Causes of atopic dermatitis

Author: Dr Amy Stanway, Department of Dermatology, Waikato Hospital, February 2004


There is no known single cause for atopic dermatitis (eczema): it probably represents more than one condition. There are many theories regarding the underlying mechanisms. Current research is investigating the roles of the immune system, filaggrin gene mutations, defects in the skin cells (keratinocytes), skin surface microbes (bacteria, viruses and yeasts), and many other factors.

Current theories identify that atopic dermatitis is a disease of the immune system, with cytokines being key components to the disease. These cytokines, particularly IL-4 and IL-13 (Th2 pathway cytokines) and IL-22 (the Th22 axis cytokine) cause barrier defects that result in the clinical features of eczema.

What is atopy?

Atopy refers to the tendency to asthma, eczema and hay fever. Atopy is largely inherited (genetic). It is characterised by an overactive immune response to environmental factors. The same factors have no effect on the skin of a non-atopic. Yet, despite their genetic background, some children from an atopic family never develop atopic dermatitis and children with no family history can suffer from it.

Atopic dermatitis is a disease of the whole body that manifests in the skin. Events that upset the body in other ways (such as viral infection, teething, eating certain foods) may have an effect on the dermatitis. Flares may also occur without obvious provocation and can be very frustrating.

The inherited barrier defect – the role of filaggrin

Recently, there is emerging evidence that inflammation in atopic dermatitis is associated with immune-mediated and inherited abnormalities in the skin barrier. This barrier failure causes increased permeability of the skin and reduces its antimicrobial function.

The main inherited abnormality causing disordered barrier function is filaggrin expression. Filaggrins are filament-associated proteins which bind to keratin fibres in the epidermal cells. The gene for filaggrin resides on Chromosome 1 (1q21.3). This gene was first identified as the gene involved in ichthyosis vulgaris.

It is postulated that the loss of filaggrin results in:

The immune system

The immune system develops in the first six months of life. There is a generally an equilibrium of the two main types of T Helper lymphocytes (small white blood cells), Th-1 and Th-2. In atopic dermatitis there is often an imbalance, with far more Th-2 cells and their associated chemical messengers (cytokines). In some children there are also high levels of the antibody immunoglobulin E (IgE) antibodies and eosinophils (the white blood cells associated with allergy). 

The Th2 associated cytokines contribute to the loss of skin barrier function:  

The specialised immune cells of the epidermis (Langerhan cells) have an increased response to these antigens in atopic dermatitisand interact with dermal T cells to produce a even greater Th2 response further exacerbating the barrier defect.

So both genetic make-up of the individual and ‘external’ environmental factors contribute to the likelihood of developing eczema, its severity and its response to treatment.

Very rarely, atopic dermatitis may be due to an underlying inherited immune deficiency such as Job syndrome. In this disease, the dermatitis appears very soon after birth and is complicated by severe infections.

What makes the skin get drier?

Dry skin is a sign of the loss of barrier function. Factors that make the skin even drier may make the eczema harder to control:

A brief shower or bath once a day is enough if you have dry skin. However, your doctor may specifically recommend bathing for longer or more often during the acute blistered phase of eczema. Use a non-soap cleanser.

Regular use of an emollient helps skin retain moisture and combat dryness.

What is the role of irritants?

Most people with eczema will notice that certain things seem to irritate their skin with immediate stinging or itching and may also cause a flare of eczema (irritant contact dermatitis). These are not allergies.

It is common sense to avoid the substances that irritate.

The role of infection

Antigen stimulation

Infective organisms play an important role in triggering and aggravating atopic dermatitis. Bacteria (staphylococci and streptococci) and yeasts (malassezia and candida) on the skin provide constant stimulation to the immune system resulting in chronic inflammation.

Bacterial infection

People who have atopic dermatitis are particularly prone to skin infections withStaphylococcus aureus.

As a result people with atopic dermatitis frequently suffer from boils, folliculitis and infected eczema.

The infection causes the eczema to worsen and become more resistant to the usual treatment with emollients and topical steroids. S. aureus produces enterotoxin. This induces the production of enterotoxin specific IgE resulting in proliferation and recruitment of more T cells and aggravating the dermatitis.

Antibiotics are often required to eliminate the infection and control the eczema.

Viral infections

Fungal infections

Dermatophyte infections (tinea) do not appear to be more prevalent in atopic dermatitis.

Allergens and eczema

Food allergies

Food allergies affect about a third of children with eczema. They are most commonly to egg, cows milk, soy, wheat, peanuts and fish. The reaction may be acute urticaria (hives) sometimes accompanied by swelling of the face and tongue (angioedema) or abdominal pain shortly after ingesting the offending food. Severe allergy causes anaphylaxis and the patient may collapse and even die. Any tiny amount of the food allergen can cause this response. These reactions are not eczema.

However, eczema can be aggravated by certain foods in other ways (food intolerance).

Environmental allergies

Environmental allergens may sometimes be related to atopic dermatitis. Many children with atopic dermatitis are allergic to grass, dust mites and cat dander. Usually this manifests as an immediate reaction with runny nose, sneezing and swollen eyes, and improves after removal from the allergy source. It is uncommon for this type of allergy to cause persistent worsening of the eczema.

Allergic contact dermatitis is equally common in those without atopic dermatitis.



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