Epidermolysis Bullosa: Symptoms, Types, Causes and Treatment

Epidermolysis bullosa (EB) is a rare group of genetic skin disorders that can dramatically affect the lives of those who have it. Characterized by extreme skin fragility, even minor friction or trauma can lead to painful blistering and wounds. With over 30 subtypes and a wide range of severity, EB not only impacts the skin but also internal organs, quality of life, and emotional well-being. In this article, we’ll explore what EB is, its symptoms, the different types, what causes it, and the latest approaches to treatment and care.

Symptoms of Epidermolysis Bullosa

Epidermolysis bullosa doesn’t present the same way for every person, but its hallmark is skin vulnerability. Symptoms can range from mild and localized to severe and widespread, often appearing at birth or in early childhood. While the visible signs are striking, EB’s impact goes far beyond the skin, affecting daily comfort, sleep, emotional health, and even survival.

Symptom	Description	Impact/Severity	Source(s)
Blistering	Skin blisters after minor trauma	Ranges from mild to severe	1, 4, 8
Pruritus	Persistent itch	Disrupts sleep, daily life	2, 5
Wound Healing	Slow, chronic wounds	Risk of infection, scarring	9, 13
Scarring	Skin heals with scars, contractures	Can limit movement	4, 11
Pain	Due to wounds and erosions	Chronic, affects QOL	3, 9
Mucosal Lesions	Blisters in mouth, eyes, esophagus	Swallowing/vision issues	1, 11
Nail/Hair Changes	Nail dystrophy, alopecia	Cosmetic and functional	12
Psychosocial	Anxiety, depression, social impact	Reduces quality of life	3, 9

Table 1: Key Symptoms

Blistering and Skin Fragility

The defining symptom of EB is blister formation following minor friction, rubbing, or trauma. In some types, even gentle handling can cause the skin to separate and blister. These blisters can occur anywhere on the body but are most common on hands, feet, elbows, knees, and areas prone to friction—sometimes even in the mouth, eyes, or internal linings 1, 4.

Chronic Wounds and Scarring

Blisters often rupture, leaving open wounds that heal slowly and are prone to infection. In more severe forms, repeated cycles of blistering and healing lead to scarring and the formation of contractures (tightened skin that limits movement) 4, 11. Chronic wounds also increase the risk of developing aggressive skin cancers, especially squamous cell carcinoma 13.

Itch and Pain

Pruritus (itch) is one of the most burdensome symptoms for people with EB. Itchiness tends to worsen at night, interfering with sleep and making wound healing more difficult. The underlying causes include skin inflammation and nerve irritation due to persistent barrier disruption 2, 5. Pain is another near-universal symptom, stemming from active wounds, dressing changes, and complications.

Mucosal and Nail Involvement

EB can affect the mucous membranes, causing blisters in the mouth, eyes, esophagus, and even the urinary tract. These complications can lead to feeding difficulties, malnutrition, eye damage, and strictures (narrowing of passages) 1, 11. Nail dystrophy and early-onset hair loss (alopecia) are also reported, particularly in certain genetic subtypes 12.

Psychosocial Impact

Living with EB poses a heavy psychological burden, with many patients and caregivers reporting anxiety, depression, and reduced quality of life. The visible nature of the disease, chronic pain, and daily care demands all contribute to these challenges 3, 9.

Types of Epidermolysis Bullosa

EB isn’t a single disease, but rather a family of related disorders. Each subtype is defined by where the skin splits (the “plane of cleavage”), the specific genetic mutation, and the resulting clinical features. Understanding the types is crucial for diagnosis, management, and prognosis.

