Pediatric Epidermolysis Bullosa Clinical Presentation

  • Author: Surasak Puvabanditsin, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Aug 17, 2011
 

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.
Next

Physical

  • 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 to slit them.
  • 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 multipDystrophic epidermolysis bullosa (DEB) with multiple blisters and erosions. Dystrophic epidermolysis bullosa (DEB) with generaDystrophic epidermolysis bullosa (DEB) with generalized blistering and erosion. Dystrophic epidermolysis bullosa (DEB) that subseqDystrophic epidermolysis bullosa (DEB) that subsequently healed, with scarring. Junctional epidermolysis bullosa (JEB). Image showJunctional 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 epidDystrophic nails in a neonate with junctional epidermolysis bullosa (EB). Ruptured bullae on the abdomen in a neonate with jRuptured bullae on the abdomen in a neonate with junctional epidermolysis bullosa (JEB). A large bullae on the elbow in a neonate with juncA large bullae on the elbow in a neonate with junctional epidermolysis bullosa (JEB). Ruptured bulla of the hand in a newborn with epideRuptured 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 assJunctional epidermolysis bullosa (JEB) with an associated defect of a congenital absence of the skin. Junctional epidermolysis bullosa (JEB) with an assJunctional 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 nCongenital localized absence of skin, nose, in a neonate with junctional epidermolysis bullosa (JEB). Congenital localized absence of skin on the scrotuCongenital localized absence of skin on the scrotum in a neonate with junctional epidermolysis bullosa (JEB). Absence of the foreskin was also noted.
Previous
Next

Causes

Genetics

Most subtypes of epidermolysis bullosa simplex (EBS) are autosomal dominant disorders, rare patients with autosomal recessive have been reported.[16]

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.[17]

Types of epidermolysis bullosa and associated characteristics [7]

Table 1. Ultrastructural Findings of Major Types and Subtypes of Epidermolysis Bullosa (Open Table in a new window)

Type or SubtypeUltrastructural Site of Skin FindingsOther Ultrastructural Findings
Epidermolysis bullosa simplex
LocalizedBasal layerSplit may spread to suprabasilar layer
Dowling-MearaBasal layer in subnuclear cytoplasmDense, circumscribed clumps of keratin Filaments
Muscular dystrophyPredominantly in basal layer, above level of hemidesmosome attachment plaqueReduced integration of keratin filaments with hemidesmosome
Autosomal recessiveBasal keratinocytesAbsent or reduced keratin filaments within basal keratinocytes
SuperficialisSplit usually at interface between granular and cornified cell layers...
Lethal acantholyticSuprabasal cleavage and acantholysisPerinuclear retraction of keratin filaments
Plakophillin-1 deficiencyMid epidermal cell-cell separationDiminutive suprabasal desmosomes, perinuclear retraction of keratin filaments
Pyloric atresia (PA)Lower basal layer, above level of hemidesmosome plaqueReduced integration of keratin filaments with hemidesmosome
Junctional epidermolysis bullosa
HerlitzLamina lucidaMarkedly reduced or absent hemidesmosome, absent sub-basal dense plate
Non-HerlitzLamina lucidaHemidesmosome may be normal or reduced in size and number
Pyloric atresiaLamina lucidaSmall hemidesmosome plaques often with attenuated sub-basal dense plate
Dominant dystrophic epidermolysis bullosa
GeneralizedSub-lamina densaNormal or decreased numbers of anchoring fibrils
Bullous dermolysis of the newbornSub-lamina densaElectron-dense stellate bodies within basal layer, reduced anchoring fibrils
Recessive dystrophic epidermolysis bullosa
Severe generalizedSub-lamina densaAbsent or rudimentary anchoring fibrils
Generalized otherSub-lamina densaReduced or rudimentary-appearing anchoring fibrils
Bullous dermolysis of the newbornSub-lamina densaElectron-dense stellate bodies within basal layer, reduced anchoring fibrils

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

level of Skin CleavageMajor TypeKnown Targeted Protein
Intraepidermal (epidermolytic)Epidermolysis bullosa simplexKeratins 4 and 14; plectin; α6β4 integrin; plakophillin-1 desmoplakin
Intra-lamina lucida (lamina lucidolytic)Junctional epidermolysis bullosaLaminin-332(laminin 5); type XVII collagen; α6β4 integrin
Sub-lamina densa (dermolytic)Dystrophic epidermolysis bullosaType VII collagen
MixedKindler syndromeKindlin-1

