Deciphering the influence of smoking in adults with atopic dermatitis

Commentary on ‘Atopic Dermatitis: Disease Characteristics and Comorbidities in Smoking and Non-smoking Patients from the TREATgermany Registry’ by A.C. Pilz et al. Atopic dermatitis (AD) has been classically defined as a chronic, relapsing, inflammatory and pruritic disease since the 19th century, with crescent, global prevalence in adults from 2% to 10%, and the overall point prevalence of AD in adults in the EU is estimated in 4.4%. AD may not be restricted to the skin – it is usually the first manifestation of the atopy complex, which includes respiratory diseases such as asthma and rhinitis. The disease has a high impact on patient ́s quality of life (QoL), with a multidimensional burden over the skin, including the psychosocial, general health and economic aspects, with some gaps to be fulfilled. The hallmark of AD complex pathogenesis involves a combination of skin barrier defects (e.g. filaggrin reduced expression), immunologic dysfunction, with overexpression of inflammatory cytokines and predominance of the Th2 axis associated with IL31 secretion, leading to inflammation and severe pruritus. The defective skin barrier facilitates the penetration of microorganisms, especially Staphylococcus aureus, which colonizes close to 90% of atopic skin and perpetuates the cutaneous inflammation. Environmental triggers, components of the exposome, may exert a relevant role to either deflagrate or maintain the chronic inflammation. The advances in AD pathogenesis led us to a high level of target-specific therapeutic options. Some studies indicate that external stimuli may be disease modifiers in atopic respiratory diseases such as asthma, and their identification is key to the implementation of preventive measures. Air pollutants (tobacco smoke, particulate matter and organic compounds) are some of the reported environmental triggers in AD, but there is still the need to better characterize such triggers and explore their role in the disease pathogenesis. Epidemiology data in some populations showed that AD adults were at higher risk of systemic comorbidities such as hypertension, adult-onset diabetes, dyslipidaemia, coronary artery disease, heart attack, stroke and peripheral vascular disease; moreover, AD adults exhibited increased cigarette smoking and other poor health behaviours. The work of Pilz et al. depicts a non-interventional study of 921 AD adults with moderate to severe registered in TREATgermany. The analysis included 39 German sites and compared AD features and comorbidities in smokers versus non-smokers. Major findings revealed that smokers were predominantly males (58.7%) in their forties, exhibited higher intensity of oozing/crusts and excoriations, with predominance for the inferior limbs (feet) and less flexural involvement, more elevated scores on patient global assessment, higher IgE levels and early asthma. Even though there is an exponential increase in approved and ongoing studies of targeted oriented therapies for AD such as immunobiological agents, Janus-kinase inhibitors and other small molecules, it is a global consensus that the first steps in AD care include education, the characterization of AD phenotypes and endotypes according to age and ethnicity and the identification of environmental triggers. There is an unmet need for long-term cohort studies with identification of potential predictive factors for a chronic, inflammatory skin disease that may progress to a systemic Th2 condition such as AD, with severe consequences and burden to the patients and caregivers. The establishment of early interventions through preventive measures is only possible with an adequate mapping of AD.