You have been logged out of VisualDx or your session has expired.

Please reload this page and sign into VisualDx to continue.

  VisualDx Mobile   Select Language

Get VisualDx Mobile

There are VisualDx mobile apps available for iOS and Android devices.

You will need a VisualDx account to use the mobile apps.

Already have an account? Sign In or
sign up for a free trial.

Users with VisualDx accounts earn CME credits for using VisualDx.

Already have an account? Sign In or
sign up for a free trial.

Create a Personal Account

E-mail (username)
Verify Password
First Name
Last Name

Personal Account Created

Mobile Access

You can now download VisualDx for your iOS and Android devices. Launch the VisualDx app from your device and sign in using your VisualDx personal account username and password.

CME Certification

Sign in with your personal account to earn and claim CME credits through VisualDx. Credits can be earned by building a differential or looking up a diagnosis.

Version: 7.13.1441   (build df7aed4)
Select Language

Select Region

Send us your feedback

This field is required

Oops! There was an issue during submission. Please try again. If the problem persists, email with your feedback.

Thank You!

We appreciate your feedback and you will be hearing from us soon.


Share This Page

Thank You!

We have sent an e-mail with a link to the current page.


E-mail This Patient Information Sheet

Thank You!

We have sent an e-mail with this patient information.


Image Contributors


  • Christine Ahn MD
    Carl Allen DDS, MSD
    Brandon Ayres MD
    Howard P. Baden MD
    Robert Baran MD
    Keira Barr MD
    Gregory J. Basura MD, Ph.D
    Donald Belsito MD
    Jeffrey D. Bernhard MD
    Jesse Berry MD
    Victor Blanco MD
    Benjamin R. Bohaty MD
    William Bonnez MD
    Sarah Brenner MD
    Robert A. Briggaman MD
    Robert Brodell MD
    Roman Bronfenbrener MD
    Walter Brooks MD
    William Buckley MD
    Philip Bulterys MD, PhD (candidate)
    Susan Burgin MD
    Sonya Burton MD
    Sean P. Bush MD, FACEP
    Jeffrey Callen MD
    Scott Camazine MD
    Michael Cardwell
    Shelley D. Cathcart MD
    Robert Chalmers MD, MRCP, FRCP
    Chia-Yu Chu MD, PhD
    Flavio Ciferri MD
    Maria Rosa Cordisco MD
    Noah Craft MD, PhD
    John T. Crissey MD
    Harold E. Cross MD, PhD
    Charles E. Crutchfield III MD
    Adriana Cruz MD
    Donna Culton MD, PhD
    Bart J. Currie MBBS, FRACP, DTM&H
    Chicky Dadlani MD
    Alexander Dane DO
    C. Ralph Daniel III MD
    Thomas Darling MD, PhD
    William Delaney MD
    Damian P. DiCostanzo MD
    Ncoza Dlova MD
    James Earls MD
    Libby Edwards MD
    Melissa K. Egge MD
    Charles N. Ellis MD
    Rachel Ellis MD
    David Elpern MD
    Nancy Esterly MD
    Stephen Estes MD
    E. Dale Everett MD
    Janet Fairley MD
    David Feingold MD
    Jennifer J. Findeis-Hosey MD
    Benjamin Fisher MD
    Henry Foong MBBS, FRCP
    David Foster MD, MPH
    Brian D. Foy PhD
    Michael Franzblau MD
    Vincent Fulginiti MD
    Sunir J. Garg MD, FACS
    Kevin J. Geary MD
    Lowell Goldsmith MD, MPH
    Sethuraman Gomathy MD
    Bernardo Gontijo MD, PhD
    Kenneth Greer MD
    Kenneth G. Gross MD
    Alan Gruber MD
