ALLERGY

COMMON  INCONVENIENCES 

OCCASIONALY  SEVERE  DISEASES

INFREQUENTLY   DEVASTATING


Allergy is a disorder of the immune system, in which reactions occur to normally harmless environmental substances known as allergens. These reactions are acquired, predictable and rapid.

In 1906, Dr. von Pirquet in Vienna noted that some of his patients overreacted to innocuous things such as dust, pollen or certain foods. He coined the word “allergy”, from the Ancient Greek words of allos meaning “other” or “different”, and ergon meaning “work” or “reaction” →→ allergon or allergy, other work or different reaction.
 
Later it became clear that several different disease mechanisms were implicated, and in 1963 Philip Gell and Robin Coombs described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity. With this new classification, the word allergy is restricted exclusively to Type I hypersensitivities, also called immediate hypersensitivity or atopy.
 
Three years later, a major breakthrough in the understanding of these mechanisms, was made by Ishizaka, when he and his team isolated immunoglobulin E, known as IgE for short. It is one of the key links in the setting up, and in allowing the triggering of the allergic reaction.
 
Types of allergens and symptoms
 
Inhaled allergens can cause hay fever (sneezing and runny nose) usually accompanied by streaming eyes from contact with the allergen. They can also cause asthma, through narrowing of the airways and increased mucus production, causing coughing, shortness of breath, usually with audible wheezing.  Common inhaled allergens are pollen, dust mites, animal dander (skin and saliva), cockroach particles and molds. House dust also includes minute particles of human skin desquamation (and of the microscopic mites that feed on this), of feathers, wool and other textiles, microbes, molds (fungus), foods, toxins and chemical substances commonly employed in the home: all these can be implicated. The avoidance or the control of these factors are important in avoiding respiratory allergies. 
 
Pollen has been mentioned: there are different types of grasses, that at pollination time contaminate the atmosphere, as also happens with many species of trees. In many towns across the world the public is supplied daily with information about the “pollen count” to alert susceptible people. Unfortunately we do not have these measurements in Argentina on a public scale. The air borne spread is favoured by a warm and dry climate, with the prevailing winds determining the extent of the “allergenic area”.  
 
Certain foods can produce abdominal pain, bloating, vomiting, diarrhea, itchy skin, eczema and hives (urticaria). Infrequently it is thought to be a trigger of asthma. Every patient with this condition reacts predictably with the same symptoms, but can have different scales of severity. The most common varieties are those that affect infants and children who vomit or have diarrhea after taking cow’s milk, and occasionally this is shared with some of the aforementioned respiratory or skin problems.  Most of these allergic responses tend to disappear in later childhood. Very prevalent are peanuts and tree nuts (almonds, walnut and cashew) as causes of digestive allergy, and this tends to persist for life, if they are not avoided.  Although one can be allergic to any food, be it fruits, vegetables or meats, a 90 % of all food allergies are produced by eight foods: milk, eggs, peanuts, fruit nuts, wheat, soy, fish and shellfish.   Food preservatives and additives can also produce this type of allergy. Substances such as sulphites, used also as anti-browning agents, are used in wine, beer, dried fruit and vegetables, white vegetables (horseradish sauces and relishes, and sauerkraut), biscuits, crustaceans and mussels. Food additives made up from allergenic foods can contain residual allergens, such as lecithins: this may affect people highly sensitive to soy, rape or sunflower seeds.    In many countries, there is legislation that obliges manufacturers to display on the label of food products which of these substances have been employed.
 
Many of these allergens can work when in contact with the skin. The list is long, and the best known are adhesive tape, antibiotics and sulpha drugs applied locally, chemicals on rings, earrings and bracelets, and sap exposed  from trees when their branches are cut.
 
Drugs and medicines are also frequent offenders, the best known being aspirin and penicillin. In this case all the semisynthetic penicillins, and the cephalosporin gender of antibiotics should be avoided completely, as they can have devastating effects.  This list is also long, and it is very important to keep a record of any medicine that has produced some reaction, as many people tend to forget these things as the years go by. Bracelets, tags on neck chains or cards in a purse with the pertinent information can be critical for one’s health in the occasional emergency.
 
Bee and other insect stings, initially producing local itching, pain and swelling, can on repetition produce a life-threatening reaction called anaphylaxis: its mechanisms are a little different to the described formerly, but should be known to be forewarned. In this situation, if one has on hand a kit of adrenaline for self injection, it can be life saving. 

