Allergy

Allergy is a disorder of the immune system that is often called atopy. Allergic reactions occur to environmental substances known as allergens; these reactions are acquired, predictable and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody, known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma, food allergies, and reactions to the venom of stinging insects such as wasps and bees.

Mild allergies like hay fever, are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis and runny nose. Similarly, conditions such as asthma are common, in which allergy plays a major role. In some people, severe allergies to environmental or dietary allergens, or to medication, occur that may result in life-threatening anaphylactic reactions and potentially death.

A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of antihistamines, steroids or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy.

Classification and history

The concept "allergy" was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after noting that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods. Pirquet called this phenomenon "allergy" from the Greek words allos meaning "other" and ergon meaning "work".Historically, all forms of hypersensitivity were classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with the common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed by Philip Gell and Robin Coombs that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity. With this new classification, the word "allergy" was restricted to only type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions.

A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE) - Kimishige Ishizaka and co-workers were the first to isolate and describe IgE in the 1960s.

Signs and symptoms

Many allergens are airborne particles, such as dust or pollen. Allergic rhinitis, also known as hay fever, occurs in response to airborne pollen, and causes irritation of the nose, sneezing, and itching and redness of the eyes. Inhaled allergens can also lead to asthmatic symptoms, caused by narrowing of the airways (bronchoconstriction) and increased production of mucus in the lungs, shortness of breath (dyspnea), coughing and wheezing.

Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin, and antibiotics such as penicillin. Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhoea, itchy skin, and swelling of the skin during hives or angiooedema. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis. Insect stings, antibiotics and certain medicines produce a systemic allergic response that is also called anaphylaxis; multiple systems can be affected including the digestive system, the respiratory system, and the circulatory system. Depending of the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma and even death. This type of reaction can be triggered suddenly or the onset can be delayed. The severity of this type of allergic response often requires injections of epinephrine, sometimes through a device known as the Epi-Pen auto-injector. The nature of anaphylaxis is such that the reaction can seemingly be subsiding, but may recur throughout a prolonged period of time.

Substances that come into contact with the skin, such as latex are also common causes of allergic reactions, known as contact dermatitis or eczema. Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives and angioedema.

Cause

Risk factors for allergy can be placed in two general categories, namely host and environmental factors. Host factors include heredity, sex, race and age, with heredity being by far the most important. There are recent increases in the incidence of allergic disorders, however, that cannot be explained by genetic factors alone. The four main candidate environmental factors are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.

Genetic basis

Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins. Allergic parents are more likely to have allergic children, and their allergies are likely to be stronger than those from non-allergic parents. However some allergies are not consistent along genealogies; parents who are allergic to peanuts, may have children who are allergic to ragweed, or siblings that are allergic to different things. It seems that the likelihood of developing allergies is inherited and due to some irregularity in the way the immune system works, but the specific allergen, which causes the development of an allergy,

The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk. Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years. The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10. Overall, boys have a higher risk of developing allergy than girls, although for some diseases, namely asthma in young adults, females are more likely to be affected. Sex differences tend to decrease in adulthood. Ethnicity may play a role in some allergies, however racial factors have been difficult to separate from environmental influences and changes due to migration. Interestingly, with regards to asthma, it has been suggested that different genetic loci are responsible for asthma in people of Caucasian, Hispanic, Asian, and African origins.

Environmental factors

International differences have been associated with the number of individuals within a population that suffer from allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.

Exposure to allergens, especially in early life, is an important risk factor for allergy. Alterations in exposure to microorganisms is the most plausible explanation, at present, for the increase in atopic allergy. Since children that live in large families or overcrowded households, or attend day care, have a reduced incidence of allergic disease, a relationship has been proposed between exposures to bacteria and viruses during childhood, and protection against the development of allergy, which has been called – the "hygiene hypothesis". Exposure to endotoxin and other components of bacteria may reduce atopic diseases.Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood. Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.

Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies. Recent research has shown that some common parasites, such as intestinal worms (e.g. hookworms), secrete chemicals into the gut wall (and hence the bloodstream) that suppress the immune system and prevent the body from attacking the parasite.This gives rise to a new slant on the hygiene hypothesis theory — that co-evolution of man and parasites has led to an immune system that only functions correctly in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive. In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants. However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms. Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies. It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work