Physician Perception of Disease Severity and Treatment Outcomes for Children and Adolescents with Atopic Dermatitis in Emerging Economies

Atopic dermatitis (AD) is a chronic inflammatory systemic disease that typically presents in the early years of life, with a childhood prevalence of approximately 10–30% [1]. Although most cases resolve during childhood, some cases persist through adolescence and into adulthood [2]. It has been estimated that the disease persists through adolescence in 10–20% of children with AD, with prevalence estimates ranging from 0.9 to 21.1% [3].

AD in childhood and adolescence is associated with considerable morbidity and comorbid conditions such as allergies, asthma, and allergic rhinitis, leading to a poor quality of life (QoL) for the patient, their caregivers, and family. Intense itch and sleep disturbance are debilitating aspects of AD, reported in 90% of infants and 69% of adolescents [1, 4]. AD persisting into adolescence typically presents with more severe disease and atopic comorbidities [5]. Patients with moderate-to-severe disease suffer a considerable reduction in QoL, with > 50% of patients reporting their disease to have a “very” or “extremely” large effect [6]. Notably, depression, anxiety, and suicidal ideation are significantly higher in patients with skin diseases, including AD [7, 8]. Although there is a perception that AD reduces in severity or disappears with age, this is not the case for a minority of cases (7%, late resolving AD) [2]. As a disease with a significant burden and high prevalence in childhood, effective treatment, and understanding of how best to approach treatment in these patients, is essential.

Childhood and adolescent disease presentations often require differing approaches to treatment compared to adult patients. For topical treatments, the burden is on caregivers of younger children who are responsible for topical application [9]. Adolescents also have lower adherence to prescribed skincare regimes [1, 10]. For more severe AD, many systemic therapies are only available for off-label use in patients < 18 years of age, including treatments that have been approved for use in adults, such as cyclosporine [11]. Therefore, improving these unmet treatment needs is of particular importance for children and adolescents. This situation is changing with the recent approval of biologics in the younger age groups of ≥ 6 years [13].

Inconsistencies among healthcare professionals when recommending therapies for pediatric patients may lead to suboptimal treatment [9]. One of the biggest barriers to effective shared decision-making between patients and healthcare professionals in AD is a lack of continuity in treating physicians [14], implying variation among treatment recommended by physicians. A considerable discordance has been reported between physicians’ perception of the success of prescription medicine and the perceptions of both pediatric [15] and adult [16] patients, who are less convinced of treatment effectiveness.

Hence, to improve treatment outcomes for pediatric patients with AD, it is important to understand the perception of patients, caregivers, and healthcare professionals about the course of disease and management in real-world settings. This study aimed to characterize the attitudes, beliefs, and behavior of healthcare professionals toward the treatment of moderate-to-severe AD in children (aged 6–11 years) and adolescents (aged 12–17 years). Here, we present the results of the quantitative portion of the physician interviews.

To the best of our knowledge, this is the first study in AD that compares the difference between physician perception of patient disease status with objective assessments in key emerging economies. Younger patients are of particular interest because of the limited available therapeutic options compared with adults and because of the potential reticence among physicians to prescribe more potent therapies [15]. Relatively little is understood about patient and healthcare professional perceptions of AD in emerging countries (based on the International Monetary Fund’s definition [18]), where the burden of AD is expected to increase with urbanization as these economies develop [19]. Therefore, we focused on 11 diverse nations across Asia, Europe, Latin America, and the Middle East to gain a greater understanding of AD in these countries. Notably, despite the cultural and economic differences in the countries sampled, this study confirmed that many aspects of clinical practice and patient and disease experience are consistent.

The responses from this study highlighted discordance between physicians’ perception of a patient’s disease and the recorded disease status as well as between treatment decisions and outcomes. When comparing an initial assessment of severity (based on the physician’s opinion, without comparison against a standard definition or severity scale) against the provided definition, the vast majority of patients with severe AD were assessed as having the less severe disease. Although no criteria were set, by definition, for the physician’s assessment of severity, 7 of 11 countries included in the study recommend using SCORAD as the standard assessment of AD. It could be speculated that physicians’ perceptions would (or should) be based on the tools with which they are most familiar and/or are recommended to use in their clinic. However, even where recommended, validated tools are rarely used in typical clinical practice [20], and there may be less awareness of tools than expected. A study of US physicians found the poor awareness of standard measures “surprising,” with > 30% of dermatologists unaware of SCORAD [21]. The need for effective, validated, and reliable measures have been extensively highlighted by the Harmonising Outcome Measures for Eczema (HOME) initiative, which has recommended appropriate measures for use in both clinical trials [22] and daily clinical practice [23]. Notably, the HOME recommendation for the use of patient-oriented eczema measure (POEM) or patient-oriented (PO)-SCORAD in clinical practice is based on the instruments being “easy to use” and “free” and able to improve the “patient experience” [23].

