Filaggrin is a protein found in the outermost layer of human skin, known as the stratum corneum. This protein is formed from a larger precursor molecule called profilaggrin, which is processed into multiple filaggrin units during the maturation of skin cells. It plays a part in the skin’s structure, helping maintain its protective barrier, integrity, and hydration.
Filaggrin’s Role in Skin Barrier Function
Filaggrin helps organize keratin filaments within skin cells, contributing to their flattening and strengthening. This process forms a strong, insoluble matrix, which provides mechanical strength to the skin’s outermost layer.
The protein also breaks down into amino acids, which are part of the skin’s natural moisturizing factor (NMF). These NMF components draw and hold water, helping to keep the skin hydrated and preventing water loss. Filaggrin degradation products also help regulate the skin’s pH, maintaining its slightly acidic state, which is important for enzyme function and overall barrier health. This barrier acts as a protective shield, keeping moisture within the body while keeping out external substances such as allergens, irritants, and pathogens.
Understanding Filaggrin Mutations
A mutation in the FLG gene leads to a deficiency or dysfunction of filaggrin. These genetic changes can result in the production of abnormally short profilaggrin molecules that cannot be properly processed into functional filaggrin proteins. Consequently, this leads to a reduced amount or complete absence of filaggrin in the skin.
When filaggrin is deficient, the skin barrier becomes compromised. This impairment means the skin is less effective at retaining moisture, leading to increased water loss. It also allows environmental irritants and allergens to penetrate the skin more easily, potentially triggering immune responses. These FLG gene mutations are often inherited.
Associated Health Conditions
Mutations in the filaggrin gene are associated with several health conditions, with atopic dermatitis (eczema) is the most frequent. In individuals with atopic dermatitis, the compromised skin barrier allows allergens and irritants to penetrate the skin, leading to inflammation, dryness, and intense itching. The severity and persistence of atopic dermatitis are often greater in those with filaggrin mutations.
Beyond atopic dermatitis, FLG mutations increase the risk for other allergic conditions, a progression often referred to as the “atopic march.” This refers to the typical sequence in which allergic diseases develop, often starting with atopic dermatitis in infancy or early childhood, followed by food allergies, and then respiratory allergies like asthma and allergic rhinitis. For instance, children with FLG mutations have an almost threefold increased risk for food allergies, including common allergens like hen’s egg, cow’s milk, peanut, and hazelnut, and may experience more severe reactions. The weakened skin barrier allows allergens to enter the body through the skin, potentially leading to sensitization and subsequent allergic responses in other organ systems. Individuals with FLG mutations also have an increased risk of developing asthma, particularly if they also have atopic dermatitis.
Managing Conditions Linked to Filaggrin Mutations
Managing conditions associated with filaggrin mutations primarily involves strategies to support and repair the skin barrier. Consistent skincare routines are important for individuals with compromised skin barriers. This includes frequent application of moisturizers, especially thick ointments or creams, to help maintain skin hydration and reduce water loss. Applying moisturizers immediately after bathing can help lock in moisture.
Gentle cleansing with non-soap cleansers, which have a lower pH, is also recommended to avoid further disrupting the skin barrier. Identifying and avoiding triggers that can irritate the skin or provoke allergic reactions is another important management step. Some research suggests that certain supplements, like histidine, an amino acid that is a building block for filaggrin, may help improve filaggrin production and reduce symptoms. Consulting with healthcare professionals is advisable for personalized diagnosis and to develop a comprehensive management plan.