Atopic dermatitis (AD), or atopic eczema, is a chronic inflammatory skin disease that appears in early childhood and affects between 7% and 20% of children and between 2% and 7% of adults.1–3 Although there is evidence of great geographical variability, it appears that the incidence and prevalence of this disease have increased in recent years.3,4 The symptoms of AD are intense pruritus, dry skin, and skin lesions that appear in acute episodes of exacerbation, or flares.5,6 Because of its clinical manifestations, in many cases AD has a negative impact on the patient‘s health-related quality of life (HRQOL).7–9 In children, specifically, AD can interfere with sleep and impair performance in school and leisure activities, with the resulting consequences for patients’ personal, family, and social lives.7

The etiology of AD has been linked to genetic, biological, immunologic, and environmental factors.5,6,10 The most common gene changes associated with AD are mutations in the gene encoding filaggrin.11 In response to this etiologic complexity, a comprehensive theoretical model has been proposed that describes genetic deficiency in epithelial cells and the resulting epidermal barrier dysfunction as a predisposing factor for AD.5 This process would be exacerbated by the presence of allergens that increase immunoglobulin E (IgE) sensitization, causing the immune system to become hypersensitized. This hypersensitization would favor the persistence of underlying subclinical inflammation, which, in turn, would facilitate the appearance of new AD flares. Geographical differences in the prevalence of AD suggest that other environmental factors—related to climate3,4 and pollution1—also play a role. In addition to these factors, the occurrence of flares has also been associated with articles of clothing, the presence of mites and dust in the home, cosmetics, certain foods, dietary changes, physiological stressors (infections, sweat, etc.), and emotional stressors (psychological stress).12–14

These possible triggers were analyzed in an observational study that included 4243 children with AD under the age of 14 years and 978 controls matched for age and sex.15 The study found that colder climates (Cantabrian and continental areas of the Iberian Peninsula) were associated with a greater number of flares. The most common flare triggers were changes in climate (reported by 64% of patients), followed by stress in the patients (26%), and personal hygiene products (21%), while stress in the parents (16%), dietary changes (15%), and changes in household cleaning products (4%) were less frequent.

Because multiple factors play a role in AD, the optimal approach to treating the disease requires patient and parent education as well as the active participation of the physician.6,10 In this study, we aimed to describe the triggers that patients with moderate to severe AD perceive as having the largest influence on the exacerbation of the disease and the patient-reported degree of adherence to medical recommendations. We also evaluated the degree of disease control perceived by patients and dermatologists and the impact of the disease on HRQOL in order to obtain a picture of the real situation currently faced by patients with moderate to severe AD.

This was a multicenter, cross-sectional, epidemiologic study involving 30 dermatologists in various Spanish autonomous communities. Each dermatologist consecutively enrolled the first 5 patients he or she saw who met the inclusion criteria. Data were collected for children (aged 2-15 years) and adults (aged 16 years or older) who had been clinically diagnosed with moderate to severe AD according to the clinical judgment of the dermatologist. (Patients with a diagnosis of mild AD were excluded from the study.) Patients enrolled in the study had a disease duration of at least 12 months and, at the time of consultation, had an AD flare of moderate to severe intensity according to defined clinical criteria (Investigator‘s Global Assessment [IGA] score>2). The patients (or their legal guardians, in the case of children) were required to give written informed consent before being enrolled in the study. The study protocol was approved by the clinical research ethics committee of Hospital 12 de Octubre, and the study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki and subsequent amendments.

In the adult group (n=135), 10 patients were excluded because their disease severity at the time of consultation was mild according to the IGA scale. In the children's group, a total of 148 patients were initially enrolled in the study. After reviewing the inclusion criteria, we excluded 32 patients because their disease severity at the time of consultation was mild (n=7) or because they had been diagnosed with AD less than 12 months earlier (n=25). As a result, the study included 125 adults and 116 children, close to 50% of whom were female (Table 1) and all of whom had a moderate to severe flare (IGA>2).

