Pediatric Epidermolysis Bullosa Clinical Presentation

Updated: Feb 07, 2017
  • Author: Surasak Puvabanditsin, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Important findings in epidermolysis bullosa (EB) include the age of onset; the size, frequency, and location of blisters; and the possible inciting factors (eg, heat, trauma).

Check for a family history of blistering disease and for the patient's geographic and racial ancestry. Evaluation of any patient with suspected epidermolysis bullosa should include mapping of the family's pedigree. However, an absence of affected family members does not, by itself, establish that the mode of transmission is autosomal recessive because apparently isolated cases can be due to spontaneous mutation or incomplete penetrance of an autosomal dominant trait.

Review of systems should include a search for mucosal involvement, including oral, nasopharyngeal, ocular, genitourinary, GI, and respiratory symptoms.

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Physical Examination

Perform a complete physical examination with emphasis on inspecting all skin areas and mucosal surfaces. Evaluate the size, location, and character of the blisters and determine the level at which the blister forms.

Examine the patient for involvement of the nails, hair, or teeth.

Areas prone to blistering due to pressure, trauma, or excessive heating include the fingers, hands, elbows, feet, legs, and diaper area (in infants). See the images below.

Ruptured bulla and newly erupted bulla of the leg Ruptured bulla and newly erupted bulla of the leg in a newborn with epidermolysis bullosa simplex (EBS).
Dystrophic epidermolysis bullosa (DEB) with multip Dystrophic epidermolysis bullosa (DEB) with multiple blisters and erosions.
Dystrophic epidermolysis bullosa (DEB) with genera Dystrophic epidermolysis bullosa (DEB) with generalized blistering and erosion.
Dystrophic epidermolysis bullosa (DEB) that subseq Dystrophic epidermolysis bullosa (DEB) that subsequently healed, with scarring.
Junctional epidermolysis bullosa (JEB). Image show Junctional epidermolysis bullosa (JEB). Image shows a newborn with bulla of the finger, the usual site of blistering secondary to trauma.
Dystrophic nails in a neonate with junctional epid Dystrophic nails in a neonate with junctional epidermolysis bullosa (EB).
Ruptured bullae on the abdomen in a neonate with j Ruptured bullae on the abdomen in a neonate with junctional epidermolysis bullosa (JEB).
A large bullae on the elbow in a neonate with junc A large bullae on the elbow in a neonate with junctional epidermolysis bullosa (JEB).
Ruptured bulla of the hand in a newborn with epide Ruptured bulla of the hand in a newborn with epidermolysis bullosa simplex (EBS).

Congenital localized absence of skin is now known to be a phenotypic pattern that neonates with any major form of epidermolysis bullosa may demonstrate at birth. See the images below.

Junctional epidermolysis bullosa (JEB) with an ass Junctional epidermolysis bullosa (JEB) with an associated defect of a congenital absence of the skin.
Junctional epidermolysis bullosa (JEB) with an ass Junctional epidermolysis bullosa (JEB) with an associated defect of a congenital absence of the skin and an ear anomaly.
Congenital localized absence of skin, nose, in a n Congenital localized absence of skin, nose, in a neonate with junctional epidermolysis bullosa (JEB).
Congenital localized absence of skin on the scrotu Congenital localized absence of skin on the scrotum in a neonate with junctional epidermolysis bullosa (JEB). Absence of the foreskin was also noted.
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Causes

Genetics

Most subtypes of epidermolysis bullosa simplex (EBS) are autosomal dominant disorders; rare patients with autosomal recessive have been reported. [21]

Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder.

Dystrophic epidermolysis bullosa (DEB) is either autosomal dominant or autosomal recessive.

