DEPARTMENT
Newborn Infant With
Epidermolysis Bullosa
and Ankyloglossia
Ashley McPhie, MD, Kimberly Merkel, MD, Michele Lossius, MD,
Beverly P. Giordano, MS, CPNP, PMHS, & Maria N. Kelly, MD
KEY WORDS
Epidermolysis bullosa, blisters, pediatrics
A White male newborn was transferred to our
university-based children’s hospital within hours of
his birth for evaluation and management of skin slough-
ing and blistering over several areas of his body. A skin
biopsy demonstrated subepidermal blisters with no
inflammation. Immunomapping suggested the dystro-
phic form of epidermolysis bullosa (EB). Genetic
testing revealed two mutations on the collagen type
VII alpha 1 (COL7A1) gene that had not been reported
previously in association with EB. This case illustrates
the importance and utility of genetic testing to distin-
guish between general types of EB and subtypes. This
Ashley McPhie, Pediatrician, Tampa Family Health Centers,
Tampa, FL.
Kimberly Merkel, Clinical Assistant Professor of Dermatology,
University of Florida, Gainesville, FL.
Michele Lossius, Clinical Associate Professor of Pediatrics,
University of Florida, Gainesville, FL.
Beverly P. Giordano, Pediatric Nurse Practitioner, University of
Florida, Gainesville, FL.
Maria N. Kelly, Clinical Associate Professor Pediatrics, University
of Florida, Gainesville, FL.
Conflicts of interest: None to report.
Correspondence: Beverly P. Giordano, MS, CPNP, PMHS, 1699
SW 16th Ave, Gainesville, FL 32608; e-mail: bgiordano@peds.ufl.
edu.
J Pediatr Health Care. (2016) -, ---.
0891-5245/$36.00
Copyright Q 2016 by the National Association of Pediatric
Nurse Practitioners. Published by Elsevier Inc. All rights
reserved.
http://dx.doi.org/10.1016/j.pedhc.2015.12.005
www.jpedhc.org
Case Study—Primary Care
differentiation is important for prognosis, therapeutic
options, and family planning.
CASE PRESENTATION
The infant was born at a community hospital at
39 week’s gestation via spontaneous vaginal delivery
to a gravida one para one mother with negative serol-
ogies after an uncomplicated pregnancy. Both parents
had histories of genital herpes, but the mother had no
active lesions at the time of delivery.
Upon presentation to our children’s hospital, the in-
fant was noted to have thin lips, a high-arched palate,
and a thick fibrous tissue restriction anchoring his
tongue to the mouth floor. He had numerous multiple
bullae and shallow ulcerations on his face (including
pinna), trunk, arms, and legs, but none on his conjunc-
tiva or pharynx. Most of the bullae were ruptured. Skin
was absent on his feet and ankles, with raw red dermal
tissue present in a stocking distribution (Figures 1 and
2), resembling aplasia cutis congenita. His toenails
were absent, but fingernails were present. None of
the skin lesions had discharge, erythema, or crusting,
suggesting a lack of underlying inflammation or infec-
tion. Several blisters on the chest and arms
corresponded to the placement of monitoring equip-
ment at the birth institution.
The infant weighed 3.4 kg (44th percentile) and
had a length of 51 cm (65th percentile) and a head
circumference of 34 cm (18th percentile). His vital
signs were as follows: temperature, 36.5 C; blood
pressure, 69/48 mmHg; heart rate, 137 beats per min-
ute; and respiratory rate, 35 breaths per minute. He
was alert, active, and in no obvious discomfort. He
was able to move all his extremities and had no
obvious skeletal abnormalities. The remainder of his
examination was normal.
-/- 2016 1
FIGURE 1. Infant’s hand notable for missing skin.
This figure appears in color online at www.jpedhc.
org.
Hospital Course
The infant had been transferred to our children’s hospi-
tal for evaluation of possible EB. The general pediatric
service clinicians confirmed the suspected diagnosis
and consulted the pediatric dermatology service. Our
consultant dermatologist favored a diagnosis of dystro-
phic EB (DEB) based on the infant’s presenting physical
examination (i.e., skin involvement only) and results of
the initial skin biopsy.
During the infant’s hospital admission, he had
feeding difficulties as a result of severe ankyloglossia.
Bottle and breast feedings were creating patchy areas
of erythema and ulceration on the infant’s inner lips
and hard palate. Otolaryngology specialists were con-
sulted regarding the possibility of a frenotomy, but
correction was deferred to minimize complications
FIGURE 2. Raw dermal connective tissue present
in a stocking distribution.
This figure appears in color online at www.jpedhc.
org.
2 Volume -  Number -
from general anesthesia. After consultation with occu-
pational therapy and the nurse practitioner–lactation
consultant, the infant was able to tolerate oral feedings
with a specialty bottle designed for babies with
impaired sucking ability. This feeder is activated by
tongue and gum pressure rather than by sucking,
imitating the mechanics involved in breastfeeding.
Throughout his hospitalization, nursing staff mem-
bers avoided unnecessary contact or procedures, pro-
vided wound care of affected lesions with application
of nonstick dressings, and initiated parental education
about EB and related care. No antibiotics were
applied or administered during the hospitalization,
because there was no concern for infection. Parental
education included introduction to available EB pa-
tient and family resource sites (Box 1) and teaching
sessions with wound care specialists, occupational
therapists, nurses, and the general pediatric and
dermatology teams.
Final Diagnosis
The final skin biopsy results demonstrated subepidermal
blisters with no inflammation, compatible with EB.
Further testing using immunomapping suggested the
dystrophic form of EB, confirming the initial clinical
impression. However, unexpectedly, the infant’s genetic
testing revealed two mutations on the COL7A1 gene.
Mutations in the COL7A1 gene are associated with all
forms of DEB. The infant had a nonsense mutation
(R669X), which is associated with recessive DEB, and
he had a missense mutation (G2245S), which had not
previously been reported to be associated with DEB.
The missense mutation was a glycine substitution for
serine on exon 85. Because the nonsense mutation
was inherited recessively, it was concluded that the in-
fant actually demonstrated a recessive inheritance
pattern. Therefore, based on genetic testing, the infant
received a final diagnosis of recessive DEB (RDEB), not
the initially presumed less-lethal dominant DEB
(DDEB).
DISCUSSION
EB refers to a heterogeneous group of inherited skin
disorders characterized by blister formation and skin
fragility. Although fairly distinct in presentation,
other conditions must also be considered during
evaluation. The differential diagnosis for EB is vast
and includes both infectious and noninfectious dis-
orders (Box 2).
The prevalence and incidence of EB in the United
States is approximately 19 per 1 million live births or 8
per 1 million population (Fine, 2010). The disorder af-
fects both genders equally and occurs in every racial
and ethnic group. With new national registries, the
exact prevalence and incidence of this disease should
be better quantified in the future.
Journal of Pediatric Health Care
BOX 1. Epidermolysis bullosa resources for families and health care professionals

