Dietary regimens for atopic dermatitis in childhood - Europe PMC

JOURNAL OF THE ROYAL SOCIETY OF MEDICINE

Supplement No. 30

Volume 90

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Dietary regimens for atopic dermatitis in childhood T J David PhD MD FRCP DCH Leena Patel MD MRCP Carol Ewing MD MRCP R H J Stanton BSc SRD J R Soc Med 1997;90(Suppl. 30):9-14

Double-blind placebo-controlled food challenges (DBPCFC) in selected children with atopic dermatitis have clearly shown that some of these children have allergic reactions to food. Sampson, for example, administered selected foods in doses of 8 g or less, and in sensitive subjects this provoked an immediate (within 2 h) itchy erythematous macular rash, accompanied by a significant rise in the plasma histamine concentrationl-3. It is known that atopic dermatitis can worsen following exposure to allergic (e.g. foods, pet animals) or non-allergic (e.g. heat, skin contact with wool) triggers. The question arises as to whether these triggers cause dermatitis or simply worsen pre-existing dermatitis. The role of food allergy in the pathogenesis of atopic dermatitis is discussed by Sampson on page 2 in this supplement. The present review focuses on the different dietary approaches to the management of atopic dermatitis in childhood. SELECTION OF PATIENTS FOR DIETARY REGIMENS

The possible criteria for selecting patients for dietary treatment are shown in Table 1. Skin prick tests and RAST tests, both of which are intended to detect specific IgE antibodies, have been used in the diagnosis of food allergy, but this use is beset by problems, most notably the large number of false positive and false negative reactions4 9. In the context of food allergy and atopic dermatitis, the position is that there are no controlled trial data to indicate that skin testing or RAST testing will predict the outcome of dietary regimens. Observational data, from uncontrolled studies in which selected patients were subjected to dietary treatment, suggest that the results of these tests do not reliably predict either success or failure of various elimination diets1015. Another approach is to select for treatment those patients for whom there is a parental history of food allergy. One difficulty with this strategy is the notorious unreliability of parental observation in the diagnosis of food allergy. Studies that have employed food challenges have shown that parental reports of adverse reactions to food are unreliable. In one study which used double-blind University of Manchester Department of Child Health, Booth Hall Children's Hospital, Charlestown Road, Blackley, Manchester M9 7AA, UK Correspondence to Professor T J David

SECTION OF PAEDIATRICS, 22 OCTOBER 1996

Table 1 Possible criteria for selecting patients for dietary treatment One or more positive skin prick tests for food antigens One or more positive RAST tests for food antigens Parental report that the child has food allergy Food allergy proven by double-blind placebo-controlled food challenge Clinical criteria: Severity or extent of skin disease Age (below a specified limit) Multiple atopic features Parental criteria: Belief that food allergy could be important Desire to avoid conventional medical treatment

placebo-controlled challenges, parental reports of adverse reactions to foods could be confirmed in only 27 (33%)16. Not only were the parents' histories shown to be unreliable, but the physicians' opinions were no more accurate than the parents'. In another study which looked prospectively at 480 children in the USA up to their third birthday, 16% were reported to have had reactions to fruit or fruit juice and 28% to other food17. However open challenge confirmed reactions in only 12% of the former and 8% of the latter. As for suspected reactions to food additives, parental histories are even less reliable; in one study, double-blind placebo-controlled challenges failed to confirm parental reports of reactions to tartrazine in all 24 children studied18. Observational data, from uncontrolled studies in which selected patients were subjected to dietary treatment, suggest that the results of these tests do not reliably predict either success or failure of various elimination diets1012'14 In North America, a popular approach has been to perform skin prick tests, followed by DBPCFC proceeding to dietary elimination of foods that are thus proven to trigger an adverse reaction19-22. However, there are no controlled trial data to evaluate this strategy, and it is unknown what proportion of subjects with atopic dermatitis are helped in the short- or long-term by this type of regimen. It is common to select for dietary treatment patients with the most severe or extensive skin disease, for the simple reason that it is difficult to adhere to elimination

