Pbl 4 –HD

asem shadid

05/03/23 Basal Ganglia 1

Introduction • allergy is number of conditions caused by hypersensitivity of the

immune system to something in the environment that usually causes little problem in most people.

• Hypersensitivity (also called hypersensitivity reaction or intolerance) is a set of undesirable reactions produced by the normal immune system, including allergies and autoimmunity.

• Allergic disease is estimated to affect around 15-20% of the population of the western world, with a two- to three-fold increase being seen in the past 20-30 years (Royal College of Physicians, 2003).

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• Allergens By definition, an allergen induces type I IgE-mediated or type IV T-cell–mediated immune responses. Allergic triggers are almost always low molecular weight proteins; many of them can become attached to airborne particles.

• People who have allergies often are sensitive to more than one thing. Substances that often cause reactions are

• Pollen -Dust• Mold spores• Pet dander• Food• Insect stings• Medicines

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Classification of Hypersensitivity Reactions

• Coombs and Gell classification It divides the hypersensitivity reactions into the following 4 types:

• Hypersensitivity disorders often involve more than 1 type.• Type I reactions Type I reactions (ie, immediate hypersensitivity reactions) involve

immunoglobulin E (IgE)–mediated release of histamine and other mediators from mast cells and basophils. [2] Examples include anaphylaxis and allergic rhinoconjunctivitis.

• Type II reactions Type II reactions (ie, cytotoxic hypersensitivity reactions) involve immunoglobulin G or immunoglobulin M antibodies bound to cell surface antigens, with subsequent complement fixation. An example is drug-induced hemolytic anemia.

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Con .

• Type III reactions Type III reactions (ie, immune-complex reactions) involve circulating antigen-antibody immune complexes that deposit in postcapillary venules, with subsequent complement fixation. An example is serum sickness.

• Type IV reactions Type IV reactions (ie, delayed hypersensitivity reactions, cell-mediated immunity) are mediated by T cells rather than by antibodies. An example is contact dermatitis from poison ivy or nickel allergy.

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• Some authors believe this classification system may be too general and favor a more recent classification system proposed by Sell et al.[3] This system divides immunopathologic responses into the following 7 categories:

• Inactivation/activation antibody reactions • Cytotoxic or cytolytic antibody reactions • Immune-complex reactions • Allergic reactions • T-cell cytotoxic reactions • Delayed hypersensitivity reactions • Granulomatous reactions

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Atopic and Allergic Disorders • The terms atopy and allergy are often used interchangeably but are

different:• Atopy is an exaggerated IgE-mediated immune response; all atopic

disorders are type I hypersensitivity disorders.• Allergy is any exaggerated immune response to a foreign antigen

regardless of mechanism.• Thus, all atopic disorders are considered allergic, but many allergic

disorders (eg, hypersensitivity pneumonitis) are not atopic.

• Type I hypersensitivity reactions underlie all atopic and many allergic disorders.

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Cause - Etiology

• 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 significant.

• Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.

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Etiology - Genetic factors • Genetic factors may be involved, as suggested by familial

inheritance of disease, association between atopy and specific HLA loci, and polymorphisms of several genes, including those for the high-affinity IgE receptor β-chain, IL-4 receptor α-chain, IL-4, IL-13, CD14, dipeptidyl-peptidase 10 (DPP10), and a disintegrin and metalloprotease domain 33 ( ADAM33 ).

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Environmental factors• Environmental factors interact with genetic factors to maintain type 2 helper T (T H 2) cell–directed

immune responses. • T H 2 cells activate eosinophils, promote IgE production, and are proallergic.

• Early childhood exposure to bacterial and viral infections and endotoxins (eg, lipopolysaccharide) may normally shift native T H 2-cell responses to type 1 helper T (T H 1)–cell responses, which suppress T H 2 cells and therefore discourage allergic responses.

• Other factors thought to contribute to allergy development include chronic allergen exposure and sensitization, diet, and environmental pollutants.

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Pathophysiology

• When allergen binds to IgE-sensitized mast cells and basophils, histamine is released from their intracellular granules.

