Filaggrin Genotype – A Risk Factor for Eczema and Allergies

In addition to sensitisation to environmental and food allergens, genetic factors (such as the filaggrin genotype) can also contribute to the development of allergies. A significant proportion of the European population carries variants of the profilaggrin gene that do not produce functional filaggrin protein. This results in a severe impairment of the skin barrier. Carriers of such null or loss-of-function mutations have a significantly increased risk of developing neurodermatitis. Furthermore, the risk of food allergies and hay fever is also elevated. Patients with neurodermatitis are also at a substantially increased risk of developing allergic asthma.

Neurodermatitis, also known as atopic eczema or atopic dermatitis, is one of the most significant inflammatory skin diseases alongside allergic contact dermatitis. In approximately half of all affected individuals, symptoms appear within the first six months of life, in 60% of cases during the first year, and in over 70 to 85% of cases before the age of five. Most affected children are symptom-free by early adulthood.

Symptoms of Neurodermatitis

• Dry skin
• Mild eczema with skin redness
• Severe, sometimes weeping skin lesions with blistering, crusting, or scaling

The occurrence and severity of neurodermatitis vary depending on the disease stage (acute or chronic) and the patient’s age. The structural protein filaggrin plays a key role in proper keratinisation of the epidermis and in maintaining a suitable skin microenvironment. This skin microenvironment includes adequate levels of ceramides (lipids) and natural moisturising factors (which help prevent dryness). Preventive and therapeutic strategies primarily aim to restore and normalise the skin’s barrier function through targeted and comprehensive skincare routines.

Children and Infants Are Frequently Affected

As most individuals affected by neurodermatitis are infants or children, early identification of risk factors is essential in evaluating the need for protective intensive skin care. This aims to prevent or delay the onset of eczema or reduce the severity of chronic inflammation. Willingness to adhere to preventive measures increases significantly if a genetic predisposition can be confirmed. In this context, molecular genetic analysis of the filaggrin genotype—and the possible detection of a loss-of-function mutation—can provide valuable support for clinicians when recommending regular, intensive skincare.

Recent findings suggest that a filaggrin deficiency may also promote the development of food allergies. A clinical study on peanut allergy, for instance, demonstrated that children and adolescents with FLG null mutations have a significantly increased susceptibility to IgE-mediated food intolerances.

FLG null mutations are also associated with increased sensitisation to contact allergens and may thus contribute to the development of type IV allergies such as contact eczema. This is particularly relevant for contact reactions to nickel (commonly found in costume jewellery), other chemical allergens, and chronic irritant contact dermatitis.

Molecular genetic analysis of the filaggrin genotype can detect the four most common loss-of-function variants of the filaggrin gene.

The primary aim of basic therapy is to improve the skin barrier function by preventing moisture loss. To achieve this, topical medicinal and skincare products known as emollients or moisturisers are used (ointments, creams, lotions, etc.). They often also have re-lipidising properties. Ideally, emollients should contain filaggrin and ceramide components. Alternatively, substances that effectively replace missing natural moisturising factors (NMFs) can be used to counteract filaggrin deficiency. This helps to retain moisture in the skin and support barrier regeneration.

A common lipid-replenishing basic therapy for dry and inflamed skin is the application of urea-containing creams. Urea integrates into the skin and reduces transepidermal water loss, thereby preventing excessive skin dryness. As urea creams may cause stinging on sensitive skin, glycerine-based creams are recommended for infants and children up to four years of age.

It is important to ensure that emollients do not contain almond or peanut oils or wheat protein additives, as these are suspected of potentially triggering sensitisation and increasing the risk of developing subsequent food allergies in individuals with neurodermatitis.