Validation of the diagnostic criteria for atopic dermatitis.

OBJECTIVE: To validate the accuracy of newly proposed diagnostic criteria for atopic dermatitis (AD). DESIGN: Double-blind, cross-sectional study comparing the achievement of new criteria with the diagnosis of a dermatologist. SETTING: A private, general dermatology, outpatient clinic. PATIENTS: A sample of 416 consecutive patients attending the clinic within 2 months (146 males and 270 females), consisting of 60 patients with AD and 356 control patients with other skin diseases. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of proposed criteria in the diagnosis of AD. RESULTS: Sensitivity, specificity, and positive and negative predictive values of proposed diagnostic criteria for AD were 10.0% (95% confidence interval [CI], 4.1%-21.2%), 98.3% (95% CI, 96.2%-99.3%), 50.0% (95% CI, 22.3%-77.7%), and 86.6% (95% CI, 82.8%-89.7%), respectively. CONCLUSIONS: These diagnostic criteria for AD are highly specific and are suitable for clinical trials. However, they may not achieve enough sensitivity to be useful for large, population-based epidemiological studies or for routine clinical practice, at least in Iran.     

Alteration of stratum corneum ceramide profiles in spontaneous canine model of atopic dermatitis

Ceramides (CERs) in the stratum corneum (SC) are thought to play a key role in cutaneous barrier function. It has been reported that human SC contains 11 free CER classes and that their profiles are altered in humans with atopic dermatitis (AD). Although decreased proportions of free CERs or quantities of protein-bound CERs in the SC have been reported in dogs with AD, the overall profile of CERs in the canine SC has not been fully elucidated. The aim of this study was thus to investigate the profile of free CERs in the canine SC and to identify alterations in the CER profiles in dogs with AD. Normal-phase liquid chromatography-electrospray ionization-mass spectrometry indicated 11 clusters of peaks for free CER classes, similar to those recognized in the human SC. The fractions of free SC CER in dogs with AD and in breed- and age-matched healthy dogs were quantitatively compared using high-performance thin-layer chromatography. CER[EOS], CER[EOP] and CER[NP], which are known to be decreased in the skin of humans with AD, were also decreased in the skin of dogs with AD. These findings highlight canine AD as a spontaneous animal model for investigating the disruption of CER-associated cutaneous barrier functions in the corresponding human disease.     

Minor cutaneous features of atopic dermatitis in South Korea

BACKGROUND: Minor cutaneous features are important in atopic dermatitis (AD) because they are related to the ethnic or genetic background and to the etiopathogenesis of the disease other than atopic allergy. In addition, they can be used as auxiliary diagnostic criteria in patients with uncertain major features. It is our experience that our AD patients have characteristic features that have not been described previously in the literature. METHODS: AD patients (n = 130) and control subjects (n = 198) were examined for the 32 conventional and seven additional minor features (sandpaper-like skin lesions on elbow/knee/lateral malleolus, hangnail, ventral wrist dermatitis, itchy hyperkeratotic papules on the dorsum of the hands, oily skin, fissured heel, and palmar erythema). The frequency of each feature was compared between AD patients and controls. The diagnostic significance of these minor features was analyzed separately in the childhood and adolescent-adult AD groups, and the age-related changes were documented. RESULTS: The seven additional features were significant for the diagnosis of AD in South Korean patients. Many of the other conventional minor features were also significant. Nine features were of diagnostic importance only in the adolescent-adult AD group, and three features were characteristic only in the childhood AD group. CONCLUSIONS: Our data suggest that ethnic backgrounds influence the phenotype of AD and that an additional seven features need to be examined to confirm the ethnic effect. As the general clinical presentation of AD is dependent upon age, the frequency of minor features varied in the different age groups.     