Kindler syndrome is an autosomal recessive disorder. [22]

Types of epidermolysis bullosa and associated characteristics are outlined in the tables below. [23]

Table 1. Morphologic and molecular features of Major Types and Subtypes of Epidermolysis Bullosa (Open Table in a new window)

Type or Subtype

Level of Blister Formation

Protein Affected and Immunofluorescence Staining Pattern

Epidermolysis bullosa simplex (EBS)

Suprabasal

Suprabasal epidermis

Transglutaminase 5: Normal, reduced, or absent

 

 

Desmoplakin: Reduced or absent

 

 

 Plakoglobin: Reduced or absent

 

 

Plakophilin 1: Reduced or absent

 

Basal epidermis

Keratin 5 or keratin 14: Usually normal

 

 

Exophilin 5: Absent

 

 

Plectin: Reduced or absent

 

 

Bullous pemphigoid antigen-1: Absent

Junctional epidermolysis bullosa (JEB)

JEB, generalized severe

Intralamina lucida

Laminin-332: Absent or markedly reduced

JEB, generalized intermediate

Intralamina lucida

Laminin-332: Reduced

JEB with pyloric atresia

Intralamina lucida

Type XVII collagen: Reduced or absent

 

Intralamina lucida

α6β4 integrin: Absent or markedly reduced

JEB, late onset

Intralamina lucida

Type XVII collagen: Reduced or abnormal pattern

JEB with respiratory and renal involvement

Intralamina lucida

α6β4 integrin: Absent or normal

JEB, localized

Intralamina lucida

Type XVII collagen: Reduced or absent

 

 

α6β4 integrin: Reduced

 

 

Laminin-332: Reduced

JEB-inversa

Intralamina lucida

Laminin-332: Reduced

JEB-LOC syndrome

(LOC, laryngo-onycho-cutaneous)

No blistering

Laminin-332: Normal

Dominant dystrophic epidermolysis bullosa (DDEB)

All subtypes

Sublamina densa (dermal)

Type XVII collagen: normal or reduced 

Bullous dermolysis of the newborn

Sublamina densa (dermal)

Type XVII collagen: Granular staining within basal keatinocytes; reduced/absent staining along dermoepidermal junction during active disease; normal staining along dermoepidermal junction during inactive disease

Recessive dystrophic epidermolysis bullosa (RDEB)

Bullous dermolysis of the newborn

Sublamina densa (dermal)

Type XVII collagen: Granular staining within basal keatinocytes; reduced/absent staining along dermoepidermal junction during active disease; normal staining along dermoepidermal junction during inactive disease

Generalized  severe 

Sublamina densa (dermal)

Type XVII collagen: Absent or markedly reduced 

Generalized intermediate

Sublamina densa (dermal)

Type XVII collagen: Reduced 

Localized

Sublamina densa (dermal)

Type XVII collagen: Normal or reduced or normal

All other subtypes

Sublamina densa (dermal)

Type XVII collagen: Reduced 

Table 2. Major Epidermolysis Bullosa Types and Subtypes (Open Table in a new window)

Level of Skin Cleavage

Major Type

Known Targeted Protein

Intraepidermal 

Suprabasal epidermolysis bullosa simplex

Transglutaminase 5; plakophillin 1 desmoplakin; plakoglobin

 

Basal epidermolysis bullosa simplex

Keratins 5 and 14; plectin; exophilin 5(Slac2-b); bullous pemphigoid antigen1

Intralamina lucida

Junctional epidermolysis bullosa, generalized

Laminin-332; type XVII collagen; α6β4 integrin; α3 integrin

 

Junctional epidermolysis bullosa, localized

Type XVII collagen; laminin-332;  α6β4 integrin

Sublamina densa 

Dominant dystrophic epidermolysis bullosa

Type VII collagen

 

Recessive dystrophic epidermolysis bullosa

Type VII collagen

Mixed

Kindler syndrome

Kindlin-1

Table 3. Mutational Analyses and Inherited Epidermolysis Bullosa [24, 25, 26] (Open Table in a new window)

Epidermolysis Bullosa Subtype

Target Gene (Protein)

