The Journal of Allergy and Clinical Immunology: In Practice
Review and Feature ArticleStrategies for Successful Management of Severe Atopic Dermatitis
Introduction
Atopic dermatitis (AD) is a common inflammatory skin disease that is increasingly recognized as a global health problem.1 Data derived from the Global Burden of Disease Study showed that dermatitis including AD was the leading skin disease in terms of global burden of disease measured by disability-adjusted life-years.2 Epidemiologic studies in the United States have shown a prevalence of up to 18% in school-aged children3 and 7% in adults.4, 5 However, few studies have stratified AD by severity at the population level. This review will focus on severe AD. In one study of children and adults, 18% described their eczema as severe,6 whereas in a study limited to adults, 9.8% rated their AD as severe.7 In the recent Atopic Dermatitis in America survey,8 11% of participants assessed their AD as severe using the Patient-Oriented Eczema Measure, a validated scoring tool.9
As a chronic, relapsing pruritic disease, AD has a profound impact on the quality of life of patients and families. In a study of adults with moderate-to-severe AD, 85% reported problems with itch frequency, 41.5% reported itching for greater than or equal to 18 h/d, 55% reported AD-related sleep disturbance on more than or equal to 5 d/wk, and 21.8% reported clinically relevant anxiety or depression.10 It is noteworthy that 100% of respondents with severe patient-reported outcome scores were found to have borderline and/or abnormal Hospital Anxiety and Depression Scale scores.11 Although atopic comorbidities of AD including asthma and allergies are well recognized,12 association of AD with a number of nonatopic comorbidities including neuropsychiatric and cardiovascular are only beginning to be reported.13, 14 Severe AD in adults was recently shown to be associated with long-term risk of cardiovascular disease in a population-based cohort study in the United Kingdom.15
AD is characterized by complex immune dysregulation, as well as skin barrier abnormalities.16 A number of insights into the pathophysiology of AD have translational implications with respect to therapy. These include recognition that nonlesional skin in patients with AD is characterized by both immune abnormalities and broad terminal differentiation defects17 and that type 2 immune abnormalities present not only in the skin but also systemically are central to the disease process.18 Among patients with inflammatory skin diseases, patients with AD are unique in their colonization or infection by various microbes.19, 20 Altered epidermal lipids in AD skin are associated with staphylococcal colonization21 and have been shown to be associated with type 2 cytokine dysregulation.22 Dysbiosis of the skin microbiome appears to contribute to the disease although this is a complex and dynamic process that we are just beginning to understand.23 However, it will likely have important translational implications for the development of novel therapeutic targets. In considering severe AD, successful management strategies will require a comprehensive approach, understanding not only the complex pathophysiology and systemic nature of the disease24 but the profound impact it has on the patients' and caregivers' quality of life. In this setting, shared decision making in choosing appropriate treatment should be an integral part of management.25, 26 In addition, using a multidisciplinary team approach may benefit patients by addressing more than the skin barrier and immune abnormalities.27 In the recent past, advances in our understanding of disease mechanisms have serendipitously coincided with technological advances, ushering in a new era of targeted therapy for AD.28, 29 In this review, we will discuss our strategies for managing severe AD based on these insights.
Section snippets
Diagnosis of Severe AD
AD should be diagnosed by one of several criteria including Hanifin and Rajka,30 UK Working Party,31 or AAD Consensus criteria.32 However, the AAD criteria have not been validated or compared with other diagnostic criteria. Subsequently, severe AD should be established by minimum involvement of 10% body surface area and regardless of body surface area, individual lesions with severe features, involvement of highly visible areas or those important for function (eg, neck, face, genitals, palms,
Differential Diagnosis of Severe AD
A number of congenital disorders, inflammatory skin diseases, infectious diseases and infestations, immunodeficiencies, genetic disorders, as well as skin malignancies may present with signs and symptoms that can be misdiagnosed as severe AD. Table II lists some of the diseases that should be considered in the differential of AD. These should be considered when a patient first presents with an eczematous rash, but also when a patient diagnosed with AD fails to respond to appropriate therapy.
Management of Severe AD
Most national and international AD guidelines including the Joint Taskforce Practice Parameter address AD care in a stepwise fashion.26, 45, 46, 47, 48, 49, 50, 51 These guidelines recommend components of basic daily AD management aimed at preventing dry skin, treating the eczematous rash, maintaining the skin barrier, improving the itch, and minimizing exposure to triggers. Treatment guidelines emphasize the following: (1) Frequent and liberal use of moisturizers in conjunction with warm baths
Systemic Therapy for Severe AD
In the authors' AD Program, the decision to initiate systemic therapy for patients with severe AD involves a careful reevaluation of the patient's diagnosis, understanding of their disease including psychosocial aspects, previous treatment, adherence issues, as well as systemic treatment options with risks versus benefits (Figure 1).27 A similar approach has recently been described by the International Eczema Council.81 Current preferred therapeutic options have been proposed in recent
Conclusions
Severe AD may present a diagnostic as well as therapeutic challenge. Patients with this degree of disease severity suffer disproportionately as reflected by patient-reported outcome scores. Thus, clinicians need to approach the management of severe disease in a comprehensive manner. A number of practical pearls may be helpful to incorporate into a successful treatment strategy (Table IV). In the past year, approval of dupilumab, a biologic targeting key cytokine abnormalities in AD, has
Acknowledgments
We acknowledge all the members of our multidisciplinary Atopic Dermatitis Day Program team and thank Dusty Christian for help with our manuscript.
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Cited by (31)
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2022, Clinical Immunology: Principles and Practice, Sixth EditionAtopic Dermatitis and Allergic Contact Dermatitis
2022, Allergy EssentialsOcular complications induced during dupilumab treatment of atopic dermatitis
2021, Revue Francaise d'AllergologieDaily Moisturization for Atopic Dermatitis: Importance, Recommendations, and Moisturizer Choices
2021, Journal for Nurse PractitionersCitation Excerpt :A similar study noted significant improvement in mean moisturizer use, a decrease in sleep disturbance, and an improved feeling of control among caregivers who underwent a multifaceted educational support program.20 A decrease in disease severity and a reduction in sleep disturbance were also reported in a pilot study of 1,638 parents who underwent individually tailored nurse consultations in 22 centers;21 the value of nurse practitioners (NPs)/physician assistants (PAs) in the management of severe AD has also been shown in a 2019 publication.22 Besides the exceptional improvement of compliance rates, this type of intervention has been shown to be cost-effective.23
Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials
2021, Pharmacology and TherapeuticsCitation Excerpt :Patients with moderate-to-severe AD may require systemic treatment with glucocorticoids, calcineurin inhibitors, and anti-metabolites, such as methotrexate, cyclosporin A, and mycophenolate mofetil, or phototherapy (Wong, Tsuyuki, Cresswell-Melville, Doiron, & Drucker, 2017) (Saini and Pansare, 2019). However, these traditional approaches have limited clinical efficacies and are associated with topical and systemic adverse events (AE), demonstrating a need for new therapeutic agents (Brar, Nicol, & Boguniewicz, 2019). Emerging findings on the pathogenesis of AD offer hope for the development of novel and promising treatments.
Conflicts of interest: M. Boguniewicz has served as a consultant for Regeneron and Sanofi-Genzyme. The rest of the authors declare that they have no relevant conflicts of interest.