Atopic Dermatitis and Food Hypersensitivity in Children A. Wesley Burks, M.D., Larry Williams, M.D., J. Gary Wheeler, M.D., and Gail Wilson, B.S.N.
ABSTRACT Atopic dermatitis is a common condition of early childhood. The association of atopic dermatitis and allergy has been sllldied for several years. Recent work has shown that food hypersensitivity does playa role as an exacerbating factor in some children with atopic dermatitis. This hypersensitivity wi/I be limited typically to one or two food antigens. Children placed on appropriate elimination diets can be expected to have significant improvement in their clinical course. (Allergy Proc 13, 6:285-288, 1992)
,ltopic dermatitis,
a common disorder of childhood, is characterized by marked pruritus, frequent onset in infancy, and typically a chronic course. The disease has no unique cutaneous lesions, no distinctive histologic features, and no characteristic laboratory findings. This inflammatory disorder is characterized by an erythematous, papulovesicu]ar, intensely pruritic rash that progresses to a scaly, lichenified dermatitis. This disorder accounts for I % of all visits to pediatricians.1 The association of atopic dermatitis with allergy originally was suggested by Besnier in the 1890s.2 Severa] studies show that IgE-mediated hypersensitivity can contribute to its pathogenesis. Evidence of a role for IgE includes the observations that two thirds of children with atopic dermatitis have positive family histories for
ft
From the University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Department of Pediatrics, Division of Allergy! Immunology, Lillie Rock, Arkansas Presented in part at the Eastern Allergy Conference, Southwest Allergy Forum. April 30, 1992 Reprint requests: Wesley Burks, M.D., Pediatric Immunology, Arkansas Children '.I' Hospital. 800 Marshall St., LillIe Rock, AR 72202
atopic disease, that 50 to 80% of children with the disease develop other atopic disorders (asthma or allergic rhinitis), that serum IgE concentrations are elevated in 80% of these children, that the majority have either positive allergy prick skin tests or radioallergosorbent tests (RAST) to various allergens, and that several mediators released by mast cells playa part in the disease. 1.3 One of the best early rep0l1s for this association was by Engman et a1.4 in ] 936, who described a child with atopic dermatitis that flared with wheat challenge. The majority of the recent work relating atopic dermatitis and food hypersensitivity has been done by Sampson and co-workers. 3 These studies have shown clearly that food allergy plays a role as an exacerbating factor in some children with atopic dermatitis.
LATE-PHASE IGE RESPONSE
T
he proposed mechanism by which adverse food reactions exacerbate skin symptoms involves both immediate and the late-phase IgE response, although the latter appears to be mostly responsible for clinical symptomatology.3 After exposure to an allergen, cutaneous mast cells become activated and release histamine and other mediators into the ]ocal tissue. The mediators provoke pruritus, vasodilatation (erythema), and capillary leakiness (edema). This reaction generally subsides within 30 to 90 minutes after the appearance of symptoms. Three to four hours after the im mediate skin reaction begins to subside, the late-phase response begins as mild itching. The clinical manifestations of this reaction in experimental models are preceded by the sequential infiltration of leukocytes into the skin lesion.s This mixed infiltrate is primarily an accumulation of neutrophi]s and eosinophils, reaching a maximum concentration at 6 to 8 hours. In the experimental mode, marked perivascular fibrin deposition is noted
AllergybyProc. Delivered Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 285 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
to persist for 24 to 48 hours. By this time, a mononuclear, round cell infiltrate consisting of monocytes and lymphocytes predominates. The histology of this lesion is indistinguishable from that found in atopic dermatitis.