特应性皮炎临床特征及诊断标准评估：基于2000—2020年165例住院患者的回顾性分析

【摘要】 目的 分析和总结特应性皮炎（AD）患者临床特点,探讨Williams、日本和中国AD诊断标准的满足情况及差异。方法 回顾性分析陆军军医大学西南医院2000年10月至2020年5月期间根据Williams标准或中国张氏标准确诊的165例特应性皮炎住院患者病历资料。采用Williams、日本和中国AD诊断标准重新评估,比较不同标准之间的差异。计量资料组间比较采用t检验、方差分析或秩和检验;计数资料组间比较采用卡方检验或Fisher确切概率检验。结果 165例AD患者中,66例（40.00%）2岁之前发病;95例（57.58%）伴有个人和/或家族特应性疾病史,其中75例伴有个人特应性疾病史,最常见的是过敏性鼻炎（28.48%）、哮喘（20.00%）,50例伴有家族特应性疾病史,30例同时伴有个人和家族特应性疾病史。98例（59.39%）对尘螨过敏,其中Ⅵ级过敏48例。外源性AD 130例（78.79%）,内源性AD 35例（21.21%）,两组发病年龄、嗜酸性粒细胞计数差异均有统计学意义（均P < 0.001）。满足Williams标准142例（86.06%）,不满足者23例,两组之间发病年龄差异有统计学意义（P = 0.007）;满足中国张氏标准150例（90.91%）,不满足者15例,两组之间嗜酸性粒细胞计数差异有统计学意义（P = 0.001）;满足中国姚氏标准160例（96.97%）;全部满足日本标准。满足Williams标准、日本标准、张氏标准和姚氏标准的患者之间发病年龄、嗜酸性粒细胞计数、总IgE水平差异均无统计学意义（P > 0.05）。结论 早期发病的AD更易合并最高级别的尘螨过敏;外源性AD较内源性AD患者发病年龄更低,嗜酸性粒细胞计数更高;满足Williams标准的患者较不满足的患者发病年龄更低,满足中国张氏标准的患者较不满足的患者嗜酸性粒细胞计数更高。     

Most common inhalant allergens in atopic dermatitis, atopic dermatitis/allergic rhinitis, and atopic dermatitis/bronchial asthma patients: a five-year retrospective study

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with a distinctive clinical appearance and distribution. Around 85% of patients have positive immediate skin reaction or specific IgE to different airborne allergens that are in association with respiratory allergy. The aim of this retrospective, open and uncontrolled study was to identify the most common inhalant allergens in AD patients, AD/allergic rhinitis patients, and AD/bronchial asthma patients by skin prick test per year during the 2001-2005 period.     

Senile type atopic dermatitis

Twenty-five patients older than 50 years with atopic dermatitis (AD) diagnosed by the criteria of Tokyo Medical College were investigated on the basis of clinical course and features, IgE RIST, skin reactions, IgE RAST score to several antigens, and IgG4 levels in order to clarify the character of senile AD. The results were compared with the data from younger patients. It was found that the senile type AD showed various type of eczematous lesions whose onset was in the fourth decade of life, and higher IgE RIST and IgG4 levels than healthy people, but lower than younger AD patients. Immediate skin reactions to dermatophagoides and house dust were highly positive in the senile group like the younger group, while the reaction to spices was more highly positive (43%) than in younger persons. Clinically the recognition of the existence of senile type AD and the introduction of antiallergic therapy for severe eczema of old persons are important.     

Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting

Summary One reason why so little is known about the epidemiology of atopic dermatitis (AD) is lack of suitable diagnostic criteria. A simple list of diagnostic criteria for AD for use in epidemiological studies has recently been developed by a U.K. working party. These have performed well in hospital validation studies of subjects with skin diseases. This study sought to validate the newly proposed criteria for AD in a population setting by conducting a cross-sectional survey of 695 schoolchildren aged 3–11 years in three randomly selected primary schools in West Lambeth, London. As a point prevalence measure, the U.K. criteria had a sensitivity of 70%, a specificity of 93%, and a positive predictive value of 47% when compared with a dermatologist's examination findings. Subsequent analysis suggested that most children classified as false positives had suffered from AD in the last year, but were inactive at the time of examination. When adjusted for these cases, the sensitivity and specificity increased to 80 and 97%, respectively, corresponding to positive and negative predictive values of 80 and 97%, respectively. The U.K. diagnostic criteria for AD appear to work well as a 1-year period prevalence measure in London schoolchildren. Further validation in adults and other countries are needed.     

Langerhans cell hyperplasia and IgE expression in canine atopic dermatitis

Langerhans cells appear to be critical for IgE-mediated allergen capture and presentation in human atopic dermatitis. The present study sought to determine whether epidermal (i.e Langerhans cells) and dermal dendritic cells in the skin of dogs with atopic dermatitis are hyperplastic and expressed surface IgE. Frozen sections of lesional or nonlesional atopic and normal control canine skin were immunostained with CD1a-, CD1c-, and IgE-specific monoclonal antibodies. The enumeration of cells was performed by morphometry in both the epidermis and the dermis. Cell counts were compared with each individual’s total serum IgE levels. Higher numbers of epidermal and dermal dendritic cells were present in atopic dogs than in normal control animals. Epidermal Langerhans cell counts were significantly higher in lesional than in nonlesional atopic specimens. IgE⁺ dendritic cells were observed in lesional atopic epidermis and dermis, and nonlesional atopic dermis, but not in normal control skin specimens. The percentages of IgE⁺ dendritic cells were correlated with each patient’s total serum IgE levels. These results demonstrate dendritic cell hyperplasia and IgE expression in canine atopic dermatitis. Increased epidermal Langerhans cell counts in lesional specimens suggest an epidermal allergen contact in canine atopic dermatitis.     