Type	Skin Layer Affected	Main Features	Source(s)
EB Simplex (EBS)	Epidermis (upper layer)	Blisters at basal layer, mild-moderate	1, 10
Junctional EB (JEB)	Lamina lucida (middle layer)	Severe, mucosal involvement	1, 6
Dystrophic EB (DEB)	Below basement membrane	Scarring, risk of cancer	1, 4, 13
Kindler EB	Multiple levels	Mixed features, photosensitivity	1, 12

Table 2: Main Types of EB

EB Simplex (EBS)

EBS is the most common and usually the mildest form. Blistering occurs in the basal layer of the epidermis, often limited to the hands and feet. There are several subtypes, ranging from localized (mainly on feet) to generalized forms. EBS is typically inherited in an autosomal dominant pattern and caused by mutations in keratin genes (KRT5, KRT14) 1, 10.

Junctional Epidermolysis Bullosa (JEB)

JEB is generally more severe, with blistering occurring in the lamina lucida of the basement membrane. It often involves mucous membranes, leading to feeding difficulties, dental problems, and respiratory issues. Some subtypes of JEB can be life-threatening in infancy 1, 6.

Dystrophic Epidermolysis Bullosa (DEB)

In DEB, blistering happens below the basement membrane, and wounds heal with significant scarring. There are dominant and recessive forms, with recessive dystrophic EB (RDEB) being particularly severe. Patients are at high risk for contractures, fusion of fingers and toes, and aggressive squamous cell carcinoma 1, 4, 13.

Kindler Epidermolysis Bullosa

Kindler EB is rarer and unique because blistering can occur at multiple skin levels. Patients often display photosensitivity, poikiloderma (skin thinning, pigment changes), and mucosal involvement. Multi-systemic features, such as nephropathy (kidney involvement), have also been reported in some genetic variants 1, 12.

Causes of Epidermolysis Bullosa

At its core, EB is a genetic condition caused by mutations in the genes responsible for skin integrity. These mutations disrupt the proteins that hold the skin layers together, making the skin fragile and prone to blistering.

Cause	Genetic Basis/Mechanism	Proteins Involved	Source(s)
Genetic Mutation	Inherited (autosomal dom/rec)	Keratins, collagens, laminins	1, 10, 11
Defective Proteins	Disrupted adhesion at skin layers	K5, K14, type VII collagen, etc.	1, 11, 12
Subtype-Specific	Subtype linked to gene/protein	e.g., KRT5/14 (EBS), COL7A1 (DEB)	10, 11
Acquired Forms	Autoimmune (rare, EBA)	Antibodies to type VII collagen	14

Table 3: Causes and Mechanisms

Genetic Mutations and Inheritance

Most forms of EB result from inherited mutations in over 20 different genes. These genes encode for structural proteins vital for skin stability, including keratins (EBS), collagens (DEB), and laminins (JEB) 1, 10, 11. EB can be inherited in an autosomal dominant or recessive pattern, depending on the subtype.

• EBS: Mutations in KRT5 and KRT14 (keratin 5 and 14) disrupt the basal keratinocyte structure, leading to skin fragility 10.
• DEB: Mutations in the COL7A1 gene affect type VII collagen, a key anchoring protein, causing deeper skin separation and scarring 11.
• JEB: Mutations in genes encoding laminin-332 and collagen XVII cause separation at the basement membrane 1, 11.
• Kindler EB: Mutations in FERMT1 or, rarely, CD151, lead to mixed skin cleavage and multi-system involvement 12.

Protein Dysfunction

The faulty proteins can no longer anchor the skin layers tightly, making the skin vulnerable to separation and blistering from everyday activities. In some subtypes, the lack of specific proteins also affects internal linings, leading to complications beyond the skin 1, 11.

Acquired Forms

While most forms of EB are inherited, a rare acquired type, Epidermolysis Bullosa Acquisita (EBA), results from autoimmune attack against type VII collagen. EBA behaves similarly to inherited DEB but is not present from birth and is associated with autoimmunity 14.

Treatment of Epidermolysis Bullosa

Currently, there is no cure for EB, but significant advances are being made. Treatment is centered around symptom management, wound care, prevention of complications, and improving quality of life. Emerging molecular therapies offer hope for the future.

