Epidermolysis Bullosa
Disease Details
Family Health Simplified
- Description
- Epidermolysis bullosa is a group of genetic disorders that cause the skin to be extremely fragile and to blister easily in response to minor injury or friction.
- Type
-
Epidermolysis bullosa (EB) is classified into four main types:
1. Epidermolysis Bullosa Simplex (EBS)
2. Junctional Epidermolysis Bullosa (JEB)
3. Dystrophic Epidermolysis Bullosa (DEB)
4. Kindler Syndrome
The type of genetic transmission for these varies:
- EBS: Predominantly autosomal dominant
- JEB: Autosomal recessive
- DEB: Can be autosomal dominant or autosomal recessive, depending on the subtype
- Kindler Syndrome: Autosomal recessive - Signs And Symptoms
-
Epidermolysis bullosa (EB) is a group of genetic disorders that cause the skin to be very fragile and to blister easily. The signs and symptoms of EB can vary widely depending on the specific type and severity but generally include:
- Blisters on the skin, especially on the hands and feet, due to minor injuries or friction
- Blistering of the mucous membranes inside the mouth, eyes, nose, throat, and digestive tract
- Thickened skin on the palms and soles of the feet
- Deformities such as fusion of fingers or toes (syndactyly) or abnormal nail growth/loss of nails
- Hair loss or scarring of the scalp
- Dental problems, such as tooth decay from enamel erosion
- Difficulty swallowing (dysphagia) due to blistering in the esophagus
- Anemia and nutritional deficiencies due to chronic wounds and difficulties eating
Severity ranges from mild, causing minor problems, to severe, which can be life-threatening. - Prognosis
- A 2014 study classified cases into three types—EBS, JEB and DEB—and reviewed their times of death. The first two types tended to die in infancy and the last in early adulthood. In a survey of 11 families affected by the disease, lack of awareness of the disease by both the public and health care providers raised concerns about the care provided.
- Onset
- Epidermolysis bullosa (EB) can present at birth or within the first few weeks of life. Some milder forms may not become apparent until later in childhood or adolescence.
- Prevalence
- Epidermolysis bullosa (EB) is a group of rare inherited disorders that cause fragile skin and mucous membranes, leading to the formation of blisters and erosions in response to minor trauma. The prevalence of EB varies by type, but it is generally estimated to occur in approximately 1 in 20,000 live births worldwide.
- Epidemiology
- An estimated 20 per million live births are diagnosed with EB, and 9 per million people in the general population have the condition. Of these cases, approximately 92% are EBS, 5% are DEB, 1% are JEB, and 2% are unclassified. Carrier frequency ranges from 1 in 333 for JEB, to 1 in 450 for DEB; the carrier frequency for EBS is presumed to be much higher than JEB or DEB.The disorder occurs in every racial and ethnic group and affects both sexes.
- Intractability
- Epidermolysis bullosa (EB) is generally considered intractable, as there is currently no cure. The disease is characterized by fragile skin that blisters easily, and management primarily focuses on symptomatic relief, wound care, and preventing complications. Advances in gene therapy and other research hold promise, but as of now, treatment is largely supportive.
- Disease Severity
- Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by fragile skin that blisters easily. The severity of EB varies widely, ranging from mild to life-threatening. The most severe forms, such as Junctional Epidermolysis Bullosa (JEB) and Dystrophic Epidermolysis Bullosa (DEB), can lead to significant complications, including infections, scarring, and a shortened lifespan. Conversely, milder forms like Epidermolysis Bullosa Simplex (EBS) may present with less frequent blistering and minimal complications. The severity is generally determined by the specific genetic mutation involved and the type of EB diagnosed.
- Healthcare Professionals
- Disease Ontology ID - DOID:2730
- Pathophysiology
- The human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers (Dermo epidermal junction) that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, resulting in extremely fragile skin—even minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. EB individuals manifest unremitting skin blistering that evolves into chronic wounds, inflammation, and fibrosis. People with EB have compared the sores with third-degree burns. Furthermore, as a complication of the chronic skin damage, people with EB have an increased risk of malignancies (cancers) of the skin. Virtually any organ lined or covered by epithelium may be injured in inherited EB. External eye, esophagus, upper airway, and genitourinary tract are the epithelial surfaced tissues that are at particular risk.
- Carrier Status
-
Epidermolysis bullosa (EB) is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Carrier status for EB typically refers to individuals who carry one mutated gene copy of a recessive form of the condition, but do not show symptoms themselves. These carriers have a 50% chance of passing the mutated gene to their offspring, who would only develop the condition if they inherit two mutated gene copies—one from each parent.
For dominant forms of EB, carriers usually do manifest symptoms because they only need one copy of the mutated gene to exhibit the condition. - Mechanism
-
Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by fragile skin that blisters easily. The mechanism of EB involves defects in the proteins that provide structural stability to the skin.
**Molecular Mechanisms:**
1. **Epidermolysis Bullosa Simplex (EBS):**
- **Genes involved:** KRT5, KRT14.
