Microbiological Aspects of Atopic Dermatitis and Their Relationship to Current and Candidate Treatments: A Review. Linking Skin Dysbiosis to Topical Therapy

Abstract

Atopic dermatitis (AD) is a common, chronic, relapsing inflammatory skin disease characterized by xerosis, pruritus and eczematous lesions, arising from the interplay between skin barrier dysfunction and a predominantly T-helper-2 (Th2)-polarized immune response. A defining and clinically important feature of AD is its relationship with the cutaneous microbiome: patients with AD show reduced skin microbial diversity and a marked, disease-activity-dependent expansion of Staphylococcus aureus, which colonizes the skin of 80-100% of patients, correlates with clinical severity, and is accompanied by a deficiency of endogenous antimicrobial peptides. This review summarises the pathogenesis of AD, the evidence linking cutaneous dysbiosis and S. aureus colonization to disease activity, and the extent to which current and candidate topical therapies act upon this microbiological substrate. Topical corticosteroids and the calcineurin inhibitor tacrolimus, the mainstay of AD treatment, reduce S. aureus colonization indirectly, through suppression of cutaneous inflammation and restoration of barrier lipids, rather than through direct antimicrobial action. Dapsone and clofazimine, by contrast, are dual-function agents combining established direct antimicrobial activity against staphylococci and other Gram-positive organisms with a broad anti-inflammatory or immunosuppressive profile encompassing neutrophil, eosinophil and T-lymphocyte function. This mechanistic combination provides a pharmacological rationale for evaluating dapsone and clofazimine as candidate topical agents for AD that could address both the microbial and inflammatory components of the disease. Direct clinical evidence for either agent in AD is currently lacking, and dedicated preclinical and clinical studies, including comparison with tacrolimus, are required before their therapeutic role in AD can be defined.