eMedicine Specialties > Dermatology > Bullous Diseases

Epidermolysis Bullosa

Author: M Peter Marinkovich, MD, Associate Professor, Department of Dermatology and Program in Epithelial Biology, Stanford University Medical Center
Contributor Information and Disclosures

Updated: Nov 12, 2008

Introduction

Background

Epidermolysis bullosa (EB) is a group of inherited bullous disorders characterized by blister formation in response to mechanical trauma. Historically, EB subtypes have been classified according to skin morphology. Recent discoveries of the molecular basis of EB have resulted in the development of new 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, new treatments (eg, gene or protein therapy) may provide solutions to the skin fragility found in patients with EB.

Related eMedicine articles include Epidermolysis Bullosa Acquisita and Epidermolysis Bullosa (pediatrics version). Additionally, the Medscape Genomic Medicine Resource Center may be of interest.

Pathophysiology

EB is classified into 3 major categories, including (1) EB simplex (EBS; intraepidermal skin separation), (2) junctional EB (JEB; skin separation in lamina lucida or central BMZ), and (3) dystrophic EB (DEB; sublamina densa BMZ separation; see Media Files 5-6). Researchers have proposed a new category termed hemidesmosomal EB (HEB), which produces blistering at the hemidesmosomal level in the most superior aspect of the BMZ. EBS usually is associated with little or no extracutaneous involvement, while the more severe hemidesmosomal, junctional, and dystrophic forms of EB may produce significant multiorgan system involvement.1,2

Significant progress has been achieved in finding specific molecular therapies for EB, including protein and gene therapy. Type VII collagen and laminin-5 gene therapy have been proven effective through in vivo models. Type VII collagen protein therapy has similarly been shown to be effective in an in vivo model. Currently, these therapies are being extensively studied at the preclinical stage, in animal models.

Frequency

United States

Assuming that mild cases of EBS are reported only 10% of the time, the affected population in the United States is approximately 12,500 persons. According to a National Epidermolysis Bullosa Registry report,3 50 EB cases occur per 1 million live births. Of these cases, approximately 92% are EBS, 5% are DEB, 1% are JEB, and 2% are unclassified. Patients with HEB probably constitute much less than 1% of total EB cases.

International

According to the National Epidermolysis Bullosa Registry,3 the number of EB cases in Norway is 54 cases per million live births, in Japan is 7.8 cases per million live births, and in Croatia is 9.6 cases per million live births.

Mortality/Morbidity

Infancy is an especially difficult time for EB patients. Generalized blistering caused by any subtype may be complicated by infection, sepsis, and death. Severe forms of EB increase the mortality risk during infancy. Patients with the Herlitz or letalis form of JEB have the highest risk during infancy with an estimated mortality rate of 87% during the first year of life. In patients with EB that survive childhood, the most common cause of death is metastatic squamous cell carcinoma (SCC) (see Media File 9). This skin cancer occurs specifically in patients with recessively inherited EB (RDEB) who most commonly are aged 15-35 years. In contrast, dominantly inherited EBS and DEB and milder forms of JEB may not affect a patient's life expectancy adversely.

Age

Onset of EB is at birth or shortly after. The exception occurs in mild cases of EBS, which may remain undetected until adulthood or occasionally remain undiagnosed.

Clinical

History

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 EB subtypes includes alteration of growth or development and evidence of mucosal involvement, including oral, nasopharyngeal, ocular, genitourinary, GI, or respiratory symptoms. A family history of blistering disease is an important finding to identify (see Media File 8).

Physical

Perform a complete physical examination with an emphasis on inspection of all skin, as well as conjunctival, oral, and genital mucosae. Evaluate the size, location, and character of blisters. Attempt to assess the general level at which lesions split. Usually, superficial blisters manifest as crusted erosions, intraepidermal blisters are flaccid and may expand under pressure, and intralamina lucida blisters are tense and heal with atrophy but no scarring. Sublamina densa blisters heal with scarring and milia formation. Assess for involvement of nails, hair, or teeth.

