List of four important allergies seen in humans: 1. Antibody-Mediated Hypersensitivity 2. Allergic Rhinitis 3. Hypersensitivity Pneumonitis 4. Cellular- Mediated Hypersensitivity.
1. Antibody-Mediated Hypersensitivity:
Immediate hypersensitivity is related to the development of reaginic antibodies, usually Immunoglobulin E (IgE) and less often IgG, in sufficient quantities to evoke the symptoms of hay fever, asthma, hives, and anaphylactic shock.
ADVERTISEMENTS:
These antibodies are produced following allergen contact, locally within plasma cells embedded in the mucosa of target areas of the nasopharynx and the respiratory and gastrointestinal ‘ tracts, as well as elsewhere in the lymphatic system.
After diffusing into the tissue fluid and serum the antibodies attach to mast cells, basophils and platelets. Allergen then binds to this cellbound reagin, triggering the release of histamine and other vasoactive substances (kinins, serotonin, slow reacting substances) that cause the allergic symptoms of bronchospasm, vasodilation, smooth muscle contraction
and increased bronchial and nasal secretion. However, clinical manifestations are often not apparent until repeated exposures to the allergen have increased the number of cells involved.
An inciting allergen can be identified from among a host of possible candidates by several provocative in vivo tests. The most frequently employed are skin tests that involve the introduction of dilute concentrations of allergen into the skin by intradermal injection or through pricking.
If a specific reaginic antibody is present in the skin, the characteristic wheal and erythema of a cutaneous anaphylaxis reaction appear within a few minutes. More rarely, tests using the conjunctiva or nasal mucosa as target organs have also been found effectual.
Since the induction of systemic anaphylactic shock is always a possibility during such testing, however, it is recommended that the procedures always be carried out under careful medical supervision and that an antianaphylactic drug (i.e., epinephrine) be available.
ADVERTISEMENTS:
Sensitive in vitro tests are also now employed. The radioallergosorbent test (RAST) is based on binding antibody to antigen in a system containing radiolabeled anti-antibody (anti-IgG, anti-IgE, anti- IgA). When necessary, the use of different radioactive iodine isotopes as labels allows for the simultaneous detection of reaginic IgE and blocking IgG in a patient’s serum.
Other tests have been devised that detect reaginic antibody through its ability to release histamine from mast cells or nonallergic donor leukocytes in the presence of allergen. Results of the passive leukocyte sensitizing test (PLS) have been used to link fluctuation in serum reagin content to the seasonal prevalence of allergen such as ragweed.
Allergic symptoms may be reduced by immunotherapy consisting of careful injection of small amounts of the allergen (often into site that is not the target area, e.g., upper arm instead of respiratory tract) to elicit specific blocking antibodies (IgA or IgG), or a white cell response.
In some way, this response binds the allergens and prevents reagin-allergen complexes from forming (hyposensitisation), reduces the amount of IgE from being formed (tolerance) or, by neutralisation of reagin with excess antigen (desensitisation), reduces the amount of IgE antibody available in target areas.
ADVERTISEMENTS:
In seasonal spore and pollen allergie hyposensitisation may be attempted preseasonally, ensuring that blocking antibodies are at their highest titre during the provocative period, since treatment during the symptomatic period (coseasonal) is less satisfactory. For allergies that occur throughout the year, such as those elicited with fungal spores, it may be necessary to maintain treatment year-round.
Anaphylactic Shock:
Systemic anaphylaxis, a rare event in man, is the most severe of all allergic reactions.
Typically, it can occur after an inciting dose has been given intravenously to a hypersensitive individual, but it has also been noted after oral, subcutaneous, or intramuscular administration. It is characterised by sudden vasomotor collapse leading to shock, paroxysmal bronchoconstriction and if treatment is not undertaken immediately, death.
ADVERTISEMENTS:
Most cases have been associated with serum therapy (serum sickness), penicillin therapy and insect stings (especially the wasp, bee and hornet). However, the following case history underlines the danger of chamomile tea ingestion by an individual known to have ragweed and Chrysanthemum atopic disease and other allergies.