At the time of diagnosis, 72.8% of adults and 70.7% of children were diagnosed with moderate AD. At the time of consultation, nearly 50% of adults and 53.4% of children had moderate erythema according to the IGA scale. SCORAD results showed that most patients—both adults and children—had moderate to severe AD at the time of consultation (Table 1). Although patients were included in the study only if they presented erythema and/or papulation of at least moderate intensity (IGA>2), 7.2% of adults and 6.0% of children had a SCORAD result of less than 15 points. According to the CGI-S values assigned by the dermatologists, nearly 58% of adults were moderately ill and 5% were severely ill (figures consistent with the results of the specific tests) while 47.5% of children were markedly ill and 5.2% were severely ill (Table 1).

The most common factors perceived by patients as triggers of flares (Figs. 1 and 2) were perfumes and personal hygiene products (44% of adults, 34.5% of children), articles of clothing (41.6% of adults, 37.1% of children), presence of mites or dust in the home (40% of adults, 36.2% of children), sudden changes in temperature (36% of adults, 42.2% of children), and stress (40% of adults, 36.2% of children). In adults, the foods most frequently perceived as triggers were sweets (3.88%), seafood (2.33%), and eggs (2.33%); in children, eggs (7.63%) and fish (3.05%) were the most common.

Figure 1.

Percentage of adults in whom atopic dermatitis lesions were associated with a possible trigger, both generally in the course of their illness and specifically in relation to the current flare.

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Figure 2.

Percentage of children in whom atopic dermatitis lesions were associated with a possible trigger, both generally in the course of their illness and specifically in relation to the current flare.

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In 76.8% of adults and 82.8% of children, emollients were the therapeutic approach of choice during the flare (Fig. 3). The emollient was applied directly on the lesions in 22.4% of adults and 34.5% of children. In contrast, 19.2% of adults and 24.1% of children avoided active lesions when applying the emollient. Topical pharmacotherapy was used by 84.8% of adults and 77.6% of children. However, at least 13.6% of adults and 17.2% of children were not using any topical pharmacotherapy at the time of consultation, even though there was no difference in disease severity (as measured by the SCORAD index) between these patients and those who were using topical pharmacotherapy. The differences in SCORAD scores (mean [SD]) between treated adults (49.12 [20.86]) and untreated adults (48.72 [15.51]) and between treated children (43.44 -[9.88]) and untreated children (46.42 [14.67]) were not statistically significant (Mann-Whitney U test, P>.1in both comparisons).

Figure 3.

Site of application in patients who use emollients, by study group.

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Corticosteroids were the most frequently recommended topical treatment (72% of adults and 85.3% of children). Calcineurin inhibitors were used by 59.2% of adults and 47.4% of children. Antihistamines were taken by 59.2% of adults and 51.7% of children. Maintenance pharmacotherapy was used for disease control by 47.2% of adults and 49.15% of children.

As for adherence to administration recommendations, pharmacotherapy was first applied on the day the symptoms appeared in 38.4% of adults and 37.9% of children. Pharmacotherapy was initiated within 3 days of the appearance of symptoms in 15.2% of adults and 13.8% of children and even later—within the first week—in 18.4% of adults and 13.8% of children. In fact, more than a week elapsed before pharmacotherapy was started in 13.6% of adults and 12.1% of children. According to these findings, no treatment was initiated at the onset of the flare in 47.2% of adults and 39.7% of children. An additional 13.6% of adults and 17.2% of children had not applied any topical pharmacotherapy, despite the presence of a moderate to severe flare.

A majority of patients declared that they adhered to the following medical recommendations: application of pharmacotherapy, skin moisturizing, and the use of special soaps for their skin type (Table 2). The recommendations followed least often by the patients in their daily lives were avoidance of sudden changes in temperature and dietary advice.

Disease control was seen as insufficient or worse in a large percentage of cases (Table 3). The dermatologists rated the degree of disease control as excellent, good, or sufficient in only 38.4% of adults and 40.5% of children. From the patients’ perspective, disease control was excellent, good, or sufficient in 55.2% of adults and 67.2% of children.

In adults, significant differences were found in perceived disease control and HRQOL as a function of symptom severity at the time of consultation (mild or moderate vs severe SCORAD scores) (P<.01; Table 4). In children, differences in these variables were also present in the same direction, but they were only significant in the case of HRQOL (Table 4). Moods and personal and social performance were affected in some patients in both groups, as reflected in the total scores on the various scales used to assess HRQOL (Table 5).