  • EBS is a collection of keratin disorders characterized by intraepidermal blistering with relatively mild internal involvement. Lesions typically heal without scarring. Most commonly, these diseases are dominantly inherited, but recessively inherited cases have been reported. The more severe EBS subtypes include Koebner, Dowling-Meara, and Weber-Cockayne forms. An EBS variant associated with mottled pigmentation has been described in several families.
    • Mild EBS: Weber-Cockayne subtype is the most common form of EBS (see Media File 1). Blisters usually are precipitated by a clearly identified traumatic event. They can be mild to severe and most frequently occur on the palms and soles. Hyperhidrosis can accompany this disorder.
    • Severe EBS: Usually, a generalized onset of blisters occurs at or shortly after birth. Hands, feet, and extremities are the most common sites of involvement. Palmoplantar hyperkeratosis and erosions are common, especially in Koebner EBS (see Media Files 2-3). Dowling-Meara EBS involves more oral mucosa and manifests with grouped herpetiform blisters (hence the term EBS herpetiformis).
  • HEB includes 2 rare diseases. The first arises from a disorder of the protein plectin (HD1) and is associated with muscular dystrophy. The second arises from a defect of the a6b4 integrin receptor and is associated with pyloric atresia. Each disease shows intraepidermal blistering at the most basal aspect of the lower cell layer.
  • EB with muscular dystrophy: This condition is characterized initially by variable blistering activity, followed by onset of muscular dystrophy later in life. The degree of blistering activity does not correlate necessarily with the degree of muscular dystrophy. Some patients can present with dental abnormalities.
  • EB with pyloric atresia: This condition always is associated with pyloric atresia at birth and usually is accompanied by severe generalized blistering. In most patients, prognosis is poor despite correction of the pyloric atresia because the internal involvement is extensive. While this subtype typically is fatal during infancy, some patients with a milder case of the disease have survived into childhood.
  • JEB is a collection of diseases characterized by intralamina lucida blistering. Primary subtypes include a lethal subtype termed Herlitz or JEB letalis, a nonlethal subtype termed JEB mitis, and a generalized benign type termed generalized atrophic benign EB (GABEB).
  • Lethal JEB: The Herlitz or letalis form of JEB is characterized by generalized blistering at birth and arises from an absence or a severe defect in expression of the anchoring filament glycoprotein laminin 5 (see Media File 4). Patients with lethal forms of JEB show characteristic periorificial erosions around the mouth, eyes, and nares, often accompanied by significant hypertrophic granulation tissue. Multisystemic involvement of the corneal, conjunctival, tracheobronchial, oral, pharyngeal, esophageal, rectal, and genitourinary mucosae is present. Internal complications of the disease include a hoarse cry, cough, and other respiratory difficulties. Patients with Herlitz JEB are at increased risk for death from sepsis or other complications secondary to the profound epithelial disadhesion, and usually, they do not survive past infancy.
