Epidermolysis bullosa (dystrophic, recessive)

Overview

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited disorder that makes the skin exceptionally fragile. Even slight friction or pressure can lead to painful blistering and open wounds, similar to severe burns [PMID:33994356]. These blisters can appear anywhere on the body, including the mouth, throat, eyes, and internal organs. The condition is one of several types of Epidermolysis Bullosa (EB), distinguished by the specific layer of skin affected and its inheritance pattern.

RDEB is a significant condition that often requires ongoing medical attention. The symptoms typically become apparent at birth or during early infancy. The severity can vary, but generally, RDEB is considered one of the more severe forms of EB, leading to a range of potential health challenges throughout a person's life. It affects approximately 1 in 50,000 individuals, though exact prevalence can vary [PMID:30608779].

Symptoms & clinical features

The primary symptom of RDEB is recurrent blistering and erosions of the skin. These can heal with scarring, which can accumulate over time and lead to contractures, particularly in the hands and feet, often resulting in fused digits sometimes described as 'mitten deformities' [PMID:33994356]. Blistering can also affect mucous membranes like the lining of the mouth, oesophagus, and eyes, causing pain, difficulty eating, and vision problems.

Chronic wounds are common, which can increase the risk of infection. Other potential symptoms include anaemia due to chronic blood loss from wounds, nutritional deficiencies from difficulty eating, tooth decay, and thinning hair. In severe cases, extensive scarring in the oesophagus can cause strictures, making swallowing very difficult. There is also an increased risk of developing specific types of skin cancer later in life [PMID:30608779].

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Affected organs

RDEB primarily affects the skin, causing widespread fragility, blistering, and scarring. However, its impact extends beyond the skin to several other body systems.

Mucous membranes are frequently involved, including the lining of the mouth, throat, oesophagus, and eyes. This can lead to issues with eating, swallowing, and vision. Internal organs, such as the digestive tract, can also be affected by blistering and scarring, contributing to nutritional challenges. Fingernails and toenails are typically thickened or absent, and extensive scarring can lead to deformities of the hands and feet.

Multiple body systems

Systemic involvement

Cellular impact

Mechanism at cellular level

Risks & severity

The severity of RDEB can range from moderate to severe, with widespread and often highly debilitating symptoms. The condition typically manifests at birth or in early infancy, requiring immediate medical attention. Lifetime risks include chronic pain, infections from open wounds, and progressive scar formation that can lead to physical disabilities, such as contractures and fused digits.

Individuals with RDEB also have a significantly increased lifetime risk of developing aggressive squamous cell carcinoma (SCC), a type of skin cancer, often in early adulthood. Regular screening and monitoring are crucial for early detection and management of this serious complication [PMID:30608779].

Genetic causes

RDEB is caused by genetic changes (pathogenic variants) in the COL7A1 gene. This gene provides instructions for making a protein called type VII collagen [PMID:33994356]. Type VII collagen is a crucial component of anchoring fibrils, which are specialised structures found in the dermal-epidermal junction - the area where the outer layer of the skin (epidermis) meets the underlying layer (dermis).

Anchoring fibrils act like strong ropes, firmly attaching the epidermis to the dermis. When there are pathogenic variants in COL7A1, the body produces either a non-functional type VII collagen or no type VII collagen at all. This lack of functional anchoring fibrils makes the skin layers unable to withstand even minor shearing forces, leading to the characteristic blistering and fragility seen in RDEB.

• COL7A1
  collagen type VII alpha 1 chain
  The COL7A1 gene encodes the alpha 1 chain of Type VII collagen, a crucial protein for the structural integrity and stability of the skin.

Inheritance pattern

RDEB is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the COL7A1 gene - one from each parent - to develop the condition. If a person inherits only one altered copy and one normal copy, they are considered a carrier. Carriers typically do not show symptoms of RDEB.

When both parents are carriers of a pathogenic variant in COL7A1, there is a 1 in 4 (25%) chance with each pregnancy that their child will inherit two altered copies and develop RDEB. There is a 2 in 4 (50%) chance that their child will be a carrier, and a 1 in 4 (25%) chance that their child will inherit two normal copies of the gene and will not be affected or a carrier.

Diagnosis & testing

Diagnosis of RDEB is typically suspected based on the characteristic skin blistering and fragility observed at or shortly after birth. Confirmation often involves a skin biopsy, where a small tissue sample is taken and examined under a microscope [PMID:33994356]. Immunofluorescence microscopy (IFM) or transmission electron microscopy (TEM) can help identify the level of skin separation and missing or abnormal type VII collagen.

Definitive diagnosis relies on genetic testing, usually through a blood test. This testing analyses the COL7A1 gene to identify specific pathogenic variants. Genetic testing for RDEB is part of the NHS Genomic Medicine Service, often initiated following referral to a clinical genetics service or specialist dermatologist, and falls under specific R-codes for rare inherited skin blistering disorders.

Management & lifestyle

Managing RDEB focuses on protecting the skin, preventing complications, and improving quality of life. This involves careful wound care, including non-adhesive dressings to minimise trauma and promote healing, and managing pain. Infection prevention is vital, often requiring antibiotics for bacterial infections. Nutritional support may be necessary due to difficulty eating and chronic inflammation, potentially including dietary supplements or feeding tubes.

Regular monitoring for complications, particularly oesophageal strictures and skin cancer, is essential. Surgical interventions, such as hand reconstruction to manage 'mitten deformities' or dilations for oesophageal strictures, may be considered. Access to a multidisciplinary team, including dermatologists, genetic counsellors, pain specialists, dietitians, and physiotherapists, is key for comprehensive care. Research into gene therapy and other treatments for RDEB is ongoing, offering future possibilities.

UK care pathway

In the UK, individuals with RDEB are typically managed through specialist NHS services. Following a clinical diagnosis, a referral to a Clinical Genetics service is often made to facilitate genetic testing, usually through the NHS Genomic Medicine Service. Genetic counselling is an integral part of this pathway, providing information about the condition, its inheritance, and support for families. The testing for inherited epidermolysis bullosa is covered by specific NHS National Genomic Test Directory R-codes (e.g., R150 for Epidermolysis bullosa). Care is often coordinated through specialist EB centres, ensuring access to experienced multidisciplinary teams.

Related conditions

While RDEB is a specific type of epidermolysis bullosa, several other forms exist, such as Epidermolysis Bullosa Simplex (EBS) and Junctional Epidermolysis Bullosa (JEB). These conditions also cause fragile skin and blistering but differ in their genetic causes, the skin layers affected, and their typical severity. For instance, EBS generally affects the outermost layer of the skin (epidermis) and is often less severe than RDEB. These related conditions share symptoms like blistering but require accurate diagnosis due to distinct genetic backgrounds and management approaches.

Frequently asked questions