Contact hypersensitivity to Indian standard patch test series correlates with disease severity among children with atopic dermatitis

Key Message

In this study, nearly one-fifth (20.6%) of children with atopic dermatitis had a positive patch test. The most common allergens were fragrance mix, potassium dichromate, cobalt and nickel. Greater disease severity was associated with patch test positivity.

Plain Language Summary

In this study, we tried to analyse the association between eczema in children and certain common allergy inducing chemicals present in various items of daily life, by means of a simple, non-invasive office-based patch test. We found that nearly one-fifth (20.6%) of children with eczema had a positive result. The most common allergens were those found in fragrances and cement as well as metals such as nickel and cobalt.

Introduction

There is a complex, though yet not fully understood relationship between atopic dermatitis (AD) and allergic contact dermatitis (ACD). Immunologic pathways, influenced by both genetic and environmental triggers, contribute to the development of both conditions. There is emerging evidence supporting the existence of a substantial relationship between them, though the data available are scarce with conflicting viewpoints. Predisposing factors such as deficiency in filaggrin, altered pH, the cutaneous acid mantle, microbial colonisation by Staphylococcus aureus and low vitamin D levels contribute to the immunopathogenesis and elicitation of both atopic dermatitis and allergic contact dermatitis. It is important to diagnose contact dermatitis (CD) in patients with atopic dermatitis as atopy amplifies the effects of contact irritants and allergens on the skin. This is seen with hand eczema in adult patients with atopic dermatitis in certain occupations (hairdressers, cleaners, metalworkers, mechanics and nurses). Contact sensitization may negatively influence the skin of atopic dermatitis patients; therefore, identifying an aggravating factor, such as a contact allergen, and avoidance of the allergen can lead to the improvement of dermatitis.¹

Contact allergy is common in both children and adults and may affect up to 20% of the general population.² Among the commonly implicated contact allergens, metals, fragrance materials and preservatives are found in commonly used products such as cosmetics and jewellery. Another important consideration in atopic individuals is that topical therapy is inevitably prescribed, often for longer periods to inflamed skin resulting in near continuous exposure. While experimental models provide some insights into a possible interplay between contact allergy and atopic dermatitis, they do not and cannot simulate real-time human exposure. Hence, epidemiological studies have so far been unable to provide definitive conclusions on the possible relationship between atopic dermatitis and contact allergy.

Thus, this study was conducted to detect the frequency of contact hypersensitivity to Indian standard series among children with atopic dermatitis by patch testing and to correlate the clinical disease severity with the contact hypersensitivity observed in these children.

Methods

This was a single-centre, cross-sectional study conducted in the Paediatric Dermatology clinic of the Postgraduate Institute of Medical education and Research (PGIMER) in Chandigarh, North India, between April 2017 and September 2018 after obtaining approval from the institute’s ethics committee. Written informed consent was taken from the parents. Children aged between 6 months and 12 years diagnosed with atopic dermatitis according to Hanifin and Rajka criteria were included. These children did not have any contraindication to patch testing and had controlled disease, such that the back and the forearms were free from active dermatitis and suitable for application of test patches. Children aged < 6 months and > 12 years; immunocompromised children; those with severe exacerbation of the disease and active dermatitis; patients on oral corticosteroid equivalent to or more than 15 mg of prednisolone (arbitrarily defined as 0.25 mg/kg/day) or equivalent doses of steroid-sparing adjuvant drugs; those with dermatitis at the test site, i.e., upper back; inability to adhere to instructions including three visits over 1-week period and to keep patch test in place till last reading is taken; and those whose parents did not consent to their child’s inclusion in the study were excluded. Detailed history was recorded regarding the duration of symptoms, extent of symptoms, aggravating and relieving factors, treatment and family history. Clinical examination was performed inclusive of severity grading using SCORAD scores for all patients at the time of recruitment. The severity of eczema was graded according to the SCORAD index as mild (<25), moderate (26–50) and severe (>50) atopic dermatitis. Serum IgE levels were also measured before patch testing in all patients.

Results

Out of totally 136 patients, 80 were boys. The mean age of the study population was 5.6 + 3.2 years. The youngest child was 11-months old, and 18 children were aged 2 years or less. The mean duration of disease was 33.6 + 28.5 months. The mean SCORAD of the study population was 21.6 + 11.6. According to SCORAD, the severity of atopic dermatitis was mild in 71, moderate in 54 and severe in 11 patients. Atopy was seen in 32 (23.5%) patients. Topical corticosteroids were prescribed in 111 (81.6%) patients and topical tacrolimus in 85 (59.6%). Systemic therapy including oral corticosteroids, cyclosporine and azathioprine was given to only six (4.4%) patients. Raised serum IgE was observed in 104 (76.5%) patients, and the mean serum IgE of the study population was 1395.2 + 3257.7 IU/mL. Clinicodemographic characteristics of the study population are summarised in Table 1.

