Dystrophic EB

Restricted primarily to the hands, feet, or pretibial areas (shins). May present at birth or develop later.

Skin in affected areas is fragile, leading to recurrent blistering with minimal trauma. 

Mild scarring and nail dystrophy (nail loss or deformities) often occur in the affected regions.

Rare or mild involvement of oral or esophageal areas.

Risk for squamous cell carcinoma (SCC) exists but is much lower compared to more severe forms, and tends to develop later in life. 

Widespread blistering, scarring and milia from birth or early childhood, with a predilection for bony prominences including the elbows, knees, ankles and dorsa of the hands and feet.

Mild flexion contractures (tightening of joints) and a striate-pattern of keratoderma (thickened skin) on the fingers may occur. Limited to moderate fusion of fingers or toes may develop. 

The risk of squamous cell carcinoma (SCC) is increased in intermediate RDEB, but tending to occur later in adulthood.

Blistering, erosions, and scarring of the oral mucosa are possible. Progressive strictures can severely restrict nutritional intake.

Recurrent blistering and fissuring around the anal margin are frequent, contributing to pain and difficulty during defecation. Constipation is exacerbated by pain and reduced intake of fiber-rich foods.

The conjunctiva and cornea are often affected, leading to corneal erosions, scarring, pannus (clouding of the cornea), symblepharon (adhesion of the eyelid to the eye), and reduced visual acuity.

Nail dystrophy or loss due to trauma is common 

Nutritional issues arise from reduced intake caused by factors such as microstomia (small mouth opening), dental caries, and esophageal strictures. The increased metabolic demands from chronic wounds, infection, and inflammation contribute to nutritional challenges.

Widespread and extensive blistering and skin fragility present from birth, often with areas of missing skin, especially on limbs (congenital skin ulceration). 

Persistent, non-healing wounds at sites of repeated blistering. These contribute to chronic inflammation, infection, and tissue breakdown.

Extensive scarring leading to flexion contractures of large joints and pseudosyndactyly (digital fusion), resulting in classic mitten deformities of hands and feet. 

Blistering and scarring may be more pronounced over pressure points like elbows, knees, ankles, and the dorsa of hands/feet.

Pigmented, wart-like skin lesions that may develop over time. 

Scarring alopecia (hair loss) and scalp crusting are common and worsen with age. 

Fragile nails prone to trauma, often lost progressively within the first few years of life. 

Severe blistering, erosions, and scarring of the oral mucosa. May lead to microstomia (small mouth opening), ankyloglossia (tongue tethering), dental overcrowding and caries 

Blistering and progressive scarring cause strictures that impair swallowing and nutrition, requiring regular surgical dilation. 

Recurrent blistering around the anal margin leads to painful defecation.  

May occur due to mucosal scarring. 

Chronic constipation, possible dysmotility, and pain contribute to further nutritional challenges.

Blistering and inflammation of the conjunctiva and cornea, leading to corneal erosions, pannus formation, symblepharon (adhesions), scarring and visual impairment 

Due to microstomia, dental issues, esophageal disease, chronic wounds, and high metabolic demand. This can lead to failure to thrive, weight loss, and growth delay. 

A mixed type due to iron deficiency, chronic blood loss from wounds, and inflammation.  

Poor bone density common, caused by reduced mobility, chronic inflammation, vitamin D and calcium deficiencies, pubertal delay. 

Increased risk of fractures, including vertebral compression fractures. 

Short stature and delayed puberty are frequently observed. 

SCC is aggressive and the leading cause of death in severe RDEB, often develops during adolescence or early adulthood, with increasing incidence from teen years onward.

Can include post-streptococcal glomerulonephritis, renal amyloidosis, IgA nephropathy and progression to renal failure.

Rare but possible as part of long-term systemic disease. 

Often restricted to the hands, feet, or pretibial area (shins). May appear at birth or develop later in life, often after minor trauma.  

Fragile skin in localized areas leads to frequent blistering and chronic wounds in affected regions. 

Nail loss or deformities are common, especially with trauma or repetitive injury to the nails.