  • Nonlethal JEB: Patients with JEB manifesting generalized blistering who survive infancy and clinically improve with age have JEB mitis. Usually, these patients do not present with the same type of hoarse cry or other significant respiratory symptoms as do patients with the Herlitz form. Instead, scalp, nail, and tooth abnormalities increasingly may become apparent. Periorificial erosions and hypertrophic granulation tissue can be present. Mucous membranes often are affected by erosions, resulting in strictures. Some patients with JEB mitis can present with blistering localized to the intertriginous regions.
  • GABEB: This is a relatively mild subtype characterized by generalized cutaneous blistering and presenting at birth. Blistering activity is worsened by increased ambient temperature, and blisters heal with a distinctive atrophic appearance. Extracutaneous involvement is rare, with the exception of teeth. Hypoplastic enamel formation results in significant tooth decay. Nail dystrophies and alopecia are other common clinical manifestations. Individuals with GABEB have the potential to bear children and have a typical life expectancy.
  • DEB: This is a group of diseases caused by defects of anchoring fibrils. Blisters heal followed by dystrophic scarring. Formation of milia (1- to 4-mm white papules) results as a consequence of damage to hair follicles.
    • Dominantly inherited DEB: The onset of disease usually is at birth or during infancy, with generalized blistering as a common presentation. With increasing age, an evolution to localized blistering is present. A common variant described by Cockayne-Touraine has an acral distribution and minimal oral or tooth involvement. Another variant described by Pasini features more extensive blistering, scarlike papules on the trunk (termed albopapuloid lesions), and involvement of the oral mucosa and teeth. Dystrophic or absent nails are common in both of these dominantly inherited DEB variants.
    • RDEB: This group of diseases ranges from mild to severe in presentation.
      • A localized form, termed RDEB mitis, often involves acral areas and nails but shows little mucosal involvement. This subtype also demonstrates clinical manifestations similar to the dominantly inherited forms of DEB.
      • Severe RDEB, as described by Hallopeau-Siemens, usually shows generalized blistering at birth and subsequent extensive dystrophic scarring that is most prominent on the acral surfaces. This can produce pseudosyndactyly (mitten-hand deformity) of the hands and feet (see Media File 7). Flexion contractures of the extremities are increasingly common with age. Nails and teeth also are affected. Involvement of internal mucosa can result in esophageal strictures and webs, urethral and anal stenosis, phimosis, and corneal scarring. Malabsorption commonly results in a mixed anemia resulting from a lack of iron absorption, and overall malnutrition may cause failure to thrive (see Diet). Patients with severe RDEB who survive to childhood are at significant risk of developing aggressive SCC in areas of chronic erosions.
  • Ectodermal dysplasia-skin fragility syndrome: This is a rare disorder characterized by skin erosions, skin fragility and peeling beginning at birth or infancy that may be accompanied by alopecia, palmoplantar keratoderma, painful fissures, and nail dystrophy. Failure to thrive, cheilitis, hypohidrosis, and pruritus are other potential complications. The underlying molecular defect has been shown to be loss of function of the desmosomal protein plakophillin 1. Plakophillin is expressed mainly in suprabasilar keratinocytes and outer root sheath cells. Microscopic findings in this disease usually show intraepidermal acantholysis, located in the areas where plakophillin 1 is normally expressed. The molecular defect involves loss of function mutations in the PKP1 gene coding for plakophillin 1.4

