Fig.1
Two weeks old baby boy, first born to a young woman. The baby developed multiple erosions and bullae predominantly on the torso. This was associated with nail dystrophy. A biopsy from an unknown site of the intact and bullous skin was examined ultrastructurally.
Hematoxylin and eosin-stained section of the skin biopsy involved with a bullous lesion.
Fig.1
An electron micrograph (Fig. 2) provides details of a basal keratinocyte from normal human skin attached to the basal lamina with many hemidesmosomes.
Electron micrographs of the infant's skin biopsy (Figs. 3 to 5). Junctional bulla formed through the lamina lucida with the lamina densa present at the floor of the bulla and keratinocytes at the roof of the bulla. There are some areas of disruption of the lamina densa by neutrophilic infiltrate and fibrin deposits related to secondary infection and inflammation. The anchoring fibrils are present with a normal morphology on the dermal side of the lamina densa (Fig. 3). In both of the areas of the bulla (Fig. 4) and areas where the skin is intact (Fig. 5), there is abnormal morphology of the hemidesmosomes attaching the keratinocytes to the lamina densa. There is total absence of the sub-basal dense plaques of the hemidesmosomes of the basal keratinocytes. The rest of the epidermis appears to be within normal limits, with no aggregation of collagen products in the Rough Endoplasmic Reticulum of the basal keratinocytes as one would see in transient bullous dermatosis. Keratinization appears to be normal.
Fig. 2 
Fig. 3 
Fig. 4 
Fig. 5
The abnormality present in the hemidesmosomes is consistent with
a diagnosis of Epidermolysis Bullosa-Letalis Type (junctional)
Epidermolysis Bullosa is a group of hereditary disorders of the skin whose common feature is the formation of blisters, following minor trauma. A simple classification of classic types of EB that takes into account histologic, genetic and clinical features are presented in Table I.
| Epidermolytic epidermolysis bullosa (recurrent bullous eruption of hands and feet) | Dominant | Weber-Cockayne Syndrome |
| Epidermolysis bullosa simplex | Dominant | Koebner type |
| Junctional epidermolysis bullosa | Recessive | Epidermolysis bullosa hereditaria letalis
Herlitz-Pearson disease *Junctional bullous epidermatosis |
| Dermolytic bullous dermatosis
Dominant dystrophic | Dominant (2 types) | Hyperplastic dystrophic EB of Cockayne and Touraine Albopapuloid dystrophic EB of Pasini |
| Recessive dystrophic | Recessive | Polydysplastic EB mutilans |
*This rare type of junctional EB is associated with scarring and atrophy.
For a more detailed description and classification of the 26 overlapping phenotypes of Epidermolysis Bullosa, we refer you to recent literature.
Transmission electron microscopy has been important for more than 30 years, in identifying the subtypes of Epidermolysis Bullosa, through the ultrastructural examination of the appearances of hemidesmosomes, anchoring fibrils, basal dense placques and the exact location of the split through the basal lamina.
Immunofluorescent testing of the basement membrane antigens, such as laminin and type IV collagen often backs up the accuracy of the final diagnosis.
In recent years, molecular biology is playing an important role in understanding the pathogenesis of the subtypes of Epidermolysis Bullosa. Molecular assessment of the expression of various proteins of the basement membrane zone such as laminin (nicein/kalinin) and type VII collagen etc. and identification of certain mutation in these structural proteins is becoming an adjunct for the diagnosis of EB subtypes and raises hopes for gene therapy in the future.
