Variant Of Epidermolysis Bullosa Research Articles

Epidermolysis bullosa: treatment and prevention

Congenital epidermolysis bullosa is considered as a phenotypically and genetically heterogeneous group of genodermatoses caused by various mutations in the genes that control the synthesis of structural proteins of the skin, carrying out epider­mal-dermal bonds.In this article, we aimed to indicate the polymorphism of clinical manifestations of epidermolysis bullosa, which must be confirmed by immunohistochemical studies.Numerous literature data were used on the clinical variants of epidermolysis bullosa, which consider not only 4 classical forms of the disease (simple, boundary, dystrophic and Kindlers syndrome), but also subtypes of each form of genoderma­tosis. Separately we discussed issues related to conducting immunohistological research in various forms of epidermolysis bullosa, when the localization of such protein components as collagen type IV, laminin and others was determined with the help of special antiserums. It was noted that the gold standard for histological examination in patients with epidermolysis bullosa is immunohistological methods that allow determining the deposition of immunoglobulins and complement components in the skin by means of the immunofluorescence method.Each nosological form of epidermolysis bullosa has genetic (study of genealogical charts) features of inheritance and an immunohistologic characteristic, which makes it possible to conduct differential diagnostics with other varieties of epidermolysis bullosa.Not in all cases, the clinical findings of epidermolysis bullosa can help to make the correct diagnosis and determine the specific form of epidermolysis bullosa. In this regard, additional research methods are important, including genetic ones, conducted in the process of adequate symptomatic therapy.

Detection of novelLAMA3mutation in Herlitz junctional epidermolysis bullosa in a Jordanian family

The Herlitz junctional epidermolysis bullosa (H-JEB) subtype usually presents as a severe lethal inherited variant of epidermolysis bullosa (EB) caused by a homozygous mutation in the genes LAMA3, LMAB3, or LAMAC3. Each gene encodes one of the three chains of heterotrimer laminin-332 proteins (including the alpha-3 chain, beta-3 chain and gamma-2-chain) responsible for the adherence of the epidermis to the underlying dermis. The aim of this report is to add to the existing knowledge about EB by describing a novel mutation in a gene responsible for genodermatosis. A case of a Jordanian male neonate, born to healthy, first cousin consanguineous parents, who developed nonhealing blistering skin and mucous membrane lesions, crusted erosions with significant granulation tissue and dystrophic nails immediately after birth is described. The patient was diagnosed as having a novel LAMA3 mutation causing (H-JEB) by immunofluorescence mapping and molecular analysis. Both parents and this baby's sibling were shown to be heterozygous carriers of the same mutation. Pre-implantation diagnosis using molecular analysis for subsequent pregnancies in this family is crucial for managing any new pregnancy.

Light and transmission electron microscopy of generalized dystrophic epidermolysis bullosa (Pasini's albopapuloid subtype)

Pasini's albopapuloid epidermolysis bullosa is a very rare subtype of generalized dystrophic dominant epidermolyis bullosa. A 30 year-old white female patient presented since her childhood disseminated small blisters and papules. Light microscopy of a blister showed dermal-epidermal cleavage; moreover, focal areas of dermal-epidermal splitting were also observed. Transmission electron microscopy also identified focal areas of cleavage, which were seen below the lamina densa. It is important to recognize this condition as a variant of epidermolysis bullosa, since the most important cutaneous findings are generalized papules and not blisters and erosions as in other forms of epidermolysis bullosa.

Zebrafish: A Model System to Study Heritable Skin Diseases

Heritable skin diseases represent a broad spectrum of clinical manifestations due to mutations in ∼500 different genes. A number of model systems have been developed to advance our understanding of the pathomechanisms of genodermatoses. Zebrafish (Danio rerio), a freshwater vertebrate, has a well-characterized genome, the expression of which can be easily manipulated. The larvae develop rapidly, with all major organs having developed by 5-6 days post-fertilization, including the skin, consisting of the epidermis comprising two cell layers and separated from the dermal collagenous matrix by a basement membrane. This perspective highlights the morphological and ultrastructural features of zebrafish skin, in the context of cutaneous gene expression. These observations suggest that zebrafish provide a useful model system to study the molecular aspects of skin development, as well as the pathogenesis and treatment of select heritable skin diseases.

Progress in epidermolysis bullosa: genetic classification and clinical implications.

