Thursday, May 16, 2013

x1901-1920: Hay fever becomes allergy

Paul Portier
The term hay fever was used for the first time in medical nomenclature in 1812 by Dr. John Bostock to describe seasonal allergy symptoms associated with the hay season. The term had been used by lay people much longer than that. So, even while many physicians doubted it was an appropriate term, it stuck in medical nomenclature like gum on a little boy's shoe.
However, a series of discoveries shortly after the turn of the 20th century would introduce the world to a series of new terms, such as anaphylaxis, atopy, and allergy.

In 1901, the Prince of Morocco summoned two scientists, Paul Portier and Charles Richet, to study a sea anemones called the Portuguese man-of-war. Their job was to learn how to protect swimmers from its sting, which caused painful blisters. (1, page 608)
Charles Richot

Initially, the two believed the painful blisters were caused by toxins from the animal's tentacles once they were entered into the skin of humans.  Back then vaccination was becoming a household name, and so the two set out to create an antitoxin vaccine.  (1, page 608)

Richet started the experiment by extracting toxins from sea anemones, and gave them in small amounts to test dogs.  After the initial injection they figured the dogs would develop antibodies that would protect them from a second exposure of the toxin.  In this way they would develop a natural protection against it, or prophylaxis.
However, when they extracted the toxin of sea anemones and inserted it into test animals (dogs in this case), the reaction they got was the opposite of what they expected.  The first two doses did no harm to the animals, but subsequent doses caused many of the dogs to go into a state of shock, and most did not recover.  Richet and Portier determined the animals died due to the effects of the toxins.

Instead of prophylaxis The animals developed aniphylaxis, a new term devised by the two men.

It's time for some definitions:
  • Greek pro means toward or before
  • Greek phylaxis means protection
  • Greek ani means opposite or away
  • Prophylaxis means to add protection
  • Aniphylaxis means to cause harm
So, instead of protecting the animals from developing symptoms, they caused the symptoms.  The scientists learned that a "foreign protein" was transferred from the sea anemones to the dogs making them hypersensitive to that protein. (2, page 11)

Other scientists performed similar experiments and came to similar results.

Clemons von Pirquet
In 1906, an Austrian pediatrician named Clemons Von Pirquet observed many of his patients were hypersensitive to substances that didn't bother other people.  These normally innocuous (harmless) substances were pollen, dust mites and some foods.

The purpose of the immune system is to attack foreign particles that want to harm the human body.  Yet sometimes the immune system attacks allergens that are not meant to cause harm.  Von Pirquet and Schlick observed this, and they coined the term allergy to describe when the immune system causes harm.  (5, page 53)(3)

Once again a definition is in order:
  • Greek allos means other
  • Greek ergon means action or enery
  • Allergy means the immune system causes the opposite effect as its intention (causes harms)
  • Allergen means a substance or protein that may incite the allergic response hen a hypersensitivity is present
  • Hypersensitivity means over-reaction; a hyper-reaction of the immune system; as in when exposed to allergens (Dated to 1870s)(Dictionary.com)
Von Pirquet actually believed that asthma was an allergic condition, and curing this disease was only a matter of finding the right foreign proteins to inject. History would prove him right in juxtaposing asthma and allergies, yet wrong on the front of this leading to a cure.

Also in 1906, German physician Alfred Wolff-Eisner surmised that pollen is similar to the poisons of the Portuguese man-of-war in that it could trigger the immune response in some some people.  By inserting drops of pollen into the eyes of volunteers, he was able to produce the same response suffered "during the hay fever season: red, swollen, and itchy eyes." He published his findings in 1906.  (5, page 54)

Thanks to Wolffe-Eisner's discovery linking hay fever with the immune system, hay fever was no longer believed to be a nervous disease.  It as no a disease caused by a hypersensitive immune system. This was an essential transformation because it would effect the future course of treatment for the disease.  Instead of seeking to alleviate a nervous disorder, the goal of treatment as not to fix a broken immune system.  (5, page 54)

In 1910 Samuel Melzer observed the "similarity" between anaphylaxis and asthma "in which a person became sensitized to a definite substance, and an attack occurred every time the substance entered the circulation (of that patient).  Minute quantities of the substance, if inhaled, would bring on an asthma attack." (2)

We now know that about 75 percent of asthmatics have allergies.  Yet we also know that many people have allergies and not asthma.  We also know that both conditions have been linked to the immune system and can be developed at any age.  Yet in 1906 scientists were at the dawn of such allergy wisdom.

Pirquot believed it was the body's response, not the foreign particles, that resulted in the allergic reaction. He listed as things that might cause this "hypersensitivity" as bee stings, mosquito bites, hay fever caused by pollen, and substances in certain foods such as crabs.

Soon thereafter Arthur C. Coca, founder of the Journal of Immunology, and Robert Anderson Cook, were attempting to understand studies regarding allergic conditions, used the term Atopy which literally means "strange disease."  They thought atopy should be used to describe hereditary hypersensitivities such as asthma, hay fever and eczema, and hypersensitivities that could afflict anyone should be referred to as anaphylaxis.

By 1919 two allergists, Cooke and Albert Vander veer, published the results of a study of 500 patients with asthma, hay fever, and other allergic diseases that confirmed that age old theory that these conditions were inherited and perhaps linked to other conditions.

Initially all prophylactic and anaphylactic reactions were referred to as allergies, as this as the recommendation of Van Pirquot.  He believed the two reactions should have a common name.  (3)

Yet ultimately it was learned that there were three conditions associated with hypersensitivities that didn't fit into this classification:  asthma, hay fever and eczema.  In asthma the hypersensitive response lead to constricted air passages, in hay fever it lead to a runny and stuffy nose, and in eczema it lead to red and itchy skin.

These three conditions -- asthma, hay fever and eczema -- are now often referred to as the atopic triad because in many individuals they come as a package.  One major difference between the atopic triad and anaphylactic reactions is that anaphylaxis can be induced in almost anyone, while the others occur in only a small percent (about 10 percent) of individuals and are quite often hereditary.  (4, page 608)

In subsequent years allergy was used to denote an immunal hypersensitivity or hyperresponsiveness to a foreign substance and atopy was used to denote the inherited conditions of asthma, hay fever and eczema.  Although, quite often the terms allergy, atopy and anyphylaxis are used interchangeably.

References:
  1. Klein, Jan and Vaclav Horejsi, "Immunology," 1997, page 608
  2. Brenner, Barry E, "Emergency Asthma," (ed. Barry E. Brenner), 1998, New York
  3. Ehrlich, Paul M., Elizabeth Shimer Bowers, "Living with Allergies," 2008
  4. Klein, Jan, Vaclav Horejsi, "Immunology," 1997, page 608
  5. Mittman, Gregg, "Breathing Space," 2007, New Haven, London, Yale University Press

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