Malassezia and atopic dermatitis

Molecular Mechanisms Underlying Atopic Dermatitis: The Barrier-Lipid-Mycobiome Axis: Malassezia is lipid-dependent and utilizes components of cutaneous sebum via lipases and phospholipases. This process produces free fatty acids and other lipid metabolites, which can have an irritant or immunomodulatory effect when the skin barrier is compromised. In atopic scalp and neck dermatitis, reduced levels of long-chain, barrier-relevant ceramides—including esterified ω-hydroxyacyl sphingosines—have been detected. This gives rise to a possible feedback loop: recognition by the innate immune system. Malassezia components are recognized by, among others: TLR2 and TLR4, Dectin-1 and Dectin-2, Mincle, mannose receptors, complement receptors, and presumably the NLRP3 inflammasome. The cells affected include keratinocytes, dendritic cells, monocytes, macrophages, and Langerhans cells. Malassezia can thus trigger both Type 2 and Type 17 inflammation.

Th17 axis: Malassezia induces the differentiation or activation of Th17 cells via dendritic cells and IL-23, resulting in: IL-17A and IL-17F, IL-22, recruitment of neutrophils, and induction of antimicrobial peptides. This response is fundamentally part of the regulatory antifungal immune response. However, in the presence of a barrier defect, it can exacerbate cutaneous inflammation. Experimentally, Malassezia has been shown to induce a Type 17 response that, on the one hand, supports fungal control but, on the other hand, exacerbates eczematous inflammation.

Atopic Head-and-Neck Dermatitis: Atopic “head-and-neck dermatitis” is a clinical phenotype of atopic dermatitis that primarily affects: the forehead and hairline, eyelids, perioral region, ears and retroauricular region, throat and neck region, and the upper décolletage. Typical features include relatively sharply demarcated, erythematous, scaling plaques that occur primarily in areas rich in sebaceous glands. There is often a discrepancy between pronounced head-and-neck involvement and less activity on the rest of the skin. Malassezia-specific IgE is detected significantly more frequently in this phenotype than in generalized atopic dermatitis without a head-and-neck focus.

In atopic scalp and neck dermatitis , Malassezia spp.are considered pathogenic factors that contribute to the exacerbation of the condition. In large meta-analytic observational studies (n = 840 patients), overall prevalences of Malassezia-specific IgE were found to be 79.3% in these patients (see Tow HX et al. 2024).

Changes in the mycobiome: Dupilumab generally improves the epidermal barrier and alters both the bacterial microbiome and the mycobiome. Whether this routinely leads to a quantitative increase in Malassezia has not been established. It is more likely that there is a change in the microbial composition and the immune response to existing yeasts.