Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Epidermolysis Bullosa Workup

  • Author: M Peter Marinkovich, MD; Chief Editor: William D James, MD  more...
 
Updated: Jan 08, 2014
 

Laboratory Studies

Obtain a skin biopsy following a thorough history and physical examination. Routine histologic analysis is useful only for excluding other causes of blistering. When epidermolysis bullosa (EB) is suspected, the best approach is to obtain 2 biopsy specimens. Analyze one specimen using electron microscopy (EM) and the other using immunofluorescent microscopy.

Evaluate anemia using CBC count with iron studies in patients with severe epidermolysis bullosa, especially recessively inherited epidermolysis bullosa.

Evaluate infection using bacterial cultures from poorly healing wounds or wounds that appear infected.

Next

Imaging Studies

Evaluate GI dysfunction. Esophageal strictures associated with junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, or the pyloric atresia associated with a rare form of junctional epidermolysis bullosa can be visualized best by an upper GI series or endoscopy.

Previous
Next

Other Tests

Evaluate nutrition using serum albumin, height and weight curves, diet diaries, and other analyses of nutrition and growth in patients with severe epidermolysis bullosa.

Evaluate contractures by establishing the range of motion of limbs and digits to monitor contractures and effectiveness of physical therapy.

Routine light microscopy can be used only to exclude other causes of blistering and cannot be used to make the diagnosis of epidermolysis bullosa.

Previous
Next

Procedures

Electron microscopy

Obtain a biopsy specimen from a fresh blister. The best way to obtain a fresh blister is to induce it in the office by gently rotating a pencil eraser back and forth over an area of skin until epidermal separation is appreciated. Perform the biopsy at the edge of the blister, sampling both unblistered and blistered skin. Place the specimen into the appropriate holding medium (check with the laboratory beforehand) and immediately send it for transmission EM. EM biopsy holding medium usually contains glutaraldehyde.

EM is the criterion standard for determining the level of blistering. EM can provide additional information on BMZ morphology that can be helpful in making the diagnosis. For example, intermediate filament clumping indicates Dowling-Meara epidermolysis bullosa simplex. Rudimentary hemidesmosomes often are found in junctional epidermolysis bullosa subtypes. Absent or altered anchoring fibrils often occur in dystrophic epidermolysis bullosa subtypes.

Immunofluorescent microscopy

This study can provide information on the level of the blistering. Obtain a biopsy specimen at the edge of a fresh blister for optimal results. Make arrangements with the laboratory before obtaining the specimen, and promptly send it for analysis. Zeus-holding medium is used widely for immunofluorescent microscopy.

Immunomapping with antibodies to a hemidesmosomal antigen (eg, BP230 obtained from sera of a patient with bullous pemphigus) and an antibody to a lamina densa protein (eg, type IV collagen) can distinguish epidermolysis bullosa simplex, junctional epidermolysis bullosa, and dystrophic epidermolysis bullosa. For example, in epidermolysis bullosa simplex, both antigens localize to the floor. In junctional epidermolysis bullosa, BP230 localizes to the roof of the blister, while type IV collagen localizes to the floor. In dystrophic epidermolysis bullosa, both antigens localize to the roof of the blister.

In addition to providing information about the level of the skin separation, immunofluorescent microscopy can be useful in providing an important clue regarding the underlying molecular defect. For example, the laboratory at Stanford University routinely examines biopsy specimens with a panel of antibodies against each of the antigens known to be affected in epidermolysis bullosa. Often, a specific absence of staining with a particular antibody indicates the specific molecular defect. Often, in milder disease subtypes and in dominant disease subtypes, alterations in expression of affected proteins may be too subtle to appreciate, and further tests are required. A diagram of the dermal epidermal basement membrane and level of disruption in epidermolysis bullosa subtypes is shown in the image below.

Diagram illustrating the organization of the derma Diagram illustrating the organization of the dermal epidermal basement membrane and level of disruption in epidermolysis bullosa subtypes

DNA mutation analysis

Perform mutation analysis after immunofluorescent microscopy. This is the final step in elucidating the underlying molecular defect, and in most cases, it reduces the number of genes to be screened. DNA is extracted from blood of the patient and family members. Initial mutation screening is performed by restriction fragment-length polymorphism analysis, hotspot analysis, and finally, direct DNA sequencing.