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diets, and there is likely to be less motivation to adhere to a diet in a mild case. There is, however, no objective evidence that response to dietary treatment is associated with disease severity. Although there is a lack of objective supporting data, there is a strong impression that age is a factor in predicting response to diet, the chances of benefit being greatest in the youngest patients, particularly those under 12 months of age. There is some basis for this observation, given the tendency for most children to grow out of food allergy by the age of 3 to 5 years. Sampson reported the results of 514 DBPCFC in selected children with atopic dermatitis19 21. In this study, the selection of foods for blind challenge was based on skin test and RAST test results, and/or a 'strongly suggestive history of food hypersensitivity'. As a powerful example of the poor utility of skin tests, RAST tests or history taking, a total of 334 (65%) of these blind challenges were negative, and only 180 (35%) were positive. Cutaneous reactions occurred in 143/ 180 (79%). Symptoms exclusively in the skin occurred in 29% of the reactions. Gastrointestinal symptoms were observed in 43% of the reactions, and respiratory symptoms in 28% of positive blind challenges. A possible inference is that children with atopic dermatitis and food allergy are likely to have food reactions that are not confined to the skin, and that accordingly children with multiple atopic features (rather than those with purely dermatological features) should be particularly considered for elimination diets. Although there are no objective data from controlled studies to support the notion of a better response to dietary treatment in those with multiple atopic symptoms (e.g. dermatitis, asthma and rhinitis), nevertheless multiplicity of symptoms has been used to select patients for dietary treatment. Parental wishes have an influence on the choice of treatment. Many hospital referrals in Britain occur because parents wish to explore the possibility of dietary treatment. This is partly because the possible link between food allergy and atopic dermatitis is well known, and particularly well publicized in lay information. Another factor is an equally widespread fear of topical steroid therapy23. Whatever the reasons, dietary treatment, often unsupervised by health professionals, is very widely employed in the UK. For example, in a study of the dietary habits of 73 children seen consecutively in a hospital dermatology outpatient clinic in Leicester, although most had only mild flexural dermatitis, 52 (71%) had excluded more than one food item from their diet24. Almost all diets were unsupervised, and only six children had been seen by a dietitian. For parents who are eager for dietary treatment despite our own assessment that this is unlikely to be beneficial (most commonly because of the age of the child), our own policy is to share the limited available data on outcome and leave the final choice to the parents and child. If parents are really determined to try a

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diet, we prefer that this should be done with our help and with dietetic supervision rather than risk the nutritional and other hazards of unsupervised diets25. DIETARY STRATEGIES IN ATOPIC DERMATITIS The starting point is that it is impossible to predict whether or not the patient will respond to dietary elimination. Thus

elimination diets have to be viewed as therapeutic trials, and should adhere to certain principles (Table 2). The most basic principle is that the diet should be employed for a fixed period, terminating with an assessment at which there is a decision either to abandon the diet or continue with it and to try the subsequent reintroduction, one by one, of individual foods that have been avoided. Although some patients improve within a few days, it may sometimes take 2-3 weeks for improvement to be obvious. Any diet must be pursued long enough for benefit to become evident. A practical problem is the frequency with which dermatitis flares up, for reasons such as teething, viral infections, hot weather, long car journeys etc. In practice, because of this marked day-to-day variation, we employ a 6-week period for most diets in atopic dermatitis. The aim is to avoid the niggling worry 'if only we had gone on a bit longer the diet might have helped'. If a diet fails, the parents have to be convinced it has failed; lingering doubts undermine subsequent management. The exception is the elemental diet (see below), where the regimen is so unpleasant and invasive that the rigid imposition of a 6-week period would be unacceptable. It is helpful to agree an end point, partly to ensure that parents have realistic expectations. Although we have witnessed some excellent responses to dietary treatment, we have never seen dermatitis completely disappear as a result of a diet. Accordingly it is useful for the parents to consider in advance what would constitute a worthwhile improvement, not necessarily to be rigidly adhered to, but Table 2 Elimination diets

as

therapeutic trials: important principles

Define a diet in time

To ensure diet tried long enough To avoid needless prolongation of diet Agree end point Decision-making assessment after initial period on diet Planned re-introduction of foods after initial assessment Remember improvement may be coincidence or placebo effect Involve a dietitian To completely exclude individual foods To ensure nutritional adequacy To give practical advice to parents and doctors Diet may fail for many reasons


to act as a guide when it comes to making a decision about continuation or abandonment of the diet. If, after the initial trial period, the decision is to continue with the diet, there needs to be some plan for re-introduction of foods to identify those foods that can be tolerated and those that must be avoided. The general principles are (items (v), (vi) and (vii) apply only to few food diets):

