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Keywords:

  • atopic dermatitis;
  • atopy patch test;
  • food allergy;
  • moisturizers;
  • oat

Abstract

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Background:  Topical treatments of atopic dermatitis (AD) may be responsible for cutaneous allergies. Percutaneous sensitization to oat used in emollients/moisturizers has already been reported. Our objectives were to measure the prevalence of oat sensitization in AD children, to assess its relevance, and to look at related parameters.

Methods:  We recruited prospectively children with AD referred for allergy testing between June 2001 and December 2004. Atopy patch tests (APT) and skin prick tests (SPT) to oat proteins (1%, 3% and 5%) and to the European standard series were performed followed by oral food challenge (OFC) and repeated open application test (ROAT) in the oat-sensitized group.

Results:  About 302 children were enrolled. Oat APT and SPT were positive in 14.6% and 19.2% of cases, respectively. Children under 2 years of age were more likely to have positive APT. In oat-sensitized children, OFC and ROAT were positive in 15.6% (five of 32) and 28% (seven of 25) of cases, respectively. Thirty-two percentage of oat cream users had oat-positive atopy patch test (APT) vs 0% in the nonusers group.

Conclusions:  Oat sensitization in AD children seen for allergy testing is higher than expected. It may be the result of repeated applications of cosmetics with oats on a predisposed impaired epidermal barrier. We suggest avoiding topical-containing oat proteins in infants with AD.

The prevalence of atopic dermatitis (AD) has not ceased to increase over the last 50 years in the countries of Northern Europe, from about 3% before the 1960s to 15–20% nowadays (1). Emollients/moisturizers are widely used as adjuvant therapies (2, 3). Several brands contain various molecules with a presumed or demonstrated anti-inflammatory role, such as oat proteins (4). A subgroup of patients with AD experiences a worsening of skin symptoms through contact with various allergens/irritants, including components of skin cosmetics. Contact allergy to oat protein found in moisturizers has been reported previously (5–10).

Our objectives were to measure the prevalence of sensitization to oat in children suffering from AD, to assess its relevance and to investigate associated or predisposing factors.

Patients and methods

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Study population

The inclusion criteria were as follows: children under 15 years of age suffering from AD according to the diagnostic criteria of the UK Working Party’s group (11) and admission to our unit between June 2001 and 2004 for skin testing. To investigate the APT/skin prick test (SPT) results according to age, three age groups were defined: 0–2, 2–6 and 6–15 years.

Atopy patch testing

For APT, the allergens were laid out in 10-mm Finn Chambers® (Epitest Ltd Og, Tuusula, Finland), applied on healthy back skin, and left for 48 h. A first reading was made 30 min after removal of chambers. A final reading (72 h) was carried out in doubtful cases (12).

We used the European standard battery adapted to the age of the patient (13). Oat APT were prepared with total Rhealba® oat extract (1%, 3% and 5% concentrations; Laboratoires Pierre Fabre, Lavaur, France) and with the proteinic fraction of the total Rhealba® oat extract dispersed in petrolatum (1%). Atopy patch test was interpreted according to the International Contact Dermatitis Research Group (ICDRG) modified by Fischer and colleagues (14). To avoid confusing simple irritation with true eczematous reaction, only results with (++) or more were considered positive.

Skin prick testing

For SPT, the technique was that described by Bock and colleagues (15). A standardized battery of tests was systematically applied comprising the most common aero- and food-allergens among the atopic child population, according to the literature and our own experience (16, 17). For oat SPT we used a standardized oat extract (1% P-V, oat pollen, Laboratoires Allerbio, Varennes en Argonne, France). The result was read after 20 min by noting the papule and erythema diameters for each allergen. Skin prick test were considered positive if the papule diameter was equal to or greater than that of the positive control test.

IgE

During enrolment, blood was obtained for total immunoglobulin (Ig) E and specific IgE antibodies to oat and wheat determined with the CAP-RAST FEIA (Pharmacia Diagnostics, Uppsala, Sweden) after informed consent. Sensitization was defined as a concentration of IgE of 0.35 kUI/l or greater.

Prevalence study

Prevalence was studied according to age groups and sex. The first age group (0–2 years) was selected because previous reports mentioned that AD patients in this group are more likely to have positive oat APT than older children (8, 9). The age of 6 was selected because it is the age of compulsory schooling.

Associated risks

To study the risks of oat sensitization, we suggested day care hospitalization for all the children with positive oat APT and/or SPT who had been screened in the prevalence study. During hospitalization, a single-blinded oral food challenge (OFC) was performed, followed by an oat cream repeated open application test (ROAT) at a distance from the AD flare-up.

