Neonatal epidermolysis bullosa: a clinical practice guideline.

DEBRA International is undertaking a long-term initiative to develop clinical practice guidelines (CPGs) for epidermolysis bullosa (EB), to -improve the clinical care of people living with EB. Current neonatal care is based on evidence, clinical expertise and trial and error, with collaboration between the EB specialist team, parent or carer and patient, and is dependent on the neonate's individual presentation and type of EB. Early intervention based on research and clinical practice is needed to establish a foundation of knowledge to guide international practitioners to create and improve standards of care and to be able to work effectively with those newly diagnosed with EB. This CPG was created by an international panel with expertise working with persons with EB. The CPG focuses on neonatal care using a systematic review methodology covering four key areas: (i) diagnosis and parental psychosocial support; (ii) hospital management: medical monitoring, wound care and pain; (iii) feeding and nutrition; and (iv) discharge planning and EB education. These four areas highlight the importance of a multidisciplinary team approach, to provide a patient-specific holistic care model that incorporates the needs and wishes of the parents and carers. The Hospital Implementation Tool included promotes transfer of theory to clinical practice.

Prevalence of and risk factors for nutritional deficiency and food allergy in a cohort of 21 patients with Netherton syndrome.

BACKGROUND: Netherton syndrome (NS; OMIM: 256500) is a rare autosomal recessively inherited disease due to SPINK5 mutations. Hair and inflammatory skin involvement are variable along with allergies. Morbidity and mortality are high, particularly in infancy. A detailed clinical analysis of a NS patient cohort should broaden the understanding of nutritional challenges and allergic comorbidities. METHODS: In this retrospective monocentric cohort study, medical and dietetic records of pediatric NS patients, presenting between 1999 and 2018, were reviewed. The severity of skin involvement was assessed according to the extent of the body surface area (BSA) affected by erythema. RESULTS: We identified 21 patients with NS (median age 11.6 years). Within the first 6 months of life, requirements for fluid and kcals/protein were high for all patients (average 228 ml/kg/day) and infants had an average of 1.9 feed changes (range 0-4) due to food intolerance. Clinical evidence for IgE-mediated food allergy was present in 84.2% (16/19 children, 2 no data) with a range of 1-12 food allergies per patient. In 75%, more than one food had to be avoided. Specific IgE levels were falsely positive in 38.3% and 8/18 patients (44.4%). One-third (5/15; 6 no data) of patients, all with severe disease, had anaphylactic reactions following ingestion of fish (n = 2), sesame (n = 1), cow's milk (n = 1), and both peanut and egg (n = 1). CONCLUSIONS: Our data emphasize feeding difficulties in children with NS and reveal an unexpectedly higher prevalence of food allergies that gives evidence to the importance of early coordinated multidisciplinary care for overcoming these challenges in NS.

Management of acute sloughing of the esophageal lining in patients with dystrophic epidermolysis bullosa-A series of six pediatric patients.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a subtype of an inherited skin disorder characterized by skin and mucosal fragility due to collagen VII (COL7A1) gene mutations. Esophageal strictures leading to chronic dysphagia and acute episodes are well recognized complications within this subtype. Sloughing of esophageal mucosa and the treatment of this emergency have heretofore received limited attention in the EB literature. METHODS: We retrospectively reviewed the electronic medical records of the patients who had an acute episode of sloughing of the esophageal lining between 2008 and 2021 and extracted the information regarding their clinical presentation and management. RESULTS: Six patients out of 210 with recessive DEB severe (RDEB-S) (n = 4), RDEB intermediate (RDEB-I) (n = 1) and dominant DEB (DDEB) (n = 1) were identified. The mean age at the time of the episode was 2.7 years. All patients had early-onset severe gastroesophageal reflux. Clinically, they presented with a coughing episode (n = 6), hematemesis (n = 6), vomiting (n = 6), and choking (n = 3), followed by coughing up a string like tissue of variable length, part of the esophageal mucosal lining. Four patients recovered with medical management only, two patients required gastrostomy insertions for feeding due to severe persistent dysphagia and one also required a Nissen's fundoplication to manage severe reflux. One patient had aspiration pneumonia. CONCLUSIONS: Sloughing of varying lengths of segments of the esophagus is an emergency. The lining coughed up needs to be cut at the mouth not pulled and the emergency services called immediately for urgent assessment and management. Expert multidisciplinary care is needed to manage this rare but serious condition.