Comparative efficacy of Hanifin and Rajka''s criteria and the UK working party''s diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India

BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features because no definitive diagnostic test exists. Criteria proposed by Hanifin and Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for hospital-based studies but were found not to be suitable for field studies. A UK working party formulated clinical diagnostic criteria that could be used in both hospital and epidemiological settings. Validation studies of the criteria showed widely variable results, probably due to different clinical settings and ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and Rajka's criteria and to assess the comparative efficacy of their criteria and the UK working party's diagnostic criteria in the diagnosis of AD in a hospital setting in North India. SUBJECTS AND METHODS: This study serially included 101 patients with AD and 48 controls of paediatric age group. The study period was from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and negative predictive value (NPV) 91.84%) had a statistical advantage over the UK working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV 97.75% and NPV 76.67%), with a P-value < 0.005.     

Community validation of the United Kingdom diagnostic criteria for atopic dermatitis in Romanian schoolchildren

Although the U.K. modification of Hanifin and Rajka's diagnostic criteria for atopic dermatitis (AD) for use in epidemiological studies has demonstrated good validity and repeatability when previously tested in a U.K. community setting, little is known about its performance in other countries where different cultural, educational and linguistic factors could impair validity. We used a questionnaire to test the validity of the U.K. criteria as a point prevalence measure of AD in 1114 Romanian schoolchildren aged 6–12 years against the clinical diagnosis of a dermatologist with an interest in AD, who was unaware of the questionnaire content and responses. The sensitivity and specificity of the U.K. criteria for AD in this setting was 74% and 99%, respectively, an improvement rather than a deterioration in validity when compared with the previous U.K. study. Test–retest repeatability for all of the questions pertaining to the U.K. criteria using the chance-corrected kappa statistic was high, with values of 0.72 and over. The positive predictive value of the criteria was lower than in the U.K. study (63% compared with 80%, respectively) due to the very low prevalence of AD in this study (2.4%). The validity of a parental report of 'eczema' was poor, with a sensitivity of 22%, specificity of 97% and positive predictive value of 18%. This study suggests that the U.K. criteria perform well in settings outside the U.K., although care has to be taken when using the criteria to ascertain cases in settings where the prevalence of AD is very low.     

Frequency of atopic dermatitis and relevance of food allergy in adults in Germany

Many factors may aggravate atopic dermatitis. The aim of this study was to determine the frequency of atopic dermatitis in an unselected population sample and to evaluate the role of food allergy. Patients with atopic dermatitis were recruited from the population in Berlin, Germany, using a postal questionnaire. Skin prick tests for allergens were performed, followed by food challenges. A total of 1739 questionnaires was returned. In all, 23.5% of patients stated that they had atopic dermatitis, and 146 persons (8.4%) fulfilled our atopic dermatitis criteria after a detailed telephone interview. Of these, 111 were examined, and 28 (1.6%) were identified as currently suffering from atopic dermatitis. Twenty-seven patients were further evaluated: 9/27 were found to be skin prick test negative, 19/27 were skin prick test positive either to pollen and/or food allergens. Nine of 27 were challenged with the suspected food allergen: 1/9 showed a worsening of the eczema, 3/9 had oral symptoms, and 5/9 were negative. In conclusion, only 20% of adults with a positive history of atopic dermatitis show active eczema lesions at a given time point. The data indicate that most individuals with atopic dermatitis were sensitized against pollen allergens and according to that, pollen-associated food allergens. A non-selected AD patient cohort does not frequently suffer from clinically relevant pollen-associated food allergy.     