Approach	Method/Goal	Application/Progress	Source(s)
Supportive Care	Wound care, pain/itch relief	Daily care, critical for QOL	1, 9
Multidisciplinary	Care teams: dermatology, nutrition, psych	Comprehensive management	1, 3, 9
Infection Control	Antibiotics, dressing techniques	Prevent/limit infections	1, 9
Cancer Surveillance	Screening, early intervention	High risk in severe types	13
Psychosocial Support	Counseling, support groups	Address mental health, QOL	3, 9
Molecular Therapies	Gene, protein, cell therapies	Clinical trials ongoing	15, 16, 17, 18
Experimental Drugs	Small molecules, repurposed meds	In trials (e.g., pruritus)	17
EBA Treatments	Immunosuppressants, IVIG	For acquired EB	14

Table 4: Current and Emerging Treatments

Supportive and Symptom Management

• Wound care is the cornerstone of management. This involves gentle cleansing, non-adhesive dressings, and careful handling to prevent further trauma. Specialized wound dressings are crucial to minimize pain and risk of infection 1, 9.
• Pain and itch relief is essential. Medications may include topical anesthetics, systemic painkillers, and antihistamines. Managing pruritus is particularly important as it can disrupt sleep and wound healing 2, 5, 9.
• Infection prevention through proper wound care and sometimes antibiotics is vital, as chronic wounds are at high risk for bacterial colonization and sepsis.

Multidisciplinary and Psychosocial Care

EB management requires a team approach:

• Dermatologists oversee wound and skin care.
• Nutritionists address feeding difficulties and malnutrition, especially in severe forms.
• Psychologists and social workers provide mental health support, as EB takes a heavy emotional toll on both patients and caregivers 3, 9.
• Surgeons may be involved for contracture release or cancer excision 13.

Cancer Surveillance

Regular screening for squamous cell carcinoma, especially in patients with severe forms like RDEB, is essential. Early detection and intervention can be lifesaving 13.

Molecular and Experimental Therapies

Significant progress has been made in developing treatments that target the underlying genetic defects:

• Gene therapy: Early clinical trials have shown that gene-corrected skin grafts or genetically modified stem cells can restore some skin integrity in JEB and DEB 15, 16, 17.
• Protein replacement: Recombinant proteins (e.g., type VII collagen) are being tested to supplement missing or defective structural proteins 15, 17.
• Cell-based therapy: Transplantation of fibroblasts, mesenchymal stromal cells, or bone marrow-derived cells is being explored for wound healing and reducing inflammation 15, 17.
• Drug repurposing and small molecules: New medications are under investigation to manage symptoms like pruritus, inflammation, and fibrosis 17.

Treatments for Acquired EB (EBA)

For the rare autoimmune EBA, immunosuppressive therapies such as corticosteroids, cyclosporine, colchicine, and intravenous immunoglobulin (IVIG) may be used, sometimes with success in refractory cases 14.

Conclusion

Epidermolysis bullosa is a complex, challenging condition that touches every aspect of life for patients and families. While there is still no cure, remarkable progress in research and care is bringing hope closer than ever.

Key Points:

• EB is a diverse group of rare inherited disorders characterized by skin fragility and blistering from minimal trauma 1, 8.
• Symptoms include blistering, chronic wounds, pain, itch, scarring, and mucosal involvement, with a significant impact on quality of life 1, 2, 3, 4, 5.
• There are four major types: EB Simplex, Junctional EB, Dystrophic EB, and Kindler EB, each defined by genetic mutations and clinical features 1, 4, 6, 10, 12.
• EB is caused by mutations in genes encoding structural skin proteins, leading to weak connections between skin layers 1, 10, 11.
• Current treatment focuses on supportive care, wound management, infection control, and psychosocial support, with multidisciplinary teams essential for optimal outcomes 1, 3, 9.
• Emerging molecular therapies—gene, protein, and cell-based—are in clinical trials, offering real hope for the future 15, 16, 17, 18.

If you or someone you know is affected by EB, know that research and advocacy are advancing rapidly. Support, education, and early involvement in expert care centers can make a significant difference in quality of life and long-term outcomes.