Canada)
Patricia Coutts Nurse (Canada)
John Wagner MD, Bone marrow transplant
(United States)
Upton Allen MD, Pediatrics, Infectious Diseases
(Canada)
Gary Sibbald, co-chair Dermatology, Medicine (Canada)
External Reviewers
Edward Barrett (Canada) Andrew Lin (Canada)
Anna Bruckner (United
States)
Anne Lucky (United States)
Maya El Hachem (Italy)
Celia Moss (United Kingdom)
Louise Foret-Lalonde
(Canada)
Dedee Murrell (Australia)
Gerry Kelly-Mancuso
(United States)
Annmarie Ormonde (Italy)
Michelle Lee (Canada)
Francis Pallison (Chile)
Agnes Schwieger (Germany)
Rosemarie Watson (Ireland)
Karen Wiss (United States)
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less than 2.0 to 3.0 g/dL can have a negative impact (reference
range, 3.0–5.4 g/dL).14,15 To optimize nutrition, a dietitian should
be consulted to calculate caloric intake and ensure that the diet
includes adequate amounts of protein, zinc, and iron in forms that
are palatable for patients, especially those with fragile mucosal
barriers. Feeding tubes are often required in children with RDEB
and other severe types of EB to improve growth centiles or a very
low body mass index.
Low hemoglobin can affect tissue oxygenation and will also
inhibit healing in people with EB.16 There are several reasons for
increased blood loss and decreased production of red blood cells,
including:
& increased blood loss through blisters and chronic wounds on
the skin and in the gastrointestinal tract
& chronic inflammation leading to decreased production of red
blood cells
& iron deficiency and increased iron utilization
& deficiencies of other vitamins and minerals including vitamin
B12 and folate.
Although there is evidence for targeting hemoglobin levels to
levels greater than 100 g/dL,16 for many individuals with severe
EB and chronic wounds, a hemoglobin of 80 g/dL is a more
realistic recommendation. Attempts to maintain the hemoglobin
at higher levels lead to the potential for iron overload from intra-
venous iron or blood transfusions.
Deep Infection and InflammationChronic wounds with large open areas are often stuck in the
inflammatory stage of the healing process. Proinflammatory metal-
loproteases and elastases can be derived from both the host and
critically colonizing bacteria. Antimicrobials have a known spec-
trum of antibacterial action, but some antimicrobials also have
an anti-inflammatory action that can promote healing both by
decreasing bacterial numbers in the wound but also by de-
creasing inflammation. In young infants, erythromycin is a rea-
sonable agent for anti-inflammatory and antimicrobial effects,
with trimethoprim (TMP)an appropriate alternative after 6 months
of age. Tetracyclines should be reserved for older children after the
emergence of permanent teeth.
Both infection and inflammation can impair wound healing.
All wounds are colonized with bacteria and infection results
when the bacterial load and virulence overcome the ability of the
patient’s immune system to resist invasion. Once infection oc-
curs, treatment takes 2 to 4 weeks.7 Inflammation is present in
many wounds, but can be prolonged and stall healing when deg-
radation of extracellular matrix and growth factors occurs more
rapidly than the collagen matrix synthesis.17 Observational data
have suggested that patients with more severe forms of EB treated
with long-term, low-dose, anti-inflammatory antibacterial treat-
ment, such as erythromycin or TMP, have reduced wound sever-
ity and develop fewer new blisters.18 In a small cohort of children
with EB, TMP was associated with a trend toward a greater reduc-
tion in the total wound surface area compared with placebo.18
PATIENT-CENTERED CONCERNS
3. Address pain and itch along with potentialtreatments.Pain and itch are very common and debilitating symptoms in
EB with significant effects on quality of life.19 Various recommen-
dations have been made to help prevent pain. Skin protection to
avoid trauma includes use of silicone adhesives or foam dressings,
modified sleeping and seating surfaces, and good footwear.
Releasing fluid from blisters, while leaving the roof intact, can
prevent blister expansion.6 Finally, the use of hand cleansers and
clean techniques when changing dressings can avoid potential
translocation of bacteria into areas of compromised skin and
increased risk of superficial critical colonization or deep or sec-
ondary painful infection.
Figure 2.