Within minutes of drinking a few sips of chamomile tea, a 35-year-old woman developed abdominal cramps, thickness of the tongue and a tight sensation in the throat. This was followed by angioedema of the lips and eyes, diffuse pruritus and a full sensation in the ears. There was no vomiting, diarrhea, sneezing or wheezing. Fortunately, diphenhydramine was administered immediately and a steroid shortly thereafter.
The symptoms cleared gradually over the next few hours and disappeared overnight. A subsequent scratch test with chamomile tea produced a large wheal and flare reaction with pseudopod formation. Similar reactions were also elicited among other ragweed patients, although none gave a histoiy of chamomile tea ingestion.
This suggests that allergens are shared among members of the family of which ragweed and Chrysanthemum are a part.
Prevention is empirical, but atopic individuals should be aware of the increased risk and should avoid agents having known anaphylactic potential, such as penicillin or chamomile tea.
2. Allergic Rhinitis:
Characteristic symptoms of hay fever, induced following exposure of the nasal mucosa to the allergen through inhalation, include profuse watery nasal discharge with sneezing, frequently accompanied by redness, irritated and watery eyes and headache.
The inciting allergens are often found in windborne plant structures called aeroallergens. The spores from fungi and even certain algae may persist through the year, especially under warm humid conditions; but particularly in temperate regions, wind-pollinated plants elicit symptoms during certain flowering periods.
In North America there are three peaks in the pattern of seasonal rhinitis:
The first occurs in the spring when trees shed their pollen; the second, during the summer months, involves pollen from many grasses as well as late flowering trees and weeds; and the last peak, in the autumn, is typified by weed and secondarily by grass pollen grains.
Ragweed pollen (Ambrosia) predominates during this time and is the most allergenic pollen found in North America.
In tropical areas both perennial and seasonal patterns can also be observed with this disorder. Fungal spores and grass pollen are common aeroallergens, whereas those from weeds and wind-pollinated trees are of secondary importance. However, the determination of aeroallergens in the more equatorial zones requires further study.
Although the majority of plants that induce allergic rhinitis are wind-pollinated, a number of plants that are typically pollinated by animals (insects, birds, bats) have also been implicated. For example, old- fashioned roses, which are infrequently found in gardens today, are often heavily scented and their anthers are exposed by the loose and open form of the floral bud.
Thus their attractiveness frequently used to lead to sensitisation through inhalation of the pollen and the term rose-fever or rose-cold was used to describe plant-associated rhinitis.
Pollen and their allergens:
The morphological diversity of wind-borne pollen varies from smooth-walled grains having a single pore, as found among the grasses, to the very spiny grains of ragweed and the multiporate apertures typical of pigweed. Size and shape also vary. These features, as well as their wall structures, are related to dispersal mechanisms and their significance as aeroallergens.
The majority of allergens are found in the walls of pollen and spores, but their purpose is not to elicit allergy; rather, they act as recognition proteins to stimulate the growth of the sperm-containing pollen tubes on specific “female” parts of the flower.
These proteins are concentrated below the apertures in the inline or inner wall as well as in the hard, rigid, outer wall or exine in minute micropores or even chambers. They are water soluble and when in contact with the “female” part of the flower, or the mucosa of man, the protein may be released within a few seconds.
Some of these proteins have been isolated only recently. For example, the fraction designated intigen E is the major allergenic protein of ragweed {Ambrosia). Others include antigens K, Ra, Ra3, and Ra5. Among the grasses, a number of allergens have also been identified, such as allergens A and B for timothy (Pheleumpratense) and alpha, beta and gamma allergens in rye (Lolium perenne).
Also, a number of active fractions have been isolated from alder (Alnus glutinosa). However, the majority of specific allergens remain uncharacterised.
In India since 1980s, enormous studies were carried out to evaluate the potential of pollen induced allergic disorders. A good number of flowering plants now listed out, whose pollen grains are potentially allergenic (Table 34.1).
