Prevalence of adult atopic dermatitis among nursing staff in a Taiwanese medical center: A pilot study on validation of diagnostic questionnaires

Article Outline

• Abstract
• Methods
  • Statistical analysis
• Results
• Discussion
• References
• Copyright

Background

Atopic dermatitis (AD) is a chronic, relapsing dermatosis. Previous studies have focused mostly on pediatric patients, and investigations emphasizing adult AD have been limited.

Objective

We set out to determine the 1-year prevalence and evaluate the validity of the International Study of Asthma and Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) AD questionnaires of adult AD in Taiwan.

Methods

We conducted a cross-sectional study among nursing staff at a university hospital. The 1-year prevalence of AD was assessed by ISAAC and UKWP questionnaires. Subsequently, the dermatologists' diagnosis based on Hanifin and Rajka criteria was used as a reference for validation.

Results

The overall response rate was 92.9%, equivalent to 1131 complete questionnaires. Ninety adult patients with AD (8%) were identified by dermatologists' diagnosis whereas ISAAC identified 107 (9.5%); sensitivity and specificity were 36.7% and 92.9%, respectively. UKWP identified 42 (3.7%) patients with AD; sensitivity and specificity were 42.2% and 99.6%, respectively. Using the receiver operating characteristic curve analysis, the UKWP criteria performed significantly better than its ISAAC counterpart. Further analysis indicated that modification of these criteria resulted in significant improvement in their diagnostic efficacy. More specifically, modified ISAAC showed 90.0% and 55.2% sensitivity and specificity, respectively, whereas modified UKWP demonstrated 82.2% and 94.2% sensitivity and specificity, respectively.

Limitation

Most of the study subjects were female with a high educational background.

Conclusion

Currently available questionnaire instruments do not perform well in the identification of adult patients with AD. Modification of the original questionnaires may allow for future large-scale epidemiologic studies.

Key words: adult atopic dermatitis, diagnostic criteria, prevalence

Abbreviations used: AD, atopic dermatitis, AUC, area under curve, ISAAC, International Study of Asthma and Allergies in Childhood, NPV, negative predictive value, PPV, positive predictive value, ROC, receiver operating characteristic, RV, relative value, UKWP, United Kingdom Working Party

Atopic dermatitis (AD), a chronic, relapsing inflammatory dermatosis characterized by pruritus, is often thought to be a disease that predominately affects children. Many studies have shown that the prevalence of this disease among children has increased substantially over recent years around the globe, including Taiwan.¹, ² Therefore, much effort has been spent to promote further understanding of this disease. Intriguingly, few studies have directed their attention to adult AD, despite the fact that the occurrence of AD among adults has been shown to significantly affect socioeconomic conditions in both Asian and Western countries.³, ⁴ To address this increasingly important yet still often neglected issue, epidemiologic studies that investigate the distribution and prevalence of this disease among adults are warranted. More importantly, understanding disease burden of AD among adult populations and identifying potential patients may help to develop efficient interventions for timely treatments or even early preventions. However, a validated diagnostic criterion that can be used easily and dependably in a large-scale population setting is the prerequisite to this approach.

In 1980, Hanifin and Rajka⁵ established diagnostic criteria for AD that have been considered as the most useful and valid for more than 20 years. This set of criteria, although appropriate for hospital-based and experimental studies, is impractical for use in large-scale population studies as it contains long and complicated lists of items. Several questionnaire-based instruments have since been developed for large population surveys including International Study of Asthma and Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) diagnostic criteria.⁶, ⁷, ⁸, ⁹ The ISAAC questionnaire was developed for epidemiologic studies of AD approximately a decade after the introduction of the Hanifin and Rajka⁵ criteria to determine the prevalence and severity of AD.⁶ For identification of pediatric patients with AD using this instrument, positive answers provided by parents or caregivers to the following questions are required: “Has your child ever had an itchy rash which was coming and going for at least 6 months?”; “Has your child had this itchy rash at any time in the past 12 months?”; and “Has this itchy rash at any time affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks or around the neck, ears, or eyes?”¹⁰ At approximately the same time, the UKWP attempted to develop a minimum list of practical indicators for AD based on the original Hanifin and Rajka⁵ list of features. To qualify as a patient with AD according to this particular instrument, the study subject must have an itchy skin condition (major criterion) plus 3 or more minor criteria consisting of 4 questions and one physical sign of flexural dermatitis.⁷, ⁸, ⁹

These questionnaires have been validated and used in different parts of the world, mostly among pediatric populations.¹⁰, ¹¹, ¹², ¹³ Few studies have used these criteria for the determination of adult AD prevalence, whereas the validity of how these questionnaire-based instruments performed in the general adult population has not been well confirmed.¹⁴, ¹⁵, ¹⁶ This contributes to the uncertainty in adequately describing AD disease burden among the adult population.

