Seborrheic dermatitis—Looking beyond Malassezia

Abstract

Seborrhoeic Dermatitis (SD) is a very common chronic and/or relapsing inflammatory skin disorder whose pathophysiology remains poorly understood. Yeast of the genus Malassezia has long been regarded as a main predisposing factor, even though causal relationship has not been firmly established. Additional predisposing factors have been described, including sebaceous activity, host immunity (especially HIV infection), epidermal barrier integrity, skin microbiota, endocrine and neurologic factors, and environmental influences. Genetic studies in humans and mouse models—with particularly interesting insights from examining the Mpzl3 knockout mice and their SD‐like skin phenotype, and patients carrying a ZNF750 mutation—highlight defects in host immunity, epidermal barrier and sebaceous activity. After synthesizing key evidence from the literature, we propose that intrinsic host factors, such as changes in the amount or composition of sebum and/or defective epidermal barrier, rather than Malassezia, may form the basis of SD pathobiology. We argue that these intrinsic changes provide favourable conditions for the commensal Malassezia to over‐colonize and elicit host inflammatory response. Aberrant host immune activity or failure to clear skin microbes may bypass the initial epidermal or sebaceous abnormalities. We delineate specific future clinical investigations, complemented by studies in suitable SD animal models, that dissect the roles of different epidermal compartments and immune components as well as their crosstalk and interactions with the skin microbiota during the process of SD. This research perspective beyond the conventional Malassezia‐centric view of SD pathogenesis is expected to enable the development of better therapeutic interventions for the management of recurrent SD.

An update on the microbiology, immunology and genetics of seborrheic dermatitis

“…Their proinflammatory cytokines cause barrier dysfunction, resulting in increased alteration of the skin microbiota. As a result, more Malassezia and its by‐products are able to penetrate the epidermis, resulting in a continual cycle of inflammation …”

Malassezia-Associated Skin Diseases, the Use of Diagnostics and Treatment

“…Likewise, the irritating effect on the skin through a compromised permeability barrier function (Turner et al, 2012) of free fatty acids (DeAngelis et al, 2005) and squalene peroxides (Jourdain et al, 2016) produced by Malassezia lipases as a result of its nutritional needs, are key players, at least, in the pathogenesis of dandruff. Accordingly, the skepticism expressed (Wikramanayake et al, 2019) on the implication of Malassezia yeasts in seborrheic dermatitis can be a useful starting point for future research toward the better understanding of seborrheic dermatitis pathogenesis.…”

“…Also it should be stressed that both pimecrolimus and tacrolimus have antifungal action against Malassezia yeasts (Sugita et al, 2006) so at least part of their activity in seborrheic dermatitis can be attributed to this. A variety of alternative or natural product treatments are also suggested for seborrheic dermatitis (Gupta and Versteeg, 2017) while a recent suggestion is the use of formulations that restore the barrier function of the skin (Purnamawati et al, 2017) and definitely formulations that restore the barrier function of the skin will be a useful addition to treatment (Wikramanayake et al, 2019). Furthermore various salts are also efficient, like lithium succinate, which seems to interfere with the availability of the prerequisite lipids for Malassezia growth (Mayser and Schulz, 2016).…”

Towards a renaissance of dermatoendocrinology: Selected current frontiers

“…Instead, the authors argue, the entire human "endocrinome" must be taken into consideration to fully understand the pathobiology of androgenetic alopecia. This concept may well apply to many other dermatoses, whose modulation by hormones has long been appreciated, from acne vulgaris [38,[46][47][48] via seborrhoeic dermatitis to hidradenitis suppurativa. [49,50] This concept is alos in line with newly recognized endocrine abnormalities associated with hidradentitis suppurative/ acne inversa.…”