Butterfly Disease: A Visible Condition in Need of a Cure

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Patients with dystrophic epidermolysis bullosa face near-constant pain and discomfort. While there are several measures clinicians have to help them, a curative treatment remains elusive.

Today, patients across the country struggling with dystrophic epidermolysis bullosa (DEB) await the approval of a new topical gene therapy. The anticipation leading up to the approval makes sense, given the circumstances.1

If approved, this topical gene therapy could alter many lives, as there is still no cure for the debilitating condition.

The disease is largely unknown to the general public, though for those who are aware, it is most commonly called the "butterfly disease." This nickname is due to the fragility of patients’ skin as a result of small touches, as with the wings of a butterfly. Additionally, the skin blistering and erosions that often occur in a symmetrical pattern on the body, with lesions distributed on the upper and lower extremities—forming themselves into the shape of a butterfly.

Most importantly, however, butterflies are a symbol of transformation and of resilience. It is important for the medical community to see that DEB patients are in a position in which they must exhibit these qualities to deal with the challenges of living with this chronic and potentially life-threatening condition.

The best way to spread awareness of this so-called “butterfly disease” is to examine the sum of its parts: the condition’s characteristics, its causes, its comparisons to similar conditions, its current treatment options, and its future.

Characterizing the Condition of DEB

DEB is less well-known in both the medical world and among the general public due in large part to its rarity. The condition’s exact prevalence is not well-established, although it is estimated that DEB affects about 1 in 25,000 to 50,000 people around the world.2

The butterfly disease causes patients’ skin to be fragile and to easily blister. These blisters and erosions in the skin are the results of minor touches or even simply friction such as scratching or rubbing.

“The signs and symptoms of dystrophic epidermolysis bullosa vary widely among affected individuals,” according to the National Center for Advancing Translational Sciences. “In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, scarring, and other serious medical problems.”3

Additionally, the condition may occur in anyone as males and females of all ethnic and racial groups may end up with this skin disorder. The disease’s symptoms may begin to appear as a newborn or as an infant but can appear at any age.

One of the most alarming aspects of DEB is that patients have an increased risk of developing squamous cell carcinoma. This is the result of the chronic skin damage and scarring that occurs in DEB, leading to the development of abnormal and potentially cancerous cells.4

The “butterfly disease” description is most accurate in describing the most severe form of DEB, called recessive dystrophic epidermolysis bullosa (RDEB). RDEB accounts for approximately 25% of all cases of DEB and is the primary form of DEB referred to in this feature.5

The other major subtype of DEB is dominant dystrophic epidermolysis bullosa (DDEB), which is often observed to be much less severe.

“The signs and symptoms of this condition tend to be milder than those of the recessive forms, with blistering often limited to the hands, feet, knees, and elbows,” according to the US National Library of Medicine. “The blisters heal with scarring, but it is less severe than in recessive forms of this condition.”4

Most affected patients have malformed fingernails and toenails. In fact, for the mildest cases of dominant DEB, abnormal nails are the only sign of the disease.

Causes of DEB

To understand recessive DEB, it is important to note that it is a subgroup of epidermolysis bullosa (EB). EB describes several similar and rare genetic disorders that all cause the skin to be extremely fragile.

EB is classified into 4 main types: EB simplex; junctional EB; dystrophic EB,;and Kindler syndrome. DEB specifically occurs due to a mutation in the COL7A1 gene, which provides instructions for producing collagen VII, a protein that helps to anchor the layers of skin together.6

“The blistering can occur in the top layer of the skin known as the epidermis, below the epidermis or in the dermis, and so does dystrophic EB,” Karan Lal, DO, the Affiliated Dermatology Scottsdale director of pediatric dermatology and cosmetic surgery, told HCPLive. “It’s due to a defect in collagen VII, and collagen VII is part of the dermis and is responsible for the integrity of the skin.”7

Lal explained the characteristics of DEB, treatment options for patients, and the condition’s known causes. His insights helped shed light on the experiences of patients.

DEB is usually inherited in an autosomal recessive manner. In other words, an affected individual must inherit 2 copies of the mutated gene, 1 from each parent. In some cases, DEB can occur as a result of a spontaneous mutation and can be without a family history of the condition.

It is important for clinicians and patients alike to be aware of the background of this disorder as well as its heritability.

Comparison to Other EB Types

The main difference between other EB forms and the DEB subtype is the level at which the blistering occurs in the skin. For DEB patients, blistering occurs within the dermis, the layer below the epidermis.

This contrasts with other subtypes such as epidermolysis bullosa simplex (EBS) and junctional epidermolysis bullosa (JEB), with blisters occurring in the epidermis or at the junction between the epidermis and dermis.5

Another unique element of DEB is that blistering and erosions often lead to scarring and skin contractures, which can cause long-term disability and deformity. This is a hallmark feature of DEB, and is less common or absent in other subtypes of EB.

As stated before, patients affected by DEB can have their skin easily damaged by minor trauma or friction, leading to blisters, wounds, and scarring.

Blistering occurs below the basement membrane zone of the skin, which is the layer that separates the epidermis from the dermis. This type of blistering can lead to more severe scarring and deformities compared to other subtypes of EB.

“Recessive dystrophic EB is more of a multi-system disease,” Lal said. “These patients can get kidney failure, widespread infections, because they have open wounds.”8

Methods of Treatment for DEB

In addition to the butterfly disease’s tremendous burden on patients, one of the most difficult facts to accept is that there is currently no cure for DEB.