We set out to perform a large-scale cross-sectional study to validate the core ISAAC and UKWP criteria among Taiwanese adults. The physicians' diagnosis based on Hanifin and Rajka⁵ AD criteria was used as the gold standard for comparison. The primary objective of this investigation was to determine the 1-year prevalence of adult AD among nursing staff in a university hospital setting and to propose a set of more efficient diagnostic criteria for identifying adult AD using the questionnaire format.

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Methods 

This was a government-sponsored dermatitis project¹⁷ (National Health Research Institute) and was conducted from August 2007 to May 2008. The study subjects were recruited from the nursing staff of the Kaohsiung Medical University Hospital, which is a highly regarded medical center located in southern Taiwan.

In this investigation, a total of 1218 nursing staff members from various departments of this hospital were invited to participate in this research. Among them, 1131 subjects agreed to participate (response rate, 92.9%), with a comparable pattern for sex and educational level between participants and nonparticipants (P for Chi-squared tests, .462 and .211, respectively) and completed a self-administered questionnaire that included a series of questions with regard to the core ISAAC and the UKWP criteria for the determination of AD (Table I). After completing the study questionnaire, the participants were visited and examined by dermatologists for establishment and confirmation of AD diagnosis based on the Hanifin and Rajka⁵ AD criteria during the past year.

Table I. Sensitivity, specificity, and positive and negative predictive values for individual features of International Study of Asthma and Allergies in Childhood and United Kingdom Working Party diagnostic criteria for atopic dermatitis

ISAAC, International Study of Asthma and Allergies in Childhood; NPV, negative predictive value; PPV, positive predictive value; RV, relative value (sensitivity + specificity – 100); UKWP, United Kingdom Working Party.

This study was approved by the institutional review board and informed consent was given by the participating staff.

Statistical analysis 

Using the AD diagnosis from dermatologists according to the Hanifin and Rajka⁵ approach as a gold standard, the sensitivity and specificity as well as the positive predictive value (PPV) and negative predictive value (NPV) of AD diagnosed based on each individual diagnostic feature for the ISAAC criteria and for the UKWP approach were evaluated, respectively. To assess the efficiency of accurately discriminating the occurrence of AD for individual criteria of the two AD screening strategies, the relative value (RV) (sensitivity + specificity – 100), a measure that simultaneously takes the values of sensitivity, specificity, and chance (50% for each) into account, was introduced. A higher level of RV indicates a higher comparative efficacy for disease diagnosis. This index has been used for studying the efficiency of individual criteria in diagnosing different diseases including AD previously.¹⁸, ¹⁹

Sensitivity and specificity of certain combinations of these individual criteria were also evaluated. For the UKWP approach, these statistics were assessed, separately, while considering itch plus one or more minor criteria. To compare diagnostic accuracy of the two AD diagnostic methods, we performed the receiver operating characteristic (ROC) curve analysis.²⁰ The cutoff value corresponding to the optimal diagnostic accuracy (ie, the highest sum of the respective values for sensitivity and specificity) and the area under curve (AUC) of ROC plot analysis were determined for each diagnostic method. The Hanley and McNeil²¹ approach was used to test the statistical significance of the difference between the areas under the two ROC curves studied. Furthermore, the discrepancy in diagnostic results between the ISAAC and the UKWP approaches was evaluated using the McNemar test.²² For all statistical analysis, P less than .05 was considered significant.

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Results 

Among the nursing staff who participated in this investigation, 90 (8.0%) were given the diagnosis of AD by the dermatologists and 1041 (92.0%) were free from this disease. Most participants were women (99.4%). There was a trend of decreasing prevalence with advancing age that did not achieve statistical significance. More specifically, the prevalence for those aged 29 years or younger, 30 to 39 years, and 40 years or older were 9.1%, 7.2%, and 6.4%, respectively.

The statistical values with regard to the diagnostic accuracy for individual features of the ISAAC and the UKWP diagnostic approaches are shown in Table I. The sensitivity and specificity for individual ISAAC criteria ranged from 48.9% to 83.3% and from 63.1% to 85.2%, respectively. Although a high NPV (95.1%-97.8%) for these diagnostic features was found, the RV was only 34.1% to 46.4%. All UKWP individual criteria had a high specificity (91%-100%). The feature of itchy skin in the last 12 months displayed an 84.3% RV, with 93.3% sensitivity. In contrast, the feature of onset at age younger than 2 years only showed a 10.0% RV, with a very low sensitivity (10%).