Causes

Many stratified squamous epithelial tissues, such as the skin and oral mucosa, contain a complex BMZ. The BMZ is composed of many specialized components that combine to form anchoring complexes. At the superior aspect of the BMZ, keratin-containing intermediate filaments of the basal cell cytoskeleton insert on basal cell plasma membrane condensations termed hemidesmosomes. Anchoring filaments extend from the basal cell plasma membrane into the extracellular environment and span the lamina lucida, connecting hemidesmosomes with the lamina densa. At the most inferior aspect of the BMZ, type VII collagen-containing anchoring fibrils extend from the lamina densa into the papillary dermis, connecting the lamina densa to anchoring plaques, trapping interstitial collagen fibrils. Thus, the cutaneous BMZ connects the extensive basal cell cytoskeletal network with the abundant network of interstitial collagen fibrils in the dermis.

  • Keratin filaments: Keratins 5 and 14 combine to form intermediate filaments in basal keratinocytes. Keratins contain a central alpha-helical rod with several nonhelical interruptions, as well as nonhelical carboxyterminal and aminoterminal regions. The regions of highest conservation between the keratins are located on the ends of the keratin rod in the helix boundary motifs. Keratin intermediate filaments insert upon electron-dense structures termed hemidesmosomes.
  • Hemidesmosomes: These structures contain intracellular proteins, including plectin and BP230. Plectin (HD1) is a 500-kd protein that binds intermediate filaments. BP230, also termed BPAG1, is a 230-kd protein that has homology to both desmoplakin and plectin. BP230, like plectin, functions in the connection between hemidesmosomes and intermediate filaments. Hemidesmosomes also contain the intracellular portions of the transmembrane proteins collagen XVII (BP180) and a 6 b 4 integrin. The b 4 integrin subunit performs a central role in hemidesmosome formation and contains an especially large cytoplasmic domain, which interacts with other proteins of the hemidesmosomal plaque. Collagen XVII is a transmembrane collagenous protein that interacts with b 4 integrin and BP230 intracellularly and with laminin 5 extracellularly.
  • Anchoring filaments: These structures contain the extracellular portions of collagen XVII (BP180) and a 6 b 4 integrin. In addition, anchoring filaments contain the molecules laminin 5 and laminin 6. Similar to all members of the family of laminin proteins, laminin 5 is a large heterotrimeric molecule, containing a 3, b 3, and g 2 chains. Laminin 5 forms a disulfide-bonded attachment to laminin 6, the other known anchoring filament laminin, which contains a 3, b 1, and g 1 chains. Laminin 5 also forms a strong association with type VII collagen, which serves to connect anchoring filaments with anchoring fibrils.
  • Anchoring fibrils: Type VII collagen is the primary component of anchoring fibrils. Type VII collagen contains a large N-terminal globular domain (NC-1), which interacts with laminin 5 in the lamina densa; a long collagenous domain; and a smaller C-terminal globular domain (NC-2), which is cleaved proteolytically during anchoring fibril formation. Type VII collagen chains form a triple helix; then, 2 molecules join together in an antiparallel fashion. Next, anchoring fibrils are formed by lateral associations of antiparallel dimers. Anchoring fibrils wind around the dermal interstitial collagen fibrils and reinsert back upon the lamina densa, attaching the BMZ to the underlying dermis.
  • Molecular pathology of EBS
    • Most cases of EBS are associated with mutations of the genes coding for keratins 5 and 14. The level of skin separation is at the mid basal cell associated with variable intermediate filament clumping.
    • Most EBS keratin gene mutations are inherited dominantly and interfere with keratin filament assembly. A smaller subset of patients with recessively inherited disease of varying severity exists.
    • Mutations coding for the most conserved regions of keratins 5 and 14 (helix boundary domains) produce the most severe forms of EBS. Of the severe forms, the Dowling-Meara subtype exhibits intermediate filament clumping. Conversely, milder forms of the disease, such as the Weber-Cockayne subtype, are associated with mutations at the less conserved regions of keratin 5 and keratin 14 genes.
    • In patients with EBS, the mutations that code for the amino terminus of keratin 5 are associated with mottled pigmentation. A small group of patients with recessively inherited EBS has been shown to have associated muscular dystrophy caused by mutations of the gene coding for HD1/plectin.
  • Molecular pathology of JEB
    • JEB has a highly variable molecular etiology and represents a collection of different diseases. These diseases all cause blistering in the lamina lucida and variable hemidesmosomal abnormalities. Mutations in genes coding for laminin 5 subunits (a 3 chain, laminin b 3 chain, laminin g 2 chain), collagen XVII (BP180), a 6 integrin, and b 4 integrin have been demonstrated.
    • More than one half of JEB cases are caused by 1 of 2 recurrent nonsense mutations in the LAMB3 gene, which is helpful for mutation analysis and prenatal testing.
    • Herlitz (letalis) JEB is characterized by null mutations of laminin-5 genes, resulting in a lack of laminin-5 expression in the tissues of patients.
    • Missense mutations of laminin-5 genes that result in expression of presumably dysfunctional laminin 5 can result in a milder phenotype, such as GABEB. GABEB also can be caused by mutations of the gene coding for collagen XVII (BP180).
    • Mutations of the genes coding for b 4 and a 6 integrin also have been associated with JEB. In this group of diseases, separation of the skin occurs at the level of the hemidesmosome region. The resultant molecular defects contribute to the clinical manifestation of pyloric atresia.
  • Molecular pathology of DEB
    • DEB thus far has been associated in all cases with mutations of the gene coding for type VII collagen (COL7A1). Anchoring fibrils are affected in patients with DEB, and the degree of involvement ranges from subtle changes to complete absence.
    • In all patients, a sublamina lucida plane of blister cleavage is present. In some patients, defects of type VII collagen secretion are present.
    • In the recessive forms, COL7A1 mutations usually cause premature termination codons, resulting in an absence of type VII collagen in tissue. COL7A1 mutations, which do not cause premature termination codons, usually produce less severe disease. For example, mutations that produce glycine substitutions of the triple helical region can interfere with triple helical assembly of the type VII collagen molecule. These types of mutations, which exert a dominant-negative type of effect, are present in many patients with milder dominant forms of this disease.

