
==== Front
Dermatol Ther (Heidelb)
Dermatol Ther (Heidelb)
Dermatology and Therapy
2193-8210
2190-9172
Springer Healthcare Cheshire

39162764
1246
10.1007/s13555-024-01246-5
Original Research
Management of Moderate-to-Severe Atopic Dermatitis in Adults: A Cross-Sectional Survey of Dermatologists Within the Asia–Pacific Region
Chu Chia-Yu 1
Chan Yung 2
Wananukul Siriwan 3
Cheng Hao 4
Chandran Nisha Suyien 5
Bhat Ramesh 6
Son Sang Wook 7
Liao Han-Fang 8
http://orcid.org/0009-0008-9193-9844
Gardiner Sean Sean.Gardiner@pfizer.com

9
http://orcid.org/0009-0005-6929-665X
Ng Qi Qing 10
http://orcid.org/0000-0001-8658-8172
Yeo See-Hwee 10
http://orcid.org/0000-0003-2874-1786
Chen Sophie Bozhi 10
Kataoka Yoko 11
1 grid.19188.39 0000 0004 0546 0241 Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
2 Apex Dermatology Institute, Hong Kong, China
3 grid.7922.e 0000 0001 0244 7875 Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
4 https://ror.org/00ka6rp58 grid.415999.9 0000 0004 1798 9361 Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
5 https://ror.org/04fp9fm22 grid.412106.0 0000 0004 0621 9599 Division of Dermatology, Department of Medicine, National University Hospital, Singapore, Singapore
6 grid.414767.7 0000 0004 1765 9143 Father Muller Medical College, Mangalore, India
7 grid.222754.4 0000 0001 0840 2678 Department of Dermatology, Korea University College of Medicine, Seoul, South Korea
8 Pfizer Ltd, Taipei, Taiwan
9 Pfizer Singapore, 80 Pasir Panjang Road, #16-81/82 Mapletree Business City II, Singapore, 117372 Singapore
10 IQVIA Solutions Asia, Real World Solutions, Singapore, Singapore
11 Department of Dermatology, Osaka Habikino Medical Center, Habikino, Japan
20 8 2024
20 8 2024
9 2024
14 9 25592576
27 5 2024
25 7 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Introduction

Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia.

Methods

Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia–Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory.

Results

Data from 271 dermatologists were included for analysis. About one-third (31.7%) reported that they referred to the Hanifin and Rajka criteria during diagnosis. The majority of dermatologists used clinical impression when assessing AD severity and treatment response. Reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. More than half of dermatologists preferred adding systemic anti-inflammatory medication for patients who did not respond to maximized topical treatment, while 43.6% would switch to another systemic medication for those failing to respond to maximized systemic treatment. Topical corticosteroids were frequently selected by dermatologists. For systemic therapies, oral corticosteroids were most frequently used, followed by cyclosporin and dupilumab. Narrow-band ultraviolet B was the most common phototherapy reported (84.9%). There was considerable variation in estimated average and maximum durations of therapies used to treat AD.

Conclusion

This study has provided insights on the real-world management of moderate-to-severe AD in the Asia–Pacific region. The diverse approaches in diagnosis and treatment highlight the multifactorial nature of AD, reliance on clinical judgement, and importance of personalized care. To improve outcomes in patients with AD, it will be crucial to develop biomarkers for diagnosis, reduce subjectivity in assessment, as well as promote access to newer and effective therapies.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-024-01246-5.

Keywords

Asia
Atopic dermatitis
Cross-sectional
Dermatologist
Eczema
Management
Questionnaire
Real-world
Survey
Treatment
http://dx.doi.org/10.13039/100018372 Pfizer Hong Kong issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
==== Body
pmcKey Summary Points

A multinational cross-sectional survey was conducted among dermatologists to assess current approaches in atopic dermatitis (AD) diagnosis and management in Asia.	
Dermatologists commonly used the Hanifin and Rajka criteria, local guidelines, and their clinical impression to diagnose AD.	
For patients who did not respond to maximized topical treatment, dermatologists preferred to add on systemic anti-inflammatory medication.	
Topical corticosteroids were most frequently selected for AD management, while narrow-band ultraviolet B was the most common phototherapy used.	
For systemic treatment, oral corticosteroids were most commonly selected, followed by cyclosporin and dupilumab.	
There was considerable variation in reported average and maximum durations of therapies used to treat AD.	

Introduction

Atopic dermatitis (AD) is a common chronic and relapsing inflammatory skin disease that affects people of all ages and ethnicities. Although often considered a childhood disease, AD affects a significant number of adults, with a prevalence of up to 10% in developed countries [1] and an increasing trend in developing countries [2]. In the Asia–Pacific region, some countries (e.g. Singapore, Malaysia) have a higher prevalence of AD in adults than other countries (e.g. China), possibly due to higher rates of disease onset in adulthood [3]. AD is the leading cause of global burden from skin disease which significantly impacts patients’ quality of life, causing symptoms such as erythema, edema, xerosis, and pruritus [4, 5]. It is also associated with substantial psychosocial issues such as sleep disturbance, depression, and anxiety, contributing to work absenteeism and decreased productivity [6–8]. For those with moderate-to-severe AD, the worsening symptoms bring about heavier psychological and economic burden [9]. These patients may also suffer from concomitant atopic (e.g. asthma, food allergy) and/or non-atopic comorbidities (e.g. anxiety, depression).

The pathogenesis of AD is multifactorial and involves the complex interplay of impaired skin barrier function, immune dysregulation, genetic susceptibility, and environmental factors. Currently, there is no cure for AD. Disease management goals include symptom reduction and flare prevention [10]. While many patients respond to basic skin care (e.g. emollients), environment control, and topical medications including topical corticosteroids (TCS) and calcineurin inhibitors (TCIs), a significant percentage of them have recalcitrant disease which requires more holistic and systemic treatment [11]. Adults with moderate-to-severe AD refractory to topical treatments may be considered for phototherapy, which involves exposing the skin to specific wavelengths of ultraviolet (UV) light under controlled conditions [12]. In addition, systemic drugs such as corticosteroids and biologics taken orally or injected to manage moderate-to-severe AD are also considered when topical treatments are ineffective [12]. Although treatment guidelines are available, adherence to recommendations (especially systemic treatments) is low in Asian countries [13]. A previous review across several continents including Asia revealed that treatment modalities can vary across countries, potentially due to differences in patient preferences, availability of new therapies in the market, and multiple existing guidelines recommended for AD treatment [13]. For example, TCIs are recommended as first-line treatment in various guidelines including the ones adopted in the Middle East and Latin America, whereas they are recommended as second-line treatment in other guidelines more commonly used in Asia.