Organizations
 Children’s Skin Disease Foundation: https://www.csdf.org
 ClinicalTrials.gov: http://clinicaltrials.gov (offers up-to-date information for locating federally and privately supported clin-
ical trials for epidermolysis bullosa)
 Debra of America, Inc. (Dystrophic Epidermolysis Bullosa): http://www.debra.org (has a ‘‘new parent’’ program that pro-
vides practical information about wound care, medical supplies, and medical insurance)
 Dermatlas.org: http://www.dermatlas.net (an interactive dermatology atlas that can be searched by diagnosis, lesion
characteristics, patient demographics, and treatments)
 EB Info World: http://blog.ebinfoworld.com (provides feeding suggestions)
 EB Medical Research Foundation: http://www.ebkids.org
 Epidermolysis Bullosa Action Network: http://www.ebanusa.org
 Genetic and Rare Diseases (GARD) Information Center: http://rarediseases.info.nih.gov/GARD
 National Epidermolysis Bullosa Society
 National Institute of Arthritis and Musculoskeletal and Skin Diseases: http://www.niams.nih.gov/Health_info/
epidermolysis_Bullosa
 National Institutes of Health, severe junctional EB clinical trials: prpl@cc.nih.gov; (800) 411-1222
 RareConnect: www.rareconnect.org; http://www.rareconnect.org (patient-hosted online community for patients and
caregivers)
Book
Fine, J. D., & Hintner, H. (Eds.). (2009). Life with epidermolysis bullosa (EB): Etiology, diagnosis, multidisciplinary care and
therapy. New York, NY: Springer Wien.
Camps for Children With Severe Skin Conditions
 Camp Wonder: http://www.csdf.org
 Camp Spirit: www.campspiritcolorado.com
 Camp Discovery: www.aad.org/dermatology-a-to-z/for-kids/camp-discovery