MEDIATORS Histamine
T
he initial mediator examined in patients with atopic dermatitis and food hypersensitivity was histamine.6 After positive food challenges, histamine levels were found to be significantly elevated. Those patients who had positive double-blind, placebo-controlled food challenges had a 3- to 4-fold rise in their plasma histamine after the challenge. C3a des arg and C5a des arg did not significantly change after the challenges. The lack of change in these complement fractions that degranulate mast cells excludes the possibility of complement activation during the challenge.3
EOSINOPHILS
E at the peak of late-phase osinophils account
for 25% of the cellular infiltrate
response.s Eosinophils are not prevalent in skin biopsies from lesions in atopic dermatitis; however, lesions contain a large amount of major basic protein (MBP), a cytolytic protein secreted almost exclusively by eosinophils. MBP, a polypeptide localized to the eosinophil granule, produces histologic damage similar to that seen in the lung in asthma. It also induces histamine release from human basophils but not mast cells. In one study, it was shown that MBP without accompanying eosinophils was distributed in a fibrillular pattern throughout the entire upper dermis of all biopsy specimens of patients with chronic eczematous lesions.? Absent from these specimens was the presence of eosinophils. Because mast cells contain no MBP and basophils contain only 5% of that found in eosinophils, it is likely that the MBP was from eosinophi Is. Sampson) demonstrated the deposition of both eosinophils and MBP in biopsies of skin rashes provoked by positive double-blind, placebo-controlled food challenges. Taken together these studies seem to indicate the late-phase IgE response contributes to the deposition of MBP in the lesions of patients with atopic dermatitis. It is presumed that cutaneous mast cell histamine and other eosinophil chemotactic factors draw eosinophils to the inflammatory site where they release MBP as one of their several mediators. MBP then stimulates mast cell and basophil degranulation and release of histamine. Other eosinophil-associated enzymes, including eosinophil-derived neurotoxin and eosinophil cationic protein, apparently also contribute to the inflam matory process.)
286
HISTAMINE-RELEASING
FACTOR
H
istamine-releasing factors (HRF) have been identified from several different sources including lymphocytes, monocytes, neutrophils, and platelets.8 By binding to surface-bound IgE molecules on mast cells and basophils, these factors augment the release of histamine. They may help induce allergic reactions that appear too late or are too prolonged to be explained by the classic antigen-igE-mediated phenomenon. In a related study, Sampson et a\.9 found that peripheral blood mononuclear cells of food-allergic patients produced a HRF that was able to activate basophils from other food-sensitive patients but not basophils from subjects who were not sensitive to food. Furthermore, this study showed that peripheral blood basophils of nondieting children with food hypersensitivity and atopic dermatitis have a high spontaneous release of histamine in vitro, whereas spontaneous basophil histamine release is close to normal in children with atopic dermatitis and food hypersensitivity whose skin lesions have cleared on a food-allergen avoidance diet. Therefore, HRFs might activate or lower the activation threshold ofbasophils and mast cells and could account for both the high spontaneous basophil histamine release and the increased basophil releasability seen in some patients with atopic dermatitis. MacDonald et a\.lo proposed that allergic persons have a subset of IgE molecules different from the IgE of normal subjects and that this IgE interacts with various HRFs. This hypothesis could account for the 20% of patients with atopic dermatitis who have normal serum IgE levels.
LANGERHANS CELLS
R
ecent evidence has demonstated that IgE binds to epidermal Langerhans' cells only in patients with atopic dermatitis. I I Langerhans' cells serve as antigenpresenting cells in the skin and in addition, synthesize various mediators, especially prostaglandin O2• IgE binds to Langerhans' cells by FcE receptors. As antigenpresenting cells they could contribute to pathogenic skin changes in atopic dermatitis initially by regulating the IgE response mediated by T and B cells and, secondly, by secreting mediators that promote the inflammatory process.