Mild scarring in localized areas, especially in places prone to friction or pressure, such as the hands and feet. 

Squamous cell carcinoma (SCC) is possible but less, typically developing later in life. 

Rare or mild. Mucosal blistering in the mouth and esophagus may occur. 

Blistering tends to affect larger areas of the body, particularly over bony prominences such as elbows, knees, ankles, and the backs of hands and feet. 

Scarring occurs in affected areas and is often accompanied by small white cysts (milia). The skin may become thicker and more fragile over time. 

Mild contractures, keratoderma (thickened skin) in a striate pattern on the fingers, and limited webbing or fusion between digits may develop. 

Blistering, erosions, and scarring may affect the mouth and esophagus, leading to nutritional challenges, strictures, or difficulty swallowing. 

SCC can develop, tending to occur later in adulthood. 

The conjunctiva and cornea can be affected, leading to erosions or scarring. 

Nails may be damaged or lost, especially following trauma or blistering.

Recurrent fissures or blistering around the anal area can cause pain and constipation. GI involvement can also lead to nutritional challenges. 

Noted Clinical Symptoms

• Usually presents initially as localized or intermediate DDEB or RDEB in childhood and early adulthood.  
• Characterized by intensely pruritic, excoriated violaceous papules or linear plaques and scars particularly on the lower legs, thighs and arms which can become more progressive from adolescence through adulthood.  
• Nail dystrophy and milia are common.  
• May co-exist with non-pruriginosa DEB within families.  

Genetics

• Autosomal dominant or autosomal recessive inheritance.  
• Monoallelic or biallelic mutations in COL7A1 similar to those identified in non-pruriginosa DDEB or RDEB without identification of a specific genotype-phenotype correlation for the pruriginosa phenotype.102–104  

syn. bullous dermolysis of the newborn

Noted Clinical Symptoms 

• Skin blistering presents at or shortly after birth, usually on the extremities.  
• Aplasia cutis of the lower limbs may be present.  
• Scarring and milia occur at sites of blistering.  
• Skin fragility improves spontaneously and may resolve completely over the first year or two of life although nail dystrophy, particularly of the toenails, may persist throughout life.  

Genetics

• Autosomal dominant or autosomal recessive.  
• COL7A1 missense mutations, especially glycine substitutions, are most commonly associated but in-frame deletion, premature termination codon and alternative splicing mutations also described. 
• Characteristic intra-epidermal retention of type VII collagen on immunohistochemistry and stellate bodies in dilated rough endoplasmic reticulum on transmission electron microscopy. These changes tend to improve in parallel with phenotypic improvement.  

Noted Clinical Symptoms  

• In the neonatal period and childhood skin blistering is usually generalized and of intermediate severity.  
• From adolescence to early adulthood, a predilection for flexural sites develops, specifically in the axillae, groins, perianal area and natal cleft. In women, there may be marked vulvovaginal and inframammary skin blistering.  
• Mucosal disease with blistering and scarring in the mouth and oesophagus is characteristic.  
• Involvement of the external auditory canal may lead to narrowing or complete occlusion.  
• Nail involvement is common.  

Genetics

• Autosomal recessive inheritance.  
• Usually results from compound heterozygosity for a loss-of-function COL7A1 mutation in combination with a missense mutation; specific glycine and arginine substitutions have been suggested as causative for this specific phenotype. 

Noted Clinical Symptoms 

• Skin fragility usually presents at or shortly after birth but may rarely be of late onset in adulthood.  
• Blistering is limited in extent; it may affect predominantly the hands and feet, but in others may be restricted to the pretibial area.  
• Nail dystrophy and loss are common.  
• Oral and esophageal mucosal involvement are usually mild or absent.  

Genetics

• Autosomal recessive inheritance.  
• Compound heterozygosity for COL7A1 missense, splice site and frameshift mutations described. 

Noted Clinical Symptoms  

• Severe skin and mucosal fragility presenting from birth indistinguishable from severe RDEB.  
• May have a family history of DDEB in family members.  

Genetics

• Compound heterozygosity for a dominant COL7A1 glycine substitution mutation and a recessive mutation on the second allele.