Types of Known Mutations

Epidermolysis bullosa simplex (EBS) - Suprabasal

PKP1 (plakophilin1)

Splice site, nonsense, deletion, deletion/insertion, insertion

 

DSP (desmoplakin)

Nonsense, deletion, missense

 

TGMS

Missense, deletion, deletion/insertion

 

JUP

Nonsense, splice site

EBS - Basal

KRT5 (keratin-5)

Missense, deletion, splice site,  nonsense, deletion/insertion

 

KRT14 (keratin-14)

Missense,  deletion, nonsense, splice site, deletion/insertion, insertion

 

PLEC (plectin)

 Nonsense, deletion, insertion, deletion/insertion, splice site, missense,

 

EXPH5

Deletion, nonsense, insertion

 

DST

Nonsense

Junctional epidermolysis bullosa (JEB)  - Generalized

LAMA3

Nonsense, deletion, splice site

 

LAMB3

Nonsense, deletion, splice site, insertion,

 

LAMC2 

Nonsense, deletion, splice site, deletion/insertion

JEB,  generalized/localized

LAMA3 

Missense, nonsense, insertion, splice site

 

LAMB3

Missense, nonsense, splice site, deletion, insertion, deletion/insertion

 

LAMC2 

Nonsense, deletion, deletion/insertion, insertion, splice site

 

COL17A1 (type XVII collagen)

Nonsense, deletion, splice site, insertion, missense

 

ITGB4 (α6β4 integrin)

Deletion, splice site, missense

JEB, late onset 

COL17A1 (type XVII collagen)

Missense

JEB with pyloric atresia

ITGB4 (α6β4 integrin)

 

Nonsense, missense, deletion, splice site, insertion deletion/insertion

 

ITGA6

Deletion, missense, nonsense, splice site

JEB with pyloric atresia

ITGA3

Missense, deletion, splice site

JEB with respiratory and renal involvement

LAMA3A

Insertion, nonsense

JEB, severe generalized

COL17A1 (type VII collagen)

Nonsense, deletion,  splice site, insertion, deletion/insertion, missense,

Dystrophic epidermolysis bullosa, generalized and localized

COL17A1 (type VII collagen)

Missense, nonsense, deletion, insertion, splice site, deletion/insertion

Dystrophic epidermolysis bullosa (all subtypes)

COL17A1 (type VII collagen)

Missense, splice site, deletion

Kindler syndrome

KIND1 (kindling-1)

Nonsense, deletion, splice site, insertion, deletion/insertion

Table 4. Major Epidermolysis Bullosa Subtypes and Their Targeted Proteins (2008 International Consensus Report [27] ) (Open Table in a new window)

Major Epidermolysis Bullosa Type

Major  Epidermolysis Bullosa  Subtypes

Targeted Protein(s)

Epidermolysis bullosa simplex (EBS)

Suprabasal subtypes

 

 

Acantholytic EBS (EBS-acanth)

Desmoplakin, plakoglobin

 

Acral peeling skin syndrome (APSS)

Transglutaminase 5

 

EBS superficialis (EBSS)

Unknown

 

Plakophilin-1 deficiency

Plakophilin-1

 

Plakoglobin deficiency (EBS-plakoglobin)

Plakoglobin

 

Desmoplakin deficiency (EBS-desmoplakin)

Desmoplakin

 

Basal subtypes

 

 

EBS, localized (EBS-loc)

K5, K14

 

EBS, generalized severe (EBS-gen sev)

K5, K14

 

EBS, generalized intermediate (EBS-gen intermed)

K5, K14

 

EBS with mottled pigmentation (EBS-MP)

K5

 

EBS with migratory circinate (EBS-migr)

Plectin

 

EBS with pyloric atresia (EBS-PA)

Plectin; α6β4 integrin

 

EBS, autosomal recessive K14 (EBS-AR K14)

K14

 

EBS with muscular dystrophy (EBS-MD)