More on Epidermolysis Bullosa

Overview: Epidermolysis Bullosa
Differential Diagnoses & Workup: Epidermolysis Bullosa
Treatment & Medication: Epidermolysis Bullosa
Follow-up: Epidermolysis Bullosa
Multimedia: Epidermolysis Bullosa
References
[ CLOSE WINDOW ]

References

  1. Fine JD, Eady RA, Bauer EA, Briggaman RA, Bruckner-Tuderman L, Christiano A, et al. Revised classification system for inherited epidermolysis bullosa: Report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa. J Am Acad Dermatol. Jun 2000;42(6):1051-66. [Medline].

  2. Fine JD, McGrath J, Eady RA. Inherited epidermolysis bullosa comes into the new millenium: a revised classification system based on current knowledge of pathogenetic mechanisms and the clinical, laboratory, and epidemiologic findings of large, well-defined patient cohorts. J Am Acad Dermatol. Jul 2000;43(1 Pt 1):135-7. [Medline].

  3. 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.

  4. Ersoy-Evans S, Erkin G, Fassihi H, Chan I, Paller AS, Sürücü S, et al. Ectodermal dysplasia-skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1. J Am Acad Dermatol. Jul 2006;55(1):157-61. [Medline].

  5. Ortiz-Urda S, Garcia J, Green CL, Chen L, Lin Q, Veitch DP. Type VII collagen is required for Ras-driven human epidermal tumorigenesis. Science. Mar 18 2005;307(5716):1773-6. [Medline].

  6. Woodley DT, Keene DR, Atha T, Huang Y, Lipman K, Li W. Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa. Nat Med. Jul 2004;10(7):693-5. [Medline].

  7. Woodley DT, Keene DR, Atha T, Huang Y, Ram R, Kasahara N, et al. Intradermal injection of lentiviral vectors corrects regenerated human dystrophic epidermolysis bullosa skin tissue in vivo. Mol Ther. Aug 2004;10(2):318-26. [Medline].

  8. Mavilio F, Pellegrini G, Ferrari S, Di Nunzio F, Di Iorio E, Recchia A, et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. Dec 2006;12(12):1397-402. [Medline].

  9. Allman S, Haynes L, MacKinnon P, Atherton DJ. Nutrition in dystrophic epidermolysis bullosa. Pediatr Dermatol. Sep 1992;9(3):231-8. [Medline].

  10. Ames WA, Mayou BJ, Williams KN, Williams K. Anaesthetic management of epidermolysis bullosa. Br J Anaesth. May 1999;82(5):746-51. [Medline].

  11. Bauer EA, Herron GS, Marinkovich MP, Khavari PA, Lane AT. Gene therapy for a lethal genetic blistering disease: a status report. Trans Am Clin Climatol Assoc. 1999;110:86-92. [Medline].

  12. Cameli N, Picardo M, Pisani A, Ortonne JP, Tosti A. Characterization of the nail matrix basement membrane zone: an immunohistochemical study of normal nails and of the nails in Herlitz junctional epidemolysis bullosa. Br J Dermatol. Jan 1996;134(1):182-4. [Medline].

  13. Ciccarelli AO, Rothaus KO, Carter DM, Lin AN. Plastic and reconstructive surgery in epidermolysis bullosa: clinical experience with 110 procedures in 25 patients. Ann Plast Surg. Sep 1995;35(3):254-61. [Medline].

  14. Darling TN, Bauer JW, Hintner H, Yancey KB. Generalized atrophic benign epidermolysis bullosa. Adv Dermatol. 1997;13:87-119; discussion 120. [Medline].

  15. Falabella AF, Valencia IC, Eaglstein WH, Schachner LA. Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds. Arch Dermatol. Oct 2000;136(10):1225-30. [Medline].

  16. Fassihi H, Eady RA, Mellerio JE, Ashton GH, Dopping-Hepenstal PJ, Denyer JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years' experience. Br J Dermatol. Jan 2006;154(1):106-13. [Medline].

