Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation

Abstract

Introduction & objectivesHead and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur.Materials and methodsTo identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry.ResultsIncreased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-β, TNF-α, and IL-1β levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited.ConclusionsUnder decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.

Background factors predicting the occurrence of herpes zoster in atopic dermatitis patients treated with upadacitinib

“…33 Malassezia disrupts the barrier of the stratum corneum, allowing the permeation of various allergens and sensitization to them. 34 AD patients with occurrence of HZ during upadacitinib treatment had higher baseline LDH values compared to those without.…”

“…Malassezia colonizes the face and contributes to the development of head and neck rash in patients with AD 33 . Malassezia disrupts the barrier of the stratum corneum, allowing the permeation of various allergens and sensitization to them 34 . A previous study reported that AD patients with head and neck rash had elevated levels not only of Malassezia ‐specific IgE, but of total IgE 34 .…”

“…Malassezia disrupts the barrier of the stratum corneum, allowing the permeation of various allergens and sensitization to them 34 . A previous study reported that AD patients with head and neck rash had elevated levels not only of Malassezia ‐specific IgE, but of total IgE 34 . It is thus hypothesized that AD patients with severe head and neck rash may have systemic Th2‐skewed immunity with relative decrease in Th1 activity, which might increase the susceptibility to HZ triggered by upadacitinib treatment.…”

Therapeutic effectiveness of upadacitinib on individual types of rash in Japanese patients with moderate‐to‐severe atopic dermatitis

“…Second, Malassezia furfur abundantly colonized on head and neck may contribute to the pathogenesis of treatment‐resistant erythema in AD patients 27 . M. furfur may disrupt the barrier of stratum corneum by reducing the esterified omega‐hydroxyacyl‐sphingosine content and inducing the expression of VEGF, IL‐31, and IL‐33 in epidermal keratinocytes and of VEGF receptor, TNF‐α, and IL‐1β in dermal endothelial cells, which may promote inflammation and angiogenesis, leading to the generation of treatment‐resistant erythema 28 …”

“…27 M. furfur may disrupt the barrier of stratum corneum by reducing the esterified omega-hydroxyacyl-sphingosine content and inducing the expression of VEGF, IL-31, and IL-33 in epidermal keratinocytes and of VEGF receptor, TNFα, and IL-1β in dermal endothelial cells, which may promote inflammation and angiogenesis, leading to the generation of treatment-resistant erythema. 28 This study has some limitations. First, the sample size is small.…”