CLINICAL AND LABORATORY INVESTIGATIONS Pediatric Dermatology Vol. 9 No. 3 231-238
Nutrition in Dystrophic Epidermolysis BuUosa Susan AUman, S.R.D.,* Lesley Haynes, S.R.D.,* Petrina MacKinnon, S.R.N.,t and David J. Atherton, FRCPt *Dietetic Department, and tDepartment of Dermatology, Hospital for Sick Children, London
A b s t r a c t : in dystrophic epidermolysis bullosa (EB), a combination of diminished food intake and increased nutritional requirements commonly leads to malnourishment. Adequate nutrition in these patients could provide many benefits, including improved growth, accelerated heaiing, decreased susceptibility to infection, and enhanced weli-being. We assessed nutrition status of children with dystrophic EB, and evaluated the benefits of nutritional advice in those who were considered malnourished. The majority of patients had inadequate Intakes of a wide spectrum of nutrients, inciuding those who appeared to be relatively mildiy affected. We were unable to secure persisting substantial improvements in dietary intake despite thorough counseling. Adequate nutrition in patients with dystrophic EB depends on active nutritional support starting from birth. The need for more invasive techniques of nourishment, such as nasogastric and gastrostomy feeding, may have to be considered earlier than is currently the case.
Children with dystrophic epidermolysis bullosa (EB) have a number of problems that tend to compromise their food intake, and occur in the face of increased nutritional requirements. The effects of the resulting deficiencies include growth retardation, poor wound healing, iron deficiency, anemia, and increased susceptibility to infection. Although it is widely recognized that these children have food intakes that are inadequate for their needs, little in the literature documents this, and no data are available on the effectiveness or otherwise of dietary intervention. The study reported here was undertaken to document further the nature of the nutritional deficiencies encountered in children with dystrophic EB, and to evaluate the benefits of dietary advice.
METHODS Patients
Fifteen children with dystrophic EB (10 females, 5 males; age range 1-8 yrs) who were attending this hospital's EB clinic were invited to take part in the study. In each patient the diagnosis had been made clinicEilly, with confirmation by immunohistochemical and electron microscopic examination of an appropriate skin biopsy specimen. Disease severity varied widely in these patients. The presence of clinical features such as oral ulceration, dental CEiries, dysphagia, and constipation were recorded. Eleven of the patients experienced recurrent oral ulceration causing pain on eating. Seven had some degree of dysphagia, and nine com-
Address correspondence to David J. Atherton. FRCP. Hospital for Sick Children, Great Ormond Street, Lotidon WCIN 3JH, UK.
231
232 Pediatric Dennatoiogy Vol. 9 No. 3 September 1992 plained of constipation. All the children were seen by a member of our pediatric dental department. Seven were considered to have caries, but none complained of discomfort from their teeth, and none were considered to have evidence of dental enamel hypoplasia. Barium swallows were performed in 12 patients—in 6 of 7 with dysphagia, and 6 of 8 who had not reported dysphagia. In four children with dysphagia the examinations were abnormal. A prominent anterior mucosal fold at the junction of the upper and middle third without obstructed barium flow was observed in one patient. The remaining three had a total of five strictures, all in the thoracic esophagus or at the cervicothoracic junction; substantial obstruction of barium flow was observed in only one child. Two patients with strictures also had a hiatal hernia with gastroesophageal reflux, and another demonstrated reduced esophagea! motility. The barium swallow was considered nonnal in two patients who complained of dysphagia. One of these, a 9-year-old girl, had experienced dysphagia severe enough to require hospital admission and intravenous feeding at times when she was unable to swallow her own Sciliva. In the children with no dysphagia, the barium swallow was considered normal in five. It was abnormal in one who had had a stricture at the cervicothoracic junction, without obstruction of barium flow and with a hiatal hernia and gastroesophageal reflux. Of the nine patients who complained of constipation, eight were taking laxatives. All nine found it painful to pass stools and therefore tended to avoid attempting to do so. Evaluations An initial assessment was made of the nutrition status of these patients. Eight had a second assessment after an interval of at least six months, and they were then given careful dietary advice with the aim of improving their intake. A final nutrition assessment was made on these eight patients after another six months to evaluate the degree of benefit resulting from the advice. At each assessment the dietary intake was recorded, height and weight were measured, and blood was drawn for hematologic and biochemical tests. Nutritional intake was assessed by seven-day, weighed dietary records (2) immediately after each
