A Research Guide for
Living with Epidermolysis Bullosa

FDA-APPROVED Beremagene geperpavec (Vyjuvek, also known as B-VEC) is the first gene therapy approved for any form of EB. It is approved for dystrophic EB (DEB) with COL7A1 mutations — originally for patients 6 months and older, and (since the September 2025 label update) for patients of all ages from birth. The therapy uses a modified herpes simplex virus type 1 (HSV-1) vector to deliver a functional copy of the COL7A1 gene directly to wound cells. When applied topically to EB wounds, the cells take up the gene and begin producing type VII collagen — the protein that is missing or dysfunctional in DEB. In the GEM-3 trial, 67% of Vyjuvek-treated wounds achieved complete closure at 6 months compared to 22% with placebo gel. It is applied weekly and, since the 2025 update, may be applied at home by patients or caregivers.

APPROVED (EMA/FDA) Filsuvez (birch bark extract, containing betulin as the active component) is a topical gel approved for the treatment of partial-thickness wounds in patients with junctional EB (JEB) and dystrophic EB (DEB). It was first approved by the EMA in June 2022 and subsequently by the FDA in December 2023. In the EASE trial, Filsuvez improved wound healing time compared to control gel. It works by promoting wound re-epithelialization through anti-inflammatory and wound-healing mechanisms. It is applied directly to wounds at each dressing change.

INVESTIGATIONAL / LIMITED USE Allogeneic hematopoietic stem cell transplant (HSCT) for severe RDEB was pioneered at the University of Minnesota. The rationale is that donor bone marrow cells can migrate to the skin, produce functional type VII collagen, and partially correct the underlying defect. Results have shown meaningful improvement in wound healing and skin integrity in some patients. However, the procedure carries significant risks including transplant-related mortality (historically 15–20% in early studies, improved with modified conditioning). It remains an option at a small number of specialized centers for the most severe cases.

INVESTIGATIONAL In a landmark 2017 case, a child with severe JEB had nearly 80% of his skin replaced with gene-corrected epidermal grafts. Stem cells were taken from a small area of his skin, the LAMB3 gene was corrected using a retroviral vector, and the corrected cells were grown into sheets of skin in a laboratory, then grafted onto his body. The child, who had been near death, survived and his regenerated skin remained stable years later. This proof-of-concept demonstrated that gene-corrected skin grafts can replace large areas of EB skin, though it has not yet been scaled to routine clinical use.

• What specific type and subtype of EB do I/does my child have?
• Has genetic testing been performed to identify the exact mutation?
• What is the inheritance pattern, and what does this mean for other family members?
• Should we have genetic counseling?
• What complications should I watch for with this specific type?
• Am I eligible for any gene therapy or clinical trials?
• Is there a multidisciplinary EB clinic I should be referred to?
• How often should I have skin cancer screening?

Immunofluorescence antigen mapping (IFM) is performed on a fresh skin biopsy taken from the edge of a new blister or from rubbed but unblistered skin. Fluorescent antibodies are used to identify the level of skin separation and the specific proteins present or absent. This test determines whether the blistering is within the epidermis (EBS), at the junction (JEB), or below the junction (DEB), and can identify which protein is affected.

TEM examines the ultrastructure of the skin at extremely high magnification. It can directly visualize structural abnormalities — such as absent or reduced anchoring fibrils in DEB, or abnormal hemidesmosomes in JEB. While less commonly used today due to the availability of genetic testing, it remains valuable when other tests are inconclusive.

Genetic testing is now the gold standard for EB diagnosis. It identifies the specific gene mutation causing EB, which:

• Confirms the EB type and subtype definitively
• Determines the inheritance pattern (important for family planning)
• Predicts disease severity to some extent (e.g., null mutations typically cause more severe disease)
• Determines eligibility for gene therapy (Vyjuvek requires COL7A1 mutations)
• Enables prenatal or preimplantation genetic testing for future pregnancies

Next-generation sequencing panels covering all known EB genes are widely available. Turnaround time is typically 4–8 weeks.

• Lance blisters early. New blisters should be lanced (punctured) with a sterile needle to drain the fluid before they enlarge and cause more damage. The blister roof (top skin layer) should be left in place as a natural dressing.
• Do not peel or debride the blister roof unless it is heavily contaminated or the wound beneath needs assessment.
• Drain from the side. Insert the needle at the edge of the blister at a low angle. Press gently to express the fluid.
• Hygiene. Clean hands, sterile needle, and clean workspace for every blister lancing.