    Nathan D. Gundacker MD
    Akshya Gupta MD
    Vidal Haddad MSC, PhD, MD
    Edward Halperin MD, MA
    Ronald Hansen MD
    John Harvey
    Rizwan Hassan MD
    Michael Hawke MD
    Jason E. Hawkes MD
    Peter W. Heald MD
    David G. Hicks MD
    Sarah Hocker DO
    Ryan J. Hoefen MD, PhD
    Li-Yang Hsu MD
    William Huang MD
    Sanjana Iyengar MD
    Alvin H. Jacobs MD
    Saagar Jadeja MD
    Shahbaz A. Janjua MD
    Joshua J. Jarvis MD
    Kit Johnson
    Zachary John Jones MD
    Robert Kalb MD
    A. Paul Kelly MD
    Henry Kempe MD
    Loren Ketai MD
    Sidney Klaus MD
    Ashwin Kosambia MD
    Jessica A. Kozel MD
    Carl Krucke
    Mario E. Lacouture MD
    Joseph Lam MD
    Alfred T. Lane MD
    Edith Lederman MD
    Nahyoung Grace Lee MD
    Pedro Legua MD, PhD
    Robert Levin MD
    Bethany Lewis MD
    Sue Lewis-Jones FRCP, FRCPCH
    Taisheng Li MD
    Christine Liang MD
    Shari Lipner MD, PhD
    Adam Lipworth MD
    Jason Maguire MD
    Mark Malek MD, MPH
    Jere Mammino DO
    Ricardo Mandojana MD
    Lynne Margesson MD
    Thomas J. Marrie MD
    Maydel Martinez MD
    Ralph Massey MD
    Patrick McCleskey MD
    Karen McKoy MD
    Thomas McMeekin MD
    Josette McMichael MD
    Somchai Meesiri MD
    Joseph F. Merola MD
    Mary Gail Mercurio MD
    Anis Miladi MD
    Larry E. Millikan MD
    Dan Milner Jr. MD
    Zaw Min MD
    Stephanie Montero
    Alastair Moore MD
    Keith Morley MD
    Dean Morrell MD
    Samuel Moschella MD
    Rehan Naseemuddin MD
    Taimor Nawaz MD
    Vic Newcomer MD
    John Nguyen MD
    Matilda Nicholas MD
    Thomas P. Nigra MD
    Steven Oberlender MD, PhD
    Maria Teresa Ochoa MD
    Art Papier MD
    Lawrence Parish MD
    Tanner Parrent MD
    Mukesh Patel MD
    Lauren Patty-Daskivich MD
    David Peng MD, MPH
    Robert Penne MD
    Nitipong Permpalung MD
    Miriam Pomeranz MD
    Doug Powell MD
    Harold S. Rabinovitz MD
    Christopher J. Rapuano MD
    Sireesha Reddy MD
    Angela Restrepo MD, PhD
    Bertrand Richert MD, PhD
    J. Martin Rodriguez, MD, FACP
    Theodore Rosen MD
    Misha Rosenbach MD
    Scott Schiffman MD
    Robert H. Schosser MD
    Glynis A. Scott MD
    Carlos Seas MD, MSc
    Deniz Seçkin MD
    Daniel Sexton MD
    Paul K. Shitabata MD
    Tor Shwayder MD, FAAP, FAAD
    Elaine Siegfried MD
    Gene Sienkiewicz MD
    Christye Sisson
    Philip I. Song MD
    Mary J. Spencer MD, FAAP
    Lawrence B. Stack MD
    Sarah Stein MD
    William Van Stoecker MD
    Frances J. Storrs MD
    Erik J. Stratman MD
    Lindsay C. Strowd MD
    Erika Summers MD
    Belinda Tan MD, PhD
    Robert Tomsick MD
    Hensin Tsao MD, PhD
    Richard P. Usatine MD
    Jenny Valverde MD
    Vishalakshi Viswanath MD
    Susan Voci MD
    Lisa Wallin ANP, FCCWS
    Douglas Walsh MD
    Ryan R. Walsh MD
    George Watt MD
    Clayton E. Wheeler MD
    Sally-Ann Whelan MS, NP, CWOCN
    Jan Willems MD, PhD
    James Henry Willig MD, MPH
    Karen Wiss MD
    Vivian Wong MD, PhD
    Sook-Bin Woo MS, DMD, MMSc
    Jamie Woodcock MD
    Stephen J. Xenias MD
    Nathaniel Yohannes
    Lisa Zaba MD
    Vijay Zawar MD
    Bonnnie Zhang MD
    Carolyn Ziemer MD
    Jeffrey P. Zwerner MD, PhD