Table 3. Mutational Analyses and Inherited Epidermolysis Bullosa (Open Table in a new window)

Epidermolysis Bullosa SubtypeTarget Gene(Protein)Types of Known Mutations
Epidermolysis bullosa simplex - SuprabasalPKP1 (plakophilin1)Splice site, deletion, nonsense
DSP (desmoplakin)Nonsense, deletion
Epidermolysis bullosa simplex - BasalKRT5 (keratin-5)Missense, nonsense, deletion, splice site
KRT14 (keratin-14)Missense, nonsense, deletion, insertion, splice site, in-frame deletion/insertion
PLEC1 (plectin)Missense, nonsense, deletion, insertion, in-frame deletion/insertion
ITGA6, ITGB4 (α6β4 integrin)missense, nonsense, deletion, insertion, splice site
Junctional epidermolysis bullosa - HerlitzLAMA3, LAMB3, LAMC2 (laminin-332)Nonsense, deletion, insertion, splice site
Junctional epidermolysis bullosa - OtherLAMA3, LAMB3, LAMC2 (laminin-332)Missense, nonsense, deletion, insertion, splice site
COL17A1 (type XVII collagen)Missense, nonsense, deletion, insertion, splice site
ITGA6, ITGB4 (α6β4 integrin)Missense, nonsense, deletion, insertion, splice site
Dystrophic epidermolysis bullosa - DominantCOL17A1 (type VII collagenMissense, splice site
Dystrophic epidermolysis bullosa - RecessiveCOL17A1 (type VII collagenMissense, nonsense, deletion, insertion, splice site
Kindler syndromeKIND1 (kindling-1)Nonsense, deletion, insertion, splice site

Table 4. Major EB Subtypes and Their Targeted Proteins (2008 International Consensus Report[18] ) (Open Table in a new window)

Major EB TypeMajor EB SubtypesTargeted Protein(s)
EB simplex (EBS)suprabasal subtypes
lethal acantholytic EBSdesmoplakin
plakophilin-1 deficiencyplakophilin-1
EBS superficialis (EBSS)?
basal subtypes
EBS, localized (EBS-loc)K5, K14
EBS, Dowling-Meara (EBS-DM)K5, K14
EBS, other generalized (EBS,-gen nDM)K5, K14
EBS with mottled pigmentation (EBS-MP)K5
EBS with muscular dystrophy (EBS-MD)plectin
EBS with pyloric atresia (EBS-PA)plectin; α6β4 integrin
EBS, autosomal recessive (EBS-AR)K14
EBS, Ogna (EBS-Og)plectin
EBS, migratory circinate (EBS-migr)K5
Junctional EB (JEB)JEB, Herlitz (JEB-H)laminin-332
JEB, generalized non-Herlitz (JEB-nH gen)laminin-332; type XVII collagen
JEB, localized non-Herlitz (JEB-nH loc)type XVII collagen
JEB with pyloric atresia (JEB-PA)α6β4 integrin
JEB, inversa (JEB-I)laminin-332
JEB, late onset (JEB-lo)?
LOC syndromelaminin-332 α3 chain
Dominant dystrophic EB (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 EB (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 syndromekindlin-1
Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Surasak Puvabanditsin, MD  Assistant Professor of Pediatrics, UMDNJ-New Jersey Medical School; Associate Professor of Pediatrics, St George's University School of Medicine, Grenada; Associate Professor of Pediatrics, Seton Hall University School of Graduate Medical Education

Surasak Puvabanditsin, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Erik Brandsma, MD  Fellow, Division of Neonatology, Department of Peditrics, UMDNJ-Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Nisha Patel, MD  Resident Physician, Westchester Medical Center, Maria Ferrari Children's Hospital

Nisha Patel, MD is a member of the following medical societies: American Medical Student Association/Foundation and Phi Beta Kappa

Disclosure: Nothing to disclose.