Selecting the right dressings is critical. EB dressings must be non-adherent, provide moisture balance, and be comfortable. Key principles:

• Primary (contact) layer: Non-adherent dressings such as Mepitel (silicone mesh), Adaptic, or Mepilex Lite. Never use standard gauze directly on EB wounds — it will adhere and cause further damage.
• Secondary layer: Absorbent padding (e.g., soft gauze rolls, Mepilex foam) over the primary layer to absorb exudate.
• Retention: Self-adherent wrap (Coban or similar) or tubular bandages (Tubifast). Never use adhesive tape directly on EB skin.
• Frequency: Dressing changes typically every 1–3 days depending on wound drainage. Bathing before dressing changes can help soften and remove old dressings.

• Lukewarm baths (not hot) help soften dressings for removal, clean wounds, and reduce bacterial load.
• Add a small amount of table salt (approximately 1/4 to 1/2 cup per tub) or use a gentle cleanser to approximate normal saline concentration.
• Some families add dilute bleach (1/4 cup household bleach per full bathtub) 2–3 times per week to reduce bacterial colonization, particularly with recurrent infections.
• Soaking time: 15–30 minutes. Longer soaking helps remove adherent dressings.
• Pat dry gently — never rub.

EB wounds are chronically colonized with bacteria and at constant risk of infection. Signs of wound infection include:

• Increasing redness, warmth, or swelling around a wound
• Foul odor or change in wound drainage (purulent, green, or brown)
• Increased pain at the wound site
• Fever
• Delayed healing or wound deterioration

Topical antimicrobials (medical-grade honey such as Medihoney, polyhexamethylene biguanide [PHMB], silver-containing dressings) are commonly used. Topical mupirocin may be used for specific infections. Systemic antibiotics are reserved for clinical infection (cellulitis, spreading redness, fever).

Avoid: Prolonged use of topical antibiotics to reduce resistance risk. Iodine-based products should be used cautiously due to potential thyroid effects with large wound surface areas.

• What specific dressings do you recommend for my/my child’s wounds?
• Can I get a wound care nurse to help train me in proper technique?
• How do I recognize the difference between colonization and true infection?
• Is my child a candidate for Vyjuvek (gene therapy) or Filsuvez (birch bark extract)?
• How often should dressing changes be done?
• What pain management should be used before dressing changes?
• Are there any wound care supplies covered by my insurance?
• Should I be using bleach baths or antimicrobial rinses?

• Before dressing changes: Oral acetaminophen or ibuprofen given 30–60 minutes before. For severe pain, stronger analgesics may be needed. Sucrose solutions for infants.
• During dressing changes: Distraction techniques (videos, music, storytelling), optimal positioning, allowing the patient control over the process when possible.
• Chronic pain: Gabapentin or pregabalin for neuropathic pain. Low-dose tricyclic antidepressants. Psychological support including cognitive behavioral therapy.
• Topical: Lidocaine-based products can help with specific wound pain. Apply to intact skin surrounding painful wounds.
• Non-pharmacologic: Warm (not hot) baths, music therapy, relaxation techniques, physical therapy, occupational therapy.

Itching in EB can be severe and debilitating. It disrupts sleep, causes scratching that creates new wounds, and significantly reduces quality of life.

• First-line: Non-sedating antihistamines (cetirizine, loratadine) during the day; sedating antihistamines (hydroxyzine, diphenhydramine) at night.
• Second-line: Gabapentin or pregabalin (particularly effective for EB-related itch). Doxepin (topical or oral).
• Topical: Cooling moisturizers, menthol-containing creams, colloidal oatmeal baths.
• Keep skin moisturized: Dry skin increases itching. Emollients (white soft paraffin, coconut oil, specialized EB moisturizers) applied to unblistered skin.
• Environmental: Keep the room cool; dress in loose, soft cotton clothing; use soft bedding.