When EB is suspected by physical examination, a or electron microscopy (Gonzalez, 2013; Murrell,

skin biopsy should be obtained from the edge of a fresh 2013). A skin biopsy can help distinguish between the
blister and sent for immunofluorescence mapping and/ major types of EB; however, the subtypes are more
difficult to classify and require genetic investigations.
Genetic testing is available and important for assisting
BOX 2. Differential diagnosis for skin blistering in with patient prognosis and family planning. This
infants and young children testing is expensive and not easily available, but it
remains important in establishing a definitive
Infectious diagnosis, as in our patient (Murrell, 2013).
 Herpes simplex virus Ten different genes have been discovered to have
 Bullous impetigo mutations that lead to the different forms of EB
 Staphylococcal scalded skin syndrome (Sawamura, Nakano, & Matsuzaki, 2010). In particular,
 Neonatal varicella DEB has three further divided phenotypes that are all
 Neonatal candidiasis caused by a mutation on the COL7A1 gene that encodes
 Congenital syphilis
collagen type VII (Sawamura, Nakano, & Matsuzaki,
Noninfectious
2010). Collagen VII is important in anchoring the base-
 Traumatic blisters (sucking blisters)
Genetic ment membrane to the dermis and maintaining skin
 Aplasia cutis congenita (bullous type) integrity. As was present in our patient, glycine substitu-
 Epidermolytic ichthyosis tions are the major mutations being reported in associ-
 Incontinentia pigmenti ation with DEB (Sawamura et al., 2010).
 Epidermolysis bullosa There are four main types of EB: epidermolysis bul-
Autoimmune losa simplex (EBS), junctional epidermolysis bullosa
 Bullous pemphigoid (JEB), dystrophic epidermolysis bullosa (DEB), and
 Pemphigoid gestationis Kindler syndrome, which is a combination of DEB
 Linear IgA bullous dermatosis and congenital poikiloderma (Table). Additional sub-
Other
types are also characterized within each main type.
 Bullous mastocytosis
The main types of EB are defined on the basis of the
 Transient bullous dermolysis of the newborn
location of skin separation or disruption. The severity

www.jpedhc.org -/- 2016 3

 TABLE. Major classifications of epidermolysis bullosa and underlying gene/protein defects
Major type Level of skin cleavage Major subtypes Inheritance Protein
EB simplex Intraepidermal (within the basal keratinocyte) Basilar AD (most) Keratin 5 and 14
Suprabasilar AR Desmoplakin
Plectin
Junctional EB Lamina lucida JEB, Herlitz AR Laminin 332
JEB, non-Herlitz Type XVII collagen
a6 b4 integrin
Dystrophic EB Dermis (sublamina densa) DDEB AD Collagen VII
RDEB AR
Kindler syndrome Varies AR Kindlin-1
Note. AD, autosomal dominant; AR, autosomal recessive; DDEB, dominant dystrophic epidermolysis bullosa; JEB, junctional epidermolysis
bullosa; RDEB, recessive dystrophic epidermolysis bullosa.
From Fine, J.-D., Eady, R. A., Bauer, E. A., Bauer, J. W., Bruckner-Tuderman, L., Heagery, A., . Zambruno, G. (2008). The classification of
inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. Journal of
the American Academy of Dermatology, 58(6), 931-950.