Rungtiwa Weerasethsiri, MD  General Pediatrician, Merced Facuty Associates, California

Rungtiwa Weerasethsiri, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Alexis A D'Elia, MD  Resident Physician, Department of Internal Medicine, Winthrop University Hospital

Alexis A D'Elia, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Kevin P Connelly, DO  Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center

Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgments

The authors thank Judy Wilkinson, librarian at the Jersey City Medical Center, for her assistance. The authors also thank Sylvia Sutton-Thorpe Chrystal Puvabandistin and Christina Puvabanditsin for supporting this effort and preparing the manuscript.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Eugene Garrow, MD, to the original writing and development of this article.

References

  1. PEARSON RW. Studies on the pathogenesis of epidermolysis bullosa. J Invest Dermatol. Dec 1962;39:551-75. [Medline].

  2. Hintner H, Stingl G, Schuler G, et al. Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in the mechanobullous diseases. J Invest Dermatol. Feb 1981;76(2):113-8. [Medline].

  3. Heagerty AH, Kennedy AR, Leigh IM, Purkis P, Eady RA. Identification of an epidermal basement membrane defect in recessive forms of dystrophic epidermolysis bullosa by LH 7:2 monoclonal antibody: use in diagnosis. Br J Dermatol. Aug 1986;115(2):125-31. [Medline].

  4. McGrath JA, McMillan JR, Dunnill MG, et al. Genetic basis of lethal junctional epidermolysis bullosa in an affected fetus: implications for prenatal diagnosis in one family. Prenat Diagn. Jul 1995;15(7):647-54. [Medline].

  5. Smith LT. Ultrastructural findings in epidermolysis bullosa. Arch Dermatol. Dec 1993;129(12):1578-84. [Medline].

  6. Pulkkinen L, Christiano AM, Airenne T, et al. Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nat Genet. Mar 1994;6(3):293-7. [Medline].

  7. [Guideline] 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. Jun 2008;58(6):931-50. [Medline].

  8. Fine JD. Inherited epidermolysis bullosa. Orphanet J Rare Dis. May 28 2010;5:12. [Medline]. [Full Text].

  9. Horn HM, Priestley GC, Eady RA, Tidman MJ. The prevalence of epidermolysis bullosa in Scotland. Br J Dermatol. Apr 1997;136(4):560-4. [Medline].

  10. McKenna KE, Walsh MY, Bingham EA. Epidermolysis bullosa in Northern Ireland. Br J Dermatol. Oct 1992;127(4):318-21. [Medline].

  11. Inaba Y, Kitamura K, Ogawa H, Manabe M, Sasai Y. [A study on the estimation of prevalence of epidermolysis bullosa in Japan]. Nihon Hifuka Gakkai Zasshi. Aug 1989;99(9):1021-6. [Medline].

  12. Pavicic Z, Kmet-Vizintin P, Kansky A, Dobric I. Occurrence of hereditary bullous epidermolyses in Croatia. Pediatr Dermatol. Jun 1990;7(2):108-10. [Medline].

  13. Fine JD, Johnson LB, Weiner M, et al. Inherited epidermolysis bullosa and the risk of death from renal disease: experience of the National Epidermolysis Bullosa Registry. Am J Kidney Dis. Oct 2004;44(4):651-60. [Medline].

  14. Fine JD, Johnson LB, Weiner M, Suchindran C. Cause-specific risks of childhood death in inherited epidermolysis bullosa. J Pediatr. Feb 2008;152(2):276-80. [Medline].

  15. Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. Feb 2009;60(2):203-11. [Medline].

  16. Fine JD. Epidermolysis bullosa: a genetic disease of altered cell adhesion and wound healing, and the possible clinical utility of topically applied thymosin beta4. Ann N Y Acad Sci. Sep 2007;1112:396-406. [Medline].

  17. Fischer IA, Kazandjieva J, Vassileva S, Dourmishev A. Kindler syndrome: a case report and proposal for clinical diagnostic criteria. Acta Dermatovenerol Alp Panonica Adriat. Jun 2005;14(2):61-7. [Medline].

  18. 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. Jun 2008;58(6):931-50. [Medline].

  19. Sawamura D, Nakano H, Matsuzaki Y. Overview of epidermolysis bullosa. J Dermatol. Mar 2010;37(3):214-9. [Medline].

  20. Rubin AI, Garzon MC, Morel KD. Herpetic infection in epidermolysis bullosa. Pediatr Dermatol. Jul-Aug 2006;23(4):355-7. [Medline].

