Understanding dystrophic epidermolysis bullosa (DEB)

DEB is a type of epidermolysis bullosa (EB)1-4

EB refers to a group of genetic blistering disorders characterized by skin fragility due to the separation of connective tissues, ultimately causing blistering and wounds in response to minimal friction or trauma.

There are 3 major types of EB1,5-8*

Each EB type is defined by unique underlying gene mutations that determine where skin layer separation occurs.

Despite the underlying cause of each EB type being different, all EB types present with similar dermatologic manifestations. Differentiating DEB is critical because patients with DEB require active and vigilant surveillance for progressive and potentially life-threatening external and internal complications.

Affected genes, proteins, and skin layers by EB type

Affected genes

Affected proteins

Affected skin layer

Epidermolysis bullosa simplex (EBS)

CD151, DST, EXPH5, KLHL24, KRT5, KRT14, PLEC

BPAG1, Exophilin 5, Kelch-like protein 24, Keratin 5, Keratin 14, Plectin, Tetraspanin 24

Epidermis

Occurs in approx.

70%

of patients

Dystrophic epidermolysis bullosa (DEB)

COL7A1

Collagen VII

Sublamina densa

Occurs in approx.

25%

of patients

Junctional epidermolysis bullosa (JEB)

COL17A1, ITGA3, ITGA6, ITGB4, LAMA3, LAMB3, LAMC2

Collagen XVII, Integrin α3 subunit, Integrin α6b4, Laminin-332

Lamina lucida

Occurs in approx.

5%

of patients

Affected genes

Affected proteins

Affected skin layer

Affected genes

CD151, DST, EXPH5, KLHL24, KRT5, KRT14, PLEC

Affected proteins

BPAG1, Exophilin 5, Kelch-like protein 24, Keratin 5, Keratin 14, Plectin, Tetraspanin 24

Affected skin layer

Epidermis

Occurs in approx.

70%

of patients

Affected genes

Affected proteins

Affected skin layer

Affected genes

COL7A1

Affected proteins

Collagen VII

Affected skin layer

Sublamina densa

Occurs in approx.

25%

of patients

Affected genes

Affected proteins

Affected skin layer

Affected genes

COL17A1, ITGA3, ITGA6, ITGB4, LAMA3, LAMB3, LAMC2

Affected proteins

Collagen XVII, Integrin α3 subunit, Integrin α6b4, Laminin-332

Affected skin layer

Lamina lucida

Occurs in approx.

5%

of patients

*Kindler EB (KEB) is a very rare type of EB that occurs in <1% of patients and is caused by mutation of the FERMT-1 gene, resulting in mixed separation of multiple layers due to lack of the protein kindlin-1.

Adapted from De Rosa L, Latella MC, Secone Seconetti A, et al. Cold Spring Harb Perspect Biol. 2020.

DEB is caused by mutations in the COL7A1 gene3,4

In healthy skin, collagen VII plays a critical role in anchoring fibrils to maintain cohesion between the epidermis and dermis.2,4,6

  1. Anchoring fibrils

In DEB, the mutated COL7A1 gene leads to reduced or absent collagen VII, causing a loss of anchoring fibrils and disrupting the connection between the epidermis and dermis.2-4

This results primarily in skin fragility and blistering of not only the skin but also the mucosa and epithelial lining of organs.3,9

  1. Blister

Adapted from De Rosa L, Latella MC, Secone Seconetti A, et al. Cold Spring Harb Perspect Biol. 2020.

There are 2 types of DEB, based on inheritance pattern:

dominant DEB (DDEB) and recessive DEB (RDEB)2

DDEB10,11

(Nearly half of patients in the US)

At least 1 parent is affected

  • 50% chance the child will be an unaffected noncarrier
  • 50% chance the altered gene will be passed to their child, resulting in DEB

RDEB10,11

(Nearly half of patients in the US)

Neither parent is affected, but both are carriers

  • 25% chance the altered gene will be passed to their child, resulting in DEB
  • 50% chance the child will be an unaffected carrier
  • 25% chance the altered gene will not be passed, and the child will be an unaffected noncarrier
  • Unaffected
  • Carrier
  • DEB