• High protein: EB patients need significantly more protein than normal to support wound healing. Target 115–200% of normal protein requirements.
• High calorie: Chronic wound healing is metabolically expensive. Caloric supplementation is often needed.
• Iron supplementation: Iron-deficiency anemia is nearly universal in severe EB due to chronic blood loss from wounds and poor iron absorption. Oral iron is often insufficient; IV iron infusions may be needed.
• Zinc: Important for wound healing. Deficiency is common in EB. Supplement with zinc sulfate or gluconate.
• Vitamin D: Deficiency is common due to limited sun exposure (wounds, bandaging, photosensitivity in Kindler EB). Supplement routinely.
• Vitamin C: Supports collagen synthesis and wound healing.
• Fiber and fluids: Constipation is extremely common in EB due to reduced mobility, opioid use, and anal blistering. Adequate fiber, fluids, and stool softeners are essential.

• Oral blistering: Blisters on the tongue, gums, palate, and inside of cheeks can make eating painful. Soft, cool foods are tolerated best. Avoid sharp, crunchy, or acidic foods.
• Microstomia: Progressive scarring can reduce mouth opening in DEB, making dental care and eating increasingly difficult.
• Dental caries: EB patients have very high rates of dental decay due to enamel defects, difficulty brushing, and soft food diets. Regular dental care with an EB-experienced dentist is essential.
• Esophageal strictures: In RDEB, repeated esophageal blistering leads to narrowing (strictures) that can cause dysphagia (difficulty swallowing) and food impaction. Endoscopic balloon dilatation may be needed. Strictures may recur.
• Gastrostomy (G-tube): When oral intake is insufficient despite optimization, a feeding tube placed directly into the stomach can be life-saving for maintaining nutrition. This is common in severe JEB and RDEB.

• Is my child growing appropriately for their age?
• Should we see a dietitian experienced with EB?
• Does my child need iron studies, and could IV iron be beneficial?
• Are vitamin D, zinc, and other levels being monitored?
• Should we consider a gastrostomy tube for supplemental feeding?
• How often should esophageal dilatation be considered?
• What dental care plan do you recommend?

• SCC typically develops in areas of chronic wounds or scarring, often on the extremities
• Metastasis is more common and more rapid than in non-EB SCC
• Any wound that is not healing, looks different from other wounds, is growing rapidly, has raised or rolled edges, or bleeds easily should be biopsied immediately
• Regular full-body skin examinations by a dermatologist experienced with EB are essential, starting in adolescence for RDEB patients
• Treatment typically involves wide surgical excision; amputation may be necessary for limb SCC
• Chemotherapy and immunotherapy (cemiplimab) are used for advanced/metastatic SCC

In RDEB, repeated blistering and scarring of the fingers and toes leads to fusion (pseudosyndactyly) and contractures, creating a “mitten” deformity that progressively reduces hand function. This is one of the most disabling complications of severe RDEB.

• Prevention: Daily finger wrapping with individual finger dressings to prevent skin-to-skin contact and fusion. Silicone finger separators. Occupational therapy to maintain range of motion.
• Surgical release: Surgical separation of fused fingers can restore function temporarily, but recurrence is common. Multiple surgeries over a lifetime may be needed.

• Eyes: Corneal abrasions and blistering can cause pain, light sensitivity, and scarring. Regular ophthalmology exams. Lubricating eye drops. Avoid rubbing eyes.
• Ears: External ear canal blistering can cause conductive hearing loss. Regular audiology assessments.
• Airway: Laryngeal and tracheal involvement can cause hoarseness and, in severe cases, airway obstruction. This is rare but requires monitoring.

• Anemia: Chronic blood loss from wounds plus chronic inflammation leads to severe anemia of chronic disease plus iron deficiency. Require regular monitoring and aggressive iron replacement (often IV).
• Osteoporosis: Limited mobility, poor nutrition, low vitamin D, and chronic inflammation all contribute. DEXA scans should be performed. Bisphosphonates may be needed.
• Renal disease: Chronic renal disease can develop in EB from a combination of amyloidosis, chronic infections, and nephrotoxic medications. Regular kidney function monitoring is essential.
• Cardiomyopathy: Dilated cardiomyopathy has been reported, particularly in RDEB, likely related to chronic anemia, iron overload from transfusions, and selenium/carnitine deficiency.