  21. Fine JD, Johnson LB, Weiner M, Suchindran C. Gastrointestinal complications of inherited epidermolysis bullosa: cumulative experience of the National Epidermolysis Bullosa Registry. J Pediatr Gastroenterol Nutr. Feb 2008;46(2):147-58. [Medline].

  22. Shaw DW, Fine JD, Piacquadio DJ, et al. Gastric outlet obstruction and epidermolysis bullosa. J Am Acad Dermatol. Feb 1997;36(2 Pt 2):304-10. [Medline].

  23. Puvabanditsin S, Garrow E, Kim DU, Tirakitsoontorn P, Luan J. Junctional epidermolysis bullosa associated with congenital localized absence of skin, and pyloric atresia in two newborn siblings. J Am Acad Dermatol. Feb 2001;44(2 Suppl):330-5. [Medline].

  24. Fine JD, Johnson LB, Weiner M, et al. Genitourinary complications of inherited epidermolysis bullosa: experience of the national epidermylosis bullosa registry and review of the literature. J Urol. Nov 2004;172(5 Pt 1):2040-4. [Medline].

  25. Rubin AI, Moran K, Fine JD, Wargon O, Murrell DF. Urethral meatal stenosis in junctional epidermolysis bullosa: a rare complication effectively treated with a novel and simple modality. Int J Dermatol. Oct 2007;46(10):1076-7. [Medline].

  26. Fine JD, Johnson LB, Weiner M, et al. Eye involvement in inherited epidermolysis bullosa: experience of the National Epidermolysis Bullosa Registry. Am J Ophthalmol. Aug 2004;138(2):254-62. [Medline].

  27. Fine JD, Johnson LB, Weiner M, Suchindran C. Tracheolaryngeal complications of inherited epidermolysis bullosa: cumulative experience of the national epidermolysis bullosa registry. Laryngoscope. Sep 2007;117(9):1652-60. [Medline].

  28. Ayman T, Yerebakan O, Ciftcioglu MA, Alpsoy E. A 13-year-old girl with recessive dystrophic epidermolysis bullosa presenting with squamous cell carcinoma. Pediatr Dermatol. Sep-Oct 2002;19(5):436-8. [Medline].

  29. Bart BJ. Epidermolysis bullosa and congenital localized absence of skin. Arch Dermatol. Jan 1970;101(1):78-81. [Medline].

  30. Bart BJ, Gorlin RJ, Anderson VE, Lynch FW. Congenital localized absence of skin and associated abnormalities resembling epidermolysis bullosa. A new syndrome. Arch Dermatol. Mar 1966;93(3):296-304. [Medline].

  31. Bart BJ, Lussky RC. Bart syndrome with associated anomalies. Am J Perinatol. Oct 2005;22(7):365-9. [Medline].

  32. Bello YM, Falabella AF, Schachner LA. Management of epidermolysis bullosa in infants and children. Clin Dermatol. Jul-Aug 2003;21(4):278-82. [Medline].

  33. Butler DF, Berger TG, James WD, et al. Bart's syndrome: microscopic, ultrastructural, and immunofluorescent mapping features. Pediatr Dermatol. Feb 1986;3(2):113-8. [Medline].

  34. Cetinkursun S, Ozturk H, Celasun B, Sakarya MT, Alpasian F. Epidermolysis bullosa associated with pyloric, esophageal, and anal atresia: a case report. J Pediatr Surg. Oct 1995;30(10):1477-8. [Medline].

  35. Chang CH, Perrin EV, Bove KE. Pyloric atresia associated with epidermolysis bullosa: special reference to pathogenesis. Pediatr Pathol. Oct-Dec 1983;1(4):449-57. [Medline].

  36. Christiano AM, Bart BJ, Epstein EH Jr, Uitto J. Genetic basis of Bart's syndrome: a glycine substitution mutation in type VII collagen gene. J Invest Dermatol. Apr 1996;106(4):778-80. [Medline].

  37. Cooper TW, Bauer EA. Epidermolysis bullosa: a review. Pediatr Dermatol. Jan 1984;1(3):181-8. [Medline].

  38. Cowton JA, Beattie TJ, Gibson AA, et al. Epidermolysis bullosa in association with aplasia cutis congenita and pyloric atresia. Acta Paediatr Scand. Jan 1982;71(1):155-60. [Medline].

