GENERAL CONCEPTS IN ALLERGY

Allergy denotes a specific type of hypersensitivity reactions mediated by IgE antibodies and provoked by specific antigens, i.e. allergens.

Allergen d enote a substance capable of inducing IgE mediated reactions on exposure.

Atopy denotes an inherited or familial predisposition for allergic disorders.

General pathophysiology: Allergic reactions are triggered by the binding of an allergen to specific or

reaginic IgE antibodies, attached on the surface receptors of circulatory basophils and tissue mast cells.

These reaginic antibodies are formed after an earlier exposure to same allergen, i.e. sensitization. On subsequent exposure, antigen-IgE binding on the surface of basophils/mast cells provokes two different types of reactions:

a. Early-phase reactions within 20 minutes, due to degranulation of mast cells and release of pre-formed chemical mediators, e.g. histamine and eosinophil chemotactic factors, presenting as urticaria, pruritis, sneezing, wheezing and hypotension, e.g. anaphylaxis, asthma, allergic rhinitis or insect allergy.

b. Late-phase reactions after 4-12 hours, due to influx of other allergic (basophils, eosinophils, mast cells) and inflammatory cells (polymorphs, lymphocytes) at the site of allergen exposure and consequent release of other chemical mediators, e.g. leukotrienes and prostaglandins. These mediators amplify allergic inflammation and facilitate further differentiation of allergic cells and IgE-producing B cells. Late-reactions have been implicated in development of long-term nasobronchial hyperreactivity in allergic individuals.

General principles in diagnosis: Clinical spectrum of allergic disorders is extremely wide, ranging from life­threatening anaphylaxis to system-specific disorders, e.g.

• Chronic course with intermittent exacerbations.

• Cause-effect relationship with allergen.

• Family history of atopic disorders.

• In vitro laboratory abnormalities, e.g.

- Peripheral eosinophilia (AEC gt;600 cell/mm³)

- Presence of eosinophils in body secretions

- Elevated IgE levels (N: 10-20 IU#8725;ml)

- Presence of allergen-specific IgE antibodies

• In vivo positive challenge tests, e.g.

- Allergen skin testing

- Provocation tests.

Allergen skin test is an important diagnostic tool to identify causative allergen in many allergic disorders, e.g. asthma or allergic rhinitis. These tests involve intradermal injections of miniscule quantities of a battery of commercial available allergens, (e.g. mites, dusts, pollens, danders and fungi), along with a negative (saline) and a positive (histamine) control, over forearm or back. Local response to each allergen injection, i.e. erythema and wheel size is noted and compared with controls, after 10 minutes (early response) and 2-3 hours (late response). Severity of response indicates strength of cause-effect relationship, though false-positive and false-negative results are common and results must be correlated with clinical observations.

Provocation or challenge tests involve deliberate exposure of the affected mucus membrane to suspected allergen, which may induce the allergen-specific clinical reaction. Commonly used provocation tests include bronchial provocation test in asthma (nebulization of suspected allergen to see spirometric changes) and oral provocation tests in food allergy or atopic dermatitis (ingestion of suspected food item to see reappearance of diarrhea or skin lesions). Although useful in cases with equivocal in vitro laboratory results or skin testing, these tests are rarely used due to the risk of life-threatening reactions.

General principles of management in allergic disorders include: (a) avoidance of suspected allergens if possible; (b) immunotherapy (desensitization) against unavoidable allergens; (c) specific pharmacotherapy to block the release or action of chemical mediators.

While specific therapeutic measures in management of individual allergic disorders have been discussed in respective chapters, some general principles are as follows: a. Avoidance of allergens: Common allergens may be divided into 3 categories:

1. Inhalant allergens, e.g. pollens, dust, dust-mite, danders and fungi,

2. Ingestant allergens, e.g. food, and

3. Contactant allergens, e.g. synthetic fabrics or elastics.

In addition, viral infections and smoke exposure, though not allergenic by themselves, are common triggering events for precipitation of acute attacks in children.

As the dictum goes, anything above the earth and below the sky may be allergenic. Further, atopic children are often allergic to many allergens at the same time. Considering this biological diversity, it is often difficult to identify and avoid specific allergens, though following precautions may be helpful:

• Avoidance of outdoor allergens, e.g. dust exposure, visit to flowery gardens, etc.

• Avoidance of indoor allergens with wet mopping of floor (dust); removal of indoor plants, soft toys and carpets (mites), avoidance of pets (danders), regular cleaning of AC filters (fungi), pest control (cockroaches), etc.

• Avoidance of suspected dietary substances is often overemphasized, without much scientific basis. However, a proven cause-effect observation with particular food stuff may be indication to avoid canned foods with preservatives, coloring agents, etc.

• Avoidance of other triggering factors, e.g. smoke exposure, viral infections, etc.

b. Immunotherapy: Some allergens are unavoidable, e.g. pollens, dust mites, etc. Immunotherapy is an option to desensitize the child against these identified but unavoidable allergen/s, by repeated intradermal

injections of the increasing dose of allergen/s as an aqueous extract (up to 10 allergens may be combined in same solution), once/ twice a week (interval is increased gradually), till the optimal maintenance dose is reached and continued for another 3-6 months.

Although with a sound physiological basis, immuno­therapy is often ineffective due to: (a) inadequate quality and unknown doses of currently available commercial allergen extracts, (b) frequent reappearance of hypersen­sitivity after discontinuation of maintenance doses, (c) change-over hypersensitivity from one to another aller­gen in inherently atopic child, and (d) poor compliance to multiple injections. However, it may be tried in selected cases of asthma or allergic rhinitis, where avoidance of suspected allergen is not possible.

c. Pharmacotherapy of allergic disorders may be broadly divided into preventors, i.e. drugs to prevent the attacks and rescuers—drugs to combat acute response. These drugs aim to:

• Block the release of chemical mediators, e.g. mast cell stabilizers, e.g. cromolyn sodium, nedocromil sodium, lodoxamide, olopatadine (last two for topical use only in allergic conjunctivitis),

• Block the action of these mediators, e.g. antihistaminics, steroids, leukotriene inhibitors, (montelukast, etc.)

• Antagonise the physiological response of mediators, e.g. #946;-agonists, acetylcholine inhibitors, etc.

While first two groups of drugs prevent the allergic attack and are used on long-term basis, the last group is useful only to control acute clinical manifestations. Important pharmacological agents in various atopic disorders have been discussed in respective chapters.

Antihistamines are competitive antagonists for H₁ histamine receptors, more effective in preventing than reversing the action of histamine. Consequently, these drugs are more effective in preventing, rather than treating, an established attack. As histamine is not the only chemical mediator of allergic response, these drugs are poorly effective in asthma or atopic dermatitis.

However, antihistamines are extremely valuable in the management of acute allergic rhinitis or anaphylaxis which are predominantly histamine-mediated. While large number of antihistamines are available with near­comparable efficacy, second generation histamines, e.g. cetirizine, loratidine, terfenadine are preferable due to less side-effects, e.g. drowsiness.

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