Of the 136 patients, 24 (17.6%) patients had positive patch tests at 48 h while 28 (20.6%) patients had patch test positivity at 96 h. Eleven (8.1%) patients had positive patch tests with > 2 allergens. Among patients with patch test positivity at 48 h, fragrance mix was the commonest allergen (7 of 24 patients, 29.2%) while potassium dichromate, cobalt chloride hexahydrate and nickel positivity were observed in five patients each [Figure 1]. Similarly, at 96 h, fragrance mix and cobalt chloride hexahydrate were positive in seven patients each, and potassium dichromate and nickel positivity were seen in five patients each [Figure 2]. Gentamicin sulphate was found positive in four patients. Table 2 describes the patch test positivity with Indian standard series components in detail with the grading of positive reactions. On comparing patients having a positive patch test with those having negative patch tests, no significant difference was observed for age, sex, disease duration, presence of atopy and mean serum IgE levels [Table 3]. However, SCORAD was significantly higher in patients with positive patch tests as compared to patients with negative patch tests (27.4 ± 13.3 vs 20.5 ± 11.0, respectively; P = 0.009). Raised IgE levels were observed in 25/28 (89.3%) patients with positive patch tests as compared to 79/104 (75.9%) patients with negative patch tests (P = 0.08).

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Figure 1:

Patch test positivity (2+) to both parthenium and thiuram mix at 96 h.

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Figure 2:

Patch test positivity (2+) to cobalt sulphate at 96 h.

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Discussion

It continues to be a matter of debate whether or not atopic dermatitis increases the risk of contact allergy. Clinically, it is difficult to differentiate contact dermatitis from atopic dermatitis, especially in the common areas of involvement, such as the eyelids, lips, hands and flexural areas of the neck, and also when there is dermatitis with a scattered generalised distribution. A patch test is useful in this regard to determine sensitisation to specific allergens. However, the clinical relevance of positive patch test reactions should be established by carefully correlating the patient’s history including details regarding possible exposure to the allergen, site and type of exposure, with the test results. It is the role of the clinician to determine if a positive patch test result is relevant or not, and this is often one of the most difficult aspects of patch testing. Reported relevance in published studies is determined by standards used by the North American Contact Dermatitis Group (NACDG).³ NACDG defines current relevance as definite if there is a positive patch test or provocative use test of an article belonging the patient known to contain the allergen, probable if the antigen is present in known skin contactants and the clinical presentation is consistent with that exposure, or possible if skin contact with materials known to contain the allergen is likely. The most concrete proof of relevance is the improvement or resolution of dermatitis after avoidance of the allergen.⁴ Past relevance is considered if the patch test is positive, but Table 3 exposure was in the past and the patient is not currently exposed to that allergen.⁵

A limited number of studies have investigated the overlap of atopic dermatitis and allergic contact dermatitis in children. A systematic review of patch test results in children found studies both revealing and refuting a statistical difference between patients with and without atopic dermatitis.⁶ In addition, uncovering any allergic contact dermatitis and subsequent avoidance of allergens could lead to improvement in the patient’s atopic dermatitis symptoms. Patch test positivity in children ranges from 20 to 95.6%.^6–8 In a cross-sectional survey of 82 children with atopic dermatitis who were patch tested with the children’s baseline series and a corticosteroid series, positive reactions were seen in 26.8%.⁹ In a recent review of contact allergy in children, the prevalence of positive patch test results in selected populations (children with suspected allergic contact dermatitis, recalcitrant atopic dermatitis or eczema) ranged from 27 to 96%, with relevance established in 52–100%.¹⁰ In a study from north India, patch test positivity was found in 33% of atopic dermatitis patients with common allergens being nickel, cobalt chloride, neomycin sulphate, fragrance mix, potassium dichromate and paraphenylenediamine.¹¹ In another north Indian study, patch test positivity was high with 54.3% of patients being positive for one or more allergens, and nickel sulphate was the most common allergen.¹² In our study, 20.6% of children were positive for various allergens of Indian standard series at 96 h. Multiple studies have found increased sensitisation rates to various allergens among children with atopic dermatitis, including potassium dichromate, compositae mix, disperse blue, balsam of Peru, fragrance mix, nickel, cobalt, wool alcohols, neomycin, colophony, thiomersal and lanolin.^7,9,13 Similarly, the most common allergens in our study were fragrance mix, potassium dichromate, cobalt chloride and nickel sulphate. The relevance of positive patch tests was difficult to be established in our cohort. Due to the ubiquitous nature of the allergens, especially fragrance, metals and rubber chemicals, they were deemed relevant. We could not establish relevance in children positive for the other allergens. The majority of patients in our study with positive patch tests were boys in contrast to the previous study on contact sensitisation in a paediatric atopic dermatitis population in Laos.⁸ A retrospective analysis showed that eczema area and severity index scores greater than 10 correlated with a higher probability of more than three positive patch tests.⁷ In our study, higher SCORAD was found to be associated with patch test positivity. Similarly, a prospective study from Tunisia of 89 children and adults with atopic dermatitis found that the more severe the atopic dermatitis, the more frequent was the patch test positivity.¹⁴

In a retrospective case review of 1142 children patch tested by 84 health care providers from across the United States,¹⁵ patch-tested patients with atopic dermatitis were found to be significantly younger with more generalised and a longer history of dermatitis compared with those without atopic dermatitis. In our study, no difference in age and duration of disease was found between patch-test positive and -negative patients.

Inability to establish relevance in about 50% of the patients was a limitation of our study. Participants and their parents were advised to avoid the allergens which they had tested positive for. Follow-up data regarding assessment of the impact of allergens avoidance was not available and hence are not included in this study.

Conclusion

In the present study, approximately one-fifth of the atopic dermatitis patients were found to have a positive patch test. The most common allergens resulting in positive patch tests were fragrance mix, potassium dichromate, cobalt chloride hexahydrate and nickel. High SCORAD, i.e., higher disease severity was found to be associated with patch test positivity.