(i) Try only one new food at a time, otherwise it is impossible to determine which of two or more foods is responsible for a flare-up of dermatitis. (ii) Try one new food for a week, giving it at least once a day in normal amounts, because some patients have delayed reactions that are only detected after several doses of the food have been taken. (iii) Trying a new food may be associated with a flare-up of the dermatitis for reasons other than food allergy (e.g. teething, virus infection), and the presence of confounding variables means that at the end of a week on a new food it may be unclear whether the skin has worsened because of the food or some other factor. Under these circumstances, the only option is to avoid the food, and try it again on another occasion. (iv) If a food is to be implicated as a trigger, then there are two requirements, one being worsening after consuming the food, and improvement after the food has been withdrawn. Thus, if at the end of a week, a food is suspected as a trigger, the next step is to defer further food re-introductions, waiting for some improvement over the next few days after the test food has been withdrawn. Failure of the skin to improve suggests either an alternative cause for the flare-up or a continuing confounding factor that is making the dermatitis worse (e.g. bacterial skin infection). (v) Delay trying foods that are highly likely to act as food triggers (e.g. egg or fish) in favour of those that are less likely to act as food triggers (e.g. chicken, banana). (vi) Initially try to choose foods that have some important nutritional value (e.g. when a child is only taking six foods, lettuce would not be a useful early choice). (vii) Initially select foods that are useful food ingredients (e.g. maize is useful, not just as sweetcorn itself, but also as corn flour and corn oil). (viii) Avoid exposing the child to a food for which there is a history of life-threatening reactions. (ix) In order to detect the development of tolerance, re-try foods that are not tolerated every 6-12 months. It is important to remember that improvement associated with an elimination diet may be a coincidence or a placebo effect.

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The dietitian has an important role, to help the parents to completely exclude individual foodstuffs, to ensure that the resulting diet does not lead to nutritional deficiency2637, particularly ensuring an adequate calcium intake38'39, and to give practical advice to the parents. It is helpful to consider why diets may fail. The most obvious reasons are that the child does not have food allergy, or the period of elimination has been too short. Other common reasons are the incomplete elimination of a trigger food (e.g. parent allowing a child on a cow's milk free diet to have a manufactured food that contains casein or whey, not realizing that these are both derived from cow's milk), non-adherence to the diet4041, or intolerance to other food items still being consumed. A further possibility is intolerance to a cow's milk substitute in a child with cow's milk protein allergy. Double-blind challenges studies have shown that approximately 8% of children with cow's milk protein allergy are also allergic to soya. Less common is allergy to whey hydrolysates, and there is rarely allergy to casein hydrolysate milk formulae. Co-existing disease may occasionally mask a beneficial response to an appropriate diet. Finally, the symptoms may have been imagined or

fabricated42. TYPES OF DIET

If the food triggers have not been identified, then there are three main types of dietary strategy, the simple elimination of cow's milk protein and egg, the few food diet, and the so-called elemental diet. These will be briefly described. Cow's milk-protein free and egg-free diet In the absence of any specific pointers to individual food triggers, the simplest approach is to exclude cow's milk protein and egg. This approach has been tested by controlled trial. Atherton and colleagues studied 36 children with atopic dermatitis, using a control diet which contained cow's milk and dried egg43. 20 children, median age 6 years, completed the study; 14 patients responded more favourably to the milk- and egg-free diet, whereas only one patient responded more favourably to the control diet than the milk- and egg-free diet. Three patients experienced a severe exacerbation of eczema within a few days of starting the control diet period, probably because the control diet included added egg, and these cases were excluded. Furthermore, there appeared to be relatively little benefit associated with the control diet, an unusual feature for diets usually have a marked placebo effect. It has been suggested that this study showed a placebo effect from a milk- and egg-free diet, this effect being masked in the control diet by the inclusion of added egg which exacerbated the eczema. A further controlled study of dietary avoidance of cow's milk protein and egg in 53