CLINICAL STUDIES
F
ood hypersensitivity has been defined as an immunologic reaction (generally IgE mediated) resulting from the ingestion of a food or food additive.'2 Several studies have shown that food hypersensitivity reactions playa role in exacerbations of atopic dermatitis.1J-'5 More than 60% of children with severe atopic dermatitis had food hypersensitivity reactions in double-blind, placebo-controlled, food challenges (OBPCFC).3 These
November-December,
1992, Vol. 13, NO.6
Delivered by Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
children were referred for severe atopic dermatitis and had failed standard therapy. Approximately 75% of them had been given oral steroids on at least one occasion for control of their skin symptoms. The selection of foods for the challenges was based on prick skin tests, RAST, and/or a strongly suggestive history of food allergy. The evaluation of 160 patients (median age 5.3 years) with 514 DBPCFC revealed 189 positive DBPCFCs. Ninety-eight (61 %) patients had positive DBPCFCs. In the positive challenges the patients had cutaneous (79%), gastrointestinal (43%), and respiratory (28%) symptoms. Six foods accounted for 90% of the positive challenges (in order of frequency): egg, peanut, milk, fish, soy, and wheat. In this group, 78% of the children reacted to only one or two foods. In another recent study, 140 patients (mean age 4.2 years) with mild to severe atopic dermatitis were evaluated for possible food hypersensitivity.J6.17 These patients were a combination of primary and tertiary care referrals. The patients were screened by allergy prick skin testing and had DBPCFCs to foods with a positive skin test. Seventy-seven (59%) patients had a positive prick skin test to one of the 20 foods tested. In these 77 patients, 46 (33%) had positive DBPCFCs. Peanut, egg, milk, wheat, and soy accounted for 82% of the positive challenges. Skin symptoms occurred in 92%, respiratory symptoms in 48%, and gastrointestinal symptoms in 33% of the positive challenges. Ninety-one percent of the patients reacted to only one or two foods. Because allergens with a common botanical lineage often demonstrate a similar pattern of skin test reactivity, it was thought for a number of years that if a person was allergic to one food in a family, all foods within that family should be avoided. However, recent studies have shown that positive food challenges are very specific. A patient who reacts to one food within a botanical species need not avoid all foods within that c1ass.3.16.18 Because approximately one third of children with food allergy will lose their clinical sensitivity over time, future challenges should be a necessary part of followup of these children. IS Sensitivity to peanut and fish do not appear to be lost as quickly as to milk, egg, and soy. The loss of this sensitivity should encourage compliance with appropriate dietary regimens. EVALUATION
T
he time at which a child with atopic dermatitis should be evaluated for food hypersensitivity has not been fully determined. It seems reasonable to suggest, based on previous studies, 13-17that any child who has atopic dermatitis unresponsive to routine therapy of lubricating creams or ointments, topical corticosteroids, antihistamines, and antibiotics should be evaluated. Children who respond to this therapy but continue
Allergy Proc.
to need daily treatment after several months should also be evaluated. The most sensible approach to screening, as suggested by Sampson, would be the use of an open or singleblind challenge after prick skin tests.3.IS RAST to determine which foods should be avoided are definitely not better than prick skin tests, nor do they add to the diagnostic capabilities.'9 If the patient has a positive prick skin test to a food, this food should be eliminated from the diet for a period of 3 or 4 weeks. If there is unequivocal improvement and only one "major" food
(egg, milk, wheat, soy) or one or two "minor" foods (peanut, beef, chicken, fish, etc.), the diet would not be unnecessarily restricted and should be acceptable. If the patient has equivocal results to the food elimination, food challenges should be done. Patients who have more than three positive challenge reactions should undergo a DBPCFC to validate the results. This protocol will allow the patients a nutritionally balanced diet to which patients and parents can reasonably adhere. Any patient who has been placed on a restricted diet should have good follow-up with periodic rechallenges to the specific foods previously eliminated. The data reviewed here suggest that IgE-mediated food hypersensitivity plays a pathogenic role in some patients with atopic dermatitis. This hypersensitivity will be limited in most cases to one or two food antigens and most likely will be lost after several years of allergen avoidance. Elimination diets, if the family is given adequate nutritional information, can be followed appropriately. Children who are diagnosed appropriately and placed on elimination diets can be expected to have significant improvement in their clinical course.