Spore and pollen incitants in man:
Many kinds of fungi and flowering plants are responsible for allergic rhinitis. The most important fungal allergens are found in the Deuteromycetes, particularly the families Dematiaceae and Moniliaceae, which include such ubiquitous genera as Alternaria, Cladosporium, Aspergillus and Penicillium.
Of these, Alternaria possesses the most allergenic substances and affects the greatest number of individuals, especially in the Midwestern United States. Even though they produce abundant amounts of windborne pollen, the Gymnosperms rarely elicit allergic rhinitis, whereas most windborne pollen grains from Angiosperms are common incitors.
Overall, the most troublesome trees in North America are oaks (Quercus), hickories (Carya), and elms (Ulmus), but weedy urban box elder (Acer) pollen has recently been shown to have the highest level of allergenicity among tree pollen.
Therapy:
The control and treatment of allergic rhinitis falls into three major categories. The first is related to controlling contact with allergic material. Often referred to as environmental control, this function might include the elimination of the affecting plants, the filtering of aeroallergens by appropriate air-conditioning and, probably more important, moving away from the location of the offending allergens.
It is surely relevant to consider the allergic person when plantings in urban developments are being designed.
Another prophylactic measure is hyposensitisation of the patient with the affecting allergen. This regimen, administered by an allergist, involves injection of increasing amounts of the allergen to develop a high titre of blocking antibodies prior to normal exposure. Today this is the most satisfactory form of prophylactic treatment, but its effect is directly related to the potency of the allergen in the antigens administered.
Finally, as an adjunct to hyposensitisation, acute symptoms are also treated by the administration of antihistamines and vasoconstrictors such as ephedrine (Ephedra sinica). Corticosteroid therapy, which may be employed to terminate a single severe attack, is often effective, though not curative. Prolonged use of steroids may be dangerous and possible benefits must always be weighed against deleterious effects.
Asthma:
Attacks of bronchial asthma are usually precipitated by inhalation of the specific allergen and this form of allergy often has a more chronic course than that seen in allergic rhinitis even though the eliciting agents may be the same.
Histamine and, perhaps, serotonin, are involved in symptoms that are characterised by bronchospasm and accompanied with excessive viscid bronchial secretion, which produces the asthmatic “wheezing“. Extrinsic asthma occurs typically in children and young adults and is often aggravated by emotional factors.
It is considered to be an IgE mediated disease caused by the inhalation of aeroallergens such as pollen, spores, feathers and animal danders. Although not a common aeroallergen, pollen from the lodgepole pine of Colorado (Pinus contorta) has also been known to cause bronchial asthma.
The mechanism for induction of intrinsic asthma is somewhat more obscure and is generally found in an older age group. The likely agents are allergic reactions to infectious materials, such as bacteria or viruses, or the inflammatory processes they elicit.
Unlike extrinsic asthma antigens cannot be demonstrated and thus skin testing is of no value. The separation of purely extrinsic from intrinsic asthma can be diagnostically difficult whenever allergic phenomena are combined with infectious factors.
Possibly another IgE-mediated Type I disease is the coffee bean and castorbean workers disease that is characterised by rhinitis, asthma and dermatitis following inhalation of the hapten, chlorogenic acid.
As it is widespread in plants and is concentrated in coffee beans and castorbeans, chlorogenic acid may act more as a universal allergen than was first suspected.
3. Hypersentivity Pneumonitis:
Another type of allergic respiratory condition—known as hypersensitivity pneumonitis or extrinsic allergic alveolitis—is often associated with specific professions. In these instances, animal, vegetable or bacterial enzyme material may induce the disease.
For example, inhalation of Thermoactinomyces vulgaris or fungal spores of Microsporumfaeni, which can contaminate hay, moldy sugarcane, or mushroom compost, have been causally related to farmer’s (thresher’s) lung, bagassosis and mushroom worker’s lung.