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patients wtih atopic dermatitis of varying ages failed to show significant benefit4. The few food diet

This is a diet in which all but a handful of foods is excluded. An example used in Manchester permits the child to eat lamb, potato, rice (and Rice Crispies), one of the Brassica family (cauliflower, cabbage, brussel sprouts or broccoli), pears (in restricted quantities to avoid loose stools caused by the high fructose content) and tap water. This diet is used for an initial period (6 weeks in our unit, but 4-6 weeks in some other units), before the child is reassessed. Dietetic supervision and family motivation are both essential. Early uncontrolled studies suggested benefit from this regimen. Thus Pike et al. studied 66 selected children with atopic dermatitis and a mean age of 4.2 years, and found an unquantified benefit associated with a few food diet in 24 (36%), this benefit being sustained in 12 (18%)45. 41 (62%) patients were unresponsive to this treatment. There was no control group. Neither skin prick tests nor RAST tests were of any value in predicting trigger foods. Double-blind placebo-controlled challenges were performed in 10 of the 15 diet-responsive patients. The parents and doctor each identified the active period incorrectly on five occasions and correctly on five occasions, suggesting to the authors that parental identification of food triggers was unreliable. In a prospective but uncontrolled follow-up study in Manchester, 63 children (median age 2.9 years) with atopic dermatitis were selected for treatment with a few food diet10. Nine patients (14%) abandoned the diet before the initial 6-week treatment period had been completed. Of the 54 patients who completed 6 weeks of treatment, 33 (52%) showed a greater than 20% improvement in the disease severity score and were categorized as having improved. 21 (39%) failed to show a greater than 20% improvement, and were classed as treatment failures. All groups were followed up, and the key finding (Table 3) was that at 12 months all three groups had markedly improved, irrespective of whether they had responded to the diet or not. The conclusion was that, although the diet was Table 3 Outcome of few food diet in 63 children with atopic dermatitis Disease severity score

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Initial response to diet

Pre-diet

1 year

Unable to cope (n=9) Improved on diet (n=33) No improvement on diet (n=21)

50 70 60

17 15 16

For details of disease

severity score (see Ref 10)

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associated with short-term benefit in some patients, there was no evidence of long-term benefit, and all patients showed a marked tendency to improvement over time. In the only randomized controlled trial of a few food diet, 85 children (median age 2.3 years) with refractory atopic dermatitis affecting more than 12% of the body surface area, were randomly allocated to receive a few foods diet supplemented with either a whey hydrolysate (n=27) or a casein hydrolysate formula (n=32), or to remain on their usual diet and act as controls (n=26), for a 6-week period46. 35 patients who received the diet and 4 controls had to be withdrawn because of non-adherence with the diet or intercurrent illness. The change in dermatitis severity was evaluated by a 'blind' observer who estimated the extent of the dermatitis and severity, using a skin severity score. After 6 weeks, there was a signficiant reduction in all three groups in the percentage of surface area involved. 16 (73%) of the 22 controls and 15 (58%) of the 24 who received the diet showed a greater than 20% improvement in the skin severity score. This study failed to show benefit from a few foods diet. Elemental diet In the so-called elemental diet, more accurately described as a non-macromolecular diet, ordinary foodstuffs are all avoided, and the patient receives a liquid diet which contains amino acids, carbohydrate, fat, minerals and vitamins. The chances of an allergic reaction are minimal, but the palatability of so-called elemental formulae such as Vivonex or ElementalO28 is very poor. Because of this, some units administer these formulae by nasogastric tube, whereas others use every trick imaginable to persuade the child to drink the formula in adequate volumes. Munkvad et al. reported on a controlled study of an elemental formula Vivasorb47. 33 adults with atopic dermatitis entered the study, and 23 patients completed the study. The patients were hospitalized and randomized to receive the elemental diet or a control diet which comprised normal food that had been liquidized. The conclusion was that there was no significant difference between the two groups. Studies of eosinophil count, IgE concentration, orosomucoid and skin biopsies showed no significant difference between the two groups. The conclusion was that food intolerance plays little role in adults with atopic dermatitis. The only large study of elemental diets in children with atopic dermatitis was uncontrolled. 37 children, median age 3 years, with refractory and widespread atopic dermatitis were admitted to hospital and received an elemental formula (Vivonex) for a mean duration of 29 days11. Complications included greater than 10% body weight loss in 10 patients, loose stools in seven, and a mean fall in the