Prenatal diagnosis [8, 9, 10, 11]

Once the mutations are identified in a family, reliable prenatal diagnosis is possible. DNA for prenatal diagnosis can be obtained as a chorionic villi sample as early as the ninth week of gestation. Alternatively, amniotic fluid drawn after the eleventh week can provide the necessary DNA. Schedule the procedure in close conjunction with the diagnostic laboratory that will receive the sample.

Those interested in genetic analysis of epidermolysis bullosa patients should contact GeneDx.

Previous
 
 
Contributor Information and Disclosures
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 Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

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 Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, 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, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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.

References
  1. Fine JD. Inherited epidermolysis bullosa: past, present, and future. Ann N Y Acad Sci. 2010 Apr. 1194:213-22. [Medline].

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

  3. 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. [Medline].

  4. McGrath JA, Mellerio JE. Epidermolysis bullosa. Br J Hosp Med (Lond). 2006 Apr. 67(4):188-91. [Medline].

  5. 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.

  6. 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. [Medline].

  7. 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. [Medline].

  8. 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. [Medline].

  9. 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. [Medline].

  10. 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. [Medline].

  11. 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. [Medline].

  12. Ortiz-Urda S, Garcia J, Green CL, et al. Type VII collagen is required for Ras-driven human epidermal tumorigenesis. Science. 2005 Mar 18. 307(5716):1773-6. [Medline].

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

  14. [Guideline] American Academy of Pediatric Dentistry Council on Clinical Affairs. Guideline on management of dental patients with special health care needs. Pediatr Dent. 2008-2009. 30(7 Suppl):107-11. [Medline].

  15. 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. [Medline].

  16. 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. [Medline].

  17. 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. [Medline].

  18. 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].

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

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

  21. 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. [Medline].

  22. 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. [Medline].

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

  24. 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. [Medline].

  25. 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. 1996 Jan. 134(1):182-4. [Medline].

  26. 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. 1995 Sep. 35(3):254-61. [Medline].

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

  28. 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. 1991 Jan. 24(1):119-35. [Medline].

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

  30. 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. 2007 Sep 4. 104(36):14460-5. [Medline].

  31. 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. 1986 Jul-Aug. 12(4):251-6. [Medline].

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

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

  34. Marinkovich MP, Herron GS, Khavari PA, Bauer EA. Inheritied Epidermolysis Bullosa. 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.

  35. Marinkovich MP, Verrando P, Keene DR, et al. Basement membrane proteins kalinin and nicein are structurally and immunologically identical. Lab Invest. 1993 Sep. 69(3):295-9. [Medline].

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

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

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

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

  40. Mellerio JE, Weiner M, Denyer JE, et al. Medical management of epidermolysis bullosa: Proceedings of the IInd International Symposium on Epidermolysis Bullosa, Santiago, Chile, 2005. Int J Dermatol. 2007 Aug. 46(8):795-800. [Medline].

  41. 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. 1992 Dec. 1(5):221-9. [Medline].

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

  43. 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. 2003 Jan. 111(2):251-5. [Medline].

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

  45. 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. 2005 Nov. 30(6):682-7. [Medline].

  46. Ryan MC, Christiano AM, Engvall E, et al. The functions of laminins: lessons from in vivo studies. Matrix Biol. 1996 Dec. 15(6):369-81. [Medline].

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

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

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

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

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

  52. 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. 2000 Apr. 114(4):734-7. [Medline].

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

  54. Vaisanen L, Has C, Franzke C, et al. Molecular mechanisms of junctional epidermolysis bullosa: Col 15 domain mutations decrease the thermal stability of collagen XVII. J Invest Dermatol. 2005 Dec. 125(6):1112-8. [Medline].

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

 
Previous
Next
 
Epidermolysis bullosa simplex, Weber-Cockayne subtype. This mild bullous disease is characterized by localized blistering at sites of trauma such as the feet.
Epidermolysis bullosa simplex, Koebner subtype. Palmoplantar blistering and hyperkeratosis are noted.
Epidermolysis bullosa simplex, Koebner subtype. Close-up image shows hyperkeratotic papules and plaques on the palm.
Junctional epidermolysis bullosa, Herlitz 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
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.