REFERENCES 1. Buckley RH. Allergic eczema. In: Kelly VC, ed. Practice of Pediatrics, Vol 2. Philadelphia. PA: Harper & Row. 1984, pp. 1-29. 2. Hanifin 1M. Atopic dermatitis. Comprehensive Immunology, No, 7. In: Safai B, Good RA, eds. Immunodcrmatology. New York: Plenum Medical Book Co .. 1981, pp. 301-330. 3. Sampson HA. Late-phase response to food in atopic dermatitis. Hosp Prac 22:91-106,1987. 4. Engman MF, Weiss RS, Engman MF lr. Eczema and environment. Med Clin North Am 20:651-653, 1936. 5. Gleich Gl. The late-phase of immunoglobulin E-mediated reaction: A link between anaphylaxis and common allergic disease. 1 Allergy Clin Immunol 70: 160-169, 1982. 6. Sampson HA, lolie PL. Increased plasma histamine conccntrations after food challenges in children with atopic dermatitis. N Engl J Med 311:372-376,1984. 7. Leiferman KM, Ackerman Sl, Sampson HA, Haugen HS, Veneneie PY, Gleich Gl. Dermal deposition of eosinophil granule major basic protein in atopic dermatitis: Comparison with onchocerciasis. N Engl 1 Med 313:282-285, 1985. 8. Sedgwick 10, Holt PG, Turner Kl. Production ofa histaminereleasing Iymphokine by antigen- or mitogcn-stimulated human peripheral T cells. Clin Exp ImmunoI45:409-418, 1981. 9. Sampson HA, Broadbent KR, Broadbent lB. Spontaneous
287
Delivered by Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
10.
II.
12. 13.
14.
288
release of histamine from basophils and histamine-releasing factor in patients with atopic dermatitis and food hypersensitivity. N Engl J Med 321 :228-232. 1989. MacDonald SM, Lichenstein LM, Proud 0, Plaut M. Naclerio RM. MacGlashan OW. Kagey-Sobotka A. Studies of IgEdependent histamine releasing factors: Heterogeneity of IgE. J ImmunoI139:506-512. 1987. Bruynzeel-Koomen C. van Wichen OF, Toonstra J. Berrens L. Bruynzeel PL. The presence ofIgE molecules on epidermal Langerhans cells in patients with atopic dermatitis. Arch Dermatol Res 278: 199-205, 1986. Anderson JA, Sogn DO. Adverse reactions to foods. National Institutes of Health Publication 84-2442. 1984. pp 1-6. Sampson HA. Role of immediate food hypersensitivity in the pathogenesis of atopic dermatitis. J Allergy C]in Immunol 71:473-480,1987. Sampson HA. McCaskill Cc. Food hypersensitivity in atopic dermatitis: Evaluation of 113 patients. J Pediatr 107:669-
15.
16.
17.
18.
19.