  17. Fassihi H, Eady RA, Mellerio JE, Ashton GH, Dopping-Hepenstal PJ, Denyer JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years' experience. Br J Dermatol. Jan 2006;154(1):106-13. [Medline].

  18. Fine JD, Bauer EA, Briggaman RA, Carter DM, Eady RA, Esterly NB, 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].

  19. Haynes L, Atherton D, Clayden G. Constipation in epidermolysis bullosa: successful treatment with a liquid fiber-containing formula. Pediatr Dermatol. Sep-Oct 1997;14(5):393-6. [Medline].

  20. Heagerty AH, Eady RA, Kennedy AR, Nicolaides KH, Rodeck CH, Hsi BL, et al. Rapid prenatal diagnosis of epidermolysis bullosa letalis using GB3 monoclonal antibody. Br J Dermatol. Sep 1987;117(3):271-5. [Medline].

  21. Kerns ML, DePianto D, Dinkova-Kostova AT, Talalay P, Coulombe PA. Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex. Proc Natl Acad Sci U S A. Sep 4 2007;104(36):14460-5. [Medline].

  22. Lansdown R, Atherton D, Dale A, Sproston S, Lloyd J. Practical and psychological problems for parents of children with epidermolysis bullosa. Child Care Health Dev. Jul-Aug 1986;12(4):251-6. [Medline].

  23. Lin AN, Carter DM. Epidermolysis bullosa. Annu Rev Med. 1993;44:189-99. [Medline].

  24. Marinkovich MP. Update on inherited bullous dermatoses. Dermatol Clin. Jul 1999;17(3):473-85, vii. [Medline].

  25. Marinkovich MP, Herron GS, Khavari PA, Bauer EA. Inheritied Epidermolysis Bullosa. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB, eds. Fitzpatrick's Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill; 2003:596-609.

  26. Marinkovich MP, Meneguzzi G, Burgeson RE, Blanchet-Bardon C, Holbrook KA, Smith LT, et al. Prenatal diagnosis of Herlitz junctional epidermolysis bullosa by amniocentesis. Prenat Diagn. Nov 1995;15(11):1027-34. [Medline].

  27. Marinkovich MP, Verrando P, Keene DR, Meneguzzi G, Lunstrum GP, Ortonne JP, et al. Basement membrane proteins kalinin and nicein are structurally and immunologically identical. Lab Invest. Sep 1993;69(3):295-9. [Medline].

  28. McAllister JC, Peter Marinkovich M. Advances in inherited epidermolysis bullosa. Adv Dermatol. 2005;21:303-34. [Medline].

  29. McGrath JA, Eady RA. Molecular basis of blistering skin diseases. Hosp Med. Jan 1998;59(1):28-32. [Medline].

  30. McGrath JA, Ishida-Yamamoto A, Tidman MJ, Heagerty AH, Schofield OM, Eady RA. Epidermolysis bullosa simplex (Dowling-Meara). A clinicopathological review. Br J Dermatol. May 1992;126(5):421-30. [Medline].

  31. McGrath JA, Schofield OM, Mayou BJ, McKee PH, Eady RA. Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases. J Cutan Pathol. Apr 1992;19(2):116-23. [Medline].

  32. Meneguzzi G, Marinkovich MP, Aberdam D, Pisani A, Burgeson R, Ortonne JP. Kalinin is abnormally expressed in epithelial basement membranes of Herlitz's junctional epidermolysis bullosa patients. Exp Dermatol. Dec 1992;1(5):221-9. [Medline].

  33. Olivry T, Dunston SM, Marinkovich MP. Reduced anchoring fibril formation and collagen VII immunoreactivity in feline dystrophic epidermolysis bullosa. Vet Pathol. Nov 1999;36(6):616-8. [Medline].

  34. Ortiz-Urda S, Lin Q, Green CL, Keene DR, Marinkovich MP, Khavari PA. Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue. J Clin Invest. Jan 2003;111(2):251-5. [Medline].