serum albumin of 9.6 g/L. Food challenges were performed at intervals of 7 days, and the patients followed-up for at least 12 months. 40/185 food challenges in hospital were positive, and 28/40 were delayed reactions only detectable 1-7 days after a food was introduced. After discharge, 19/ 37 patients experienced allergic reactions to pets, house dust or grass. 10/37 (27%) either failed to respond to the regimen or relapsed within 12 months. Sustained improvement in the dermatitis was seen in 27/37 (73%) patients, and by discharge from hospital their disease severity score had fallen to a mean of 29% of the pretreatment figure and only 1/27 required topical steroids. There were no clinical or laboratory findings which could be used to predict the outcome. The lack of a control group means that it is impossible to tell how much of the benefit was a placebo effect associated with diet, hospitalization and pet avoidance. Elemental diets are highly invasive, and are best seen either as a last resort or as the ultimate diagnostic test for food allergy48 4 Maternal dietary exclusion in breast-fed infants with atopic dermatitis Cant et al. studied 37 breast-fed infants with atopic dermatitis50. 19 mothers and babies took part in a doubleblind cross-over trial of exclusion of egg and cow's milk, and 18 took part in open exclusion of 1 1 foods followed by double-blind challenge to those mothers whose infants seemed to respond. Nearly half (46%) of the babies showed an improvement in their dermatitis during the exclusion periods, but the authors admitted that had the mothers not returned to a normal diet they would have thought that dietary exclusion was beneficial when 'in fact the improvement was probably spontaneous'. In 6 of the 37 babies, however, the eczema did seem to respond by both improving when the mothers avoided egg and cow's milk and relapsing when these foods were re-introduced. No specific factors predicted which babies would respond to maternal dietary exclusion, and skin prick tests were unhelpful. The authors concluded that atopic dermatitis in breast-fed infants has a high rate of spontaneous improvement, which is often wrongly attributed to maternal dietary exclusion, but that nevertheless a subgroup of such babies do seem to be genuinely affected by foods in their mothers' diets. CONCLUSIONS

The first concept, the terra firma, is that, in certain children, eating specific food triggers can cause pre-existing atopic dermatitis to worsen. The second concept, which by no means follows from the first, is that avoidance of selected foods can cause atopic dermatitis to improve. The

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transatlantic differences in the approach to the problem are as different as cricket and baseball. In the USA, the approach has been to prove a diagnosis of food allergy by screening with skin prick tests and RAST tests and then performing DBPCFC before proceeding to an elimination diet, using a challenge protocol that makes it difficult or impossible to detect delayed reactions, which may be of equal or greater relevance to patients with atopic dermatitis. Having proven that selected patients have food allergy, there has been a reluctance to then enter such patients into controlled studies of dietary treatment. In the UK, the approach has been to avoid allergy tests because of their unreliability, and to avoid blind challenges particularly because of the great difficulty in performing these to include documentation of delayed reactions. The uncertainty about whether an individual patient does or does not have food allergy means that it is possible to enter the patient into randomized controlled trials of dietary treatment. Such studies are bedevilled by the lack of proof of food allergy in individual cases. Given the small number of subjects who have been entered into controlled trials, this means that a beneficial effect of dietary treatment could have been missed. The adverse reactions to foods in children with atopic dermatitis result in urticaria, angioedema, worsening of eczema, vomiting, diarrhoea, abdominal pain and rhinitis. These reactions mostly occur soon after ingestion, and avoidance of an identified trigger food makes sense. However, there are no convincing controlled trial data to show that cow's milk and egg-free diets, few foods diets, or elemental diets are beneficial in children with atopic dermatitis. The results of our own controlled studies have undoubtedly dimmed our enthusiasm for the dietary treatment of atopic dermatitis. The occasional dramatically good response to diet, and pressure from parents to try diets, however, means that in our clinic a place will remain for elimination diets, performed as a supervised therapeutic trial. In view of the natural history of food allergy, the patients who are most likely to benefit are those under 12 months of age.

