Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder

Abstract

Atopic dermatitis comorbidities extend well beyond the march to allergic conditions (food allergy, asthma, allergic rhinitis, allergic conjunctivitis, and eosinophilic esophagitis), suggesting both cutaneous and systemic immune activation. In reviewing atopic dermatitis comorbidities, Councilors of the International Eczema Council found a strong pattern of immune activation in peripheral blood and the propensity to both skin and systemic infections. Associations with cardiovascular, neuropsychiatric, and malignant diseases were increasingly reported, but confirmation of their link with atopic dermatitis requires longitudinal studies. Given the possibility of atopic dermatitis-related systemic immune activation, future investigations of new interventions should concurrently examine the impact on these comorbidities.

Biomarkers for atopic dermatitis

“…Recent studies have also shown associations between AD and alopecia areata, neuropsychiatric and cardiovascular diseases (CVD). 57 The association between adult AD and CVD, would be consistent with a recent study that showed the occurrence of severe CVD and metabolic abnormalities in a mouse model of severe dermatitis resulting from persistent release of IL-1 family cytokines from the skin. 58 Interestingly, these pathologies were ameliorated by combination treatment with anti-IL-1α-and anti-IL-1β neutralizing antibodies.…”

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

“…Based on our observations of hormonal imbalance in allergic children (described above), we hypothesize that dysregulation of the endocrine system could represent a missing systemic link underlying susceptibility to initial barrier dysfunction. Remarkable similarities in the biology of barrier dysfunction across different allergic diseases (Figure 1), including upper and lower “unified” airway responses and non-lesional defects in clinically unaffected skin of atopic dermatitis patients, all support the existence of such a systemic trigger of disease 131–133 . Transgenic mouse models with defects in proteins maintaining epithelial homeostasis, such as filaggrin, are also characterized by spontaneous allergic sensitization and enhanced allergic inflammation 134–137 .…”

Verbascoside Alleviates Atopic Dermatitis-Like Symptoms in Mice via Its Potent Anti-Inflammatory Effect

“…Several observations suggest that AD is the cutaneous manifestation of a systemic disorder that also gives rise to asthma, food allergy, and allergic rhinitis [8,9]. These conditions are all characterized by elevated serum IgE levels and peripheral eosinophilia [10,11]. The major elements involved in the immune dysregulation are Langerhans cells, inflammatory dendritic epidermal cells, monocytes, macrophages, lymphocytes, mast cells, and keratinocytes.…”