Head and neck atopic dermatitis: still a challenging manifestation in the biologic era

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases affecting 5–20% of children and 2–10% of adults worldwide [1]. It is clinically characterized by intense itch and eczematous lesions having a preferential body distribution based on the age of the subject [1]. The involvement of the head-and-neck area, associated or not with lesions occurring in other body regions, likely represents the most typical localization in both childhood and adulthood, as it is observed in up to 38% of both AD children and adults [1]. Notably, the localization of AD at the head-andneck area, greatly than other areas, has been associated with social embarrassment, stigmatization, and deterioration of patients’ quality of life [2,3]. A US Delphi study reported the AD localization at head-and-neck area in 68% of the study population, and this localization resulted significantly associated with both an increased impact of the disease on anxiety and depression (measured by the EuroQol 5-Dimension tool) and a higher prevalence of bothersome symptoms (Itch, soreness, pain, and stinging) [2]. Moreover, a recently published real-life experience analyzed sectorial Eczema Area and Severity Index (EASI) score of the head-andneck region, revealing an association between head-and-neck localization and a worse patient’s quality of life (assessed by Dermatology Life Quality Index [DLQI]), whereas a worse patient’s quality of life was not associated with other body areas [3]. In line with these observations, an expert-based consensus considered head-and-neck involvement in AD as one of the criteria, independently from total EASI score, to define AD as moderate-to-severe [4]. The drug-induced achievement of a stable remission of AD in the head-and-neck area might be difficult to obtain because of constant exposition to irritants, allergens, or because of a hypersensitivity to Malassezia yeast [5,6]. Indeed, a selective localization of AD lesions in seborrheic areas is quite common, especially in adulthood, and several studies detected significantly higher levels of Malassezia-specific IgE in patients with head-and-neck involvement in comparison with patients without AD manifestations in that body area [5]. Thereby, an empirical therapy with topical and/or oral antifungals is suggested, though responsiveness to this therapeutic approach is controversial [5,7]. In addition, long-term application of topical steroids on the face is not recommended due to potential side effects (atrophy, dyschromia, and telangiectasias), while application of topical calcineurin inhibitors (tacrolimus and pimecrolimus) is often limited because of the drug-related burning sensation and discomfort [5]. In recent years, dupilumab, the first biologic agent approved for AD that inhibits the signaling of two pathogenic inflammatory type 2 cytokines, interleukin (IL)−4 and IL−13, has revolutionized the therapeutic management of moderate-to-severe AD in both children and adults, enabling a stable, long-term control of disease manifestations in a large percentage of patients and combining a favorable safety profile [8]. Although no warning signal emerged during clinical trials, several case reports and case series reported the occurrence or worsening of dermatitis in the head-and-neck region during dupilumab treatment [9]. Several hypotheses have been proposed to explain the occurrence of this adverse event, including corticosteroid withdrawal, rosacea, allergic contact dermatitis, Malassezia colonization involving face and/or neck, seborrheic dermatitis, photosensitivity, and alcoholinduced facial redness [9].