Oral food challenge consisted in giving increasing oat amounts under medical supervision, according to the procedure described by Bock and colleagues (18). The ROAT was performed in children with positive APT and/or SPT as a 14-day use test on a 5 × 5 cm area on the volar forearm. The parents applied the provided emollient Exomega® cream [whole Rhealba® oat extract and omega-6 polyunsaturated fatty acids (3.25%), glycerine (5%) and vitamin E (0.5%); Laboratoires Ducray, Lavaur, France] twice a day, according to published procedures (19, 20), and the test was stopped after 14 days or earlier if a reaction occurred. The test was considered as positive if papules, vesicles or bullous reactions appeared, and doubtful reactions characterized only by erythema were considered as negative.

Related factors

To study the factors promoting sensitization to oat, we submitted a standard questionnaire to a subgroup of consecutive children seen from April to December 2004. Data collection was performed during a face-to-face meeting with at least one of the parents before APT reading to avoid biases. The questionnaire comprised questions about family and personal history of atopy (asthma, allergic rhinitis or only AD), food or airborne allergies, the consumption of cereals containing oat and its tolerance, and housing (specifying if the housing was in urban or rural areas). To assess the use and tolerance of cosmetic products containing oat, a leaflet summarizing all the oat-containing products available in France (including the name and a packaging picture) was shown to the parents, and the child was considered to have been exposed if the product had been applied for at least 3 days. SCORAD and location of the lesions were recorded (21). The oat and wheat pollen environment of these patients was also evaluated with respect to data on cereal production in the district where the participant resided (agricultural census 2000, latest to date).

To determine which factors promote oat sensitization, we compared the children with positive reactions to oat APT to the negative oat APT group for each questionnaire item.

Statistics

For statistical analysis, data were captured under Epidata® and were processed with Epiinfo® (Centers for Disease Control and Prevention, Atlanta, GA, USA) and SAS® (SAS Institute Inc., Cary, NC, USA). The chi-squared test was used for qualitative variables and the Student’s t-test for quantitative variables. A multivariate analysis was carried out by logistical regression for the variables associated with a P-value of <0.02 at univariate analysis.

Results

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Prevalence study

We enrolled 302 AD-afflicted children (152 males) aged from 4 months to 15 years (mean 5 ± 3.65). Oat sensitization was found in 32.5% of our sample (98 of 302), 14.6% (44 of 302) when considering only APT results and 19.2% (58 of 302) when considering only SPT results (Table 1). Only four children (1.3%) were both APT- and SPT-positive. For APT, 16 of 44 children tested positive with the 5% concentration, six tested positive for both 5% and 3%, and the remaining 22 tested positive for all three concentrations. There was no significant difference according to sex. With respect to age, the percentage of children with oat-positive APT was greater in the younger age group (0–2) with a subsequent age-dependant decrease. On the contrary, the frequency of oat-positive SPT increased with age (Fig. 1).

Table 1.   Oat APT and SPT results according to age groups (in years)
 0–2 (n = 55)2–6 (n = 160)6–15 (n = 87)Total (n = 302)
  1. APT, atopy patch test; SPT, skin prick test.

APT+ SPT−2413340 (13.2%)
APT− SPT+0312354 (17.8%)
APT− SPT−3011460204 (67.5%)
APT+ SPT+1214 (1.5%)
APT+25 (45.5%)15 (9.3%)4 (4.6%)χ2 52.5, P < 10−4
SPT+1 (1.8%)33 (20.6%)24 (27.6%)χ2 = 14.86, P < 10−3
image

Figure 1.  Comparison between percentage of positive atopy patch test and skin prick test results according to age groups (χ2 = 52.57, P < 10−4).

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Relevance of oat sensitization

Thirty-two of 98 sensitized patients accepted hospitalization for OFC. There were 16 males and 16 females aged 7 months to 15 years with a mean age of 4.9 ± 3.95 years. Sensitized children having accepted hospitalization were comparable in every respect with those who had refused it. Five of the 32 children challenged had a positive OFC (15.6%) after a dose of 1 (three cases), 5 (one case) and 10 g (one case) of oat flakes. Three of them had a positive APT and two a positive SPT. For all these children, their affliction with oat meal allergy was neither known to the parents nor suspected by history taking or clinical examination. Two children had digestive symptoms (vomiting, abdominal pain and diarrhoea), two had respiratory disturbances (one had repeated coughing fits and one had a mild asthma attack), and two had cutaneous reactions (facial erythema with pruritus in one case, clear aggravation of previous AD lesions in the other). One child had both cutaneous and respiratory symptoms.