To date, the available evidence on real-world management of moderate-to-severe AD among Asian adults remains limited. The variability in diagnostic criteria, treatment preferences, and clinical decision-making may lead to inconsistencies in patient care and outcomes. This cross-sectional study aims to address this gap by evaluating the real-world practices in the diagnosis and treatment of moderate-to-severe AD, providing a comprehensive picture of the patient’s journey from diagnosis to treatment.

Methods

Setting

Practising dermatologists who regularly treat patients with AD were recruited from eight Asia–Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. Ethical approval was received from the following institutional review boards (IRBs): Korea University Ansan Hospital, Chulalongkorn University, Father Muller Hospital, NPO MINS, National Taiwan University Hospital, Hong Kong Doctors Union, and Sir Run Run Shaw Hospital. The Parkway Independent Ethics Committee granted an exemption from review. The study was conducted in accordance with the protocol, Guidelines for Good Pharmacoepidemiology Practices, and the Declaration of Helsinki. All participants provided informed consent.

Study Population

To be eligible for participation, a physician was required to have at least 2 years of experience as a board-certified dermatologist, treat an average of two or more adult patients with moderate-to severe AD per month, and spend at least 60% of their working time in direct patient care (equivalent to three out of five working days).

We identified potential participants through physician panels, contact lists, and other relevant directories/databases in each territory of interest. Contact was established with eligible dermatologists via a study invitation email containing materials including links to screener, participant information sheet, informed consent form, and survey questionnaire. Interested physicians underwent a screening process to confirm their eligibility. All participants received fair compensation for their time spent in completing the survey.

Study Instrument

The survey was designed to capture information related to AD diagnosis and management from the perspective of practising dermatologists. Items to be included in the questionnaire were initially developed on the basis of a comprehensive literature review which included systematic reviews, clinical guidelines, and key primary studies focused on the management of moderate-to-severe AD in adult patients [14–16]. These proposed items were then selected by members of a steering committee (StC) on the basis of their clinical knowledge to ensure relevance and accuracy within the local context. The StC, comprising one dermatology expert from each territory, totalling eight members, was formed as part of the research team. The StC played a critical role in validating the study design and refining study materials. Multiple online meetings with the StC members were conducted to improve the clarity, comprehensibility, and clinical relevance of the survey questionnaire. Specific suggestions included rephrasing ambiguous questions, adding options for commonly used diagnostic criteria, and ensuring that the treatment options are appropriate in local context and able to comprehensively cover all common therapies used in the included territories. Subsequently, the questionnaire was revised by incorporating feedback from the StC and translated into local languages by a professional translation agency. The translated study materials were reviewed by the IRB in each territory. After IRB approval was obtained, the local language version of the survey was piloted among two dermatologists (including one StC member and one eligible dermatologist) from each territory to ensure that there was no issue with language and survey programming. The survey was then finalized, and enrolment continued.

The 33 items in the questionnaire were finalized and sorted into three sections: diagnosis of moderate-to-severe AD (6 items), overall management (7 items), and specific treatment options (20 items). For the purpose of results interpretation, moderate-to-severe AD was defined as a condition not adequately controlled by standard and optimised topical treatment (including emollients, TCS, and TCI), apart from occasional short-term flares caused by factors such as skin infection [16]. The detailed questionnaire is included in the Supplementary Materials.

Data Collection

The survey was administered from March to June 2023. During data collection, we observed varied responses rates across different territories, with some regions showing lower participation. To address this, we extended the data collection period and used multiple channels (e.g. emails, phone calls) to reach out to potential participants. To reduce selection biases, dermatologists were randomly invited from physician panels and relevant directories in each territory to ensure a more representative sample. In addition, participants’ identities were kept confidential to avoid response bias. The questionnaire was pilot tested among a small group of dermatologists, including StC members, to refine the questions and improve clarity. Data from the pilot phase were excluded from the final analysis.

Statistical Analysis

Only data from fully completed submissions were analysed using descriptive statistics. Categorical variables were reviewed for consistency and encoded appropriately. Where applicable, integer values were assigned to categories of an ordinal variable based on their order, while each category of a nominal variable was represented using binary values in a separate column. Categorical variables were presented using frequencies and percentages, while continuous variables were presented using medians and interquartile ranges (IQRs).

Results

A total of 271 dermatologists from eight territories were included for analysis. As presented in Table S1 (see Supplementary Materials), more than half (59.0%) had more than 10 years of post-training experience in AD management. The recruited dermatologists reported that they treat a median of 30 (IQR 50.0) patients with moderate-to-severe AD monthly. The majority practised in university teaching hospitals (32.8%), followed by public or government hospitals (26.9%), private clinics (26.2%), and private hospitals (15.2%).

Diagnosis of AD

Higher proportions of dermatologists reported that they referred to the Hanifin and Rajka criteria (31.7%) and local guidelines (27.7%), compared to other international guidelines; 21.4% of them also indicated that their diagnosis of AD was based on their own clinical judgment or impression (Table 1). The majority assessed the severity of AD on the basis of clinical impression (74.5%), instead of subjective symptoms only or utilizing existing severity measurement scales such as the Eczema Area and Severity Index (EASI) and Scoring atopic dermatitis (SCORAD). Similarly, more dermatologists used clinical impression (61.3%) than scoring tools (55.7%) when differentiating between mild and moderate-to-severe AD. When asked about how they would define a flare, most dermatologists defined it as the return of symptoms (80.4%), or an episode requiring either escalation of treatment or seeking additional medical advice (74.2%).Table 1 Diagnosis of atopic dermatitis in clinical practice

	N = 271	
n	%	
Criteria for AD diagnosis	
 The Hanifin and Rajka criteria	86	31.7	
 Local guidelines	75	27.7	
 Clinical impression	58	21.4	
 American Academy of Dermatology (AAD) criteria	32	11.8	
 The UK Working Party diagnostic schemes	15	5.5	
 Others (e.g. Willams criteria, Zhang’s criteria)	5	1.8	
Methods to assess AD severitya,b	
 Clinical impression	202	74.5	
 Eczema Area and Severity Index (EASI)	146	53.9	
 Scoring atopic dermatitis (SCORAD)	112	41.3	
 Body surface area	111	41.0	
 Subjective symptoms only (including pruritus, sleep loss)	108	39.9	
 Investigator’s Global Assessment (IGA)	49	18.1	
 Laboratory test	44	16.2	
Ways to differentiate mild AD from moderate-to-severe ADa	
 Clinical impression	166	61.3	
 Severity scores using scoring tools	151	55.7	
 Body surface area involved with severe inflammation	139	51.3	
 Need for systemic anti-inflammatory therapy	116	42.8	
 Level of impact on patient’s everyday activities and psychosocial well-being, sleep condition etc.	112	41.3	
 Need for higher potency topical steroids	58	21.4	
 No clear differentiation	4	1.5	
Definition of flarea	
 Return of symptoms including a red, itchy skin rash	218	80.4	
 Episode requiring escalation of treatment or seeking additional medical advice	201	74.2	
 Need to use topical steroids or further anti-inflammatory medications	116	42.8	
 Self-defined by patient	95	35.1	
 Increment of Investigator’s Global Assessment (IGA) score of at least 2 points	72	26.6	
 Reached IGA score of 4 or higher	25	9.2	
AD atopic dermatitis

aAs multiple options can be selected, the sum of frequencies across all categories exceeds 100%

bOther methods, including Six Area Six Sign Atopic Dermatitis (SASSAD), Patient-Oriented Eczema Measure (POEM), and Three Item Severity Scale (TISS), are mentioned by a limited number of participants (i.e. less than 3%), hence they are not presented in this table