Table II presents the sensitivity, specificity, and predictive values of different combinations of the ISAAC and UKWP criteria, as well as the results from ROC analyses. The sensitivity, specificity, PPV, and NPV were 36.7%, 92.9%, 30.8%, and 94.4%, respectively, for ISAAC criteria. The corresponding values for the UKWP original criteria were 42.2%, 99.6%, 90.5%, and 95.2%. Both screening approaches displayed a reasonable efficiency for detecting adult AD, with the AUC of ROC plot being 0.789 and 0.897 (both P < .05). The optimal cutoff value for the ISAAC diagnostic method is the patient having any one criterion (sensitivity + specificity = 145.2%); in contrast, the cutoff value for the UKWP diagnostic method is to identify patients as having AD if itchy skin plus any one criteria were observed (sensitivity + specificity = 176.4%). The sensitivity and specificity for the cutoff value were 90.0% and 55.2% for the ISAAC approach and 82.2% and 94.2% for the UKWP approach, respectively.

Table II. Receiver operating characteristic analysis for detecting atopic dermatitis using International Study of Asthma and Allergies in Childhood and United Kingdom Working Party diagnostic criteria

AUC, Area under curve of receiver operating characteristic plot analysis; CI, confidence interval; ISAAC, International Study of Asthma and Allergies in Childhood; NPV, negative predictive value; PPV, positive predictive value; UKWP, United Kingdom Working Party.

∗Cutoff point that corresponds to optimal diagnostic accuracy.

†Diagnostic results using ISAAC and UKWP criteria.

As compared with the diagnostic discrimination of AD for the ISAAC screening method, the UKWP diagnostic approach showed a significantly higher accuracy in identifying patients with AD (Fig 1) (ROC area: UKWP > ISAAC, P = .0002). In contrast, almost similar diagnostic accuracy was found between the original UKWP criteria (AUC = 0.987) and that excluding the individual feature of onset at age younger than 2 years (AUC = 0.986).

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• Fig 1. 

  Receiver operating characteristic (ROC) curve analysis of United Kingdom (UK) Working Party criteria (A), UK criteria excluding onset at age younger than 2 years (B), and International Study of Asthma and Allergies in Childhood diagnostic criteria (C) for detecting adult atopic dermatitis. Each point on ROC plot represents sensitivity/specificity pair corresponding to particular decision threshold. Significantly different area under curve (AUC) values were obtained between criteria A and C (P value = .0002).

As shown in Table III, the criteria of itch plus any one individual feature of the UKWP criteria produced a significantly better diagnostic result compared with the original UKWP criteria (itchy condition plus 3 minor features) in the evaluation of AD (McNemar test, P = .0001). Compared with the ISAAC diagnostic criteria, a significant difference was also observed (P < .0001).

Table III. Diagnostic comparison for atopic dermatitis between International Study of Asthma and Allergies in Childhood and original United Kingdom Working Party criteria and the modified optimal criteria identified from receiver operating characteristic analysis^∗

ISAAC, International Study of Asthma and Allergies in Childhood; UKWP, United Kingdom Working Party.

∗Modified optimal atopic dermatitis criteria are itch plus any one individual feature of UKWP criteria.

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Discussion 

In this study, we showed that the overall prevalence of AD among our study subjects was 9.5%, 3.7%, and 8% according to ISAAC, UKWP criteria, and physician diagnosis, respectively. As demonstrated in Fig 1, the UKWP criteria served as a better instrument for identifying adult AD as compared with its ISAAC counterpart in Taiwan. Therefore, an effort to evaluate how to optimally apply the UKWP criteria is warranted. Our study further showed that there is a 4.3% difference in AD prevalence with regard to the use of UKWP criteria (3.7%) and dermatologists' diagnosis (8.0%). Intriguingly, similar findings were observed in the reports from a Japanese investigation, in which the prevalence of adult AD was estimated to be approximately 2.9% using the UKWP criteria, but about 6.9% for the counterpart as diagnosed by the dermatologists.¹⁵, ²³ These results suggested that UKWP criteria underestimate the true prevalence of adult AD, and proper modification of this questionnaire may enhance its diagnostic efficacy in identifying adult patients with AD.

A more in-depth analysis of our results revealed that the diagnostic sensitivity for the original UKWP criteria, which requires one major and 3 minor criteria, was rather low (42.2%), although it is highly specific (specificity = 99.6%). In contrast, by fulfilling the major plus one minor criteria, a higher RV (sensitivity + specificity – 100 = 76.4%) was identified, and a significantly better diagnostic accuracy was obtained as compared with the original UKWP and ISAAC criteria (both P < .05, McNemar test). Therefore, we propose that this modified UKWP criteria may be more suitable for identifying adult patients with AD in Taiwan. It is worthwhile to note that a previous report from a hospital-based setting has suggested that the UKWP criteria may be adequate for Chinese patients among all ages.²⁴ However, in their report, the number of adult patients included was small (17 patients with AD aged > 16 years) and may not adequately reflect the validity of the UKWP criteria for adults.

