EB or not EB: why this is an important question
The 2019 DEBRA EB Classification Consensus meeting was held on 1 and 2 April in London, funded by DEBRA Austria and DEBRA UK. These periodic meetings are important, with major implications for clinical care provision as well as prioritising research into EB diagnostics and therapies. Previous meetings have also been supported by DEBRA, and the outcomes published in widely read peer-reviewed dermatology journals. DEBRA hosts the members of the worldwide senior EB community to carry out this exercise every ~3-5 years. The 20-25 invited participants consider new genetic, molecular, and clinical data, and thus what conditions are considered to be EB, and what are instead other skin-fragility disorders/connective tissue diseases. The purpose is to help scientific understanding and also to ensure that the classification is useful to clinicians to best target clinical diagnosis, prognosis, and care.
The focus of the 2019 meeting was on applying the criteria for EB rigorously, ensuring that any classification scheme changes are not only scientifically correct based on the best information currently available, but will also be useful to practising clinicians. Changes to classification are not undertaken lightly, because of the recognised burden that changing information can place on busy clinicians, and for maintaining continuity of records, such as in patient registers. Nevertheless, improved classification will eventually lead to more accurate diagnostics and better targeted therapies. The reason that it is important to reconsider EB classification every few years is because new genes and mutations are discovered, mainly as a result of patients with no known mutations but clinical symptoms resembling EB being identified. If people are identified as having EB, then appropriate clinical care and advice can be given; if they do not have EB, then different treatments may be needed. In addition, knowing the type of EB, and the exact mutation any individual has, will be essential for safe effective treatment via the majority of gene-, cell-, and drug-based ‘curative’ (i.e. addressing the underlying cause of EB) therapies currently being developed. Many non-EB connective-tissue disorders also show skin fragility which, although sometimes problematic for the patient, are not a major feature of the disease: these are not considered to be EB types. Other disease mechanisms (e.g. metabolic malfunction, infections) can also cause blistering or erosions but again, these need to be distinguished from EB. Indeed, the condition known as ‘EB acquisita’ which is severe and resembles RDEB symptomatically, is in fact an autoimmune disease where the person makes antibodies against their own collagen VII protein – that person needs to be treated for autoimmunity. Inherited EB is a group of skin and mucosal blistering conditions, with underlying genetic mutations that cause an absence or reduction of the important proteins that hold the outer epidermis and deeper dermis layers of skin together: it is the resulting mechanical fragility that characterises EB. The outcomes and recommendations from the April 2019 EB Classification Consensus meeting will be published shortly. The previous consensus document ‘Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification’, J-D Fine et al., was published in 2014, (JAAD Vol. 70, pp 1103–1126). Clare Robinson, Head of Research, DEBRA International