Vincent St Aubyn Crump – March 2004
The role of food allergy in atopic dermatitis, which has never been in doubt amongst practising Allergists, has been the source of more controversy than any other subject matter amongst dermatologists. Some of the confusion arises from dermatologists who assume that because atopics will have several positive IgE-mediated reactions to foods and inhalants, "it is not possible to make a definitive diagnosis of clinically relevant food allergy". Every clinician treating infants with atopic dermatitis successfully will agree that a significant proportion of these kids with severe eczema will be found to have a relevant food allergy, if it is looked for.
Several published prospective studies have determined the incidence of the common food allergies in children as:
- Cow's milk: 2.5%
- Eggs: 2%
- Peanuts: 0.5 – 0.7%
Cow's milk allergy / intolerance & atopic dermatitis (AD) in infancy & childhood
Symptoms suggestive of CMPA/CMPI are seen in about 5-15% of infants, but the "true incidence" ranges from 2% to 3%, when the strict diagnostic criteria are used (1)
Adverse reaction to cow's milk should be the term used to describe cow's milk protein allergy (CMPA) & cow's milk protein intolerance (CMPI), because no differentiation is possible on the basis of symptoms, and there is no reliable single lab test available for the diagnosis of CMPA or CMPI.
Approximately one third of AD children have a diagnosis of CMPA/CMPI according to elimination diet and challenge tests, and about 40-50% of children <1 year of age with CMPA/CMPI have AD.
CMPA/CMPI may induce a diverse range of symptoms including:
- Skin (most common) – AD, urticaria, angioedema (swelling of various body parts)
- Respiratory – rhinitis, asthma, cough
- Gastrointestinal – vomiting, diarrhoea, colic, gastroesophageal reflux
- Non-specific – failure to thrive, irritability.
AD is the most common skin manifestation of CMPA/CMPI.
AD is a chronic inflammatory disease in which the individual's genes, environment, psychic, immune system and drug therapy contributes to its severity.
Immunologic findings include:
- Increased IgE
- Increased eosinophils
- Increased spontaneous histamine release from mast cells
- Increased IL-4 and Il-5 secreting Th2 cells
- Decreased numbers of interferon-gamma secreting Th1 cells.
Koch's postulate of causality in AD
Over the past 2 decades several studies have fulfilled Koch's postulate of causality:
- Removal of causative agent leads to resolution
- Introduction of causative agent leads to the disease
- Avoidance of the causative agent leads to prevention of the disease.
In studies in children with food-related AD where oral controlled food challenges were used (2,3) skin reactions occurred in three fourths of the positive challenges and consisted of itchy, measles-like or flat red lesions in the usually affected sites of AD.
Most of the reactions occurred within an hour after beginning the oral challenge. Eggs, milk and peanut were the most common foods responsible for the reactions. Milk-induced reactions were 10-40% of the positive response (2).
Prognosis of food Allergy in infants with atopic dermatitis
Most food allergy is acquired in the first one to two years of life. The prevalence of food allergy peaks at 5% – 8% at one year of age and then falls progressively until late childhood, after which the prevalence remains stable at 1- 2%.
Most food allergy is indeed lost over time. It is therefore not surprising that dermatologists treating only adults with atopic dermatitis will see relatively few with food allergy. In a prospective study by Bock (6) almost all of the adverse reactions had been lost by the age of three years. Among these, there were 11 children with confirmed milk allergy, all of whom were able to tolerate milk by the age of three. The median duration of adverse reactions to milk was only 9 months.
All the studies looking at egg allergy in infancy shows that the vast majority of egg allergy is also outgrown by the school-age years.
Peanut allergy is likely to be lifelong for most but not all patients. About 20% of children with peanut allergy will outgrow their allergy. The more severe the allergy the least likely it is to be out-grown.
Important studies from around the world linking AD with foods
Atopic Dermatitis and food Hypersensitivity reactions
Burks AW; James JM et al, Dept. Paediatrics, Univ. Arkansas, Little Rock, USA
Paediatrics, 132(1): 132-6 1998 Jan
To determine the role of food hypersensitivity in atopic dermatitis and to determine whether patients with atopic dermatitis who had food hypersensitivity could be identified by screening prick skin tests using a limited number of food allergens.
Patients with atopic dermatitis attending Arkansas Children's Hospital Paed. Allergy Clinic underwent allergy skin prick testing to a battery of food allergens. Patients with positive skin prick tests underwent double-blind, placebo-controlled food challenges.
165 patients were enrolled and completed the study. Patients ranged in age from 4 months to 21.9 years (mean 48.9 months). 98 (60%) of the children had at least 1 positive prick test. A total of 266 DBPC food challenges were performed. 64 children (38.7% of total) were interpreted as having a positive challenge. Seven foods (milk, egg, peanut, soy, wheat, fish, and cashew) accounted for 89% of the positive challenges. By use of screening prick skin tests of these 7 foods we could identify 99% of the food allergic patients correctly.
This study confirms that most children with atopic dermatitis have food allergy that can be diagnosed by a skin prick test for the 7 foods.
The incidence of food allergy in atopic dermatitis
Ogura Y, Ogura H, Zusi N., Dept of Clinical Research & Paed Allergy, Kochi National Hospital, Japan
Arerugi 2001 Jul; 50(7): 621-8
To clarify the incidence of food allergy in atopic dermatitis, 226 non-selected cases with AD attending their hospital were evaluated by oral food challenges based on masked food challenges.
