Epidermolysis bullosa herpetiformis (Dowling-Meara type) exhibits ultrastructural derangement of tonofilaments and desmosomes

Ultrastructural and immunohistochemical studies of clinically intact skin obtained from three severe neonatal cases of epidermolysis bullosa herpetiformis (Dowling-Meara type) demonstrated disorders in the assembly of keratin intermediate filaments and desmosomes of the keratinocytes. During mitosis, K5- and K14-positive and K1- and K10-negative tonofilaments were disrupted and formed spherical bodies associated with intracytoplasmic desmosomes by invagination of the desmosomes and the adjacent plasma membrane. During the invagination process, destructive changes in the internalized membrane were noted. These were accompanied by gradual loss of reactivity with a monoclonal antibody ZK31, which detected plasma membrane adjacent to the attachment plaques of desmosomes. However, the reactivity of the attachment plaques of the internalized desmosomes for desmoplakins and desmoglein did not decline during the process of internalization. In the suprabasal layers of the epidermis, filamentous substructures and K1 and K10 appeared at the periphery of the spherical bodies. Simultaneously, the desmosomes that were sparsely located in the lower epidermis, increased in number as cell differentiation progressed. Thus, the keratinocytes attained an almost normal appearance with respect to tonofilaments and desmosomes by the time they reached the upper layer of the epidermis. These findings may be relevant to the mechanism responsible for the clinical appearance of the herpetiform blisters in epidermolysis bullosa herpetiformis, which are also characterized by spontaneous involution during childhood or when exposed to high ambient temperatures.Part of this work was presented at the annual meeting of the Japanese Society for Ultrastructural Cutaneous Biology, 12 May 1990, Tokushima, Japan, at the joint meeting of the Society for Cutaneous Ultrastructure Research and the Japanese Society for Ultrastructural Cutaneous Biology, 23–25 May 1991, Vienna, Austria, and at the sixth Conference on Disorders of Keratinization, 6 July 1991, Tokyo, Japan     

Epidermolysis bullosa simplex (Dowling-Meara). A clinicopathological review

The clinicopathological features of 22 cases of the Dowling-Meara form of epidermolysis bullosa simplex (DM-EBS) (11 males, 11 females; aged 5 days-46 years) were reviewed using data collected over a 10-year period. All cases presented clinically within the first 5 days of life. Early blisters were often large (up to 5 cm in diameter), and were mostly acral and particularly periungual. Some cases presented with more widespread erosive skin changes, and two neonates with extensive skin involvement died as a result of overwhelming sepsis. After the neonatal period a different pattern of blistering occurred with more proximal haemorrhagic, herpetiform clusters of blisters. Central healing with recurrent blistering at the margins of these areas was frequently noted. Other physical signs included varying degrees of intra-oral blistering, nail shedding, nail dystrophy, minor scarring, palmo-plantar keratoderma, a lack of seasonal variation and improvement during later childhood. The underlying pathological mechanism in DM-EBS is basal cell cytolysis, or rarely acantholysis, in association with tonofilament (TF) clumping. TF clumping was found in lesional, perilesional and some non-lesional skin, suggesting that the tonofilament abnormality may be of primary aetiological significance in DM-EBS. TF clumping may be due to specific keratin abnormalities because the altered TF were found in a distribution similar to the known distribution of the basal cell keratins, K5 and K14. The level of blistering was invariably very low within the epidermal basal layer and often less than 0.5 microns above the basement membrane. We conclude that DM-EBS is a distinct, and probably under-recognized genodermatosis which tends to have a good prognosis. However, the disease can occasionally be severe, especially during the neonatal period, when it may be confused with junctional or severe recessive dystrophic EB. Electron microscopy is the best means for demonstrating the characteristics cytoskeletal disorder and confirming the diagnosis.     

Keratin expression in epidermolysis bullosa simplex (Dowling-Meara)

The Dowling-Meara variant of epidermolysis bullosa simplex (EBS) is characterized microscopically by clumping of the keratin tonofilaments within areas of incipient blistering, thereby raising the possibility that an abnormality of the keratin cytoskeleton might underlie blister formation in this condition. In order to investigate keratin expression in Dowling-Meara EBS, the staining profile of a panel of antikeratin monoclonal antibodies was examined in perilesional skin from 5 affected subjects, using a standard immunoperoxidase technique. Normal labelling characteristics were demonstrated by antibodies identifying keratins of the basal and suprabasal compartments of normal interfollicular epidermis and of simple epithelia (keratin 19). In addition, a keratin expressed in hyperproliferative epidermal states was shown to be absent. The results suggest that the profile of keratin synthesis is normal in Dowling-Meara EBS and that the tonofilament clumping may be, therefore, the result of a post synthetic modification of keratin molecules.     

Epidermolysis bullosa

A case of recurrent vesiculobullous eruptions over shins, clinically diagnosed as epidermolysis bullosa of pretibial variety confirmed by electron microscope is reported here as a rare variety of localised epidermolysis bullosa (EB).     

Epidermolysis bullosa dystrophica Bart (Bart syndrome)

This is a report on a child with epidermolysis bullosa dystrophica Bart (Bart's syndrome), which is characterized by the following symptoms: congenital, localized absence of skin; blistering of skin and mucous membranes only in the first years of life; absence and deformity of nails. The favorable prognosis of this disease, with spontaneous improvement of the blistering, emphasizes the importance of knowledge of this rare syndrome.     

Epidermolysis bullosa acquisita in an 8-year-old girl

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Epidermolysis bullosa simplex Dowling-Meara due to an arginine to cysteine substitution in exon 1 of keratin 14

Epidermolysis bullosa simplex (EBS) is a blistering disorder affecting the basal layer of the epidermis usually inherited in an autosomal dominant fashion. Most cases are caused by mutations in the genes encoding keratin 5 (K5) and keratin 14 (K14) and are characterized by cytolysis within the basal layer of the epidermis. We report a patient manifesting the Dowling-Meara variant of EBS in whom we characterized a cytosine to thymine transition at codon 125 (R125C) in K14. This missense mutation is located at the amino terminus of the helical rod domain of the keratin 14 molecule, resulting in defective pairing with K5, thereby disrupting keratin tonofibril integrity.