The average number of days with a flare for patients in this study was estimated at 263 days per year. This is more than double the estimate of Zuberier et al. [24], who reported patients spending 1 in 3 days in flare, and is a significant and potentially unnecessary burden for patients whose quality of life is affected by the active disease. Furthermore, fewer than 10% of patients (including those with no flares) with the most severe disease in this study showed no signs or symptoms between flares and ~ 75% experienced unpredictable flares. Because there is no standard definition of flare, either in standard clinical practice or among trials [25, 26], it is difficult to assess how the physicians interviewed for the current study have defined flare. According to their assessments, the mean treatment time for flares ranged from 17 to 22 days, depending upon the severity, implying that “successful” treatment of flares did not result in complete resolution of flare symptoms. This further indicates an inclination to accept a baseline level on ongoing disease among physicians and the lack of an aggressive treatment strategy to completely resolve symptoms. Moreover, because control is defined as disease activity between flares, the low level of the uncontrolled disease reported in this study could be interpreted as a consequence of the relatively few flare-free days lived by patients and/or that the definition of control used in this study did not capture the true extent of the disease burden.

Few physicians agreed that their patients would be disease-free by 18 years of age, while more physicians agreed that their patients with moderate and mild disease were expected to fully recover. Childhood skin diseases are often considered relatively benign, manageable, and self-resolving [5], and although the effects of AD on quality of life are poorly understood [27, 28], they are reported to be comparable to serious chronic diseases such as cystic fibrosis [29]. Overestimates of remission may contribute to physicians actively avoiding the use of systemic therapies in younger patients, leaving them under-treated and at greater risk of comorbidities. A survey of healthcare providers in Finland indicated that 90% were confident about treating AD in children under 1 year of age, despite 56% of this population selecting inadequate therapies [30] likely to contribute to under-treatment.

Current management of childhood and adolescent AD relies on a limited number of treatments with varying effectiveness [11, 31]. Our study reported low satisfaction with available treatments. New therapeutic options are needed in this population, and those that have recently become available [13, 31] need to be effectively integrated into treatment regimens for patients with moderate-to-severe disease.

Two-thirds of physicians reported being unable to frequently completely eliminate itching and skin symptoms in patients with severe AD, and a similar number were unable to frequently prevent disease progression. This failure to reach goals is despite the use of potent or super-potent topical corticosteroids in the vast majority of patients and a high proportion of systemic corticosteroid and immunosuppressant usage. It is well established that treatment adherence is challenging in this population. Children rely on caregivers to administer systemic and apply topical therapies [9], with the challenge of low adherence [29] exacerbated by parents’ well-documented concerns about corticosteroid use [32]. Adherence among adolescents, who have greater responsibility for self-management, is also low [1, 10]. Low adherence results in poorer resolution, despite high levels of prescription of disease-modifying therapies. There may also be reticence among physicians about prescribing potent or systemic therapies for long periods, especially in patients who do not consider having severe disease. There is a growing understanding that personalized treatment strategies to achieve patient-led goals should be used to guide therapeutic choices that result in effective outcomes [22, 27, 30]. A US survey of physicians and patients under 15 years of age (or their parents) indicated that there was 95% agreement between the two groups in their perception of disease severity [15]. If similar concordance is seen in emerging nations, this would indicate that both patients and physicians underestimate severity, which, in turn, might contribute to under-treatment and/or disappointment with prescribed therapies.

The use of biologic therapy was low in this cohort, which might be due to low availability, high cost, or lack of confidence and experience in biologic use in an adolescent population. Notably, biologics were not licensed for use in the countries at the time of the study; yet the proportion of patients receiving off-label biologics was 8%. These factors combined are likely to contribute to the failure to achieve desired goals. Outcomes from real-world clinical studies support the need for greater use of more effective therapies, including biologics [33] and personalized treatment approaches to achieve the most beneficial outcomes [34]. Clear treatment models that can be followed by all specialties involved in the care of children and adolescents with AD and the need for aggressive treatment strategies, such as the AD Yardstick step-up approach recommending phototherapy, dupilumab, and systematic immunosuppressant therapy for the treatment of patients showing signs and symptoms of poorly or inadequately controlled AD despite an aggressive course of topical prescription therapy for ≥ 3 weeks, have been cited as necessary to lessen disease burden in AD [20].

There are limitations to the current study. Fundamental to the questionnaire- and interview-based research is the selection of participants, who may or may not be representative of local practice. Additionally, spontaneous responses to questions about disease and patients rely on memory and provide no standard baseline on what constitutes severity, control, or flares. Because this research was quantitative, no qualitative follow-up questions were included to assess why particular beliefs were held or responses provided; as such, we can only speculate on the reasons for the apparent discordance between some initial responses and the PRF data. No age-matched, healthy volunteer data are included to compare or provide a baseline for comorbidities or quality of life assessments, and this physician-focused study did not collect patient data to assess concordance between physician and patient perception. Nevertheless, the large number of physicians included and general concordance of responses across countries indicate robust data that need to be considered to improve outcomes for children and adolescents with AD.

In conclusion, children and adolescents’ AD severity appears to be underestimated in emerging economy countries. The significant burden of disease is likely exacerbated by under-treatment and subsequent poorer outcomes for patients, including the associated psychosocial burden suffered by younger patients, their caregivers, and family. Data presented here, as well as surveys from the US and Europe [21, 30], demonstrate that the development and everyday use of practical, easy-to-use, and validated objective measures for a holistic assessment of disease severity and control are essential to ensure that patients are appropriately and effectively treated. Combined with timely guidance on the use of new treatments as they become available, accurate assessment of disease and symptom control in a patient-guided approach will improve AD management and disease control.