  39. Dank JP, Kim S, Parisi MA, et al. Outcome after surgical repair of junctional epidermolysis bullosa-pyloric atresia syndrome: a report of 3 cases and review of the literature. Arch Dermatol. Oct 1999;135(10):1243-7. [Medline].

  40. Das BB, Sahoo S. Dystrophic epidermolysis bullosa. J Perinatol. Jan 2004;24(1):41-7. [Medline].

  41. Devries DT, Johnson LB, Weiner M, Fine JD. Relative extent of skin involvement in inherited epidermolysis bullosa (EB): composite regional anatomic diagrams based on the findings of the National EB Registry, 1986 to 2002. J Am Acad Dermatol. Apr 2004;50(4):572-81. [Medline].

  42. Duran-McKinster C, Rivera-Franco A, Tamayo L, et al. Bart syndrome: the congenital localized absence of skin may follow the lines of Blaschko. Report of six cases. Pediatr Dermatol. May-Jun 2000;17(3):179-82. [Medline].

  43. Eady RA. Epidermolysis bullosa: scientific advances and therapeutic challenges. J Dermatol. Nov 2001;28(11):638-40. [Medline].

  44. Fine JD. Inherited Epidermolysis Bullosa: Selected Outcomes and a Revised Classification System. Pediatr Dermatol. Jan 2000;17(1):75-83. [Medline].

  45. Fine JD, Bauer EA, Briggaman RA, et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol. Jan 1991;24(1):119-35. [Medline].

  46. Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. Feb 2009;60(2):203-11. [Medline].

  47. Fivenson DP, Scherschun L, Choucair M, et al. Graftskin therapy in epidermolysis bullosa. J Am Acad Dermatol. Jun 2003;48(6):886-92. [Medline].

  48. Frieden IJ. Aplasia cutis congenita: a clinical review and proposal for classification. J Am Acad Dermatol. Apr 1986;14(4):646-60. [Medline].

  49. Hayashi AH, Galliani CA, Gillis DA. Congenital pyloric atresia and junctional epidermolysis bullosa: a report of long-term survival and a review of the literature. J Pediatr Surg. Nov 1991;26(11):1341-5. [Medline].

  50. Heagerty AH, Kennedy AR, Eady RA, et al. GB3 monoclonal antibody for diagnosis of junctional epidermolysis bullosa. Lancet. Apr 12 1986;1(8485):860. [Medline].

  51. Heagerty AH, Kennedy AR, Gunner DB, Eady RA. Rapid prenatal diagnosis and exclusion of epidermolysis bullosa using novel antibody probes. J Invest Dermatol. May 1986;86(5):603-5. [Medline].

  52. Herod J, Denyer J, Goldman A, Howard R. Epidermolysis bullosa in children: pathophysiology, anaesthesia and pain management. Paediatr Anaesth. Jun 2002;12(5):388-97. [Medline].

  53. Horn HM, Tidman MJ. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol. Feb 2002;146(2):267-74. [Medline].

  54. Hurwitz S. Clinical Pediatric Dermatology. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1993:432-5.

  55. Kanzler MH, Smoller B, Woodley DT. Congenital localized absence of the skin as a manifestation of epidermolysis bullosa. Arch Dermatol. Aug 1992;128(8):1087-90. [Medline].

  56. Kodama Y, Kawamoto M, Iwashita K, et al. Congenital pyloric atresia. A report on a successfully treated case and existing research. Nippon Ika Daigaku Zasshi. Aug 1986;53(4):409-15. [Medline].

  57. Lepinard C, Descamps P, Meneguzzi G, et al. Prenatal diagnosis of pyloric atresia-junctional epidermolysis bullosa syndrome in a fetus not known to be at risk. Prenat Diagn. Jan 2000;20(1):70-5. [Medline].

  58. Lestringant GG, Akel SR, Qayed KI. The pyloric atresia-junctional epidermolysis bullosa syndrome. Report of a case and review of the literature. Arch Dermatol. Aug 1992;128(8):1083-6. [Medline].