  35. Pfendner E, Rouan F, Uitto J. Progress in epidermolysis bullosa: the phenotypic spectrum of plectin mutations. Exp Dermatol. Apr 2005;14(4):241-9. [Medline].

  36. Powell AM, Sakuma-Oyama Y, Oyama N, Black MM. Collagen XVII/BP180: a collagenous transmembrane protein and component of the dermoepidermal anchoring complex. Clin Exp Dermatol. Nov 2005;30(6):682-7. [Medline].

  37. Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol. Feb 1999;18(1):29-42. [Medline].

  38. Ryan MC, Christiano AM, Engvall E, Wewer UM, Miner JH, Sanes JR, et al. The functions of laminins: lessons from in vivo studies. Matrix Biol. Dec 1996;15(6):369-81. [Medline].

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

  40. Seitz CS, Giudice GJ, Balding SD, Marinkovich MP, Khavari PA. BP180 gene delivery in junctional epidermolysis bullosa. Gene Ther. Jan 1999;6(1):42-7. [Medline].

  41. Shaw DW, Fine JD, Piacquadio DJ, Greenberg MJ, Wang-Rodriguez J, Eichenfield LF. Gastric outlet obstruction and epidermolysis bullosa. J Am Acad Dermatol. Feb 1997;36(2 Pt 2):304-10. [Medline].

  42. Tabas M, Gibbons S, Bauer EA. The mechanobullous diseases. Dermatol Clin. Jan 1987;5(1):123-36. [Medline].

  43. Terrill PJ, Mayou BJ, McKee PH, Eady RA. The surgical management of dystrophic epidermolysis bullosa (excluding the hand). Br J Plast Surg. Aug-Sep 1992;45(6):426-34. [Medline].

  44. Terrill PJ, Mayou BJ, Pemberton J. Experience in the surgical management of the hand in dystrophic epidermolysis bullosa. Br J Plast Surg. Aug-Sep 1992;45(6):435-42. [Medline].

  45. Tong L, Hodgkins PR, Denyer J, Brosnahan D, Harper J, Russell-Eggitt I, et al. The eye in epidermolysis bullosa. Br J Ophthalmol. Mar 1999;83(3):323-6. [Medline].

  46. Uitto J, Eady R, Fine JD, Feder M, Dart J. The DEBRA International Visioning/Consensus Meeting on Epidermolysis Bullosa: summary and recommendations. J Invest Dermatol. Apr 2000;114(4):734-7. [Medline].

  47. Uitto J, Pulkkinen L, McLean WH. Epidermolysis bullosa: a spectrum of clinical phenotypes explained by molecular heterogeneity. Mol Med Today. Oct 1997;3(10):457-65. [Medline].

  48. Vailly J, Gagnoux-Palacios L, Dell'Ambra E, Roméro C, Pinola M, Zambruno G, et al. Corrective gene transfer of keratinocytes from patients with junctional epidermolysis bullosa restores assembly of hemidesmosomes in reconstructed epithelia. Gene Ther. Oct 1998;5(10):1322-32. [Medline].

  49. Väisänen L, Has C, Franzke C, Hurskainen T, Tuomi ML, Bruckner-Tuderman L, et al. Molecular mechanisms of junctional epidermolysis bullosa: Col 15 domain mutations decrease the thermal stability of collagen XVII. J Invest Dermatol. Dec 2005;125(6):1112-8. [Medline].

  50. Wright JT, Fine JD, Johnson L. Hereditary epidermolysis bullosa: oral manifestations and dental management. Pediatr Dent. Jul-Aug 1993;15(4):242-8. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

epidermolysis bullosa, EB, epidermolysis bullosa simplex, EBS, hemidesmosomal epidermolysis bullosa, HEDB, junctional epidermolysis bullosa, JEB, dystrophic epidermolysis bullosa, DEB, dominant dystrophic epidermolysis bullosa, DDEB, recessive dystrophic epidermolysis bullosa, RDEB

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

M Peter Marinkovich, MD, Associate Professor, Department of Dermatology and Program in Epithelial Biology, Stanford University Medical Center
M Peter Marinkovich, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

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 and American Dermatological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.