181 of 200 cases (26 cases dropped out) showed a positive reaction to at least one challenge test.
The incidence of food allergy in AD was 90.5%, and egg allergy, cow's milk allergy, soy bean allergy, wheat allergy, rice allergy were 83.5%, 51.5%, 33.5%, 20.0%, 2.5% respectively in the 200 cases.
The association of atopic dermatitis in infancy with IgE-mediated food sensitisation
Hill DJ, Sporik R, Thorburn J, Hosking CS, Dept. Allergy, Royal Children's Hosp., Melbourne, Australia
J Paediatrics 2000 Oct; 137(4): 475-479
To prospectively investigate the association of high levels of IgE sensitisation to foods and the presence of AD (judged by reported topical steroid use during the first 16 months of life) in a birth cohort of 620 Australian children "at risk" of allergic disease because of family history.
A total of 559 of the children in the cohort were fully evaluated, and the cumulative prevalence of AD was 24%. More children in the cohort who had AD had strongly positive skin test results, consistent with IgE sensitization to either cow's milk, egg, or peanut at 6 months (22% vs 5%, and at 12 months 36% vs 11%) than those without AD. The calculated attributable risk percent for IgE food sensitisation as a cause of AD was 65% and 64% at these times. In a separate group of infants with severe AD, the equivalent rates of IgE food sensitisation at 6 months were 83% and at 12 months, 65%.
IgE food sensitisation is a major risk factor for the presence of AD in infancy.
Evidence that Atopic Dermatitis is part of a systemic TH2 disease (Atopy), which also includes asthma and allergic rhinitis:
- Patients with AD have elevated total IgE level and specific IgE (CAP – RAST)
- Nearly 80% of children with AD eventually go on to have asthma or allergic rhinitis.
- When mice are sensitised through the skin with protein antigen, it induces a localised allergic dermatitis, elevated serum IgE, airway eosinophilia, and hyperresponsiveness to methacholine, suggesting that the skin exposure to allergen in AD may enhance the development of allergic asthma.
Laboratory correlates of AD & Food Allergy
- AD associated with elevated food specific IgE antibodies
- Ingested food proteins can trigger skin mast cells (Walzer, J Immunol 1927)
- AD with food allergy have GI malabsorption
- Plasma histamine rises during positive food challenges (Sampson et al NEMJ 1984)
Eosinophils are activated when causal foods are being ingested J Roy Soc Med 1997; 90 (S30): 3-9]
Diagnosis of food allergy in atopic dermatitis
The value of skin prick tests (SPT) in diagnosis of food allergy in AD
From a study published by Sporik et al. Clin Exp Allergy 2000; 30:1540-1646, the size of the SPT wheal can predict with 100% accuracy that the open food challenge will be positive.
Milk Egg Peanut
Children: 0-2 years of age >6mm >5mm >4mm
Children: all ages (median=3 yrs) >8mm >7mm >8mm
Value of specific IgE antibody (CAP-RAST) in the diagnosis of food allergy
Recently, new developments in the lab (in-vitro) diagnostics for IgE-mediated food allergies have occurred. Correlating food allergen-specific IgE concentrations in the serum (Immuno-CAP RAST) and skin prick test wheal diameters with patient histories and outcome of DBPCFC diagnostic decision points have been established for peanut, egg, milk and fish.
Diagnostic decision points that are 90% to 100% predictive of clinical reactivity to common food allergens.
(Hugh Sampson) JACI 2001; 107: 891-896
Allergen Decision point (KUA/l) ppv Sensitivity Specificity
Egg 7 98% 61% 98%
Milk 15 95% 57% 94%
Peanut 14 100% 57% 100%
Soy 30 73% 44% 94%
Wheat 26 74% 61% 92%
Atopy Patch Test (APT) (4)
Recently, the atopy patch test (APT) has been used to supplement the skin prick test in the diagnosis of food allergy in children with atopic eczema. These tests are particularly useful in investigating delayed reactions to milk and improves the accuracy of skin prick tests, since about half of the reactions following the ingestion of milk are not mediated by specific IgE antibodies to milk protein (delayed hypersensitivity) (5).
Food allergy and atopic eczema are both common diseases in infancy. Atopic eczema "is a complex disease with many triggers, foods being very important and often missed in infancy". From the very good studies carried out in recent years, showing clear causality between foods and eczema in infants, it is time for egos and emotions to give way to rationality.
(1) Host A & Halken S. Epidemiology and prevention of cow's milk allergy. Allergy 1998;56 (suppl 45): 111-113
(2) Sampson HA & McCaskill CC. Food Hypersensitivity and atopic dermatitis: evaluation of 113 patients. J Pediatrics 1985;56: 669-675
(3) Burks AW, James JM et al. Atopic dermatitis and food hypersensitivity reactions. J Paediatrics 1998;56: 132-136
(4) Niggeman B, Reibel S and Whan U. The atopy patch test (APT) – a useful tool for diagnosis of food allergy in children with atopic dermatitis. Allergy 2000;56: 281-285
(5) Host A. Cow's milk protein allergy and intolerance in infancy: some clinical, epidemiological and immunological aspects. Paediatr Allergy Immunol 1994;56: 5-36
(6) Bock SA. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. Pediatrics 1987:79:683-8.