  59. Mallipeddi R. Epidermolysis bullosa and cancer. Clin Exp Dermatol. Nov 2002;27(8):616-23. [Medline].

  60. Melhem RE, Salem G, Mishalany H, Slim M, Der Kaloustian VM. Pyloro-duodenal atresia. A report of three families with several similarly affected children. Pediatr Radiol. Jan 24 1975;3(1):1-5. [Medline].

  61. Moore CC. Congenital gastric outlet obstruction. J Pediatr Surg. Dec 1989;24(12):1241-6. [Medline].

  62. Moss C. Skin and kin. J R Soc Med. May 2005;98(5):200-2. [Medline].

  63. Muller M, Morger R, Engert J. Pyloric atresia case report of four cases and review of the literature. Pediatr Surg Int. 1990;5 vol:276-9.

  64. Okoye BO, Parikh DH, Buick RG, Lander AD. Pyloric atresia: five new cases, a new association, and a review of the literature with guidelines. J Pediatr Surg. Aug 2000;35(8):1242-5. [Medline].

  65. Pai S, Marinkovich MP. Epidermolysis bullosa: new and emerging trends. Am J Clin Dermatol. 2002;3(6):371-80. [Medline].

  66. Pearson RW. Clinicopathologic types of epidermolysis bullosa and their nondermatological complications. Arch Dermatol. May 1988;124(5):718-25. [Medline].

  67. Pfendner EG, Nakano A, Pulkkinen L, Christiano AM, Uitto J. Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive pregnancies at risk. Prenat Diagn. Jun 2003;23(6):447-56. [Medline].

  68. Rodeck CH, Eady RA, Gosden CM. Prenatal diagnosis of epidermolysis bullosa letalis. Lancet. May 3 1980;1(8175):949-52. [Medline].

  69. Rowe MI, O'Neill JA, Grosfeld JL. Essential of Pediatric Surgery. St Louis, Mo: Mosby; 1995:486, 501-2.

  70. Schober-Flores C. Epidermolysis bullosa: a nursing perspective. Dermatol Nurs. Aug 1999;11(4):243-8, 253-6. [Medline].

  71. Skoven I, Drzewiecki KT. Congenital localized skin defect and epidermolysis bullosa hereditaria letalis. Acta Derm Venereol. 1979;59(6):533-7. [Medline].

  72. Swinburne L, Kohler HG. Symmetrical congenital skin defects in sibs. Arch Dis Child. 1968;43:499.

  73. Teran Ac, Cobo BJ, Guijarro MG. Atrsia de piloro en un recien nacido con epidermolisis ampullosa. Bol Catedra Padiatr (Madrid). 1972;1647-78.

  74. Tong L, Hodgkins PR, Denyer J, et al. The eye in epidermolysis bullosa. Br J Ophthalmol. Mar 1999;83(3):323-6. [Medline].

  75. Uitto J, Christiano AM. Molecular genetics of the cutaneous basement membrane zone. Perspectives on epidermolysis bullosa and other blistering skin diseases. J Clin Invest. Sep 1992;90(3):687-92. [Medline].

  76. Uitto J, Pulkkinen L. Molecular genetics of heritable blistering disorders. Arch Dermatol. Nov 2001;137(11):1458-61. [Medline].

  77. Uitto J, Richard G. Progress in epidermolysis bullosa: from eponyms to molecular genetic classification. Clin Dermatol. Jan-Feb 2005;23(1):33-40. [Medline].

  78. Vidal F, Aberdam D, Miquel C, et al. Integrin beta 4 mutations associated with junctional epidermolysis bullosa with pyloric atresia. Nat Genet. Jun 1995;10(2):229-34. [Medline].

  79. Weinel S, Lucky AW, Uitto J, Pfendner EG, Choo D. Dystrophic epidermolysis bullosa with one dominant and one recessive mutation of the COL7A1 gene in a child with deafness. Pediatr Dermatol. Mar-Apr 2008;25(2):210-4. [Medline].

  80. Wojnarowska FT, Eady RA, Wells RS. Dystrophic epidermolysis bullosa presenting with congenital localized absence of skin: report of four cases. Br J Dermatol. Apr 1983;108(4):477-83. [Medline].

  81. Yan EG, Paris JJ, Ahluwalia J, Lane AT, Bruckner AL. Treatment decision-making for patients with the Herlitz subtype of junctional epidermolysis bullosa. J Perinatol. May 2007;27(5):307-11. [Medline].

