Atopic dermatitis is the most common chronic skin disease in childhood.1 Although itching and chronic/relapsing course are the predominant features, it has a varied range of manifestations as presentation, distribution and severity.2 There is not a diagnostic laboratory marker or diagnostic criteria accepted as the gold standard. This may cause over/under diagnosis and prevent eligible therapy.

The Hanifin-Rajka criteria (HRC) are the first developed and most cited diagnostic criteria in studies.3,4 Since the 1980s, they had been used to bring uniformity to the diagnosis. The items of HRC defined by dermatologists empirically on “clinical experience” and consensus between experts, especially for use in hospital settings,4 but had only been validated in two studies.5,6 However, some of the items were found to be useless because of requiring invasive tests and being non-specific for AD by Williams et al.7 But HRC still remains an important tool particularly in cases of atypical presentation.4

The United Kingdom Working Party criteria (UKC) were defined as a refinement of the original HRC in 1994 to be easier to use and better applicable for population-based studies.7,8 They are the only diagnostic criteria with several validation studies both in hospital and population-based settings.4,7,9,10 However, efficacy studies in children generated large variations in sensitivities (10–100%) and specificities (89–99%) in different age and ethnic groups.4,5,9,11 To date, HRC and UKC are the most validated and used criteria.2,8 In this study, we aimed to compare the diagnostic efficacy of HRC and UKC in outpatient clinics for children with AD.

The challenge for establishing diagnostic criteria for AD is going on. There have been several diagnostic criteria developed over time. One of the main problems is the need for consistent description of the patients, which is essential for comparability and interpretability of studies and avoiding misdiagnosis of patients8 In our study, the clinical efficacy and accuracy of HRC and UKC were compared with the clinical diagnosis. The study population was composed of children with AD and controls with similar age and sex. As a result, the HRC had the highest accuracy and compatibility with clinical diagnosis.

As in most of the literature about diagnostic criteria, clinical diagnosis by a group of experts was determined as the gold standard in our study.2,4 De et al. and Shultz Larsen et al. had investigated the efficacy of HRC with the same study plan — using the clinical diagnosis as reference standard- and a pediatric patient population.5,12 The sensitivity of HRC in our study (94%) was similar to those studies, in which the sensitivities were 88% and 96%, respectively. However, the specificities of their studies (94% and 78%, respectively) were higher than in our study (71%).5,12 This might be due to the younger age of our study population than the participants in those studies (4.8 and 7 years old, respectively).5,12 Accordingly, the accuracy rate (87%) and compatibility (kappa value [KV]) (0.68) of our study was similar to the study of Johnke et al. in which they compared visible eczema with HRC in children younger than two years old and found an accuracy rate of 93% and a KV of 0.62.11

Similar to the literature, “dermatitis in classical morphology and distribution” and “chronic/relapsing dermatitis” were the major items with the highest sensitivity and RV for HRC.5 Nevertheless, the specificity of all major items was lower than it was in the literature.5 Also, Kanwar et al. argued the specificity of major items of HRC for the diagnosis of AD.21–23 They noted that “pruritus” may change from person to person and may be found in many other dermatologic diseases such as urticaria, contact dermatitis or seborrheic dermatitis which are in the differential diagnosis of AD. This is also right for the item of “chronic/relapsing dermatitis”.21 Prevalence of allergic diseases has been increasing gradually, so “family history of atopy” may not be specific for AD.21 Besides this, some of the children with AD do not have atopic features in the early years of life. This could be attributed to the fact that AD is the initial step of the “allergic march” and often develops during the first months of life.1,15 Consequently, it could be noted that major items are needed, but are not enough to diagnose AD without minor items.