675, 1985. Sampson HA, Scanlon SM. Natural history of food hypersensitivity in children with atopic dermatitis. J Pediatr 115:2327,1989. Burks AW, Mallory SB. Williams LW. Shirrell MA. Atopic dermatitis: Clinical relevance of food hypersensitivity reactions. J Pediatr 113:447-451. 1989. Shirrell MA, Wilson G, Burks AW. Role offood hypersensitivity in mild to severe atopic dermatitis. J Allergy C1in Immunol 89(A 158): 184. 1992. Broadbent JB, Taylor S, Sampson HA. Cross-allergenicity in the legume botanical family in children with food hypersensitivity. ]1. Laboratory correlates. J Allergy (lin Immunol 84:701-709.1989. Sampson HA, Albergo R. Comparison of results of skin tests, RAST, and double-blind placebo-controlled food challcnges in children with atopic dermatitis. J Allergy Clin Immunol 74:26-33, 1984. 0
November-December,
1992, Vol. 13, NO.6
Delivered by Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
ABSTRACT Atopic dermatitis is a common condition of early childhood. The association of atopic dermatitis and allergy has been sllldied for several years. Recent work has shown that food hypersensitivity does playa role as an exacerbating factor in some children with atopic dermatitis. This hypersensitivity wi/I be limited typically to one or two food antigens. Children placed on appropriate elimination diets can be expected to have significant improvement in their clinical course. (Allergy Proc 13, 6:285-288, 1992)
,ltopic dermatitis,
a common disorder of childhood, is characterized by marked pruritus, frequent onset in infancy, and typically a chronic course. The disease has no unique cutaneous lesions, no distinctive histologic features, and no characteristic laboratory findings. This inflammatory disorder is characterized by an erythematous, papulovesicu]ar, intensely pruritic rash that progresses to a scaly, lichenified dermatitis. This disorder accounts for I % of all visits to pediatricians.1 The association of atopic dermatitis with allergy originally was suggested by Besnier in the 1890s.2 Severa] studies show that IgE-mediated hypersensitivity can contribute to its pathogenesis. Evidence of a role for IgE includes the observations that two thirds of children with atopic dermatitis have positive family histories for
ft
From the University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Department of Pediatrics, Division of Allergy! Immunology, Lillie Rock, Arkansas Presented in part at the Eastern Allergy Conference, Southwest Allergy Forum. April 30, 1992 Reprint requests: Wesley Burks, M.D., Pediatric Immunology, Arkansas Children '.I' Hospital. 800 Marshall St., LillIe Rock, AR 72202
atopic disease, that 50 to 80% of children with the disease develop other atopic disorders (asthma or allergic rhinitis), that serum IgE concentrations are elevated in 80% of these children, that the majority have either positive allergy prick skin tests or radioallergosorbent tests (RAST) to various allergens, and that several mediators released by mast cells playa part in the disease. 1.3 One of the best early rep0l1s for this association was by Engman et a1.4 in ] 936, who described a child with atopic dermatitis that flared with wheat challenge. The majority of the recent work relating atopic dermatitis and food hypersensitivity has been done by Sampson and co-workers. 3 These studies have shown clearly that food allergy plays a role as an exacerbating factor in some children with atopic dermatitis.
LATE-PHASE IGE RESPONSE
T
he proposed mechanism by which adverse food reactions exacerbate skin symptoms involves both immediate and the late-phase IgE response, although the latter appears to be mostly responsible for clinical symptomatology.3 After exposure to an allergen, cutaneous mast cells become activated and release histamine and other mediators into the ]ocal tissue. The mediators provoke pruritus, vasodilatation (erythema), and capillary leakiness (edema). This reaction generally subsides within 30 to 90 minutes after the appearance of symptoms. Three to four hours after the im mediate skin reaction begins to subside, the late-phase response begins as mild itching. The clinical manifestations of this reaction in experimental models are preceded by the sequential infiltration of leukocytes into the skin lesion.s This mixed infiltrate is primarily an accumulation of neutrophi]s and eosinophils, reaching a maximum concentration at 6 to 8 hours. In the experimental mode, marked perivascular fibrin deposition is noted
AllergybyProc. Delivered Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 285 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
to persist for 24 to 48 hours. By this time, a mononuclear, round cell infiltrate consisting of monocytes and lymphocytes predominates. The histology of this lesion is indistinguishable from that found in atopic dermatitis.