ADVANCED THERAPIES FOR EB
A, Alex, a person with EB. B, Two pieces of Graftskin applied. C, One piece of Graftskin is covered with a nanocrystalline silver dressing. D, Both pieces have moisture balancing foam
with soft silicone. E, Only piece under silver and foam dressing survives at 1 week.
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Table 2.
WOUND CARE RECOMMENDATIONS FOR PERSONS WITH EPIDERMOLYSIS BULLOSA
Main Themes Specific Themes Specific Recommendations
A. Treat the cause Assess the patient’s
ability to heal
Evaluate EB type–specific involvement (simplex, junctional,
dystrophic, Kindler syndrome) and comorbidities
Consider age of the patient
Assess nutrition status: growth centiles, body mass index
Monitor hemoglobin levels
Develop individualized goals
and plan of care
Low hemoglobin consider:
iron supplementation, transfusion(s)
Low albumin: protein supplements, feeding tube
Address other specific subtype involvement
B. Patient-centered
concerns
Address and support
management of patient-centered
concerns to enable healing
Pain:
World Health Organization pain ladder for nociceptive pain
Neuropathic pain: consider tricyclics, gabapentin, pregabalin
Local or topical approaches
Nonpharmacological approaches
Itch (only partly histamine mediated)
Combine nonsedating H1 antihistamine in the morning with sedating
preparations at night
Consider liquid quick onset preparations for breakthrough
Activities of daily living:
Consider rehabilitation consult
Provide education and support
to the patient/parent and their
circle of care to increase treatment
adherencea
Build confidence with patient and their circle of care individuals,
to increase adherence
Develop interprofessional team
Explore the support from established EB centers
Consult:
ebcare network ([email protected])
DebRA programs (http://www.debra.org/international)
C. Local wound care Assess wound(s) location
and characteristics
Location
Target wound or wounds
Longest length x widest width at right angles
MEASURE mnemonic
Gently cleanse wounds with
low-toxicity solutions
Saline, water, or acetic acid (0.5%–1.0%)
Consider baths, whirlpool ± with salt, bleach, other antimicrobials
Debridement Drain blisters with a sterile needle to prevent tracking but leave
roof on blister
Consider nontraumatic conservative debridement of slough
Assess and treat Superficial critical colonization (NERDS) and abnormal inflammation
Deep/surrounding tissue infection (STONEES)/generalized
inflammationcontinues
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To help treat pain, it is important to distinguish nociceptive from
neuropathic pain. Nociceptive pain is characteristically described
as gnawing, aching, tender, or throbbing, provoked by stimulus,
and can be treated with a stepwise approach proposed in the
World Health Organization’s pain ladder.20,21 Acetaminophen
is used first, with subsequent addition of nonsteroidal anti-
inflammatory medications (ibuprofen or naproxen) and then
narcotics (morphine, hydromorphone) as needed for optimal
pain control. Neuropathic pain is burning, stinging, shooting, or
stabbing and requires modalities such as tricyclic antidepressants
(amitriptyline, or more selective nortriptyline or desipramine) or
anticonvulsants (gabapentin, pregabalin).
It is important to obtain a good history of the presence and
timing of itch, in order to tailor therapies to target or prevent
triggers. For patients who experience nighttime itch, a sedating
medication such as diphenhydramine may be beneficial. Uncom-
monly, diphenhydramine may produce paradoxical excitement
instead of sedation or leave patients groggy in the morning. In
these cases, hydroxyzine or doxepin may be helpful alternatives.
Hydroxyzine syrup allows for very small doses to be adminis-
tered, and the drowsiness is often less severe by morning, but the
effect in the skin may last for up to 72 hours. For daytime itch,
nonsedating antihistamines, such as cetirizine or loratadine, can
be used; however, a small subset of patients may experience drows-
iness with these products. Refrigeration of topical products used on
the skin can also produce a cooling sensation and minimize itch.
4A. Consider activities of everyday living andrestrictions.Epidermolysis bullosa patients carry a large disease burden with
impacts on all aspects of daily living. It is helpful to involve oc-
cupational and physiotherapists to maximize independence in
activities of daily living, as well as leisure activities. It is also
important to screen for concurrent anxiety or depression with
Table 2.