In a similar way, Cryptostroma corticale has been associated with maple bark disease of woodworkers, Penicillum caseii to cheeseworker’s disease, Aspergillus clavatus and A. fumigatus to brewer’s lung disease and Graphium and Aureobasidium pullulans to sequoiosis. By inhalation of the enzyme of Bacillus subtilis, those who work with detergents may also develop an allergic pneumonitis.
Diseases produced by inhalation of airborne algae such as Gloecapsa and chlorella, are of more general incidence, however.
Wood and paper mill workers may also develop bronchial asthma through sawdust inhalation of the Gymnosperms, redwood (Sequoia sempervirens), western red cedar (Thuja plicata), cedar of Lebanon (cedrus libani) and the Angiosperms, iroko or African oak (Chlorophora excelsa), Nicaragua rosewood (Dalbergia retusa), and other exotic woods.
The immunopathology suggests that a mixture of many types of immune or allergic reactions may be involved in extrinsic allergic alveolitis and thus is classified as Type III.
It is also possible that symptoms similar to those of allergic respiratory illness may be elicited by inhalation of airborne leaf hairs. Such a series of cases was recently reported among gardeners who had • tended saplings of Oriental sycamores or the tree of Hippocrates (Platanus orientalis) at a medical school campus.
It is interesting that, about 2000 years ago, Dioscorides (40-90 AD) had noted watery eyes, sneezing, an irritating sensation in the nasal passages, soreness of the throat, an irritating dry cough and other similar symptoms.
Therapy:
A regimen of environmental control and hyposensitisation is normally prescribed for pollinosis.
Currently, three basic drugs have preempted ephedrine for use in the control of asthmatic attacks:
Epinephrine (adrenalin) and its congeners administered by aerosol, the methylxanthines administered intravenously for acute attacks and orally for chronic asthma, and the steroids (cortisone) for severe and intractable states, in combination with other drugs mentioned.
In prophylaxis, particularly where hyposensitisation fails, cromolyn sodium is used; this new compound, obtained from the seeds oiAmmi visnaga (Apiaceae), is believed to affect the release of vasoactive substances and, therefore, through a regimen of frequent inhalation, acts to prevent or modify the asthma.
This plant, known as khella from its native Mediterranean region, has a long history of use as an antiasthmatic among the Arab peoples, who also believe it is useful in the treatment of angina pectoris.
Although other plants used in domestic medicine to treat asthma have rarely been studied, the recent Indian research using the leaves of Tylophora indica (Asclepiadaceae) furnishes an interesting exception.
It is claimed that complete to moderate relief of nasobronchial allergic symptoms can be maintained up to one week after ingestion of but a few leaves of the plant. Typical of members of this family, T. indica, is, however, very toxic and also has blistering or vesicant properties.
Ingestant Allergy:
Symptoms from ingesting a potential allergen can vary from urticaria to vomiting, diarrhea and intestinal wall edema. It is sometimes difficult to differentiate between true atopy and toxicity, since clinical symptoms can be initiated by interaction of substances in foods with several different mediating systems.
Therefore the appearance of hives (urticaria) after consumption of strawberries and citrus fruits can be traced to direct chemical mast cell degranulation; those of coeliac disease with intolerance to gluten (gliadin in wheat); and gastrointestinal upset associated with milk are traceable to inherited disaccharidase (lactase) deficiencies.
Furthermore, several foodstuffs, particularly shellfish and mushrooms, contain notorious poisons. In susceptible persons, moreover, ricin (a phytotoxin from peanuts and castor beans), gossypol, aflatoxins, histamine or tyramine (in cheese or yeast products) may also produce symptoms.
It is also possible that certain nonallergenic components in food can trigger built-in labilities of mediator systems or can activate the complement system (CI and C3 : see Glossary) to generate anaphalatoxin-like agents.
Likewise, physiological age may also have a bearing on an individual’s ability to absorb or reject certain allergens. Many food allergies of childhood are altered as the digestive system matures.