- **Proteins affected:** Keratin 5, Keratin 14.
- **Mechanism:** Mutations impair the formation of keratin intermediate filaments in the basal keratinocytes, leading to cellular fragility and skin blistering.
2. **Junctional Epidermolysis Bullosa (JEB):**
- **Genes involved:** LAMB3, LAMC2, LAMA3, COL17A1.
- **Proteins affected:** Laminin-332, Collagen XVII.
- **Mechanism:** Mutations lead to defects in the proteins essential for the formation and maintenance of the dermo-epidermal junction, resulting in separation and blistering at this level.
3. **Dystrophic Epidermolysis Bullosa (DEB):**
- **Genes involved:** COL7A1.
- **Proteins affected:** Collagen VII.
- **Mechanism:** Mutations affect the anchoring fibrils that connect the epidermis to the dermis, causing sub-epidermal blistering.
4. **Kindler Syndrome:**
- **Genes involved:** FERMT1.
- **Proteins affected:** Kindlin-1.
- **Mechanism:** Mutations disrupt cell adhesion and signal transduction, leading to skin fragility, photosensitivity, and progressive skin thickening.
Each type of EB arises from mutations in specific genes that alter the production or function of crucial structural proteins, compromising the integrity of the skin and leading to blister formation. - Treatment
- Research has focused on changing the mixture of keratins produced in the skin. There are 54 known keratin genes—of which 28 belong to the type I intermediate filament genes and 26 to type II—which work as heterodimers. Many of these genes share substantial structural and functional similarity, but they are specialized to cell type and/or conditions under which they are normally produced. If the balance of production could be shifted away from the mutated, dysfunctional keratin gene toward an intact keratin gene, symptoms could be reduced. For example, sulforaphane, a compound found in broccoli, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 μmol/day = 0.9 mg) and applied topically to newborns (1 μmol/day = 0.2 mg in jojoba oil).As of 2008 clinical research at the University of Minnesota has explored allogeneic bone marrow transplantation for RD and junctional EB, treating a two-year-old child who is one of two brothers with EB. A second transplant has also been performed on the child's older brother. A Missouri boy has also successfully undergone the transplant, as well as a 5 year old boy from Alabama. So far there have been 12 successful transplants. Another transplant is scheduled for a California baby. A clinical trial is planned for 30 subjects. However, the immune suppression that bone marrow transplantation requires causes a risk of serious infections with large scale blisters and skin erosion. Indeed, at least four people have died in the course of either preparation for or institution of bone marrow transplantation for EB, out of only a small group of patients treated so far. The mechanism of action of this therapy is unclear as hematopoietic stem cells are not thought to contribute to epithelial lineages. Rather, it is speculated that cross-correction from tissue-resident graft-derived immune cells contributes to the observed clinical benefit.A pilot study performed in 2015 suggests that systemic granulocyte-colony stimulating factor (G-CSF) may promote increased wound healing in people with dystrophic EB. Transplanting skin derived from genetically modified stem cells onto the wound surfaces has been studied with a report of improvements in one person.A 2017 clinical trial with male RDEB (recessive dystrophic EB) patients conducted successful grafting of type VII gene corrected keratinocytes (COL7A1 gene correction using retrovirus transduction), without any serious adverse effects. Type VII collage formation was observed at the dermis-epidermis junction in significant amounts.A 2020 study demonstrated the safe allogenic grafting of acellular dermal matrix/scaffolds in EB patients without any observed infection or necrosis and instead noted fewer required dressing changes, promoted wound healing, pain reduction, and an overall improvement in the quality of life of the patients.In 2022, a pharmaceutical gel made out of birch bark extract from Betula pendula and Betula pubescens was approved by the European Union as a treatment for epidermolysis bullosa.
- Compassionate Use Treatment
-
Epidermolysis bullosa (EB) is a group of genetic conditions that cause the skin to be very fragile and to blister easily. For patients with severe forms of EB, traditional treatments focus on wound care, pain management, and infection prevention. However, several compassionate use treatments, off-label, or experimental therapies may be considered:
1. **Gene Therapy**: Experimental approaches in clinical trials are exploring ways to correct the genetic defects that cause EB. Some therapies use viral vectors to deliver functional copies of the faulty gene to skin cells.
2. **Protein Replacement Therapy**: This involves administering recombinant proteins to patients. For instance, a topical gel containing a protein missing in certain types of EB is under investigation.
3. **Cell Therapy**: A promising approach includes the use of stem cells or gene-corrected cells. Techniques using fibroblasts or keratinocytes, either derived from the patient and genetically corrected or from healthy donors, are being tested.
4. **CRISPR/Cas9 Technology**: This gene-editing tool is being studied for its potential to directly repair genetic mutations associated with EB.
5. **Repurposing Drugs**: Some existing medications are used off-label to treat symptoms or underlying mechanisms of EB. Examples include drugs that reduce inflammation or modulate immune responses.