FDA-APPROVED (May 2023)

• Indication: Dystrophic EB (DEB) with COL7A1 mutation(s), for wounds. Originally approved for ages 6 months and older; the FDA expanded the label in September 2025 to include patients from birth.
• Mechanism: A non-replicating HSV-1 viral vector carrying a functional copy of the COL7A1 gene. Applied topically to wounds. The viral vector delivers the gene to wound cells, which then produce type VII collagen.
• Key trial (GEM-3, NCT04491604): Randomized, placebo-controlled. 67% of Vyjuvek-treated wounds achieved complete closure at 6 months vs. 22% with placebo. Statistically significant improvement in wound healing.
• Administration: Applied weekly to selected wounds. As of the September 2025 label update, patients or caregivers may apply Vyjuvek at home (it no longer must be applied by a healthcare provider), with added flexibility for dressing changes. The gel is spread on the wound surface and covered with a non-adherent dressing.
• Safety: Generally well-tolerated. Most common side effects were local wound reactions (itching, redness). The HSV-1 vector is non-replicating and does not cause herpes infection, but patients should be monitored for symptoms.
• Limitations: Treats individual wounds, not all skin. Gene expression is transient, requiring repeated application. Long-term durability data still being collected.
• Cost: Extremely expensive. Access may be challenging. Patient assistance programs are available from the manufacturer (Krystal Biotech).

FDA-APPROVED

Zevaskyn (prademagene zamikeracel, “pz-cel”; from Abeona Therapeutics; previously studied as “EB-101”) was FDA-approved on April 29, 2025 — the first and only cell-based gene therapy for recessive dystrophic EB (RDEB). A small skin biopsy is taken, the cells are genetically corrected in the laboratory to make working type VII collagen, grown into sheets of skin, and then surgically grafted onto the patient’s chronic wounds in a single application. Unlike Vyjuvek (a topical gel that delivers the gene to existing wound cells and is re-applied), Zevaskyn creates permanently gene-corrected skin in one procedure.

• Who it’s for: adults and children with RDEB (confirmed COL7A1 mutations), applied to selected large or persistent wounds.
• Key trial (VIITAL, NCT04227106): a single application achieved meaningful wound healing and pain reduction sustained over months.
• Practical notes: it is a surgical, one-time-per-wound therapy delivered at qualified treatment centers (e.g., Stanford), and is high-cost; discuss eligibility with your EB specialist. Vyjuvek, Zevaskyn, and Filsuvez are not used together on the same wound.
• The “Butterfly Child” case: In 2017, a boy with severe JEB (LAMB3 mutation) had ~80% of his skin replaced with gene-corrected epidermal grafts that remained intact for years — an early proof-of-concept for the gene-corrected-skin approach now realized in Zevaskyn.

• Is Vyjuvek appropriate for my/my child’s wounds?
• How do I access Vyjuvek, and is it covered by my insurance?
• Are there any gene therapy clinical trials I should consider?
• What are the realistic expectations for gene therapy — which wounds can be treated?
• Are there any risks I should know about?
• How long does the effect of Vyjuvek last?

APPROVED (EMA 2022 / FDA 2023)

• Indication: Partial-thickness wounds in JEB and DEB patients aged 6 months and older
• Mechanism: Betulin (from birch bark) has anti-inflammatory and wound-healing properties. Promotes keratinocyte migration and re-epithelialization.
• Key trial (EASE, NCT03068780): Randomized, vehicle-controlled. Showed faster wound closure with Filsuvez compared to control gel.
• Use: Applied at every dressing change as a thin layer on wounds. Can be used alongside standard dressings.
• Safety: Generally well-tolerated. Local wound reactions may occur.

INVESTIGATIONAL / LIMITED USE

HSCT for RDEB aims to provide donor-derived cells that can migrate to the skin and produce functional type VII collagen. Pioneered at the University of Minnesota.

• Studies have shown improvements in wound healing, blister formation, and overall skin integrity in some patients
• Benefits may take months to appear and tend to be partial rather than curative
• Significant risks: transplant-related mortality (reduced with improved conditioning regimens but still present), graft-versus-host disease, infections during immunosuppression
• Best outcomes seen in young children transplanted early, before extensive scarring develops
• Not standard of care — considered on a case-by-case basis at specialized centers

INVESTIGATIONAL

• Recombinant type VII collagen (PTR-01): Intravenous infusion of recombinant human type VII collagen for RDEB. Early trials showed that IV-delivered C7 localizes to the dermal-epidermal junction. Phase II/III trials have been conducted.
• Cell-based therapies: Injection of fibroblasts or mesenchymal stem cells into EB wounds to provide local collagen production. Several small studies have shown temporary benefit.
• Gene editing (CRISPR/Cas9): Preclinical and early clinical work on using CRISPR to directly correct EB-causing mutations in patient cells. Not yet in clinical use but represents a future direction.
• Gentamicin (readthrough therapy): The aminoglycoside antibiotic gentamicin can cause readthrough of premature stop codon mutations, producing some functional protein. Topical gentamicin has shown some evidence of type VII collagen restoration in RDEB patients with nonsense mutations. Not FDA-approved for this indication.