MEDIATORS Histamine
T
he initial mediator examined in patients with atopic dermatitis and food hypersensitivity was histamine.6 After positive food challenges, histamine levels were found to be significantly elevated. Those patients who had positive double-blind, placebo-controlled food challenges had a 3- to 4-fold rise in their plasma histamine after the challenge. C3a des arg and C5a des arg did not significantly change after the challenges. The lack of change in these complement fractions that degranulate mast cells excludes the possibility of complement activation during the challenge.3
EOSINOPHILS
E at the peak of late-phase osinophils account
for 25% of the cellular infiltrate
response.s Eosinophils are not prevalent in skin biopsies from lesions in atopic dermatitis; however, lesions contain a large amount of major basic protein (MBP), a cytolytic protein secreted almost exclusively by eosinophils. MBP, a polypeptide localized to the eosinophil granule, produces histologic damage similar to that seen in the lung in asthma. It also induces histamine release from human basophils but not mast cells. In one study, it was shown that MBP without accompanying eosinophils was distributed in a fibrillular pattern throughout the entire upper dermis of all biopsy specimens of patients with chronic eczematous lesions.? Absent from these specimens was the presence of eosinophils. Because mast cells contain no MBP and basophils contain only 5% of that found in eosinophils, it is likely that the MBP was from eosinophi Is. Sampson) demonstrated the deposition of both eosinophils and MBP in biopsies of skin rashes provoked by positive double-blind, placebo-controlled food challenges. Taken together these studies seem to indicate the late-phase IgE response contributes to the deposition of MBP in the lesions of patients with atopic dermatitis. It is presumed that cutaneous mast cell histamine and other eosinophil chemotactic factors draw eosinophils to the inflammatory site where they release MBP as one of their several mediators. MBP then stimulates mast cell and basophil degranulation and release of histamine. Other eosinophil-associated enzymes, including eosinophil-derived neurotoxin and eosinophil cationic protein, apparently also contribute to the inflam matory process.)
286
HISTAMINE-RELEASING
FACTOR
H
istamine-releasing factors (HRF) have been identified from several different sources including lymphocytes, monocytes, neutrophils, and platelets.8 By binding to surface-bound IgE molecules on mast cells and basophils, these factors augment the release of histamine. They may help induce allergic reactions that appear too late or are too prolonged to be explained by the classic antigen-igE-mediated phenomenon. In a related study, Sampson et a\.9 found that peripheral blood mononuclear cells of food-allergic patients produced a HRF that was able to activate basophils from other food-sensitive patients but not basophils from subjects who were not sensitive to food. Furthermore, this study showed that peripheral blood basophils of nondieting children with food hypersensitivity and atopic dermatitis have a high spontaneous release of histamine in vitro, whereas spontaneous basophil histamine release is close to normal in children with atopic dermatitis and food hypersensitivity whose skin lesions have cleared on a food-allergen avoidance diet. Therefore, HRFs might activate or lower the activation threshold ofbasophils and mast cells and could account for both the high spontaneous basophil histamine release and the increased basophil releasability seen in some patients with atopic dermatitis. MacDonald et a\.lo proposed that allergic persons have a subset of IgE molecules different from the IgE of normal subjects and that this IgE interacts with various HRFs. This hypothesis could account for the 20% of patients with atopic dermatitis who have normal serum IgE levels.
LANGERHANS CELLS
R
ecent evidence has demonstated that IgE binds to epidermal Langerhans' cells only in patients with atopic dermatitis. I I Langerhans' cells serve as antigenpresenting cells in the skin and in addition, synthesize various mediators, especially prostaglandin O2• IgE binds to Langerhans' cells by FcE receptors. As antigenpresenting cells they could contribute to pathogenic skin changes in atopic dermatitis initially by regulating the IgE response mediated by T and B cells and, secondly, by secreting mediators that promote the inflammatory process.