Among the total of 271 dermatologists, 258 provided responses on the frequency of clinical tests performed for diagnosing AD, while 13 indicated that they have never conducted any test. As shown in Table 2, serum IgE and differential blood count were the most frequently conducted tests, with 121 (46.9%) and 113 (43.8%) dermatologists performing them for more than 50% of the time, respectively. Patch testing, skin biopsies, potassium hydroxide preparation, and skin prick test were less commonly used, with over 80% of dermatologists reporting that they either never used these tests or used them for less than 25% of the time. Genetic testing was least frequently used, with 83.3% of dermatologists indicating that they did not utilize it at all.Table 2 Frequency of clinical tests performed for the diagnosis of atopic dermatitis

N = 258a	Not at all	< 25% of the time	25–49% of the time	50–74% of the time	≥ 75% of the time	All the time	
n	%	n	%	n	%	n	%	n	%	n	%	
Serum IgE	26	9.6	74	27.3	37	13.7	29	10.7	49	18.1	43	15.9	
Differential blood count	46	17.8	55	21.3	44	17.1	24	9.3	40	15.5	49	19.0	
Patch testing	73	28.3	134	51.9	31	12.0	13	5.0	5	1.9	2	0.8	
Skin biopsies	82	31.8	159	61.6	13	5.0	4	1.6	0	0.0	0	0.0	
Potassium hydroxide (KOH) preparation	103	39.9	121	46.9	21	8.1	8	3.1	4	1.6	1	0.4	
Skin prick test	118	43.5	102	37.6	28	10.3	7	2.6	3	1.1	0	0.0	
Genetic testing	215	83.3	41	15.9	2	0.8	0	0.0	0	0.0	0	0.0	
aAmong all 271 respondents, 13 (4.8%) indicated that they never conducted any clinical tests

Management of AD

Almost all dermatologists (97.8%) indicated that they routinely distinguish between acute and chronic phases of AD during their clinical practice. The reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. While promoting healthy skin lesions was identified as a prominent objective in treating acute AD (57.7%), the management focus shifted towards enhancing productivity in daily activities for chronic AD (46.0%). In both conditions, preventing exacerbations remained a key priority, with 47.2% and 64.9% of physicians indicating this for acute and chronic AD, respectively. More details are presented in Fig. S1 (see Supplementary Materials).

Figure 1a illustrates the treatment preferences of dermatologists when managing adult patients with moderate-to-severe AD who did not respond to maximized topical treatment. Of all surveyed dermatologists, 265 (97.8%) would add on treatment for such patients. Among them, the majority (50.9%) favoured using systemic anti-inflammatory medication as the primary or first choice add-on treatment option. This was followed by phototherapy (26.8%), biologics (17.0%), and small molecules (3.0%). Figure 1b shows the preferred strategies for patients who did not respond to maximized systemic treatment, based on responses from 257 (94.8%) dermatologists. For this group, the most common choice was switching to another systemic medication (43.6%). Other alternatives included augmenting treatment with phototherapy (20.6%), adding another systemic treatment (17.5%), or supplementing with topical treatments (16.7%). Few of them expressed preference for switching to phototherapy as their primary option.Fig. 1 a if patients do not respond to maximized topical treatment and b maximized systemic treatment

The main reasons for dermatologists’ choice of different add-on agents when managing patients with moderate-to-severe AD who were not responding to maximized topical treatment are shown in Table S2 (see Supplementary Materials). When asked about the main reason for choosing systematic anti-inflammatory medication as their first choice, the majority of 135 dermatologists who selected this treatment reasoned that it costs less (39.3%) or has higher efficacy (34.1%) than other therapies. Other dermatologists indicated phototherapy, biologics, and small molecules as their most preferred add-on treatment options mainly due to relatively fewer side effects, compared to systemic anti-inflammation medication.

As presented in Table 3, most dermatologists (76.8%) evaluated the patient’s response to treatment based on clinical judgment or observation, including the pattern and distribution of skin lesions. In addition, some dermatologists (18.5%) utilized scoring tools, while a smaller percentage (4.8%) relied on patient’s self-reported symptoms as their primary method. Treatment failure was predominantly defined as no improvement in clinical efficacy after continuous treatment for 3 months and 1 month by 49.1% and 47.1% of dermatologists, respectively.Table 3 Clinical management of atopic dermatitis

	N = 271	
n	%	
Methods to assess response to treatment	
 Clinical assessment or observation, including the pattern and distribution of skin lesions	208	76.8	
 Patient self-report	13	4.8	
 Scoring tools	50	18.5	
Main definition of treatment failure	
 Unacceptable adverse events	8	3.0	
 No improvement in clinical efficacy after continuous treatment for 1 month	113	41.7	
 No improvement in clinical efficacy after continuous treatment for 3 months	133	49.1	
 No improvement in clinical efficacy after continuous treatment for 6 months	11	4.1	
 Patient preference of new treatment	2	0.7	
 Patient non-adherence	4	1.5	

Topical Treatment

Topical agents serve as the cornerstone of AD management, often complemented by systemic or phototherapy in moderate-to-severe cases. When addressing acute flares, a comparatively higher proportion of dermatologists (43.5%) chose high-potency TCS for non-sensitive areas (Fig. 2a), while a respective 35.1% and 35.8% favoured medium-potency and low-potency TCS for sensitive areas (Fig. 2b). For treatment of chronic AD, high-potency (28.4%) and medium-potency (26.9%) TCS were predominantly selected as the top choices for non-sensitive areas (Fig. 2c). However, low-potency TCS (30.6%) and tacrolimus (29.5%) were the preferred options for treating sensitive areas (Fig. 2d).Fig. 2 Relative reported priority of atopic therapies in the management of a non-sensitive areas in patients with acute flares, b sensitive areas in patients with acute flares, c non-sensitive areas in patients with chronic AD, and d sensitive areas in patients with chronic AD. AD atopic dermatitis, TCS topical corticosteroid. Crisaborole was unavailable in some markets including India, Japan, Thailand, and Korea at the time of the survey

Super high-potency TCS were used by some dermatologists as most preferred treatment for non-sensitive areas in both acute and chronic AD (24.4% and 15.9%, respectively), although their application in sensitive areas was much less frequently reported. Most dermatologists also did not report use of crisaborole as treatment for acute or chronic AD.

