Novel insights into the epidemiology of epidermolysis bullosa (EB) from the Dutch EB Registry: EB more common than previously assumed?

BACKGROUND: Epidermolysis bullosa (EB) is a heterogeneous group of rare and incurable genetic disorders characterized by fragility of the skin and mucosae, resulting in blisters and erosions. Several epidemiological studies in other populations have been carried out, reporting varying and sometimes inconclusive figures, highlighting the need for standardized epidemiological analyses in well-characterized cohorts. OBJECTIVES: To evaluate the epidemiological data on EB in the Netherlands, extracted from the molecularly well-characterized cohort in the Dutch EB Registry. METHODS: In this observational study all EB-patients that were based in the Netherlands and captured in the Dutch EB Registry between 1988 and 2018 were included. The epidemiological outcomes were based on complete diagnostic data (clinical features, immunofluorescence, electron microscopy and mutation analysis), with longitudinal follow-up. RESULTS: A total of 464 EB-patients (287 families) were included. The incidence and point-prevalence of EB in the Netherlands were 41.3 per million live births and 22.4 per million population, respectively. EB Simplex (EBS), Junctional EB (JEB), Dystrophic EB (DEB) and Kindler EB were diagnosed in 45.7%, 18.8%, 34.7% and 0.9% of the EB-patients, respectively, with an incidence and point-prevalence of 17.5 and 11.9 (EBS), 9.3 and 2.1 (JEB), 14.1 and 8.3 (DEB), 0.5 and 0.2 (Kindler EB). In 90.5% of the EB-patients the diagnosis was genetically confirmed. During the investigated time period 73 EB-patients died, 72.6% of whom as a direct consequence of their EB. CONCLUSION: The epidemiological outcomes of EB in the Netherlands are high, attributed to a high detection rate in a well-organized set-up, indicating that EB might be more common than previously assumed. These epidemiological data help to understand the extensive need for (specialized) medical care of EB-patients and is invaluable for the design and execution of therapeutic trials. This study emphasizes the importance of thorough reporting systems and registries worldwide.

Living Donor Kidney Transplantation in a Patient With Epidermolysis Bullosa: A Case Report.

Severe recessive dystrophic epidermolysis bullosa is a very rare inherited disease with excessive blisters forming starting at birth. Surgical intervention in this population creates a challenge: preventing formation of new lesions while managing previously scarred tissues. We present a case of a 27-year-old patient with end-stage renal disease caused by rapidly progressive IgA nephropathy. Living donor kidney transplantation was performed under local, spinal and epidural anesthesia. Living kidney transplantation in epidermolysis bullosa patients with end-stage renal disease should not be a contraindication for transplantation and should be considered as a viable and feasible option after careful preparation.

Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases.

Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care-based interventions. Opioid-based therapies underpin pain care in EB; however, they are unable to provide adequate analgesia in a significant proportion of patients. Cannabinoid-based medicines (CBMs) have been studied increasingly for pain conditions of various aetiologies and pose as a novel dimension for pain care in EB. We present three patients with EB who were prescribed pharmaceutical-grade sublingually administered CBMs comprising tetrahydrocannabinol and cannabidiol. All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake.

The needs of parents with children suffering from lethal epidermolysis bullosa.

BACKGROUND: Some subtypes of the heterogeneous genetic blistering disease epidermolysis bullosa (EB) lead to lethality in childhood. The severity and extent of blistering leaves these patients living in excruciating pain and distress their entire lives. Parents of these patients experience some specific problems, such as the unfamiliarity of EB amongst healthcare professionals and the suffering and loss of their child. OBJECTIVE: To identify the needs of parents who have lost their child to lethal EB. METHODS: A qualitative study was performed, comprising semistructured, in-depth interviews with 16 parents. The transcripts were analysed and common themes were identified. RESULTS: Parents indicated that they have the need (i) for a fast and correct referral to a specialized EB clinic, (ii) to be informed as honestly as possible about the diagnosis and lethal prognosis, (iii) to have a structured network of caregivers in the palliative care, (iv) to be involved in the care and the medical decisions involving their child, (v) to be informed about the end of life and to discuss euthanasia, (vi) for guidance and to have remembrances of their child, and (vii) for genetic counselling. CONCLUSIONS: Our job as healthcare professionals is to provide the best care not only for children suffering from lethal EB, but also for their parents. In this study, parents have provided us with some guidelines to care for them. However, it is important to keep in mind that every parent is different, and that the guidance should be tailored to their individual needs.

Long-term follow-up of patients with Herlitz-type junctional epidermolysis bullosa.

BACKGROUND: Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a rare, autosomal recessive disease caused by absence of the epidermal basement membrane adhesion protein laminin-332. It is characterized by extensive and devastating blistering of the skin and mucous membranes, leading to death in early childhood. OBJECTIVES: To present the results of the long-term follow-up of a cohort of patients with JEB-H, and to provide guidelines for prognosis, treatment and care. METHODS: All patients with JEB-H included in the Dutch Epidermolysis Bullosa (EB) Registry between 1988 and 2011 were followed longitudinally by our EB team. Diagnosis was established using immunofluorescence antigen mapping, electron microscopy and DNA analysis. RESULTS: In total, we included 22 patients with JEB-H over a 23-year period. Their average age at death was 5.8 months (range 0.5-32.6 months). The causes of death were, in order of frequency: failure to thrive, respiratory failure, pneumonia, dehydration, anaemia, sepsis and euthanasia. The pattern of initial weight gain was a predictor of lifespan in these patients. Invasive treatments to extend life did not promote survival in our patients. CONCLUSIONS: It is important to diagnose JEB-H as soon as possible after birth so that the management can be shifted from life-saving to comfort care. The palliative end-of-life care can take place in hospital, but is also safe in the home setting. Suffering in patients with JEB-H can become so unbearable that in some patients who do not respond to adequate analgesic and sedative treatment, newborn euthanasia, performed according to the Groningen protocol, is legally permitted in the Netherlands.

[From gene to disease; epidermolysis bullosa due to mutations in proteins in or around the hemidesmosome]. / Van gen naar ziekte; epidermolysis bullosa door mutaties in eiwitten in of rond het hemidesmosoom.

Epidermolysis bullosa is a group of hereditary mechanobullous dermatoses in which detachment of the skin and mucosa in or around the epidermal basement membrane takes place from birth on. The clinical manifestations vary from abnormalities in the nails to painful mutilation of the skin, eyes, mouth, throat, oesophagus and locomotor apparatus. Ten genes have been identified that can cause a form of epidermolysis bullosa. These genes code for proteins in or around the hemidesmosome, the site of anchorage of the basal cell to the basement membrane. The prevalence of epidermolysis bullosa is about 1 in 22,000. The diagnosis is on the basis of the medical history, clinical findings, immunofluorescence microscopy, electron microscopy and DNA studies. The current treatment is still primarily symptomatic and prophylactic.