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 apersons immune system against a normallyharmless substance. A person withoutallergies would have no reaction to thissubstance, but when a person who is allergicencounters the trigger, the body reacts byreleasing chemicals which cause allergysymptoms.
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 substanceresponsible for causing the allergy, orallergen, binds to allergic antibodiespresent on allergic cells in a personsbody, including mast cells and basophils.These cells then release chemicals suchas histamine and leukotrienes, resultingin 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 whichcommonly occurs in infancy and earlychildhood but can continue or start in adults.Like other allergies and asthma, atopicdermatitis tends to run in families. It isimportant to note that atopic dermatitis is nota rash that itches. Rather, it is an itch, thatwhen scratched, results in a rash.
diagnose atopic dermatitis1. Atopy. The person must be atopic, or have afamily history of allergic diseases in close relatives.2. Pruritis. If the skin or areas of the rash do not itchor have not been scratched, then the person does nothave atopic dermatitis.3. Eczema. The rash appears red, with small blistersor bumps present. These may ooze or flake withfurther scratching. Over the long-term the skinappears 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 SymptomsApproximately 8% of children and 2% ofadults suffer from true food allergies. Whenthe culprit food is eaten, most allergicreactions will occur within minutes. Skinsymptoms (itching, urticaria, angioedema) arethe most common, and occur during mostfood 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 TreatmentOral anti-histamines. This is the most common class ofmedications used for allergic rhinitis. The first generationanti-histamines, which includes Benadryl®, are generallyconsidered too sedating for routine use. These medicationshave been shown to affect work performance and alter apersons ability to operate an automobile.Topical nasal steroids. This class of allergy medications isprobably the most effective at treating nasal allergies, as wellas non-allergic rhinitis. There are numerous topical nasalsteroids on the market, and are all available by prescription.Some people note that one smells or tastes better thananother, 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, commonlycause cough, sore throat, and sometimes bodyaches and fever, but not itchy, watery eyes.Allergies can last for a month or more,commonly cause itchy eyes, and dont causefevers or body aches; plus, they tend to causecoughing only in those who have asthma
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.