• DEBRA International: The global EB patient organization; publishes clinical practice guidelines and coordinates care standards
• EB-CLINET: European EB Clinical Network of reference centers
• NICE (UK): Technology appraisals for EB treatments
• Mellerio et al. (2020): Best Practice Guidelines for Skin and Wound Care in EB
• DEBRA of America: US-based patient support, research funding, advocacy
• DEBRA UK: UK patient support and EB community nursing service
• DEBRA Australia: Australian EB patient organization

FAILED Rigosertib, a PI3K/PLK pathway inhibitor, was explored as a treatment for SCC arising in EB patients. Clinical development did not demonstrate sufficient efficacy to support regulatory approval for this indication.

LIMITED BENEFIT Intradermal injection of allogeneic fibroblasts was investigated as a cell-based therapy for RDEB wounds. While some early studies showed temporary increases in type VII collagen at injection sites, the benefit was transient and not durable enough to change the disease course. The approach has largely been superseded by gene therapy strategies.

NOT EFFECTIVE Because EB simplex is a structural protein disorder, not an immune-mediated disease, systemic immunosuppressants (corticosteroids, methotrexate, cyclosporine) are not effective and expose patients to unnecessary side effects. They should not be used for any form of inherited EB (as distinct from EB acquisita, which is autoimmune).

WARNING Some unregulated clinics market “stem cell treatments” for EB with no published evidence of efficacy. These are often expensive and potentially dangerous. Legitimate EB stem cell research is conducted through regulated clinical trials at established medical centers. Always verify that any proposed treatment is part of a registered clinical trial (ClinicalTrials.gov) or an approved therapy.

• Am I/is my child eligible for Vyjuvek gene therapy?
• Should we consider bone marrow transplant, and what are the risks vs. benefits?
• Are there any clinical trials we should consider?
• What new therapies are in the pipeline for our specific EB type?
• How should we be screening for squamous cell carcinoma?
• Is there a protein replacement trial available?
• What is the evidence for the treatment being proposed?

• Create a routine. Consistent daily wound care at the same time reduces anxiety for both the patient and caregiver.
• Organize supplies. Keep all wound care supplies organized and easily accessible. Many families use a dedicated wound care cart or station.
• Pre-medicate for pain. Give pain medication 30–60 minutes before dressing changes to ensure it takes effect.
• Let the patient participate. Even young children can be given age-appropriate choices and control during wound care (e.g., choosing which wound to start with, holding supplies).
• Bath before bandages. Bathing before dressing changes softens old dressings and makes removal less traumatic.
• Cut dressings in advance. Pre-cutting dressings to the right sizes before starting saves time during the actual dressing change.

• Clothing: Soft, seamless clothing (turned inside out if seams are rough). Avoid rough fabrics, labels, and tight waistbands. Specialized EB clothing is available from some organizations.
• Footwear: Soft, well-fitting shoes with seamless socks. Custom orthotics may help redistribute pressure. Some patients find sheepskin boot liners helpful.
• Temperature: Heat worsens blistering in many EB types. Keep rooms cool. Avoid prolonged sun exposure.
• Handling infants: Never lift an EB infant under the arms. Support under the buttocks and behind the head/neck. Use thick padding (sheepskin or padded mattresses) in cribs and car seats.
• School and play: Work with schools to accommodate EB needs (padded seating, avoidance of contact sports, access to wound care supplies, air conditioning).

• Caregiver burnout is real and predictable. The physical and emotional demands of EB care are extraordinary. Seek help before you are exhausted.
• Connect with other EB families. DEBRA organizations facilitate family connections, camps, and support groups. Other EB families understand in a way that no one else can.
• Professional support. Mental health support for caregivers and patients should be considered part of standard EB care, not an optional extra.
• Respite care. If available, respite services can provide temporary relief for primary caregivers. DEBRA may help arrange trained respite providers.
• Financial assistance. EB care is expensive. DEBRA of America, EB Research Partnership, and other organizations offer financial aid, insurance navigation, and dressing supply assistance.