In some cases, DEB can occur de novo, confirmed by the absence of an affected COL7A1 gene in both parents.12

Both DEB subtypes can present with similar dermatologic symptoms, a range in severity, and potential for serious complications. Regardless of severity, both DDEB and RDEB share an increased risk for complications, including squamous cell carcinoma (SCC).7,9,13-15

Recognizing DEB

DEB can easily be missed or misdiagnosed when looking at symptoms alone1,7,16,17

Testing for DEB

Diagnosing DEB accurately is critical7

References: 1. Bruckner AL, Losow M, Wisk J, et al. The challenges of living with and managing epidermolysis bullosa: insights from patients and caregivers. Orphanet J Rare Dis. 2020;15(1):1. doi:10.1186/s13023-019-1279-y 2. Denyer J, Pillay E, Clapham J. Best practice guidelines for skin and wound care in epidermolysis bullosa. Wounds International. May 3, 2017. Accessed September 21, 2021. https://www.woundsinternational.com/resources/details/best-practice-guidelines-skin-and-wound-care-in-epidermolysis-bullosa 3. Fortuna G, Aria M, Cepeda-Valdes R, Trevino MGM, Salas-Alanís JC. Pain in patients with dystrophic epidermolysis bullosa: association with anxiety and depression. Psychiatry Investig. 2017;14(6):746-753. doi:10.4306/pi.2017.14.6.746 4. Eichstadt S, Tang JY, Solis DC, et al. From clinical phenotype to genotypic modelling: incidence and prevalence of recessive dystrophic epidermolysis bullosa (RDEB). Clin Cosmet Investig Dermatol. 2019;12:933-942. doi:10.2147/CCID.S232547 5. Condorelli AG, Dellambra E, Logli E, Zambruno G, Castiglia D. Epidermolysis bullosa–associated squamous cell carcinoma: from pathogenesis to therapeutic perspectives. Int J Mol Sci. 2019;20(22):5707. doi:10.3390/ijms20225707 6. De Rosa L, Latella MC, Secone Seconetti A, et al. Toward combined cell and gene therapy for genodermatoses. Cold Spring Harb Perspect Biol. 2020;12(5):a035667. doi:10.1101/cshperspect.a035667 7. Has C, Liu L, Bolling MC, et al. Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa. Br J Dermatol. 2020;182(3):574-592. doi:10.1111/bjd.18128 8. Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183(4):614-627. doi: 10.1111/bjd.18921 9. Fine J-D, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I. Epithelial associated tissues. J Am Acad Dermatol. 2009;61:367-384. doi:10.1016/j.jaad.2009.03.052 10. Fine J-D. Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the National Epidermolysis Bullosa Registry. JAMA Dermatol. 2016;152(11):1231-1238. doi:10.1001/jamadermatol.2016.2473 11. Slide show: how genetic disorders are inherited. Mayo Clinic. Updated February 15, 2020. Accessed September 21, 2021. https://www.mayoclinic.org/tests-procedures/genetic-testing/multimedia/genetic-disorders/sls-20076216?s 12. Autosomal dominant. Medlineplus.gov. Accessed October 4, 2021. https://medlineplus.gov/ency/article/002049.htm 13. Das BB, Sahoo S. Dystrophic epidermolysis bullosa. J Perinatol. 2004;24(1):41-47. doi:10.1038/sj.jp.7211019 14. Fine J-D, Bruckner-Tuderman L, Eady RAJ, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70(6):1103-1126. doi:10.1016/j.jaad.2014.01.903 15. EB in Depth. Debra of America. Accessed September 21, 2021. https://debra.org/about-eb/eb-depth 16. Kao C-H, Chen S-J, Hwang B, Yang A-H, Hsu C-Y, Huang C-H. Junctional epidermolysis bullosa. J Chin Med Assoc. 2006;69(10):503-506. 17. Tabor A, Pergolizzi JV Jr, Marti G, Harmon J, Cohen B, Lequang JA. Raising awareness among healthcare providers about epidermolysis bullosa and advancing toward a cure. J Clin Aesthet Dermatol. 2017;10(5):36-48.