Clinical Pearls: Eb

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EB Simplex

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EB is a group of mechano bullous disorders with one unifying diagnostic feature: fragility of skin. The severity of skin involvement and association of extracutaneous findings produces a broad spectrum of clinical manifestations. This clinical complexity, compounded with a plethora of eponyms, has resulted in the identification of as many as 30 different subtypes (Lamprecht IA, Gedde Dahl T. Epidermolysis Bullosa. In: Rimoin, Connor M, Pyeritz RE, et al. Principles and Practice of Medical Genetics, 4th edition. New York: Churchill Livingstone, 2002.). More recently, molecularly based classification recognizes four major categories (simplex, hemidesmosomal, junctional, and dystrophic), and distinct mutations in 10 different genes expressed at the cutaneous basement membrane zone have been identified.

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EB Simplex

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The level of expression of the mutated genes along the basement membrane zone and in extracutaneous tissues, the types and combinations of mutations, their positions along the mutated genes, and their consequences at the mRNA and protein levels, when superimposed on individuals' genetic background, explain the tremendous phenotypic variability in this group of diseases. Precise classification of individual cases requires determination of the level of tissue separation by diagnostic im¬munoepitope mapping and/or transmission electron microscopy. Routine light microscropy may be helpful in identification of the simplex forms, but is often not diagnostic for the junctional and dystrophic subtypes.

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Junctional EB

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Before the biopsy, it is helpful to induce small mini blisters by lightly rotating a pencil eraser at the site of the biopsy. Alternatively, a biopsy could be taken from the outer edge of a blister; never biopsy center of the blister, as the dermis and epidermis become separated and lost, and secondary changes complicate the diagnosis. Molecular diagnostics can be used to confirm the assignment of the patient to a subcategory, but mutation analysis by itself cannot be performed without prior knowledge of the candidate gene/proteins through ultrastructural and immunologic analysis. The impact of molecular genetics is most evident in terms of prenatal diagnosis that is readily available for all major subtypes by DNA based analysis from chorionic villus sample as early as the tenth week of gestation.

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Junctional EB

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The mutation analysis is also helpful in deciphering the mode of inheritance in instances where there is no previous family history of EB and thereby assisting in accurate genetic counseling regarding the recurrence risk. Specifically, molecular diagnostics of type VII collagen mutations can distinguish between de novo dominant dystrophic EB and mild recessive (mitis) EB. Similarly, mutation analysis of keratin 5 and 14 genes can distinguish between de novo dominant and relatively rare autosomal recessive forms of EBS. Some families may also be interested in preimplantation genetic diagnosis that, when performed in the context of in vitro fertilization, makes the diagnosis before the pregnancy starts and therefore avoids the ethical issues related to termination of pregnancy.

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Dystrophic EB

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As a general principle, patients with EB should be managed with a team of specialists that in addition to a dermatologist may include a gastroenterologist, nutritionist, ophthalmologist, orthopedic surgeon, hands surgeon, psychiatrist, and others, depending on the extent of the disease.

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Dystrophic EB

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The general aims include avoidance of trauma, control of infections, and maintenance of appropriate nutritional status. If regular food intake is not able to sustain normal growth and development of the child with EB, direct gastric feeding through a button is most helpful. Infection prevention includes use of mild disinfectants in bath or whirlpool water and treatment of infections with topical Bactroban. Patients with severe recessive dystrophic EB with fusion of the digits are at special risks for development of aggressive squamous cell carcinomas which may start as early as late teens. Therefore, exercise vigilance in detecting and biopsying suspect lesions with signs of squamous metaplasia.