visit. All food and drink consumed by the children were recorded by the parents. All measurements were made at home on Soenhle 800 digital scales (Murhardt, FRG). Parents were fully instructed how to use the scales and how to record food consumption. Results were analyzed using Microdiet computer program (Salford University, Salford, UK). Height and weight were always measured by the same person and were plotted on TannerWhitehouse growth charts (3). Bone age was estimated by radiologic examination of the left hand and wrist (4). Weight and height velocities were calculated using the measurements taken at the first and second visits, except in the case of children who attended on only one occasion; for them, measurements taken on the one visit and on previous clinic examinations were used. Plasma calcium, phosphate, alkaline phosphatase, albumin, total protein, and urea were measured by standard spectrophotometric methods on a Monarch analyzer (Instrumentation Laboratories, Lexington, MA). Plasma copper and zinc were measured by atomic absorption spectrophotometry. Amino acid profiles were obtained by thin-layer chromatography. Serum immunoglobulin (Ig)A, IgG, and IgM were measured by the rate immunoturbidimetric method. All patients had red cell and serum folate measured by a microbiologic method after their first visit, but subsequently by radioimmunoassay (Simultrak, Becton Dickinson Immunodiagnostics, New York, NY). Serum iron and total iron-binding capacity (TIBC) were measured using a colorimetric method; hemoglobin concentration was measured on a Coulter counter. Dietary advice was given on an individual basis to attempt to meet the requirements of each patient and to achieve four principal aims: 1. To increase the energy content of the diet by the use of high-energy foods, including proprietary fortified cow's milk supplements such as Fresubin (Fresenius AG, Oberusel, PTIG). 2. To increase fiber intake by encouraging highfiber foods. 3. To emphasize items in the diet that would provide specific nutrients where the intake of these had been inadequate. Thus, if iron intake were poor or the child were anemic, iiver and other good sources of iron would be recommended. 4. To introduce or modify vitamin and mineral supplements.
Aliman et al: Nutrition in Dystrophic Epidermolysis Bullosa
Three vitamin and mitieral supplements were used. Zinc Sustained-release zinc sulfate monohydrate capsules (Z-Span spansules. Smith, Klitie & French Laboratories, Welwyn Garden City, UK) were prescribed for patients with low plasma zinc or a dietary intake below the recommended dietary allowance (RDA) set by the U.S. National Research Council (5); that is, 10 mg/day for children between ages I atid 10 years. These capsules each contain 22.5 mg of zinc in the form of small granules that can be sprinkled on food. Iron Sodium iron edetate elixir, containing 22.5 mg iron/5 ml (Sytron, Parke Davis Research Laboratories, Eastleigh, UK), was prescribed to children who had an increase in TIBC, low serum iron, or dietary iron intake below the RDA of 10 mg/day for children between ages 1 and 10 years (5). Vitamins Ketovite liquid and tablets (Paines & Byrne, Greenford, UK) provide a complete vitamin supplement and were prescribed when dietary vitamin intake was poor. RESULTS Patients' weight and height centiles, and weight and height velocity centiles are shown in Table 1. Four children had height on or below the third centile, and five had weights on or below the third centile.
233
In nine the weight centile was lower than the height centile, and in three both weight and height fell below the third centile. In 14 patients we were able to measure weight and height velocities prior to the provision of dietary advice and nutritional supplements over a period exceeding six months. Two of them had height velocities at or below the third centile, and five had weight velocities at or below the third centile. Bone age was not markedly different from chronologic age in the majority of patients. Unfortunately, this measurement was made in only one child whose height fell below the tenth centile, and it demonstrated an appreciable delay (bone age 2 yrs at chronologic age 3.2 yrs). Hematologic and biochemical abnormalities were identified in 14 children, the most notable being low hemoglobin (12 patients) and serum iron (13 patients) levels (Fig. 1). Mean corpuscular volume was low in two and mean corpuscular hemoglobin was low in four. The TIBC was measured in 12 patients, and was low in 3 and normal in the others. Serum folate was low in four patients (2.8, 3.3, 3.6, and 4.9 (lg/L; normal 6-21 jAg/L) and high in one (>32 |xg/L). Red cell folate was high in one (837 (jig/L; normal 150-650 (ig/L). Plasma phosphate and calcium levels were normal in all 13 patients in whom they were measured. Plasma alkaline phosphatase levels were reduced in three of them (Fig. 2). Plasma zinc levels were low in 5 of 13 and plasma albumin levels were low in 5 of 14 children, although all had normal plasma total protein concentrations. Only one child had both low plasma zinc and low plasma albumin levels. This
TABLE 1. Data on 15 Children with Dystrophic EB
Sex F F M M F F M F M F F F F F M
EB Type SRD SRD MSRD SRD SDD MRD MSRD MRD SRD SRD MSRD SRD SRD MDD MSRD
Chronologic Age (yrs) 7.3 3.2 4.3 8.8 l.I 4.3 6.5 2.2 6.8 7.1 2.1 4.3 7.4 3.3 6.3
Bone Age (yrs) 7.8 2.0 4.0 — 1.0 4.2 5.0 2.5 1.5 3.0 7.4 3.3 —
Height (centile) 90
Nutrition in Dystrophic Epidermolysis BuUosa Susan AUman, S.R.D.,* Lesley Haynes, S.R.D.,* Petrina MacKinnon, S.R.N.,t and David J. Atherton, FRCPt *Dietetic Department, and tDepartment of Dermatology, Hospital for Sick Children, London
A b s t r a c t : in dystrophic epidermolysis bullosa (EB), a combination of diminished food intake and increased nutritional requirements commonly leads to malnourishment. Adequate nutrition in these patients could provide many benefits, including improved growth, accelerated heaiing, decreased susceptibility to infection, and enhanced weli-being. We assessed nutrition status of children with dystrophic EB, and evaluated the benefits of nutritional advice in those who were considered malnourished. The majority of patients had inadequate Intakes of a wide spectrum of nutrients, inciuding those who appeared to be relatively mildiy affected. We were unable to secure persisting substantial improvements in dietary intake despite thorough counseling. Adequate nutrition in patients with dystrophic EB depends on active nutritional support starting from birth. The need for more invasive techniques of nourishment, such as nasogastric and gastrostomy feeding, may have to be considered earlier than is currently the case.