Phototherapy

Figure 3 shows that the majority (84.9%) of dermatologists chose narrow-band ultraviolet B (NB-UVB) as their most preferred modality and broad-band UVB as second choice (31.7%). Although the combination of psoralen and long-wave ultraviolet A (PUVA) was rarely indicated as the most preferred agent, it was ranked as the third choice (24.7%). High proportions of dermatologists indicated that they would never consider the use of UVA1 and UVA (TL09) (79.3% and 73.8%, respectively).Fig. 3 Relative reported priority for phototherapy selection by dermatologists in the management of moderate-to-severe atopic dermatitis. PUVA psoralen and long-wave ultraviolet A (PUVA), UV ultraviolet

Systemic Treatment

As shown in Fig. 4, oral steroids (39.9%) emerged as the most commonly selected systemic treatment agent, ahead of alternatives including cyclosporin, dupilumab, methotrexate, azathioprine, and upadacitinib. Notably, cyclosporin was frequently utilized as either the second (24.0%) or third (17.7%) choice for systemic treatment. In contrast, the usage of mycophenolate mofetil appeared to be limited. Systemic omalizumab, rituximab and abrocitinib, apremilast, baricitinib and upadacitinib were rarely selected (data not shown in figure).Fig. 4 Relative reported priority of systemic therapies in the management of moderate to severe atopic dermatitis. Systemic omalizumab, rituximab and abrocitinib, apremilast, baricitinib and upadacitinib were seldom selected and not shown here

Figure 5a shows marked differences in the average duration of treatment among agents. Among dermatologists who opted for oral steroids, the typical prescription duration averaged less than 1 month. Conversely, dermatologists indicated longer treatment timeframes for azathioprine, cyclosporin, and mycophenolate mofetil, typically spanning 3–6 months. Notably, a considerable proportion of dermatologists reported using cyclosporin and mycophenolate mofetil for a maximum of 7–12 months, compared with 1–2 months for oral steroids, 3–6 months for azathioprine and methotrexate (Fig. 5b). However, some indicated that the maximum duration for using oral steroids exceeded 3 months, and in certain instances it was more than 1 year.Fig. 5 a Average and b maximum duration of treatment reported by dermatologists for specified therapeutic agents

Discussion

To the best of our knowledge, this multinational cross-sectional study is the first to capture information on diagnosis and treatment approaches for moderate-to-severe AD across eight Asia–Pacific territories. We found that diagnostic practices frequently incorporated the Hanifin and Rajka criteria, local guidelines, and serum IgE test results. When assessing severity of AD, most dermatologists leaned heavily on clinical impression rather than more objective scoring tools. In cases where topical treatments were insufficient, dermatologists predominantly opted for adding systemic anti-inflammatory medication because of their lower costs and higher efficacy. Clinical judgment also played a central role in assessing treatment response. The diverse preferences for topical treatment, systemic treatment, and phototherapy indicate diverse AD management and practices in the region. Dermatologists frequently chose between different potencies of TCS on the basis of the nature (acute vs. chronic) and location (sensitive vs. non-sensitive area) of AD. Oral steroids were commonly selected as systemic therapies, while NB-UVB was the most common form of phototherapy used.

Our study showed that dermatologists practising in the Asia–Pacific region often relied on clinical judgment, local guidelines, and a range of clinical tests, particularly serum IgE levels when diagnosing AD. These findings align with the multifactorial nature of AD [5]. Existing guidelines in the USA highlight the importance of considering individual patient characteristics in clinical practice [5]. The detection of total and specific IgE antibodies to inhalant and/or food allergens is one important aspect in diagnosing AD, though concerns about its limited clinical relevance and low specificity exist [17]. Incorporating possible differential diagnoses into assessment has been recommended to exclude various skin diseases (e.g. allergic contact eczema, microbial eczema, cutaneous lymphoma) that clinically resemble AD and could be associated with increased total serum IgE [18]. Use of clinical judgment based on the presence and distribution pattern of lesions with specific morphologic features, relevant clinical findings, and personal or family medical history is in line with recommendations from various sources from Europe [19–21]. This emphasizes the critical role of holistic assessment including clinical judgment combined with other tests in the accurate diagnosis of AD.

The diversity in use of diagnostic criteria (e.g. Hanifin and Rajka, American Academy of Dermatology, local guidelines) suggests that none of these criteria are considered wholly or mutually exclusive in the diagnosis of AD. Dermatologists may also depend on their clinical experience to make the final diagnosis. In particular, the Hanifin and Rajka criteria were used by a considerable proportion of physicians in our study. This could reflect that respondents are experienced dermatologists who are familiar with the classical criteria, which include precise description of the skin disorder. Additionally, this may be due to its frequent use in randomized controlled trials (RCTs), as reported by a systematic review of AD diagnostic criteria [22]. Both our study and the review indicate a similar lack of uniformity in AD diagnosis [22].

To date, topical treatments are deemed the mainstay of AD therapy [12, 23]. Consistent with existing evidence in Europe, our findings suggest that adults with moderate-to-severe AD refractory to topical treatments are considered for add-on therapy, primarily systemic anti-inflammatory medications such as oral steroids, cyclosporin, and methotrexate [24]. When patients do not respond to maximized systemic treatment or have concerns about adverse effects from continuous usage of the systemic agent, dermatologists preferred switching to another systemic medication. The preference for systemic anti-inflammatory medications as a first choice for add-on treatment echoes guidelines in Europe and the USA [19, 25] and a systematic review [26], reflecting the widespread acceptability of this approach for managing moderate-to-severe AD. However, concerns about their safety profiles remain. To improve long-term management of patients with AD, it is important to continue development of treatment options that are synergistic, effective, fast-acting, and with fewer serious adverse effects.

While some studies have recommended measurement scales, especially EASI and SCORAD, as objective instruments to evaluate the AD severity [27], our study suggests that dermatologists predominantly used clinical assessment and observation to assess skin lesions and determine treatment response. The commonly selected definitions of treatment failure (i.e. no improvement after continuous treatment for 1 vs. 3 months) are likely attributable to expectations regarding a treatment’s onset of action and hence response. Given that the choice of assessment method may impact treatment decisions and patient outcomes [27, 28], additional efforts to standardize AD assessment through guidelines and consensus meetings may be necessary to ensure greater consistency and objectivity in clinical practice.

