Recent intelligence on the evil triad of allergy, asthma, and eczema

New research into an allergic skin condition, atopic dermatitis, shows that the genes controlling the structure of the skin’s outer layers may also open doors to allergy and asthma. Researchers at University of Dundee in Scotland brought together colleagues from Dublin, several US centres, Paris, and Copenhagen to publish their discoveries in the March and April issues of Nature Genetics.

Atopic dermatitis is the most common cause of the itchy, red inflammation of the skin called eczema. In severe cases, the itching drives patients to distraction, sometimes becoming a major focus of their lives. Children have trouble resisting the urge to scratch, and when they do, they damage their skin and cause infections. The disorder is becoming more common in the developed world.

Allergy, asthma, and atopy

Atopic dermatitis is part of a trio of related disorders caused by an immune system that becomes oversensitive to materials commonly found in the environment. The other members of the unfortunate alliance are asthma and allergy. Collectively, the three are called atopy, from the Greek word for “out of place.” The body’s immune system normally responds to threats like cancer cells or invading bacteria or viruses; in atopy, the immune system incorrectly recognizes and attacks substances that should be harmless. Atopy tends to run in families.

Asthma is the member of this trio that most frequently puts children into an Emergency Department, and its frequency is also increasing.

• Asthma is the leading chronic disease of children in industrialized countries and the most common childhood illness after the common cold.
• Asthma is the leading cause of hospital admission in children.
• In Canada, approximately 20 children and 500 adults die each year from asthma.

Atopic conditions like asthma, hay fever, atopic dermatitis, food and pet allergies, and life–threatening anaphylaxis are common in the affluent, industrialized world. Nearly one in three Canadians now suffers from some form of allergic illness. The health care and socio–economic costs are huge. Biomedical research has long struggled against the evil atopic triad, and some chinks in the enemy’s armour are finally becoming evident.

Key barrier missing in skin

Researchers at the University of Dundee were looking at a skin disorder passed from parents to children. The disorder, ichthyosis vulgaris, results in scaly dry skin that can flake off. They found a single gene called FLG was abnormal in family members suffering from ichthyosis vulgaris.

Because we have two copies of most genes, people with one good copy of FLG were mildly affected. These people had dry skin — not usually enough to drive them to seek medical help. But a genetic roll of the dice sometimes means that a child receives a bad copy of FLG from both parents. In this case, the child is entirely unable to make filaggrin, an important protein barrier that forms in the outermost layer of skin. It keeps water in and helps keep allergens out. These individuals had serious skin issues from a young age and needed care from a dermatologist.

While investigating this hereditary skin condition, the researchers met several people with atopic dermatitis. Pursuing this connection, they found that two different abnormal versions of the FLG gene are quite common in European populations, showing up in about 9% of the population. This unlucky fraction has about ten times the normal chance of developing atopic dermatitis. With collaborators, they eventually looked at groups from Norway, France, Ireland, and the United States, and in each case found that less FLG meant more atopic dermatitis.

Under the skin: Asthma

Most investigations of atopic disease have focused on the immune system, so a strong connection to a genetic defect of the skin raised many eyebrows. Even more surprising, the atopy in people missing a copy of FLG often went beyond the skin to the lungs. Some people with asthma have two normal FLG genes and do not have atopic dermatitis. But in someone with atopic dermatitis, FLG raised the risks of asthma significantly, suggesting that one subtype of asthma might be directly related to the skin. Some cases of asthma may occur when the airways overreact to a substance that previously attracted the immune system’s attention by coming in through the skin.

Environment affects allergic diseases

Fortunately for parents who have an atopic disorder themselves, genetics does not always sentence children to a similar struggle. Environment has its role as well. The city of Berlin, previously divided between West and East Germany, was a natural laboratory for atopy investigations after the fall of the Berlin Wall. Research there showed that the two populations were genetically the same, and that something in their environment or behaviour created a large surplus of atopy on the western, more affluent side of the wall. When the wall was dismantled and Germany united, former East Germans had to deal with a rapid rise in atopic disorders. Their genes had not changed, but somehow their new environment had brought atopy to them.