Children with dystrophic epidermolysis bullosa (EB) have a number of problems that tend to compromise their food intake, and occur in the face of increased nutritional requirements. The effects of the resulting deficiencies include growth retardation, poor wound healing, iron deficiency, anemia, and increased susceptibility to infection. Although it is widely recognized that these children have food intakes that are inadequate for their needs, little in the literature documents this, and no data are available on the effectiveness or otherwise of dietary intervention. The study reported here was undertaken to document further the nature of the nutritional deficiencies encountered in children with dystrophic EB, and to evaluate the benefits of dietary advice.
METHODS Patients
Fifteen children with dystrophic EB (10 females, 5 males; age range 1-8 yrs) who were attending this hospital's EB clinic were invited to take part in the study. In each patient the diagnosis had been made clinicEilly, with confirmation by immunohistochemical and electron microscopic examination of an appropriate skin biopsy specimen. Disease severity varied widely in these patients. The presence of clinical features such as oral ulceration, dental CEiries, dysphagia, and constipation were recorded. Eleven of the patients experienced recurrent oral ulceration causing pain on eating. Seven had some degree of dysphagia, and nine com-
Address correspondence to David J. Atherton. FRCP. Hospital for Sick Children, Great Ormond Street, Lotidon WCIN 3JH, UK.
231
232 Pediatric Dennatoiogy Vol. 9 No. 3 September 1992 plained of constipation. All the children were seen by a member of our pediatric dental department. Seven were considered to have caries, but none complained of discomfort from their teeth, and none were considered to have evidence of dental enamel hypoplasia. Barium swallows were performed in 12 patients—in 6 of 7 with dysphagia, and 6 of 8 who had not reported dysphagia. In four children with dysphagia the examinations were abnormal. A prominent anterior mucosal fold at the junction of the upper and middle third without obstructed barium flow was observed in one patient. The remaining three had a total of five strictures, all in the thoracic esophagus or at the cervicothoracic junction; substantial obstruction of barium flow was observed in only one child. Two patients with strictures also had a hiatal hernia with gastroesophageal reflux, and another demonstrated reduced esophagea! motility. The barium swallow was considered nonnal in two patients who complained of dysphagia. One of these, a 9-year-old girl, had experienced dysphagia severe enough to require hospital admission and intravenous feeding at times when she was unable to swallow her own Sciliva. In the children with no dysphagia, the barium swallow was considered normal in five. It was abnormal in one who had had a stricture at the cervicothoracic junction, without obstruction of barium flow and with a hiatal hernia and gastroesophageal reflux. Of the nine patients who complained of constipation, eight were taking laxatives. All nine found it painful to pass stools and therefore tended to avoid attempting to do so. Evaluations An initial assessment was made of the nutrition status of these patients. Eight had a second assessment after an interval of at least six months, and they were then given careful dietary advice with the aim of improving their intake. A final nutrition assessment was made on these eight patients after another six months to evaluate the degree of benefit resulting from the advice. At each assessment the dietary intake was recorded, height and weight were measured, and blood was drawn for hematologic and biochemical tests. Nutritional intake was assessed by seven-day, weighed dietary records (2) immediately after each
visit. All food and drink consumed by the children were recorded by the parents. All measurements were made at home on Soenhle 800 digital scales (Murhardt, FRG). Parents were fully instructed how to use the scales and how to record food consumption. Results were analyzed using Microdiet computer program (Salford University, Salford, UK). Height and weight were always measured by the same person and were plotted on TannerWhitehouse growth charts (3). Bone age was estimated by radiologic examination of the left hand and wrist (4). Weight and height velocities were calculated using the measurements taken at the first and second visits, except in the case of children who attended on only one occasion; for them, measurements taken on the one visit and on previous clinic examinations were used. Plasma