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topic dermatitis (AD) is a chronic relapsing inflammatory skin disease commonly associated
with atopy. It affects up to 10% of children.1,2 The
characteristic rash in AD has a typical distribution,
found in the antecubital and popliteal fossas, wrist
creases, scalp, eyelids, and flexor surfaces. AD is frequently the initial manifestation of atopy and often
affects very young children early within the 1st year of
life. Many children who develop AD go on to develop
other allergic diseases such as food allergy, asthma, or
allergic rhinitis (the atopic march).3 The clinical features of AD are well described and include, pruritus, a
relapsing eczematous rash typically found over flexor
surfaces, and a personal history of atopy. Minor features include elevated serum IgE, cutaneous skin infection (Staphylococcus, Streptococcus, or fungus); Dennie-Morgan lines, keratoconus, allergic shiners, white
dermatographism, ichthyosis, nonspecific hand/food
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From the University of Michigan Food Allergy Center, Division of Allergy and
Clinical Immunology, The University of Michigan Medical School, The University of
Michigan Health Systems, Ann Arbor, Michigan
Presented at the Eastern Allergy Conference, Palm Beach Florida, May 7, 2010
Received nonfinancial research support from the Food Allergy & Anaphylaxis Network
Disclosures/Conflicts: The author had nothing pertinent to this review
M. Greenhawt received speaking honorarium from Phadia, is a member of the medical
advisory team for Kids With Food Allergies, and is a member of speakers bureau for
Nutricia and Sepracor
Address correspondence and reprint requests to Matthew Greenhawt, M.D., M.B.A.,
The University of Michigan Food Allergy Center, Division of Allergy and Clinical
Immunology, The University of Michigan Medical School, The University of Michigan Health Systems, 24 Frank Lloyd Wright Drive, Lobby H-2100, Box 442, Ann
Arbor, MI 48106
E-mail address: mgreenha@med.umich.edu
Copyright 2010, OceanSide Publications, Inc., U.S.A.
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PREVALENCE
Most studies suggest that the prevalence of AD is
high and the incidence is increasing, which may mirror
the overall increase in atopy among the population. A
large Danish twin concordance study found that the
rates increased from 3% between 1960 and 1964 to 7%
between 1975 and 1979.4 A 1992 European cross-sectional study confirmed a prevalence rate of 15.6%.5 A
similar study of U.S. children aged 59 years found a
rate of 17%.6 Two studies from Japan found an 11.2%
point prevalence of AD in 1st graders and 6th graders
and a rate of 24% among children aged 5 6 years.7,8
Theories to explain the rise in AD include a decrease in
the amount of children who are exclusively breast-fed,
an overall increased awareness of AD, increased exposure to air pollution, and increased exposure to allergens.9,10
THE ROLE OF IgE AND CYTOKINE
IMMUNOBIOLOGY IN AD
Two distinct subtypes of AD have been identified.
The extrinsic subtype is associated with elevated serum IgE levels in up to 80% of affected patients,
whereas the intrinsic subtype lacks this and also is not
associated with allergen sensitization.9,11 Both subtypes are associated with peripheral eosinophilia.12
IgE-mediated responses in AD provoke pruritus, erythema, and mediator release from mast cells.9 Cyclic
adenosine monophosphatephosphodiesterase expression in leukocytes taken from patients afflicted with
AD is overactive, which contributes to increased IgE
production and increased IL-4 secretion.13 Similarly,
increased CD86 expression on B cells of patients with
AD compared with controls also promotes increased
IgE production.14 There is increased expression of
high-affinity IgE receptor (FcR-1) on Langerhans cells
and inflammatory dendritic epidermal cells, resulting
from increased FcR-1 -chain synthesis.15 Both cell
types are highly effective at antigen presentation and
are highly efficient at activating TH2 cells and inducing
further T-cell proliferation specific to particular antigen.16 Inflammatory dendritic epidermal cell stimulation through FcR-1 promotes more TH1 cytokine release, as opposed to FcR-1 stimulation on Langerhans
cells.17
Although food allergy is usually a type I hypersensitivity, involving IgE, AD is a mixed IgE and cellularmediated event, with a mechanism mediated through
T cells. However, the cytokine profile expressed by
these T cells in acute AD is characterized by IL-4,
IL-5, and IL-13, a TH2 milieu similar to that seen in
IgE-mediated reactions.1,18 T-cell cytokine expression more characteristic of delayed-type hypersensitivity involves interferon and IL-2.19,20 Several studies have shown a link between food ingestion,
symptom development, and release of specific cellular
markers that are elevated in patients with AD. Sampson noted that children with AD and food-specific IgE
undergoing challenge to that food had a detectable
elevation of plasma histamine levels compared with
control patients.21 He later showed that chronic ingestion of allergenic foods was associated with higher
spontaneous basophil histamine release in cell cultures
of patients with AD compared with controls.22 Suomalainen and Magnarin showed increased eosinophil
granule release in AD patients undergoing food challenge and food-induced symptoms correlated to
plasma eosinophil activation in these patients.23,24 A
recent Korean study suggested that elevated peripheral eosinophil counts may aid as a predictive tool in
the evaluation of patients with AD triggered by food
allergy, and showed a significant decrease in the eosinophilia after following a milk elimination diet in
patients with milk-triggered AD.25 Several groups
have described food-specific T cells reactive to casein,
ovalbumin, and peanut in serum of patient with
food-induced AD.26 29 Food-specific T cells have
been cloned from both affected and normal skin of
patients with AD. In addition, cutaneous lymphocyte antigen bearing T cells have been found in high
percentages in milk-allergic patients with AD but
not in milk-allergic patients without milk-induced
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Table 1 Prevalence of food allergy confirmed by double-blind placebo-controlled food challenge in patients
with known atopic dermatitis
Authors
Sampson73
Burks51
Eigenmann39
Burks52
Niggemann49
Eigenmann58
Breuer47
Year
Allergy (%)
Country
1985
1988
1998
1998
1999
2000
2004
113
46
63
165
107
74
64
56
33
37
39
51
34
46
Yes
Yes
No
Yes
Yes
No
Yes
United States
United States
United States
United States
Germany
Switzerland
Germany
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CONCLUSION
A subset of children with AD have food allergy, but
a larger percentage have clinically irrelevant food sensitization. Care and caution must be undertaken when
evaluating the patient with AD suspected of having
food allergy, given poor PPV of both food sensitization, and parental histories. Food challenge is highly
recommended to confirm sensitization and to ensure
that a particular dietary avoidance is necessary. Attention must be paid to other confounding factors, such as
the role of cutaneous infection or genetically conferred
barrier dysfunction, and treatment options beyond dietary intervention should be maximized. In cases of
children allergic to eggs, wheat, and milk, the natural
history is to outgrow these sensitivities (as opposed to
peanut), although many children who develop AD at a
young age may develop other food sensitivities or
develop worsening food allergy with more classic
symptoms. Preventive strategies have not been well
established.
