CLASSIFICATION

Inherited EB can be classified based on phenotype and genotype, subdividing EB into types and subtypes as follows:

1. 
   

   Epidermolysis bullosa simplex (EBS, with intraepidermal bullae)

   
   
   
   
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     Major subtypes:

     
     
     
     
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       EBS, localized (also known as EBS, Weber–Cockayne).

       
       
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       EBS, generalized intermediate (also known as EBS, Koebner).

       
       
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       EBS, generalized severe (also known as EBS, Dowling-Meara).

       
       
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       EBS with muscular dystrophy.

     
     
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     Minor subtypes:

     
     
     
     
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       EBS with mottled pigmentation.

       
       
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       Autosomal recessive EBS.

       
       
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       EBS, Ogna.

       
       
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       EBS with pyloric atresia.

       
       
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       EBS superficialis/suprabasal EBS.

   
   
2. 
   

   Junctional epidermolysis bullosa (JEB, with bullae cleavage plane at lamina lucida)

   
   
   
   
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     Major subtypes:

     
     
     
     
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       JEB, generalized severe (also known as JEB, Herlitz).

       
       
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       JEB, generalized intermediate (also known as JEB, non-Herlitz).

       
       
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       JEB with pyloric atresia.

     
     
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     Minor subtypes:

     
     
     
     
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       JEB inversa.

       
       
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       JEB localized.

       
       
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       JEB laryngo-onycho-cutaneous syndrome.

   
   
3. 
   

   Dystrophic epidermolysis bullosa (DEB, with bullae cleavage plane below lamina densa)

   
   
   
   
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     Major subtypes:

     
     
     
     
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       Dominant (D) DEB.

       
       
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       Recessive (R) DEB, generalized severe (also known as RDEB, Hallopeau– Siemens).

       
       
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       RDEB, generalized intermediate (also known as RDEB non-Hallopeau– Siemens).

     
     
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     Minor subtypes:

     
     
     
     
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       DDEB, pretibial.

       
       
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       DDEB pruriginosa.

       
       
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       RDEB inversa.

       
       
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       RDEB centripetalis.

       
       
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       DEB, transient bullous dermolysis of the newborn.

       
       
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       DEB, autosomal, dominant/autosomal, recessive heterozygote.

EPIDERMOLYSIS BULLOSA SIMPLEX

SYNONYM Epidermolytic EB.

EPIDEMIOLOGY

AGE

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  Major subtypes:

  
  
  
  
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    EBS, localized (Weber–Cockayne): Blisters may appear in first 2 years of life. It can also begin in adolescence.

    
    
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    EBS, generalized intermediate (Koebner): Bullae at birth, at areas of friction; improves in adolescence.

    
    
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    EBS, generalized severe (Dowling-Meara): Bullae at birth; widespread, severe, and extensive spontaneous blisters; improves in adolescence.

    
    
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    EBS with muscular dystrophy: Bullae at birth.

INCIDENCE 10 per 1 million live births. EBS, localized (Weber–Cockayne) variant is most common, estimated at 1/50,000 live births.

GENDER M = F.

ETIOLOGY Mutations in genes encoding keratins 5 or 14, or mutations in gene encoding plectin. See Table 5-1.

GENETICS Autosomal dominant in inheritance, rarely can be autosomal recessively inherited. See Table 5-1.

PRECIPITATING FACTORS Bullae are mechanically induced by friction and can be exacerbated by warm temperatures, running, prolonged walking, and other sources of trauma.

PATHOPHYSIOLOGY

Mutations in the genes encoding keratin 5 (chromosome 12q) or 14 (chromosome 17q) or plectin (chromosome 8q) cause abnormal keratinocyte tonofilaments or hemidesmosomes in the basal cell layer of the skin. Trauma leads to intraepidermal cleavage at the level of the basal cell layer with resultant blister formation.

HISTORY

Healthy infants are born with seemingly fragile skin. Blisters form in areas of greatest friction, but blistering tendency usually improves with age.

PHYSICAL EXAMINATION

Skin Findings

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  Major subtypes:

  
  
  
  
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    EBS, localized (Weber–Cockayne): flaccid bullae on hands and feet (Fig. 5-1).

    
    
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    EBS, generalized intermediate (Koebner): generalized bullae with milia formation on healing areas. Little to no mucosal involvement, 20% with nail dystrophy.