Establishing an appropriate level of vitamin D supplementation in paediatric patients with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Paediatric patients with recessive dystrophic epidermolysis bullosa (RDEB) are at risk of vitamin D deficiency, owing to lack of sunlight from reduced mobility and having large areas of skin being covered with dressings, and to impaired nutritional intake and status. AIM: To establish an appropriate level of vitamin D supplementation in paediatric patients with RDEB. METHODS: Patients with RDEB attending the EB tertiary multidisciplinary team clinic were enrolled. Serum levels of total 25(OH)D were retrospectively recorded for the study period 2012-2018. Data from clinical records on supplements, bone mineral density (BMD) Z scores, compliance, and use of enteral feeds and/or formula were also recorded. RESULTS: In total, 24 patients met the inclusion criteria: 20 with severe RDEB, 3 with RDEB inversa and 1 with intermediate RDEB. Of the 24 patients, 21 (88%) were advised to take a vitamin D3 supplement in line with Department of Health Guidelines (UK), with the remaining 3 patients receiving sufficient intake from formula or enteral feeds. Thirteen of the 24 (54%) had vitamin D deficiency or insufficiency despite advice to supplement; 9 of these 13 (69%) subsequently started or increased the dosage of vitamin D supplements and levels became sufficient (> 50 nmol/L), while the remaining 4 patients (31%) continued to have persistent insufficient levels due to noncompliance with supplements. Reasons for noncompliance were palatability, cost and forgetting to take the tablets. The dose required to maintain sufficient serum levels increased with age, up to 300% of the reference nutrient intake (RNI). CONCLUSION: All patients with RDEB require a supplement or a formula or enteral/sip feed containing vitamin D to maintain sufficient serum vitamin D. The dose required increases with age and can be up to three times higher than the RNI for the normal population. Compliance may improve using a once-weekly loading dose of vitamin D3. Vitamin D deficiency was not solely causative of a low BMD Z score.

The impact of using a multistrain probiotic supplement on gastrointestinal function in children and adolescents with severe recessive dystrophic epidermolysis bullosa.

BACKGROUND: Children and adolescents with severe recessive dystrophic epidermolysis bullosa (RDEB-S) often have severe constipation in addition to gastrointestinal dysbiosis, due to frequent antibiotic use and reduced oral diet. Constipation is treated with long-term use of high daily doses of macrogol gel (Movicol Paediatric PlainTM or LaxidoTM). Constipation is refractory to increases in fibre and fluids, and impacts severely on quality of life. AIM: To study the initial impact and efficacy of using a multistrain probiotic supplement daily for 12 weeks in patients with RDEB-S. The authors sought to determine the impact of such a supplement on  gastrointestinal symptoms, stool consistency and the use of macrogol gel to treat constipation, as well as understanding patient reaction, palability and ease of use. METHODS: Patients were identified through the epidermolysis bullosa tertiary multidisciplinary team clinic in July 2021. Patients were included if they had a diagnosis of RDEB-S, prescribed at least one sachet of macrogol gel and provided written consent to take part. Patients were provided, proprietary liquid multistrain probiotic supplement (Symprove™) with a high bacterial count, at a dose of 1 mL kg-1 once a day. Each patient completed an anonymous, nine-question, electronic survey to document symptoms and report overall findings at the start and end of a 12-week trial period. RESULTS: Four patients with RDEB-S (two boys and two girls; age range 7-14 years) who met the inclusion criteria were approached to take part. All patients had chronic constipation requiring daily macrogol gel use (range 2-5 sachets per day). Three out of four (75%) completed the 12-week course. At baseline (before supplementation commenced), all three (100%) patients reported poor oral appetite, constipation, flatulence, abdominal bloating and pain, and frequent skin infections requiring oral antibiotics, with two of the three (66%) patients also having nausea. After 12 weeks of supplementation, all three patients (100%) reported a significant improvement in abdominal pain and bloating, nausea, stool consistency, stool frequency, flatulence and increased appetite. Two of the three patients (66%) were able to reduce their macrogol gel usage and the third patient (33%) was able to stop macrogol gel usage altogether during the study period. All three patients said they would choose to continue using the supplement if it was available. CONCLUSION: We have shown in this case series that giving a multistrain probiotic supplement in patients with RDEB-S has the potential to improve stool consistency and reduce or prevent the need for chronic macrogol gel use. Future larger-scale, placebo-controlled trials are needed to confirm these results.