CLINICAL STUDIES
F
ood hypersensitivity has been defined as an immunologic reaction (generally IgE mediated) resulting from the ingestion of a food or food additive.'2 Several studies have shown that food hypersensitivity reactions playa role in exacerbations of atopic dermatitis.1J-'5 More than 60% of children with severe atopic dermatitis had food hypersensitivity reactions in double-blind, placebo-controlled, food challenges (OBPCFC).3 These
November-December,
1992, Vol. 13, NO.6
Delivered by Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
children were referred for severe atopic dermatitis and had failed standard therapy. Approximately 75% of them had been given oral steroids on at least one occasion for control of their skin symptoms. The selection of foods for the challenges was based on prick skin tests, RAST, and/or a strongly suggestive history of food allergy. The evaluation of 160 patients (median age 5.3 years) with 514 DBPCFC revealed 189 positive DBPCFCs. Ninety-eight (61 %) patients had positive DBPCFCs. In the positive challenges the patients had cutaneous (79%), gastrointestinal (43%), and respiratory (28%) symptoms. Six foods accounted for 90% of the positive challenges (in order of frequency): egg, peanut, milk, fish, soy, and wheat. In this group, 78% of the children reacted to only one or two foods. In another recent study, 140 patients (mean age 4.2 years) with mild to severe atopic dermatitis were evaluated for possible food hypersensitivity.J6.17 These patients were a combination of primary and tertiary care referrals. The patients were screened by allergy prick skin testing and had DBPCFCs to foods with a positive skin test. Seventy-seven (59%) patients had a positive prick skin test to one of the 20 foods tested. In these 77 patients, 46 (33%) had positive DBPCFCs. Peanut, egg, milk, wheat, and soy accounted for 82% of the positive challenges. Skin symptoms occurred in 92%, respiratory symptoms in 48%, and gastrointestinal symptoms in 33% of the positive challenges. Ninety-one percent of the patients reacted to only one or two foods. Because allergens with a common botanical lineage often demonstrate a similar pattern of skin test reactivity, it was thought for a number of years that if a person was allergic to one food in a family, all foods within that family should be avoided. However, recent studies have shown that positive food challenges are very specific. A patient who reacts to one food within a botanical species need not avoid all foods within that c1ass.3.16.18 Because approximately one third of children with food allergy will lose their clinical sensitivity over time, future challenges should be a necessary part of followup of these children. IS Sensitivity to peanut and fish do not appear to be lost as quickly as to milk, egg, and soy. The loss of this sensitivity should encourage compliance with appropriate dietary regimens. EVALUATION
T
he time at which a child with atopic dermatitis should be evaluated for food hypersensitivity has not been fully determined. It seems reasonable to suggest, based on previous studies, 13-17that any child who has atopic dermatitis unresponsive to routine therapy of lubricating creams or ointments, topical corticosteroids, antihistamines, and antibiotics should be evaluated. Children who respond to this therapy but continue
Allergy Proc.
to need daily treatment after several months should also be evaluated. The most sensible approach to screening, as suggested by Sampson, would be the use of an open or singleblind challenge after prick skin tests.3.IS RAST to determine which foods should be avoided are definitely not better than prick skin tests, nor do they add to the diagnostic capabilities.'9 If the patient has a positive prick skin test to a food, this food should be eliminated from the diet for a period of 3 or 4 weeks. If there is unequivocal improvement and only one "major" food
(egg, milk, wheat, soy) or one or two "minor" foods (peanut, beef, chicken, fish, etc.), the diet would not be unnecessarily restricted and should be acceptable. If the patient has equivocal results to the food elimination, food challenges should be done. Patients who have more than three positive challenge reactions should undergo a DBPCFC to validate the results. This protocol will allow the patients a nutritionally balanced diet to which patients and parents can reasonably adhere. Any patient who has been placed on a restricted diet should have good follow-up with periodic rechallenges to the specific foods previously eliminated. The data reviewed here suggest that IgE-mediated food hypersensitivity plays a pathogenic role in some patients with atopic dermatitis. This hypersensitivity will be limited in most cases to one or two food antigens and most likely will be lost after several years of allergen avoidance. Elimination diets, if the family is given adequate nutritional information, can be followed appropriately. Children who are diagnosed appropriately and placed on elimination diets can be expected to have significant improvement in their clinical course.