of the subtypes can range from mild to severe within
each of the main types.
DEB has several subtypes that display a range of clin-
ical severity, including DDEB and two forms of RDEB.
RDEB is classified as either severe generalized (RDEB-
sev gen) or RDEB generalized other (RDEB-O;
Sawamura et al., 2010). In DDEB, blistering is usually
less severe and localized to weight-bearing or high-
friction areas such as the hands, feet, knees, and el-
bows; however, it can generalize to other body areas.
RDEB is typically more generalized and severe than
DDEB. As in our patient, affected infants are typically
born with widespread blistering and areas of missing
skin, often caused by birth trauma. Epithelial bullae for-
mation and fragility also affect mucous membranes
such as the conjunctiva, oral mucosa, and digestive
tract. Malformed or missing fingernails and toenails
and scarring with milia formation occur in both types
of DEB. Our patient presented with many of these
classic DEB features.
Our patient had RDEB, the most severe form of this
condition. RDEB is associated with many complica-
tions. Repetitive blister formation and healing can
cause severe scarring and stricture formation. Patients
may experience fusion of the fingers and toes (pseudo-
syndactyly), loss of fingernails and toenails, joint defor-
mities (contractures) that restrict movement, and
corneal scarring with vision loss. Scarring in the mouth
and esophagus can cause difficulty with chewing and
swallowing of food, which can ultimately lead to
chronic malnutrition and affect overall growth. It is
not uncommon for children with RDEB to experience
anemia from blood loss through wounds, poor nutri-
tional intake, poor iron absorption, and bone marrow
suppression from chronic inflammation. They also
may have failure to thrive, recurrent skin infections,
renal disease, esophageal strictures, and osteoporosis.
Patients with RDEB also are at increased risk for
squamous cell carcinoma of the skin, usually occurring
in the third and fourth decades of life (Uitto, McGrath,
Rodeck, Bruckner-Tuderman, & Robinson, 2010).
These complications lead to early mortality, with an
average life span of 30 to 40 years among persons
with RDEB (Intong & Murrell, 2012).
Living with EB can be extremely challenging for both
patients and caretakers. Treatment focuses on manag-
ing wounds, monitoring for potential disease complica-
tions, and improving overall quality of life. Bathing
must be individualized, because children may benefit
from diluted bleach
baths, vinegar soaks, Treatment focuses
or salt baths (Pope
on managing
et al., 2012). Nonstick
dressings must be wounds,
used in areas of blister monitoring for
formation or on skin le-
potential disease
sions. Foam dressings
must be used to protect complications, and
areas of bony promi- improving overall
nence that are at risk
quality of life.
of skin breakdown or
blister formation. Par-
ents must routinely check the children’s skin and be
comfortable identifying areas of potential infection.
Thorough examinations of the skin surface need to be
performed at least every 6 months by a medical profes-
sional (dermatologist or pediatric clinician) familiar
with EB. Skin surface areas to be examined can be
rotated with each visit (Pope et al., 2012).
Primary care providers (PCPs) serve important roles
in the care of children with EB. In addition to moni-
toring the growth and development of these children,
PCPs must screen for complications associated with
EB and serve as gatekeepers for the many specialty re-
ferrals and services these children and their family
members require. PCPs can offer practical guidance