6. **Bone Marrow Transplant**: Experimental but potentially curative in some severe cases, this treatment may help by introducing stem cells that can produce healthy skin proteins.
7. **Collagenase Ointment**: Off-label use of collagenase-based treatments may aid in debriding chronic wounds and promoting healing.
8. **Small Molecule Therapies**: Compounds that could potentially upregulate the production of missing or defective proteins in EB patients are also under investigation.
It is important to consult with specialized healthcare providers to understand the risks, potential benefits, and the current status of these treatments. - Lifestyle Recommendations
-
For epidermolysis bullosa, lifestyle recommendations include:
1. **Skin Care:** Regularly apply moisturizing ointments to prevent skin dryness and cracking. Use non-adhesive dressings to protect wounds.
2. **Clothing:** Wear soft, non-abrasive clothing made from materials like cotton. Avoid seams and tags that might irritate the skin.
3. **Bathing:** Use mild, fragrance-free soaps. Keep bath water lukewarm and pat the skin dry gently with a soft towel.
4. **Nutrition:** Maintain a balanced diet to support overall health and skin repair. Consider supplements if nutritional deficiencies are identified.
5. **Activity:** Avoid activities that can cause trauma or blisters. Swimming may be less traumatic than other forms of exercise.
6. **Footwear:** Choose soft, well-fitted shoes and check feet regularly for blisters or injuries.
7. **Environment:** Keep living areas at a comfortable temperature to avoid excessive sweating, which can aggravate the condition.
8. **Infection Prevention:** Regularly clean wounds and monitor for signs of infection. Consult healthcare providers for appropriate antibiotic use if necessary. - Medication
-
Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by fragile skin that blisters easily. Medications used to manage EB focus on symptom relief and preventing complications. Common interventions include:
1. **Topical Antibiotics**: To prevent or treat secondary bacterial infections in wounds (e.g., mupirocin or fusidic acid).
2. **Pain Management**: Pain relievers such as acetaminophen, ibuprofen, or stronger pain medications as needed.
3. **Anti-inflammatory Medications**: Corticosteroids or other anti-inflammatory drugs may be prescribed for inflammatory symptoms.
4. **Wound Care Products**: Special dressings and ointments that promote healing and protect the skin.
Nanotechnology is an emerging area in the treatment of EB, focusing on targeted drug delivery systems, wound healing, and gene therapy. Experimental approaches include nanoparticles loaded with therapeutic agents to enhance skin repair and reduce inflammation.
Always consult a healthcare provider for accurate diagnosis and tailored treatment plans. - Repurposable Drugs
-
Epidermolysis bullosa (EB) is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Some drugs that have shown potential for repurposing in the treatment of EB include:
1. **Epinephrine (adrenaline)**: Used in topical formulations to reduce blistering and promote wound healing.
2. **Losartan**: Originally used for hypertension, it may help in reducing fibrosis in certain types of EB.
3. **Gentamicin**: An antibiotic that has shown promise in promoting read-through of certain genetic mutations causing EB, potentially improving skin integrity.
Research is ongoing to evaluate the efficacy and safety of these drugs in treating EB. - Metabolites
-
Epidermolysis bullosa (EB) is a group of genetic disorders characterized by fragile skin that blisters easily. Metabolite analysis related to EB can be crucial for understanding the disease. Some studies have identified altered levels of certain metabolites, such as amino acids and proteins, which can be indicative of the body's response to damage and repair mechanisms. These alterations might reveal potential therapeutic targets or biomarkers for disease severity.
However, specific metabolite data in EB is complex and requires comprehensive biochemical analysis to pinpoint exact metabolic disruptions. If you need in-depth data on specific metabolites, a detailed examination of scientific literature or genomics databases might be required. - Nutraceuticals
-
Epidermolysis bullosa (EB) is a group of genetic conditions causing fragile skin that blisters easily. While there is no cure, nutraceuticals may offer supportive benefits. Commonly considered nutraceuticals for EB include:
1. **Vitamin C:** Supports collagen synthesis and overall skin health.
2. **Zinc:** Important for immune function and wound healing.
3. **Vitamin E:** Acts as an antioxidant, potentially aiding in skin repair.
4. **Omega-3 Fatty Acids:** May reduce inflammation and promote skin integrity.
It is essential to consult healthcare providers before starting any nutraceutical regimen for EB to ensure safety and suitability. - Peptides
-
Epidermolysis bullosa (EB) is a group of genetic conditions that result in fragile skin which blisters easily. Peptides are short chains of amino acids that can play a role in wound healing, inflammation reduction, and skin regeneration, making them a potential therapeutic option for EB. Research is ongoing to develop peptide-based treatments that could help manage the symptoms and promote healing in patients with EB.
Nanotechnology (NAN) in the context of EB involves the development of nanoscale materials and delivery systems. These can be used for targeted drug delivery, improving the effectiveness and reducing the side effects of treatments. Nanotechnology holds promise in delivering gene-editing tools, growth factors, and other therapeutic agents directly to the affected skin layers in EB, potentially improving treatment outcomes.