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Inherited epidermolysis bullosa (EB) encompasses a number of genetic disorders characterized by structural skin fragility and mucosal abnormalities, particularly following trauma. Clinical manifestations vary widely, from minor functional discomfort (blistering of the extremities after a forced march) to death in children during the neonatal period. Typically, 4 major types of epidermolysis bullosa are distinguished based on the site of skin cleavage: epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), junctional epidermolysis bullosa (JEB) and each group comprise numerous subtypes that are defined based on phenotypic differences. The phenotypic differences may be interfamilial or even intrafamilial for a given mutation. The classification of inherited epidermolysis bullosa has been simplified and is based on site of cleavage, clinical data, the structural protein implicated and molecular biology. Advances in research offer hope for treatment by gene therapy, cell therapy, protein therapy or a combination of the different therapies in some cases, but currently, management is still symptomatic as no cure exists.
Management differs depending on type and subtype. The localized forms affecting only the fingers and toes are “relatively” easy to manage, requiring the use of topical antiseptics or topical and/or systemic analgesics. However, the treatment of the complications caused by skin-mucosal detachment and palliative care is more problematic with the generalized forms of EB, particularly Hallopeau-Siemens recessive dystrophic EB characterized by diffuse lesions, synechia of the fingers and toes and mucosal lesions, and lethal junctional Herlitz-type EB. The aim of treatment is to provide children presenting with sometimes severe lesions from birth and their families as much comfort as possible.
With the severe forms of the disease, one of the most difficult things to determine during the neonatal periods is the amount of intensive care a child should receive to increase his/her chances of survival with the fewest possible sequelae. Unfortunately, currently, the Herlitz-type forms are beyond treatment. With these forms, the following extremely difficult question needs to be answered: up to what point should an infant in intense pain be maintained artificially in life by means of life-sustaining measures that should never go beyond being palliative?
Histological studies do not always enable the specific identification of a given subtype of epidermolysis bullosa. Diagnostic classification begins by the identification of the level of the skin cleavage with the use of immunofluorescence antigen-mapping. In difficult cases, electron microscopy remains useful for the better understanding of the ultrastructural abnormality, but sometimes, a definite diagnosis can only be made following genetic studies.
It is important to try and make a definitive diagnosis as soon as possible in order to anticipate and better manage the complications inherent to each form. So, the first stage of diagnosis involves taking a skin biopsy when EB is suspected and in most cases, the deficient protein can be identified by immunohistochemical analysis. Molecular diagnostic testing is essential each time the severity of the type of inherited EB ethically justifies prenatal diagnosis, based on the parents’ demand.
INFORMATION FOR FAMILIES
Learning that a child has a genetic disease is always a difficult step for the families, particularly when the condition is visible from the very first weeks of the child’s life and the newborn cannot be taken home immediately like with epidermolysis bullosa. The information must be given calmly, preferentially in the presence of a psychologist familiar with these types of situations. It is important for the whole family to be examined to try to better understand the mode of transmission of the disease taking into consideration small signs that might seem only secondary (e.g. big toe nail dystrophy in one of the parents presenting with dominant dystrophic epidermolysis bullosa). Histological results can be used to more specifically explain the structural abnormalities involved, preferably with the help of a diagram, but without making hasty conclusions about outcome during the neonatal period. The parents must start being educated in the management of a chronic disease from the very first time of contact because the symptomatic management of this chronic disease requires all parties, including the family, to work as a team. The healthcare staff needs to be extremely available when managing a patient with epidermolysis bullosa. When the time is right, the family may be put in contact with a geneticist who will work with the team to provide them with personalized genetic counselling.
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