4 Volume -  Number - Journal of Pediatric Health Care

on skin protection. For example, they can recommend CONCLUSION
that parents adjust the children’s clothing by applying EB is a rare, inherited, blistering disorder that is variable
additional padding at the legs and waists of diapers; in the severity of skin findings and clinical course.
dressing children in loose-fitting garments; having chil- Because this disease can mimic other neonatal blistering
dren wear garments inside-out to avoid irritation from lesions, it is important
seams; removing tags, cuffs, and necklines from to obtain a thorough Although genetic
clothing; and purchasing loosely fitted, padded shoes birth and family history testing is
for these children to wear. Parents also can use sheep- to evaluate the sus- expensive, it
skin or foam padding on surfaces (e.g., chairs, car seats, pected disease process.
and beds) that may cause friction. Early dermatologist distinguishes
Patients and their family members require extensive involvement between general
education, beginning with diagnosis and continuing is imperative, and a skin types and subtypes
throughout the child’s life. Resources should include, biopsy can help
but not be limited to, therapists, support groups, and establish an initial diag- of EB, which is
online EB resources. Patients should have access to nosis. Although genetic important and
comprehensive management by dermatologists who testing is expensive, it useful for
specialize in EB (Arbuckle, 2010). distinguishes between
Although no cure for EB currently exists, several general types and sub- prognosis, family
innovative treatment strategies (e.g., gene therapy, pro- types of EB, which is planning, and
tein replacement therapy, and allogenic stem cell trans- important and useful therapeutic
plant) are being offered at some centers. The first stem for prognosis, family
cell transplant in a patient with RDEB was completed in planning, and thera- options.
2007 (Uitto et al., 2010). Other researchers are attempt- peutic options.
ing to prevent genes from expressing faulty keratin. Careful wound care is integral to the care of children
Ova that do not contain EB-producing genes can be with EB. Regular monitoring of the growth and devel-
identified and selected for in vitro fertilization to opment of these children in conjunction with screening
improve chances of having healthy children in families for complications is a critical component of compre-
with the EB gene. hensive pediatric care. Nutritional challenges require
consultation with dietitians, monitoring metabolic
OUTCOME indices, creativity in meal planning, and accommoda-
Our patient has had few problems since being diag- tions in school.
nosed with RDEB. He had one episode of cellulitis Disease education for patients, caretakers, and
that occurred after the initial skin biopsy. He experi- health care providers is essential to prevent unneces-
enced symptoms of esophageal erosions at 1 year of sary stress and trauma for these patients and their
age, but discomfort with feeding resolved when he families. The disease is so rare that most physicians
began taking a proton pump inhibitor. He has seen an and nurses may never encounter a case during their
ophthalmologist for bilateral amblyopia and had a careers and thus may be unable to help these pa-
baseline visit with a pediatric gastroenterologist to tients and families. As one parent stated, ‘‘Imagine
monitor for symptoms of esophageal stricture forma- having to wrap each tiny little infant finger with
tion. He has seen a clinical nutritionist several times Vaseline gauze to prevent scarring and contractures.
for consultation about feeding issues. He has right Imagine a child who will never know what it’s like
hand contractures that prevent a normal grip and wears to run, skip, or jump to play games with other chil-
a splint on this hand at night. dren because even the slightest physical contact will
At his recent 4-year well-child check, he was growing injure his skin. Imagine a child who screams each
appropriately (height, 37th percentile, and weight, time she is bathed, because water touching open
32nd percentile for age). He was taking daily multivi- wounds creates incredible pain. Imagine an active
tamin and iron supplements and ranitidine on an as- baby with blood-soaked knees from the normal act
needed basis. His speech was not all understandable of crawling and a teenager with stumps for hands,
and he was unable to hop or ride a bicycle, but other- caused by scarred fingers’’ (EB Info World, 2015).
wise was developmentally appropriate for his age. He
was up to date on immunizations. His parents changed
his bandages every other day, inspected his skin twice REFERENCES
daily, and rubbed lotion into the skin twice a day. He Arbuckle, H. A. (2010). Epidermolysis bullosa care in the United
States. Dermatologic Clinics, 28(2), 387-389.
had been participating in occupational therapy and EB Info World. (2015). Welcome to EB Info World. Retrieved from
physical therapy until he reached the number of limits http://blog.ebinfoworld.com
authorized per annum by his insurance company. His Fine, J. D. (2010). Inherited epidermolysis bullosa. Orphanet Journal
parents had attended a recent EB conference. of Rare Diseases, 5, 12.

www.jpedhc.org -/- 2016 5

Gonzalez, M. E. (2013). Evaluation and treatment of the newborn with
epidermolysis bullosa. Seminars in Perinatology, 37(1), 32-39.
Intong, L. R. A., & Murrell, D. F. (2012). Inherited epidermolysis bul-
losa: New diagnostic criteria and classification. Clinical Derma-
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Murrell, D. F. (2013). The pitfalls of skin biopsies to diagnose epider-
molysis bullosa. Pediatric Dermatology, 30(2), 273-275.
Pope, E., Lara-Corrales, I., Mellerio, J., Martinez, A., Schultz, G., Bur-
rell, R., . Sibbald, G. (2012). A consensus approach to wound
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care in epidermolysis bullosa. Journal of the American Academy
of Dermatology, 67(5), 904-917.
Sawamura, D., Nakano, H., & Matsuzaki, Y. (2010). Overview
of epidermolysis bullosa. Journal of Dermatology, 37(3), 214-
219.
Uitto, J., McGrath, J. A., Rodeck, U., Bruckner-Tuderman, L., & Rob-
inson, E. C. (2010). Progress in epidermolysis bullosa research:
Toward treatment and cure. Journal of Investigative Derma-
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Journal of Pediatric Health Care