A positive ROAT was observed in seven of the 25 tested children (28%). Seven children were not tested with the ROAT because their parents refused it. Eczema occurred in six and prurigo-like lesions in the remaining case. When the SPT was positive in isolation, the risk of having a positive ROAT was 12% (one of eight), whereas the risk was 27% (four of 15) when only the APT was positive.

Factors associated with oat sensitization

Among 79 consecutive children recruited for study of the factors promoting oat sensitization, 67 medical files were complete. Mean SCORAD was 39 (range: 7–87), 13% had mild AD, 55% had moderate AD and 31% had severe AD (22).

Fifty of the 67 children (74.6%) had previously used emollient creams containing oat. Among them, eight of 50 (16%) experienced skin manifestations when applying these creams, i.e. AD flares in five cases, pruritus in two cases and widespread erythema in the remaining cases.

Forty children were tested for IgE. The values of the total and specific IgE increased with age, notably the specific wheat pollen IgE (g 15; Table 2). Fourteen of 40 (35%) children were oat flower IgE- and oat pollen IgE-positive; 14 of 39 (35.9%) children were wheat flower IgE- and 16 of 40 (40%) were wheat pollen IgE-positive. Eighty percentage of the children had oat- and wheat-specific IgE <1 kUI/l.

Table 2.   Total and specific IgE (kUI/l) to oat and wheat according to age groups
 Total IgEf7 (oat flower)g14 (oat pollen)f4 (wheat flower)g15 (wheat pollen)
  1. Values are expressed as mean IgE (kUI/l).

  2. Cut-off value for total IgE = 45; cut-off value for specific IgE = 0.5.

  3. IgE, immunoglobulin E.

0–2 years (n = 10)
 Mean IgE (SD)91.8 (71)1.6 (3)0 (0)0.9 (2.3)0 (0)
 Number of children   with IgE higher   than cut-off value73 3 
2–6 years (n = 26)
 Mean IgE (SD)1350 (4944)1.5 (5.8)4.3 (13.6)4.3 (13.6)0.7 (1.8)
 Number of children   with IgE higher   than cut-off value187759
6–15 years (n = 9)
 Mean IgE (SD)2816 (4506)3.1 (6.2)5.5 (14)12.9 (35.2)14.4 (33.4)
 Number of children   with IgE higher   than cut-off value93434

For these 67 children, house dust mite was the most common positive allergen on SPT and APT testing (Table 3). The younger the child, the greater the number of positive APT: 80% of the 0- to 2-year-old children had positive APT vs only 33% for the 6- to 15-year-old group.

Table 3.   Positive APT results (%) for oat and other common allergens
 Our studyRancé and colleagues (27)
  1. nt, not tested; APT, atopy patch test.

House dust mite34.335.7
Oat23.92.4
Birch pollen12nt
Nickel8.912.4
Potassium dichromate6nt
Ambrosia4.5nt
Fragrance mix4.55.2
Lanolin35.6

The 2000 agricultural census data showed that the oat-cultivated land in the region of Aquitaine, France, did not exceed 29 ha, i.e. one of the lowest figures for a French region. Moreover, we found no correlation between type of residence (a city or in the countryside, proximity of cereal cultures) and the prevalence of positive oat and wheat SPT or APT.

Univariate analysis was performed to correlate APT results and various recorded parameters (Table 4). Multivariate analysis indicated that the only risk factor of positive oat APT was the application of a moisturizer containing oat proteins (Table 5). Indeed, 32% of oat cream users had positive oat APT, whereas no case of oat sensitization was found among nonusers (P = 0.0068).

Table 4.   Univariate analysis of oat APT results and various recorded parameters
  1. Only variables associated with a P-value below 0.02 were considered for multivariate analysis.

  2. NS, not significant; AD, atopic dermatitis; APT, atopy patch test; SPT, skin prick test; IgE, immunoglobulin E.

Clinical features (asthma, hay fever, severity of AD)NS
Housing (urban vs rural area)NS
Cereal production in district of housing0.196
Previous consumption of cereals containing oatNS
SPT results to oat0.183
SPT results to grass mix, cereal pollen mix and wheat pollenNS
Oat- and wheat-specific IgENS
Previous use of oat-containing emollient<0.001
Table 5.   Comparison between oat-containing product users and nonusers
 NonusersUsersTotalP-value
  1. APT, atopy patch test.