  82. Yiasemides E, Walton J, Marr P, Villanueva EV, Murrell DF. A comparative study between transmission electron microscopy and immunofluorescence mapping in the diagnosis of epidermolysis bullosa. Am J Dermatopathol. Oct 2006;28(5):387-94. [Medline].

  83. Zelickson B, Matsumura K, Kist D, Epstein EH Jr, Bart BJ. Bart's syndrome. Ultrastructure and genetic linkage. Arch Dermatol. Jun 1995;131(6):663-8. [Medline].

 
Previous
Next
 
Ruptured bulla and newly erupted bulla of the leg in a newborn with epidermolysis bullosa simplex (EBS).
Dystrophic epidermolysis bullosa (DEB) with multiple blisters and erosions.
Dystrophic epidermolysis bullosa (DEB) with generalized blistering and erosion.
Dystrophic epidermolysis bullosa (DEB) that subsequently healed, with scarring.
Junctional epidermolysis bullosa (JEB). Image shows a newborn with bulla of the finger, the usual site of blistering secondary to trauma.
Junctional epidermolysis bullosa (JEB) with an associated defect of a congenital absence of the skin.
Junctional epidermolysis bullosa (JEB) with an associated defect of a congenital absence of the skin and an ear anomaly.
Contrast-enhanced radiograph of the abdomen suggestive of pyloric atresia (PA) in a patient with junctional epidermolysis bullosa (JEB). The association between PA and EB is a distinct entity and is now referred to as PA-EB syndrome.
Electron micrograph of a skin sample shows cleavage in the intralaminar lucida in a neonate with junctional epidermolysis bullosa (JEB).
Dystrophic nails in a neonate with junctional epidermolysis bullosa (EB).
Congenital localized absence of skin, nose, in a neonate with junctional epidermolysis bullosa (JEB).
Ruptured bullae on the abdomen in a neonate with junctional epidermolysis bullosa (JEB).
A large bullae on the elbow in a neonate with junctional epidermolysis bullosa (JEB).
Congenital localized absence of skin on the scrotum in a neonate with junctional epidermolysis bullosa (JEB). Absence of the foreskin was also noted.
Severe right hydronephrosis in a neonate with junctional epidermolysis bullosa (JEB).
Genitourinary obstruction in a fetus with junctional epidermolysis bullosa (JEB). Prenatal ultrasonography reveals severe right hydronephrosis.
Ruptured bulla of the hand in a newborn with epidermolysis bullosa simplex (EBS).
Abdominal radiography revealing a single gastric bubble in a neonate with pyloric atresia (PA) and junctional epidermolysis bullosa (JEB).
Table 1. Ultrastructural Findings of Major Types and Subtypes of Epidermolysis Bullosa
Type or SubtypeUltrastructural Site of Skin FindingsOther Ultrastructural Findings
Epidermolysis bullosa simplex
LocalizedBasal layerSplit may spread to suprabasilar layer
Dowling-MearaBasal layer in subnuclear cytoplasmDense, circumscribed clumps of keratin Filaments
Muscular dystrophyPredominantly in basal layer, above level of hemidesmosome attachment plaqueReduced integration of keratin filaments with hemidesmosome
Autosomal recessiveBasal keratinocytesAbsent or reduced keratin filaments within basal keratinocytes
SuperficialisSplit usually at interface between granular and cornified cell layers...
Lethal acantholyticSuprabasal cleavage and acantholysisPerinuclear retraction of keratin filaments
Plakophillin-1 deficiencyMid epidermal cell-cell separationDiminutive suprabasal desmosomes, perinuclear retraction of keratin filaments
Pyloric atresia (PA)Lower basal layer, above level of hemidesmosome plaqueReduced integration of keratin filaments with hemidesmosome
Junctional epidermolysis bullosa
HerlitzLamina lucidaMarkedly reduced or absent hemidesmosome, absent sub-basal dense plate