Among cereals, for example, skin test reactions with rice indicate, that there is a lower degree of reactivity among the few children affected; the opposite is true among adults and higher reactivity involving greater frequency is typical. Any ingestant may prove to have an allergic potential; skin testing, the usual method of determining such susceptibility, may not accurately reflect the true allergic state.
Rather, susceptibility is better determined by demonstrating symptoms after deliberate feeding tests. Therapy related to the ingestant is used thereafter. Other techniques include using the rectal mucosa as a shock organ or feeding the test ingestant in dilute form and observing changes in the intestinal tract by X-ray.
Among the active allergens isolated from food, there is good evidence that tomato allergens fall into the same category of active glycoproteins described for inhalant allergens, as do the ovomucoids of egg white, whereas allergens of fish are simple amines.
The major symptom of ingestant hypersensitivity is urticaria, in which wheals and erythematous areas of the skin cause intense pruritus and discomfort. Local edema (angioedema) sometimes accompanies urticaria and this condition may be life-threatening if it affects the mucosa of the pharynx or larynx, since this may result in severe respiratory obstruction.
Atopic dermatitis, a common infant and childhood affliction, is often the first indicator of allergic predisposition.
This infantile or atopic eczema may be clinically present as a persistent, pruritic dermatitis that may be papular, exudative or lichenified, involving the head, neck and flexor aspects of the trunk and extremities. Most provoking allergens are difficult to identify, varying from animal epidermal allergens (hair) to various foods in the diet.
Therapy:
Whenever it is possible to identify the allergen, avoidance is the best therapy. Otherwise, ephedrine is administered orally and topical steroids are applied if skin lesions are severe. Antihistamines are useful when pruritus complicates atopic dermatosis or if there is urticaria.
When angioedema is a complicating factor, epinephrine is most useful and can be used concurrently with intravenous antihistamine and steroids for severe cases that involve the larynx.
Irritant Dermatitis:
Plants can mediate inflammatory reactions of the skin, which mimic in many ways the “wheal and erythematous flare” of immediate hypersensitivity, or the more severe reactions associated with the delayed response. In some instances this effect is attributable to the nature of the plant itself, that is, spines, thorns, bristles and hairs causing mechanical injury.
Moreover, the needle-sharp calcium oxalate crystals found in the outer layers of many Narcissus species and hyacinth bulbs can elicit the formation of wheals (bulb fingers), a symptom suggestive of histamine release. However, most forms of irritation are related to specific substances produced by plants and the mechanism for the adverse reaction is usually unclear.
Of the many plants that transfer their toxins by means of stinging hairs, the nettles (Urtica dioica and Laportea canadensis) contain histamine-like substances found in bladders within the leaf. A more severe reaction is elicited by another species of Urticaceae, Urera baccifera, which is found in tropical America. The material in its spinelike hairs causes considerable pain followed by numbness lasting for several days.
Similarly, the spurge nettle, Cnidoscolus stimulosus (Euphorbiaceae), can elicit painful irritation and itching following transfer of a caustic irritant. Perhaps the most painful reaction of all comes from Mucuna pruriens (Fabaceae), whose barbed spines covering the seed pods contain a highly irritating proteolytic enzyme called mucunain.
Poisoning can take place long after the pods have dried, even from herbarium collections. However, the ultimate in adaptation is exemplified by Gurania guaransenia (Cucurbitaceae), which, in addition to its own stinging hairs, harbors a butterfly larva having similar devices.
The sap of other plants, itself caustic and corrosive, results in severe inflammatory reactions, including blistering of the skin on contact. Many of these plants are tropical, although a number are widely cultivated.-
A characteristic of several of these irritant plant families is their milky or yellowish latex, usually found throughout the plant. Although some latex-possessing plants are harmless, a majority cause either irritant or contact dermatitis and as a general precaution they all should be avoided.
Apart from dermatitis, a hazard to those who prune or tend horticultural varieties is the eye damage and blindness that can result from contact between the eye and the caustic sap.
Several of these irritant factors have been characterised. Members of the Brassicaceae contain sinigrin; this glucoside is harmless if dried, but it can be converted into an irritant mustard oil in the presence of water.