WOUND CARE RECOMMENDATIONS FOR PERSONS WITH EPIDERMOLYSIS BULLOSA, CONTINUED
Main Themes Specific Themes Specific Recommendations
Select an appropriate dressing/
topical therapy based on the
subtype of EB
Autolytic debridement: alginates, hydrogels
Superficial critical colonization: silver, honey,
polyhexamethylene biguanide
Moisture balance with silicone coatings to prevent trauma, pain
Evaluate the expected rate of
healing or reassess wound goals
of care
Reassess individuals not healing at the expected rate
Low hemoglobin
Low albumin
Infection
Systemic organ compromise
Edge effect: If a wound is stalled
or the edge/other areas appear
atypical, consider a skin biopsy to
rule out squamous cell carcinoma
or other complications prior to
considering active therapeutic
options
Determine if wound is healable but stalled
Consider advanced or active therapies
Skin graftsbLiving skin equivalents (beware of potential HLA sensitization for
future bone marrow transplant and other procedures)
Biological agents
D. Provide organizational
support
Consider a healthcare system
support structure including
specialized nurses,
interprofessional clinics, and a
structured approach to new cases
Each new case needs diagnosis and
typing/subtyping ASAP
Develop healthcare system support for new patients
(existing models)
Individual patients need community virtual interprofessional team
http://www.internationalebforum.org
aFor professionals requiring further support, contact DebRA or other established EB centers.bIf cellular therapy candidate (identify early, especially junctional EB): use filtered blood products; consider the risk of HLA exposure with any cellular products (eg, allogeneic skin grafting);
optimization of the vaccine strategies for potentially immunocompromised individuals.
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appropriate referralswhere indicatedandprovidepsychosocial sup-
port with information about support and patient advocacy groups.
4B. Quality of life is affected by local wound care.The frequency of dressing changes and time involved depends on
the extent of the wounds and the dressings used. Although many
foam dressings can be left in place for up to 7 days, most patients
with severe EB require dressing changes every day to every 1 to
3 days. The amount of exudate from the wound along with odor
or discomfort will often determine the frequency of dressing
changes. If materials stick, dressing changes may be facilitated by
bathtub bathing and soaking. Baths are preferred over showers
that can cause extension of the blisters due to pressure from the
water stream.
The dressing changes take time, and the dressings themselves
can be hugely expensive. Community nurses are sometimes re-
quired to help with dressing changes, which adds a layer of
scheduling inconveniences and system costs above those already
mentioned. The dressing changes are often very painful, and if
so, it is important to recommend that the patient take an anal-
gesic approximately 30 minutes before the anticipated change.
The need for dressing changes and limitations on mobility makes
schooling and employment challenging for many of the more
severe types of EB patients.
Figure 3.
TYPES OF EB PRESENTATION
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LOCAL WOUND CARE
5. Document thewoundsand their ability toheal.Documentation of wounds is best achieved by locationVa body
diagram with the wound location and size is often useful. It is
also important to see the entire skin of a person with EB at least
every 6 months. A rotational system should be worked out with
the patient and his/her circle of care, so that at each visit the most
severe wound is examined along with the needed other areas of
the body to complete the every-6-months skin rotation. Any
wound that appears atypical with stalled healing should be
biopsied. This is particularly important for people with RDEB,
where aggressive squamous cell carcinomas are very common and
can develop at a very young age. The current recommendation is
screening surveillance every 6 months from the age of 10 years in
this group of patients. The risk of developing these lesions in-
creases to 90% of individuals who survive over the age of 50 years.22
One framework that can be used for wound assessment is the
modified MEASURE paradigm (measure size, exudate [amount
and characteristics], appearance [base or granulation tissue],
suffering [pain], undermining [depth measured in centimeters],
re-evaluate, and edge).23 This documentation provides a good
assessment of the extent of the wound in its current state, as well
as a good tool for monitoring the healing process. A modified
model tailored to patients with EB is outlined below in more
detail, with the deletion of undermining.
& Size: This is measured with the longest length and the widest
width at right angles to the longest length.
& Exudate: Exudate is derived from the dermis or deeper struc-
tures and consists of varying amounts of serum, blood, or pus. The
most predominant component should be listed first and then the
subsequent component(s). For example, serosanguineous exu-
date has more serum than blood, or all 3 components may be
present such as sero–pustular-sanguineous.