APT−17 (100%)34 (66.7%)510.0068
APT+016 (33.3%)16
Total175067 

Discussion

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

In the population of children referred to our centre for allergy testing, nearly one-third was sensitized to oat. This finding is in itself surprising but may reflect the situation in France in children referred for allergy testing, as there was no major bias for severity of disease in this population of young children. The percentage of children having oat-positive APT decreased with age (Fig. 1). This significant correlation between age and oat APT results is in accordance with previous studies carried out with other allergens (23). It could be due to a more severe impairment of an immature epidermal barrier in young children (22). Indeed, the role of a genetically impaired epidermal barrier as the primary cause of AD and respiratory signs of atopy is now widely admitted and concerns several genes that encode for stratum granulosum/corneum proteins, i.e. filaggrin and LEKTI (24, 25).

Our study also showed that the prevalence of oat sensitization – measured with SPT or APT – was higher than in the four other published studies, whereas other tested allergens were in the same range of prevalence (Table 3). This may be due to the widespread use of oat-containing topicals from very early age in France, especially in AD-afflicted children. Indeed, 74.6% of children had previously been treated with emollients containing oat.

Concerning the oat APT results, no sensitization to oat could be detected in 65 AD patients in an Italian paediatric series (26). Moreover, APT was performed with a much lower oat concentration (0.007% and 0.7%) that was probably insufficient to detect oat-sensitized children.

Regarding the SPT results, the marked differences observed between our findings and those of the two studies published previously (27, 28) are difficult to interpret, as the allergen source was different as well as the SPT interpretation method. Moreover, one of the studies (28) concerned older AD patients (44 adults and six children), whereas ours was exclusively paediatric. This is in accordance with a recent study showing that oat-sensitized children may desensitize with age (29).

We found a poor correlation between positive oat APT/SPT and ROAT. First, this may be due to the fact that positive APT could be triggered with weaker concentrations than those used with ROAT because of occlusion (30). Secondly, as ROAT was performed at home by the parents, tests may have been carried out improperly. Thirdly, in children suspected of having oat allergy prior to the ROAT, including those who experienced skin manifestations when applying oat-containing creams and those with positive OFC, some of the parents may have refused the ROAT procedure, so the real percentage of children with positive ROAT may have been underestimated. While tests such as the ROAT increase the refinement of evidence-based diagnosis of clinical relevance (31), recent overviews have shown that it was negative in approximately half of the cases of seemingly reliable patch tests, that prolonged ROAT procedures (4 weeks or more) produce a higher degree of positivity, and that regional variation in reactivity may affect test results, with maximal reactivity in the upper back compared to the forearm (30, 31). Our ROAT-positive results are thus probably underestimated, so it is hardly surprising that at least one-third of our patients with positive APT and/or SPT have clinically relevant oat allergy.

A more frequent sensitization to oat pollen has been reported in farmers than in teachers, and cross-sensitization between wheat and oat has been shown in farmers (32, 33). In this study, we found no relationship between oat and wheat pollen environment and risks for oat sensitization. On the other hand, repeated application of cosmetics with oat components appeared to be an associated factor in our series. This is at variance with the work of Rancé and colleagues, in which oat APT were positive in four of 105 (3.8%) of the children using such creams and two of 98 (2%) of nonusers (27). However, in that study, the concentration of oat extracts was twofold less than in our study and children applying oat-based topicals used them for a shorter time. This argues in favour of percutaneous sensitization at a very young age.

While no oat-sensitized child experienced any severe reactions during OFC, five children did have positive reactions. The risk of percutaneous sensitization with food products is now considered real (34–37). For example, experimental studies in mice showed that ovalbumin exposure through the skin could trigger egg allergy, with a high level of ovalbumin-specific IgE and subsequent symptoms of systemic anaphylaxis during OFC (34). Moreover, T cells responsive to peanut antigens were found in the skin of an atopic infant before the development of peanut oral allergy (35). Furthermore, in a prospective study of 49 children with peanut allergy, a significant independent relation between peanut allergy and the use of cosmetics containing peanut oil was found (36). Thus, oat may be added to the list of food products (peanut, ovalbumin, almond, etc.) responsible for food allergy triggered by a possible percutaneous sensitization (37). In a very recent randomized-controlled study, it was shown that emollients containing oat proteins may reduce high-potency topical corticosteroid use in children with moderate-to-severe AD (38). That study argues in favour of the steroid-sparing effect of emollient therapy but the beneficial effect of oat proteins is unproven. As a safety-first principle to limit percutaneous sensitization by applying topical adjuvant treatments containing oat proteins, we recommend not using them before the age of 2 in predisposed children.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

We thank the children and their families who made this study possible. We would particularly like to thank Nathalie Chung and Marie-Berthe Chabat, the nurses whose personal involvement greatly facilitated the study management, and Ray Cooke for his helpful comments during the revision of the manuscript.

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  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
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