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ACKNOWLEDGMENTS
The author thanks James Baldwin, M.D., and Georgiana Sanders,
M.D., M.S., of the Division of Allergy and Clinical Immunology, The
University of Michigan Health Systems, for their assistance in reviewing this article.
REFERENCES
1.
2.
3.
395
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
396
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24.
25.
26.
27.
28.
29.
30.
31.
32.
Magnarin M, Knowles A, Ventura A, et al. A role for eosinophils in the pathogenesis of skin lesions in patients with foodsensitive atopic dermatitis. J Allergy Clin Immunol 96:200 208,
1995.
Noh G, Jin H, Lee J, et al. Eosinophilia as a predictor of food
allergy in atopic dermatitis. Allergy Asthma Proc 31:e18 e24.
Abernathy-Carver KJ, Sampson HA, Picker LJ, and Leung DY.
Milk-induced eczema is associated with the expansion of T cells
expressing cutaneous lymphocyte antigen. J Clin Invest 95:913
918, 1995.
Reekers R, Beyer K, Niggemann B, et al. The role of circulating
food antigen-specific lymphocytes in food allergic children with
atopic dermatitis. Br J Dermatol 135:935941, 1996.
van Reijsen FC, Bruijnzeel-Koomen CA, Kalthoff FS, et al. Skinderived aeroallergen-specific T-cell clones of Th2 phenotype in
patients with atopic dermatitis. J Allergy Clin Immunol 90:184
193, 1992.
van Reijsen FC, Felius A, Wauters EA, et al. T-cell reactivity for
a peanut-derived epitope in the skin of a young infant with
atopic dermatitis. J Allergy Clin Immunol 101:207209, 1998.
Beyer K, Castro R, Feidel C, and Sampson HA. Milk-induced
urticaria is associated with the expansion of T cells expressing
cutaneous lymphocyte antigen. J Allergy Clin Immunol 109:
688 693, 2002.
Lee LA. Atopic dermatitis and allergy in children: A dynamic
relationship. Food Chem Toxicol 46(suppl 10):S6 S11, 2008.
Jones SM, and Burks AW. Atopic dermatitis and food hypersensitivity. In Pediatric Allergy: Principles and Practice. Leung
DYM, Sampson HA, Geha RS, and Szefler SJ (Eds). Chap. 51.
St. Louis, MO: Mosby, 538 545, 2003.
Baurecht H, Irvine AD, Novak N, et al. Toward a major risk
factor for atopic eczema: Meta-analysis of filaggrin polymorphism data. J Allergy Clin Immunol 120:1406 1412, 2007.
Rodriguez E, Baurecht H, Herberich E, et al. Meta-analysis of
filaggrin polymorphisms in eczema and asthma: Robust risk
factors in atopic disease. J Allergy Clin Immunol 123:13611370,
e7, 2009.
van den Oord RA, and Sheikh A. Filaggrin gene defects and risk
of developing allergic sensitisation and allergic disorders: Systematic review and meta-analysis. BMJ 339:b2433, 2009.
Sicherer SH, and Sampson HA. Food allergy. J Allergy Clin
Immunol 125:S116 S125.
Hill DJ, Sporik R, Thorburn J, and Hosking CS. The association
of atopic dermatitis in infancy with immunoglobulin E food
sensitization. J Pediatr 137:475 479, 2000.
Hill DJ, Heine RG, Hosking CS, et al. IgE food sensitization in
infants with eczema attending a dermatology department. J Pediatr 151:359 363, 2007.
Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of
IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 101:E8, 1998.
Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: An updated practice parameter. Ann Allergy Asthma Immunol 100:S1S148, 2008.
Sicherer SH, and Sampson HA. Food hypersensitivity and
atopic dermatitis: Pathophysiology, epidemiology, diagnosis,
and management. J Allergy Clin Immunol 104:S114 S122, 1999.
Chafen JJ, Newberry SJ, Riedl MA, et al. Diagnosing and managing common food allergies: A systematic review. JAMA 303:
1848 1856.
Sampson HA, and Ho DG. Relationship between food-specific
IgE concentrations and the risk of positive food challenges in
children and adolescents. J Allergy Clin Immunol 100:444 451,
1997.
Sampson HA. Utility of food-specific IgE concentrations in
predicting symptomatic food allergy. J Allergy Clin Immunol
107:891 896, 2001.
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33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
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P
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
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D
60.
61.
62.
63.
64.
65.
66.
67.
68.
O
N
T
69.
70.
71.
72.
73.
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