What is the pathogenesis of seborrheic dermatitis?

From the Guidelines

The pathogenesis of seborrheic dermatitis is primarily driven by the interaction of Malassezia yeast with the skin, particularly in sebum-rich areas, leading to inflammation and skin barrier damage. The presence of Malassezia yeast, such as Malassezia furfur, is a key factor in the development of seborrheic dermatitis, as it metabolizes sebum and produces irritating byproducts like oleic acid 1. This process is further complicated by genetic predisposition, neurogenic factors, hormonal influences, and environmental factors, which all contribute to the characteristic inflammatory skin condition. Some key points to consider in the pathogenesis of seborrheic dermatitis include:

• Genetic predisposition, with certain immune system variations increasing susceptibility
• Neurogenic factors, such as stress, fatigue, or neurological disorders like Parkinson's disease, which can exacerbate symptoms
• Hormonal influences, particularly the increase in sebum production after puberty, which can contribute to the development of seborrheic dermatitis
• Environmental factors, such as cold, dry weather, which can compromise skin barrier function and worsen symptoms
• Immune dysregulation, with abnormal inflammatory responses to Malassezia yeast, which is typically tolerated by normal skin 1. Overall, the pathogenesis of seborrheic dermatitis is a complex process involving multiple factors, and understanding these factors is crucial for effective management and treatment of the condition.

From the FDA Drug Label

Mode of Action:In vitro studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated that the therapeutic effect of ketoconazole in seborrheic dermatitis is due to the reduction of M. ovale, but this has not yet been proven. The pathogenesis of seborrheic dermatitis is postulated to be related to the presence of Malassezia ovale, but this has not been proven 2.

• The exact mechanism is unclear, but it is thought that the reduction of M. ovale may play a role in the therapeutic effect of ketoconazole in seborrheic dermatitis.
• No conclusive evidence is provided in the drug label to fully explain the pathogenesis of seborrheic dermatitis.

From the Research

Pathogenesis of Seborrheic Dermatitis

The pathogenesis of seborrheic dermatitis is a complex process that involves multiple factors, including:

• Malassezia species, which are lipophilic yeasts that form part of the normal cutaneous microflora of humans 3
• Inflammatory response to Malassezia species, which is considered basic in the etiology of seborrheic dermatitis 3
• Immune system activation by Malassezia hydrolysation of free fatty acids, leading to the activation of pattern recognition receptors, inflammasome, IL-1β, and NF-kB 4
• Production of irritating oleic acids by M. restricta and M. globosa, leading to IL-8 and IL-17 activation 4

Key Factors Involved in Pathogenesis

Some key factors involved in the pathogenesis of seborrheic dermatitis include:

• Malassezia proliferation and inflammation, which are the primary underlying pathogenic mechanisms 5
• Immune mechanisms, including non-immune and immune mechanisms (nonspecific and specific) 3
• Genetic predisposition, with certain increased-risk human leucocyte antigen (HLA) alleles, such as A32, DQB105, and DRB1*01 4
• Systemic disease, such as HIV and Parkinson's disease, which can contribute to the development of seborrheic dermatitis 4

Mechanisms of Disease

The mechanisms of seborrheic dermatitis are not fully elucidated, but they are thought to involve:

• Malassezia species causing seborrheic dermatitis by involving and combining both non-immune and immune mechanisms 3
• IL-17 and IL-4 playing a big role in pathogenesis, although this needs to be further studied using novel biologics 4
• Complement system dysfunction, which can impair the ability of the immune system to restrict Malassezia growth 4