In recent years, a generalized consensus has emerged in leading scientific publications that AD is a disease of multifactorial etiology that requires a multifactorial, individualized approach in order to strengthen the effectiveness of the overall treatment.6,10 Therefore, during flares, topical moisturizing treatment and the avoidance of patient-specific trigger factors should therefore be recommended in addition to various pharmacological disease-control strategies such as topical corticosteroids. As an alternative to corticosteroids, anti-inflammatory treatments based on topical calcineurin inhibitors are very important in the treatment of flares; they also allow a proactive treatment approach that reduces the number of flares and increases flare-free time.22,23 Antibiotics for microbial infections, phototherapy, dietary recommendations, psychological care to reduce stress, and educational programs round out the clinical arsenal currently used to manage AD.

Educational programs for patients and caregivers generally focus on raising awareness about the chronicity and unpredictable course of AD, describe the important role of the epidermal barrier, and highlight the importance of the multidisciplinary approach followed by healthcare professionals in order to optimize long-term disease control.19,24 These programs usually stress the importance of skin care adapted to the needs of patients with AD and avoidance of specific triggers. They also include psychological counseling aimed at helping patients to manage stress, control the itching-scratching cycle, and cope with the disease. Although there have been exceptions, educational programs have generally succeeded at improving doctor-patient relationships, adherence, and HRQOL of patients and their families.24–26 In any case, these experiences show that the patient's attitude and motivation are extremely important for the control of AD because they influence adherence to the physician's prevention and treatment indications. This is why, in the present study, we chose to focus on the perspective of the patients, including the exogenous or environmental factors that they believe trigger flares, their attitudes towards treatment, their adherence to recommendations, and their perceived degree of disease control.

The main perceived trigger factors were cosmetics, articles of clothing, airborne allergens, stress, and sudden changes in temperature. These are the same factors that have generally been reported in the scientific literature.15 However, diet was not identified as an exacerbating factor in the current flare, despite the fact that it should be considered as a possible trigger. It is possible that patients did not mention diet because they habitually avoid certain foods—although food avoidance is not the most strictly followed indication, especially among adults—or because they perceive foods as having no exacerbating effect (as has been found in adolescents).27 Another possible explanation is the fact that we excluded patients under age 2 years, a group in which dietary recommendations could have a larger role.

Although most patients reported a high degree of adherence to medical recommendations—especially with regard to skin moisturizing, the use of special soaps, and the application of topical pharmacotherapies—deficiencies were observed in the application of emollients and pharmacotherapies. Emollients were not used to moisturize the skin in 23.2% of adults and 17.2% of children. In addition, between 15% and 23% of adults and children applied no pharmacotherapy whatsoever, even though they had a flare of at least moderate severity and a mean disease duration of 239.08 and 68.72 months, respectively. In addition, only 38.4% of adults and 37.9% of children started using topical agents on the first day the symptoms appeared. It would be interesting to determine the reasons for the patients’ treatment adherence problems, which are consistent with the results of earlier studies.21,28 These problems may reflect the patients’ fear of adverse effects, ignorance regarding proper application, and lack of information about the safety of the treatments.8,21,28,29

Finally, the degree of disease control was considered to be insufficient or worse by most dermatologists and a large percentage of patients (41.6% of adults and 27.6% of children). In this regard, the situation in Spain does not appear to have improved since 2006, when the study by Zuberbier et al.,21 was published.

The chief limitation of our study was its cross-sectional design, which prevented us from analyzing in detail the relationship between adherence and disease control, or changes in these variables and HRQOL, for example, when a flare is not present. However, we were interested in analyzing adherence to recommendations and disease control at the time of consultation for a flare, which is precisely when higher adherence rates would be expected.30 Another limitation of the study was the exclusion of children less than 2 years of age. Because of this, we were unable to analyze triggers or adherence to medical recommendations in that group of patients.

It is clear that much work is still needed in the design and introduction of specific protocols for informing patients about the correct multidisciplinary approach to AD and the safety profiles of the available treatments. As mentioned above, such protocols would probably be very useful for improving adherence to medical recommendations and disease control in AD.

Funding for this study was provided by Astellas Pharma S.A.

Dr. A. M. Mora is employed by Astellas Pharma España.

The other authors declare that they have no conflicts of interest.