Parent watch

A full understanding of how the environment promotes atopy is a long way off. When two parents with asthma have a child who suffers from atopic dermatitis instead, geneticists are mystified by the switch. Scientists still do not agree on whether it may be helpful to protect a fetus, newborn, or infant from substances that cause many allergies. But there are ways you can help your child deal with an atopic disorder.

• Weigh the risks. “You can't believe everything you read about maternal or infant diets,” according to Dr. Adelle Atkinson of Division of Immunology and Allergy at the Hospital for Sick Children in Toronto (SickKids). Dr. Atkinson, who is currently working on a review of the scientific evidence dealing with the prevention of atopy, sees a lot of questionable information in the mass media and on the Internet. “If you have a prevention question, see your family physician or paediatrician,” she advises. Dr. Atkinson also points out that the cost of avoiding fish, eggs, milk, and nuts throughout a pregnancy can be significant, making it difficult to ensure a properly balanced diet.
• Spot atopic dermatitis before it makes your child miserable. The skin will become inflamed and dry, and your child will tell you that it’s very itchy. This rash is often found where the skin flexes, like the hands, face, elbows and the backs of the knees. The affected skin will remain dry and rough no matter how much moisturizer you try to put on it. Only controlling the inflammation will improve the situation. See a doctor.
• Step in early and control an episode of worsening dermatitis. Dr. Elena Pope, Director of the Paediatric Dermatology Clinic at SickKids, advises: “You need to stay on top of the disease. This means avoiding possible allergens and irritants, avoiding overheating and dryness in the home, and fighting skin dryness with frequent bathing and moisturization. You can treat the inflammation with anti-inflammatories such as topical steroids, and topical immunomodulators [see Treatment, below], and use antihistamines to treat the itching.” For children with atopic dermatitis, bathing means water, but not necessarily soap. Drying off means patting the skin with a towel, not rubbing.
• Consider allergy shots, also called immunotherapy. Taken faithfully, these injections of small amounts of allergen can slowly build up the body’s tolerance and reduce allergy symptoms. Immunotherapy is effective for dust, pollen, insect sting, and mold allergies, but not for food allergies.

Treatment for atopy

• Find food triggers. Finding and avoiding foods your child is allergic to is most important if they have a food allergy. Surprisingly, this approach is not helpful to a majority of people with atopic dermatitis.
• Antihistamines may help with itching and let children sleep.
• Corticosteroid ointments decrease the inflammation in the skin by suppressing the immune system’s response to an allergen. In low to moderate strength, corticosteroids are not absorbed into the rest of the body and should have no side effects. One drawback is that the skin gets used to a particular steroid over time, requiring higher concentrations or a different formulation to get the same effect. To combat this, it is important to treat the patches of eczema as recommended by your doctor and discontinuing the treatment when the skin has returned to normal.
• Tacrolimus (Protopic) and pimecrolimus (Elidel) are drugs approved in Canada for atopic dermatitis that is not responding to corticosteroids. These drugs specifically block one molecular messenger in the immune system, interleukin-2. Short time studies have declared these drugs safe, but their long-term safety has not been proven. Currently they are not used in children less than 2 years of age.

A future without atopy?

While Dr. Atkinson is hoping to get some answers from a thorough look back across previous experiments, McMaster University’s Dr. Judah Denberg is working to build a prospective study of atopic disorders, following 10,000 Canadian children from the womb to adulthood. While it may be small consolation to someone with an itch to scratch right now, there’s every reason to think that in another generation, we’ll have much more effective treatments and prevention for atopy, thanks to a detailed understanding of the immune system that is just starting to take form.

Resources

The Eczema Society of Canada website: 
http://www.eczemahelp.ca/

The Asthma Society of Canada website:
http://www.asthma.ca/

The Allergy/Asthma Information Association website:
http://www.aaia.ca/

Tai Viinikka
Medical writer/editor
AboutKidsHealth