allergies gk

Allergies

Atopy

• The predisposition to produce high quantities of Immunoglobulin (Ig)-E

• Immediate (Type I hypersensitivity)

• Mast cells, basophils, eosinophils, Th2 cells

Allergy

• Allergic Disease is mediated by IgE• First described by Prausnitz & Kustner in

1921• Proposed the existence of “atopic reagin” in

serum of allergic subjects• 45 years later Ishizaka described a new

class of immunoglobulin - IgE

What is an Allergy?

An allergy is an abnormal reaction by a person's immune system against a normally harmless substance. A person without allergies would have no reaction to this substance, but when a person who is allergic encounters the trigger, the body reacts by releasing chemicals which cause allergy symptoms.

Allergic Disease

• Seen in 30-35% of the population• Perennial & seasonal allergic rhinitis• Allergic (extrinsic asthma)• Atopic and contact dermatitis• Urticaria• Food intolerance

What is Happening During an Allergic Reaction?

During an allergic process, the substance responsible for causing the allergy, or allergen, binds to allergic antibodies present on allergic cells in a person's body, including mast cells and basophils. These cells then release chemicals such as histamine and leukotrienes, resulting in allergic symptoms.

Allergy Symptoms

• In children, allergic disease first occurs as atopic dermatitis (eczema) or food allergies.

• Typically, atopic dermatitis goes away by adulthood, as do many types of food allergies. Allergic rhinitis and asthma, however, most often start during the adolescent, teenage and young adult years, and are likely to persist throughout a person’s life. The severity of allergic symptoms, however, may wax and wane, and even temporarily disappear during a person’s life.

Eczema (atopic dermatitis)

is a chronic, recurrent skin disease which commonly occurs in infancy and early childhood but can continue or start in adults. Like other allergies and asthma, atopic dermatitis tends to run in families. It is important to note that atopic dermatitis is not a rash that itches. Rather, it is an itch, that when scratched, results in a rash.

diagnose atopic dermatitis

1. Atopy. The person must be atopic, or have a family history of allergic diseases in close relatives.

2. Pruritis. If the skin or areas of the rash do not itch or have not been scratched, then the person does not have atopic dermatitis.

3. Eczema. The rash appears red, with small blisters or bumps present. These may ooze or flake with further scratching. Over the long-term the skin appears thickened and leathery.

Treatment of Atopic Dermatitis• Topical steroids. These medications are the first line

therapy for atopic dermatitis, as side effects such as thinning of the skin, pigment changes of the skin, and absorption into the body are possible.

• Topical calcineurin inhibitors. Elidel® and Protopic®, are approved for short-term use in children older than 2 years of age for atopic dermatitis.

• Oral steroids. Rarely, short courses of oral steroids are required to achieve control of a severe flare of atopic dermatitis. Extreme caution should be used, as while the eczema typically gets better on the oral steroids, a “rebound effect” can occur with worsening of the skin soon after the steroids are stopped.

Food Allergy Symptoms

Approximately 8% of children and 2% of adults suffer from true food allergies. When the culprit food is eaten, most allergic reactions will occur within minutes. Skin symptoms (itching, urticaria, angioedema) are the most common, and occur during most food reactions.

Allergic rhinitis

• Seasonal (pollen, spores) or perennial (house dust mite)

• Mucus production (Runny nose, nasal stuffiness

• Itching & sneezing• Treat with antihistamines or nasal steroids

How is allergic rhinitis diagnosed?

• Presence of other atopic diseases (such as atopic dermatitis)

• Family history of allergic diseases • Symptoms associated with a season or trigger

(such as a cat) • Improvement of the allergy symptoms with

medications • The presence of itching (of the nose, eyes, ears,

roof of mouth) is highly suggestive of allergies

Hay Fever Treatment

Oral anti-histamines. This is the most common class of medications used for allergic rhinitis. The first generation anti-histamines, which includes Benadryl®, are generally considered too sedating for routine use. These medications have been shown to affect work performance and alter a person's ability to operate an automobile.

Topical nasal steroids. This class of allergy medications is probably the most effective at treating nasal allergies, as well as non-allergic rhinitis. There are numerous topical nasal steroids on the market, and are all available by prescription. Some people note that one smells or tastes better than another, but they all work about the same.