  • Am. Journal of Trop. Med & Hygiene
  • Armed Forces Pest Management Board
  • Blackwell Publishing
  • Bugwood Network
  • Centers For Disease Control and Prevention
  • Centro Internacional de Entrenamiento e Investigaciones Mèdicas (CIDEIM)
  • Dermatology Online Journal
  • East Carolina University (ECU), Division of Dermatology
  • International Atomic Energy Agency
  • Massachusetts Medical Society
  • Oxford University Press
  • Radiological Society of North America
  • Washington Hospital Center
  • Wikipedia
  • World Health Organization
ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyReferencesView all Images (43)
Emergency: requires immediate attention
Junctional epidermolysis bullosa in Infant/Neonate
Other Resources UpToDate PubMed
Emergency: requires immediate attention

Junctional epidermolysis bullosa in Infant/Neonate

Print Images (43)
Contributors: Jo-David Fine MD, MPH, Lowell A. Goldsmith MD, MPH
Other Resources UpToDate PubMed


Junctional epidermolysis bullosa (JEB) is one of the four major types of epidermolysis bullosa (others include EB simplex, dystrophic EB, and Kindler syndrome) and, like all other types of EB, is a genodermatosis characterized by inherently fragile skin that blisters following minor traction to its surface. With only one reported kindred as an exception, all forms of JEB are transmitted as autosomal recessive traits, each subtype of JEB resulting from a mutation within one of the genes encoding for proteins that play an integral role in maintaining adhesion of the epidermis to the underlying dermis. The ultrastructural locations for these JEB-associated proteins are within the upper half (lamina lucida) of the skin basement membrane zone (dermoepidermal junction) or the hemidesmosome, the latter of which is a cell membrane-associated structure lying directly above the lamina lucida.

All patients with the most severe subtype of generalized JEB, JEB-Herlitz (JEB-H, previously referred to as EB letalis or EB atrophicans generalisata gravis), have mutations within any of the three genes corresponding to the three subunits of the cross-configured extracellular matrix protein laminin-332 (previously named laminin-5). Similarly, the majority of JEB patients with generalized but clinically less severe disease (JEB-non Herlitz [JEB-nH], previously named generalized atrophic benign EB [GABEB] or EB atrophicans generalisata mitis) have structurally less severe mutations within the same three laminin-332 genes. A minority of JEB-nH patients have their mutations instead within the gene encoding for type XVII collagen, which is the same protein that is the primary autoantigen in patients with bullous pemphigoid. Rare subtypes of JEB may have mutations within the genes encoding for other structural proteins residing near or within the hemidesmosome, the most notable example being patients with JEB associated with pyloric atresia (JEB-PA); these patients have their mutations within either of the two genes encoding for the two subunits of a6b4 integrin. A rare genodermatosis named the laryngo-onycho-cutaneous syndrome (LOC syndrome, previously named Shabbir syndrome), which was recently included among the subtypes of JEB, is notable for having mutations within the gene encoding for the a3 chain of laminin-332. Autosomal recessive mutations of integrin alpha-3 (ITGA3) are associated with junctional skin lesions, interstitial skin disease, and the nephrotic syndrome.

The three most common subtypes of JEB are JEB-H (Herlitz), JEB-nH (non-Herlitz), and JEB inversa, the latter of which is characterized by cutaneous disease activity primarily localized symmetrically to body folds (axillary and inguinal vaults, perineum), nape of the neck, and the lumbosacral area. Both JEB-H and JEB-nH are usually associated with generalized blisters, erosions, atrophic scars, and oftentimes extensive postinflammatory hypo- or depigmentation. A characteristic, if not pathognomonic, finding in JEB-H is the development of thick exuberant granulation tissue in periorificial array, as well as within the nares, upper back and nape of the neck, and periungual folds. The same process may eventually totally occlude the nasal passage and even progress into the uppermost airway. Patients with JEB-H invariably have profound growth retardation and severe multifactorial anemia. The oral cavity and upper esophagus are oftentimes severely affected in JEB-H, as well as in JEB inversa. Findings may include marked microstomia, ankyloglossia, and primary enamel hypoplasia, the latter resulting in pitting of the teeth, severe secondary caries, and eventual premature loss of most or all of the primary and permanent teeth. Esophageal stenoses or strictures may occur in JEB, similar to those seen in severe generalized recessive dystrophic EB. Scarring alopecia of the scalp and delayed puberty are common features of JEB-H. Only about 3% of these patients develop even partial webbing deformities of the hands or feet compared with patients with severe generalized recessive dystrophic EB, who invariably get this deforming musculoskeletal complication.