The amount of exudate is then quantitated as none, scant,
mild, moderate, or heavy. For example, when the dressing is
removed, if there is less than 25% of the surface soiled, the
exudate could be categorized as scant; with 25% to 50%, it would
be a mild exudate; 50% to 75%, moderate exudate; and more
than 75% or wound exudate dressing strikethrough (leakage)
would indicate a heavy exudate.
&Appearance: The wound base and the margin should be as-
sessed. The base can have black, yellow, or red-pink tissue. Black
tissue usually indicates necrosis or tissue death. Yellow can be
fibrin in the wound base that may be healthy, and the lattice
framework for pink buds of healthy granulation to appear. This
needs to be distinguished from loose yellow slough that represents
dead surface cells. Healthy granulation tissue is firm and pink. It
needs to fill the wound base to the level of the wound edge for
epithelium to migrate across the surface as quickly as possible.
Unhealthy granulation tissue has a bright red color, is friable, and
bleeds easily. When a dressing is removed, blood may be obvious
on the inner aspects of the dressing, and punctate bleeding points
are seen on the wound surface. This type of granulation is often
associated with critical colonization of the wound surface and
may respond to topical antimicrobial agents. The wound base can
be characterized as having 50% healthy pink granulation and 30%
unhealthy bright red friable granulation, with 20% yellow slough.
Wound edges may be healthy or unhealthy. A healthy wound
edge often has a tapered appearance like a sandy beach and water
interface. This is often surrounded by a rim of new epithelium that
is often purple in color. A stalled or nonhealing chronic wound often
has a cliff-like edge due to stalled epithelial migration. Unhealthy
wound margins may be red, warm, and edematous with infection
spreading into the wound margin or macerated if there is excess
exudate in the wound base that is not managed by the dressing.
& Suffering (Pain): Pain needs to be documented and is best
measured with an 11-point numerical rating scale. The patient is
given direction that 0 is no pain and 10 is like slamming your
finger in a car door, with 5 representing a bee sting, where is your
pain now? The pain can then be characterized as nociceptive or
neuropathic and treated by the criteria in the section above on
patient-centered concerns.20 Young infants may relate best to the
pictures in the Faces Pain Scale. Most individuals can live with a
pain level of 2 to 3 out of 10. Pain levels of 4 or higher should be
treated. Itch can be as troublesome as pain and needs treatment,
despite the less than optimal results from many of these patients
with traditional sedating antihistamines.
Reassessment: Wounds that are not 30% smaller by week 2 to
4 are unlikely to heal by week 12.24 Because many patients with
EB, especially severe cases, have multiple medical problems and
suboptimal hemoglobin and serum albumin levels, maintenance
or nonhealable wounds are common. Healing may not always be
the primary goal; however, it is desirable. Controlling pain and
preventing infection are often the most important elements.
Edge Effect: This is where patients who have had optimal
treatment of the cause and aggravating factors (where possible),
along with patient-centered concerns and local wound care, may
benefit from advanced therapies as outlined in Figure 2.
6. Gently cleanse wounds with low-toxicitysolutions.Once the old dressing has been removed, the area should be
gently cleaned with solutions with low or no toxicity. Options
include saline solution, water, or solutions with low concentra-
tions of acetic acid (white vinegarV5% diluted 1 in 5 or 1 in 10),
benzalkonium chloride, and/or chlorhexidine. Some patients
may not tolerate the vinegar because of burning or stinging, and
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the cleansing agent should be rotated in these cases. The gauze
can be saturated with the solution and applied as a soak to hy-
drate the wound surface with the net movement of liquid from
the gauze to the wound surface. Alternately the same material
can be squeezed or wrung out leaving damp gauze to apply to
the wound, resulting in a compress that acts as an astringent
(coagulates protein). The net movement from a compress is from
the wound surface to the gauze and results in removal of surface
debris. With both methods, the cloth should be changed every
30 to 60 seconds to complete the cleansing process. Irrigation is
too harsh for the fragile skin associated with EB.