Non-HerlitzLamina lucidaHemidesmosome may be normal or reduced in size and number
Pyloric atresiaLamina lucidaSmall hemidesmosome plaques often with attenuated sub-basal dense plate
Dominant dystrophic epidermolysis bullosa
GeneralizedSub-lamina densaNormal or decreased numbers of anchoring fibrils
Bullous dermolysis of the newbornSub-lamina densaElectron-dense stellate bodies within basal layer, reduced anchoring fibrils
Recessive dystrophic epidermolysis bullosa
Severe generalizedSub-lamina densaAbsent or rudimentary anchoring fibrils
Generalized otherSub-lamina densaReduced or rudimentary-appearing anchoring fibrils
Bullous dermolysis of the newbornSub-lamina densaElectron-dense stellate bodies within basal layer, reduced anchoring fibrils
Table 2. Major Types of Epidermolysis Bullosa
level of Skin CleavageMajor TypeKnown Targeted Protein
Intraepidermal (epidermolytic)Epidermolysis bullosa simplexKeratins 4 and 14; plectin; α6β4 integrin; plakophillin-1 desmoplakin
Intra-lamina lucida (lamina lucidolytic)Junctional epidermolysis bullosaLaminin-332(laminin 5); type XVII collagen; α6β4 integrin
Sub-lamina densa (dermolytic)Dystrophic epidermolysis bullosaType VII collagen
MixedKindler syndromeKindlin-1
Table 3. Mutational Analyses and Inherited Epidermolysis Bullosa
Epidermolysis Bullosa SubtypeTarget Gene(Protein)Types of Known Mutations
Epidermolysis bullosa simplex - SuprabasalPKP1 (plakophilin1)Splice site, deletion, nonsense
DSP (desmoplakin)Nonsense, deletion
Epidermolysis bullosa simplex - BasalKRT5 (keratin-5)Missense, nonsense, deletion, splice site
KRT14 (keratin-14)Missense, nonsense, deletion, insertion, splice site, in-frame deletion/insertion
PLEC1 (plectin)Missense, nonsense, deletion, insertion, in-frame deletion/insertion
ITGA6, ITGB4 (α6β4 integrin)missense, nonsense, deletion, insertion, splice site
Junctional epidermolysis bullosa - HerlitzLAMA3, LAMB3, LAMC2 (laminin-332)Nonsense, deletion, insertion, splice site
Junctional epidermolysis bullosa - OtherLAMA3, LAMB3, LAMC2 (laminin-332)Missense, nonsense, deletion, insertion, splice site
COL17A1 (type XVII collagen)Missense, nonsense, deletion, insertion, splice site
ITGA6, ITGB4 (α6β4 integrin)Missense, nonsense, deletion, insertion, splice site
Dystrophic epidermolysis bullosa - DominantCOL17A1 (type VII collagenMissense, splice site
Dystrophic epidermolysis bullosa - RecessiveCOL17A1 (type VII collagenMissense, nonsense, deletion, insertion, splice site
Kindler syndromeKIND1 (kindling-1)Nonsense, deletion, insertion, splice site
Table 4. Major EB Subtypes and Their Targeted Proteins (2008 International Consensus Report[18] )
Major EB TypeMajor EB SubtypesTargeted Protein(s)
EB simplex (EBS)suprabasal subtypes
lethal acantholytic EBSdesmoplakin
plakophilin-1 deficiencyplakophilin-1
EBS superficialis (EBSS)?
basal subtypes
EBS, localized (EBS-loc)K5, K14
EBS, Dowling-Meara (EBS-DM)K5, K14
EBS, other generalized (EBS,-gen nDM)K5, K14
EBS with mottled pigmentation (EBS-MP)K5
EBS with muscular dystrophy (EBS-MD)plectin
EBS with pyloric atresia (EBS-PA)plectin; α6β4 integrin
EBS, autosomal recessive (EBS-AR)K14
EBS, Ogna (EBS-Og)plectin
EBS, migratory circinate (EBS-migr)K5
Junctional EB (JEB)JEB, Herlitz (JEB-H)laminin-332
JEB, generalized non-Herlitz (JEB-nH gen)laminin-332; type XVII collagen
JEB, localized non-Herlitz (JEB-nH loc)type XVII collagen
JEB with pyloric atresia (JEB-PA)α6β4 integrin
JEB, inversa (JEB-I)laminin-332
JEB, late onset (JEB-lo)?
LOC syndromelaminin-332 α3 chain
Dominant dystrophic EB (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 EB (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 syndromekindlin-1
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.