Practice Essentials

Epidermolysis bullosa (EB) is a group of inherited bullous disorders characterized by blister formation in response to mechanical trauma. Historically, epidermolysis bullosa subtypes have been classified according to skin morphology.^{[1, 2]}

Discoveries of the molecular basis of epidermolysis bullosa have resulted in the development of diagnostic tools, including prenatal and preimplantation testing. Based on a better understanding of the basement membrane zone (BMZ) and the genes responsible for its components, newer treatments (eg, gene or protein therapy) may provide solutions to the skin fragility found in patients with epidermolysis bullosa.

Related articles include Epidermolysis Bullosa Acquisita and Pediatric Epidermolysis Bullosa.

Signs and symptoms

Important general points include age of onset; size, frequency, and location of blisters; possible inciting factors; prior diagnostic attempts; prior therapies; and extent of pain or pruritus.

Review of systems information that can be associated with different epidermolysis bullosa (EB) subtypes includes alteration of growth or development and evidence of mucosal involvement, including oral (which is demonstrated in the image below), nasopharyngeal, ocular, genitourinary, GI, or respiratory symptoms. A family history of blistering disease is an important finding to identify.

Recessively inherited dystrophic epidermolysis bullosa; oral cavity blistering and scarring.

View Media Gallery

Perform a complete physical examination with an emphasis on inspection of all skin, as well as conjunctival, oral, and genital mucosae.