Dilute acetic acid will lower the pH of the wound surface, and
this is often helpful to remove Pseudomonas or other gram-
negative organisms from the wound surface that thrive in an
alkaline environment. Pseudomonas has a lower virulence than
most gram-positive organisms (eg, Staphylococcus aureus or Strep-
tococcus) and can often be treated topically rather than with systemic
antibiotics, and it is best to consider 2 topical antimicrobials
(such as acetic acid with silver or iodine preparations).
7. Debridement.The inherent skin fragility of patients with EB requires that extra
care be taken in the changing of dressings and local wound care
in order to prevent further skin damage from mechanical fric-
tion or trauma. Bathing or soaking areas before removing old
dressings can minimize pain and avoid tearing off a superficial
blister roof. Bath water can be made antimicrobial by adding
dilute acetic solution (5% white vinegar diluted to 0.25%–1.0%),
or bleach (5–10 mL in 5 L of water) may decrease the bacterial
carriage.25 It is important to rinse off either of these solutions
with clean water after bathing.
If intact blisters are present, they should be punctured with a
sterile needle and gentle pressure applied to remove the contents.
The roof should be left to act as a natural biologic dressing. If crusts
(scabs) have formed over the wound, they should be soaked and
carefully lifted off as the presence of the eschar can impair heal-
ing and create a proinflammatory stimulus.
8. Assess and treat superficial criticalcolonization, deep and surrounding infection,or inflammation.The presence of infection or inflammation should be clinically
assessed and documented. Helpful tools include the mnemonics
NERDS (nonhealing; increased exudate; red, friable tissue;debris,
dead slough; smell) and STONEES (increased size; temperature
[3- F warmer than contralateral skin]; os, exposed/probing to bone;
new areas of breakdown; erythema/edema of surrounding skin;
increased exudate and smell).26
If there are 3 or more NERDS criteria, a topical antimicrobial
agent may be beneficial including topical dressings with silver,
iodine, polyhexamethylene biguanide, honey, or topical surfac-
tants. Care should be taken using silver dressings or topical prod-
ucts in children as systemic absorption occurs. Some of these
dressings may sting and burn on application, and often it is im-
portant to respect patient preference with careful monitoring of
the clinical results. More detail on these choices can be found in
Wound Bed Preparation 20117 or the complete report on the
consensus document.2
For deep infections, treatment will be based on empirical choices
that should have broad-spectrum coverage, and then more specific
anibiotics can be ordered based on the culture and sensitivity results.
9. Moisture balanceVuse silicone foamsinstead of adhesives.The choice of dressing depends on the wound characteristics,
but should be selected with a goal of optimal moisture balance.
In EB patients, silicone foam dressings work well as they allow
large amounts of fluid to be absorbed while providing protective
padding and will not adhere strongly to the skin when removed
preventing pain and trauma on removal.2 Other nonadherent
moisture balance dressings will also be useful with calcium algi-
nates for areas of bleeding or hydrogels/hydrofibers for gentle
moisture balance where fluid donation or fluid lock is required.
Some highly exudative wounds require fluid lock technology with
superabsorbent dressings with diaper-like technology.
10/11. Evaluate stalled but healable chronicwoundsVedge effect: when to use advancedtherapies.Healable wounds should be 30% smaller by week 4 to heal by
week 12. If a wound has not healed at the expected rate, it
may be stalled. Advanced therapies can be considered in these
circumstances and include advanced wound care matrices, a
group of cellular (living cells) or acellular (biologically inert)
products derived from biological (animal, human, or plant),
synthetic, or composite (combined) sources.27 Unfortunately, the
evidence to date for these therapies has resulted from studies of
other chronic wounds and has not been evaluated in wounds on
patients with EB.7 Apligraf and Dermagraft are living skin sub-
stitutes, both supplying a dermal layer with fibroblasts and colla-
gen, which produce matrix proteins. Apligraf also has an epidermal
layer produced from multiplying keratinocytes forming a replicated
architecture of human epidermis. Studies of the use of Apligraf and
Dermagraft in EB have shown promising effects,4 but further eval-
uation needs to be completed to demonstrate cost-effectiveness
in patients with EB to facilitate healthcare system coverage.
12. Healthcare system support.The treatment of EB is complex and requires a host of inter-
professional team members for optimal care (Figure 4).