Community validation of the U.K. diagnostic criteria for atopic dermatitis in Japanese elementary schoolchildren

BACKGROUND: A simple list of diagnostic criteria for atopic dermatitis for use in epidemiological studies was developed by a U.K. working party. This list served well for both hospital patients with skin diseases and in general population within the U.K. OBJECTIVES: To validate the U.K. diagnostic criteria in Japanese elementary schoolchildren, we collected the questionnaires on regular health checkups, which had been completed by parents of schoolchildren in 2001/2002 and 2004/2005. METHODS: Elementary schoolchildren were examined by dermatologists in eight areas (16,152 children) in 2001/2002 and in three areas (3849 children) in 2004/2005. The questionnaire was distributed to the parents 2 weeks before the skin examination, completed by the parents and collected after the survey. RESULTS: In 2002/2002 comparing the U.K. diagnostic criteria with the findings on clinical examination used as the reference standard, the U.K. criteria (1-year prevalence measure) showed a sensitivity of 71.8%, specificity of 89.3% and positive predictive value of 44.7%. In 2004/2005 we confirmed that the U.K. criteria for a point prevalence measure showed a higher positive predictive value (59.9%) compared with that for 1-year prevalence measure (49.3%). CONCLUSION: Now that we know the sensitivity and specificity of the U.K. criteria in the population examined in this study, we will be able in the near future to estimate the prevalence of atopic dermatitis in a similar population with reverse operation by questionnaires alone using these criteria without examination by dermatologists. Therefore, the validation study of U.K. criteria could be useful for future epidemiologic surveys.     

Diagnostic criteria for atopic dermatitis: a systematic review

BACKGROUND: Atopic dermatitis (AD) has a wide spectrum of dermatological manifestations and despite various validated sets of diagnostic criteria that have been developed over the past decades, there is disagreement about its definition. Nevertheless, clinical studies require valid diagnostic criteria for reliable and reproducible results. OBJECTIVE: To summarize the evidence concerning the validity of diagnostic criteria for AD. METHODS: All data sources were identified through searches on Medline, Embase and Cochrane databases. The Quality Assessment of Diagnostic Accuracy tool (QUADAS) was used. Results are presented in a receiver operating characteristic (ROC) plot. RESULTS: Out of the 20 articles that met the criteria, 27 validation studies were identified. In two studies concerning Hanifin and Rajka diagnostic criteria sensitivity and specificity ranged from 87.9% to 96.0% and from 77.6% to 93.8%, respectively. Nineteen validation studies of the U.K. diagnostic criteria showed sensitivity and specificity ranging from 10% to 100% and 89.3% to 99.1%, respectively. Three validation studies concerning the Schultz-Larsen criteria showed sensitivity from 88% to 94.4% and specificity from 77.6% to 95.9%. In one article concerning the criteria of Diepgen, the sensitivity ranged from 83.0% to 87.7% and the specificity from 83.9% to 87.0%. One article studied the Kang and Tian criteria and reported 95.5% sensitivity and 100% specificity. One article validating the International Study of Asthma and Allergies in Childhood (ISAAC) criteria showed a positive and negative predictive value of 48.8% and 91.1%, respectively. CONCLUSION: With this systematic review of the existing sets of diagnostic criteria for AD a varying number of validation studies with varying methodological quality was found. The U.K. diagnostic criteria are the most extensively validated. However, improvement of methodological design for validation studies and uniformity in well-validated and applicable diagnostic criteria are needed to improve future intervention studies and to compare study results.     

Clinical evaluation of atopic hand-foot dermatitis

Clinical manifestations of atopic hand-foot (H-F) dermatitis have not been well studied. This study examined 108 atopic dermatitis (AD) patients with H-F dermatitis between May 1997 and July 1999 at our AD clinic to determine the clinical characteristics of atopic H-F dermatitis and to assess its etiologic associations. It usually began in childhood with an early onset of AD. Pruritus was the most frequent symptom, and erythema, scales, lichenification, hyperkeratosis, fissures, and keratolysis exfoliativa were also common signs. Both the hands and feet were involved in 47 (44.0%) patients, and either hand or foot involvement was observed in 15 (13.9%) and 46 (42.6%) patients, respectively. Palmar or plantar surfaces were more frequently involved than the dorsal aspects. The great toe was affected more often than the other toes. Two-thirds of patients presented with manifestations of the ichthyosis triad and sandpaper-like skin lesions on the elbow, knee, and lateral malleolus. Palmar or plantar hyperhidrosis was reported in 15% and 20%, respectively. The ichthyosis triad-associated group showed a significantly higher incidence of sandpaper-like (thickened, roughened) skin lesions, and these patients had lesions on the dorsal hands or heels and lateral malleolus more frequently than ichthyosis triad-absent patients. The hyperhidrosis-associated group showed an association with glassy lesions, localized to palmar or plantar areas. Atopic H-F dermatitis is associated with the nonallergic etiologies of AD and clinical subgroups can be identified on the basis of nonallergic backgrounds.     