Fine JD. Inherited epidermolysis bullosa: past, present, and future. Ann N Y Acad Sci. 2010 Apr. 1194:213-22. [QxMD MEDLINE Link].
Sawamura D, Nakano H, Matsuzaki Y. Overview of epidermolysis bullosa. J Dermatol. 2010 Mar. 37(3):214-9. [QxMD MEDLINE Link].
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 Jun. 58(6):931-50. [QxMD MEDLINE Link].
McGrath JA, Mellerio JE. Epidermolysis bullosa. Br J Hosp Med (Lond). 2006 Apr. 67(4):188-91. [QxMD MEDLINE Link].
Gong Z, Zou X, Xue R, et al. Large intragenic deletion of KRT14 causes autosomal-dominant epidermolysis bullosa simplex with generalized hyperpigmentation. J Dermatol Sci. 2023 Mar 13. [QxMD MEDLINE Link].
Kotalevskaya YY, Stepanov VA. Molecular genetic basis of epidermolysis bullosa. Vavilovskii Zhurnal Genet Selektsii. 2023 Mar. 27 (1):18-27. [QxMD MEDLINE Link]. [Full Text].
Ersoy-Evans S, Erkin G, Fassihi H, et al. Ectodermal dysplasia-skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1. J Am Acad Dermatol. 2006 Jul. 55(1):157-61. [QxMD MEDLINE Link].
Lai-Cheong JE, Tanaka A, Hawche G, Emanuel P, Maari C, Taskesen M, et al. Kindler syndrome: a focal adhesion genodermatosis. Br J Dermatol. 2009 Feb. 160 (2):233-42. [QxMD MEDLINE Link].
Has C, Wessagowit V, Pascucci M, Baer C, Didona B, Wilhelm C, et al. Molecular basis of Kindler syndrome in Italy: novel and recurrent Alu/Alu recombination, splice site, nonsense, and frameshift mutations in the KIND1 gene. J Invest Dermatol. 2006 Aug. 126 (8):1776-83. [QxMD MEDLINE Link].
Lanschuetzer CM, Muss WH, Emberger M, Pohla-Gubo G, Klausegger A, Bauer JW, et al. Gene symbol: Kind1. Disease: kindler syndrome. Hum Genet. 2004 Jul. 115 (2):175. [QxMD MEDLINE Link].
Ashton GH. Kindler syndrome. Clin Exp Dermatol. 2004 Mar. 29 (2):116-21. [QxMD MEDLINE Link].
Fine JD. Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates From the National Epidermolysis Bullosa Registry. JAMA Dermatol. 2016 Jul 27. [QxMD MEDLINE Link].
Fine JD, Bauer EA, McGuire J, Moshell A, eds. Epidermolysis Bullosa: Clinical, Epidemiologic, and Laboratory Advances and the Findings of the National Epidermolysis Bullosa Registry. Baltimore, Md: Johns Hopkins University Press; 1999.
Risser J, Lewis K, Weinstock MA. Mortality of bullous skin disorders from 1979 through 2002 in the United States. Arch Dermatol. 2009 Sep. 145(9):1005-8. [QxMD MEDLINE Link].
Kiritsi D, Garcia M, Brander R, Has C, Meijer R, Jose Escámez M, et al. Mechanisms of natural gene therapy in dystrophic epidermolysis bullosa. J Invest Dermatol. 2014 Aug. 134 (8):2097-104. [QxMD MEDLINE Link].
Yuniati R, Hellmi RY, Dwijayanti GC, et al. Epidermolysis Bullosa and Rickets in a 21-Year-Old Female: A Case Report. Case Rep Dermatol. 2022 Sep-Dec. 14 (3):291-301. [QxMD MEDLINE Link]. [Full Text].
Fassihi H, Eady RA, Mellerio JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years' experience. Br J Dermatol. 2006 Jan. 154(1):106-13. [QxMD MEDLINE Link].
Fassihi H, Eady RA, Mellerio JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years' experience. Br J Dermatol. 2006 Jan. 154(1):106-13. [QxMD MEDLINE Link].
Heagerty AH, Eady RA, Kennedy AR, et al. Rapid prenatal diagnosis of epidermolysis bullosa letalis using GB3 monoclonal antibody. Br J Dermatol. 1987 Sep. 117(3):271-5. [QxMD MEDLINE Link].
Marinkovich MP, Meneguzzi G, Burgeson RE, et al. Prenatal diagnosis of Herlitz junctional epidermolysis bullosa by amniocentesis. Prenat Diagn. 1995 Nov. 15(11):1027-34. [QxMD MEDLINE Link].
Guide SV, Gonzalez ME, Bağcı IS, Agostini B, Chen H, Feeney G, et al. Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med. 2022 Dec 15. 387 (24):2211-2219. [QxMD MEDLINE Link].
Kern JS, Sprecher E, Fernandez MF, Schauer F, Bodemer C, Cunningham T, et al. Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study. Br J Dermatol. 2023 Jan 23. 188 (1):12-21. [QxMD MEDLINE Link]. [Full Text].
Tong L, Hodgkins PR, Denyer J, et al. The eye in epidermolysis bullosa. Br J Ophthalmol. 1999 Mar. 83(3):323-6. [QxMD MEDLINE Link].
Woodley DT, Keene DR, Atha T, Huang Y, Lipman K, Li W, et al. Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa. Nat Med. 2004 Jul. 10(7):693-5. [QxMD MEDLINE Link].
Woodley DT, Keene DR, Atha T, et al. Intradermal injection of lentiviral vectors corrects regenerated human dystrophic epidermolysis bullosa skin tissue in vivo. Mol Ther. 2004 Aug. 10(2):318-26. [QxMD MEDLINE Link].
Mavilio F, Pellegrini G, Ferrari S, et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. 2006 Dec. 12(12):1397-402. [QxMD MEDLINE Link].
Petrof G, Martinez-Queipo M, Mellerio JE, Kemp P, McGrath JA. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial. Br J Dermatol. 2013 Nov. 169 (5):1025-33. [QxMD MEDLINE Link].
Venugopal SS, Yan W, Frew JW, Cohn HI, Rhodes LM, Tran K, et al. A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2013 Dec. 69 (6):898-908.e7. [QxMD MEDLINE Link].
Siprashvili Z, Nguyen NT, Gorell ES, Loutit K, Khuu P, Furukawa LK, et al. Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. JAMA. 2016 Nov 1. 316 (17):1808-1817. [QxMD MEDLINE Link].
Terrill PJ, Mayou BJ, Pemberton J. Experience in the surgical management of the hand in dystrophic epidermolysis bullosa. Br J Plast Surg. 1992 Aug-Sep. 45(6):435-42. [QxMD MEDLINE Link].
Ames WA, Mayou BJ, Williams KN. Anaesthetic management of epidermolysis bullosa. Br J Anaesth. 1999 May. 82(5):746-51. [QxMD MEDLINE Link].
Falabella AF, Valencia IC, Eaglstein WH, Schachner LA. Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds. Arch Dermatol. 2000 Oct. 136(10):1225-30. [QxMD MEDLINE Link].
[Guideline] Liy-Wong C, Tarango C, Pope E, et al. Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa. Orphanet J Rare Dis. 2023 Feb 23. 18 (1):38. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Epidermolysis bullosa simplex localized (formerly termed Weber-Cockayne subtype). This mild bullous disease is characterized by localized blistering at sites of trauma such as the feet.
Epidermolysis bullosa simplex, generalized (formerly termed Koebner subtype). Palmoplantar blistering and hyperkeratosis are noted.
Epidermolysis bullosa simplex, generalized (formerly termed Koebner subtype). Close-up image shows hyperkeratotic papules and plaques on the palm.
Junctional epidermolysis bullosa, generalized severe (formerly termed Herlitz or letalis) subtype. This severe disease is characterized by generalized intralamina lucida blistering at birth, significant internal involvement, and a poor prognosis.
Dominantly inherited dystrophic epidermolysis bullosa. The blistering in this disease often is localized and is characterized by scarring and milia in healed blister sites.
Dominantly inherited dystrophic epidermolysis bullosa. This subtype, similar to other dystrophic and junctional epidermolysis bullosa subtypes, can result in nail dystrophy and loss.
Recessively inherited dystrophic epidermolysis bullosa pseudosyndactyly (mitten-hand deformity) of the hands and feet.
Recessively inherited dystrophic epidermolysis bullosa; oral cavity blistering and scarring.
Recessively inherited dystrophic epidermolysis bullosa; squamous cell carcinoma.
Diagram illustrating the organization of the dermal epidermal basement membrane and level of disruption in epidermolysis bullosa subtypes. EBS: epidermolysis bullosa simplex. JEB: junctional epidermolysis bullosa. DEB: dystrophic epidermolysis bullosa.

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#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

Author

M Peter Marinkovich, MD Associate Professor, Department of Dermatology and Program in Epithelial Biology, Stanford University Medical Center; Dermatology Service, VA Palo Alto Health Care System

M Peter Marinkovich, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Emeritus Professor, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, American Contact Dermatitis Society, Association of Military Dermatologists, Association of Professors of Dermatology, American Dermatological Association, Women's Dermatologic Society, Medical Dermatology Society, Dermatology Foundation, Society for Investigative Dermatology, Washington DC Dermatological Society, Atlantic Dermatologic Society, Philadelphia Dermatological Society, Pennsylvania Academy of Dermatology, College of Physicians of Philadelphia

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Jean Paul Ortonne, MD Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Ngoc Pham, MD, to the development and writing of this article.

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