Recognizing dystrophic epidermolysis bullosa (DEB)

DEB symptoms can range from mild to severe1-4

DEB is a serious genetic blistering disease caused by mutations in the COL7A1 gene.

DEB can be either dominant (DDEB) or recessive (RDEB) based on inheritance pattern. Both DDEB and RDEB can present with similar dermatologic signs and symptoms, a range in severity, and potential for serious complications.

Across DDEB and RDEB, severity ranges from localized to intermediate to severe:

Signs and symptoms across DEB4-8

Localized DDEB

  • Fragile skin localized to fingers and toes
  • Sometimes only nails thicken and discolor

Shared Intermediate DDEB and RDEB

  • Fragile skin
  • Milia
  • Abnormal blistering
  • Abnormal skin pigmentation
  • Chronic wounds
  • Atypical and atrophic scarring
  • Skin infection
  • Inflammation
  • Fusion of fingers and toes
  • Affected eyes and mouth
  • Affected GI and genitourinary tracts
  • Constipation
  • Oral mucosal blisters
  • Esophageal strictures
  • Osteoporosis/joint contractures
  • Squamous cell carcinoma (SCC)

Severe RDEB

  • Mitten deformity
  • Nail and hair loss
  • Anemia
  • Weak bones
  • Growth delay
  • Renal amyloidosis
  • Cardiomyopathy
  • SCC
  • Early mortality (primarily SCC related)

Regardless of severity, both DDEB and RDEB share an increased risk for complications, including SCC.8

Image sources: (Localized DDEB): Reprinted from Orphanet Journal of Rare Diseases, 5, Fine JD. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-12. 2010;5(1):12:1-17. Copyright (2010). Licensed under the https://creativecommons.org/licenses/by-nd/2.0/. (Intermediate DDEB): Reprinted from JAAD International, 2, Rogers CL, Gibson M, Kern JS, et al. A comparison study of outcome measures for epidermolysis bullosa: Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and the Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB). 2021;2:134-152. Copyright (2021), with permission from Elsevier. (Intermediate RDEB): Reprinted from Journal of Tissue Viability, 30, Wong T-W, Yang C-C, Hsu C-K, Liu C-H, Yu-Yun Lee J. Transplantation of autologous single hair units heals chronic wounds in autosomal recessive dystrophic epidermolysis bullosa: a proof-of-concept study. 2021;30(1):36-41. Copyright (2021), with permission from Elsevier. (Severe RDEB): Reprinted from Actas Dermo-Sifiliográficas (English Edition), 110, Imbernón-Moya A, Maseda-Pedrero R, Feito M, de Lucas R. Dilated cardiomyopathy in a child with recessive dystrophic epidermolysis bullosa. 2019;110(1):81-83. Copyright (2019), with permission from Elsevier.

A missed DEB diagnosis can happen

DEB and other EB types have similar symptoms, making symptom-based diagnosis unreliable.3,9,10

Shared external symptoms across EB types4,8,11-18

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External symptoms

DEB

EB Simplex (EBS)

Junctional EB (JEB)

Kindler EB (KEB)

Fragile skin

Abnormal blistering of the skin

Abnormal skin pigmentation

Aplasia/hypoplasia of the nails
(absent/small nails)

Atrophic scars
(sunken or indented skin due to damage)

Atypical scarring of the skin

Dystrophic fingernails
(poor fingernail formation)

Dystrophic toenails
(poor toenail formation)

Oral mucosal blisters
(blisters of the mouth)

Milia
(milk spot)

Recurrent skin infections

Differentiating DEB from other EB populations is critical. Diagnosing DEB accurately can enable greater vigilance and proactive care.8‑10,19,20

Diagnosis of EB is frequently made through external dermatological symptoms alone

Nearly half of all patients with EBS (the most prevalent EB type) are DIAGNOSED BASED ON SYMPTOMS ALONE, despite challenges with this approach10,21

Overlapping symptoms across non-EB skin blistering conditions cloud DEB recognition further9

A missed DEB diagnosis can occur since DEB also has overlapping symptoms with other non-EB blistering disorders that are genetic, autoimmune, and bacterial in nature.

Shared external symptoms across skin conditions4,8,11-18,22-33

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GENETIC BLISTERING CONDITIONS

AUTOIMMUNE BLISTERING DISORDERS

INFECTIOUS DISEASES

External symptoms

EB

Epidermolytic ichthyosis

Eczema of the hand

Linear IgA bullous dermatosis

Bullous pemphigoid

Pemphigus vulgaris

Staphylococcal scalded skin syndrome

Blistering is the predominant shared symptom across a variety of skin conditions

Abnormal blistering of the skin

Skin ulcer

Atypical scarring of the skin

Erythema/reddening of the skin

Nail abnormalities

Infection

Inflammation

Affected eyes and mouth

GI tract

Osteoporosis/joint contractures

Despite the greater vigilance required for patients with DEB, they can be undermanaged due to missed or delayed diagnosis.7

Some patients with DEB may initially be misdiagnosed

Initial symptoms

Blisters starting at age 44

Lifelong dystrophic toenails

Original diagnosis

From initial presentation at age 44, autoimmune, bacterial infection, or some type of EB based on symptoms and biopsies

Diagnostic testing

Symptoms and biopsy used to inform prior diagnosis

Genetic test ordered, revealed COL7A1 mutation

Confirmed diagnosis

DDEB diagnosis confirmed at age 49

Jenny, 49, living with DDEB

Initial symptoms

Blistering and missing skin at birth

Original diagnosis

Junctional epidermolysis bullosa (JEB)