Plectin

 

EBS, Ogna (EBS-Og)

Plectin

 

EBS, migratory circinate (EBS-migr)

K5

 

EBS, autosomal recessive-BP230 deficiency

(EBS-AR BP230)

Bullous pemphigoid antigen-1 (BP230)

 

EBS, autosomal recessive-exophilin 5 deficiency

(EBS-AR exophilin 5)BP230

Exophilin 5

Junctional epidermolysis bullosa (JEB)

JEB, generalized severe (JEB-gen sev)

laminin-332

 

JEB, generalized intermediate (JEB-gen intermed)

laminin-332; type XVII collagen

 

JEB late onset (JEB-LO)

type XVII collagen

 

JEB with pyloric atresia (JEB-PA)

α6β4 integrin

 

JEB, with respiratory and renal involvement (JEB-RR)

α3 integrin

 

JEB localized (JEB-loc)

type VII collagen, α6β4 integrin, 

laminin-332

 

JEB, inversa (JEB-inv; JEB-I)

laminin-332

 

JEB-LOC syndrome

laminin-332, isoform α3 chain

Dominant dystrophic epidermolysis bullosa (DDEB)

DDEB, generalized (DDEB-gen)

type VII collagen 

 

DDEB, acral (DDEB-ac)

type VII collagen

 

DDEB, pretibial (DDEB-Pt)

type VII collagen

 

DDEB, pruriginosa (DDEB-Pr)

type VII collagen

 

DDEB, nails only (DDEB-na)

type VII collagen

 

DDEB, bullous dermolysis of newborn (DDEB-BDN)

type VII collagen

Recessive dystrophic epidermolysis bullosa (RDEB)

RDEB, severe generalized (RDEB-sev gen)

type VII collagen

 

RDEB, generalized other (RDEB, generalized mitis (RDEB-O)

type VII collagen

 

RDEB, inversa (RDEB-I)

type VII collagen

 

RDEB, pretibial (RDEB-Pt)

type VII collagen

 

RDEB, pruriginosa (RDEB-Pr)

type VII collagen

 

RDEB, centripetalis (RDEB-Ce)

type VII collagen

 

RDEB, bullous dermolysis of newborn (RDEB-BDN)

type VII collagen

Kindler syndrome

 

kindlin-1

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Complications

Complications include the following:

  • Secondary infections (eg, pseudomonal, staphylococcal, beta-hemolytic streptococcal, and herpes organisms) [28]

  • Mitten deformities (pseudosyndactyly) of the fingers and toes [21]

  • Scarring of the skin

  • Pigmentary changes

  • Anonychia

  • Dental anomalies

  • GI complications: These may arise within the esophagus, stomach, small and large intestines, rectum, and anus. Esophageal stricture and growth retardation are commonly reported in patients with the more severe epidermolysis bullosa subtype. [29, 30, 31]

  • Genitourinary tract complications: These include urethral meatal stenosis, urinary retention, bladder hypertrophy, hydronephrosis secondary to ureteral strictures, pyelonephritis, and cystitis. The complications occur in a minority of patients across all major epidermolysis bullosa subtypes, with the highest frequency seen in Herlitz junctional epidermolysis bullosa (JEB-H). [32, 33]

  • Ocular diseases: Ocular diseases in epidermolysis bullosa include corneal erosions or blistering, corneal scarring, cornea opacity, cornea ulcerations, symblepharons, blepharitis, ectropions, red watery eyes, photophobia, conjunctival injection, conjunctival edema, limbal broadening, pannus formation, ectropions, ocular pain, lacrimal duct obstruction, impair vision, and blindness. [34] The most common complications include corneal erosions and blisters, and frequencies mirror relative severity of the skin disease.

  • Ear, nose, and throat: These complications include tracheolaryngeal stenosis or stricture, chronic otitis media, chronic otitis externa, and hearing loss. [35]

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