Anaphylaxis

• Very acute and severe reaction to allergen• Peanuts, shellfish, penicillin, insect stings• Allergen moves from gut to blood stream• Massive histamine release from mast cells

and basophils• Vasodilatation leads to dramatic drop in

blood pressure• Often fatal if not treated with adrenaline

Cold or Allergy?

Colds last only one to two weeks, commonly cause cough, sore throat, and sometimes body aches and fever, but not itchy, watery eyes. Allergies can last for a month or more, commonly cause itchy eyes, and don't cause fevers or body aches; plus, they tend to cause coughing only in those who have asthma

Histamine

• Skin – wheal, erythema, pruritis• Eye - conjunctivitis, erythema, pruritis• Nose – nasal discharge, sneeze, pruritis• Lung – bronchospasm of smooth muscle

Histamine

• Therapeutic intervention in allergy often focused on blocking the effects of histamine

• Histamine also functions as a neurotransmitter in CNS

• Very important in maintaining a state of arousal or awareness

First Generation Antihistamines

• The first H1 antagonist synthesised by Bovet & Staub at the Institut Pasteur

• Too weak or toxic• Phenbezamine first effective antihistamine• Mepyramine maleate, diphenhydramine &

tripelennamine developed in 1940’s• Still in use today

First Generation Antihistamines

• Easily cross the blood–brain barrier.• Sedative and anticholinergic effects (sedating

antihistamines).• Short half-lives.• Limited use in the treatment of allergic

symptoms. • Still widely used, mainly as over-the-counter

products, often in combination with other drugs.

Second Generation Antihistamines

• Highly effective treatments for allergic disease • Do not cross blood-brain barrier• Lack significant CNS & anticholinergic effects• Long half life• Among the most frequently prescribed and

safest drugs - expensive

Other treatments

• Nasal steroids – must be given before season – relieve nasal blockade

• Antihistamines combined with anti-leukotriene drugs

• Avoidance -mattress covers, specialised Hoovers, wood floors,

Allergic Disease

• Dramatic increase in allergic disease over the past three decades, why is this?

• Genetics• Environmental factors - pollution• Changes in Lifestyle• Occupational  

Genetics (1)

• Family history of allergic disease is a strong risk factor for developing asthma

• Danger of developing asthma particularly if one or both parents are atopic

• Children with atopic dermatitis at risk of asthma -– “the allergic march”

Genetics (2)

• No single "allergy or asthma chromosome". Several markers demonstrated in small selected populations - much further work is required

• The genetics of allergy and asthma are polygenic - influence many factors such as IgE secretion, cytokines and inflammatory cell profiles

Environment (1)

• Children & adults 90% spent time indoors• Allergens in dust (dust mite faeces) or pets (particularly

cats) - increased risk of allergic sensitization in proportion to exposure.

• Most children and adolescents with asthma sensitized to indoor allergens - avoidance often leads to improvement in airway disease.

• Modern housing generally poorly ventilated with fitted carpets and central heating - house dust mite infestation

Environment (2)

• Children exposed to tobacco smoke more likely to develop wheezing and impaired lung function

• Outdoor allergens –seasonal variation and weather• Account for 10-20% of allergic disease in Europe -

mainly hay fever. • Increased pollution not responsible for increase in

allergic disease - pollutants worsen respiratory symptoms in asthmatics and reduce lung function

Changes in Lifestyle (1)

• Hygiene hypothesis - Past 30 years - changes in pattern of childhood infection, many no longer experienced

• Exposure to certain infections may protect against the development of allergies.

• Respiratory viruses may be a risk factor for the development of asthma

• Vaccination programmes not thought to have direct effect on the development of allergic disease

Changes in Lifestyle (2)

• Intake of fresh fruit and vegetables has declined leading to lower anti-oxidant levels.

• Certain fatty acids are able to shift the immune system towards allergic susceptibility

• Food preservatives may effect gut flora leading to allergic sensitization rather than development of tolerance

Changes in Lifestyle (3)

• The immune system is severely compromised by poor nutrition

• Paradoxically the vast improvement in nutrition in the last fifty years might have led to the immune systems of some individuals "over reacting" to benign substances i.e. allergens

Conclusion

• Atopy – propensity to produce high levels of IgE from B cells

• Allergens mimic parasites – processed and presented by APC (e.g. dendritic cells)

• Orchestrated by Th2 cells – cytokine release• Effector cells – mast cells, basophils• Mediators – cytokines, histamine,

leukotrienes, PAF etc.