This study revealed varied dermatologist preferences for topical treatments for AD, influenced by the affected area’s nature and location. For acute flares, super high-potency and high-potency TCS were preferred for non-sensitive body parts where the skin is less delicate or more resilient (e.g. back, chest, outsides of elbows, or fronts of knees) to quickly reduce symptoms [29, 30]. In contrast, for sensitive areas where the skin is delicate and thinner (e.g. face or genital areas), medium to low-potency TCS were chosen to minimize side effects such as skin atrophy, striae, or rosacea [31]. For chronic AD, high-potency TCS continued to be favoured for non-sensitive areas, in line with consensus-based European guidelines that recommend the use of high-potency topical TCS as first-line treatment for moderate-to-severe AD, regardless of the area affected [21]. For sensitive areas, there was a cautious shift towards lower-potency TCS and TCIs (including tacrolimus and pimecrolimus) [32, 33], though their use was less than expected, possibly because of side effects and cost issues [34]. Although newer treatment such as crisaborole (phosphodiesterase 4 inhibitor) has been recommended in some guidelines from the USA [12], our study reported minimal use of it in clinical practice. This is likely due to limited availability and reimbursement in markets including India [35], Japan [36], Korea [37], and Thailand [38].

In addition to topical treatment, NB-UVB was the most preferred phototherapy modality in managing moderate-to-severe AD. It works by suppressing the itch and immune system, and reducing inflammation in the skin [39]. The preference for NB-UVB is supported by its superior efficacy, more favourable side effect profile, and improved re-pigmentation and colour matching, compared with other phototherapies (e.g. PUVA) [40]. Our findings are in alignment with emerging evidence from RCTs, and are consistent with Asia and international guidelines recognizing NB-UVB as an effective AD treatment option [41–45].

Oral corticosteroids, despite their unfavourable long-term risk-to-benefit ratio [46], have emerged as the first-line systemic treatment among most dermatologists. However, as reported by our study participants, they were often prescribed for short durations, typically less than 1 month. Such practice is supported by regional and international guidelines recommending short-term use of systemic steroids for acute flares, but discouraging them from prolonged use [19, 25, 47]. Oral corticosteroids may cause wide-ranging systemic side effects such as weight gain, high blood pressure, diabetes mellitus, adrenal suppression, and osteoporosis. Abrupt discontinuation of systemic corticosteroids may result in withdrawal syndrome, characterized by the extreme recurrence or worsening of generalized AD symptoms and rebound flares [19, 25, 47], occasionally accompanied by adrenal insufficiency. The reported utilization of cyclosporin as the most common second-line option aligns with its immunosuppressive properties [48] and rapid onset of action [49]. Guidelines and real-world studies in Asia [19, 47] and Europe [50–52] have also indicated cyclosporin as a suitable alternative for managing moderate-to-severe AD. Meanwhile, other immunosuppressants appeared to be less frequently prescribed. Previous research has demonstrated that azathioprine and mycophenolate mofetil have delayed time to effect in AD treatment, and methotrexate may reach maximum efficacy after 3–4 months even with dose escalation [16]. Dupilumab was the preferred newer systemic treatment, supported by phase 3 trials [53] and real-world settings [54, 55]. However, its limited use in our study could be due to it being reserved for patients who have a poor response to other more established therapies, high costs, and the risk of serious side effects.

Though most dermatologists adhered to recommendations for systemic steroids for a maximum of 6 weeks [56], more than 30% of dermatologists reported using oral steroids for more than 1 month on average and a surprisingly high percentage (37.7%) even estimated the maximum duration to be more than 2 months. This finding may be attributed to factors such as lack of effective alternatives for certain patients with more serious AD, challenges in tapering off medication before another flare, or patient preferences. The reported average and maximum durations with cyclosporin, azathioprine, methotrexate, and mycophenolate mofetil are consistent with guidelines from the Asian Pacific Journal of Allergy and Immunology (APJAI) guidelines [38], suggesting an average of 3–6 months of use, with possible extension up to 12 months with close monitoring. This indicates that some dermatologists considered them as longer-term alternatives to oral corticosteroids. Differences in treatment durations for each systemic agent might reflect variations in prescription practices, with some physicians opting for very low doses over longer periods as maintenance treatment.

The treatment goals were categorized into acute and chronic phases. In the acute phase, goals included reducing dermatitis and itching, and early resolution of symptoms, while the emphasis in the chronic phase was on the minimization of side effects. Other goals were similar in both phases. Many physicians prioritized enhancing productivity in daily activities for chronic AD and preventing exacerbations in both the acute and chronic phases, indicating a need for continuing treatment in the chronic phase. Hence, it is important to promote the use of systemic drugs with superior long-term safety profiles as alternatives to current standard systemic treatments.

This is the first survey study which investigated the treatment approaches of dermatologists across eight Asia–Pacific territories. We received responses from a good cross-section of experienced dermatologists working in various clinical settings. However, there are several limitations to be acknowledged. As our participants were recruited from physician panels, the selected sample may have a stronger interest in research compared with other practising dermatologists. In addition, some patients with AD could be managed by general practitioners, whose clinical management of AD will not be reflected in this study. These, combined with the relatively small sample size in each territory, could limit the generalizability of our findings. Furthermore, this study used a self-reported questionnaire, which is a subjective measure. Although the questionnaire was developed on the basis of existing literature and experts’ opinion, its reliability and validity have not been assessed in the target populations. Self-reporting may introduce measurement error and recall bias, hence potentially affecting the accuracy of our findings. Another limitation is the varying availability of treatments across territories, which may influence dermatologists’ responses. Differences in healthcare access, drug availability, and reimbursement policies could affect treatment choices and management practices. Future research to study drug utilization and management of patients with AD using electronic medical records may be useful to validate our study findings.

Conclusion

Our study has provided insights into the management of moderate-to-severe AD in the Asia–Pacific region. Clinical judgment plays a central role in AD diagnosis, assessment of severity, and treatment response in real-world practice. The diversity in management approaches and choice of medications reflects the inherent multifactorial nature of AD and clinicians’ consideration of individual patient needs. Oral corticosteroids were frequently selected as systemic treatment. However, physicians should avoid prolonged use of oral corticosteroids because of potentially serious adverse effects. With the availability of newer therapies, dermatologists now have more treatment options at their disposal. To improve outcomes in patients with AD, international collaboration among dermatologists, researchers, and policymakers will be crucial to develop useful biomarkers for diagnosis, reduce subjectivity in assessment, and promote more equitable access to novel treatments.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (PDF 360 KB)

Acknowledgements

The authors would like to thank Dr James Wee from Pfizer and Chee Wen Eng from IQVIA for their contribution in managing this project (at time of data collection) as well as Xiaoyun Chen from IQVIA for performing the statistical analysis. In addition, the authors would like to extend our gratitude to the participants of the study.

Medical Writing Assistance

Medical writing support was provided by Rachel Lee-Yin Tan from IQVIA.