There are more studies about minor items of the HRC in the literature. Several studies demonstrated that there was no clinical significance of “nipple eczema”, “cheilitis”, “recurrent conjunctivitis”, “perifollicular accentuation”, “ichthyosis”, “hypopigmented patches”, and “aggravation by foods” in discriminating children with AD.13,22,23 Similarly, our results demonstrated that those minor items had no clinical significance except “ichthyosis” and “aggravation by foods”. Moreover, Rudzki et al. demonstrated that “infraorbial folds” and “anterior neck folds” were important in diagnosing AD.24 We also found “anterior neck folds” to be significantly more prevalent in the AD group, but not “infraorbital folds”. In addition to the above-mentioned minor items, De et al. demonstrated that the frequency of “facial pallor/erythema”, “aggravation by emotional factors”, “susceptibility to cutaneous infections” and “hand and foot dermatitis” had no significance for discriminating AD in young children.5 According to our study, “susceptibility to cutaneous infections” and “hand and foot dermatitis” were more frequent in AD group, but their RV was low. Frequency of “early age of onset” was not different for the groups in our study, either. The minor items with the highest RV in our study were “xerozis”, “elevated serum total IgE” and “aggravation by woolens and solvents” (Table 2).

In their studies, Nagaraja et al. and Rudzki et al. argued that the specificity and prevalence of both major and minor items of HRC could be affected by the age of the patients.24,25 The age of our patients was younger than those in the studies discussed above. Accordingly, different age groups in different studies may be a factor of different frequency, sensitivity and specificity values of HRC among studies. Similarly, some researchers claimed that minor items might change by gender, race or ethnic origin.13,23

The HRC had been point of origin and reference criteria for most of the other diagnostic criteria such as the UKC.2 The researchers tried to define the most practical and reliable criteria for their study population and age group. One of the reasons for the need for a new set of diagnostic criteria is that some of the items of the HRC are difficult to evaluate objectively and so may vary in results from physician to physician for the same patient. Besides this, the application of the HRC requires invasive tests and time.11,13,14 In the literature, the sensitivity, specificity, PPV and NPV of the UKC showed a wide variety in studies with children of different age groups.8,9,20 De et al. highlighted that the statistical values of the UKC were lower in children younger than 12 months old, when compared with their whole study population whose median age was 4.8 years.5 Herein, we have demonstrated similar results with the aforementioned study. Similarly, the UKC had lower sensitivity and specificity regarding the patients younger than 12 months than the rest of the cases in our study (data not shown). In the study of Johnke et al. evaluating visible eczema in children younger than two years old, accuracy rate and kappa value were 93% and 0.580 for UKC, respectively.11 The Kappa value was comparable with our results (0.56), but the accuracy rate in our study was much lower (78%). Hereby, the younger the age is, the lower the diagnostic efficacy of the UKC seems to be.

The most valuable items of the UKC in the previous studies were “visible flexural dermatitis”, “history of flexural dermatitis”, “itchy skin” and “dry skin”, as they were in our study.5,9,20 All of these items were altogether reflecting the items of “dermatitis in classical morphology and distribution”, “pruritus” and “xerozis” in the HRC. “History of atopy” and “onset before two years old–for >4 years old-“were the items with the lowest sensitivity and NPV, as they were in the literature.5 As regards “personal and family history of atopy” and “early age of onset” in the HRC, these items were not suitable to distinguish AD in younger children. As a result, the items of the UKC with higher efficacy to diagnose AD corresponded to “dermatitis in classical morphology and distribution”, “pruritus” and “xerosis” items of HRC.

The UKC is more compatible with the HRC for determining controls rather than diagnosing AD patients. This could be interpreted as the UKC being more appropriate for population-based studies. It supports the fact that the UKC were developed as a refinement of the HRC to be easier to use and suitable for population-based studies.8

The limitation of our study is that clinical diagnosis by the consensus of the panel of pediatric allergists is accepted as the reference method. This might have led to overestimation of sensitivity and specificity.26 But, there is no other choice than assessing the clinical diagnosis as the gold standard at the moment. This problem could be partly solved with a panel of experts instead of evaluating the patients by only one physician.

While the need for establishing the ideal diagnostic criteria is continuing, the HRC seems to discriminate young children with AD in hospital settings better than the UKC. The HRC were the most commonly used in all ages, regions and interventions up to date.8 In order to contribute to the attempts of generating an international consensus for diagnosing AD, the HRC might be recommended to be kept in mind particularly for future studies with young children.

The authors have no conflicts of interest related to the manuscript.