Treatment for the condition focuses mostly on managing symptoms and preventing complications, including wound care, pain management, nutritional support, and surgical interventions.

  • Wound care: DEB patients must take special care to protect their affected skin from damage and to prevent infection. Wound care measures can include dressing changes, use of bandages, and careful handling of the skin during daily activities.
  • Managing pain: The pain aspect of DEB can be a significant issue for patients, and various medications such as acetaminophen or opioids are often prescribed to help to manage it.
  • Nutritional support: Those with DEB may actually have difficulty eating due to blistering in the mouth and throat. Nutritional supplements, including high-calorie liquid formulas, may be required in order to maintain patients’ nutritional needs.
  • Skin grafts: In some cases, surgery is recommended for DEB patients to help them remove damaged skin and replace it with healthy skin from another region of the body.

It is important for patients to work with a healthcare team experienced in managing DEB to determine the best treatment plan for each case.

Arguably the most challenging aspects of DEB are the daily struggles experienced by individuals facing the condition, in terms of pain and skin traumas caused by daily activities. These daily challenges take tremendous courage for patients to deal with on a regular basis.

What’s Next for Treatment?

While treatment options are primarily supportive and focused on managing symptoms and complications, there are experimental gene and cell therapies being evaluated in clinical trials that may hold promise for patients.

There are several therapies under evaluation for DEB, including stem cell therapy, protein replacement therapy, exon skipping therapy, and CRISPR/Cas9 gene editing.

Most of these are in early stages of development, but there is one particular therapy with significant data behind it and the potential for approval by the US Food and Drug Administration (FDA) in only a few months.9

Beremagene geperpavec (B-VEC) therapy is one of the most anticipated new therapies being investigated for DEB. It is a topical gene therapy currently being evaluated for the treatment of recessive DEB.

The development of B-VEC therapy involved modifying a herpes simplex virus type 1 (HSV-1) vector, within which there were placed 2 copies of the COL7A1 coding sequence. The therapy’s gene delivery system then transcribes the viral DNA, translating it into C7 leading and secreting it into the extracellular space.6

B-VEC therapy uses a modified form of the adeno-associated virus (AAV) as a vector to deliver a functional copy of the COL7A1 gene to the skin cells of individuals with DEB. The AAV vector is designed to specifically target and deliver the COL7A1 gene to the cells in the skin that produce type VII collagen.

After the copy of the COL7A1 gene is delivered to the skin cells, it can be incorporated into the cells' DNA, leading to the production of type VII collagen. The goal is to restore the production of type VII collagen in the skin and to improve the integrity of the skin to reduce the frequency and severity of skin damage.

A year ago, Peter Marinkovich, MD, associate professor of dermatology for Stanford University School of Medicine, spoke with HCPLive about the therapy’s development.10

“It may be the case that more dermatologists will be seeing these patients, because the therapy is such an easy therapy to use,” Marinkovich said. “You use it at an outpatient basis, you can just use it in the clinic to treat these patients’ wounds. I think it’s really a cutting-edge type of therapy that, if everything goes well, may be approved in a year or so.”

That time may now be here, as the FDA scheduled the therapy’s PDUFA data on May 19 of 2023, along with a regulatory update. B-VEC’s phase 3 trial data showed around 70% of DEB patient wounds closing by 6 months compared to only about 20% for placebo.9

With the potential for a newfound cure on the horizon, individuals struggling with the butterfly disease may now be able to look into the future with some measure of hope.

The resilience shown by patients with DEB is astounding, and the clinicians and researchers working tirelessly to ensure their health and continued well-being are well aware of this. With the promise of new therapies comes the possibility of a new outlook for those who have had to face this disorder.


  1. Smith, T. (2023, January 12). FDA Extends PDUFA Date for B-VEC Gene Therapy for Dystrophic Epidermolysis Bullosa. HCPLive. Accessed March 30, 2023.
  2. Stanford Medicine Dermatology. Epidermolysis Bullosa Frequently Asked Questions. Stanford Medicine Dermatology website. Accessed March 30, 2023.
  3. National Institutes of Health. Dystrophic Epidermolysis Bullosa. Office of Rare Diseases Research website. Accessed March 30, 2023.
  4. MedlinePlus. Dystrophic Epidermolysis Bullosa. MedlinePlus website. Accessed March 30, 2023.,and%20other%20serious%20medical%20problems
  5. Smith, T (2023, March 28). Karan Lal, DO: Forms of Dystrophic Epidermolysis Bullosa. HCPLive. Accessed March 30, 2023.
  6. Mayo Clinic Staff. Epidermolysis bullosa. Mayo Clinic website. Accessed March 30, 2023.
  7. Smith, T (2023, January 3). Dystrophic Epidermolysis Bullosa: Positive Results from Topical Gene Therapy. HCPLive. Accessed March 30, 2023.
  8. Smith, T (2023, January 13). Karan Lal, DO: Experience Treating Patients with ‘Butterfly Disease’ Dystrophic Epidermolysis Bullosa. HCPLive. Accessed March 30, 2023.
  9. Smith, T (2023, January 12). FDA Extends PDUFA Date for B-VEC Gene Therapy for Dystrophic Epidermolysis Bullosa. HCPLive. Accessed March 30, 2023.
  10. Kunzmann, K (2022, March 26). Topical Gene Therapy B-VEC Reaches Phase 3 Efficacy Endpoints for DEB Disease Reversal. HCPLive. Accessed March 30, 2023.