Author Contributions

All authors were involved in the conception and design of this study, interpretation of the results, and critical revision of the manuscript. Sophie Bozhi Chen and See-Hwee Yeo were involved in data analysis and drafting the manuscript. All authors read and approved the final manuscript.

Funding

This study (including publication fees) was funded by Pfizer Hong Kong Corporation Limited. IQVIA was contracted to conduct study activities. The sponsor was also involved in the study design, data interpretation and manuscript review.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Han-Fang Liao and Sean Gardiner are employees of Pfizer. Yoko Kataoka has received lecturer honoraria from Sanofi, AbbVie, Pfizer and Maruho, and research funding from Sanofi, Leo Pharma, Pfizer, Maruho, Lilly, AbbVie, Otsuka, Taiho and Amgen. Yung Chan is a speaker for AbbVie, Bioderma, Galderma, Inova, Eli Lily, Lumenis, Menarini and Pfizer; an advisory board member for AbbVie, Bayer, Bioderma, CeraVe, Eli Lilly, Menarini, Pfizer, Sanofi, Quanta System and Janssen. Chia-Yu Chu is an investigator for AbbVie, Amgen, Dermira, Eli Lilly, Janssen, Novartis, Oneness Biotech, Pfizer, Regeneron Pharmaceuticals Inc., Roche and Sanofi; a consultant for AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche and Sanofi; a speaker for AbbVie, Eli Lilly, GlaxoSmithKline, Janssen, Mylan, Novartis, Pfizer, Roche, Sanofi and Viatris; and an advisory board member for AbbVie, Amgen, Mylan, Pfizer, Roche, Sanofi and Viatris. Nisha Suyien Chandran has received fees for participation in advisory boards from AbbVie, Johnson & Johnson, Sanofi, Pfizer, DKSH, L’Oreal and Novartis; investigator fees for clinical trials from AbbVie, Novartis, Amgen, Sanofi and Boehringer Ingelheim; and speaker honoraria from Galderma, Johnson & Johnson, LEO, Pfizer, Sanofi and Lion Corporation. All other authors have no conflict of interest.

Ethical Approval

Ethical approval was received from the following IRBs: Korea University Ansan Hospital, Chulalongkorn University, Father Muller Hospital, NPO MINS, National Taiwan University Hospital, Hong Kong Doctors Union, and Sir Run Run Shaw Hospital. The Parkway Independent Ethics Committee granted an exemption from review. The study was conducted in accordance with the protocol, Guidelines for Good Pharmacoepidemiology Practices, and the Declaration of Helsinki. All participants provided informed consent.
==== Refs
References