Evaluation of diagnostic criteria for atopic dermatitis: validity of the criteria of Williams et al. in a hospital-based setting

BACKGROUND: Surveys of the prevalence of atopic dermatitis (AD) have been carried out world-wide, but the results vary widely. The differences probably result from the use of different diagnostic criteria. Williams et al. proposed minimum, simplified, diagnostic criteria that require no invasive test and are easy to use. Pilot studies in European countries showed their suitability for implementation both in hospitals and in the community, and their high sensitivity and specificity. OBJECTIVES: To evaluate the potential practical value of the criteria of Williams et al. in the Chinese population. METHODS: The criteria of Hanifin and Rajka (gold standard), Williams et al. and Kang and Tian were applied and compared in 111 patients with AD and 121 control subjects with other skin diseases in three out-patient centres in China. RESULTS: The criteria of Williams et al. showed a similar diagnostic efficiency to that of the gold standard, with the sensitivity, specificity and kappa value reaching 95.50%, 97.52% and 0.93, respectively. No significant difference was found between the criteria of Williams et al. and those of Kang and Tian (chi2 = 0.69, P > 0.05). 'Onset under the age of 2 years', a criterion of Williams et al. could be used in subjects of any age. CONCLUSIONS: The diagnostic efficiency of the criteria of Williams et al. was basically similar to those of Hanifin and Rajka and of Kang and Tian in our out-patient settings. However, those of Williams et al. were easier to apply and required no invasive tests.     

Qualitative vs. quantitative atopic dermatitis criteria – in historical and present perspectives

This review summarizes historical aspects, clinical expression and pathophysiology leading to coining of the terms atopy and atopic dermatitis, current diagnostic criteria and further explore the possibility of developing quantitative diagnostic criteria of atopic dermatitis (AD) based on the importance of atopic features – subjective, objective, and those derived from laboratory tests – the new partly promising AD biomarkers. ‘Atopy’, introduced in 1923, denoted ‘the sense of a strange disease without a precise place in the body’. A decade later, Sulzberger and Hill, first defined ‘atopic dermatitis’. The pioneering well‐recognized criteria, ‘Hanifin & Rajka’ (Acta Derm Venereol, 92 , 1980, 44), were developed empirically on ‘clinical experience’ and expert consensus. As opposed to the widely used, rather anamnestic ‘UK Criteria’ (1994), they have few formal validation studies, but appear to well embrace various atopic phenotypes. Pruritus, xerosis, typical morphology/distribution of dermatitis and tendency to a relapsing/chronic course are common basic features in AD criteria, whereas skin sensitivity, heredity and various ill‐defined atopic stigmata also seem to comprise the atopic phenomenon. Specific pheno‐ and endotypes are now emerging potentially enabling us to better classify patients with AD, but the influence of these on the diagnosis of AD is so far unclear. Few diagnostic models use quantitative scoring systems to establish AD cases from normal population, which, however, may be useful to better study and manage this disease. Long‐term prospective observational studies, from which few are available at this point, along with interventional studies, are a perquisite and will provide the best option to improve our understanding of its complex characteristics and etiology.     

The diagnostic value of atopy patch testing and prick testing in atopic dermatitis: facts and controversies

We conducted a systematic Medline search of the literature (1998-2008) on the criteria for performing the skin prick test and atopy patch testing (APT) to determine their utility in atopic dermatitis (AD). The skin prick, scratch, and skin patch tests are performed to identify which allergen is causing eczematous skin symptoms in patients with AD, or sneezing, nasal congestion, itchy eyes, wheezing, skin rash, and swelling. Many allergens in foods, drugs, and environmental substances (eg, ragweed and fungus), as well as contact allergens, can elicit eczematous skin reactions after epicutaneous application. Because no gold standard exists for aeroallergen provocation in AD, the APT is currently used to evaluate allergen without comparison with another accurate and reliable method. The APT is presumed to reflect delayed-phase clinical reactions. Even with delayed onset of symptoms (more than 2 hours after food ingestion), APT findings were not consistent among AD children. The APT could be used in children with gastrointestinal reactions to foods as well as AD. After standardization, the APT may provide further diagnostic information in addition to the skin prick test and serum immunoglobulin E values and may be able to evaluate the actual clinical relevance of immunoglobulin E-mediated sensitizations for eczematous lesions. The European APT model used with standardization of allergen concentration and vehicle may provide an important diagnostic tool to select patients for avoidance and for procedures of allergen-specific immunotherapy, but the clinical relevance of positive APT reactions awaits standardized provocation and avoidance testing.     

The millennium criteria for the diagnosis of atopic dermatitis

Abstract: Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnositic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.