Isheo Research Bulletin 1.2021 on Rare Disease
The unmet need of patients with
Get the RIGHT ACCESS
The access of patients with rare diseases matters, it is not just a slogan but a way to remember that patients with rare diseases often find it difficult to access the best innovative therapies that research makes available.
This short report focuses on Epidermolysis Bullosa, a rare disease also known as “Butterfly Children” because the child’s skin seems as fragile as a butterfly wing.
Epidermolysis bullosa (EB) is a group of rare genetic conditions characterized by fragile skin that blisters in response to friction, minor injury, or trauma
There are at least 31 subtypes of EB. The classification of EB is based upon the location of the cleavage plane in the skin: simplex or epidermolytic with blistering within the epidermis, junctional with blisters in the epidermal-dermal junction, dystrophic or dermolytic with blistering in the dermis, and Kindler syndrome with multiple splits in the skin.
Over recent years, our understanding of the mechanisms that give rise to the spectrum of clinical phenotypes of EB has greatly improved with advances in molecular and cell biology. The majority of forms of EB arise from mutations in different genes that make structural proteins that are responsible for dermal-epidermal integrity
The prevalence of EB is about 60 cases per million in Europe (approximately 30.000 individuals) and 8 cases per million within the US. Approximately 400- 500.000 people worldwide are affected by EB.
The symptoms can range from mild to severe, based on the types/subtypes of EB and the inheritance pattern.
- From moderate to severe pain
- Skin wounds
Diagnosis of Epidermolysis Bullosa
EB can be diagnosed from a skin biopsy processed for immunofluorescence (IF) antigen mapping and transmission electron microscopy to confirm some of the major types. Increasingly, next generation genetic testing with a panel of EB genes is used as the main diagnostic tool for a more precise genetic diagnosis. Prenatal diagnosis can also be accomplished using amniocentesis or chorionic villus sampling as early as the first trimester of pregnancy.
Skin biopsy for immunofluorescence antigen mapping.
A small sample of intact skin is removed and examined with special techniques to identify the plane of blistering.
Genetic testing is the most accurate way to confirm the diagnosis and the pattern of inheritance.
Prenatal testing may be considered in families with a history of a severe form of EB.
Treatment of Epidermolysis Bullosa
Important measures for skin care include avoidance of trauma, gentle cleansing of the skin, early diagnosis and treatment of skin infections, and specialized dressings to manage chronic wounds.
Treatments may include medications, such as painkillers, iron to treat anaemia and medication to avoid constipation. Surgery may be required to treat complications such as scarring of the hands, narrowing of the oesophagus and to remove skin cancers which occur in some forms of EB.
Burden of Disease
The challenges associated with management and care of EB can pose a significant burden on the patient and caregiver. While clinical presentation or the extent of ulceration may vary according to the distinctive phenotypes, skin blistering is a common characteristic for all types of EB.
UNMET MEDICAL NEED
Treatment options for patients with EB are limited. The primary aim of the treatment is to protect the skin, reduce blistering, prevent complications, and promote healing. The prognosis of EB can vary dependent on the subtype of the disorder. While some patients have normal life expectancy, others can be at major risk of death during the first few years of life. For those who survive into adulthood, life can be severely limited.
Burden of Disease
Researchers are studying better ways to treat and relieve the symptoms of epidermolysis bullosa, including:
Bone marrow (stem cell)
Cell-based therapies transplantation
14 phase II and 4 phase III clinical trial are ongoing worldwide. One drug (Filsuvez®) have already received the orphan drug designation for the treatment of EB by Food and Drug Administration (FDA) and European Medicine Agency (EMA).
Distribution of Clinical Trials
Overview of the main phase II and phase III clinical trials
Main barriers to the market access of the innovative drugs for rare disease:
High uncertainy around products for small popoulations.
Fear of high price and high budget impact.
Fragmented EU market with decisions on Pricing and Reimbursement at National level.
An interview with Professor
Professor Jemima Mellerio is a consultant dermatologist treating both adults and children with a wide range of skin conditions.
Her research activities have focused on the field of gene discovery for novel forms of EB and other genodermatoses, as well as on clinical trials of emerging translational therapies, including cell and gene therapy, and other rare disease clinical trials. Her NHS practice is at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust where she is the Chief of Dermatology. She holds an Honorary Chair of Paediatric DermatologyatKing’sCollegeLondon.
An integrated approach that takes all aspects into account is the solution.
Fife CE, Yaakov RA, Serena TE. Epidermolysis bullosa: a case report. Chronic Wound Care Management and Research, 2018:5 17-21
Cohon HI, Teng JM. Advancement in management of epiderlolysis bullosa. Curr Opin Pediatr. 2016 Aug;28 (4):507-16