How it works:


ALLERGEN →→ Th2 Lymphocyte
        ↓
        ↓
            IL4  ↔↔ B Lymphocyte
        ↓
        ↓
         Mast cells ↔ ↔  IgE  ↔↔  Basophils
          ↓                                       
          ↓                                       ↓
ALLERGEN →→→→→→→ACTIVATED  ←←←←←←←←←
         ↓
         ↓
       DEGRANULATION
         ↓
         ↓
      CHEMICAL  MEDIATORS

 
We have white blood cells called lymphocytes circulating in the blood. Of these there are two types:                    T-lymphocytes and B-lymphocytes. Both have several subsets for different missions. When an allergen is encountered for the first time, it causes a response from a T subset called Th2 cell, which releases a chemical cytokine called Interleukin 4 - or IL4 for short (one of the many chemical mediators in our bodies). IL4 signals the B-lymphocytes to approach, inducing them to produce a special type of antibody called IgE.  These are released into the surrounding tissues and into the blood, whereupon they search and find two similar types of cells, one in the tissues (mast cells) and one circulating in the blood (basophils).  These have special receptors on their outer coating which is specific for the chemical shape of the IgE antibody (and nothing else!): when this happens, these mast cells and the basophils remain sensitized to the specific antigen which got it going:  they are activated.  On a second “presentation”, these activated cells recognize the antigen immediately: the combination of allergen plus IgE joined on to the surface receptors, cross-linking with its neighbours,  “unlock” the cell, which then releases granules loaded with chemical mediators, the best known being histamine. Others are prostaglandins, different interleukins, cytokines and leucotrienes. This is known as “degranulation”.  Locally these produce swelling, redness, itching and sometimes pain, and if they get into the bloodstream in sufficient quantities, they can produce hives (urticaria), swelling of the face, lips, tongue and upper airway, shortness of breath, and occasionally sudden death from anaphylactic shock.
 
Host Risk Factors
These include heredity, sex, race and age, with heredity being by far the most important. Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time. In non-identical twins this occurs in about a 40% of the time. Allergic patients are more likely to have allergic children, and their allergies tend to be more severe than those of non-allergic parents.   Also, parents who are allergic to peanuts may have children who are allergic to ragweed: in this case the irregularity in the immune system is inherited, but the specific allergy is not.

Young children are most at risk for allergic sensitization, hay fever and asthma being the principal conditions.  Boys have a higher risk of developing allergy than girls, although for asthma in young adults, females are the most likely affected.

Environmental Risk Factors
Four are the major environmental candidates: alterations in exposure to infectious disease during early childhood, environmental pollution, allergen levels and dietary changes. The first of these mentioned, called the Hygiene Hypothesis, has many solid arguments in its favour, and goes as follows: allergic diseases are caused by inappropriate immunological response to harmless antigens driven by the Th2 lymphocyte.  Bacteria and viruses elicit a Th1-mediated immune response, which down regulates the Th2 response.  If there was insufficient stimulation of the Th1 arm of the immune system, the Th2 arm would be overactive, and vice versa. 

 Thus, individuals living in a too sterile environment, or exposed in early life to antibiotics and to vaccines, or living in a cleaner environment, are more prone to respond to harmless antigens with an allergic response. Allergic diseases are more prevalent in small families, and in the developed and industrialized world: as a country becomes more affluent, there is an increase in immunological disorders.
 
Diagnosis
After having excluded other possible causes, the physician must try to confirm the diagnosis of allergy.  Skin testing is the preferred method, as besides being sensitive and specific, it is less expensive. It is known as the “prick test”, where small amount of allergens or of their extracts are introduced to sites on the skin marked with a pen or with dye; a small device is used to puncture the skin. If the patient is allergic to the substance, in 30 minutes a reddening and swelling can be seen at the site.

Blood tests can be performed, to determine the quantity of IgE antibodies circulating in the blood. High levels suggest probability of sensitization, low levels do not rule out the possibility.
 
Treatment
  • Avoiding the allergen in question
  • Reducing exposure
  • Pharmacotherapy
    • Antihistamines
    • Cortisone **
    • Epinephrine (adrenaline) **
    • Cromolyn
    • Antileukotrienes
           **For use in Emergencies
  • Monoclonal antibodies (Omalizumab)
  • Immunotherapy
This is a widely used method to desensitize the patient, by injecting minute quantities of the offending allergen, in a repetitive fashion, and in progressively increasing quantities. In this way the immune system begins to manufacture “blocking antibodies” of the IgG class, similar to the antibodies produced by vaccination, and later, when challenged by the antigen, IgG comes into play before the IgE, thus annulling (blocking) the allergic response.   It is not always effective, but is very useful in children, adolescents and young adults. A very effective and rapid desensitization method for penicillin has been developed, for those allergic patients that need to use penicillin or similar antibiotics only.
 
Author
References
  • Lock S, Last JM & Dunes G (Editors) “The Oxford Illustrated Companion to Medicine”, Oxford University Press, 2001.
  • Von Pirquet C (1906) “Allergie”. Munch Med Worchenschr 53:1457. Cited in http://en.wikipedia.org/wiki/Allergy
  • Ishikaza K,Ishikaza T, Hornbrook MM (1966). “Physico-chemical properties of human reaginic antibody. IV. Presence of a unique antibody as a carrier of reaginic activity”. J.Immunol. 97 (1): 75-85.
  • Marra F, Lynd L, Coombes M et al (2006). “Does antibiotic exposure during infancy lead to development of asthma ?: a systematic review and metaanalysis”. Chest 129 (3): 610-8.
  • Garn H, Renz H (2007). “Epidemiological and immunological evidence for the hygiene hypothesis”. Immunobiology 212 (6): 441-52. Cited in http://en.wikipedia.org/wiki/Allergy.