    
    
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    EBS, generalized severe (Dowling-Meara): widespread bullae with arcuate, herpetiform grouping, palmoplantar keratoderma.

    
    
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    EBS with muscular dystrophy: localized bullae.

  
  
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  Minor subtypes:

  
  
  
  
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    EBS with mottled pigmentation: bullae associated with reticulate hyperpigmented macules.

    
    
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    Autosomal recessive EBS: may be either local or generalized bullae, often presenting shortly after birth.

    
    
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    EBS, Ogna: similar phenotype to EBS, localized (Weber–Cockayne) with additional clinical feature of perilesional bruising and hemorrhagic bullae.

    
    
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    EBS with pyloric atresia: severe with bullae at birth; poor prognosis often with death in infancy.

    
    
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    EBS superficialis: superficial peeling often without blisters (split just beneath the granular layer).

LABORATORY EXAMINATION

DERMATOPATHOLOGY Light microscopy reveals an intraepidermal split consistent with basal cell cytolysis, but this is not diagnostic.

TRANSMISSION ELECTRON MICROSCOPY AND IMMUNOFLUORESCENCE ANTIGENIC MAPPING More sensitive technique demonstrating the cleavage through the basal layer and basal cell cytolysis. In EBS, generalized severe (Dowling-Meara), EM will show clumping of tonofilaments in addition to basal cell cytolysis. Immunofluorescence staining shows the BP antigen, laminin, and collagen IV to be located beneath the level of cleavage. Immunofluorescent antigenic mapping with monoclonal antibodies can demonstrate absent keratins 5 or 14 or plectin.

MOLECULAR TESTING Can be performed based on keratin gene mutations and/or abnormal production of keratins 5 or 14 or plectin.

DIFFERENTIAL DIAGNOSIS

If family history is noncontributory, clinical bullae formation in an otherwise seemingly healthy newborn should lead one to suspect mechanobullous disorders. The differential diagnosis includes other genodermatoses with blisters (bullous congenital ichthyosiform erythroderma), autoimmune bullous diseases (linear IgA, pemphigoid, pemphigus), infections (herpes, staphylococcal scalded skin, bullous impetigo), benign entities (suction blister, friction blister), or rarely signs of child abuse or neglect (scalding, thermal injury).

COURSE AND PROGNOSIS

Most common forms of EBS improve with age, and blister formation can be limited by decreasing traumatic activities. Of the common subtypes, EBS, generalized severe (Dowling-Meara) variant can be extensive enough to cause significant morbidity and mortality, and EBS associated with muscular dystrophy may have a varied phenotype with progressive muscular wasting in severe forms.

MANAGEMENT

The treatment of EBS is palliative:

1. 
   

   Bullae formation can be minimized by limiting traumatic activities; using soft, well-fitted shoes; and avoiding warm temperatures.

   
   
2. 
   

   When blisters occur, extension may be avoided by careful aseptic aspiration of the blister fluid with a sterile pin or needle. The roofs of the blisters may be carefully trimmed with sterile scissors. Then the lesion can be dressed with a hydrocolloid dressing or petrolatum-impregnated gauze that will not stick to the healing blister site.

   
   
3. 
   

   Daily baths, gentle cleansers (Aquanil or Cetaphil liquid cleansers), and bandaging can help reduce chance of secondary infection and will also help healing of the blistered area.

   
   
4. 
   

   Topical emollients (Vaseline petroleum jelly, hydrated petrolatum, or Aquaphor healing ointment) can reduce friction in the healing area.

   
   
5. 
   

   Topical antibiotics (mupirocin) may be used if evidence of bacterial secondary infection is present (yellow exudate, purulence, crusting).

   
   
6. 
   

   A water mattress with fleece covering may be necessary to reduce pressure and friction to limit extensive blistering.

   
   
7. 
   

   Widespread denudation of the skin requires hospitalization with IV fluids, IV antibiotics if appropriate, and burn unit wound care.

   
   
8. 
   

   Tissue-cultured derived artificial skin dressings are expensive, but may be helpful in nonhealing sites.

   
   
9. 
   

   Genetic counseling to the family is important and prenatal testing should be offered if available. At present, there is no gene therapy available.

   
   
10. 
    

    An international epidermolysis registry (www.debra.org) has been established and can be used as a support and informational system for families who have children with EB.