1. Langan SM Irvine AD Weidinger S Atopic dermatitis Lancet 2020 396 10247 345 360 32738956
Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345–60.32738956
2. Williams H Stewart A von Mutius E Cookson W Anderson HR International Study of Asthma and Allergies in Childhood (ISAAC) Phase One and Three Study Groups Is eczema really on the increase worldwide? J Allergy Clin Immunol 2008 121 4 947 54.e15 18155278
Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR, International Study of Asthma and Allergies in Childhood (ISAAC) Phase One and Three Study Groups. Is eczema really on the increase worldwide? J Allergy Clin Immunol. 2008;121(4):947-54.e15.18155278
3. Yong AM-Y Tay Y-K Atopic dermatitis: racial and ethnic differences Dermatol Clin 2017 35 3 395 402 28577807
Yong AM-Y, Tay Y-K. Atopic dermatitis: racial and ethnic differences. Dermatol Clin. 2017;35(3):395–402.28577807
4. Carroll CL Balkrishnan R Feldman SR Fleischer AB Jr Manuel JC The burden of atopic dermatitis: impact on the patient, family, and society Pediatr Dermatol 2005 22 3 192 199 15916563
Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB Jr, Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005;22(3):192–9.15916563
5. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338–51.
6. Linnet J Jemec GBE An assessment of anxiety and dermatology life quality in patients with atopic dermatitis Br J Dermatol 1999 140 2 268 272 10233221
Linnet J, Jemec GBE. An assessment of anxiety and dermatology life quality in patients with atopic dermatitis. Br J Dermatol. 1999;140(2):268–72.10233221
7. Cheng CM Hsu JW Huang KL Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study J Affect Disord 2015 178 60 65 25795537
Cheng CM, Hsu JW, Huang KL, et al. Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study. J Affect Disord. 2015;178:60–5.25795537
8. Kiebert G Sorensen SV Revicki D Atopic dermatitis is associated with a decrement in health-related quality of life Int J Dermatol 2002 41 3 151 158 12010340
Kiebert G, Sorensen SV, Revicki D, et al. Atopic dermatitis is associated with a decrement in health-related quality of life. Int J Dermatol. 2002;41(3):151–8.12010340
9. Girolomoni G Luger T Nosbaum A The economic and psychosocial comorbidity burden among adults with moderate-to-severe atopic dermatitis in Europe: analysis of a cross-sectional survey Dermatol Ther (Heidelb) 2021 11 1 117 130 33180320
Girolomoni G, Luger T, Nosbaum A, et al. The economic and psychosocial comorbidity burden among adults with moderate-to-severe atopic dermatitis in Europe: analysis of a cross-sectional survey. Dermatol Ther (Heidelb). 2021;11(1):117–30.33180320
10. Krakowski AC Eichenfield LF Dohil MA Management of atopic dermatitis in the pediatric population Pediatrics 2008 122 4 812 824 18829806
Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics. 2008;122(4):812–24.18829806
11. Flohr C How we treat atopic dermatitis now and how that will change over the next 5 years Br J Dermatol 2022 188 6 718 725
Flohr C. How we treat atopic dermatitis now and how that will change over the next 5 years. Br J Dermatol. 2022;188(6):718–25.
12. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116–32.
13. Carrera YIL Al Hammadi A Huang Y-H Llamado LJ Mahgoub E Tallman AM Epidemiology, diagnosis, and treatment of atopic dermatitis in the developing countries of Asia, Africa, Latin America, and the Middle East: a review Dermatol Ther (Heidelb) 2019 9 4 685 705 31650504
Carrera YIL, Al Hammadi A, Huang Y-H, Llamado LJ, Mahgoub E, Tallman AM. Epidemiology, diagnosis, and treatment of atopic dermatitis in the developing countries of Asia, Africa, Latin America, and the Middle East: a review. Dermatol Ther (Heidelb). 2019;9(4):685–705.31650504
14. Taylor K Swan DJ Affleck A Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists Br J Dermatol 2017 176 6 1617 1623 27943248
Taylor K, Swan DJ, Affleck A, et al. Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists. Br J Dermatol. 2017;176(6):1617–23.27943248
15. Sastre J Baldrich ES Armario Hita JC Consensus on the clinical approach to moderate-to-severe atopic dermatitis in Spain: a Delphi survey Dermatol Res Pract 2020 2020 1524293 32318104
Sastre J, Baldrich ES, Armario Hita JC, et al. Consensus on the clinical approach to moderate-to-severe atopic dermatitis in Spain: a Delphi survey. Dermatol Res Pract. 2020;2020:1524293.32318104
16. Boguniewicz M Alexis AF Beck LA Expert perspectives on management of moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and emerging therapies J Allergy Clin Immunol Pract 2017 5 6 1519 1531 28970084
Boguniewicz M, Alexis AF, Beck LA, et al. Expert perspectives on management of moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and emerging therapies. J Allergy Clin Immunol Pract. 2017;5(6):1519–31.28970084
17. Wichmann K Heratizadeh A Werfel T In-vitro diagnostic in atopic dermatitis: options and limitations Allergologie Select 2017 1 2 150 30402613
Wichmann K, Heratizadeh A, Werfel T. In-vitro diagnostic in atopic dermatitis: options and limitations. Allergologie Select. 2017;1(2):150.30402613
18. Silvestre Salvador J Romero-Pérez D Encabo-Durán B Atopic dermatitis in adults: a diagnostic challenge J Investig Allergol Clin Immunol 2017 27 2 78 88 28071589
Silvestre Salvador J, Romero-Pérez D, Encabo-Durán B. Atopic dermatitis in adults: a diagnostic challenge. J Investig Allergol Clin Immunol. 2017;27(2):78–88.28071589
19. Saeki H Nakahara T Tanaka A Clinical practice guidelines for the management of atopic dermatitis 2016 J Dermatol 2016 43 10 1117 1145 27076388
Saeki H, Nakahara T, Tanaka A, et al. Clinical practice guidelines for the management of atopic dermatitis 2016. J Dermatol. 2016;43(10):1117–45.27076388
20. Bieber T D'Erme AM Akdis CA Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol 2017 139 4s S58 S64 28390478
Bieber T, D’Erme AM, Akdis CA, et al. Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol. 2017;139(4s):S58–S64.28390478
21. Wollenberg A Barbarot S Bieber T Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I J Eur Acad Dermatol Venereol 2018 32 5 657 682 29676534
Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2018;32(5):657–82.29676534
22. Vakharia PP Chopra R Silverberg JI Systematic review of diagnostic criteria used in atopic dermatitis randomized controlled trials Am J Clin Dermatol 2018 19 1 15 22 28624959
Vakharia PP, Chopra R, Silverberg JI. Systematic review of diagnostic criteria used in atopic dermatitis randomized controlled trials. Am J Clin Dermatol. 2018;19(1):15–22.28624959
23. Sideris N Paschou E Bakirtzi K New and upcoming topical treatments for atopic dermatitis: a review of the literature J Clin Med 2022 11 17 4974 36078904
Sideris N, Paschou E, Bakirtzi K, et al. New and upcoming topical treatments for atopic dermatitis: a review of the literature. J Clin Med. 2022;11(17):4974.36078904
24. Adam DN Gooderham MJ Beecker JR Expert consensus on the systemic treatment of atopic dermatitis in special populations J Eur Acad Dermatol Venereol 2023 37 6 1135 1148 36695072
Adam DN, Gooderham MJ, Beecker JR, et al. Expert consensus on the systemic treatment of atopic dermatitis in special populations. J Eur Acad Dermatol Venereol. 2023;37(6):1135–48.36695072
25. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327–49.
26. Megna M Napolitano M Patruno C Systemic treatment of adult atopic dermatitis: a review Dermatol Ther (Heidelb) 2017 7 1 1 23 28025775
Megna M, Napolitano M, Patruno C, et al. Systemic treatment of adult atopic dermatitis: a review. Dermatol Ther (Heidelb). 2017;7(1):1–23.28025775
27. Schmitt J Langan S Deckert S Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation J Allergy Clin Immunol 2013 132 6 1337 1347 24035157
Schmitt J, Langan S, Deckert S, et al. Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation. J Allergy Clin Immunol. 2013;132(6):1337–47.24035157
28. Boguniewicz M Fonacier L Guttman-Yassky E Ong PY Silverberg JI Farrar JR Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape Ann Allergy Asthma Immunol 2018 120 1 10 22 29273118
Boguniewicz M, Fonacier L, Guttman-Yassky E, Ong PY, Silverberg JI, Farrar JR. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120(1):10–22.29273118