REFERENCES 1. Buckley RH. Allergic eczema. In: Kelly VC, ed. Practice of Pediatrics, Vol 2. Philadelphia. PA: Harper & Row. 1984, pp. 1-29. 2. Hanifin 1M. Atopic dermatitis. Comprehensive Immunology, No, 7. In: Safai B, Good RA, eds. Immunodcrmatology. New York: Plenum Medical Book Co .. 1981, pp. 301-330. 3. Sampson HA. Late-phase response to food in atopic dermatitis. Hosp Prac 22:91-106,1987. 4. Engman MF, Weiss RS, Engman MF lr. Eczema and environment. Med Clin North Am 20:651-653, 1936. 5. Gleich Gl. The late-phase of immunoglobulin E-mediated reaction: A link between anaphylaxis and common allergic disease. 1 Allergy Clin Immunol 70: 160-169, 1982. 6. Sampson HA, lolie PL. Increased plasma histamine conccntrations after food challenges in children with atopic dermatitis. N Engl J Med 311:372-376,1984. 7. Leiferman KM, Ackerman Sl, Sampson HA, Haugen HS, Veneneie PY, Gleich Gl. Dermal deposition of eosinophil granule major basic protein in atopic dermatitis: Comparison with onchocerciasis. N Engl 1 Med 313:282-285, 1985. 8. Sedgwick 10, Holt PG, Turner Kl. Production ofa histaminereleasing Iymphokine by antigen- or mitogcn-stimulated human peripheral T cells. Clin Exp ImmunoI45:409-418, 1981. 9. Sampson HA, Broadbent KR, Broadbent lB. Spontaneous
287
Delivered by Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
10.
II.
12. 13.
14.
288
release of histamine from basophils and histamine-releasing factor in patients with atopic dermatitis and food hypersensitivity. N Engl J Med 321 :228-232. 1989. MacDonald SM, Lichenstein LM, Proud 0, Plaut M. Naclerio RM. MacGlashan OW. Kagey-Sobotka A. Studies of IgEdependent histamine releasing factors: Heterogeneity of IgE. J ImmunoI139:506-512. 1987. Bruynzeel-Koomen C. van Wichen OF, Toonstra J. Berrens L. Bruynzeel PL. The presence ofIgE molecules on epidermal Langerhans cells in patients with atopic dermatitis. Arch Dermatol Res 278: 199-205, 1986. Anderson JA, Sogn DO. Adverse reactions to foods. National Institutes of Health Publication 84-2442. 1984. pp 1-6. Sampson HA. Role of immediate food hypersensitivity in the pathogenesis of atopic dermatitis. J Allergy C]in Immunol 71:473-480,1987. Sampson HA. McCaskill Cc. Food hypersensitivity in atopic dermatitis: Evaluation of 113 patients. J Pediatr 107:669-
15.
16.
17.
18.
19.
675, 1985. Sampson HA, Scanlon SM. Natural history of food hypersensitivity in children with atopic dermatitis. J Pediatr 115:2327,1989. Burks AW, Mallory SB. Williams LW. Shirrell MA. Atopic dermatitis: Clinical relevance of food hypersensitivity reactions. J Pediatr 113:447-451. 1989. Shirrell MA, Wilson G, Burks AW. Role offood hypersensitivity in mild to severe atopic dermatitis. J Allergy C1in Immunol 89(A 158): 184. 1992. Broadbent JB, Taylor S, Sampson HA. Cross-allergenicity in the legume botanical family in children with food hypersensitivity. ]1. Laboratory correlates. J Allergy (lin Immunol 84:701-709.1989. Sampson HA, Albergo R. Comparison of results of skin tests, RAST, and double-blind placebo-controlled food challcnges in children with atopic dermatitis. J Allergy Clin Immunol 74:26-33, 1984. 0
November-December,
1992, Vol. 13, NO.6
Delivered by Ingenta to: Washington University School of Medicine Library IP: 5.101.220.54 On: Thu, 16 Jun 2016 14:11:17 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