JEB-nH can be contrasted to JEB-H by the infrequency of clinically significant growth impairment or anemia, lack of exuberant granulation tissue, and relatively mild intraoral disease activity.

Since the characteristic distinguishing clinical features of JEB-H and JEB-nH may not become obvious for at least the first 1-2 years of life, some authorities prefer to classify those children as having a "JEB indeterminant subtype" pending more definitive clinical or laboratory data that will allow more precise subclassification and prognostication.

Infants with both JEB-H and JEB-nH run significant risk of death during the first few years of life from sepsis, failure to thrive, and/or upper airway obstruction. As an example, approximately half of all JEB children enrolled in the National (United States) EB Registry died within their first year of life. Tracheolaryngeal obstruction particularly is a major threat in both of these JEB subtypes; the risk may persist until as late as about age 6. The earliest sign of tracheolaryngeal involvement is a persistent hoarse or weak cry. If progressive, stridor and sudden (and often fatal) airway obstruction may occur. This is a potential complication that must be carefully watched for, so that lifesaving intervention can be implemented.

As opposed to recessive dystrophic EB, eventual development of potentially lethal squamous cell carcinomas or renal failure are rarely seen in JEB, although these low frequencies may at least in part reflect the limited number of children with generalized JEB who live beyond earliest young adulthood.

The external eye may also be involved in both JEB-H and JEB-nH, resulting in acute onset of severe pain and blistering. If untreated, corneal scarring and even blindness may rarely ensue.

JEB-PA (associated with pyloric atresia) is a very rare EB subtype that can be readily diagnosed during the first day of life, on the basis of clinical and radiological findings of pyloric atresia. Some of these patients also have a variety of genitourinary tract anomalies.

The cutaneous involvement in LOC syndrome (laryngo-onycho-cutaneous syndrome) predominantly involves the facial and neck regions and is associated with particularly severe involvement of the larynx and conjunctiva.

For more information on JEB-H, see OMIM.

For more information on JEB-nH, see OMIM.

Related topics: Generalized severe epidermolysis bullosa simplex, Epidermolysis bullosa acquisita


Q81.8 – Other epidermolysis bullosa

399971009 – Junctional epidermolysis bullosa

Look For

Subscription Required

Diagnostic Pearls

Subscription Required

Differential Diagnosis & Pitfalls

The diagnosis of JEB-H is easily made on clinical grounds alone in older children. Similarly, inverse EB (to include both junctional and recessive EB subtypes) can be made solely on the basis of the unique distribution of lesions in adults.

In neonates and infants, however, the differential diagnosis of any child suspected of having JEB may include but not be confined to:
Onset of inherited EB during childhood may also be confused with several autoimmune bullous diseases (such as bullous pemphigoid and EB acquisita).

Best Tests

Subscription Required

Management Pearls

Subscription Required


Subscription Required


Subscription Required

Last Updated: 08/31/2018
Copyright © 2018 VisualDx®. All rights reserved.
Emergency: requires immediate attention
Junctional epidermolysis bullosa in Infant/Neonate
Print 43 Images Filter Images
View all Images (43)
(with subscription)
Junctional epidermolysis bullosa : Bullae, Hoarseness, Intertriginous, Oral mucosa, Posterior neck, Anemia, Skin erosions, Atrophic scars
Clinical image of Junctional epidermolysis bullosa
Copyright © 2018 VisualDx®. All rights reserved.