REFERENCES 1 Sampson HA, Jolie PL. Increased plasma histamine concentrations after food challenges in children with atopic dermatitis. N Engi J Med 1984;311:372-6 2 Sampson HA, McCaskill CC. Food hypersensitivity and atopic dermatitis: evaluation of 113 patients. J Pediatr 1985;107:669-75 3 Burks AW, Mallory SB, Williams LW, Shirrell MA. Atopic dermatitis: clinical relevance of food hypersensitivity reactions. J Pediatr 1988;113:447-51 4 Bock SA, Buckley J, Holst A, May CD. Proper use of skin tests with food extracts in diagnosis of hypersensitivity to food in children. Clin Allergy 1977;7:375-83

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5 Aas K. The diagnosis of hypersensitivity to ingested foods. Reliability of skin prick testing and the radioallergosorbent test with different materials. Clin Allergy 1978;8:39-50 6 Lessof MH, Buisseret PD, Merrett J, Merrett TG, Wraith DG. Assessing the value of skin tests. Clin Allergy 1980;10: 115-20 7 Bousquet J. In vivo methods for study of allergy: skin tests, techniques, and interpretation. In: Middleton E, Reed CE, Ellis EF, Adkinson NF, Yunginger JW, eds. Allergy. Principles and Practice, 3rd edn. St Louis: Mosby, 1988:419-36 8 Hill DJ, Duke AM, Hosking CS, Hudson IL. Clinical manifestations of cows' milk allergy in childhood. II. The diagnostic value of skin tests and RAST. Clin Allergy 1988;18:481-90 9 Meglio P, Farinella F, Trogolo E, Giampietro PG. Immediate reactions following challenge-tests in children with atopic dermatitis. Allerg Immunol 1988;20:57-62 10 Devlin J, David TJ, Stanton RHJ. Six food diet for childhood atopic dermatitis. Acta Derm Venereol 1991 ;71 :20-4 11 Devlin J, David TJ, Stanton RHJ. Elemental diet for refractory atopic eczema. Arch Dis Child 1991;66:93-9 12 Atherton DJ. Dietary antigen avoidance in the treatment of atopic dermatitis. Acta Derm Venereol 1980:99-102 13 Businco L, Ferrara M, Cantani A. Food allergy and atopic dermatitis. Pediatr Allergy Immunol 1991 ;2: 18-22 14 Meglio P, Giampietro PG, Farinella F, Cantani A, Businco L. Personal experience in the diagnostic procedures in children with atopic dermatitis and food allergy. Allergy 1989;44:165-73 15 Vierrucci A, Novembre E, De Martino M, Lucci A, Dini L. Reliability of tests for specific IgE to food in atopic dermatitis. Allergy 1989;44:90-6 16 May CD, Bock SA. A modern clinical approach to food hypersensitivity. Allergy 1978;33: 166-88 17 Bock SA. Prospective appraisal ofcomplaints of adverse reactions to foods in children during the first three years of life. Pediatrics 1987;79:683-8 18 David TJ. Reactions to dietary tartrazine. Arch Dis Child 1987;62: 119-22 19 Broadbent JB, Sampson HA. Food hypersensitivity and atopic dermatitis. Pediatr Clin N Am 1988;35:1115-30 20 Sampson HA. Role of immediate food hypersensitivity in the pathogenesis of atopic dermatitis.JAllergy Clin Immunol 1983;71 :473-80 21 Sampson HA. The role of food allergy and mediator release in atopic dermatitis. J Allergy Clin Immunol 1988;81 :635-45 22 Sampson HA. Late-phase response to food in atopic dermatitis. Hosp Pract 1987;22:111-28 23 David TJ. Steroid scare. Arch Dis Child 1987;62:876-8 24 Webber SA, Graham-Brown RAC, Hutchinson PE, Burns DA. Dietary manipulation in childhood atopic dermatitis. BrJ Dermatol 1989;121:91-8 25 David TJ. Food and Food Additive Intolerance in Childhood. Oxford: Blackwell Scientific Publications, 1993 26 Lloyd-Still JD. Chronic diarrhoea of childhood and the misuse of elimination diets. J Pediatr 1979;95: 10-13 27 Roberts IF, West RJ, Ogilvie D, Dillon MJ. Malnutrition in infants receiving cult diets: a form of child abuse. BMJ 1979;1:296-8 28 Tripp JH, Francis DEM, Knight JA, Harries JT. Infant feeding practices: a cause for concern. BMJ 1979;2:707-9 29 Anonymous. Exotic diets and the infant. BMJ 1978;1:804-5