29. Symptoms. https://www.nhs.uk/conditions/atopic-eczema/symptoms/?ssp=1&setlang=en-SG&safesearch=moderate. Accessed 13 Nov 2023.
30. Mehta A Nadkarni N Patil S Godse K Gautam M Agarwal S Topical corticosteroids in dermatology Indian J Dermatol Venereol Leprol 2016 82 371 27279294
Mehta A, Nadkarni N, Patil S, Godse K, Gautam M, Agarwal S. Topical corticosteroids in dermatology. Indian J Dermatol Venereol Leprol. 2016;82:371.27279294
31. Hengge UR Ruzicka T Schwartz RA Cork MJ Adverse effects of topical glucocorticosteroids J Am Acad Dermatol 2006 54 1 1 5 16384751
Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006;54(1):1–5.16384751
32. Charman C Morris AD Williams HC Topical corticosteroid phobia in patients with atopic eczema Br J Dermatol 2000 142 5 931 936 10809850
Charman C, Morris AD, Williams HC. Topical corticosteroid phobia in patients with atopic eczema. Br J Dermatol. 2000;142(5):931–6.10809850
33. Wollenberg A Oranje AP Deleuran M ETFAD/EADV eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients J Eur Acad Dermatol Venereol 2016 30 5 729 747 27004560
Wollenberg A, Oranje AP, Deleuran M, et al. ETFAD/EADV eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol. 2016;30(5):729–47.27004560
34. Luger TA Paller AS Irvine AD Topical therapy of atopic dermatitis with a focus on pimecrolimus J Eur Acad Dermatol Venereol 2021 35 7 1505 1518 33834524
Luger TA, Paller AS, Irvine AD, et al. Topical therapy of atopic dermatitis with a focus on pimecrolimus. J Eur Acad Dermatol Venereol. 2021;35(7):1505–18.33834524
35. Godse K De A Sharma N Crisaborole for the treatment of atopic dermatitis in Indian patients: an evidence-based consensus statement Indian J Drugs Dermatol 2021 7 1 7
Godse K, De A, Sharma N, et al. Crisaborole for the treatment of atopic dermatitis in Indian patients: an evidence-based consensus statement. Indian J Drugs Dermatol. 2021;7(1):7.
36. Ma L Zhang L Kobayashi M Efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥ 2 years with mild-to-moderate atopic dermatitis J Dermatol 2023 50 7 847 855 37154471
Ma L, Zhang L, Kobayashi M, et al. Efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥ 2 years with mild-to-moderate atopic dermatitis. J Dermatol. 2023;50(7):847–55.37154471
37. Lee JH Kim JE Park G-H Consensus update for systemic treatment of atopic dermatitis Ann Dermatol 2021 33 6 497 34858001
Lee JH, Kim JE, Park G-H, et al. Consensus update for systemic treatment of atopic dermatitis. Ann Dermatol. 2021;33(6):497.34858001
38. Kulthanan K Tuchinda P Nitiyarom R Clinical practice guidelines for the diagnosis and management of atopic dermatitis Asian Pac J Allergy Immunol 2021 39 3 145 155 34246205
Kulthanan K, Tuchinda P, Nitiyarom R, et al. Clinical practice guidelines for the diagnosis and management of atopic dermatitis. Asian Pac J Allergy Immunol. 2021;39(3):145–55.34246205
39. Dogra S Kanwar AJ Narrow band UVB phototherapy in dermatology Indian J Dermatol Venereol Leprol 2004 70 205 209 17642615
Dogra S, Kanwar AJ. Narrow band UVB phototherapy in dermatology. Indian J Dermatol Venereol Leprol. 2004;70:205–9.17642615
40. Rodrigues M Ezzedine K Hamzavi I Pandya AG Harris JE Current and emerging treatments for vitiligo J Am Acad Dermatol 2017 77 1 17 29 28619557
Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE. Current and emerging treatments for vitiligo. J Am Acad Dermatol. 2017;77(1):17–29.28619557
41. Fekete GL Fekete L Clinical and therapeutic trial for the efficacy of narrow band—UVB phototherapy versus systemic therapy in moderate and severe atopic dermatitis of the adult Acta Medica Marisiensis 2018 64 1 17 21
Fekete GL, Fekete L. Clinical and therapeutic trial for the efficacy of narrow band—UVB phototherapy versus systemic therapy in moderate and severe atopic dermatitis of the adult. Acta Medica Marisiensis. 2018;64(1):17–21.
42. Vangipuram R Feldman SR Ultraviolet phototherapy for cutaneous diseases: a concise review Oral Dis 2015 22 4 253 259 26464123
Vangipuram R, Feldman SR. Ultraviolet phototherapy for cutaneous diseases: a concise review. Oral Dis. 2015;22(4):253–9.26464123
43. Katayama I Aihara M Ohya Y Japanese guidelines for atopic dermatitis 2017 Allergol Int 2017 66 2 230 247 28209325
Katayama I, Aihara M, Ohya Y, et al. Japanese guidelines for atopic dermatitis 2017. Allergol Int. 2017;66(2):230–47.28209325
44. Hönigsmann H Phototherapy for psoriasis Clin Exp Dermatol 2001 26 4 343 350 11422187
Hönigsmann H. Phototherapy for psoriasis. Clin Exp Dermatol. 2001;26(4):343–50.11422187
45. Ring J Alomar A Bieber T Guidelines for treatment of atopic eczema (atopic dermatitis) part I J Eur Acad Dermatol Venereol 2012 26 8 1045 1060 22805051
Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol. 2012;26(8):1045–60.22805051
46. Girolomoni G Busà VM Flare management in atopic dermatitis: from definition to treatment Ther Adv Chronic Dis 2022 13 20406223211066728 35070252
Girolomoni G, Busà VM. Flare management in atopic dermatitis: from definition to treatment. Ther Adv Chronic Dis. 2022;13:20406223211066730.35070252
47. Kim JE Kim HJ Lew BL Consensus guidelines for the treatment of atopic dermatitis in Korea (part II): systemic treatment Ann Dermatol 2015 27 5 578 592 26512172
Kim JE, Kim HJ, Lew BL, et al. Consensus guidelines for the treatment of atopic dermatitis in Korea (part II): systemic treatment. Ann Dermatol. 2015;27(5):578–92.26512172
48. Khattri S Shemer A Rozenblit M Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology J Allergy Clin Immunol 2014 133 6 1626 1634 24786238
Khattri S, Shemer A, Rozenblit M, et al. Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology. J Allergy Clin Immunol. 2014;133(6):1626–34.24786238
49. Lee S Tan A Giam Y Cyclosporin in the treatment of severe atopic dermatitis: a retrospective study Ann Acad Med Singap 2004 33 311 313 15175770
Lee S, Tan A, Giam Y. Cyclosporin in the treatment of severe atopic dermatitis: a retrospective study. Ann Acad Med Singap. 2004;33:311–3.15175770
50. O'Donovan P Perrett CM Zhang X Azathioprine and UVA light generate mutagenic oxidative DNA damage Science 2005 309 5742 1871 1874 16166520
O’Donovan P, Perrett CM, Zhang X, et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science. 2005;309(5742):1871–4.16166520
51. Taylor K Swan DJ Affleck A Flohr C Reynolds NJ Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists Br J Dermatol 2017 176 6 1617 1623 27943248
Taylor K, Swan DJ, Affleck A, Flohr C, Reynolds NJ. Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists. Br J Dermatol. 2017;176(6):1617–23.27943248
52. Ring J Alomar A Bieber T Guidelines for treatment of atopic eczema (atopic dermatitis) Part II J Eur Acad Dermatol Venereol 2012 26 9 1176 1193 22813359
Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) Part II. J Eur Acad Dermatol Venereol. 2012;26(9):1176–93.22813359
53. Simpson EL Bieber T Guttman-Yassky E Two phase 3 trials of dupilumab versus placebo in atopic dermatitis N Engl J Med 2016 375 24 2335 2348 27690741
Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–48.27690741
54. Faiz S Giovannelli J Podevin C Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort J Am Acad Dermatol 2019 81 1 143 151 30825533
Faiz S, Giovannelli J, Podevin C, et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J Am Acad Dermatol. 2019;81(1):143–51.30825533
55. Jang DH Heo SJ Jung HJ Park MY Seo SJ Ahn J Retrospective study of dupilumab treatment for moderate to severe atopic dermatitis in Korea: efficacy and safety of dupilumab in real-world practice J Clin Med 2020 9 6 1982 32599878
Jang DH, Heo SJ, Jung HJ, Park MY, Seo SJ, Ahn J. Retrospective study of dupilumab treatment for moderate to severe atopic dermatitis in Korea: efficacy and safety of dupilumab in real-world practice. J Clin Med. 2020;9(6):1982.32599878
56. Arkwright PD Motala C Subramanian H Spergel J Schneider LC Wollenberg A Management of difficult-to-treat atopic dermatitis J Allergy Clin Immunol Pract 2013 1 2 142 151 24565453
Arkwright PD, Motala C, Subramanian H, Spergel J, Schneider LC, Wollenberg A. Management of difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract. 2013;1(2):142–51.24565453