ADVANCES IN SKIN & WOUND CARE & VOL. 26 NO. 4 186 WWW.WOUNDCAREJOURNAL.COM
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Over the past decade, EB specialized clinics have opened in
16 countries. Other resources exist in DebRA programs world-
wide (http://www.debra.org/international) or through http://www.
internationalebforum.org/index.php?id=16.
Each new case requires a diagnosis and typing or subtyping
as soon as possible. Healthcare systems need to build support
networks such as the one established in the United Kingdom
that provides ongoing support from knowledgeable practition-
ers. Families need to regroup, and healthcare providers need to
be flexible to build trust and improve patient outcomes.
SUMMARYEpidermolysis bullosa is a highly complex, multisystem disease,
with severe EB types having devastating effects on the quality of
life and life span of affected patients and their families. Wound
care requires an interprofessional coordinated approach that ad-
dresses the patient as a whole. The authors have brought together
experts in the field of EB, the science of wound care, and clinical
wound care practice to provide the best available approaches for
optimal wound care to people with EB. Until a definitive cure be-
comes available, these practice goals are to minimize suffering, im-
prove wound healing, and prepare patients for potential corrective
procedures, thereby improving the lives of affected individuals.&
REFERENCES1. Fine JD, Eady RA, Bauer EA, et al. The classification of inherited epidermolysis bullosa
(EB): report of the Third International Consensus Meeting on Diagnosis and Classification
of EB. J Am Acad Dermatol 2008;58:931-50.
2. Pope E, Lara-Corrales I, Mellerio J, et al. A consensus approach to wound care in
epidermolysis bullosa. J Am Acad Dermatol 2012;67:904-17.
3. Fivenson DP, Scherschun L, Choucair M, et al. Graftskin therapy in epidermolysis bullosa.
J Am Acad Dermatol 2003;48:886-92.
Figure 4.
PATIENT, FAMILY & CIRCLE OF CARE
PRACTICE PEARLS
& Epidermolysis bullosa is a rare group of inherited diseaseswith 4 subtypes that serves as a model for a fragile skin.
& Junctional and recessive dystrophic variants of EB develop
chronic wounds.
& The Wound Bed Preparation paradigm can be used as a
guide to the management of EB associated chronic wounds
(including hemoglobin > 80 and albumin > 2.0).
& Pain and itch are often more important to patients thanhealthcare providers (consider soft silicone dressings, ap-
propriate systemic therapy).
& Atypical nonhealing ulcers should be biopsied to rule out
squamous cell carcinoma.
& Gene therapy and skin equivalents along with other active
therapies may have an important future role in the manage-
ment of EB.
ADVANCES IN SKIN & WOUND CARE & APRIL 2013187WWW.WOUNDCAREJOURNAL.COM
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
4. Sibbald RG, Zuker R, Coutts P, Coelho S, Williamson D, Queen D. Using a dermal skin
substitute in the treatment of chronic wounds secondary to recessive dystrophic epidermolysis
bullosa: a case series. Ostomy Wound Manage 2005;51(11):22-46.
5. Sibbald RG, Orsted H, Schultz GS, Coutts P, Keast D; International Wound Bed Preparation
Advisory Board; Canadian Chronic Wound Advisory Board. Preparing the wound bed 2003:
focus on infection and inflammation. Ostomy Wound Manage 2003;49(11):23-51.
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preparation. Adv Skin Wound Care 2006;19:506-17.
7. Sibbald RG, Goodman L, Woo KY, et al. Special considerations in wound bed preparation
2011: an update. Adv Skin Wound Care 2011;24:415-36.
8. Kiuru M, Itoh M, Cairo MS, Christiano AM. Bone marrow stem cell therapy for recessive
dystrophic epidermolysis bullosa. Dermatol Clin 2010;28:371-82.
9. Wagner JE, Ishida-Yamamoto A, McGrath JA, et al. Bone marrow transplantation for recessive
dystrophic epidermolysis bullosa. N Engl J Med 2010;363:629-39.
10. Sibbald RG, Krasner DL, Lutz J. SCALE: Skin Changes at Life’s End: final consensus statement:
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fication. Clin Dermatol 2012;30:70-7.
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epidermolysis bullosa. J Invest Dermatol 2008;128:2179-89.
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correlates with fragmentation of serum albumin but not ceruloplasmin, transferrin, or
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66:264-70.
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