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30 Dagnelie PC, Vergote FJVRA, Van Staveren WA, Van den Berg H, Dingjam PG, Hautvast JGAJ. High prevalence of rickets in infants on macrobiotic diets. Am] Clin Nutr 1990;51:202-8 31 Tarnow-Mordi WO, Moss C, Ross K. Failure to thrive owing to inappropriate diet free ofgluten and cows' milk. BMJ 1984;289: 1113-14 32 David TJ. The overworked or fraudulent diagnosis of food allergy and food intolerance in children. J R Soc Med 1985;78:21-31 33 Hughes M, Clark N, Forbes L, Colin-Jones DG. A case of scurvy. BMJ 1986;293:366 34 Davidovits M, Levy Y, Avramovitz T, Eisenstein B. Calcium-deficiency rickets in a four-year-old boy with milk allergy. J Pediatr 1993; 122:249-51 35 David TJ. Unhelpful recent developments in the diagnosis and treatment of allergy and food intolerance in children. In: Dobbing J, ed. Food Intolerance. London: Bailliere Tindall, 1987:185-214 36 Labib M, Gama R, Wright J, Marks V, Robins D. Dietary maladvice as a cause of hypothyroidism and short stature. BMJ 1989;298:232-3 37 Dagnelie PC, Van Staveren WA, Hautvast JGJA. Stunting and nutrient deficiencies in children on alternative diets. Acta Paediatr Scand 1991;Suppl 374:111-18 38 David TJ, Waddington E, Stanton RHJ. Nutritional hazards of elimination diets in children with atopic eczema. Arch Dis Child 1984;59:323-5 39 Devlin J, Stanton RHJ, David TJ. Calcium intake and cows' milk free diets. Arch Dis Child 1989;64:1183-4 40 David TJ. Dietary treatment of atopic eczema. Arch Dis Child 1989;64: 1506-9 41 Hathaway MJ, Warner JO. Compliance problems in the dietary management of eczema. Arch Dis Child 1983;58:463-4 42 Warner JO, Hathaway MJ. Allergic form of Meadow's syndrome (Munchausen by proxy). Arch Dis Child 1984;59:151-6 43 Atherton DJ, Sewell M, Soothill JF, Wells RS. A double-blind controlled crossover trial of an antigen-avoidance diet in atopic eczema. Lancet 1978;1:401-3 44 Neild VA, Marsden RA, Bailes JA, Bland JM, Egg and milk exclusion diets in atopic eczema. BrJDermatol 1986;114:117-23 45 Pike MG, Carter CM, Boulton P, Turner MW, Soothill JF, Atherton DJ. Few food diets in the treatment of atopic eczema. Arch Dis Child 1989;64: 1691-8 46 Mabin DC, Sykes AE, David TJ. Controlled trial of a few foods diet in severe atopic dermatitis. Arch Dis Child 1995;73:202-7 47 Munkvad M, Danielsen L, Hoj L, Povlsen CO, Secher L, Svejgaard E, et al. Antigen-free diet in adult patients with atopic dermatitis. A double-blind controlled study. Acta Derm Venereol 1984;64:524-8 48 Carmichael AJ, Stephenson J, Foulds IS. Elemental diet in detecting food intolerance in adult atopic eczema (abstract). Br J Dermatol 1989;121 :37-8 49 Galant SP, Franz ML, Walker P, Wells ID, Lundak RL. A potential diagnostic method for food allergy: clinical application and immunogenicity evaluation of an elemental diet. Am J Clin Nutr 1977;30:512-16 50 Cant AJ, Bailes JA, Marsden RA, Hewitt D. Effect of maternal dietary exclusion on breast-fed infants with eczema: two controlled studies. BMJ 1986;293:231-3