Epidermolysis bullosa (EB) represents a rare group of mechanobullous dermatoses defined as the prototype of genetic disorders with skin fragility, according to the 2020 consensus statement introducing the concept of these conditions.1 EB, which affects an estimated 500,000 individuals globally, is linked to substantial morbidity and mortality.2
The 4 primary classical EB types are EB simplex, dystrophic EB (DEB), junctional EB, and Kindler syndrome, and more than 30 subtypes of EB have been identified thus far.3 EB has a significant heterogeneity in disease presentation and severity depending on type and subtype, ranging from painful localized bullae and wounds to generalized bullae and erosions with extensive multisystemic involvement.2
Because EB has no curative treatment, disease management consists of supportive therapies to facilitate wound care and symptom control.3 However, advances in “understanding the molecular genetics and underlying pathomechanisms of different forms of EB” has led to promising developments in research exploring novel treatments for the disease, wrote Has et al in a review published in June 2020 in Molecular Diagnosis and Therapy.4
An important ally in the search for such therapies is the EB Research Partnership (EBRP), the largest global nonprofit organization supporting EB research. The EBRP was cofounded by Eddie Vedder of the iconic rock band Pearl Jam, together with his wife Jill Vedder, an activist and philanthropist who serves as the EBRP’s vice chairperson. They were inspired to become involved in EB efforts when the child of a family friend was born with EB.5
Among their many efforts to advance the pursuit of curative therapies in EB research, the Vedders recently helped to raise nearly $2 million through Venture Into Cures, a live benefit show that aired in November 2020 and featured appearances by numerous other celebrities including Billie Eilish, Andra Day, Jimmy Kimmel, and Chris Hemsworth.6
To date, the EBRP has funded 94 projects, raised $40 million for research, and led to a 15-fold increase in the number of clinical trials focused on EB – including several phase 3 clinical trials.7,8 A key feature of their innovative model is the EB Clinical Research Consortium (EBCRC), which prioritizes “collaboration and shared data” so that “every research team has the opportunity to benefit from the others.”5
To discuss treatment challenges, emerging developments, and remaining needs pertaining to EB, we interviewed the head of the EBCRC, Anna L. Bruckner, MD, MSCS, professor of dermatology and pediatrics and head of pediatric dermatology at the University of Colorado School of Medicine and Children’s Hospital Colorado in Aurora.
What are some of the top challenges in managing EB?
EB is a family of genetic skin disorders with a range of severities and manifestations. Even though it is often thought of as a skin condition, many forms of EB are truly multisystem disorders, which makes coordinating the care complex. For instance, individuals with recessive DEB require daily skin and wound management, nutritional therapies, and ongoing management of their eyes, teeth, esophagus, blood (for anemia), and bones. Patients can be bothered by pain and itch, which are difficult to manage.
On top of all this, because EB is rare, there is a lot of ignorance about the needs of patients, which are often not met by insurers and care providers. It can be a challenge for families to get insurance coverage for the wound care supplies they need. Many patients and parents are not able to find or pay for well-trained help for the care that occurs at home, so the burden of care on the family is very high.9
Psychosocial support for the patient and family is critical.3 Now that patients are living longer, transitioning care to adult providers is also a challenge.
In addition to dermatologists, what is the role of other specialists in EB care?
Pediatricians who focus on children with complex medical needs are key to coordinating care among the following specialists:
- Dietitian/nutritionist. Patients may not be able to eat enough by mouth to meet their nutritional needs and often require special formulas or feeds given by gastrostomy tube. They require extra vitamin and mineral supplements to prevent deficiencies and related problems such as anemia.
- Gastroenterologist. We have close relationships with 2 or 3 in our hospital who perform a procedure called esophageal dilation to open strictures in the esophagus that are common in patients with recessive DEB.
- Physical therapist and occupational therapist to help optimize mobility and function.
- Nurse coordinator/wound care nurse specialist.
- Anesthesiologist trained in the perioperative management of EB. It’s very important to minimize unintentional trauma to the skin and mucous membranes during procedures requiring general anesthesia.
- Dentist. Patients are at higher risk for dental disease and require a gentle approach to dental care. Tooth enamel is abnormal in some forms of EB.
- Ophthalmologist to treat abrasions and erosions that involve the cornea and monitor for corneal scarring.
- Psychosocial support from social workers and other mental health clinicians.Child life specialists can be very helpful in the clinic to help with distraction or coping to get the child through difficult visits or procedures.
- Hand surgeon to correct the contractures and mitten deformity that can occur in patients with recessive DEB.
What are the most notable recent developments in EB research and treatment?
This is an exciting time for research in EB, and there are currently a variety of treatments being studied.2,4,10 Some are topical medications used in wound care to accelerate wound healing and may have applications across different types of EB. Disease-specific treatments for recessive DEB include systemic protein replacement (an IV infusion of recombinant collagen VII) and localized gene therapy (at least 3 different approaches are being studied now).
We are learning more about the secondary inflammatory effects that result from the skin and mucosal fragility. Addressing the inflammation may help to improve symptoms and quality of life for many patients.
What are additional needs in this area in terms of education and advocacy?
The Dystrophic EB Research Association (DEBRA, a patient advocacy and support organization, debra.org) has called EB the “worst disease you’ve never heard of” – highlighting the rarity of EB. Educating the medical community and the general population about the treatment and impact of EB is critical, as is advocacy to help patients get the care and resources they need. There are a limited number of centers with EB expertise in the US.
1. 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
2. Prodinger C, Reichelt J, Bauer JW, Laimer M. Epidermolysis bullosa: advances in research and treatment. Exp Dermatol. 2019;28(10):1176-1189. doi:10.1111/exd.13979
3. Martin K, Geuens S, Asche JK, et al. Psychosocial recommendations for the care of children and adults with epidermolysis bullosa and their family: evidence based guidelines. Orphanet J Rare Dis. 2019;14(1):133. doi:10.1186/s13023-019-1086-5
4. Has C, South A, Uitto J. Molecular therapeutics in development for epidermolysis bullosa: update 2020. Mol Diagn Ther. 2020;24(3):299-309. doi:10.1007/s40291-020-00466-7
5. Venture into cures: building a faster path to curing epidermolysis bullosa. Epidermolysis Bullosa Research Partnership. https://www.ebresearch.org/uploads/1/0/4/4/104465755/ebrp_ventureintocures_campaign-overview_1.pdf. Accessed April 6, 2021.
6. Jill and Eddie Vedder and friends raise more than $1.8 million for EB Research Partnership, to find a cure for epidermolysis bullosa. PR Newswire. https://www.ebresearch.org/uploads/1/0/4/4/104465755/ebrp_ventureintocures_campaign-overview_1.pdf. November 23, 2020. Accessed April 6, 2021.
7. Our impact. Epidermolysis Bullosa Research Partnership. https://www.ebresearch.org/our-impact.html. Accessed April 6, 2021.
8. Clinical Trials – EB Research Partnership. Epidermolysis Bullosa Research Partnership. https://www.ebresearch.org/clinical-trials.html. Accessed April 6, 2021.
9. 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
10. Prodinger C, Bauer JW, Laimer M. Translational perspectives to treat epidermolysis bullosa —-Where do we stand? Exp Dermatol. 2020;29(11):1112-1122. doi:10.1111/exd.14194