ReviewA nutrition-based approach to epidermolysis bullosa: Causes, assessments, requirements and management
Introduction
Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of rare diseases characterized by skin and mucous membrane fragility [1]. Four major types of EB are recognized, based on the site of blister formation: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome (KS) [1]. They differ in the extent and severity of skin and mucous membrane lesions and in organ involvement; severity also varies with age [1]. There is currently no cure [1]. Patient management is centred on skin care, prevention and early recognition and symptomatic treatment of complications [1]. The cornerstones for improving patients’ quality of life are wound management, control of infections, pain relief and improving individual nutritional status [2].
EB primarily involves the skin: the most severe complication is the development of cutaneous squamous cell carcinomas. However, some types and subtypes are also associated with the development of extracutaneous manifestations and complications affecting other epithelial tissues (external eye, upper airway, and genitourinary and gastrointestinal tracts) or organs, leading to a wide variety of complications (growth retardation, musculoskeletal deformities, osteoporosis, cardiomyopathy, dental complications, infections, anaemia, delayed puberty and psychological complications) [3], [4], [5].
Nutritional status only partly depends on the molecular form of EB. In general, it is more compromised in recessive DEB (RDEB) and JEB, and less compromised in EBS, but patients with mild JEB and RDEB may show only minor signs, while some patients with severe EBS (Dowling-Meara subtype) may have major complications and poor nutritional status [6]. As also affirmed by Haynes [2], we think that the aims of nutritional support in EB can be summarized as follows: combating undernutrition, alleviating the stress of oral feeding, minimizing nutritional deficiencies and improving growth while promoting pubertal development. This multilevel approach also addresses bowel function, immune status and wound healing [2].
A different approach is indicated in JEB generalized severe. This has a poor prognosis [6] and is usually fatal in infancy; nutritional intervention is only palliative [6].
It is well known that more severely affected EB patients have a negative nutritional balance [2], due to:
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factors limiting nutritional intake;
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hyper-metabolism (mainly associated with open skin lesions) leading to increased protein turnover and heat loss [2].
The main gastrointestinal and extraintestinal factors affecting nutritional balance (Table 1) are briefly considered below, followed by investigations and related interventions to improve the nutritional status of EB patients.
The aim of this review is to discuss knowledge of different aspects of the disease in relation to nutrition and growth.
Section snippets
Methods
A search was conducted in PubMed database. This involved the following steps:
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Search using the keywords “epidermolysis bullosa” and “nutrition”;
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Examination of the 87 recovered articles. Those potentially useful for this review were selected and those that could not be used were discarded;
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Identification of 22 articles useful for this review (covering the period from 1988 to 2018);
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Follow-up of some of the references cited in each article to complete the topic, leading to a total of 44 articles
Gastrointestinal involvement
One of the most common sites of extracutaneous involvement is the gastrointestinal tract. This can lead to blistering and erosion in the oral cavity, fixation of the tongue and progressive contraction and closure of the mouth, blistering of the pharynx and oesophagus, gastroesophageal reflux (GER) disease, hiatal hernia, gastritis, peptic ulcer disease, erosion and fissures of the anus, constipation, and protein-losing enteropathy [3], [7].
In a review of gastrointestinal disease in 223
Growth: weight, length/height, body mass index (BMI)
Fox et al. postulated that RDEB children have significantly lower birth weight than unaffected children and that growth retardation even begins in utero [20]. Another study reported that EB children are born at term with appropriate birth weight and length, although EB subtypes were not specified [21]. A more recent study evaluated birth weight in 30 EB patients; birth weight was appropriate for gestational age in 97% and only one patient, with EBS, was small for gestational age [22].
In any
Stepwise evaluation of nutritional status in Eb
An appropriate evaluation of nutritional status should involve a number of steps, to give an overall picture of the patient, and include the evaluation of growth. Weight and length/height of children should be measured regularly (every 3–6 months) [15]. Checking the weight of severely compromised EB patients on growth charts for healthy children may be useful to plan dietary interventions, but should always be considered in the context of the severity of the disease as a whole [7]. Growth
Newborns and infants
Breast milk may satisfy nutritional requirements in less severely affected newborns [1], [16]. Soft paraffin can be applied to the nipple and breast as well as to the infant's face and lips, to reduce friction for the rooting reflex [1]. If breastfeeding is not possible and the child has difficulty in sucking, commercially available teats should be softened with warm boiled water and the teat hole enlarged to facilitate sucking [1]. A Haberman feeder reduces the sucking effort and minimizes
Conclusions
Nutritional support in EB patients must be started early, with constant dietary advice to increase energy and protein intake in line with the individual patient's real needs in order to combat undernutrition, minimize nutritional deficiencies, optimize growth, bowel function, immune status and wound healing and promote pubertal development.
Comparing the weight and length/height of severely compromised EB patients against growth charts for healthy children should always be considered in the
Funding information
This study was partly funded by the Italian Ministry of Health (Ricerca Corrente grant 2018 850/02). The funder had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
Author contributions
Simona Salera wrote the first draft of the manuscript; Claudia Giavoli, Gianluca Tadini, Donata Rossetti, Francesca Sofia Grassi, Giulia Rodari and Paola Marchisio revised the text; Carlo Agostoni and Sophie Guez critically revised the text and made substantial scientific contributions. All the authors approved the final version of the manuscript, which has been revised by a professional native English translator/editor.
Conflict of interest
The authors declare no conflicts of interest.
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