A decomposition product of another glucoside, anemonin, has been isolated from the buttercup (Ranunculus) and produces blisters on the face and around the lips of children who may chew the leaves or stems of injured plants.
Furthermore, the pineapple (Ananas comosus, Bromeliaceae) possesses a proteolytic enzyme, bromelain, which causes separation of the superficial layers of the skin and increases skin and capillary permeability in a manner not unlike that found in the allergic wheal and flare reaction.
4. Cellular- Mediated Hypersentivity:
Delayed hypersensitivity may take days or weeks to develop; often prolonged contact with an antigen is necessary and the reaction depends on the formation of specifically modified lymphocytes from the thymus-dependent series (T cells).
Through specific receptors or other mechanisms, these cells are capable of responding specifically to antigens deposited at a local site and also of mobilising non-sensitised phagocytic cells to localise there and participate with them in tissue destruction. Unlike immediate hypersensitivity, a reaction is not apparent for 12-24 hours, when inflammation and necrosis appear in the affected area.
To test for contact hypersensitivity, the candidate allergen is usually applied as a patch to the unbroken skin and observed for 24 hours for characteristic changes.
The tolerance by deliberate desensitisation through administration of repeated injection of antigen are often short-lived and frequently precipitate severe allergic reactions.
Substances of plant origin or chemicals including heavy metals can act as haptens to mediate a delayed hypersensitivity response after prolonged or repeated contact with the skin.
Sensitisation is dependent on attachment of the chemical to the structural proteins of the skin, which results in a change of the skin proteins. Alone or through release of substances from epidermal cells, this type of antigenic alteration can stimulate a specific inflammatory response that produces, after 24-48 hours, symptoms of pruritis, burning or stinging, erythematous macules, papules, vesicles, exudation and crusting.
Drug Sensitivity Reactions:
Atopy that develops from the therapeutic administration of drugs may take many forms depending on the type of drug involved, the duration of contact and the method of administration. Moreover, from clinical symptoms, it may not always be possible to differentiate between drug toxicity or allergic phenomena.
Penicillin with its antigenic benzyl penicilloyl antigenic determinants and other haptenic moieties is perhaps the worst offender and some type of allergy appears in from 0.5% to 18% of patients using this drug therapeutically.
The likelihood of these reactions occurring increases with age, the number of injections, the larger the doses given and the way it is administered (with a greater risk through injection rather than orally).
Type I reactions are the most common and usually appear shortly after administration as hives (2-48 hours) or generalised anahphylaxis (20 minutes). When large intravenous doses of benzylpenicillin have been given a hemolytic anemia suggestive of a Type II reaction has also been known to develop.
The somewhat later appearing (3-5 weeks), maculopapular eruptions are, however, most likely Type III reactions, whereas the delayed cutaneous responses are of Type IV. The cephalosporins with their common 7-amino-cephalosporonic acid nucleus have cross-allergenicity with penicillin and have been known to cause thrombocytopenia, a Type II reaction.
Similar Type II reactions have also been reported for quinidine, amidopyrine, chlorpromazine, chloramphenicol and the sulfonamides. Type IV reactions including maculopapular skin eruptions, fever and hepatic dysfunction have been associated with sulfonamide therapy as well as in patients receiving paraaminosalicylic acid (PAS).
Because at least 5% of patients were so afflicted, ethambutol has now replaced PAS in tuberculosis therapy.
In patients with a history of antibiotic hypersensitivity it is not recommended to use the offending drug at all. Too often, allergic symptoms can only become aggravated or life-threatening. Nowadays, alternatives to penicillin are available that in most instances can be used as a satisfactory substitute without fear of eliciting an allergic response.
For symptomatic treatment, antihistamines and corticosteroids are used and if systemic anaphylaxis occurs, epinephrine is administered. As over two-thirds of the cases of anaphylaxis develop obstructive edema of the respiratory tract, tracheostomy should be considered to prevent death.