Epidermolysis bullosa (EB), a heterogenous group of genodermatoses, is characterized by fragility and blistering of the skin associated with extracutaneous manifestations. Based on clinical severity, constellation of the phenotypic manifestations, and the level of tissue separation within the cutaneous basement membrane zone (BMZ), EB has been divided into distinct subcategories. Traditionally, these include the simplex, junctional, and dystrophic forms of EB, and recently attention has been drawn to hemidesmosomal variants demonstrating tissue separation at the level of the hemidesmosomes. Specific mutations in ten distinct genes expressed within the cutaneous BMZ have been delineated in >500 families with different variants of EB. The types of mutations, their positions along the affected genes, and their consequences at the mRNA and protein levels provide explanation for the phenotypic variability and genetic heterogeneity of this group of genodermatoses. Elucidation of mutations in different forms of EB has direct translational applications for improved diagnosis and molecularly based classification with prognostic implications as well as for genetic counseling and DNA-based prenatal testing in families with EB.

Three new cases of transient bullous dermolysis of the newborn

We present 3 new patients with transient bullous dermolysis of the newborn (TBDN), which is a form of dystrophic epidermolysis bullosa. TBDN may be diagnosed by electron microscopy showing a sublamina densa cleavage; immunofluorescence antigenic mapping demonstrating bullous pemphigoid antigen, laminin-1, and type IV collagen along the epidermal roof of subepidermal clefts; and indirect immunofluorescence with monoclonal antibodies revealing intraepidermal type VII collagen. Although intraepidermal type VII collagen has been reported in other forms of dystrophic epidermolysis bullosa, we believe that the presence of type VII collagen in a striking intraepidermal granular array is a finding unique to TBDN. Our cases demonstrate the importance of immunodermatologic studies in the diagnosis of bullous disorders that are seen at birth because accurate diagnosis carries prognostic implications. This variant of epidermolysis bullosa, in contrast to other forms of dystrophic epidermolysis bullosa, is a benign, self-limited disease. (J Am Acad Dermatol 1999;40:471-6.)

Rapid Diagnosis of Major Variants of Congenital Epidermolysis Bullosa Using a Monoclonal Antibody against Collagen Type IV

A simple and rapid procedure to diagnose major variants of congenital epidermolysis bullosa (EB) by means of immunohistochemical staining of collagen IV (CIV) in formalin-fixed and paraffin-embedded samples is described. Sixteen cases were stained with a monoclonal antibody (clone CIV 22) against collagen IV present in the lamina densa layer of the basement membrane. Electron microscopy was performed simultaneously. Twelve cases showed one of two staining patterns: an EB simplex pattern (seven cases) consisting of linear and continuous staining on the "floor" of the blister and an EB dystrophica pattern (five cases) showing a linear and discontinuous staining on the "roof" of the blister. In four cases, collagen IV staining was not reactive because of irreversible antigen loss due to inadequate fixation and/or embedding. In those cases with positive staining, an excellent correlation with electron microscopic diagnosis was achieved. This procedure allows a rapid diagnosis of major EB variants, especially where electron microscopy is not available, and also facilitates diagnosis by optimally orienting specimens for ultrastructural examination when available.

In Reply: Epidermolysis Bullosa Letalis

Doctor Mautner is correct in claiming to have described the first indisputable case of epidermolysis bullosa letalis under the name of pemphigus hereditarius (Monatschr. f. Kinderheil., 22:15, 1922). We certainly did not intend to deprive him of the credit for this achievement. In our article, however, we did not claim that epidermolysis bullosa letalis was first described by Herlitz. We merely credited Herlitz with first defining this condition as an entity, since he recognized it as one of the variants of epidermolysis bullosa and coined the term epidermolysis bullosa hereditria letalis.

EPIDERMOLYSIS BULLOSA LETALIS

Three cases of epidermolysis bulbosa letalis are described. The infants were born within 10 miles of one another and the three mothers were related, but showed no evidence of the disease. The fathers also were apparently healthy. At birth all the infants had bullous skin lesions. These progressed in spite of meticulous nursing care, massive doses of antibiotics, corticosteroid therapy and increased dietary protein. The babies became pyrexial and the levels of serum albumin decreased markedly. At necropsy none of the infants had any significant lesions apart from the skin. It therefore seems that loss of serum albumin and electrolytes, and dermal sepsis were responsible for the deaths. Corticosteroid therapy appeared to be of no value. Replacement of lost fluids, on the other hand, would seem to be logical in such cases and should probably be a routine procedure. Abnormalities were observed in the histology of the skin. The earliest lesion was a vesicular degeneration of the basal cells of the epidermis, followed by cleavage at the dermoepidermal junction. In the opinion of the authors, these early lesions produce a diagnostic histologic picture differing from other bullous dermatoses, except possibly some of the other variants of epidermolysis bullosa. A study of the epidermis in future cases of this disease by histochemistry or electron microscopy is likely to elucidate further the nature of the congenital defect in the basal part of the epidermis.