Diagnostic testing

Symptoms and biopsy used to inform prior diagnosis

Genetic test ordered, revealed COL7A1 mutation

Confirmed diagnosis

RDEB confirmed via genetic testing at 8 months

Abby, 15, living with RDEB

Initial symptoms

Blisters starting at age 44

Lifelong dystrophic toenails

Original diagnosis

From initial presentation at age 44, autoimmune, bacterial infection, or some type of EB based on symptoms and biopsies

Diagnostic testing

Symptoms and biopsy used to inform prior diagnosis

Genetic test ordered, revealed COL7A1 mutation

Confirmed diagnosis

DDEB diagnosis confirmed at age 49

Jenny, 49, living with DDEB

Initial symptoms

Blistering and missing skin at birth

Original diagnosis

Junctional epidermolysis bullosa (JEB)

Diagnostic testing

Symptoms and biopsy used to inform prior diagnosis

Genetic test ordered, revealed COL7A1 mutation

Confirmed diagnosis

RDEB confirmed via genetic testing at 8 months

Abby, 15, living with RDEB

It’s important to look beyond symptoms to determine an accurate DEB diagnosis.

Watch stories about living with DEB

Testing for DEB

Diagnosing DEB accurately is critical7

Free sponsored test available

Know whether it’s DEB with genetic testing at NO CHARGE to patients through Krystal Decode DEBTM

References: 1. 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 2. 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 3. 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 4. Das BB, Sahoo S. Dystrophic epidermolysis bullosa. J Perinatol. 2004;24(1):41-47. doi:10.1038/sj.jp.7211019 5. 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 6. 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 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. EB in depth. Debra of America. Accessed September 21, 2021. https://www.debra.org/about-eb/eb-depth 9. 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. 10. 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 11. Dystrophic epidermolysis bullosa. Genetic and Rare Diseases Information Center. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/2150/dystrophic-epidermolysis 12. Dystrophic EB. Debra-international.org. Accessed October 12, 2021. https://www.debra-international.org/dystrophic-eb 13. Epidermolysis bullosa simplex. Genetic and Rare Diseases Information Center. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/10752/epidermolysis-bullosa-simplex/ 14. Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010;28(1):23-32. 15. Junctional epidermolysis simplex. Genetic and Rare Diseases Information Center. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/2152/junctional-epidermolysis-bullosa 16. Junctional epidermolysis bullosa. Dermnetnz.org. Accessed October 11, 2021. https://dermnetnz.org/topics/junctional-epidermolysis-bullosa 17. Kindler EB. Debra-international.org. Accessed October 11, 2021. https://www.debra-international.org/kindler-eb 18. Kindler syndrome. Genetic and Rare Diseases Information Center. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/4391/kindler-syndrome 19. Fine J-D, Johnson LB, Weiner M, et al. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. 2009;60(2):203-211. doi:10.1016/j.jaad.2008.09.035 20. Montaudié H, Chiaverini C, Sbidian E, Charlesworth A, Lacour J-P. Inherited epidermolysis bullosa and squamous cell carcinoma: a systematic review of 117 cases. Orphanet J Rare Dis. 2016;11(1):117. doi:10.1186/s13023-016-0489-9 21. Feinstein JA, Jambal P, Peoples K, et al. Assessment of the timing of milestone clinical events in patients with epidermolysis bullosa from North America. JAMA Dermatol. 2019;155(2):196-203. 22. Epidermolytic ichthyosis. Genetic and Rare Diseases Information Center. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/1039/epidermolytic-ichthyosis 23. Epidermolytic ichthyosis. Firstskinfoundation.org. Accessed September 21, 2021. https://www.firstskinfoundation.org/types-of-ichthyosis/epidermolytic-ichthyosis 24. Oakley A. Hand dermatitis. DermNet NZ. Updated March 2018. Accessed September 21, 2021. https://dermnetnz.org/topics/hand-dermatitis/ 25. Oakley A. Linear IgA bullous disease. DermNet NZ. Updated February 2015. Accessed September 21, 2021. https://dermnetnz.org/topics/linear-iga-bullous-disease/ 26. Bullous pemphigoid. Genetic and Rare Diseases Information Center. Updated August 10, 2016. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/5972/bullous-pemphigoid 27. Bullous pemphigoid – NORD (national organization for rare disorders). Rarediseases.org. Published February 11, 2015. Accessed September 21, 2021. https://rarediseases.org/rare-diseases/bullous-pemphigoid/ 28. Bullous pemphigoid. Medlineplus.gov. Accessed September 21, 2021. https://medlineplus.gov/ency/article/000883.htm 29. Pemphigus vulgaris. Genetic and Rare Diseases Information Center. Accessed September 21, 2021. https://rarediseases.info.nih.gov/diseases/7355/pemphigus-vulgaris 30. Pemphigus: signs and symptoms. Aad.org. Accessed September 21, 2021. https://www.aad.org/public/diseases/a-z/pemphigus-symptoms 31. Brar SK, Bhale GN, Brar BK. A localized non-healing ulcer: an unusual clinical presentation of pemphigus vulgaris. Int J Res Dermatol. 2020;6(3):413. 32. Staphylococcal scalded skin syndrome. Johns Hopkins Medicine. Accessed September 21, 2021. https://www.hopkinsmedicine.org/health/conditions-and-diseases/staphylococcal-scalded-skin-syndrome 33. Staphylococcal scalded skin syndrome – NORD (national organization for rare disorders). Rarediseases.org. Published February 11, 2015. Accessed September 21, 2021. https://rarediseases.org/rare-diseases/staphylococcal-scalded-skin-syndrome/