calcium, phosphate, alkaline phosphatase, albumin, total protein, and urea were measured by standard spectrophotometric methods on a Monarch analyzer (Instrumentation Laboratories, Lexington, MA). Plasma copper and zinc were measured by atomic absorption spectrophotometry. Amino acid profiles were obtained by thin-layer chromatography. Serum immunoglobulin (Ig)A, IgG, and IgM were measured by the rate immunoturbidimetric method. All patients had red cell and serum folate measured by a microbiologic method after their first visit, but subsequently by radioimmunoassay (Simultrak, Becton Dickinson Immunodiagnostics, New York, NY). Serum iron and total iron-binding capacity (TIBC) were measured using a colorimetric method; hemoglobin concentration was measured on a Coulter counter. Dietary advice was given on an individual basis to attempt to meet the requirements of each patient and to achieve four principal aims: 1. To increase the energy content of the diet by the use of high-energy foods, including proprietary fortified cow's milk supplements such as Fresubin (Fresenius AG, Oberusel, PTIG). 2. To increase fiber intake by encouraging highfiber foods. 3. To emphasize items in the diet that would provide specific nutrients where the intake of these had been inadequate. Thus, if iron intake were poor or the child were anemic, iiver and other good sources of iron would be recommended. 4. To introduce or modify vitamin and mineral supplements.
Aliman et al: Nutrition in Dystrophic Epidermolysis Bullosa
Three vitamin and mitieral supplements were used. Zinc Sustained-release zinc sulfate monohydrate capsules (Z-Span spansules. Smith, Klitie & French Laboratories, Welwyn Garden City, UK) were prescribed for patients with low plasma zinc or a dietary intake below the recommended dietary allowance (RDA) set by the U.S. National Research Council (5); that is, 10 mg/day for children between ages I atid 10 years. These capsules each contain 22.5 mg of zinc in the form of small granules that can be sprinkled on food. Iron Sodium iron edetate elixir, containing 22.5 mg iron/5 ml (Sytron, Parke Davis Research Laboratories, Eastleigh, UK), was prescribed to children who had an increase in TIBC, low serum iron, or dietary iron intake below the RDA of 10 mg/day for children between ages 1 and 10 years (5). Vitamins Ketovite liquid and tablets (Paines & Byrne, Greenford, UK) provide a complete vitamin supplement and were prescribed when dietary vitamin intake was poor. RESULTS Patients' weight and height centiles, and weight and height velocity centiles are shown in Table 1. Four children had height on or below the third centile, and five had weights on or below the third centile.
233
In nine the weight centile was lower than the height centile, and in three both weight and height fell below the third centile. In 14 patients we were able to measure weight and height velocities prior to the provision of dietary advice and nutritional supplements over a period exceeding six months. Two of them had height velocities at or below the third centile, and five had weight velocities at or below the third centile. Bone age was not markedly different from chronologic age in the majority of patients. Unfortunately, this measurement was made in only one child whose height fell below the tenth centile, and it demonstrated an appreciable delay (bone age 2 yrs at chronologic age 3.2 yrs). Hematologic and biochemical abnormalities were identified in 14 children, the most notable being low hemoglobin (12 patients) and serum iron (13 patients) levels (Fig. 1). Mean corpuscular volume was low in two and mean corpuscular hemoglobin was low in four. The TIBC was measured in 12 patients, and was low in 3 and normal in the others. Serum folate was low in four patients (2.8, 3.3, 3.6, and 4.9 (lg/L; normal 6-21 jAg/L) and high in one (>32 |xg/L). Red cell folate was high in one (837 (jig/L; normal 150-650 (ig/L). Plasma phosphate and calcium levels were normal in all 13 patients in whom they were measured. Plasma alkaline phosphatase levels were reduced in three of them (Fig. 2). Plasma zinc levels were low in 5 of 13 and plasma albumin levels were low in 5 of 14 children, although all had normal plasma total protein concentrations. Only one child had both low plasma zinc and low plasma albumin levels. This
TABLE 1. Data on 15 Children with Dystrophic EB
Sex F F M M F F M F M F F F F F M
EB Type SRD SRD MSRD SRD SDD MRD MSRD MRD SRD SRD MSRD SRD SRD MDD MSRD
Chronologic Age (yrs) 7.3 3.2 4.3 8.8 l.I 4.3 6.5 2.2 6.8 7.1 2.1 4.3 7.4 3.3 6.3
Bone Age (yrs) 7.8 2.0 4.0 — 1.0 4.2 5.0 2.5 1.5 3.0 7.4 3.3 —
Height (centile) 90