In this study, the modified (major plus one minor) UKWP diagnostic criteria were found to have a higher sensitivity (82.2%) than the original (major plus 3 minor) UKWP criteria (42.2%). This implies that the modified diagnostic approach creates a lower false-negative rate (17.8%) and that it can accurately identify more than 82% of adult patients with AD. However, this modified UKWP criteria revealed a lower PPV (55.2%) than the original United Kingdom criteria (90.5%). This result suggests that subjects given the diagnosis of the modified approach should be further confirmed with another supplementary diagnostic parameter to improve the accuracy of the diagnosis. Alternatively, revision of the minor criteria may also increase PPV of the modified UKWP criteria.

It should be mentioned that when extrapolating our findings to general population screening settings, the original UKWP criteria require a larger sample size to accurately identify an adult AD case as compared with the modified criteria. More specifically, about 30 subjects were required to correctly identify an adult patient with AD in our study using the original criteria (1131/38) as compared with the modified diagnostic approach, which requires screening of approximately 15 subjects to identify an adult patient with AD (1131/74). Several reasons may contribute to the low sensitivity of original UKWP criteria. First, a criterion such as onset at age younger than 2 years and a history of asthma or hay fever may contribute to the poor sensitivity for identifying adult patients with AD given the natural course of allergic disease. It is well recognized that a significant portion of childhood AD and asthma improves with age.²⁵ Therefore, adult patients with AD may not remember whether the onset of their disease occurred before 2 years of age or whether they ever had childhood asthma. Recalling symptoms from long ago is probably not an appropriate criterion for identification of adult AD. In contrast to adult AD, the answers to these two particular questions present no problems for the pediatric population because the answers were usually provided by parents or caregivers, who would have little trouble giving correct answers because such conditions are not likely to be forgotten. In support of this hypothesis, the diagnostic accuracy was similar with or without including the individual criterion of onset at age younger than 2 years as demonstrated in Fig 1. The different predominant clinical manifestations between pediatric and adult AD also likely contributes to the low sensitivity of the UKWP criteria. It has been well recognized that the striking features of childhood AD include xerotic and lichenified flexural eczema of the extremities whereas adult AD is characterized by a prominently red face and chronic lichenified eczema of the trunk.²⁶, ²⁷, ²⁸, ²⁹, ³⁰ It is worthwhile to note that one of the minor UKWP criteria, “visible flexural dermatitis,” showed the highest PPV of 81% although the sensitivity of this criterion was rather low (42.2%). Therefore, incorporation of prominent adult AD features into adult AD diagnostic criteria will likely increase the sensitivity of the test.

It should also be noted that it is not surprising that, as compared with its ISAAC counterpart, the UKWP questionnaire and dermatologists' diagnosis showed better correlation because they are both based on the same criteria. However, as Hanifin and Rajka⁵ AD criteria have been commonly used for more than 20 years, use of the UKWP questionnaire allows for international cross-sectional and longitudinal comparisons. Therefore, the UKWP criteria may have an intrinsic advantage over the ISAAC questionnaire in this regard.

The strengths of this study include the high response rate to the questionnaires, the relatively large study sample size, and confirmation of the diagnosis by dermatologists. In addition, because this study evolved from a government-funded project for occupational dermatitis in the health care sector, the majority of the subjects of this study were well educated with an adequate medical background. For the purpose of validating a diagnostic tool, misclassification because of inadequate understanding of the study questions in this sample should be substantially limited. It should also be noted that this university hospital recruits its nursing staff from all over Taiwan and, therefore, the study population is a good representation of the island population. On the other hand, because the majority of the participants were highly educated women, they may not well reflect the true prevalence of adult AD in Taiwan because there may be education and sex differences in terms of adult AD prevalence. This issue warrants further investigation.

In this study, we demonstrated that the UKWP criteria compared favorably with the ISAAC criteria for identification of adult AD. However, the use of the original UKWP criteria for identification of adult patients with AD in Taiwan is suboptimal. Instead, certain modifications of the original criteria may enhance its diagnostic efficacy for identifying adult AD in the general population. Although very few studies have been performed focusing on adult AD as compared with its pediatric counterpart, it is obvious that adult AD is a commonly encountered condition with a significant impact on quality of life and with negative socioeconomic implications. Therefore, further studies are needed to address this important yet still often neglected issue.

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