• Mast cells are widely distributed but are most concentrated in skin, lungs, and GI mucosa; histamine facilitates inflammation and is the primary mediator of clinical atopy.

• Physical disruption of tissue and various substances (eg, tissue irritants, opiates, surface-active agents, complement components C3a and C5a) can trigger histamine release directly, independent of IgE.

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Con .• Histamine causes the following:• Local vasodilation (causing erythema)• Increased capillary permeability and edema (producing a wheal)• Vasodilation of surrounding arterioles mediated by neuronal reflex

mechanisms (causing flare—the redness around a wheal)• Stimulation of sensory nerves (causing itching)• Smooth muscle contraction in the airways (bronchoconstriction) and

in the GI tract (increasing GI motility)• Increased nasal, salivary, and bronchial gland secretioson

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Con .• When released systemically, histamine is a potent arteriolar dilator

and can cause extensive peripheral pooling of blood and hypotension; cerebral vasodilation may be a factor in vascular headache.

• Histamine increases capillary permeability; the resulting loss of plasma and plasma proteins from the vascular space can worsen circulatory shock.

• This loss triggers a compensatory catecholamine surge from adrenal chromaffin cells.

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Symptoms and Signs• Common symptoms include• Rhinorrhea, sneezing, and nasal congestion (upper respiratory

tract)• Wheezing and dyspnea (lower respiratory tract)• Itching (eyes, nose, skin)• Signs may include nasal turbinate edema, sinus pain during

palpation, wheezing, conjunctival hyperemia and edema, urticaria, angioedema, dermatitis, and skin lichenification. Stridor, wheezing, and hypotension are life-threatening signs of anaphylaxis

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• Diagnosis• Clinical evaluation• Sometimes CBC and occasionally serum IgE

levels (nonspecific tests)• Often skin testing and allergen-specific serum

IgE testing (specific tests)• Rarely provocative testing

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Nonspecific tests• Blood tests (in vitro immunoglobulin E antibody tests) can be useful for those who

shouldn't undergo skin tests. • Blood tests aren't done as often as skin tests because they can be less sensitive than

skin tests and are more expensive.• CBC to detect eosinophilia if patients are not taking corticosteroids, which reduce

the eosinophil count. • However, CBC is of limited value because although eosinophils may be increased

in atopy or other conditions .• Serum IgE levels are elevated in atopic disorders but are of little help in diagnosis

because they may also be elevated in parasitic infections, infectious mononucleosis, autoimmune disorders, drug reactions, immunodeficiency disorders

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Allergy skin tests• During allergy skin tests, your skin is exposed to (allergens) and is then observed for signs of an

allergic reaction.

• Along with your medical history, allergy tests may be able to confirm whether or not a particular substance you touch, breathe or eat is causing symptoms.

• Allergy skin tests are widely used to help diagnose allergic conditions, including:• Hay fever (allergic rhinitis)• Allergic asthma• Dermatitis (eczema)• Food allergies• Penicillin allergy• Bee venom allergy• Latex allergy

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     ) األنف ) حساسية القش حمىالتحسسي     الربو

) األكزيما     ) الجلد التهابالطعام     حساسية

البنسلين     حساسيةالنحل     سم الحساسية

الالتكس     حساسية

Management• Several medications maybe used to block the action of allergic

mediators, or to prevent activation of cells and degranulation processes.

• These include antihistamines, glucocorticoids, epinephrine, mast cell stabilizers, and antileukotriene agents are common treatments of allergic diseases.

• Anti-cholinergics, decongestants, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. Epinephrine is important in anaphylaxi

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epinephrine pen• Epinephrine auto-injector is an emergency injection ("shot") of epinephrine. It is a

medicine used for life-threatening allergic reactions such as severe swelling, breathing problems, or loss of blood pressure.

• It is administered by injection into the middle of the outer side of the thigh (upper leg) and begins working rapidly.3,4

• Remember: Use of epinephrine auto-injector must be followed by emergency medical care.

• Epinephrine auto-injector is designed for self-administration. The press-and-hold technique - press hard, hold in the middle of the outer side of the thigh (upper leg) for 10 seconds - is designed to deliver the full dose of epinephrine.

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Thanks

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