Atopic Dermatitis: A Heterogeneous Disorder

Atopic dermatitis (AD) is a fascinating disorder. If one had to summarize AD in one word, perhaps the best descriptor would be “heterogeneity.” That is, all aspects of the disease, including its name, epidemiology, clinical course, and treatment approaches, have a considerable amount of heterogeneity. Such heterogeneity begs the question, is AD one disease or a spectrum of diseases with a shared phenotype? Much of the scientific and clinical literature about AD has been relegated to childhood disease, with limited data available even in that subgroup. As it turns out, AD may be far more common in adults than previously recognized, whether through persistence or adult onset. Little is known about AD in adults. Is it the same disease as pediatric AD or not?

AD can be hard to define and diagnose (particularly in adults) given its many clinical presentations. Thomas Bieber masterfully reviews the heterogeneous definitions used for AD, how valid they are, and the impact of their use in different settings. Moreover, Professor Bieber provides important perspective on the future of molecular diagnostics and a more refined definition of AD. This outlook will in the future clarify the true nature of disease and allow us to project to patients a more accurate view of their clinical future.

AD is one of the most burdensome of all skin disorders globally, owing to its high prevalence and patient burden. Jonathan Silverberg reviews the public health burden and epidemiology of pediatric and adult AD. The burden of AD now rivals the impact of many chronic illnesses and identifies AD as a serious and even a systemic condition.

AD is a chronic disorder that can have a heterogeneous clinical course. For some, the disease is more episodic or seasonal, while others can have a more chronic persistent course. Children with AD may have persistent disease well into adulthood. Katrina Abuabara and colleagues review the long-term course of AD, how to define different concepts pertaining to a longitudinal course of AD, and their relevance in different settings. Many studies have shown high rates of self-reported adult-onset disease. However, the matter of adult-onset AD remains quite controversial. Jon Hanifin discusses whether adult-onset AD is fact or fancy. This is a very clinically relevant question because the differential diagnosis of adult-onset AD is quite broad and difficult to rule out.

There are important AD patient subsets that require special consideration with respect to both assessment and management. AD is likely not one illness, but a constellation of linked cutaneous manifestations that appear throughout a lifetime. Professors Nanette Silverberg and Carola Durán-McKinster review important physical manifestations, comorbidities, and treatment considerations in pediatric AD. Yong-Kwang Tay and Adeline Mei-Yen Yong review important racial and ethnic differences of AD epidemiology, phenotype, distribution, severity, genetics, and even treatment. Recognition of AD as clinically variable by age, race, and ethnicity highlights the variable roles that genetics and environment play on the emergence of clinical features and therapeutic outcomes.

The profound symptom-burden and heterogeneous manifestations of AD negatively impact upon quality of life in a variety of ways. Aaron Drucker and Cathryn Sibbald review the impact of the profound symptom burden and stigma of AD on quality of life. The quality of life impairment appears to be directly related to AD severity in most cases and in turn warrants improved prevention strategies and better long-term disease control, the latter being the holy grail of AD care.

James Prezzano and Lisa Beck comprehensively review long-term treatment strategies for chronic AD, including skin care recommendations, proactive topical therapy, long-term safety and efficacy of topical corticosteroids and calcinuerin inhibitors, phototherapy, and systemic immunosuppressants.

Pruritus or itch is the hallmark symptom of AD and can be very challenging to treat, often failing to clear with sedating antihistamines, which may be associated with undesirable side effects. Sarina Elmariah reviews the impact of current standard of care topical and/or systemic therapies on pruritus. Furthermore, she reviews a variety of adjunctive anti-itch strategies, including topical agents, antiepileptics, antidepressants, neurokinin-1 receptor antagonists, opioid modulators, and alternative therapies.

Jacob Thyssen and colleagues review the diagnostic and therapeutic considerations for yet another important patient subset, atopic hand eczema. Hand eczema can develop secondary to lower irritant threshold or superimposed allergic contact dermatitis in persons with AD. This is a very clinically relevant and important subset because failure to adequately avoid exogenous triggers may result in treatment-refractory hand eczema.

The last decade has witnessed major strides in our understanding of the pathogenesis of AD. Tali Czarnowicki and colleagues do a wonderful job reviewing the pathways implicated in the pathophysiology, barrier disruption, and immune dysregulation of AD. One of the most promising new developments in our understanding of AD is the recognition that AD is an immune-mediated disorder largely driven by T-helper 2 cytokines, interleukin-4, and/or interleukin-13. Jonathan Silverberg and Robert Kantor review the role of interleukin-4 and/or interleukin-13 in the pathogenesis of AD. These insights have directly translated into the development of novel biologic agents targeting these cytokine pathways. The first such biologic agent to be approved by the US Food and Drug Administration for AD was dupilumab, with multiple other biologic, systemic, and topical agents in the pipeline for AD.

AD has just begun to command the respect it deserves as a chronic disease with negative life impact and comorbidities. The future holds new definitions, better recognition of disease manifestations, superior surveillance for comorbidities, and an impressive improvement in therapeutic interventions. This is truly an exciting time for patients with AD, the people who suffer with them, and clinicians who treat AD.

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